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Combining bronchodilators with different mechanisms of action may improve efficacy and reduce risk of side effects compared to increasing the dose of a single agent in chronic obstructive pulmonary disease (COPD).,We investigated this by combining two long-acting bronchodilators: once-daily muscarinic antagonist tiotropium and once-daily β2-agonist olodaterol.,Two replicate, double-blind, randomized, 12-week studies (ANHELTO 1 [NCT01694771] and ANHELTO 2 [NCT01696058]) evaluated the efficacy and safety of olodaterol 5 μg once daily (via Respimat®) combined with tiotropium 18 μg once daily (via HandiHaler®) versus tiotropium 18 μg once daily (via HandiHaler®) combined with placebo (via Respimat®) in patients with moderate to severe COPD.,Primary efficacy end points were area under the curve from 0-3 hours of forced expiratory volume in 1 second (FEV1 AUC0-3) and trough FEV1 after 12 weeks (for the individual trials).,A key secondary end point was health status by St George’s Respiratory Questionnaire (SGRQ) total score (combined data set).,Olodaterol + tiotropium resulted in significant improvements over tiotropium + placebo in FEV1 AUC0-3 (treatment differences: 0.117 L [P<0.001], ANHELTO 1; 0.106 L [P<0.001], ANHELTO 2) and trough FEV1 (treatment differences: 0.062 L [P<0.001], ANHELTO 1; 0.040 L [P=0.0029], ANHELTO 2); these were supported by secondary end points.,These effects translated to improvements in SGRQ total scores (treatment difference −1.85; P<0.0001).,The tolerability profile of olodaterol + tiotropium was similar to tiotropium monotherapy.,These studies demonstrated that olodaterol (Respimat®) and tiotropium (HandiHaler®) provided bronchodilatory effects above tiotropium alone in patients with COPD.,In general, both treatments were well tolerated.

GSK233705 is an inhaled, long-acting muscarinic antagonist in development for the treatment of chronic obstructive pulmonary disease (COPD).,This study was performed to see if the addition of GSK233705 to salmeterol would provide greater bronchodilation than salmeterol or tiotropium alone in COPD.,In an incomplete-block, three-period, crossover design, dually responsive patients received three of the following five treatments: GSK233705 20 μg plus salmeterol 50 μg twice-daily; GSK233705 50 μg plus salmeterol 50 μg twice-daily; salmeterol 50 μg or placebo, each twice-daily; and tiotropium 18 μg or placebo once-daily for 7 days.,Each treatment period was separated by a 14-day washout.,The primary efficacy endpoint was morning (trough) forced expiratory volume in 1 second (FEV1) on Day 8, following 7 days of treatment.,Secondary endpoints included pulmonary function, plethysmography, pharmacokinetics of GSK233705 and salmeterol, adverse events (AEs), electrocardiograms (ECGs), vital signs, and laboratory parameters.,A total of 47 patients were randomized.,The mean % predicted normal postbronchodilator FEV1 was 55% at screening.,Compared with placebo (n = 24), the adjusted mean change from baseline in trough FEV1 on Day 8 was 215 mL higher with GSK233705 20 μg + salmeterol (n = 23) and 203 mL higher with GSK233705 50 μg + salmeterol (n = 27), whereas with salmeterol (n = 27) and tiotropium (n = 28) the changes were 101 mL and 118 mL higher, respectively.,The primary efficacy results were supported by the results from the other secondary lung function assessments.,AEs were reported by similar proportions of patients across the treatment groups, with headache the most frequently reported treatment-related AE reported by one subject receiving each of GSK233705 20 μg + salmeterol, tiotropium, and placebo.,No significant differences were seen in vital signs, ECGs, or laboratory parameters between the groups.,The addition of GSK233705 to salmeterol in partially reversible COPD patients resulted in greater bronchodilation than salmeterol or tiotropium alone and was well tolerated.

Background: Glycopyrrolate administered by a novel, investigational eFlow® Closed System (CS) nebulizer (eFlow CS) is being evaluated for the maintenance treatment of chronic obstructive pulmonary disease (COPD).,The eFlow CS is a hand-held, vibrating membrane nebulizer optimized to deliver 1 mL of glycopyrrolate solution into the lung in <3 minutes.,Clinical studies have shown improvements in lung function of subjects treated with nebulized glycopyrrolate.,Methods: The aerosol performance of the eFlow CS nebulizer was characterized by delivered dose, aerodynamic droplet size distribution and nebulization time.,Simulated use nebulizer performance over 60 days was assessed by volume median diameter (VMD), nebulized amount, and nebulization time.,Nebulization outputs were assayed to ensure adequate delivery of glycopyrrolate with an acceptable impurity profile.,Aerosol condensates were analyzed for glycopyrrolate concentration and impurities by ultra-high-performance liquid chromatography and compared with non-nebulized samples.,Results: The mean mass median aerodynamic diameter, geometric standard deviation, and fine particle fraction were 3.7 μm, 1.7, and 72%, respectively, and independent of formulation strength (25 and 50 μg/mL).,Delivered dose was 88% of the nominal dose for both formulation strengths.,The mean delivered dose, assessed by breathing simulation, was 56.8% for 25 μg/mL and 62.6% for 50 μg/mL.,Nebulization times were 1-2.5 minutes with no apparent increasing trend with use over a 60-day period.,The nebulized amount showed no significant changes, whereas the VMD showed a slight, but not pharmaceutically relevant, increase (0.1-0.2 μm) after 60-day simulated use.,Glycopyrrolate concentration and impurity levels of nebulized samples were statistically similar to those of non-nebulized samples.,Conclusion: The eFlow CS generates glycopyrrolate aerosols with high delivered dose, short treatment time, and small droplet size with narrow size distribution suitable for central and peripheral airway deposition.,The unit dose vial mitigates medication misuse and ensures dose uniformity.,Results support the use of glycopyrrolate/eFlow CS for the treatment of COPD.

Chronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations.,This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE).,We studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers.,In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography.,COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function.,Co-morbidities were more prevalent in COPD patients than in controls, and occurred to the same extent irrespective of the GOLD stage.,The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, presence of co-morbidity, exercise capacity and number of exacerbations reported in the year before the study.,The distribution of these variables within each GOLD stage was wide.,Even in subjects with severe airflow obstruction, a substantial proportion did not report symptoms, exacerbations or exercise limitation.,The amount of emphysema increased with GOLD severity.,The prevalence of bronchiectasis was low (4%) but also increased with GOLD stage.,Some gender differences were also identified.,The clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease.

Influenza is a frequent cause of exacerbations of chronic obstructive pulmonary disease (COPD).,Exacerbations are associated with worsening of the airflow obstruction, hospitalisation, reduced quality of life, disease progression, death, and ultimately, substantial healthcare-related costs.,Despite longstanding recommendations to vaccinate vulnerable high-risk groups against seasonal influenza, including patients with COPD, vaccination rates remain sub-optimal in this population.,We conducted a systematic review to summarise current evidence from randomised controlled trials (RCTs) and observational studies on the immunogenicity, safety, efficacy, and effectiveness of seasonal influenza vaccination in patients with COPD.,The selection of relevant articles was based on a three-step selection procedure according to predefined inclusion and exclusion criteria.,The search yielded 650 unique hits of which 48 eligible articles were screened in full-text.,Seventeen articles describing 13 different studies were found to be pertinent to this review.,Results of four RCTs and one observational study demonstrate that seasonal influenza vaccination is immunogenic in patients with COPD.,Two studies assessed the occurrence of COPD exacerbations 14 days after influenza vaccination and found no evidence of an increased risk of exacerbation.,Three RCTs showed no significant difference in the occurrence of systemic effects between groups receiving influenza vaccine or placebo.,Six out of seven studies on vaccine efficacy or effectiveness indicated long-term benefits of seasonal influenza vaccination, such as reduced number of exacerbations, reduced hospitalisations and outpatient visits, and decreased all-cause and respiratory mortality.,Additional large and well-designed observational studies would contribute to understanding the impact of disease severity and patient characteristics on the response to influenza vaccination.,Overall, the evidence supports a positive benefit-risk ratio for seasonal influenza vaccination in patients with COPD, and supports current vaccination recommendations in this population.,The online version of this article (doi:10.1186/s12890-017-0420-8) contains supplementary material, which is available to authorized users.

Chronic obstructive pulmonary disease (COPD) is a progressive chronic disease where treatment decisions should be based on disease severity and also should be equally distributed across age, gender, and social situation.,The aim of this study was to determine to what extent patients with COPD are offered evidence-based interventions and how the interventions are distributed across demographic and clinical factors in the sample.,Baseline registrations of demographic, disease-related, and management-related variables of 7,810 patients in the Swedish National Airway Register are presented.,One-third of the patients were current smokers.,Patient-reported dyspnea and health-related quality of life were more deteriorated in elderly patients and patients living alone.,Only 34% of currently smoking patients participated in the smoking cessation programs, and 22% of all patients were enrolled in any patient education program, with women taking part in them more than men.,Less than 20% of the patients had any contact with physiotherapists or dieticians, with women having more contact than men.,Men had more comorbidities than women, except for depression and osteoporosis.,Women were more often given pharmacological treatments.,With increasing severity of dyspnea, participation in patient education programs was more common.,Dietician contact was more common in those with lower body mass index and more severe COPD stage.,Both dietician contact and physiotherapist contact increased with deteriorated health-related quality of life, dyspnea, and increased exacerbation frequency.,The present study showed that COPD management is mostly equally distributed across demographic characteristics.,Only a minority of the patients in the present study had interdisciplinary team contacts.,Thus, this data shows that the practical implementation of structured guidelines for treatment of COPD varies, to some extent, with regard to age and gender.,Also, disease characteristics influence guideline implementation for each individual patient.,Quality registers have the strength to follow-up on compliance with guidelines and show whether an intervention needs to be adapted prior to implementation in health care practice.

With great interest we read and commend the study done by Russo et al. [1], highlighting their findings that nicotine induces an increase in angiotensin-converting enzyme 2 (ACE-2) expression in human bronchial epithelial cells (HBEpC) and is mediated by α7-subtype nicotinic receptors (α7-nAChR).,It raises the concern that all electronic nicotine-delivery systems may put users at greater risk of succumbing to coronavirus disease 2019 (COVID-19).,Absolute cessation of any tobacco product in any form: implications for COVID-19https://bit.ly/3cyk9ra

We explore potential dysregulation of macrophage phenotypes in COPD pathogenesis through integrated study of human small airway tissue, bronchoalveolar lavage (BAL) and an experimental murine model of COPD.,We evaluated human airway tissue and BAL from healthy controls, normal lung function smokers (NLFS), and COPD subjects.,Both small airways and BAL cells were immunohistochemically stained with anti-CD68 for total macrophages and with anti-CD163 for M2, and anti-iNOS for M1 macrophages.,Multiplex ELISA measured BAL cytokines.,Comparable cigarette smoke-induced experimental COPD mouse model was assessed for relevant mRNA profiles.,We found an increase in pro-inflammatory M1s in the small airways of NLFS and COPD compared to controls with a reciprocal decrease in M2 macrophages, which remained unchanged among pathological groups.,However, luminal macrophages showed a dominant M2 phenotype in both NLFS and COPD subjects.,BAL cytokine skewed towards an M2 profile with increase in CCL22, IL-4, IL-13, and IL-10 in both NLFS and COPDs.,The mouse-model of COPD showed similar increase in mRNA for M2 markers.,Our finding suggests abnormal macrophage switching in both mucosal and luminal areas of COPD patients, that strongly associated with cytokine balance.,There may be potential for beneficial therapeutic cytokine manipulation of macrophage phenotypes in COPD.

Poor inhaler technique and nonadherence impair the efficacy of medications for asthma and chronic obstructive pulmonary disease (COPD).,A range of factors, including age, dexterity, inspiratory capacity, cognitive ability, health literacy, and ethnicity, can impact a patient's ability and intention to use their device.,Treatment success can also be influenced by patient preferences and perceptions.,Therefore, it is important that healthcare professionals effectively match inhaler devices to individual patients' needs and abilities and empower patients by including them in treatment decisions.,Physicians must, therefore, fully understand the characteristics of each device, as well as their patients' demographic characteristics and comorbidities.,Following device selection, patient training and education, including a physical demonstration of the device, are key to eliminate any critical errors that may impact on health outcomes.,Inhaler technique should be frequently rechecked.,This review will examine the important role of primary care providers in the selection of appropriate inhaler devices and provision of training for patients with COPD and asthma to optimize correct inhaler use and adherence.,An overview of the key features of available devices and of the factors to consider when selecting devices will be provided in the context of current asthma and COPD guidelines.

Ipratropium bromide/albuterol Respimat inhaler (CVT-R) was developed as an environmentally friendly alternative to ipratropium bromide/albuterol metered-dose inhaler (CVT-MDI), which uses a chlorofluorocarbon propellant.,The objective of this study was to evaluate patient satisfaction, device usage, and long-term safety of CVT-R compared to CVT-MDI, and to the simultaneous administration of ipratropium bromide hydrofluoroalkane (HFA; I) and albuterol HFA (A) metered-dose inhalers as dual monotherapies (I + A).,This is a 48-week, open-label, randomized, active-controlled, parallel-group study (n = 470) comparing CVT-R to CVT-MDI and to I + A.,Patients were at least 40 years of age, diagnosed with chronic obstructive pulmonary disease (COPD), and current or exsmokers.,Patients were randomized to receive: (1) CVT-R, one inhalation four times daily (QID); or (2) CVT-MDI, two inhalations QID; or (3) I + A two inhalations of each inhaler QID.,Patient Satisfaction and Preference Questionnaire (PASAPQ) performance score (primary endpoint) and adverse events.,PASAPQ performance score was significantly higher (CVT-R versus CVT-MDI, 9.6; and CVT-R versus I + A, 6.2; both P < 0.001) when using CVT-R compared to CVT-MDI or I + A at all visits starting from week 3, while CVT-MDI and I + A treatment groups were similar.,Time to first COPD exacerbation was slightly longer in the CVT-R group compared to the other treatment groups, although it did not reach statistical significance (CVT-R versus CVT-MDI, P = 0.57; CVT-R versus I + A, P = 0.22).,Rates of withdrawal and patient refusal to continue treatment were lower in CVT-R compared with CVT-MDI and I + A groups (CVT-R versus CVT-MDI, P = 0.09; CVT-R versus I + A, P = 0.005).,The percentage of patients reporting adverse events and serious adverse events was similar across all three treatment groups.,CVT-R is an effective, environmentally friendly inhaler that provides patients with a high level of user satisfaction and may positively impact clinical outcomes while having no adverse impacts on patients using the device.

Nontypeable Haemophilus influenzae (NTHi) is the most common cause for bacterial exacerbations in chronic obstructive pulmonary disease (COPD).,Recent investigations suggest the participation of the inflammasome in the pathomechanism of airway inflammation.,The inflammasome is a cytosolic protein complex important for early inflammatory responses, by processing Interleukin-1β (IL-1β) to its active form.,Since inflammasome activation has been described for a variety of inflammatory diseases, we investigated whether this pathway plays a role in NTHi infection of the airways.,A murine macrophage cell line (RAW 264.7), human alveolar macrophages and human lung tissue (HLT) were stimulated with viable or non-viable NTHi and/or nigericin, a potassium ionophore.,Secreted cytokines were measured with ELISA and participating proteins detected via Western Blot or immunohistochemistry.,Western Blot analysis of cells and immunohistochemistry of lung tissue detected the inflammasome key components NLRP3 and caspase-1 after stimulation, leading to a significant induction of IL-1β expression (RAW: control at the lower detection limit vs.,NTHi 505±111pg/ml, p<0.01).,Inhibition of caspase-1 in human lung tissue led to a significant reduction of IL-1β and IL-18 levels (IL-1β: NTHi 24 h 17423±3198pg/ml vs.,NTHi+Z-YVAD-FMK 6961±1751pg/ml, p<0.01).,Our data demonstrate the upregulation of the NRLP3-inflammasome during NTHi-induced inflammation in respiratory cells and tissues.,Our findings concerning caspase-1 dependent IL-1β release suggest a role for the inflammasome in respiratory tract infections with NTHi which may be relevant for the pathogenesis of bacterial exacerbations in COPD.

► Nrf2 anti-oxidant function is impaired when HDAC activity is inhibited.,► HDAC inhibition decreases Nrf2 protein stability.,► HDAC2 is involved in reduced Nrf2 stability and both correlate in COPD samples.,► HDAC inhibition increases Nrf2 acetylation.,Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes.,However, where high levels of oxidative stress are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although the molecular mechanism for this defect is uncertain.,Here, we show that down-regulation of histone deacetylase (HDAC) 2 causes Nrf2 instability, resulting in reduced anti-oxidant gene expression and increase sensitivity to oxidative stress.,Although Nrf2 protein was clearly stabilized after hydrogen peroxide (H2O2) stimulation in a bronchial epithelial cell line (BEAS2B), Nrf2 stability was decreased and Nrf2 acetylation increased in the presence of an HDAC inhibitor, trichostatin A (TSA).,TSA also reduced Nrf2-regulated heme-oxygenase-1 (HO-1) expression in these cells, and this was confirmed in acute cigarette-smoke exposed mice in vivo.,HDAC2 knock-down by RNA interference resulted in reduced H2O2-induced Nrf2 protein stability and activity in BEAS2B cells, whereas HDAC1 knockdown had no effect.,Furthermore, monocyte-derived macrophages obtained from healthy volunteers (non-smokers and smokers) and COPD patients showed a significant correlation between HDAC2 expression and Nrf2 expression (r = 0.92, p < 0.0001).,Thus, reduced HDAC2 activity in COPD may account for increased Nrf2 acetylation, reduced Nrf2 stability and impaired anti oxidant defences.

The Continuing to Confront COPD International Patient Survey aimed to estimate the prevalence and burden of COPD globally and to update findings from the Confronting COPD International Survey conducted in 1999-2000.,Chronic obstructive pulmonary disease (COPD) patients in 12 countries worldwide were identified through systematic screening of population samples.,Telephone and face-to-face interviews were conducted between November 2012 and May 2013 using a structured survey that incorporated validated patient-reported outcome instruments.,Eligible patients were adults aged 40 years and older who were taking regular respiratory medications or suffered with chronic respiratory symptoms and reported either 1) a physician diagnosis of COPD/emphysema, 2) a physician diagnosis of chronic bronchitis, or 3) a symptom-based definition of chronic bronchitis.,The burden of COPD was measured with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) Dyspnea Scale.,Of 106,876 households with at least one person aged ≥40 years, 4,343 respondents fulfilled the case definition of COPD and completed the full survey.,COPD prevalence ranged from 7% to 12%, with most countries falling within the range of 7%-9%.,In all countries, prevalence increased with age, and in all countries except the US was greater among men (range 6%-14%) than among women (range 5%-11%).,A significant disease burden was observed when considering COPD symptoms or health status, and showed wide variations across countries.,Prevalence of moderate-to-severe dyspnea (mMRC scale ≥2) ranged from 27% to 61%, and mean CAT score ranged from 16.0 to 24.8, indicating medium-to-high impairment.,This survey, representing 12 countries, showed similar rates of estimated COPD prevalence across countries that were higher than those reported a decade ago in the original Confronting COPD International Survey.,A significant burden of COPD was demonstrated by symptoms and health care-resource use, similar to that reported in the original survey.

Never smokers comprise a substantial proportion of patients with COPD.,Their characteristics and possible risk factors in this population are not yet well defined.,We analyzed data from 14 countries that participated in the international, population-based Burden of Obstructive Lung Disease (BOLD) study.,Participants were aged ≥ 40 years and completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors.,A diagnosis of COPD was based on the postbronchodilator FEV1/FVC ratio, according to current GOLD (Global Initiative for Obstructive Lung Disease) guidelines.,In addition to this, the lower limit of normal (LLN) was evaluated as an alternative threshold for the FEV1/FVC ratio.,Among 4,291 never smokers, 6.6% met criteria for mild (GOLD stage I) COPD, and 5.6% met criteria for moderate to very severe (GOLD stage II+) COPD.,Although never smokers were less likely to have COPD and had less severe COPD than ever smokers, never smokers nonetheless comprised 23.3% (240/1,031) of those classified with GOLD stage II+ COPD.,This proportion was similar, 20.5% (171/832), even when the LLN was used as a threshold for the FEV1/FVC ratio.,Predictors of COPD in never smokers include age, education, occupational exposure, childhood respiratory diseases, and BMI alterations.,This multicenter international study confirms previous evidence that never smokers comprise a substantial proportion of individuals with COPD.,Our data suggest that, in addition to increased age, a prior diagnosis of asthma and, among women, lower education levels are associated with an increased risk for COPD among never smokers.

Long-acting bronchodilators have been shown to improve multiple clinical outcomes in chronic obstructive pulmonary disease (COPD) including lung function, symptoms, dyspnea, quality of life, and exacerbations.,Indacaterol is a novel, inhaled, long-acting β2-agonist providing 24-hour bronchodilation with once-daily dosing.,It is currently approved for the maintenance treatment of COPD to be administered as 150 or 300 μg once-daily doses as licensed in many countries and 75 μg as licensed in the US by means of a single-dose dry powder inhaler.,The data from clinical development support a favorable safety and tolerability profile within the β2-agonist drug class, with no relevant issues identified.,Current evidence indicates that indacaterol is suitable for use as first-line monotherapy in COPD patients with moderate disease (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage II) and beyond that do not require an inhaled corticosteroid (ICS) as per GOLD guidelines, or in combination with an ICS in severe or very severe patients with repeated exacerbations.,Data from trials with the novel once-daily β2-agonist, indacaterol, indicate superior bronchodilation and clinical efficacy over twice-daily long-acting β2-agonists and at least equipotent bronchodilation as once-daily tiotropium.,Bronchodilators are central in the symptomatic management of COPD.,It is likely that once-daily dosing of a bronchodilator would be a significant convenience and probably a compliance-enhancing advantage, leading to improved overall clinical outcomes in patients with COPD.

For optimal efficacy, an inhaler should deliver doses consistently and be easy for patients to use with minimal instruction.,The delivery characteristics, patients’ correct use, and preference of two single-dose dry powder inhalers (Breezhaler and HandiHaler) were evaluated in two complementary studies.,The first study examined aerodynamic particle size distribution, using inhalation profiles of seven patients with moderate to very severe chronic obstructive pulmonary disease (COPD).,The second was an open-label, two-period, 7-day crossover study, evaluating use of the inhalers with placebo capsules by 82 patients with mild to severe COPD.,Patients’ correct use of the inhalers was assessed after reading written instructions on Day 1, and after training and 7 days of daily use.,Patients’ preference was assessed after completion of both study periods.,Patient inhalation profiles showed average peak inspiratory flows of 72 L/minute through Breezhaler and 36 L/minute through HandiHaler.,For Breezhaler and HandiHaler, fine particle fractions were 27% and 10%, respectively.,In the second study, correct use of Breezhaler and HandiHaler was achieved by >77% of patients for any step after 7 days; 61% of patients showed an overall preference for Breezhaler and 31% for HandiHaler (P = 0.01).,Breezhaler is a low-resistance inhaler suitable for use by patients with a range of disease severities.,Most patients used both inhalers correctly after 7 days, but more patients showed an overall preference for the Breezhaler compared with the HandiHaler.,These are important factors for optimum dose delivery and successful COPD management.

To integrate evidence from randomised controlled trials (RCTs) and observational studies on the efficacy of inhaled treatments for chronic obstructive pulmonary disease using network meta-analyses.,Systematic searches MEDLINE and Embase based on predetermined criteria.,Network meta-analyses of RCTs investigated efficacy on exacerbations (long-term: ≥20 weeks of treatment; short-term: <20 weeks), lung function (≥12 weeks), health-related quality of life, mortality and adverse events.,Qualitative comparisons of efficacies between RCTs and observational studies.,212 RCTs and 19 observational studies were included.,Compared with combined long-acting beta-adrenoceptor agonists and long-acting muscarinic antagonists (LABA+LAMA), triple therapy (LABA+LAMA+inhaled corticosteroid) was significantly more effective at reducing exacerbations (long-term 0.85 (95% CI: 0.78 to 0.94; short-term 0.67 (95% CI: 0.49 to 0.92)) and mortality (0.72 (95% CI: 0.59 to 0.89)) but was also associated with increased pneumonia (1.35 (95% CI: 1.10 to 1.67)).,No differences in lung function (0.02 (95% CI: −0.10 to 0.14)), health-related quality of life (−1.12 (95% CI: −3.83 to 1.59)) or other adverse events (1.02 (95% CI: 0.96 to 1.08)) were found.,Most of the observational evidence trended in the same direction as pooled RCT data.,Further evidence, especially pragmatic trials, are needed to fully understand the characteristics of patient subgroups who may benefit from triple therapy and for those whom the extra risk of adverse events, such as pneumonia, may outweigh any benefits.,CRD42018088013.

Combinations of drugs with distinct and complementary mechanisms of action may offer improved efficacy in the treatment of chronic obstructive pulmonary disease (COPD).,In two 12-week, double-blind, parallel-group studies, patients with COPD were randomized 1:1:1 to once-daily umeclidinium (UMEC; 62.5 μg and 125 μg) or placebo (PBO), added to twice-daily fluticasone propionate/salmeterol (FP/SAL; 250/50 μg).,In both studies, the primary efficacy measure was trough forced expiratory volume in 1 second (FEV1) at Day 85.,Secondary endpoints were weighted-mean (WM) FEV1 over 0-6 hours post-dose (Day 84) and rescue albuterol use.,Health-related quality of life outcomes (St.,George's Respiratory Questionnaire [SGRQ] and COPD assessment test [CAT]) were also examined.,Safety was assessed throughout.,Both UMEC+FP/SAL doses provided statistically significant improvements in trough FEV1 (Day 85: 0.127-0.148 L) versus PBO+FP/SAL.,Similarly, both UMEC+FP/SAL doses provided statistically-significant improvements in 0-6 hours post-dose WM FEV1 versus PBO+FP/SAL (Day 84: 0.144-0.165 L).,Rescue use over Weeks 1-12 decreased with UMEC+FP/SAL in both studies versus PBO+FP/SAL (Study 1, 0.3 puffs/day [both doses]; Study 2, 0.5 puffs/day [UMEC 125+FP/SAL]).,Decreases from baseline in CAT score were generally larger for both doses of UMEC+FP/SAL versus PBO+FP/SAL (except for Day 84 Study 2).,In Study 1, no differences in SGRQ score were observed between UMEC+FP/SAL and PBO+FP/SAL; however, in Study 2, statistically significant improvements were observed with UMEC 62.5+FP/SAL (Day 28) and UMEC 125+FP/SAL (Days 28 and 84) versus PBO+FP/SAL.,The incidence of on-treatment adverse events across all treatment groups was 37-41% in Study 1 and 36-38% in Study 2.,Overall, these data indicate that the combination of UMEC+FP/SAL can provide additional benefits over FP/SAL alone in patients with COPD.

Chronic obstructive pulmonary disease (COPD) is often associated with age-related systemic abnormalities that adversely affect the prognosis.,Whether these manifestations are linked to the lung alterations or are independent complications of smoking remains unclear.,To look for aging-related systemic manifestations and telomere shortening in COPD patients and smokers with minor lung destruction responsible for a decline in the diffusing capacity for carbon monoxide (DLCO) corrected for alveolar volume (KCO).,Cross-sectional study in 301 individuals (100 with COPD, 100 smokers without COPD, and 101 nonsmokers without COPD).,Compared to control smokers, patients with COPD had higher aortic pulse-wave velocity (PWV), lower bone mineral density (BMD) and appendicular skeletal muscle mass index (ASMMI), and shorter telomere length (TL).,Insulin resistance (HOMA-IR) and glomerular filtration rate (GFR) were similar between control smokers and COPD patients.,Smokers did not differ from nonsmokers for any of these parameters.,However, smokers with normal spirometry but low KCO had lower ASMMI values compared to those with normal KCO.,Moreover, female smokers with low KCO, had lower BMD and shorter TL compared to those with normal KCO.,Aging-related abnormalities in patients with COPD are also found in smokers with minor lung dysfunction manifesting as a KCO decrease.,Decreased KCO might be useful, particularly among women, for identifying smokers at high risk for aging-related systemic manifestations and telomere shortening.

Muscle dysfunction is a major comorbidity in Chronic Obstructive Pulmonary Disease (COPD).,Several biological mechanisms including epigenetic events regulate muscle mass and function in models of muscle atrophy.,Investigations conducted so far have focused on the elucidation of biological mechanisms involved in muscle dysfunction in advanced COPD.,We assessed whether the epigenetic profile may be altered in the vastus lateralis of patients with mild COPD, normal body composition, and mildly impaired muscle function and exercise capacity.,In vastus lateralis (VL) of mild COPD patients with well-preserved body composition and in healthy age-matched controls, expression of DNA methylation, muscle-enriched microRNAs, histone acetyltransferases (HTAs) and deacetylases (HDACs), protein acetylation, small ubiquitin-related modifier (SUMO) ligases, and muscle structure were explored.,All subjects were clinically evaluated.,Compared to healthy controls, in the VL of mild COPD patients, muscle function and exercise capacity were moderately reduced, DNA methylation levels did not differ, miR-1 expression levels were increased and positively correlated with both forced expiratory volume in one second (FEV1) and quadriceps force, HDAC4 protein levels were increased, and muscle fiber types and sizes were not different.,Moderate skeletal muscle dysfunction is a relevant feature in patients with mild COPD and preserved body composition.,Several epigenetic events are differentially expressed in the limb muscles of these patients, probably as an attempt to counterbalance the underlying mechanisms that alter muscle function and mass.,The study of patients at early stages of their disease is of interest as they are a target for timely therapeutic interventions that may slow down the course of the disease and prevent the deleterious effects of major comorbidities.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease with a high prevalence of extrapulmonary manifestations and, frequently, cardiovascular comorbidity.,Resveratrol is a food-derived compound with anti-inflammatory, antioxidant, metabolic and cardioprotective potential.,Therefore, resveratrol might improve the pulmonary as well as extrapulmonary pathology in COPD.,In this review, we will evaluate knowledge on the effects of resveratrol on lung injury, muscle metabolism and cardiovascular risk profile and discuss if resveratrol is a hype or hope for patients with COPD.,Experimental models of COPD consistently show decreased inflammation and oxidative stress in the lungs after resveratrol treatment.,These beneficial anti-inflammatory and antioxidant properties of resveratrol can indirectly also improve both skeletal and respiratory muscle impairment in COPD.,Recent clinical studies in non-COPD populations show improved mitochondrial oxidative metabolism after resveratrol treatment, which could be beneficial for both lung and muscle impairment in COPD.,Moreover, preclinical studies suggest cardioprotective effects of resveratrol but results of clinical studies are inconclusive.,Resveratrol might be an interesting therapeutic candidate to counteract lung and muscle impairments characteristic to COPD.,However, there is no convincing evidence that resveratrol will significantly decrease the cardiovascular risk in patients with COPD.

Community-acquired pneumonia (CAP) is more common in patients with COPD than in the adult general population, with studies of hospitalized CAP patients consistently reporting COPD as a frequent comorbidity.,However, despite an increasing recognition of its importance, large studies evaluating the incidence patterns over time, risk factors and burden of CAP in COPD are currently lacking.,A retrospective observational study using a large UK-based database of linked primary and secondary care records was conducted.,Patients with a diagnosis of COPD aged ≥40 years were followed up for 5 years from January 1, 2010.,CAP and exacerbation episodes were identified from hospital discharge data and primary care coding records, and rates were calculated per month, adjusting for mortality, and displayed over time.,In addition, baseline factors predicting future risk of CAP and hospital admission with CAP were identified.,A total of 14,513 COPD patients were identified: 13.4% (n=1,938) had ≥1 CAP episode, of whom 18.8% suffered from recurrent (≥2) CAP.,Highest rates of both CAP and exacerbations were seen in winter.,A greater proportion of frequent, compared to infrequent, exacerbators experienced recurrent CAP (5.1% versus 2.0%, respectively, P<0.001); 75.6% of CAP episodes were associated with hospital admission compared to 22.1% of exacerbations.,Older age and increasing grade of airflow limitation were independently associated with increased odds of CAP and hospital admission with CAP.,Other independent predictors of future CAP included lower body mass index, inhaled corticosteroid use, prior frequent exacerbations and comorbidities, including ischemic heart disease and diabetes.,CAP in COPD demonstrates clear seasonal patterns, with patient characteristics predictive of the odds of future CAP and hospital admission with CAP.,Highlighting this burden of COPD-associated CAP during the winter period informs us of the likely triggers and the need for more effective preventive strategies.

The long-acting muscarinic antagonist (LAMA) umeclidinium (UMEC) and the combination of UMEC with the long-acting β2-agonist (LABA) vilanterol (UMEC/VI) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD) in the US and EU.,They are not indicated for the treatment of asthma.,In this 52-week, double-blind, placebo-controlled, parallel-group safety study (GSK study DB2113359; NCT01316887), patients were randomized 2:2:1 to UMEC/VI 125/25 mcg, UMEC 125 mcg, or placebo.,Study endpoints included adverse events (AEs), clinical chemistry and hematology parameters, vital signs, 12-lead, and 24-hour Holter electrocardiograms.,COPD exacerbations and rescue medication use were assessed as safety parameters; lung function was also evaluated.,The incidence of on-treatment AEs, serious AEs (SAEs), and drug-related AEs was similar between treatment groups (AEs: 52-58%; SAEs: 6-7%; drug-related AEs: 12-13%).,Headache was the most common AE in each treatment group (8-11%).,AEs associated with the LAMA and LABA pharmacologic classes occurred at a low incidence across treatment groups.,No clinically meaningful effects on vital signs or laboratory assessments were reported for active treatments versus placebo.,The incidences of atrial arrhythmias with UMEC/VI 125/25 mcg were similar to placebo; for UMEC 125 mcg, the incidences of ectopic supraventricular beats, sustained supraventricular tachycardia, and ectopic supraventricular rhythm were ≥2% greater than placebo.,With active treatments, COPD exacerbations were fewer (13-15% of patients reporting ≥1 exacerbation) and on average less rescue medication was required (1.6-2.2 puffs/day) versus placebo (24% reporting ≥1 exacerbation, 2.6 puffs/day).,Both active treatments improved lung function versus placebo.,UMEC/VI 125/25 mcg and UMEC 125 mcg were well tolerated over 12 months in patients with COPD.

Relationships between improvements in lung function and other clinical outcomes in chronic obstructive pulmonary disease (COPD) are not documented extensively.,We examined whether changes in trough forced expiratory volume in 1 second (FEV1) are correlated with changes in patient-reported outcomes.,Pooled data from three indacaterol studies (n = 3313) were analysed.,Means and responder rates for outcomes including change from baseline in Transition Dyspnoea Index (TDI), St.,George's Respiratory Questionnaire (SGRQ) scores (at 12, 26 and 52 weeks), and COPD exacerbation frequency (rate/year) were tabulated across categories of ΔFEV1.,Also, generalised linear modelling was performed adjusting for covariates such as baseline severity and inhaled corticosteroid use.,With increasing positive ΔFEV1, TDI and ΔSGRQ improved at all timepoints, exacerbation rate over the study duration declined (P < 0.001).,Individual-level correlations were 0.03-0.18, but cohort-level correlations were 0.79-0.95.,At 26 weeks, a 100 ml increase in FEV1 was associated with improved TDI (0.46 units), ΔSGRQ (1.3-1.9 points) and exacerbation rate (12% decrease).,Overall, adjustments for baseline covariates had little impact on the relationship between ΔFEV1 and outcomes.,These results suggest that larger improvements in FEV1 are likely to be associated with larger patient-reported benefits across a range of clinical outcomes.,ClinicalTrials.gov NCT00393458, NCT00463567, and NCT00624286

Chronic obstructive pulmonary disease (COPD) is a respiratory disease that results in airflow limitation and respiratory distress, also having many nonrespiratory manifestations that affect both function and mobility.,Preliminary evidence suggests that balance deficits constitute an important secondary impairment in individuals with COPD.,Our objective was to investigate balance performance in two groups of COPD patients with different body compositions and to observe which of these groups are more likely to experience falls in the future.,We included 27 stable COPD patients and 17 healthy individuals who performed a series of balance tests.,The COPD patients were divided in two groups: emphysematous and bronchitic.,Patients completed the activities balance confidence scale and the COPD assessment test questionnaire and afterward performed the Berg Balance Scale, timed up and go, single leg stance and 6-minute walking distance test.,We analyzed the differences in the balance tests between the studied groups.,Bronchitic COPD was associated with a decreased value when compared to emphysematous COPD for the following variables: single leg stance (8.7 vs 15.6; P<0.001) and activities balance confidence (53.2 vs 74.2; P=0.001).,Bronchitic COPD patients had a significantly higher value of timed up and go test compared to patients with emphysematous COPD (14.7 vs 12.8; P=0.001).,Patients with COPD have a higher balance impairment than their healthy peers.,Moreover, we observed that the bronchitic COPD phenotype is more likely to experience falls compared to the emphysematous phenotype.

To date, detailed analyses of walking patterns using accelerometers during the 6-min walk test (6MWT) have not been performed in patients with chronic obstructive pulmonary disease (COPD).,Therefore, it remains unclear whether and to what extent COPD patients have an altered walking pattern during the 6MWT compared to healthy elderly subjects.,79 COPD patients and 24 healthy elderly subjects performed the 6MWT wearing an accelerometer attached to the trunk.,The accelerometer features (walking intensity, cadence, and walking variability) and subject characteristics were assessed and compared between groups.,Moreover, associations were sought with 6-min walk distance (6MWD) using multiple ordinary least squares (OLS) regression models.,COPD patients walked with a significantly lower walking intensity, lower cadence and increased walking variability compared to healthy subjects.,Walking intensity and height were the only two significant determinants of 6MWD in healthy subjects, explaining 85% of the variance in 6MWD.,In COPD patients also age, cadence, walking variability measures and their interactions were included were significant determinants of 6MWD (total variance in 6MWD explained: 88%).,COPD patients have an altered walking pattern during 6MWT compared to healthy subjects.,These differences in walking pattern partially explain the lower 6MWD in patients with COPD.

While the efficacy and safety of combined tiotropium and olodaterol in patients with COPD was established in a large clinical trial program, it is important to assess whether clinical data can be applied to geographic patient groups, particularly for East Asian patients who may have a different phenotypic profile to the global trial population.,This study aimed to compare the lung function and safety profiles of tiotropium/olodaterol and monocomponents in East Asian and global populations from the TONADO® trials.,In the replicate, double-blind, parallel-group, active-controlled, randomized, 52-week, Phase III TONADO studies, patients received tiotropium/olodaterol, tiotropium, or olodaterol.,We assessed the forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 3 hours (AUC0-3) response and trough FEV1 response at 24 weeks for the approved doses, tiotropium/olodaterol 5/5 μg, tiotropium 5 μg, and olodaterol 5 μg.,Treatment-emergent adverse events were recorded throughout treatment and ≤21 days after study medication.,In the East Asian population, 1,152 patients were randomized (5,163 overall).,After 24 weeks, FEV1 AUC0-3 and trough FEV1 responses were greater (P<0.0001) with tiotropium/olodaterol 5/5 μg in both populations versus tiotropium or olodaterol.,The East Asian population showed slightly greater trough FEV1 treatment differences between tiotropium/olodaterol 5/5 μg and tiotropium compared to the overall population.,Generally, no increase in adverse events was seen with tiotropium/olodaterol 5/5 μg compared to tiotropium and olodaterol in either population.,The efficacy and safety profile of tiotropium/olodaterol 5/5 μg has been demonstrated for both East Asian and global populations.

Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.,Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks.,Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.,In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment.,Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies.,Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg.,Incidence of adverse events was comparable between the FDCs and the mono-components.,These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.,Lung function and symptomatic benefits of daily tiotropium+olodaterol fixed-dose combination in moderate to very severe COPDhttp://ow.ly/DIKiY

Chronic obstructive pulmonary disease (COPD) is characterized by an abnormal and chronic inflammatory response in the lung that underlies the chronic airflow obstruction of the small airways, the inexorable decline of lung function, and the severity of the disease.,The control of this inflammation remains a key strategy for treating the disease; however, there are no current anti-inflammatory treatments that are effective.,Although glucocorticoids (GCs) effectively control inflammation in many diseases such as asthma, they are less effective in COPD.,The molecular mechanisms that contribute to the development of this relative GC-insensitive inflammation in the lung of patients with COPD remain unclear.,However, recent studies have indicated novel mechanisms and possible therapeutic strategies.,One of the major mechanisms proposed is an oxidant-mediated alteration in the signaling pathways in the inflammatory cells in the lung, which may result in the impairment of repressor proteins used by the GC receptor to inhibit the transcription of proinflammatory genes.,Although these studies have described mechanisms and targets by which GC function can be restored in cells from patients with COPD, more work is needed to completely elucidate these and other pathways that may be involved in order to allow for more confident therapeutic targeting.,Given the relative GC-insensitive nature of the inflammation in COPD, a combination of therapies in addition to a restoration of GC function, including effective alternative anti-inflammatory targets, antioxidants, and proresolving therapeutic strategies, is likely to provide better targeting and improvement in the management of the disease.

Genetic factors play a role in chronic obstructive pulmonary disease (COPD) but are poorly understood.,A number of candidate genes have been proposed on the basis of the pathogenesis of COPD.,These include the matrix metalloproteinase (MMP) genes which play a role in tissue remodelling and fit in with the protease - antiprotease imbalance theory for the cause of COPD.,Previous genetic studies of MMPs in COPD have had inadequate coverage of the genes, and have reported conflicting associations of both single nucleotide polymorphisms (SNPs) and SNP haplotypes, plausibly due to under-powered studies.,To address these issues we genotyped 26 SNPs, providing comprehensive coverage of reported SNP variation, in MMPs- 1, 9 and 12 from 977 COPD patients and 876 non-diseased smokers of European descent and evaluated their association with disease singly and in haplotype combinations.,We used logistic regression to adjust for age, gender, centre and smoking history.,Haplotypes of two SNPs in MMP-12 (rs652438 and rs2276109), showed an association with severe/very severe disease, corresponding to GOLD Stages III and IV.,Those with the common A-A haplotype for these two SNPs were at greater risk of developing severe/very severe disease (p = 0.0039) while possession of the minor G variants at either SNP locus had a protective effect (adjusted odds ratio of 0.76; 95% CI 0.61 - 0.94).,The A-A haplotype was also associated with significantly lower predicted FEV1 (42.62% versus 44.79%; p = 0.0129).,This implicates haplotypes of MMP-12 as modifiers of disease severity.

Airway absorption and bioavailability of inhaled corticosteroids (ICSs) may be influenced by differences in pharmacokinetic properties such as lipophilicity and patient characteristics such as lung function.,This study aimed to further investigate and clarify the distribution of budesonide and fluticasone in patients with severe chronic obstructive pulmonary disease (COPD) by measuring the systemic availability and sputum concentration of budesonide and fluticasone, administered via combination inhalers with the respective long-acting β2-agonists, formoterol and salmeterol.,This was a randomized, double-blind, double-dummy, two-way crossover, multicenter study.,Following a run-in period, 28 patients with severe COPD (mean age 65 years, mean forced expiratory volume in 1 second [FEV1] 37.5% predicted normal) and 27 healthy subjects (mean age 31 years, FEV1 103.3% predicted normal) received two single-dose treatments of budesonide/formoterol (400/12 μg) and salmeterol/fluticasone (50/500 μg), separated by a 4-14-day washout period.,ICS concentrations were measured over 10 hours post-inhalation in plasma in all subjects, and over 6 hours in spontaneously expectorated sputum in COPD patients.,The primary end point was the area under the curve (AUC) of budesonide and fluticasone plasma concentrations in COPD patients relative to healthy subjects.,Mean plasma AUC values were lower in COPD patients versus healthy subjects for budesonide (3.07 μM·hr versus 6.21 μM·hr) and fluticasone (0.84 μM·hr versus 1.50 μM·hr), and the dose-adjusted AUC (geometric mean) ratios in healthy subjects and patients with severe COPD for plasma budesonide and fluticasone were similar (2.02 versus 1.80; primary end point).,In COPD patients, the Tmax and the mean residence time in the systemic circulation were shorter for budesonide versus fluticasone (15.5 min versus 50.8 min and 4.41 hrs versus 12.78 hrs, respectively) and Cmax was higher (1.08 μM versus 0.09 μM).,The amount of expectorated fluticasone (percentage of estimated lung-deposited dose) in sputum over 6 hours was significantly higher versus budesonide (ratio 5.21; p = 0.006).,Both treatments were well tolerated.,The relative systemic availabilities of budesonide and fluticasone between patients with severe COPD and healthy subjects were similar.,In patients with COPD, a larger fraction of fluticasone was expectorated in the sputum as compared with budesonide.,Trial registration number NCT00379028

The efficacy of inhaled salmeterol plus fluticasone propionate (SFC) in patients with severe or very severe COPD is well documented.,However, there are only limited data about the influence of GOLD severity staging on the effectiveness of SFC, particularly in patients with milder disease.,TORCH was a 3-year, double-blind, placebo-controlled trial of 6112 patients with moderate/severe COPD with pre-bronchodilator FEV1 < 60% predicted (mean age 65 years, 76% male, mean 44% predicted FEV1, 43% current smokers).,To understand the relative efficacy of SFC and its components by GOLD stages, we conducted a post-hoc analysis of the TORCH dataset using baseline post-bronchodilator FEV1 to segment patients into three groups: moderate COPD (GOLD stage II and above: ≥ 50%; n = 2156), severe COPD (GOLD stage III: 30% to < 50%; n = 3019) and very severe COPD (GOLD stage IV: < 30%; n = 937).,Compared with placebo, SFC improved post-bronchodilator FEV1: 101 ml (95% confidence interval [CI]: 71, 132) in GOLD stage II, 82 ml (95% CI: 60, 104) in GOLD stage III and 96 ml (95% CI: 54, 138) in GOLD stage IV patients, and reduced the rate of exacerbations: 31% (95% CI: 19, 40) in GOLD stage II, 26% (95% CI: 17, 34) in GOLD stage III and 14% (95% CI: -4, 29) in GOLD stage IV.,SFC improved health status to a greater extent than other treatments regardless of baseline GOLD stage.,Similarly, SFC reduced the risk of death by 33% (hazard ratio [HR] 0.67; 95% CI: 0.45, 0.98) for GOLD stage II, 5% (HR 0.95; 95% CI: 0.73, 1.24) for GOLD stage III, and 30% (HR 0.70; 95% CI: 0.47, 1.05) for GOLD stage IV.,The rates of adverse events were similar across treatment arms and increased with disease severity.,Overall, there was a higher incidence of pneumonia in the fluticasone propionate and SFC arms, compared with other treatments in all GOLD stages.,In the TORCH study, SFC reduced moderate-to-severe exacerbations and improved health status and FEV1 across GOLD stages.,Treatment with SFC may be associated with reduced mortality compared with placebo in patients with GOLD stage II disease.,The effects were similar to those reported for the study as a whole.,Thus, SFC is an effective treatment option for patients with GOLD stage II COPD.,Clinicaltrial.gov registration NCT00268216; Study number: SCO30003

To have a better understanding of the mechanisms of exercise limitation in mild-to-moderate chronic obstructive pulmonary disease (COPD), we compared detailed respiratory physiology in patients with COPD and healthy age- and sex-matched controls.,Data were collected during the pre-treatment, patient characterization phase of a multicenter, randomized, double-blind, crossover study.,Patients with COPD met Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 or 2 spirometric criteria, were symptomatic, and had evidence of gas trapping during exercise.,All participants completed pulmonary function and symptom-limited incremental treadmill exercise tests.,Chronic activity-related dyspnea measured by Baseline Dyspnea Index was similarly increased in patients with GOLD 1 (n = 41) and 2 (n = 63) COPD compared with controls (n = 104).,Plethysmographic lung volumes were increased and lung diffusing capacity was decreased in both GOLD groups.,Peak oxygen uptake and work rate were reduced in both GOLD groups compared with controls (p<0.001).,Submaximal ventilation, dyspnea, and leg discomfort ratings were higher for a given work rate in both GOLD groups compared with controls.,Resting inspiratory capacity, peak ventilation, and tidal volume were reduced in patients with GOLD 2 COPD compared with patients with GOLD 1 COPD and controls (p<0.001).,Lower exercise tolerance in patients with GOLD 1 and 2 COPD compared with controls was explained by greater mechanical abnormalities, greater ventilatory requirements, and increased subjective discomfort.,Lower resting inspiratory capacity in patients with GOLD 2 COPD was associated with greater mechanical constraints and lower peak ventilation compared with patients with GOLD 1 COPD and controls.,ClinicalTrials.gov: NCT01072396

The efficacy of inhaled salmeterol plus fluticasone propionate (SFC) in patients with severe or very severe COPD is well documented.,However, there are only limited data about the influence of GOLD severity staging on the effectiveness of SFC, particularly in patients with milder disease.,TORCH was a 3-year, double-blind, placebo-controlled trial of 6112 patients with moderate/severe COPD with pre-bronchodilator FEV1 < 60% predicted (mean age 65 years, 76% male, mean 44% predicted FEV1, 43% current smokers).,To understand the relative efficacy of SFC and its components by GOLD stages, we conducted a post-hoc analysis of the TORCH dataset using baseline post-bronchodilator FEV1 to segment patients into three groups: moderate COPD (GOLD stage II and above: ≥ 50%; n = 2156), severe COPD (GOLD stage III: 30% to < 50%; n = 3019) and very severe COPD (GOLD stage IV: < 30%; n = 937).,Compared with placebo, SFC improved post-bronchodilator FEV1: 101 ml (95% confidence interval [CI]: 71, 132) in GOLD stage II, 82 ml (95% CI: 60, 104) in GOLD stage III and 96 ml (95% CI: 54, 138) in GOLD stage IV patients, and reduced the rate of exacerbations: 31% (95% CI: 19, 40) in GOLD stage II, 26% (95% CI: 17, 34) in GOLD stage III and 14% (95% CI: -4, 29) in GOLD stage IV.,SFC improved health status to a greater extent than other treatments regardless of baseline GOLD stage.,Similarly, SFC reduced the risk of death by 33% (hazard ratio [HR] 0.67; 95% CI: 0.45, 0.98) for GOLD stage II, 5% (HR 0.95; 95% CI: 0.73, 1.24) for GOLD stage III, and 30% (HR 0.70; 95% CI: 0.47, 1.05) for GOLD stage IV.,The rates of adverse events were similar across treatment arms and increased with disease severity.,Overall, there was a higher incidence of pneumonia in the fluticasone propionate and SFC arms, compared with other treatments in all GOLD stages.,In the TORCH study, SFC reduced moderate-to-severe exacerbations and improved health status and FEV1 across GOLD stages.,Treatment with SFC may be associated with reduced mortality compared with placebo in patients with GOLD stage II disease.,The effects were similar to those reported for the study as a whole.,Thus, SFC is an effective treatment option for patients with GOLD stage II COPD.,Clinicaltrial.gov registration NCT00268216; Study number: SCO30003

NVA237 (glycopyrronium bromide) is a once-daily long-acting muscarinic antagonist (LAMA) in development for chronic obstructive pulmonary disease (COPD).,The GLycopyrronium bromide in COPD airWays clinical Study 2 (GLOW2) evaluated the efficacy and safety of NVA237 in moderate-to-severe COPD over 52 weeks.,Patients were randomised 2:1:1 to NVA237 50 μg, placebo or open-label tiotropium 18 μg for 52 weeks.,Primary end-point was trough forced expiratory volume in 1 s (FEV1) at 12 weeks.,1,066 patients were randomised, 810 completed the study.,At week 12, trough FEV1 increased significantly by 97 mL with NVA237 (95% CI 64.6-130.2; p<0.001) and 83 mL with tiotropium (95% CI 45.6-121.4; p<0.001).,Compared with placebo, NVA237 produced significant improvements in dyspnoea (Transition Dyspnoea Index at week 26; p=0.002) and health status (St George's Respiratory Questionnaire at week 52; p<0.001).,NVA237 significantly reduced the risk of moderate-to-severe COPD exacerbations by 34% (p=0.001) and the use of rescue medication (p=0.039), versus placebo.,NVA237-placebo and tiotropium-placebo differences were comparable for all outcomes.,Safety profiles were similar across groups.,NVA237 50 μg provided significant improvements in lung function, dyspnoea, health status, exacerbations and rescue medication use, versus placebo, and was comparable to tiotropium.,NVA237 can potentially be an alternative choice of LAMA for COPD patients.

Patients with chronic obstructive pulmonary disease (COPD) are included in several national pneumococcal vaccination recommendations whereas asthma patients are not.,The objective of this study was to evaluate pneumonia-related hospitalization risk in patients with COPD or asthma and vaccination impact.,We identified patients with documented pneumococcal vaccination from a cohort of veterans with either a diagnosis of asthma or COPD and their matched controls.,Patients were identified between October 1, 1997 and September 30, 1998 and followed for 5 years.,For each group we identified pneumococcal pneumonia hospitalizations and all pneumonia-related hospitalizations in the periods before and after vaccination.,We estimated hospitalization rates and compared rates in the asthma and COPD groups to controls using negative binomial regression models.,We identified 16,074 COPD patients (average age 65.8 years), 14,028 controls for the COPD patients (average age 67.5 years), 2,746 asthma patients (average age 53.0 years), and 1,345 controls for the asthma patients (average age 59.2 years).,Compared to controls, the adjusted risk of pneumococcal pneumonia hospitalizations before pneumococcal vaccination was COPD = 8.02 (95% CI, 4.44-14.48) and asthma = 0.76 (0.17-3.53).,For any pneumonia-related hospitalization, the adjusted risk was COPD = 3.91 (3.40-4.50) and asthma = 1.45 (0.85-2.46).,After vaccination, events decreased in all groups.,The adjusted risk for pneumococcal pneumonia hospitalizations postvaccination was COPD = 3.87 (2.55-5.88) and asthma = 0.30 (0.04-1.99).,For any pneumonia-related hospitalization the adjusted risk was COPD = 3.71 (3.33-4.13) and asthma = 0.79 (0.50-1.25).,This study supports the value of vaccinating COPD patients; however, the value of vaccination for asthma patients is less certain.

Airway mucus hypersecretion is a frequent symptom associated with acute and chronic airway disease.,Inhibition of mucus production or promotion of mucolysis not only relieved symptoms but also improved disease outcomes.,There are numerous available mucoactive medicines for prescription, and how to select them properly for different diseases is important for clinical practice.,So far, there is no one consensus or guideline reported.,A group of Chinese pulmonary physicians worked together to complete this consensus based on literature review, summarized mechanism and usage of each classical mucoactive medicine.,In general, antioxidant mucoactive medicines play an important role in chronic airway disease, including but not limited to airway mucus clearance, reduced acute exacerbation and improved pulmonary function.

To determine in patients admitted with an acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) the association between the isolation of potential pathogens in a conventional sputum culture and comorbidities.,The ESMI study is a multicenter observational study.,Patients with AE-COPD admitted to the Internal Medicine departments of 70 hospitals were included.,The clinical characteristics, treatments, and comorbidities were gathered.,The results of conventional sputum cultures were recorded.,A total of 536 patients were included, of which 161 produced valid sputum and a potentially pathogenic microorganism was isolated from 88 subjects (16.4%).,The isolation of Pseudomonas aeruginosa (30.7%) was associated with a greater severity of the lung disease (previous admissions [P= 0.026], dyspnea scale [P=0.047], post-broncodilator forced expiratory volume in 1 second (FEV1) [P=0.005], and the BODEx index [P=0.009]); also with higher prevalence of cor pulmonale (P=0.017), heart failure (P=0.048), and cerebrovascular disease (P=0.026).,Streptococcus pneumoniae (26.1%) was associated with more comorbidity according to number of diseases (P=0.018); notably, peripheral artery disease (P=0.033), hypertension (P=0.029), dyslipidemia (P=0.039), osteoporosis (P=0.0001), and depression (P=0.005).,Patients with AE-COPD and P. aeruginosa present higher severity of COPD, while those with S. pneumoniae present greater comorbidity.,The potentially pathogenic microorganism obtained in the sputum culture depends on the associated comorbidities.

Exercise limitation, dynamic hyperinflation, and exertional dyspnea are key features of symptomatic chronic obstructive pulmonary disease (COPD).,We assessed the effects of glycopyrronium bromide (NVA237), a once-daily, long-acting muscarinic antagonist, on exercise tolerance in patients with moderate to severe COPD.,Patients were randomized to a cross-over design of once-daily NVA237 50 μg or placebo for 3 weeks, with a 14-day washout.,Exercise endurance, inspiratory capacity (IC) during exercise, IC and expiratory volumes from spirometry, plethysmographic lung volumes, leg discomfort and dyspnea under exercise (Borg scales), and transition dyspnea index were measured on Days 1 and 21 of treatment.,The primary endpoint was endurance time during a submaximal constant-load cycle ergometry test on Day 21.,A total of 108 patients were randomized to different treatment groups (mean age, 60.5 years; mean post-bronchodilator, forced expiratory volume in 1 second [FEV1] 57.1% predicted).,Ninety-five patients completed the study.,On Day 21, a 21% difference in endurance time was observed between patients treated with NVA237 and those treated with placebo (P < 0.001); the effect was also significant from Day 1, with an increase of 10%.,Dynamic IC at exercise isotime and trough FEV1 showed significant and clinically relevant improvements from Day 1 of treatment that were maintained throughout the study.,This was accompanied by inverse decreases in residual volume and functional residual capacity.,NVA237 was superior to placebo (P < 0.05) in decreasing leg discomfort (Borg CR10 scale) on Day 21 and exertional dyspnea on Days 1 and 21 (transition dyspnea index and Borg CR10 scale at isotime).,The safety profile of NVA237 was similar to that of the placebo.,NVA237 50 μg once daily produced immediate and significant improvement in exercise tolerance from Day 1.,This was accompanied by sustained reductions in lung hyperinflation (indicated by sustained and significant improvements in IC at isotime), and meaningful improvements in trough FEV1 and dyspnea.,Improvements in exercise endurance increased over time, suggesting that mechanisms beyond improved lung function may be involved in enhanced exercise tolerance.,(ClinicalTrials.gov Identifier: NCT01154127).

We hypothesized that bronchodilator treatment not only improves hyperinflation and endurance capacity but also muscular efficiency in stable chronic obstructive pulmonary disease (COPD).,We aimed to demonstrate that tiotropium and salmeterol improve muscular efficiency compared with placebo.,Twenty-five COPD patients were studied, including 20 males of mean (standard deviation) age 62 years (7 years) with baseline forced expiratory volume in 1 second of 41% (10%) predicted, and maximal workload of 101 Watt (36 Watt).,Subjects were randomized for 6-week treatment with tiotropium 18 μg once daily, salmeterol 50 μg twice daily, or placebo using a double-blind, crossover design.,Muscular efficiency and endurance time were measured during cycling at 50% of maximal work load.,Resting energy expenditure was measured using a ventilated hood.,Muscular efficiency after tiotropium, salmeterol, and placebo treatment was 14.6%, 14.4%, and 14.4%, respectively (P > 0.05), and resting energy expenditure was 1485 kcal/24 hours, 1709 kcal/24 hours, and 1472 kcal/24 hours (P > 0.05), respectively.,Endurance time after tiotropium treatment was significantly higher than that after placebo (27.0 minutes versus 19.3 minutes [P = 0.02]), whereas endurance time after salmeterol treatment was not higher than that after placebo (23.3 minutes [P = 0.22]).,In this small study, we were not able to demonstrate that bronchodilator therapy improved muscular efficiency.,Apparently, reduced costs of breathing relative to total energy expenditure were too small to be detected.

The COVID-19 pandemic has impacted specialty chronic obstructive pulmonary disease (COPD) care.,We examined the degree to which care has moved to remote approaches, eliciting clinician and patient perspectives on what is appropriate for ongoing remote delivery.,Using an online research platform, we conducted a survey and consensus-building process involving clinicians and patients with COPD.,Fifty-five clinicians and 19 patients responded.,The majority of clinicians felt able to assess symptom severity (n=52, 95%), reinforce smoking cessation (n=46, 84%) and signpost to other healthcare resources (n=44, 80%).,Patients reported that assessing COPD severity and starting new medications were being addressed through remote care.,Forty-three and 31 respondents participated in the first and second consensus-building rounds, respectively.,When asked to rate the appropriateness of using remote delivery for specific care activities, respondents reached consensus on 5 of 14 items: collecting information about COPD and overall health status (77%), providing COPD education and developing a self-management plan (74%), reinforcing smoking cessation (81%), deciding whether patients should seek in-person care (72%) and initiating a rescue pack (76%).,Adoption of remote care delivery appears high, with many care activities partially or completely delivered remotely.,Our work identifies strengths and limitations of remote care delivery.

In barely nine months, the pandemic known as COVID‐19 has spread over 200 countries, affecting more than 22 million people and causing over than 786 000 deaths.,Elderly people and patients with previous comorbidities such as hypertension and diabetes are at an increased risk to suffer a poor prognosis after severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection.,Although the same could be expected from patients with chronic obstructive pulmonary disease (COPD), current epidemiological data are conflicting.,This could lead to a reduction of precautionary measures in these patients, in the context of a particularly complex global health crisis.,Most COPD patients have a long history of smoking or exposure to other harmful particles or gases, capable of impairing pulmonary defences even years after the absence of exposure.,Moreover, COPD is characterized by an ongoing immune dysfunction, which affects both pulmonary and systemic cellular and molecular inflammatory mediators.,Consequently, increased susceptibility to viral respiratory infections have been reported in COPD, often worsened by bacterial co‐infections and leading to serious clinical outcomes.,The present paper is an up‐to‐date review that discusses the available research regarding the implications of coronavirus infection in COPD.,Although validation in large studies is still needed, COPD likely increases SARS‐CoV‐2 susceptibility and increases COVID‐19 severity.,Hence, specific mechanisms to monitor and assess COPD patients should be addressed in the current pandemic.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory condition, and progresses with acute exacerbations.,(AE).,During AE, levels of acute phase reactants such as C-reactive protein (CRP) and inflammatory cells in the circulation increase.,Soluble urokinase-type plasminogen activator receptor (suPAR) levels increase in acute viral and bacterial infections and in diseases involving chronic inflammation.,The purpose of this study was to investigate the effectiveness of suPAR in predicting diagnosis of AE of COPD (AE-COPD) and response to treatment.,The study population consisted of 43 patients diagnosed with AE-COPD and 30 healthy controls. suPAR, CRP, and fibrinogen levels were measured on the first day of hospitalization and on the seventh day of treatment.,We found that fibrinogen (P<0.001), CRP (P<0.001), and suPAR (P<0.001) were significantly higher in patients with AE-COPD than in healthy controls.,Fibrinogen (P<0.001), CRP (P=0.001), and suPAR (P<0.001) were significantly decreased by the seventh day of treatment.,However, the area under receiver operator characteristic curve showed that suPAR is superior to CRP and fibrinogen in distinguishing AE-COPD.,There was a correlation between fibrinogen, CRP, and suPAR.,However, only fibrinogen was a powerful predictor of suPAR in multiple linear regression.,In multiple logistic regression, only suPAR and fibrinogen were strong predictors of AE-COPD (P=0.002 and P=0.014, respectively).,Serum suPAR was negatively correlated with forced expiratory volume in 1 second (r=−478, P=0.001).,suPAR is a marker of acute inflammation.,It is well correlated with such inflammation markers as CRP and fibrinogen. suPAR can be used as a predictor of AE-COPD and in monitoring response to treatment.

Chronic obstructive pulmonary disease (COPD) is a multicomponent condition that is characterised by airflow obstruction that is not fully reversible and is a major global cause of morbidity and mortality.,The most widely used marker of disease severity and progression is FEV1.,However, FEV1 correlates poorly with both symptoms and other measures of disease progression and thus there is an urgent need for other biological markers to better characterise individuals with COPD.,Fibrinogen is an acute phase plasma protein that has emerged as a promising biomarker in COPD.,Here we review the current clinical evidence linking fibrinogen with COPD and its associated co-morbidities and discuss its potential utility as a biomarker.,Searches for appropriate studies were undertaken on PubMed using search terms fibrinogen, COPD, emphysema, chronic bronchitis, FEV1, cardiovascular disease, exacerbation and mortality.,There is strong evidence of an association between fibrinogen and the presence of COPD, the presence and frequency of exacerbations and with mortality.,Fibrinogen is associated with disease severity but does not predict lung function decline, a measure used as a surrogate for disease activity.,The role of fibrinogen in identifying inflammatory co morbidities, particularly cardiovascular disease, remains unclear.,Fibrinogen is reduced by p38 mitogen-activated protein kinase inhibitors in individuals with stable disease and by oral corticosteroids during exacerbations.,Fibrinogen is likely to be a useful biomarker to stratify individuals with COPD into those with a high or low risk of future exacerbations and may identify those with a higher risk of mortality.

COPD has been perceived as being a disease of older men.,However, >7 million women are estimated to live with COPD in the USA alone.,Despite a growing body of literature suggesting an increasing burden of COPD in women, the evidence is limited.,To assess and synthesize the available evidence among population-based epidemiologic studies and calculate the global prevalence of COPD in men and women.,A systematic review and meta-analysis reporting gender-specific prevalence of COPD was undertaken.,Gender-specific prevalence estimates were abstracted from relevant studies.,Associated patient characteristics as well as custom variables pertaining to the diagnostic method and other important epidemiologic covariates were also collected.,A Bayesian random-effects meta-analysis was performed investigating gender-specific prevalence of COPD stratified by age, geography, calendar time, study setting, diagnostic method, and disease severity.,Among 194 eligible studies, summary prevalence was 9.23% (95% credible interval [CrI]: 8.16%-10.36%) in men and 6.16% (95% CrI: 5.41%-6.95%) in women.,Gender prevalences varied widely by the World Health Organization Global Burden of Disease subregions, with the highest female prevalence found in North America (8.07% vs 7.30%) and in participants in urban settings (13.03% vs 8.34%).,Meta-regression indicated that age ≥40 and bronchodilator testing contributed most significantly to heterogeneity of prevalence estimates across studies.,We conducted the largest ever systematic review and meta-analysis of global prevalence of COPD and the first large gender-specific review.,These results will increase awareness of COPD as a critical woman’s health issue.

There is increasing evidence that chronic obstructive pulmonary disease (COPD) is not simply a disease of old age that is largely restricted to heavy smokers, but may be associated with insults to the developing lung during foetal life and the first few years of postnatal life, when lung growth and development are rapid.,A better understanding of the long-term effects of early life factors, such as intrauterine growth restriction, prenatal and postnatal exposure to tobacco smoke and other pollutants, preterm delivery and childhood respiratory illnesses, on the subsequent development of chronic respiratory disease is imperative if appropriate preventive and management strategies to reduce the burden of COPD are to be developed.,The extent to which insults to the developing lung are associated with increased risk of COPD in later life depends on the underlying cause, timing and severity of such derangements.,Suboptimal conditions in utero result in aberrations of lung development such that affected individuals are born with reduced lung function, which tends to remain diminished throughout life, thereby increasing the risk both of wheezing disorders during childhood and subsequent COPD in genetically susceptible individuals.,If the current trend towards the ever-increasing incidence of COPD is to be reversed, it is essential to minimize risks to the developing lung by improvements in antenatal and neonatal care, and to reduce prenatal and postnatal exposures to environmental pollutants, including passive tobacco smoke.,Furthermore, adult physicians need to recognize that lung disease is potentially associated with early life insults and provide better education regarding diet, exercise and avoidance of smoking to preserve precious reserves of lung function in susceptible adults.,This review focuses on factors that adversely influence lung development in utero and during the first 5 years of life, thereby predisposing to subsequent COPD.

A reliable and fast liquid chromatography-tandem mass spectrometry method has been developed for the simultaneous determination of three oxidized nucleic acid damage products in urine, 8-oxoguanine (8-oxoGua), 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo).,We applied this method to assess the effect of various urine workup procedures on the urinary concentrations of the oxidized nucleic acid products.,Our results showed that frozen urine samples must be warmed (i.e., to 37 °C) to re-dissolve any precipitates prior to analysis.,We showed that common workup procedures, such as thawing at room temperature or dilution with deionized water, are not capable of releasing fully the oxidized nucleic acid products from the precipitates, and result in significant underestimation (up to ~ 100% for 8-oxoGua, ~ 86% for both 8-oxodGuo and 8-oxoGuo).,With this method, we further assessed and compared the ability of the three oxidized nucleic acid products, as well as malondialdehyde (MDA, a product of lipid peroxidation), to biomonitor oxidative stress in vivo.,We measured a total of 315 urine samples from subjects with burdens of oxidative stress from low to high, including healthy subjects, patients with chronic obstructive pulmonary disease (COPD), and patients on mechanical ventilation (MV).,The results showed that both the MV and COPD patients had significantly higher urinary levels of 8-oxoGua, 8-oxodGuo, and 8-oxoGuo (P < 0.001), but lower MDA levels, compared to healthy controls.,Receiver operating characteristic curve analysis revealed that urinary 8-oxoGuo is the most sensitive biomarker for oxidative stress with area under the curve (AUC) of 0.91, followed by 8-oxodGuo (AUC: 0.80) and 8-oxoGua (AUC: 0.76).,Interestingly, MDA with AUC of 0.34 failed to discriminate the patients from healthy controls.,Emerging evidence suggests a potential clinical utility for the measurement of urinary 8-oxoGuo, and to a lesser extent 8-oxodGuo, which is strongly supported by our findings.

Chronic obstructive pulmonary disease (COPD) is one of the most common chronic illnesses in the world.,The disease encompasses emphysema, chronic bronchitis, and small airway obstruction and can be caused by environmental exposures, primarily cigarette smoking.,Since only a small subset of smokers develop COPD, it is believed that host factors interact with the environment to increase the propensity to develop disease.,The major pathogenic factors causing disease include infection and inflammation, protease and antiprotease imbalance, and oxidative stress overwhelming antioxidant defenses.,In this review, we will discuss the major environmental and host sources for oxidative stress; discuss how oxidative stress regulates chronic bronchitis; review the latest information on genetic predisposition to COPD, specifically focusing on oxidant/antioxidant imbalance; and review future antioxidant therapeutic options for COPD.,The complexity of COPD will necessitate a multi-target therapeutic approach.,It is likely that antioxidant supplementation and dietary antioxidants will have a place in these future combination therapies.

There is a substantial burden of chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD), in low- and middle-income countries (LMICs).,LMICs have particular challenges in delivering cost-effective prevention, diagnosis, and management of COPD.,Optimal care can be supported by effective implementation of guidelines.,This American Thoracic Society workshop considered challenges to implementation of COPD guidelines in LMICs.,We make 10 specific recommendations: 1) relevant organizations should provide LMIC-specific COPD management guidance; 2) patient and professional organizations must persuade policy-makers of the importance of lung function testing programs in LMICs; 3) healthcare education and training should emphasize the early-life origins of COPD; 4) urgent action is required by governments to reduce airborne exposures, including exposures to tobacco smoke and indoor and outdoor air pollution; 5) guidance for COPD in LMICs should explicitly link across Essential Medicine Lists and the World Health Organization package of essential noncommunicable disease interventions for primary health care in low-resource settings and should consider availability, affordability, sustainability, and cost-effective use of medicines; 6) the pharmaceutical industry should work to make effective COPD and tobacco-dependence medicines globally accessible and affordable; 7) implementation of locally adapted, cost-effective pulmonary rehabilitation programs should be an international priority; 8) the World Health Organization Global Action Plan for the Prevention and Control of Noncommunicable Diseases should specify how improvements in respiratory health will be achieved; 9) research funders should increase the proportion of funding allocated to COPD in LMICs; and 10) the respiratory community should leverage the skills and enthusiasm of earlier-career clinicians and researchers to improve global respiratory health.

One quarter of individuals with Preserved Ratio Impaired Spirometry (PRISm) will develop airflow obstruction, but there are no established methods to identify these individuals.,We examined the utility of FVC/TLC in identifying features of obstructive lung disease.,The ratio of post-bronchodilator FVC and TLCCT from chest CT (FVC/TLCCT) among current and former smokers with PRISm (FEV1/FVC ≥ 0.7 and FEV1 < 80%) in COPDGene was used to stratify subjects into quartiles: very high, high, low, and very low.,We examined the associations between FVC/TLCCT quartiles and (1) baseline characteristics, (2) respiratory exacerbations, (3) progression to COPD at 5 years, and (4) all-cause mortality.,Among participants with PRISm at baseline (n = 1,131), the very low FVC/TLCCT quartile was associated with increased gas trapping and emphysema, and higher rates of progression to COPD at 5 years (36% versus 17%; p < 0.001) relative to the very high quartile.,The very low FVC/TLCCT quartile was associated with increased total (IRR = 1.65; 95% CI [1.07-2.54]) and severe (IRR = 2.24; 95% CI [1.29-3.89]) respiratory exacerbations.,Mortality was lower in the very high FVC/TLCCT quartile relative to the other quartiles combined.,Reduced FVC/TLCCT ratio in PRISm is associated with increased symptoms, radiographic emphysema and gas trapping, exacerbations, and progression to COPD.

To explore the effects of group singing therapy on depression symptoms and quality of life of patients with stable chronic obstructive pulmonary disease (COPD).,Patients with COPD were randomly allocated to intervention (n = 30) and control groups (n = 30).,The intervention group received group singing therapy once a week for 24 sessions along with routine health education, whereas the control group only received the routine health education.,All patients were administered the Hospital Anxiety and Depression Scale depression subscale (HADS-D) and the Clinical COPD Questionnaire (CCQ).,Data were collected at baseline and at 1, 3, and 6 months.,Fifty-six participants completed this trial.,Significant between-group differences were observed with respect to the main effect of group and time as well as the effect of group × time interaction on HADS-D score.,The HADS-D score was significantly improved 1, 3, 6 months after group singing therapy.,The CCQ total scores were significantly different between the two groups with respect to the main effect of group and time and the group × time interaction effect.,Significantly better CCQ was detected in the intervention group at 3 months and 6 months after intervention.,Group singing therapy reduces depressive symptoms and improves the quality of life of patients with stable COPD.

There is some evidence that singing lessons may be of benefit to patients with chronic obstructive pulmonary disease (COPD).,It is not clear how much of this benefit is specific to singing and how much relates to the classes being a group activity that addresses social isolation.,Patients were randomised to either singing classes or a film club for eight weeks.,Response was assessed quantitatively through health status questionnaires, measures of breathing control, exercise capacity and physical activity and qualitatively, through structured interviews with a clinical psychologist.,The singing group (n=13 mean(SD) FEV1 44.4(14.4)% predicted) and film group (n=11 FEV1 63.5(25.5)%predicted) did not differ significantly at baseline.,There was a significant difference between the response of the physical component score of the SF-36, favouring the singing group +12.9(19.0) vs -0.25(11.9) (p=0.02), but no difference in response of the mental component score of the SF-36, breathing control measures, exercise capacity or daily physical activity.,In the qualitative element, positive effects on physical well-being were reported in the singing group but not the film group.,Singing classes have an impact on health status distinct from that achieved simply by taking part in a group activity.,Registration Current Controlled Trials - ISRCTN17544114

To systematically investigate the prevalence of pain, factors related with pain and pain management interventions in patients with chronic obstructive pulmonary disease (COPD).,Systematic review and meta-analysis.,PubMed (MEDLINE), EMBASE, CINAHL and PsychINFO from 1966 to December 2013.,Studies were included if they presented clinical data on pain or symptom burden in patients with COPD, or pain as a domain of quality of life (QoL).,All types of study designs were included.,Of the 1571 articles that were identified, 39 met the inclusion criteria and were included in this review.,Fourteen studies focused on pain and symptom burden (including pain) in patients with COPD and 25 studies focused on QoL using a questionnaire that included a separate pain domain.,Reported pain prevalence in high-quality studies ranged from 32 to 60%.,Included studies report that pain is more prevalent in patients with COPD compared to participants from the general population.,Comorbidity, nutritional status, QoL and several symptoms were related to pain.,None of the included studies reported a significant relationship between lung function and pain prevalence or severity.,However, studies investigating pain in patients with moderate COPD reported higher pain prevalence compared to studies in patients with severe of very severe COPD.,Although literature on this topic is limited and shows substantial heterogeneity, pain seems to be a significant problem in patients with COPD and is related to several other symptoms, comorbidity and QoL.,Data synthesis suggests that pain is more prevalent in patients with moderate COPD compared to patients with severe or very severe COPD.,Further research is needed and should focus on determining a more accurate pain prevalence, investigating the relationship between pain prevalence, disease severity and comorbidity and explore implementation and efficacy of pain management interventions in patients with COPD.

Beta-blockers are frequently withheld in patients with cardiovascular disease who also have chronic obstructive pulmonary disease (COPD) because of concerns that they might provoke bronchospasm and cause deterioration in health status.,Although beta1-selective beta-blockers are associated with reduced mortality in COPD patients, their effects on health status are unknown.,The aim of this study was to investigate the relationship between beta-blockers and health-related quality of life (HRQOL) in patients with peripheral arterial disease and COPD.,Of the original cohort of 3371 vascular surgery patients, 1310 had COPD of whom 469 survived during long-term follow-up.,These COPD patients were sent the Short Form-36 (SF-36) health-related quality of life questionnaire, which was completed and returned by 326 (70%) patients.,No significant differences in any of the SF-36 domains were observed between COPD patients who did and did not use beta-blockers (p > 0.05 for all).,Furthermore, beta-blockers were not associated with any impairment in HRQOL among patients with COPD.,Beta-blockers had no material impact on the HRQOL of patients with peripheral arterial disease who also had COPD.,This suggests that beta-blockers can, in most circumstances, be administered to patients with COPD without impairment in HRQOL.

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are associated with a significant mortality, health and economic burden.,Their diagnosis, assessment and management remain suboptimal and unchanged for decades.,Recent clinical and translational studies revealed that the significant heterogeneity in mechanisms and outcomes of exacerbations could be resolved by grouping them etiologically.,This is anticipated to lead to a better understanding of the biological processes that underlie each type of exacerbation and to allow the introduction of precision medicine interventions that could improve outcomes.,This review summarises novel data on the diagnosis, phenotyping, targeted treatment and prevention of COPD exacerbations.

Vertebral compression fractures (VCF) are common in COPD patients, with osteoporosis being the main cause.,The clinical impact of VCF derives mostly from both pain and chest deformity, which may lead to ventilatory and physical activity limitations.,Surprisingly, the consequences of VCF on the quality outcomes of hospital care are poorly known.,To assess these indicators in patients hospitalized due to a COPD exacerbation (ECOPD) who also have VCF.,Clinical characteristics and quality care indicators were assessed in two one-year periods, one retrospective (exploratory) and one prospective (validation), in all consecutive patients hospitalized for ECOPD.,Diagnosis of VCF was based on the reduction of >20% height of the vertebral body evaluated in standard lateral chest X-ray (three independent observers).,From the 248 patients admitted during the exploratory phase, a third had at least one VCF.,Underdiagnosis rate was 97.6%, and patients with VCF had more admissions (normalized for survival), longer hospital stays, and higher mortality than patients without (4 [25th-75th percentiles, 2-8] vs 3 [1-6] admissions, P<0.01; 12 [6-30] vs 9 [6-18] days, P<0.05; and 50 vs 32.1% deaths, P<0.01, respectively).,The risk of dying in the two following years was also higher in VCF patients (odds ratio: 2.11 [1.2-3.6], P<0.01).,The validation cohort consisted of 250 patients who showed very similar results.,The logistic regression analysis indicated that both VCF and age were factors independently associated with mortality.,Although VCF is frequently underdiagnosed in patients hospitalized for ECOPD, it is strongly associated with a worse prognosis and quality care outcomes.

Nutritional depletion is an important manifestation of chronic obstructive pulmonary disease (COPD), which has been related to systemic inflammation.,It remains unclear to what degree airway inflammation contributes to the presence or progression of nutritional depletion.,To determine whether airway inflammation and lung bacterial colonization are related to nutritional status or predict progressive weight loss and muscle atrophy in patients with COPD.,Body composition using dual energy X-ray absorptiometry, indices of airway inflammation, and bacterial colonization were measured in 234 COPD patients.,Systemic inflammation was assessed from serum C reactive protein (CRP) and circulating total and differential leukocyte counts.,Nutritional depletion was defined as a body mass index (BMI) less than 21 kg/m2 and/or fat-free mass index (FFMI) less than 15 or 17 kg/m2 in women and men, respectively.,FFMI was calculated as the fat-free mass (FFM) corrected for body surface area.,Measurements were repeated in 94 patients after a median 16-month follow-up.,Regression analysis was used to assess the relationships of weight change and FFM change with indices of bacterial colonization and airway and systemic inflammation.,Nutritional depletion occurred in 37% of patients.,Lung function was worsened in patients with nutritional depletion compared to those without (forced expiratory volume in 1 second 1.17 L versus 1.41 L, mean difference 0.24, 95% confidence interval 0.10 to 0.38, P<0.01).,There were no differences in airway inflammation and bacterial colonization in patients with and without nutritional depletion.,At baseline, BMI correlated positively with serum CRP (rs=0.14, P=0.04).,Change in weight and change in FFM over time could not be predicted from baseline patient characteristics.,Nutritional depletion and progressive muscle atrophy are not related to airway inflammation or bacterial colonization.,Overspill of pulmonary inflammation is not a key driver of muscle atrophy in COPD.

The effect of smoking cessation on the oxidative stress in patients with chronic obstructive pulmonary disease (COPD) was assessed.,We recruited 73 smokers with COPD (study group), whose blood was analysed before smoking cessation, after the 1st, 2nd, and 3rd months of abstinence, 35 healthy nonsmokers (Control I), and 35 smokers with COPD (Control II).,Blood was taken once in Control I and 4 times (every month) in Control II.,In the study group conjugated dienes (CDs) level in plasma and erythrocytes before smoking cessation was 3 and 6.5 times higher than in Control I, respectively (P < 0.001), while thiobarbituric acid-reactive substances (TBARS) level was 89% (P < 0.001) and 51% higher (P < 0.01), respectively.,Superoxide dismutase (SOD) activity was 40% higher (P < 0.05) while glutathione peroxidase (GPx) was 41% lower (P < 0.001) than in Control I.,In Control II, the similar differences as compared to Control I were observed throughout the study.,Smoking cessation resulted in decrease of CDs, TBARS, and SOD and GPx increase, with no changes in catalase and vitamins A and E.,COPD is accompanied by oxidative stress.,A three-month tobacco abstinence facilitated restoring the oxidant-antioxidant balance systemically, but it did not affect spirometric parameters.

Acute myocardial infarction is a major cause of hospitalization and death in patients with chronic obstructive pulmonary disease (COPD); however, temporal trends in the management and clinical outcomes of these patients remain unclear.,We conducted an observational study by using a representative sample of 1 million beneficiaries from the Taiwan National Health Insurance Research Database.,Comorbidities, in‐hospital treatment, and outcomes were compared for patients with acute myocardial infarction with and without COPD between 2004 and 2013.,Temporal trends in treatment and outcomes were analyzed.,We included 6770 patients admitted to hospitals with acute myocardial infarction diagnoses, of whom 1921 (28.3%) had COPD.,Fewer patients with COPD received β‐blockers (adjusted odds ratio 0.66, 95% CI 0.59-0.74), angiotensin‐converting enzyme inhibitors/angiotensin II receptor blockers (adjusted odds ratio 0.83, 95% CI 0.73-0.93), statins, anticoagulants, dual antiplatelets, and coronary interventions.,These patients had higher mortality (in hospital: adjusted hazard ratio 1.25 [95% CI 1.11-1.41]; 1 year: adjusted hazard ratio 1.20 [95% CI 1.09-1.32]) and respiratory failure risk during admission.,Temporal trends showed little improvement in mortality in patients with COPD over 10 years.,Multivariable logistic regression indicated that dual antiplatelets, β‐blockers, angiotensin‐converting enzyme inhibitors/angiotensin II receptor blockers, statins, coronary angiography, and coronary artery bypass grafting surgery were significantly correlated with improved mortality in patients with COPD.,In Taiwan, a lower proportion of patients with COPD received evidence‐based therapies for acute myocardial infarction than did patients without COPD, and their clinical outcomes were inferior.,Limited improvement in mortality was observed over the preceding 10 years and is attributable to the underuse of evidence‐based treatments.

Objective To examine the effect of β blockers in the management of chronic obstructive pulmonary disease (COPD), assessing their effect on mortality, hospital admissions, and exacerbations of COPD when added to established treatment for COPD.,Design Retrospective cohort study using a disease specific database of COPD patients (TARDIS) linked to the Scottish morbidity records of acute hospital admissions, the Tayside community pharmacy prescription records, and the General Register Office for Scotland death registry.,Setting Tayside, Scotland (2001-2010),Population 5977 patients aged >50 years with a diagnosis of COPD.,Main outcome measures Hazard ratios for all cause mortality, emergency oral corticosteroid use, and respiratory related hospital admissions calculated through Cox proportional hazard regression after correction for influential covariates.,Results Mean follow-up was 4.35 years, mean age at diagnosis was 69.1 years, and 88% of β blockers used were cardioselective.,There was a 22% overall reduction in all cause mortality with β blocker use.,Furthermore, there were additive benefits of β blockers on all cause mortality at all treatment steps for COPD.,Compared with controls (given only inhaled therapy with either short acting β agonists or short acting antimuscarinics), the adjusted hazard ratio for all cause mortality was 0.28 (95% CI 0.21 to 0.39) for treatment with inhaled corticosteroid, long acting β agonist, and long acting antimuscarinic plus β blocker versus 0.43 (0.38 to 0.48) without β blocker.,There were similar trends showing additive benefits of β blockers in reducing oral corticosteroid use and hospital admissions due to respiratory disease. β blockers had no deleterious impact on lung function at all treatment steps when given in conjunction with either a long acting β agonist or antimuscarinic agent,Conclusions β blockers may reduce mortality and COPD exacerbations when added to established inhaled stepwise therapy for COPD, independently of overt cardiovascular disease and cardiac drugs, and without adverse effects on pulmonary function.

While single-inhaler triple therapy (SITT) devices were not available when the Global Initiative for Chronic Obstructive Lung Disease strategy and National Institute for Health and Care Excellence guidelines were developed, two devices are now available in the UK.,This paper offers practical, patient-focused advice to optimize placement of SITT in the management of COPD.,A survey of UK health care professionals (HCPs) identified issues around, and attitudes toward, SITT, which informed a multidisciplinary expert panel’s discussions.,The survey confirmed the need to clarify the place of SITT in COPD management.,The panel suggested three criteria, any one of which identifies a high-risk patient where escalation to triple therapy from monotherapy or double combination treatment is appropriate: 1) at least two exacerbations treated with oral corticosteroids, antibiotics, or both in the previous year; 2) at least one severe exacerbation that required hospital admission in the previous year; 3) one exacerbation a year on a repeated basis for 2 consecutive years.,Appropriate non-pharmacological management is essential for all patients and should be considered before stepping up treatment.,Regular review is essential.,During each review, HCPs should consider stepping treatment up or down.,If patients exacerbate despite adhering to triple therapy, an individualized approach should be considered if the inhaled corticosteroid (ICS) confers benefit or causes side effects.,In this situation, the blood eosinophil count could aid decision making.,ICSs should be continued when the history suggests that asthma overlaps with COPD.,Training, counseling, and education should be individualized.,HCPs should consider referral: 1) when there is limited response to treatment and persistent exacerbations; 2) where there is diagnostic uncertainty or suspected comorbidity; 3) whenever they feel “out of their depth.”,Overall, the panel concurred that when used correctly, SITT has the potential to improve adherence, symptom control, and quality of life, and reduce exacerbations.,Studies using real-world evidence need to confirm these benefits.

As lung function declines rapidly in the early stages of chronic obstructive pulmonary disease (COPD), the effects of bronchodilators in patients with moderate disease and those who have not previously received maintenance therapy are of interest.,OTEMTO® 1 and 2 were two replicate, 12-week, Phase III studies investigating the benefit of tiotropium + olodaterol on lung function and quality of life in patients with moderate to severe disease.,Post hoc analyses were performed to assess the benefits for patients according to disease severity and treatment history.,Four subgroup analyses were performed: Global initiative for chronic Obstructive Lung Disease (GOLD) 2/3, GOLD A/B/C/D, treatment naive/not treatment naive and receiving inhaled corticosteroids (ICS) at baseline/not receiving ICS at baseline.,Primary end points were change in forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h response, change in trough FEV1 and St George’s Respiratory Questionnaire (SGRQ) total score.,Transition Dyspnoea Index (TDI) focal score was a secondary end point, and SGRQ and TDI responder analyses were further end points; all were assessed at 12 weeks.,In all subgroups, patients receiving tiotropium + olodaterol responded better overall than those receiving tiotropium monotherapy.,Improvements with tiotropium + olodaterol over placebo or tiotropium monotherapy were noted across GOLD 2/3 and GOLD A/B/C/D; however, improvements in SGRQ total score were most evident in the GOLD B subgroup.,Moreover, lung-function outcomes were generally greater in those patients who had been receiving previous long-acting bronchodilator and/or ICS maintenance treatment.,These data suggest that tiotropium + olodaterol should be considered as a treatment option in patients with moderate COPD who are initiating maintenance therapy, as well as those with more severe disease.,ClinicalTrials.gov: NCT01964352 and NCT02006732.,The online version of this article (doi:10.1186/s12931-016-0387-7) contains supplementary material, which is available to authorized users.

To clarify how low BMI and weight loss were associated with risk of chronic obstructive pulmonary disease (COPD) mortality, in a large prospective cohort of the general population across Japan, the Japan Collaborative Cohort Study, conducted between 1988 and 2009.,A total of 45,837 male residents were observed for a median period of 19.1 years.,Self-administered questionnaires, collecting information on BMI, weight loss since the age of 20, lifestyles, history of diseases, as well as records of COPD mortality, were analysed at 2019.,During follow-up, 268 participants died from COPD.,The multivariate-adjusted hazard ratio (95% confidence interval) of COPD mortality associated with a 1-SD increment of body mass index (BMI) was 0.48 (0.41-0.57), while for weight change from age of 20 (+ 2.0 kg) it was 0.63 (0.59-0.68).,These associations were persistently observed after stratifications with smoking status, excluding those having airway symptoms in the baseline survey, and excluding early COPD deaths within 5, 10 and 15 years.,Our study suggests that BMI and weight change since the age of 20 could be markers for COPD prognosis, indicated by risk of COPD mortality.

Cigarette smoking is the main risk factor for COPD (Chronic Obstructive Pulmonary Disease), yet only a subset of smokers develops COPD.,Family members of patients with severe early-onset COPD have an increased risk to develop COPD and are therefore defined as “susceptible individuals”.,Here we perform unbiased analyses of proteomic profiles to assess how “susceptible individuals” differ from age-matched “non-susceptible individuals” in response to cigarette smoking.,Epithelial lining fluid (ELF) was collected at baseline and 24 hours after smoking 3 cigarettes in young individuals susceptible or non-susceptible to develop COPD and older subjects with established COPD.,Controls at baseline were older healthy smoking and non-smoking individuals.,Five samples per group were pooled and analysed by stable isotope labelling (iTRAQ) in duplicate.,Six proteins were selected and validated by ELISA or immunohistochemistry.,After smoking, 23 proteins increased or decreased in young susceptible individuals, 7 in young non-susceptible individuals, and 13 in COPD in the first experiment; 23 proteins increased or decreased in young susceptible individuals, 32 in young non-susceptible individuals, and 11 in COPD in the second experiment.,SerpinB3 and Uteroglobin decreased after acute smoke exposure in young non-susceptible individuals exclusively, whereas Peroxiredoxin I, S100A9, S100A8, ALDH3A1 (Aldehyde dehydrogenase 3A1) decreased both in young susceptible and non-susceptible individuals, changes being significantly different between groups for Uteroglobin with iTRAQ and for Serpin B3 with iTRAQ and ELISA measures.,Peroxiredoxin I, SerpinB3 and ALDH3A1 increased in COPD patients after smoking.,We conclude that smoking induces a differential protein response in ELF of susceptible and non-susceptible young individuals, which differs from patients with established COPD.,This is the first study applying unbiased proteomic profiling to unravel the underlying mechanisms that induce COPD.,Our data suggest that SerpinB3 and Uteroglobin could be interesting proteins in understanding the processes leading to COPD.

Prescribing patterns in chronic obstructive pulmonary disease (COPD) are often inconsistent with published guidelines.,This retrospective, observational study utilised data from the Optimum Patient Care Research Database to examine the changes in COPD prescribing patterns over time and to identify predictors of physician treatment choice for patients newly diagnosed with COPD.,Initial therapy was defined as the treatment(s) prescribed at or within 1 year before COPD diagnosis.,Changes over time were assessed in three cohorts based on the date of diagnosis: (1) 1997-2001; (2) 2002-2006; and (3) 2007-2010.,Factors affecting the odds of being prescribed any initial therapy or any initial maintenance therapy were identified by univariable and multivariable logistic regression.,The analysis included 20,154 patients, 45% of whom were prescribed an initial regimen containing an inhaled corticosteroid (ICS), whereas 28% received no initial pharmacological treatment.,Prescribing of ICS monotherapy decreased over time, as did the proportion of patients receiving no therapy at or within 1 year before diagnosis.,Comorbid asthma, a high exacerbation rate, increased symptoms and poor lung function each increased the likelihood of being prescribed any initial therapy or initial maintenance therapy; comorbid asthma and an annual rate of ⩾3 exacerbations were the strongest predictors.,In conclusion, our analyses revealed major differences between actual prescribing behaviour and guideline recommendations for patients with newly diagnosed COPD, with many patients receiving no treatment and large numbers of patients receiving ICS-containing regimens.,Predictors of initial therapy were identified.

Previous clinical audits for chronic obstructive pulmonary disease (COPD) have provided valuable information on the clinical care delivered to patients admitted to medical wards because of COPD exacerbations.,However, clinical audits of COPD in an outpatient setting are scarce and no methodological guidelines are currently available.,Based on our previous experience, herein we describe a clinical audit for COPD patients in specialized outpatient clinics with the overall goal of establishing a potential methodological workflow.,A pilot clinical audit of COPD patients referred to respiratory outpatient clinics in the region of Andalusia, Spain (over 8 million inhabitants), was performed.,The audit took place between October 2013 and September 2014, and 10 centers (20% of all public hospitals) were invited to participate.,Cases with an established diagnosis of COPD based on risk factors, clinical symptoms, and a post-bronchodilator FEV1/FVC ratio of less than 0.70 were deemed eligible.,The usefulness of formally scheduled regular follow-up visits was assessed.,Two different databases (resources and clinical database) were constructed.,Assessments were planned over a year divided by 4 three-month periods, with the goal of determining seasonal-related changes.,Exacerbations and survival served as the main endpoints.,This paper describes a methodological framework for conducting a clinical audit of COPD patients in an outpatient setting.,Results from such audits can guide health information systems development and implementation in real-world settings.

Cardiovascular disease is a primary cause of death in patients with chronic obstructive pulmonary disease (COPD).,Beta-blockers have been proved to reduce morbidity and improve survival in patients with cardiac diseases.,But the effects of beta-blockers on outcomes in patients with COPD remain controversial.,The objective of this meta-analysis was to assess the effect of beta-blockers on mortality and exacerbation in patients with COPD.,An extensive search of the EMBASE, MEDLINE and Cochrane was performed to retrieve the studies of beta-blockers treatment in patients with COPD.,The random effects model meta-analysis was used to evaluate effect on overall mortality and exacerbation of COPD.,Fifteen original observational cohort studies with a follow-up time from 1 to 7.2 years were included.,The results revealed that beta-blockers treatment significantly decreased the risk of overall mortality and exacerbation of COPD.,The relative risk (RR) for overall mortality was 0.72 (0.63 to 0.83), and for exacerbation of COPD was 0.63 (0.57 to 0.71).,In subgroup analysis of COPD patients with coronary heart disease or heart failure, the risk for overall mortality was 0.64 (0.54-0.76) and 0.74 (0.58-0.93), respectively.,The findings of this meta-analysis confirmed that beta-blocker use in patients with COPD may not only decrease the risk of overall mortality but also reduce the risk of exacerbation of COPD.,Beta-blocker prescription for cardiovascular diseases needs to improve in COPD patients.

COPD is associated with a relevant burden of disease and a high mortality worldwide.,Only recently, the importance of comorbidities of COPD has been recognized.,Studies postulated an association with inflammatory conditions potentially sharing pathogenic pathways and worsening overall prognosis.,More evidence is required to estimate the role of comorbidities of COPD.,Our aim was to investigate the prevalence and clustering of comorbidities associated with COPD, and to estimate their impact on clinically relevant outcomes.,In this population-based case-control study, a nation-wide database provided by the Swiss Federal Office for Statistics enclosing every hospital entry covering the years 2002-2010 (n = 12′888′075) was analyzed using MySQL and R statistical software.,Statistical methods included non-parametric hypothesis testing by means of Fisher’s exact test and Wilcoxon rank sum test, as well as linear models with generalized estimating equation to account for intra-patient variability.,Exploratory multivariate approaches were also used for the identification of clusters of comorbidities in COPD patients.,In 2.6% (6.3% in patients aged >70 years) of all hospitalization cases an active diagnosis of COPD was recorded.,In 21% of these cases, COPD was the main reason for hospitalization.,Patients with a diagnosis of COPD had more comorbidities (7 [IQR 4-9] vs.,3 [IQR 1-6]; ), were more frequently rehospitalized (annual hospitalization rate 0.33 [IQR 0.20-0.67] vs.,0.25 [IQR 0.14-0.43]/year; ), had a longer hospital stay (9 [IQR 4-15] vs.,5 [IQR 2-11] days; ), and had higher in-hospital mortality (5.9% [95% CI 5.8%-5.9%] vs.,3.4% [95% CI 3.3%-3.5%]; ) compared to matched controls.,A set of comorbidities was associated with worse outcome.,We could identify COPD-related clusters of COPD-comorbidities.

Among patients with chronic obstructive pulmonary disease (COPD), diabetes mellitus (DM) is a common comorbidity and is probably associated with increased systemic inflammation and worse prognosis.,Metformin, with its pleiotropic anti-inflammatory and antioxidant actions, may offer theoretical benefits in COPD patients with DM.,Thus, this study aimed to investigate the effects of DM and metformin use on mortality in the clinical trajectory of COPD.,This was a retrospective cohort study comprising patients with spirometry-confirmed COPD and an age of ≥40 years from 2008 to 2014.,The primary outcome of interest was all-cause mortality.,We evaluated the effects of DM on mortality through the clinical course of COPD and we also assessed the impact of metformin use on survival of the COPD population.,Among 4231 COPD patients, 556 (13%) had DM, and these patients had 1.62 times higher hazards of 2-year mortality than those without DM (95% confidence interval [CI], 1.15-2.28) after adjusting for age, gender, COPD stage, comorbidities and prior COPD hospitalization.,Over a 2-year period, metformin users had a significantly lower risk of death (hazard ratio, 0.46; 95% CI, 0.23-0.92) compared with non-metformin users in patients with coexistent COPD and DM.,Moreover, metformin users had similar survival to COPD patients without DM.,This study shows that DM is associated with an increased risk of death in COPD patients and metformin use seems to mitigate the hazard.,Our findings suggest a potential role of metformin in the management of DM in COPD.,The online version of this article (10.1186/s12931-019-1035-9) contains supplementary material, which is available to authorized users.

COPD is characterized by chronic bronchitis, chronic airway obstruction, and emphysema, leading to a progressive and irreversible decline in lung function.,Inflammation is central for the development of COPD.,Chronic inflammation in COPD mainly involves the infiltration of neutrophils, macrophages, lymphocytes, and other inflammatory cells into the small airways.,The contribution of resident airway structural cells to the inflammatory process is also important in COPD.,Airway remodeling consists of detrimental changes in structural tissues and cells including airway wall thickening, epithelial metaplasia, goblet cell hypertrophy, and smooth muscle hyperplasia.,Persistent airway inflammation might contribute to airway remodeling and small airway obstruction.,However, the underlying mechanisms remain unclear.,In this review, we will provide an overview of recent insights into the role of major immunoinflammatory cells in COPD airway remodeling.

Up to half of all smokers develop clinically significant chronic obstructive pulmonary disease (COPD).,Gaps exist in the implementation and uptake of evidence-based guidelines for managing COPD in primary care.,We describe the methodology of a cluster randomised controlled trial (cRCT) evaluating the efficacy and cost-effectiveness of an interdisciplinary model of care aimed at reducing the burden of smoking and COPD in Australian primary care settings.,A cRCT is being undertaken to evaluate an interdisciplinary model of care (RADICALS - Review of Airway Dysfunction and Interdisciplinary Community-based care of Adult Long-term Smokers).,General practice clinics across Melbourne, Australia, are identified and randomised to the intervention group (RADICALS) or usual care.,Patients who are current or ex-smokers, of at least 10 pack years, including those with an existing diagnosis of COPD, are being recruited to identify 280 participants with a spirometry-confirmed diagnosis of COPD.,Handheld lung function devices are being used to facilitate case-finding.,RADICALS includes individualised smoking cessation support, home-based pulmonary rehabilitation and home medicines review.,Patients at control group sites receive usual care and Quitline referral, as appropriate.,Follow-ups occur at 6 and 12 months from baseline to assess changes in quality of life, abstinence rates, health resource utilisation, symptom severity and lung function.,The primary outcome is change in St George’s Respiratory Questionnaire score of patients with COPD at 6 months from baseline.,This project has been approved by the Monash University Human Research Ethics Committee and La Trobe University Human Ethics Committee (CF14/1018 - 2014000433).,Results of the study will be disseminated in peer-reviewed journals and research conferences.,If the intervention is successful, the RADICALS programme could potentially be integrated into general practices across Australia and sustained over time.,ACTRN12614001155684; Pre-results.

The economic crisis in Greece has substantially affected patients with COPD.,The reduction of disposable income has its consequences on patients’ ability to afford their medication.,The aim of the study is to evaluate the cost of treatment for patients with COPD and the influence of the financial crisis to the patients.,Data were collected from 189 patients (male: 178, mean age: 70.1±8.4) who visited the outpatient department of University Hospital of Larissa in 2014 and 2015.,The pharmacological cost of treatment was calculated based on national pharmaceutical formulary prices.,COPD patients were classified into four stages according to Global Initiative for Chronic Obstructive Lung Disease (GOLD): 7.4% were in stage I, 43.4% in stage II, 34.4% in stage III, and 14.8% in stage IV.,Patients were graded as per GOLD as follows: 18% as grade A, 14.3% as B, 23.3% as C, and 44.4% as D.,The annual cost of COPD maintenance treatment per patient was €952.92 (±398.01), of which €239.91 were patients’ expenses.,The annual treatment cost for stable disease ranged from €615.44 to €1302.03 depending on disease stages (GOLD stages I-IV) and from €715.01 to €1101.05 depending on GOLD grades (grades A-D).,The cost of maintenance medication was statistically and significantly higher for patients with advanced disease (GOLD stages III-IV) and for patients at high risk (GOLD grades C-D [P=0.000]).,The pharmacological cost of treatment for COPD patients seems to be considerably high, in all disease stages.,As the average income is decreased, patients face difficulties to afford inhaled medication.

The aim of this retrospective study was to evaluate correlations between parameters of quantitative computed tomography (QCT) analysis, especially the 15th percentile of lung attenuation (P15), and parameters of clinical tests in a large group of patients with pulmonary emphysema.,One hundred and seventy-two patients with pulmonary emphysema and chronic obstructive pulmonary disease (COPD) global initiative for chronic obstructive lung disease (GOLD) stage 3 or 4 were assessed by nonenhanced thin-section CT scans in full inspiratory and expiratory breath-hold, pulmonary function test (PFT), a 6-minute walk test (6MWT), and quality of life questionnaires (SGRQ and CAT).,QCT parameters included total lung volume (TLV), total emphysema score (TES), and P15, all measured at inspiration (IN) and expiration (EX).,Differences between inspiration and expiration were calculated for TLV (TLVDiff), TES (TESDiff), and P15 (P15Diff).,Spearman correlation analysis was performed.,CT-measured lung volume in inspiration (TLVIN) correlated strongly with spirometry-measured total lung capacity (TLC) (r=0.81, p<0.001) and moderately to strongly with residual volume (RV), forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV1)/FVC (r=0.60, 0.56, and −0.49, each p<0.001).,Lung volume in expiration (TLVEX) correlated moderately to strongly with TLC, RV and FEV1/FVC ratio (r=0.75, 0.66, and −0.43, each p<0.001).,TES and P15 showed stronger correlations with the carbon monoxide transfer coefficient (KCO%) (r= −0.42, 0.44, both p<0.001), when measured during expiration.,P15Diff correlated moderately with KCO% and carbon monoxide diffusing capacity (DLCO%) (r= 0.41, 0.40, both p<0.001).,The 6MWT and most QCT parameters showed significant differences between COPD GOLD 3 and 4 groups.,Our results suggest that QCT can help predict the severity of lung function decrease in patients with pulmonary emphysema and COPD GOLD 3 or 4.,Some QCT parameters, including P15EX and P15Diff, correlated moderately to strongly with parameters of pulmonary function tests.

To assess tracheobronchial angles and their changes on combined inspiratory and expiratory thoracic computed tomography (CT) scans and to determine correlations between tracheobronchial angles and several indices of chronic obstructive pulmonary disease (COPD).,A total of 80 smokers underwent combined inspiratory and expiratory CT scans.,Of these, 65 subjects also performed spirometry and 55 patients were diagnosed with COPD.,On CT scans, 3-dimensinal tracheobronchial angles (trachea-right main bronchus [RMB], trachea-left main bronchus [LMB], and RMB-LMB) were automatically measured by software.,Lung volumes at inspiration and expiration were also automatically calculated.,Changes in tracheobronchial angles between inspiration and expiration were assessed by the Mann-Whitney test.,Correlations of the angles with lung volume, airflow limitation, and CT-based emphysema index were evaluated by Spearman rank correlation.,The trachea-LMB angle was significantly smaller and the RMB-LMB angle was significantly larger at expiration than inspiration (P<0.0001).,The trachea-LMB and RMB-LMB angles were significantly correlated with lung volume, particularly at expiration.,The RMB-LMB angle was significantly correlated with airflow limitation and CT emphysema index (P<0.001-0.05) at inspiration and expiration, suggesting that narrowed RMB-LMB angle indicates more severe airflow limitation and larger extent of emphysema.,Tracheobronchial angles change during respiration and are correlated with severity of COPD and emphysema.

Mesenchymal stem cells (MSCs) effectively reduce airway inflammation and regenerate the alveolus in cigarette- and elastase-induced chronic obstructive pulmonary disease (COPD) animal models.,The effects of stem cells are thought to be paracrine and immune-modulatory because very few stem cells remain in the lung one day after their systemic injection, which has been demonstrated previously.,In this report, we analyzed the gene expression profiles to compare mouse lungs with chronic exposure to cigarette smoke with non-exposed lungs.,Gene expression profiling was also conducted in a mouse lung tissue with chronic exposure to cigarette smoke following the systemic injection of human cord blood-derived mesenchymal stem cells (hCB-MSCs).,Globally, 834 genes were differentially expressed after systemic injection of hCB-MSCs.,Seven and 21 genes, respectively, were up-and downregulated on days 1, 4, and 14 after HCB-MSC injection.,The Hbb and Hba, genes with oxygen transport and antioxidant functions, were increased on days 1 and 14.,A serine protease inhibitor was also increased at a similar time point after injection of hCB-MSCs.,Gene Ontology analysis indicated that the levels of genes related to immune responses, metabolic processes, and blood vessel development were altered, indicating host responses after hCB-MSC injection.,These gene expression changes suggest that MSCs induce a regeneration mechanism against COPD induced by cigarette smoke.,These analyses provide basic data for understanding the regeneration mechanisms promoted by hCB-MSCs in cigarette smoke-induced COPD.

The aim of this study was to characterize the evolution of lung function and -structure in elastase-induced emphysema in adult mice and the effect of mesenchymal stromal cell (MSC) administration on these parameters.,Adult mice were treated with intratracheal (4.8 units/100 g bodyweight) elastase to induce emphysema.,MSCs were administered intratracheally or intravenously, before or after elastase injection.,Lung function measurements, histological and morphometric analysis of lung tissue were performed at 3 weeks, 5 and 10 months after elastase and at 19, 20 and 21 days following MSC administration.,Elastase-treated mice showed increased dynamic compliance and total lung capacity, and reduced tissue-specific elastance and forced expiratory flows at 3 weeks after elastase, which persisted during 10 months follow-up.,Histology showed heterogeneous alveolar destruction which also persisted during long-term follow-up.,Jugular vein injection of MSCs before elastase inhibited deterioration of lung function but had no effects on histology.,Intratracheal MSC treatment did not modify lung function or histology.,In conclusion, elastase-treated mice displayed persistent characteristics of pulmonary emphysema.,Jugular vein injection of MSCs prior to elastase reduced deterioration of lung function.,Intratracheal MSC treatment had no effect on lung function or histology.

Inhaled Corticosteroids (ICS) are commonly prescribed to patients with severe COPD and recurrent exacerbations.,It is not known what impact ICS cause in terms of COVID-19 positivity or disease severity in COPD.,This study examined 27,810 patients with COPD from the Cleveland Clinic COVID-19 registry between March 8th and September 16th, 2020.,Electronic health records were used to determine diagnosis of COPD, ICS use, and clinical outcomes.,Multivariate logistic regression was used to adjust for demographics, month of COVID-19 testing, and comorbidities known to be associated with increased risk for severe COVID-19 disease.,Amongst the COPD patients who were tested for COVID-19, 44.1% of those taking an ICS-containing inhaler tested positive for COVID-19 versus 47.2% who tested negative for COVID-19 (p = 0.033).,Of those who tested positive for COVID-19 (n = 1288), 371 (28.8%) required hospitalization.,In-hospital outcomes were not significantly different when comparing ICS versus no ICS in terms of ICU admission (36.8% [74/201] vs 31.2% [53/170], p = 0.30), endotracheal intubation (21.9% [44/201] vs 16.5% [28/170], p = 0.24), or mortality (18.4% [37/201] vs 20.0% [34/170], p = 0.80).,Multivariate logistic regression demonstrated no significant differences in hospitalization (adj OR 1.12, CI: 0.90-1.38), ICU admission (adj OR: 1.31, CI: 0.82-2.10), need for mechanical ventilation (adj OR 1.65, CI: 0.69-4.02), or mortality (OR: 0.80, CI: 0.43-1.49).,In conclusion, ICS therapy did not increase COVID-19 related healthcare utilization or mortality outcome in patients with COPD followed at the Cleveland Clinic health system.,These findings should encourage clinicians to continue ICS therapy for COPD patients during the COVID-19 pandemic.

Asthmatics and patients with chronic obstructive pulmonary disease (COPD) have more severe outcomes with viral infections than people without obstructive disease.,To evaluate if obstructive diseases are risk factors for intensive care unit (ICU) stay and death due to coronavirus disease 2019 (COVID19).,We collected data from the electronic medical record from 596 adult patients hospitalized in University Hospital of Liege between March 18 and April 17, 2020, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection.,We classified patients into 3 groups according to the underlying respiratory disease, present before the COVID19 pandemic.,Among patients requiring hospitalization for COVID19, asthma and COPD accounted for 9.6% and 7.7%, respectively.,The proportions of asthmatics, patients with COPD, and patients without obstructive airway disease hospitalized in the ICU were 17.5%, 19.6%, and 14%, respectively.,One-third of patients with COPD died during hospitalization, whereas only 7.0% of asthmatics and 13.6% of patients without airway obstruction died due to SARS-CoV2.,The multivariate analysis showed that asthma, COPD, inhaled corticosteroid treatment, and oral corticosteroid treatment were not independent risk factors for ICU admission or death.,Male gender (odds ratio [OR]: 1.9; 95% confidence interval [CI]: 1.1-3.2) and obesity (OR: 8.5; 95% CI: 5.1-14.1) were predictors of ICU admission, whereas male gender (OR 1.9; 95% CI: 1.1-3.2), older age (OR: 1.9; 95% CI: 1.6-2.3), cardiopathy (OR: 1.8; 95% CI: 1.1-3.1), and immunosuppressive diseases (OR: 3.6; 95% CI: 1.5-8.4) were independent predictors of death.,Asthma and COPD are not risk factors for ICU admission and death related to SARS-CoV2 infection.

Individuals with COPD have systemic inflammation that can be assessed by measuring C-reactive protein (CRP).,In this paper we evaluated whether CRP is related to COPD, lung function and rate of lung function decline.,We included 1237 randomly selected subjects (mean age 42, range 28-56 years) from three centers in the European Community Respiratory Health Survey: Reykjavik, Uppsala and Tartu.,CRP was measured at the end of the follow-up (mean 8.3 years) and the values were divided into 4 quartiles.,Fifty-three non-asthmatic subjects fulfilled spirometric criteria for COPD (FEV1/FVC < 70%).,COPD occurred more often in the 4th CRP quartile (OR (95% CI) 3.21 (1.13-9.08)) after adjustment for age, gender, body weight and smoking.,High CRP levels were related to lower FEV1 values in both men (−437 (−596, −279) mL) and women (−144 (−243, −44) mL).,The negative association between CRP and FEV1 was significantly larger in men than women (p = 0.04).,The decline in FEV1 was larger (16 (5, 27) mL) in men with high CRP levels whereas no significant association between CRP and FEV1 decline was found in women.,Higher CRP values are significantly associated with COPD and lower lung function in men and women.,In men higher CRP values are related to a larger decline in FEV1.

Recent reports indicate that over the next decade rates of chronic obstructive pulmonary disease (COPD) in women will exceed those in men in the western world, though in most jurisdictions, women continue to smoke less compared with men.,Whether female adult smokers are biologically more susceptible to COPD is unknown.,This study reviewed the available evidence to determine whether female adult smokers have a faster decline in forced expiratory volume in one second (FEV1) compared with male adult smokers and whether age modifies the relationship between cigarette smoke and lung function decline.,A systematic review and a meta-analysis was performed of population-based cohort studies that had a follow-up period of at least 3 years, measured FEV1 on at least two different time points, and presented FEV1 data stratified by gender and smoking status in adults.,Of the 646 potentially relevant articles, 11 studies met these criteria and were included in the analyses (N = 55 709 participants).,There was heterogeneity in gender-related results across the studies.,However, on average current smokers had a faster annual decline rate in FEV1% predicted compared with never and former smokers.,Female current smokers had with increasing age a significantly faster annual decline in FEV1% predicted than male current smokers (linear regression analysis, R2 = 0.56; p = 0.008).,Age did not materially affect the rate of decline in FEV1% predicted in male and female former and never smokers (p = 0.775 and p = 0.326, respectively).,As female smokers age, they appear to experience an accelerated decline in FEV1% predicted compared with male smokers.,Future research powered specifically on gender-related changes in lung function is needed to confirm these early findings.

The association between chronic obstructive pulmonary disease (COPD), lung function and risk of type 2 diabetes mellitus (T2DM) remains controversial.,We performed a meta-analysis to clarify this issue.,The PubMed and EMBASE databases were searched.,Cohort studies on COPD, lung function and risk of T2DM in adults were included.,A random effects model was adopted to calculate the summary risk ratio (RR) and 95% confidence interval (CI).,Dose-response analysis was conducted where possible.,A total of 13 eligible cohort studies involving 307,335 incident T2DM cases and 7,683,784 individuals were included.,The risk of T2DM was significantly higher in patients with COPD than those without COPD (RR = 1.25, 95% CI 1.16-1.34).,Compared to the highest category of percentage forced vital capacity (FVC%), the lowest category of FVC% was associated with a higher risk of T2DM (RR = 1.43, 95% CI 1.33-1.53).,Similarly, the summary RR of T2DM for the lowest versus highest category of percentage forced expiratory volume in 1 s (FEV1%) was 1.49 (95% CI 1.39-1.60).,Significant linear associations of FVC% and FEV1% with risk of T2DM were found (Pnon-linearity > 0.05); the RR of T2DM was 0.88 (95% CI 0.82-0.95) and 0.87 (95% CI 0.81-0.94) per 10% increase in FVC% and FEV1%, respectively.,There was a non-significant relationship between the FEV1/FVC ratio and the risk of T2DM.,Both COPD and impaired lung function, especially restricted ventilation dysfunction, could increase the risk of T2DM.,However, these findings should be interpreted with caution due to the limited number of studies, and need to be validated by future studies.

To evaluate risk factors associated with exacerbation frequency in primary care.,Information on exacerbations of chronic obstructive pulmonary disease (COPD) has mainly been generated by secondary care-based clinical cohorts.,Retrospective observational cohort study.,Electronic medical records database (England and Wales).,58 589 patients with COPD aged ≥40 years with COPD diagnosis recorded between 1 April 2009 and 30 September 2012, and with at least 365 days of follow-up before and after the COPD diagnosis, were identified in the Clinical Practice Research Datalink.,Mean age: 69 years; 47% female; mean forced expiratory volume in 1s 60% predicted.,Data on moderate or severe exacerbation episodes defined by diagnosis and/or medication codes 12 months following cohort entry were retrieved, together with demographic and clinical characteristics.,Associations between patient characteristics and odds of having none versus one, none versus frequent (≥2) and one versus frequent exacerbations over 12 months follow-up were evaluated using multivariate logistic regression models.,During follow-up, 23% of patients had evidence of frequent moderate-to-severe COPD exacerbations (24% one; 53% none).,Independent predictors of increased odds of having exacerbations during the follow-up, either frequent episodes or one episode, included prior exacerbations, increasing dyspnoea score, increasing grade of airflow limitation, females and prior or current history of several comorbidities (eg, asthma, depression, anxiety, heart failure and cancer).,Primary care-managed patients with COPD at the highest risk of exacerbations can be identified by exploring medical history for the presence of prior exacerbations, greater COPD disease severity and co-occurrence of other medical conditions.

Debate exists regarding which endpoints most sensitively reflect day-to-day variation in chronic obstructive pulmonary disease (COPD) symptoms and are most useful in clinical practice to predict COPD exacerbations.,We hypothesized that short-acting β2-agonist (SABA) reliever use would predict short- and long-term exacerbation risk in COPD patients.,We performed a retrospective analysis of data from a study (ClinicalTrials.gov registration: NCT00419744) comparing budesonide/formoterol 320/9 μg with formoterol 9 μg (both twice daily) in patients with moderate-to-very-severe COPD; reliever salbutamol 90 μg was provided.,First occurrence of reliever use >4 (low), >10 (medium), and >20 (high) inhalations/day was assessed as a predictor of short-term (3-week) exacerbation risk.,Mean daily reliever use in the week preceding the 2-month visit was investigated as a predictor of the long-term (10-month) exacerbation risk, using intervals of 2-5, 6-9, and ≥10 inhalations/day.,Overall, 810 patients were included (61 % male; mean age 63.2 years; post-bronchodilator forced expiratory volume in 1 s 37.7 % of predicted).,First occurrence of low, medium, or high reliever use was predictive of an exacerbation within the following 3 weeks; exacerbation risk increased significantly with increasing reliever use.,Mean reliever use over 1 week was predictive of long-term exacerbation risk.,Patients with mean use of 2-5, 6-9, and ≥10 inhalations/day exhibited 21 %, 67 %, and 135 % higher exacerbation rates, respectively, in the following 10 months, compared with <2 inhalations/day.,Budesonide/formoterol was associated with lower short- and long-term exacerbation risk than formoterol in all reliever-use groups.,SABA reliever use is a predictor of short- and long-term exacerbation risk in moderate-to-very-severe COPD patients with a history of exacerbations receiving budesonide/formoterol or formoterol.

Addition of a second bronchodilator from a different pharmacological class may benefit patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) whose symptoms are insufficiently controlled by bronchodilator monotherapy.,GLOW6 evaluated the efficacy and safety of once-daily coadministration of the long-acting β2-agonist indacaterol (IND) and the long-acting muscarinic antagonist glycopyrronium (GLY) versus IND alone in patients with moderate-to-severe COPD.,In this randomized, double-blind, parallel group, placebo-controlled, 12-week study, patients were randomized 1:1 to IND 150 μg and GLY 50 μg daily (IND + GLY) or IND 150 μg daily and placebo (IND + PBO) (all delivered via separate Breezhaler® devices).,The primary objective was to demonstrate the superiority of IND + GLY versus IND + PBO for trough forced expiratory volume in 1 second (FEV1) at week 12.,Other end points included trough FEV1 at day 1, FEV1 area under the curve from 30 minutes to 4 hours (AUC30min-4h), peak FEV1, inspiratory capacity and trough forced vital capacity (FVC) at day 1 and week 12, and transition dyspnea index (TDI) focal score, COPD symptoms, and rescue medication use over 12 weeks.,A total of 449 patients were randomized (IND + GLY, 226; IND + PBO, 223); 94% completed the study.,On day 1 and at week 12, IND + GLY significantly improved trough FEV1 versus IND + PBO, with treatment differences of 74 mL (95% CI 46-101 mL) and 64 mL (95% CI 28-99 mL), respectively (both P<0.001).,IND + GLY significantly improved postdose peak FEV1, FEV1 AUC30min-4h, and trough FVC at day 1 and week 12 versus IND + PBO (all P<0.01).,TDI focal score and COPD symptoms (percentage of days able to perform usual daily activities and change from baseline in mean daytime respiratory score) were significantly improved with IND + GLY versus IND + PBO (P<0.05).,The incidence of adverse events was similar for the two treatment groups.,In patients with moderate-to-severe COPD, once-daily coadministration of IND and GLY provides significant and sustained improvement in bronchodilation versus IND alone from day 1, with significant improvements in patient-centered outcomes.

Chronic obstructive pulmonary disease (COPD) ranks among the leading causes of morbidity and mortality worldwide.,COPD rarely occurs in isolation and is often combined with various diseases.,It is considered that systemic inflammation underlies the comorbid course of COPD.,The data obtained in recent years have shown the importance of violations of the cross-links of lipid metabolism and the immune response, which are links in the pathogenesis of both COPD and atherosclerosis.,The role of lipid metabolism disorders in the pathogenesis of the comorbid course of COPD and atherosclerosis and the participation of ATP-binding cassette (ABC) transporters in these processes is discussed in this article.,It is known that about 20 representatives of a large family of ABC transporters provide lipid homeostasis of cells by moving lipids inside the cell and in its plasma membrane, as well as removing lipids from the cell.,It was shown that some representatives of the ABC-transporter family are involved in various links of the pathogenesis of COPD and atherosclerosis, which can determine their comorbid course.

Metabolic syndrome (MetS) is frequent in both chronic obstructive pulmonary disease (COPD) and Obstructive sleep apnea (OSA).,The aim of this study was to assess the frequency of MetS and the status of systemic inflammation in overlap syndrome.,A total of 151 consecutive COPD patients were recruited in this cross‐sectional study.,Spirometry and polysomnography were done in all patients.,The MetS was defined according to the criteria of the International Diabetes Federation.,Anthropometry, metabolic parameters and inflammatory biomarkers: IL‐6, TNF‐α, leptin, resistin and adiponectin were recorded.,OSA was present in 19.2% COPD patients.,Subjects with overlap syndrome had higher neck and waist circumference compared to those with COPD alone.,Significant differences in levels of blood pressure, lipid metabolic and glucose metabolic were found between two groups with overlap and COPD, as well as inflammatory biomarkers.,Prevalence of MetS was increased in overlap group.,Multivariate logistic regression showed that BMI, systolic BP when fall asleep and recumbent angiotens levels as significant independent predictors of the presence of Mets in overlap syndrome.,This study shows that MetS is frequent in patients with overlap.,Overlap syndrome indicates a higher cardiometabolic risk and higher levels of systemic inflammatory.

Alterations in the composition of the lung microbiome associated with adverse clinical outcomes, known as dysbiosis, have been implicated with disease severity and exacerbations in COPD.,To characterise longitudinal changes in the lung microbiome in the AERIS study (Acute Exacerbation and Respiratory InfectionS in COPD) and their relationship with associated COPD outcomes.,We surveyed 584 sputum samples from 101 patients with COPD to analyse the lung microbiome at both stable and exacerbation time points over 1 year using high-throughput sequencing of the 16S ribosomal RNA gene.,We incorporated additional lung microbiology, blood markers and in-depth clinical assessments to classify COPD phenotypes.,The stability of the lung microbiome over time was more likely to be decreased in exacerbations and within individuals with higher exacerbation frequencies.,Analysis of exacerbation phenotypes using a Markov chain model revealed that bacterial and eosinophilic exacerbations were more likely to be repeated in subsequent exacerbations within a subject, whereas viral exacerbations were not more likely to be repeated.,We also confirmed the association of bacterial genera, including Haemophilus and Moraxella, with disease severity, exacerbation events and bronchiectasis.,Subtypes of COPD have distinct bacterial compositions and stabilities over time.,Some exacerbation subtypes have non-random probabilities of repeating those subtypes in the future.,This study provides insights pertaining to the identification of bacterial targets in the lung and biomarkers to classify COPD subtypes and to determine appropriate treatments for the patient.,Results, NCT01360398.

The bronchial microbiome in severe COPD during stability and exacerbation in patients chronically colonised by Pseudomonas aeruginosa (PA), has not been defined.,Our objective was to determine the characteristics of the bronchial microbiome of severe COPD patients colonised and not colonised by P. aeruginosa and its changes during exacerbation.,COPD patients with severe disease and frequent exacerbations were categorised according to chronic colonisation by P. aeruginosa.,Sputum samples were obtained in stability and exacerbation, cultured, and analysed by 16S rRNA gene amplification and pyrosequencing.,Sixteen patients were included, 5 of them showing chronic colonisation by P. aeruginosa.,Pseudomonas genus had significantly higher relative abundance in stable colonised patients (p = 0.019), but no significant differences in biodiversity parameters were found between the two groups (Shannon, 3 (2-4) vs 3 (2-3), p = 0.699; Chao1, 124 (77-159) vs 140 (115-163), p = 0.364).,In PA-colonised patients bronchial microbiome changed to a microbiome similar to non-PA-colonised patients during exacerbations.,An increase in the relative abundance over 20 % during exacerbation was found for Streptococcus, Pseudomonas, Moraxella, Haemophilus, Neisseria, Achromobacter and Corynebacterium genera, which include recognised potentially pathogenic microorganisms, in 13 patients colonised and not colonised by P. aeruginosa with paired samples.,These increases were not identified by culture in 5 out of 13 participants (38.5 %).,Stable COPD patients with severe disease and PA-colonised showed a similar biodiversity to non-PA-colonised patients, with a higher relative abundance of Pseudomonas genus in bronchial secretions.,Exacerbation in severe COPD patients showed the same microbial pattern, independently of previous colonisation by P. aeruginosa.,The online version of this article (doi:10.1007/s10096-013-2044-0) contains supplementary material, which is available to authorized users.

Chronic obstructive pulmonary disease (COPD) is a common cause of suffering and death.,Evidence-based management of COPD by general practitioners (GPs) is crucial for decreasing the impact of the disease.,Efficient strategies include early diagnosis, smoking cessation and multimodal treatment.,To describe knowledge about and skills for managing COPD in GPs in Sweden.,Prior to COPD education (the PRIMAIR Study), GPs at primary health care centers (PHCCs) in Stockholm replied to 13 written, patient-case based, multiple choice and free-text questions about COPD.,Their knowledge and practical management skills were assessed by assigned points that were analyzed with non-parametric tests.,Overall, 250 GPs at 34 PHCCs replied (89% response rate).,Total mean score was 9.9 (maximum 26).,Scores were highest on ‘management of smoking cessation’, ‘follow-up after exacerbation’ and ‘diagnostic procedures’.,Spirometry was used frequently, although interpretation skills were suboptimal.,‘Management of maintenance therapy’, ‘management of multimorbidity’ and ‘interprofessional cooperation’ had mediocre scores.,Scores were unrelated to whether there was a nurse-led asthma/COPD clinic at the PHCC.,Swedish GPs’ knowledge of COPD and adherence to current guidelines seem insufficient.,A nurse-led asthma/COPD clinic at the PHCC does not correlate with sufficient COPD skills in the GPs.,The relevance of this study to participants’ actual clinical practice and usefulness of easy-to-access clinical guides are interesting topics for future investigation.,To identify problem areas, we suggest using questionnaires prior to educational interventions.,General practitioners (GPs) play a crucial role in providing evidence-based care for patients with chronic obstructive pulmonary disease (COPD) who are treated in primary care.,Swedish GPs’ knowledge about COPD and adherence to current guidelines seem insufficient.,Areas in greatest need of improvement are spirometry interpretation, management of maintenance therapy, management of multimorbidity in patients with COPD and interprofessional cooperation.

In Denmark, the treatment of COPD is mainly managed by general practitioners (GPs).,Pulmonary rehabilitation (PR) is available to patients with COPD in the local community by GP referral, but in practice, many patients do not participate in rehabilitation.,The aim of our study was to explore 1) GPs’ perceptions of their role and responsibility in the rehabilitation of patients with COPD, and 2) GPs’ perceptions of how patients manage their COPD.,The study was based on a qualitative design with semi-structured key-informant interviews with GPs.,Investigator triangulation was applied during data generation, and analysis was done using thematic analysis methodology.,Our main findings were that GPs relied on patients themselves to take the initiative to make clinic appointments and on professionals at health centers to provide the PR including consultations on lifestyle changes.,The GPs experienced that patients chose to come to the clinic when they were in distress and that patients either declined or had poor adherence to rehabilitation when offered.,The GPs were relieved that the health centers had taken over the responsibility of rehabilitation as GPs lacked the resources to discuss rehabilitation and follow up on individual plans.,Our study suggested a potential self-reinforcing problem with the treatment of COPD being mainly focused on medication rather than on PR.,Neither GPs nor patients used a proactive approach.,Further, GPs were not fully committed to discuss non-pharmacological treatment and perceived the patients as unmotivated for PR.,As such, there is a need for optimizing non-pharmacological treatment of COPD and in particular the referral process to PR.

Efficient management of COPD represents an international challenge.,Effective management strategies within the means of limited health care budgets are urgently required.,This analysis aimed to evaluate the cost-effectiveness of a home-based disease management (DM) intervention vs usual management (UM) in patients from the COPD Patient Management European Trial (COMET).,Cost-effectiveness was evaluated in 319 intention-to-treat patients over 12 months in COMET.,The analysis captured unplanned all-cause hospitalization days, mortality, and quality-adjusted life expectancy.,Costs were evaluated from a National Health Service perspective for France, Germany, and Spain, and in a pooled analysis, and were expressed in 2015 Euros (EUR).,Quality of life was assessed using the 15D health-related quality-of-life instrument and mapped to utility scores.,Home-based DM was associated with improved mortality and quality-adjusted life expectancy.,DM and UM were associated with equivalent direct costs (DM reduced costs by EUR −37 per patient per year) in the pooled analysis.,DM was associated with lower costs in France (EUR −806 per patient per year) and Spain (EUR −51 per patient per year), but higher costs in Germany (EUR 391 per patient per year).,Evaluation of cost per death avoided and cost per quality-adjusted life year (QALY) gained showed that DM was dominant (more QALYs and cost saving) in France and Spain, and cost-effective in Germany vs UM.,Nonparametric bootstrapping analysis, assuming a willingness-to-pay threshold of EUR 20,000 per QALY gained, indicated that the probability of home-based DM being cost-effective vs UM was 87.7% in France, 81.5% in Spain, and 75.9% in Germany.,Home-based DM improved clinical outcomes at equivalent cost vs UM in France and Spain, and in the pooled analysis.,DM was cost-effective in Germany with an incremental cost-effectiveness ratio of EUR 2,541 per QALY gained.,The COMET home-based DM intervention could represent an attractive alternative to UM for European health care payers.

Patients with chronic obstructive pulmonary disease (COPD) are often nonadherent with medications and have poor inhaler technique.,Community pharmacists can help to improve health-related quality of life and overall outcomes in patients with COPD.,We aim to measure the effectiveness of a systematic, pharmacist-driven intervention on patients with diagnosed COPD.,This pragmatic, parallel-group, cluster randomized controlled trial is designed to determine the effectiveness of a multifactorial, pharmacist-led intervention on medication adherence, inhaler technique, health-related quality of life, health care resource utilization including COPD exacerbations, and use of medications.,Participating pharmacies in Newfoundland and Labrador (NL), Canada will be randomly assigned to either the intervention or the control group.,The intervention group will deliver an enhanced form of care that emphasizes COPD management.,The control group will provide usual care and a COPD education pamphlet.,Included patients will be aged 40 years or older, have a physician-confirmed diagnosis of COPD, and be able to answer questionnaires in English.,The primary outcomes are the between-group difference in the change from baseline to 6 months in medication adherence using the Medication Possession Ratio (MPR) and the Morisky Medication Adherence Scale (MMAS-8).,The secondary outcomes are also measured from baseline to 6 months, and include the proportion of patients with a clinically significant change in adherence, the proportion of patients defined as having “good adherence,” the mean MPR between groups, quality of life as measured by the St.,George’s Respiratory Questionnaire, medication inhalation technique using a pharmacist-scored checklist, health care resource utilization and antibiotic and orally administered corticosteroid use for COPD exacerbations.,Differences between groups will be analyzed at the individual patient level while controlling for clustering effect.,A pharmacist-led COPD intervention has the potential to improve patient medication adherence, thus increasing quality of life, possibly decreasing pulmonary exacerbations and reducing utilization of acute health care resources.,Methods and results taken from this study could be used to enhance the delivery of COPD care by community pharmacists in a real-world setting.,This would serve to enhance COPD population health and quality of life.,International Standard Randomized Controlled Trial Number (ISRCTN) ISRCTN78138190, registered on 3 February 2016.,The online version of this article (doi:10.1186/s13063-016-1623-7) contains supplementary material, which is available to authorized users.

The benefits of noninvasive positive pressure ventilation (NPPV) in patients with hypercapnic COPD are controversial.,It is presumed that methodology and appropriate use of NIV ventilator might be crucial for the outcomes.,With the new built-in software, the performance of NIV can be monitored at home, which can guarantee the compliance and appropriate use.,This study investigated effects of home use of NIV in hypercapnia in COPD patients using the NIV ventilator with built-in software for monitoring.,The current multicenter prospective, randomized, controlled trial enrolled patients with stable GOLD stages III and IV hypercapnic COPD.,Patients were randomly assigned via a computer-generated randomization sequence, with a block size of four patients, to continue optimized treatment (control group) or to receive additional NPPV (intervention group) for 3 months.,The primary outcome was arterial carbon dioxide pressure (PaCO2).,Data were derived from built-in software and analyzed every 4 weeks.,Analysis was carried out with the intention to treat.,This study is registered with ClinicalTrials.gov, number NCT02499718.,Patients were recruited from 20 respiratory units in China from October 1, 2015, and recruitment was terminated with a record of the vital statistics on May 31, 2016.,A total of 115 patients were randomly assigned to the NPPV group (n=57) or the control group (n=58).,Patients complied well with NPPV therapy (mean [± standard deviation] day use 5.6±1.4 h).,The mean estimation of leaks was 37.99±13.71 L/min.,The changes in PaCO2 (−10.41±0.97 vs −4.32±0.68 mmHg, P=0.03) and 6-min walk distance (6MWD) (38.2% vs 18.2%, P=0.02) were statistically significant in the NPPV group versus the control group.,COPD assessment test (CAT) showed a positive trend (P=0.06) in favor of the NPPV group.,Pulmonary function and dyspnea were not different between groups.,Ventilators equipped with built-in software provided methodology for monitoring NIV use at home, which could facilitate the improvement of compliance and quality control of NIV use.,It was shown that three months use of NIV at home could reduce the PaCO2 and improve exercise tolerance (6MWD) in chronic hypercapnic COPD patients.

High-intensity (high-pressure and high backup rate) noninvasive ventilation has recently been advocated for the management of stable hypercapnic chronic obstructive pulmonary disease (COPD).,However, the relative contributions of high inspiratory pressure and high backup rate to ventilator adherence and physiological outcome have not been investigated.,Patients with stable hypercapnic COPD (daytime PaCO2 > 6 kPa) and nocturnal hypoventilation were enrolled.,Patients were randomly allocated to high-pressure and high backup rate (high-intensity) and high-pressure and low backup rate (high-pressure) for a 6-week period.,At the end of the first treatment period, patients were switched to the alternative treatment.,The primary outcome measure was mean nightly ventilator usage.,Twelve patients were recruited, with seven completing the 12-week trial protocol.,The mean patient age was 71 ± 8 years, with a forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) of 50% ± 13% and FEV1 of 32% ± 12%.,The baseline PaCO2 and PaO2 were 8.6 ± 1.7 kPa and 7.3 ± 1.4 kPa, respectively.,There was no significant difference demonstrated in mean nightly ventilator usage between the high-intensity and high-pressure groups (difference of 4 minutes; 95% confidence interval −45 to 53; P = 0.9).,Furthermore, there were no differences in any of the secondary endpoints, with the exception of the respiratory domain of the Severe Respiratory Insufficiency questionnaire, which was lower in the high-intensity arm than in the high-pressure arm (57 ± 11 versus 69 ± 16; P < 0.05).,There was no additional benefit, in terms of night-time ventilator adherence or any of the other measured parameters, demonstrated by addition of a high backup rate to high-pressure noninvasive ventilation.,These data suggest that it is the high-pressure component of the high-intensity noninvasive ventilation approach that plays the important therapeutic role in the management of hypercapnic respiratory failure in COPD patients.

Chronic infections are associated with exacerbation in patients with chronic obstructive pulmonary disease (COPD).,The major objective of the management of these patients is the prevention and effective treatment of exacerbations.,Patients that have increased sputum production, associated with purulence and worsening shortness of breath, are the ones that will benefit from antibiotic therapy.,It is important to give the appropriate antibiotic therapy to prevent treatment failure, relapse, and the emergence of resistant pathogens.,In some patients, systemic corticosteroids are also indicated to improve symptoms.,In order to identify which patients are more likely to benefit from these therapies, clinical guidelines recommend stratifying patients based on their risk factor associated with poor outcome or recurrence.,It has been identified that patients with more severe disease, recurrent infection and presence of purulent sputum are the ones that will be more likely to benefit from this therapy.,Another approach related to disease prevention could be the use of prophylactic antibiotics during steady state condition.,Some studies have evaluated the continuous or the intermittent use of antibiotics in order to prevent exacerbations.,Due to increased bacterial resistance to antibiotics and the presence of side effects, several antibiotics have been developed to be nebulized for both treatment and prevention of acute exacerbations.,There is a need to design long-term studies to evaluate these interventions in the natural history of the disease.,The purpose of this publication is to review our understanding of the role of bacterial infection in patients with COPD exacerbation, the role of antibiotics, and future interventions.

Airway mucus hypersecretion is a frequent symptom associated with acute and chronic airway disease.,Inhibition of mucus production or promotion of mucolysis not only relieved symptoms but also improved disease outcomes.,There are numerous available mucoactive medicines for prescription, and how to select them properly for different diseases is important for clinical practice.,So far, there is no one consensus or guideline reported.,A group of Chinese pulmonary physicians worked together to complete this consensus based on literature review, summarized mechanism and usage of each classical mucoactive medicine.,In general, antioxidant mucoactive medicines play an important role in chronic airway disease, including but not limited to airway mucus clearance, reduced acute exacerbation and improved pulmonary function.

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are associated with a significant mortality, health and economic burden.,Their diagnosis, assessment and management remain suboptimal and unchanged for decades.,Recent clinical and translational studies revealed that the significant heterogeneity in mechanisms and outcomes of exacerbations could be resolved by grouping them etiologically.,This is anticipated to lead to a better understanding of the biological processes that underlie each type of exacerbation and to allow the introduction of precision medicine interventions that could improve outcomes.,This review summarises novel data on the diagnosis, phenotyping, targeted treatment and prevention of COPD exacerbations.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder of the lung and whole body caused mainly by tobacco smoking.,Patients with advanced COPD are in a state of undernutrition, referred to as pulmonary cachexia; the exercise performance and quality of life (QOL) of these patients are deteriorated, the vital prognosis is unfavorable, and the medico-economic burden posed by poorly nourished COPD patients is high.,The mainstays of COPD treatment are pharmacotherapy, mainly with bronchodilators, and non-pharmacotherapeutic approaches such as respiratory rehabilitation and nutrition counseling.,Nutritional supplement therapy, consisting primarily of high calorie intake, has been demonstrated to be effective for maintaining and improving the muscle strength and exercise tolerance in poorly nourished COPD patients.,The efficacy of intake of various nutrients, besides a high calorie intake, for amelioration of the disease state of COPD has also been reported.,The roles of adipokines in the pathophysiology of COPD have begun to receive attention recently, and not only their regulatory effects on appetite and nutritional status, but also their influence on systemic inflammation have been increasingly clarified.,We review the papers on COPD and nutrition and discuss the role of nutritional supplement therapy in the treatment of COPD.

Chronic obstructive pulmonary disease (COPD) is a major cause of mortality worldwide.,Patients with COPD frequently have systemic comorbidities that often require unscheduled hospitalization for exacerbation and deterioration of physical conditions, and can have a poor prognosis.,We verified factors affecting patients’ short-term mortality, using a national inpatient database in Japan.,We retrospectively collected data for COPD patients (age: >40 years) with emergency admission between July 2010 and March 2013, using the Diagnosis Procedure Combination database.,We performed multivariate logistic analyses fitted with a generalized estimating equation to assess factors associated with all-cause in-hospital mortality.,A total of 177,207 patients (mean age: 77.5 years; males: 72.9%) were identified.,All-cause in-hospital death occurred in 23,614 patients (13.7%).,Higher mortality was associated with older age, male sex, lower body mass index, more severe dyspnea, lower level of consciousness, and worse activities of daily life.,Higher mortality was also associated with comorbid conditions, including bacterial pneumonia, aspiration pneumonia, interstitial pneumonitis, pulmonary embolism, respiratory failure, lung cancer, heart failure, cerebral infarction, liver cirrhosis, and chronic renal failure.,Our study demonstrated that all-cause in-hospital mortality in patients with COPD who required emergency hospitalization was associated with deteriorated general conditions and comorbidities at admission.,Physicians should take into account these prognostic factors to choose better treatment options for COPD patients.

Implementation of noninvasive ventilation (NIV) as an add-on treatment has been routinely used in a non-intensive care setting since 2004 for patients with chronic obstructive pulmonary disease (COPD) and acute hypercapnic respiratory failure at a university hospital in Denmark.,Although randomized controlled trials show lowered mortality rates in highly selected patients with acute exacerbation and respiratory failure, there are only few reports on long-term survival after receiving NIV.,We present long-term all-cause mortality data from patients receiving NIV for the first time.,Data from medical records were retrospectively retrieved from all patients receiving NIV for the first time after being admitted acutely to an acute medical ward and further transfer to a respiratory ward with respiratory failure and a diagnosis of COPD in the period January 1, 2005 to December 31, 2007; patients were followed until January 2012.,Demographic data collected included age, sex, diagnoses at discharge, and, when present, FEV1; a “not-to-intubate” order was also registered when listed.,In total, 253 patients (143 female, 110 male) received NIV for the first time.,The median age was 72 years (range 46-91 years).,The 30-day mortality rate was 29.3%.,The 5-year survival rate was 23.7%.,Women showed a trend towards better survival than men (25.7% vs 19.2%, P = 0.25), and the trend was even more pronounced for patients with COPD.,The mortality rate of patients receiving NIV is high, as expected in a real-life setting, but with a 5-year survival rate of 23.7% with a trend towards more female than male long-term survivors.

The prevalence of metabolic syndrome in COPD patients and its impact on patient related outcomes has been little studied.,We evaluated the prevalence of metabolic syndrome and clinical and functional characteristics in patients with COPD and healthy subjects.,228 COPD patients and 156 healthy subjects were included.,Metabolic syndrome was defined using criteria of the IDF.,In all patients spirometry, body composition, functional exercise performance, and mood and health status were assessed.,Groups were stratified for BMI and gender.,Metabolic syndrome was present in 57% of the COPD patients and 40% of the healthy subjects.,After stratification for BMI, presence of metabolic syndrome in patients with a BMI ≥25 kg/m2 was higher than in healthy peers.,Patients with metabolic syndrome and a BMI <25 kg/m2 had higher BMI, fat free mass index and bone mineral density, and a lower 6MWD than the BMI matched patients without metabolic syndrome.,Spirometry, maximal ergometry, mood and health status, and blood gases were not different between those groups.,In COPD patients with metabolic syndrome self-reported co-morbidities and medication use were higher than in those without.,Metabolic syndrome is more prevalent in overweight or obese COPD patients than in BMI matched healthy subjects.,Metabolic syndrome did not additionally impact patients' functional outcomes, but did impact the prevalence of co-morbidities.

Respiratory syncytial viral (RSV) infections are a frequent cause of chronic obstructive pulmonary disease (COPD) exacerbations, which are a major factor in disease progression and mortality.,RSV is able to evade antiviral defenses to persist in the lungs of COPD patients.,Though RSV infection has been identified in COPD, its contribution to cigarette smoke-induced airway inflammation and lung tissue destruction has not been established.,Here we examine the long-term effects of cigarette smoke exposure, in combination with monthly RSV infections, on pulmonary inflammation, protease production and remodeling in mice.,RSV exposures enhanced the influx of macrophages, neutrophils and lymphocytes to the airways of cigarette smoke exposed C57BL/6J mice.,This infiltration of cells was most pronounced around the vasculature and bronchial airways.,By itself, RSV caused significant airspace enlargement and fibrosis in mice and these effects were accentuated with concomitant smoke exposure.,Combined stimulation with both smoke and RSV synergistically induced cytokine (IL-1α, IL-17, IFN-γ, KC, IL-13, CXCL9, RANTES, MIF and GM-CSF) and protease (MMP-2, -8, -12, -13, -16 and cathepsins E, S, W and Z) expression.,In addition, RSV exposure caused marked apoptosis within the airways of infected mice, which was augmented by cigarette smoke exposure.,RSV and smoke exposure also reduced protein phosphatase 2A (PP2A) and protein tyrosine phosphates (PTP1B) expression and activity.,This is significant as these phosphatases counter smoke-induced inflammation and protease expression.,Together, these findings show for the first time that recurrent RSV infection markedly enhances inflammation, apoptosis and tissue destruction in smoke-exposed mice.,Indeed, these results indicate that preventing RSV transmission and infection has the potential to significantly impact on COPD severity and progression.

In comparison to genome-wide association studies (GWAS), there has been poor replication of gene expression studies in chronic obstructive pulmonary disease (COPD).,We performed microarray gene expression profiling on a large sample of resected lung tissues from subjects with severe COPD.,Comparing 111 COPD cases and 40 control smokers, 204 genes were differentially expressed; none were at significant GWAS loci.,The top differentially expressed gene was HMGB1, which interacts with AGER, a known COPD GWAS gene.,Differentially expressed genes showed enrichment for putative interactors of the first three identified COPD GWAS genes IREB2, HHIP, and FAM13A, based on gene sets derived from protein and RNA binding studies, RNA-interference, a murine smoking model, and expression quantitative trait locus analyses.,The gene module most highly associated for COPD in Weighted Gene Co-Expression Network Analysis (WGCNA) was enriched for B cell pathways, and shared seventeen genes with a mouse smoking model and twenty genes with previous emphysema studies.,As in other common diseases, genes at COPD GWAS loci were not differentially expressed; however, using a combination of network methods, experimental studies and careful phenotype definition, we found differential expression of putative interactors of these genes, and we replicated previous human and mouse microarray results.

It is known that tissue macrophages derive not only from blood monocytes but also from yolk sac or fetal liver, and the tissue of residence guides their function.,When isolated, they lose tissue specific signatures, hence studies of human macrophages should be ideally done directly in the tissue.,The aim of this study was to investigate directly in human lung tissue the polarization of alveolar macrophage (AM), classic (M1) or alternative (M2), in health and disease, using COPD as a model.,Surgical lungs from 53 subjects were studied: 36 smokers whose FEV1 varied from normal to severe COPD, 11 non-smokers and 6 normal donors. iNOS and CD206 immunohistochemistry was used to quantify the percentage of AM polarized as M1 or M2 in lung sections.,The percentage of M1 and M2 increased progressively with smoking and COPD severity, from 26% to 84% for M1 and from 7% to 78% for M2.,In donors 74% of AM were negative for M1 and 93% for M2.,Confocal microscopy showed co-localization of M1 and M2 in the same AM in severe COPD.,In normal lungs alveolar macrophages were mostly non-polarized.,With smoking and COPD severity, M1 and M2 polarization increased significantly and so did the co-expression of M1 and M2 in the same alveolar macrophage.,The online version of this article (doi:10.1186/s12931-017-0522-0) contains supplementary material, which is available to authorized users.

Endpoints that evaluate deterioration rather than improvement of disease may have clinical utility in COPD.,In this analysis, we compared the effects of different maintenance treatments on the prevention of clinically important deterioration (CID) in moderate-to-severe COPD patients.,Data were analyzed from three 26-week studies comparing indacaterol/glycopyrronium (IND/GLY) with tiotropium (TIO) or salmeterol/fluticasone (SFC).,Two definitions of CID were used; each was a composite of three outcome measures typically associated with COPD.,Definition 1 (D1) comprised a ≥100 mL decrease in forced expiratory volume in 1 second (FEV1), a ≥4-unit increase in St George’s Respiratory Questionnaire, and a moderate-to-severe COPD exacerbation.,In Definition 2 (D2), a ≥1-unit decrease in transition dyspnea index replaced FEV1.,Using D1, IND/GLY significantly reduced the risk of first or sustained CID versus either TIO (hazard ratio 0.72 [0.61, 0.86], P=0.0003 and 0.73 [0.61, 0.89], P=0.001) or SFC (0.67 [0.57, 0.80] and 0.63 [0.52, 0.77], both P<0.0001).,With D2, IND/GLY significantly reduced the risk of first, but not sustained, CID versus TIO (0.80 [0.64 to 0.99], P=0.0359 and 0.85 [0.66, 1.10], P=0.2208) and both first and sustained CID versus SFC (0.73 [0.61, 0.88], P=0.001 and 0.72 [0.58, 0.90], P=0.0036).,These data confirm the utility of the CID endpoint as a means of monitoring COPD worsening in patients with moderate-to-severe COPD.,Using the CID measure, we demonstrated that dual bronchodilation with IND/GLY significantly reduced the risk of CID versus either long-acting muscarinic antagonist or long-acting β2-agonist/inhaled corticosteroid treatment, providing further evidence for the benefit of dual bronchodilation in this patient population.

Background: Combination therapy with a long-acting bronchodilator and an inhaled corticosteroid (ICS) is recommended in patients with chronic obstructive pulmonary disease (COPD) who have frequent exacerbations.,The efficacy and tolerability of the combination of budesonide/formoterol have been demonstrated in patients with COPD when administered via the dry powder inhaler (DPI) in a 1-year study and when administered via the hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) in a 6-month study.,Objective: This study assessed the long-term efficacy and tolerability of budesonide/formoterol HFA pMDI in patients with moderate to very severe COPD.,Methods: This was a 12-month, randomized, double-blind, double-dummy, parallel-group, active- and placebo-controlled, multicentre study (NCT00206167) of 1964 patients aged ≥40 years with moderate to very severe COPD conducted from 2005 to 2007 at 237 sites in the US, Europe and Mexico.,After 2 weeks of treatment based on previous therapy (ICSs, short-acting bronchodilators allowed), patients received one of the following treatments twice daily: budesonide/formoterol pMDI 160/4.5 μg × two inhalations (320/9 μg); budesonide/formoterol pMDI 80/4.5 μg × two inhalations (160/9 μg); formoterol DPI 4.5 μg × two inhalations (9 μg); or placebo.,Main outcome measures: The co-primary efficacy variables were pre-dose forced expiratory volume in 1 second (FEV1) and 1-hour post-dose FEV1.,Results: Budesonide/formoterol 320/9 μg demonstrated greater improvements in pre-dose FEV1 versus formoterol (p = 0.008), and both budesonide/formoterol doses demonstrated greater improvements in 1-hour post-dose FEV1 versus placebo (p < 0.001).,The rate of COPD exacerbations was lower in both budesonide/formoterol groups compared with formoterol and placebo (p ≤ 0.004).,Both budesonide/formoterol doses were more effective than placebo (p ≤ 0.006) for controlling dyspnoea and improving health status (St George’s Respiratory Questionnaire).,All treatments were generally well tolerated.,The incidence of pneumonia was not different for active (3.4-4.0%) and placebo (5.0%) groups.,Conclusions: Budesonide/formoterol pMDI (320/9 μg and 160/9 μg) improved pulmonary function and reduced symptoms and exacerbations over 1 year in patients with moderate to very severe COPD.,Only budesonide/formoterol pMDI 320/9 μg demonstrated greater efficacy for both co-primary variables compared with formoterol DPI 9 μg.,Both budesonide/formoterol pMDI dosages were well tolerated relative to formoterol and placebo.,Supplementary material is available for this article at 10.2165/00003495-200969050-00004 and is accessible for authorized users.

Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV1), and its ratio to forced vital capacity (FEV1/FVC).,Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV1 and FEV1/FVC across 19 studies (total N = 50,047).,We identified three novel loci not previously associated with pulmonary function.,SNPs in or near DNER (smallest P JMA = 5.00×10−11), HLA-DQB1 and HLA-DQA2 (smallest P JMA = 4.35×10−9), and KCNJ2 and SOX9 (smallest P JMA = 1.28×10−8) were associated with FEV1/FVC or FEV1 in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction.,The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated.,We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue.,DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers.,Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.

Substantial evidence suggests that there is genetic susceptibility to chronic obstructive pulmonary disease (COPD).,To identify common genetic risk variants, we performed a genome-wide association study in 2940 cases and 1380 smoking controls with normal lung function.,We demonstrate a novel susceptibility locus at 4q22.1 in FAM13A (rs7671167, OR=0.76, P=8.6×10−8) and provide evidence of replication in one case-control and two family-based cohorts (for all studies, combined P=1.2×10−11).

Relationships between airway inflammation and respiratory potentially pathogenic microorganisms (PPMs) quantified using quantitative polymerase chain reaction (qPCR) in subjects with COPD are unclear.,Our aim was to evaluate mediators of airway inflammation and their association with PPMs in subjects with COPD at stable state and during exacerbations.,Sputum from 120 stable subjects with COPD was analyzed for bacteriology (colony-forming units; total 16S; and qPCR targeting Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae), differential cell counts, and inflammatory mediators using the Meso-Scale Discovery Platform.,Subjects were classified as colonized if any PPM was identified above the threshold of detection by qPCR.,Symptoms were quantified using the visual analog scale.,At stable state, 60% of subjects were qPCR positive for H influenzae, 48% for M catarrhalis, and 28% for S pneumoniae.,Elevated sputum concentrations of IL-1β, IL-10, and tumor necrosis factor (TNF)-α were detected in samples qPCR positive for either H influenzae or M catarrhalis.,Bacterial loads of H influenzae positively correlated with IL-1β, IL-8, IL-10, TNF-α, and symptoms; and M catarrhalis correlated with IL-10 and TNF-α.,H influenzae qPCR bacterial load was an independent predictor of sputum TNF-α and IL-1β.,In 55 subjects with paired exacerbation data, qPCR bacterial load fold change at exacerbation in M catarrhalis but not H influenzae correlated to changes in sputum TNF-α and IL-1β concentrations.,At stable state, H influenzae is associated with increased airway inflammation in COPD.,The relationship between bacterial load changes of specific pathogens and airway inflammation at exacerbation and recovery warrants further investigation.

Chronic obstructive pulmonary disease (COPD) is predicted to become the third leading cause of death in the world by 2020.,It is characterized by airflow limitation that is not fully reversible.,The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles and gases, most commonly cigarette smoke.,Among smokers with COPD, even following withdrawal of cigarette smoke, inflammation persists and lung function continues to deteriorate.,One possible explanation is that bacterial colonization of smoke-damaged airways, most commonly with nontypeable Haemophilus influenzae (NTHi), perpetuates airway injury and inflammation.,Furthermore, COPD has also been identified as an independent risk factor for lung cancer irrespective of concomitant cigarette smoke exposure.,In this article, we review the role of NTHi in airway inflammation that may lead to COPD progression and lung cancer promotion.

Pneumoconiosis may play an important role in the development of chronic obstructive pulmonary disease (COPD), and the complication of COPD may impose a heavy burden of illness.,The study was conducted in Hunan Province in China from December 1, 2015, to December 1, 2016.,Consecutive underground male pneumoconiosis patients employed for at least 1 year were recruited from the Hunan Occupational Disease Prevention Institute.,Patient information, respiratory symptoms and clinical data were collected using a structured questionnaire.,The diagnosis of COPD were assessed using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.,Logistic regression analyses were conducted to examine the clinical and demographic risk factors of COPD among pneumoconiosis patients.,The prevalence of COPD in our sample of pneumoconiosis patients was 18.65% (119/638).,In pneumoconiosis patients with and without smoking history, the prevalence of COPD was 19.32 and 16.77%.,Compared with non-COPD patients, those with COPD are older in age, have longer exposure time, have lower body mass index (BMI), have a higher smoking index and have worse pulmonary function (all p < 0.05).,For the five respiratory symptoms (cough, sputum, wheeze, dyspnea, and chest tightness), only the presence of wheeze and the severity scores for wheeze or dyspnea showed significant differences between the COPD and non-COPD groups (p < 0.01).,Multivariate logistic regression analysis revealed that advanced pneumoconiosis category, older age and the presence of wheeze symptoms were significant risk factors for the development of COPD among pneumoconiosis patients.,Pneumoconiosis patients are at a high risk of COPD, and pneumoconiosis patients with COPD may suffer more severe respiratory symptoms, such as wheeze and dyspnea, than patients without COPD.,Advanced pneumoconiosis category, older age and the presence of wheeze symptoms are associated with an increased risk of COPD in pneumoconiosis.,We proposed that a routine assessment of lung function is necessary for timely and adequate clinical management.

Never smokers comprise a substantial proportion of patients with COPD.,Their characteristics and possible risk factors in this population are not yet well defined.,We analyzed data from 14 countries that participated in the international, population-based Burden of Obstructive Lung Disease (BOLD) study.,Participants were aged ≥ 40 years and completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors.,A diagnosis of COPD was based on the postbronchodilator FEV1/FVC ratio, according to current GOLD (Global Initiative for Obstructive Lung Disease) guidelines.,In addition to this, the lower limit of normal (LLN) was evaluated as an alternative threshold for the FEV1/FVC ratio.,Among 4,291 never smokers, 6.6% met criteria for mild (GOLD stage I) COPD, and 5.6% met criteria for moderate to very severe (GOLD stage II+) COPD.,Although never smokers were less likely to have COPD and had less severe COPD than ever smokers, never smokers nonetheless comprised 23.3% (240/1,031) of those classified with GOLD stage II+ COPD.,This proportion was similar, 20.5% (171/832), even when the LLN was used as a threshold for the FEV1/FVC ratio.,Predictors of COPD in never smokers include age, education, occupational exposure, childhood respiratory diseases, and BMI alterations.,This multicenter international study confirms previous evidence that never smokers comprise a substantial proportion of individuals with COPD.,Our data suggest that, in addition to increased age, a prior diagnosis of asthma and, among women, lower education levels are associated with an increased risk for COPD among never smokers.

Chronic obstructive pulmonary disease, COPD, is an increasing cause of morbidity and mortality worldwide, and an imbalance between proteases and antiproteases has been implicated to play a role in COPD pathogenesis.,Matrix metalloproteinases (MMP) are important proteases that along with their inhibitors, tissue inhibitors of metalloproteinases (TIMP), affect homeostasis of elastin and collagen, of importance for the structural integrity of human airways.,Small observational studies indicate that these biomarkers are involved in the pathogenesis of COPD.,The aim of this study was to investigate serum levels of MMP-9 and TIMP-1 in a large Swedish population-based cohort, and their association with disease severity and important clinical symptoms of COPD such as productive cough.,Spirometry was performed and peripheral blood samples were collected in a populations-based cohort (median age 67 years) comprising subjects with COPD (n = 594) and without COPD (n = 948), in total 1542 individuals.,Serum MMP-9 and TIMP-1 concentrations were measured with enzyme linked immunosorbant assay (ELISA) and related to lung function data and symptoms.,Median serum MMP-9 values were significantly higher in COPD compared with non-COPD 535 vs. 505 ng/ml (P = 0.017), without any significant differences in serum TIMP-1-levels or MMP-9/TIMP-1-ratio.,In univariate analysis, productive cough and decreasing FEV1% predicted correlated significantly with increased MMP-9 among subjects with COPD (P = 0.004 and P = 0.001 respectively), and FEV1% predicted remained significantly associated to MMP-9 in a multivariate model adjusting for age, sex, pack years and productive cough (P = 0.033).,Productive cough and decreasing FEV1 were each associated with MMP-9 in COPD, and decreasing FEV1 remained significantly associated with MMP-9 also after adjustment for common confounders in this population-based COPD cohort.,The increased serum MMP-9 concentrations in COPD indicate an enhanced proteolytic activity that is related to disease severity, and further longitudinal studies are important for the understanding of MMP-9 in relation to the disease process and the pathogenesis of different COPD phenotypes.

Little is known about gender differences in plasma biomarker levels in patients with chronic obstructive pulmonary disease (COPD).,There are differences in serum biomarker levels between women and men with COPD.,Explore gender differences in plasma biomarker levels in patients with COPD and smokers without COPD.,We measured plasma levels of IL-6, IL-8, IL-16, MCP-1, MMP-9, PARC and VEGF in 80 smokers without COPD (40 males, 40 females) and 152 stable COPD patients (76 males, 76 females) with similar airflow obstruction.,We determined anthropometrics, smoking history, lung function, exercise tolerance, body composition, BODE index, co-morbidities and quality of life.,We then explored associations between plasma biomarkers levels and the clinical characteristics of the patients and also with the clinical and physiological variables known to predict outcome in COPD.,The plasma biomarkers level explored were similar in men and women without COPD.,In contrast, in patients with COPD the median value in pg/mL of IL-6 (6.26 vs 8.0, p = 0.03), IL-16 (390 vs 321, p = 0.009) and VEGF (50 vs 87, p = 0.02) differed between women and men.,Adjusted for smoking history, gender was independently associated with IL-16, PARC and VEGF levels.,There were also gender differences in the associations between IL-6, IL-16 and VEGF and physiologic variables that predict outcomes.,In stable COPD patients with similar airflow obstruction, there are gender differences in plasma biomarker levels and in the association between biomarker levels and important clinical or physiological variables.,Further studies should confirm our findings.

Muscle wasting and chronic inflammation are predominant features of patients with COPD.,Systemic inflammation is associated with an accelerated decline in lung function.,In this study, the prevalence of sarcopenia and the relationships between sarcopenia and systemic inflammations in patients with stable COPD were investigated.,In a cross-sectional design, muscle strength and muscle mass were measured by handgrip strength (HGS) and bioelectrical impedance analysis in 80 patients with stable COPD.,Patients (≥40 years old) diagnosed with COPD were recruited from outpatient clinics, and then COPD stages were classified.,Sarcopenia was defined as the presence of both low muscle strength (by HGS) and low muscle mass (skeletal muscle mass index [SMMI]).,Levels of circulating inflammatory biomarkers (IL-6 and high-sensitivity TNFα [hsTNFα]) were measured.,Sarcopenia was prevalent in 20 (25%) patients.,Patients with sarcopenia were older, had lower body mass index, and a higher percentage of cardiovascular diseases.,In addition, they had significantly higher modified Medical Research Council scores and lower 6-minute walk distance than those without sarcopenia.,HGS was significantly correlated with age, modified Medical Research Council score, and COPD Assessment Test scores.,Both HGS and SMMI had associations with IL-6 and hsTNFα (HGS, r=−0.35, P=0.002; SMMI, r=−0.246, P=0.044) level.,In multivariate analysis, old age, lower body mass index, presence of cardiovascular comorbidities, and higher hsTNFα levels were significant determinants for sarcopenia in patients with stable COPD.,Sarcopenia is very common in patients with stable COPD, and is associated with more severe dyspnea-scale scores and lower exercise tolerance.,Systemic inflammation could be an important contributor to sarcopenia in the stable COPD population.

To evaluate the prevalence of sarcopenia in COPD patients, as well as to determine whether sarcopenia correlates with the severity and prognosis of COPD.,A cross-sectional study with COPD patients followed at the pulmonary outpatient clinic of our institution.,The patients underwent dual-energy X-ray absorptiometry.,The diagnosis of sarcopenia was made on the basis of the skeletal muscle index, defined as appendicular lean mass/height2 only for low-weight subjects and adjusted for fat mass in normal/overweight subjects.,Disease severity (COPD stage) was evaluated with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.,The degree of obstruction and prognosis were determined by the Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity (BODE) index.,We recruited 91 patients (50 females), with a mean age of 67.4 ± 8.7 years and a mean BMI of 25.8 ± 6.1 kg/m2.,Sarcopenia was observed in 36 (39.6%) of the patients, with no differences related to gender, age, or smoking status.,Sarcopenia was not associated with the GOLD stage or with FEV1 (used as an indicator of the degree of obstruction).,The BMI, percentage of body fat, and total lean mass were lower in the patients with sarcopenia than in those without (p < 0.001).,Sarcopenia was more prevalent among the patients in BODE quartile 3 or 4 than among those in BODE quartile 1 or 2 (p = 0.009).,The multivariate analysis showed that the BODE quartile was significantly associated with sarcopenia, regardless of age, gender, smoking status, and GOLD stage.,In COPD patients, sarcopenia appears to be associated with unfavorable changes in body composition and with a poor prognosis.,Avaliar a prevalência de sarcopenia em pacientes com DPOC e determinar se sarcopenia está correlacionada com a gravidade e o prognóstico de DPOC.,Estudo retrospectivo em pacientes com DPOC atendidos no ambulatório de pneumologia de nossa instituição.,Os pacientes realizaram absorciometria de dupla energia por raios X.,O diagnóstico de sarcopenia foi baseado no índice de massa muscular esquelética, definido como massa magra apendicular/altura2 somente para indivíduos com baixo peso, sendo ajustado pela massa gorda para aqueles com peso normal/sobrepeso.,A gravidade da doença (estádio da DPOC) foi avaliada com os critérios da Global Initiative for Chronic Obstructive Lung Disease (GOLD).,O grau de obstrução e o prognóstico foram determinados pelo índice Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity (BODE).,Foram incluídos 91 pacientes (50 mulheres), com média de idade de 67,4 ± 8,7 anos e média de IMC de 25,8 ± 6,1 kg/m2.,Sarcopenia foi diagnosticada em 36 (39,6%) dos pacientes, sem diferenças relacionadas a sexo, idade ou status tabágico.,Não houve associação de sarcopenia com estádios GOLD ou VEF1 (utilizado como indicador do grau de obstrução).,O IMC, a porcentagem de gordura corporal e a massa magra total foram menores nos pacientes com sarcopenia do que naqueles sem a doença (p < 0,001).,A prevalência de sarcopenia foi maior nos pacientes com BODE nos quartis 3 ou 4 que naqueles com BODE nos quartis 1 ou 2 (p = 0,009).,A análise multivariada mostrou que os quartis do BODE estavam significativamente associados à sarcopenia, independentemente de idade, gênero, status tabágico e estádio GOLD.,Em pacientes com DPOC, sarcopenia parece estar associada a alterações desfavoráveis na composição corporal e pior prognóstico.

Reduced physical activity (PA) in patients with COPD is associated with a poor prognosis.,Increasing PA is a key therapeutic target, but thus far few strategies have been found effective in this patient group.,To investigate the effectiveness of a 12-week semiautomated telecoaching intervention on PA in patients with COPD in a multicentre European randomised controlled trial.,343 patients from six centres, encompassing a wide spectrum of disease severity, were randomly allocated to either a usual care group (UCG) or a telecoaching intervention group (IG) between June and December 2014.,This 12-week intervention included an exercise booklet and a step counter providing feedback both directly and via a dedicated smartphone application.,The latter provided an individualised daily activity goal (steps) revised weekly and text messages as well as allowing occasional telephone contacts with investigators.,PA was measured using accelerometry during 1 week preceding randomisation and during week 12.,Secondary outcomes included exercise capacity and health status.,Analyses were based on modified intention to treat.,Both groups were comparable at baseline in terms of factors influencing PA.,At 12 weeks, the intervention yielded a between-group difference of mean, 95% CI (lower limit - upper limit; ll-ul) +1469, 95% CI (971 to 1965) steps/day and +10.4, 95% CI (6.1 to 14.7) min/day moderate PA; favouring the IG (all p≤0.001).,The change in 6-min walk distance was significantly different (13.4, 95% CI (3.40 to 23.5) m, p<0.01), favouring the IG.,In IG patients, an improvement could be observed in the functional state domain of the clinical COPD questionnaire (p=0.03) compared with UCG.,Other health status outcomes did not differ.,The amount and intensity of PA can be significantly increased in patients with COPD using a 12-week semiautomated telecoaching intervention including a step counter and an application installed on a smartphone.,NCT02158065.

Chronic obstructive pulmonary disease (COPD) is the leading cause of death worldwide, and poses a substantial economic and social burden.,Telemonitoring has been proposed as a solution to this growing problem, but its impact on patient outcome is equivocal.,This randomized controlled trial aimed to investigate effectiveness of telemonitoring in improving COPD patient outcome.,In total, 106 subjects were randomly assigned to the telemonitoring (n = 53) or usual care (n = 53) group.,During the two months following discharge, telemonitoring group patients had to report their symptoms daily using an electronic diary.,The primary outcome measure was time to first re-admission for COPD exacerbation within six months of discharge.,During the follow-up period, time to first re-admission for COPD exacerbation was significantly increased in the telemonitoring group than in the usual care group (p = 0.026).,Telemonitoring was also associated with a reduced number of all-cause re-admissions (0.23 vs.,0.68/patient; p = 0.002) and emergency room visits (0.36 vs.,0.91/patient; p = 0.006).,In conclusion, telemonitoring intervention was associated with improved outcomes among COPD patients admitted for exacerbation in a country characterized by a small territory and high accessibility to medical services.,The findings are encouraging and add further support to implementation of telemonitoring as part of COPD care.

The early stages of COPD have recently become a hot topic as many new risk factors have been proposed, but substantial knowledge gaps remain in explaining the natural history of the disease.,If we are to modify the outcomes of COPD, early detection needs to play a critical role.,However, we need to sort out the barriers to early detection and have a better understanding of the definition of COPD and its diagnosis and therapeutic strategies to identify and treat patients with COPD before structural changes progress.,In this review, we aim to clarify the differences between early COPD, mild COPD and early detection of COPD, with an emphasis on the clinical burden and how different outcomes (quality of life, exacerbation, cost and mortality) are modified depending on which definition is used.,We will summarise the evidence for the new multidimensional diagnostic approaches to detecting early pathophysiologic changes that potentially allow for future studies on COPD management strategies to halt or prevent disease development.,Is it possible to answer the question of whether early diagnosis of COPD is a myth or reality?,If we define the objectives clearly, early detection will play a key role in having a positive impact on the prognosis of patients with COPD.https://bit.ly/32crfPL

COPD is a disease associated with significant economic burden.,It was reported that Global initiative for chronic Obstructive Lung Disease (GOLD) guideline-oriented pharmacotherapy improves airflow limitation and reduces health care costs.,However, several studies showed a significant dissociation between international recommendations and clinicians’ practices.,The consequent reduced diagnostic and therapeutic inappropriateness has proved to be associated with an increase in costs and a waste of economic resources in the health sector.,The aim of the study was to evaluate COPD management in the Puglia region.,The study was performed in collaboration with the pulmonology centers and the Regional Health Agency (AReS Puglia).,An IT platform allowed the pulmonologists to enter data via the Internet.,All COPD patients who visited a pneumological outpatient clinic for the first time or for regular follow-ups or were admitted to a pneumological department for an exacerbation were considered eligible for the study.,COPD’s diagnosis was confirmed by a pulmonologist at the moment of the visit.,The project lasted 18 months and involved 17 centers located in the Puglia region.,Six hundred ninety-three patients were enrolled, evenly distributed throughout the region.,The mean age was 71±9 years, and 85% of them were males.,Approximately 23% were current smokers, 63% former smokers and 13.5% never smokers.,The mean post-bronchodilator forced expiratory volume in 1 second was 59%±20% predicted.,The platform allowed the classification of patients according to the GOLD guidelines (Group A: 20.6%, Group B: 32.3%, Group C: 5.9% and Group D: 39.2%), assessed the presence and severity of exacerbations (20% of the patients had an exacerbation defined as mild [13%], moderate [37%] and severe [49%]) and evaluated the appropriateness of inhalation therapy at the time of the visit.,Forty-nine percent of Group A patients were following inappropriate therapy; in Group B, 45.8% were following a therapy in contrast with the guidelines.,Among Group C patients, 41.46% resulted in triple combination therapy, whilê14% of Group D patients did not have a therapy or were following an inappropriate therapy.,In conclusion, 30% of all patients evaluated had been following an inadequate therapy.,Subsequently, an online survey was developed to inquire about the reasons for the results obtained.,In particular, we investigated the reasons why 30% of our population did not follow the therapy suggested by the GOLD guidelines: 1) why was there an excessive use of inhaled corticosteroids, 2) why a significantly high percentage was inappropriately treated with triple therapy and 3) why a consistent percentage (11%) of Group D patients were not treated at all.,The data provides an overview on the management of COPD in the region of Puglia (Italy) and represents a resource in order to improve appropriateness and reduce the waste of health resources.

Endpoints that evaluate deterioration rather than improvement of disease may have clinical utility in COPD.,In this analysis, we compared the effects of different maintenance treatments on the prevention of clinically important deterioration (CID) in moderate-to-severe COPD patients.,Data were analyzed from three 26-week studies comparing indacaterol/glycopyrronium (IND/GLY) with tiotropium (TIO) or salmeterol/fluticasone (SFC).,Two definitions of CID were used; each was a composite of three outcome measures typically associated with COPD.,Definition 1 (D1) comprised a ≥100 mL decrease in forced expiratory volume in 1 second (FEV1), a ≥4-unit increase in St George’s Respiratory Questionnaire, and a moderate-to-severe COPD exacerbation.,In Definition 2 (D2), a ≥1-unit decrease in transition dyspnea index replaced FEV1.,Using D1, IND/GLY significantly reduced the risk of first or sustained CID versus either TIO (hazard ratio 0.72 [0.61, 0.86], P=0.0003 and 0.73 [0.61, 0.89], P=0.001) or SFC (0.67 [0.57, 0.80] and 0.63 [0.52, 0.77], both P<0.0001).,With D2, IND/GLY significantly reduced the risk of first, but not sustained, CID versus TIO (0.80 [0.64 to 0.99], P=0.0359 and 0.85 [0.66, 1.10], P=0.2208) and both first and sustained CID versus SFC (0.73 [0.61, 0.88], P=0.001 and 0.72 [0.58, 0.90], P=0.0036).,These data confirm the utility of the CID endpoint as a means of monitoring COPD worsening in patients with moderate-to-severe COPD.,Using the CID measure, we demonstrated that dual bronchodilation with IND/GLY significantly reduced the risk of CID versus either long-acting muscarinic antagonist or long-acting β2-agonist/inhaled corticosteroid treatment, providing further evidence for the benefit of dual bronchodilation in this patient population.

Chronic obstructive pulmonary disease (COPD) is a debilitating condition characterized by airflow limitation that is not fully reversible.,It is a major cause of morbidity and mortality and represents substantial economic and social burden throughout the world.,A range of interventions has been developed that decrease symptoms and address complications associated with COPD.,However, to date few interventions have been unequivocally demonstrated to modify disease progression.,Assessment of the potential for interventions to modify disease progression is complicated by the lack of a clear definition of disease modification and disagreement over appropriate markers by which modification should be evaluated.,To clarify these issues, a working group of physicians and scientists from the USA, Canada and Europe was convened.,The proposed working definition of disease modification resulting from the group discussions was “an improvement in, or stabilization of, structural or functional parameters as a result of reduction in the rate of progression of these parameters which occurs whilst an intervention is applied and may persist even if the intervention is withdrawn”.,According to this definition, pharmacologic interventions may be considered disease-modifying if they provide consistent and sustained improvements in structural and functional parameters.,Smoking cessation and lung volume reduction surgery would both qualify as disease-modifying interventions.

For optimal efficacy, an inhaler should deliver doses consistently and be easy for patients to use with minimal instruction.,The delivery characteristics, patients’ correct use, and preference of two single-dose dry powder inhalers (Breezhaler and HandiHaler) were evaluated in two complementary studies.,The first study examined aerodynamic particle size distribution, using inhalation profiles of seven patients with moderate to very severe chronic obstructive pulmonary disease (COPD).,The second was an open-label, two-period, 7-day crossover study, evaluating use of the inhalers with placebo capsules by 82 patients with mild to severe COPD.,Patients’ correct use of the inhalers was assessed after reading written instructions on Day 1, and after training and 7 days of daily use.,Patients’ preference was assessed after completion of both study periods.,Patient inhalation profiles showed average peak inspiratory flows of 72 L/minute through Breezhaler and 36 L/minute through HandiHaler.,For Breezhaler and HandiHaler, fine particle fractions were 27% and 10%, respectively.,In the second study, correct use of Breezhaler and HandiHaler was achieved by >77% of patients for any step after 7 days; 61% of patients showed an overall preference for Breezhaler and 31% for HandiHaler (P = 0.01).,Breezhaler is a low-resistance inhaler suitable for use by patients with a range of disease severities.,Most patients used both inhalers correctly after 7 days, but more patients showed an overall preference for the Breezhaler compared with the HandiHaler.,These are important factors for optimum dose delivery and successful COPD management.

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and debilitating symptoms.,For patients with moderate-to-severe COPD, long-acting bronchodilators are the mainstay of therapy; as symptoms progress, guidelines recommend combining bronchodilators from different classes to improve efficacy.,Inhaled long-acting β2-agonists (LABAs) have been licensed for the treatment of COPD since the late 1990s and include formoterol and salmeterol.,They improve lung function, symptoms of breathlessness and exercise limitation, health-related quality of life, and may reduce the rate of exacerbations, although not all patients achieve clinically meaningful improvements in symptoms or health related quality of life.,In addition, LABAs have an acceptable safety profile, and are not associated with an increased risk of respiratory mortality, although adverse effects such as palpitations and tremor may limit the dose that can be tolerated.,Formoterol and salmeterol have 12-hour durations of action; however, sustained bronchodilation is desirable in COPD.,A LABA with a 24-hour duration of action could provide improvements in efficacy, compared with twice-daily LABAs, and the once-daily dosing regimen could help improve compliance.,It is also desirable that a new LABA should demonstrate fast onset of action, and a safety profile at least comparable to existing LABAs.,A number of novel LABAs with once-daily profiles are in development which may be judged against these criteria.,Indacaterol, a LABA with a 24-hour duration of bronchodilation and fast onset of action, is the most advanced of these.,Preliminary results from large clinical trials suggest indacaterol improves lung function compared with placebo and other long-acting bronchodilators.,Other LABAs with a 24-hour duration of bronchodilation include carmoterol, vilanterol trifenatate and oldaterol, with early results indicating potential for once-daily dosing in humans.,The introduction of once-daily LABAs also provides the opportunity to develop combination inhalers of two or more classes of once-daily long-acting bronchodilators, which may be advantageous for COPD patients through simplification of treatment regimens as well as improvements in efficacy.,Once-daily LABAs used both alone and in combination with long-acting muscarinic antagonists represent a promising advance in the treatment of COPD, and are likely to further improve outcomes for patients.

Chronic obstructive pulmonary disease (COPD) and chronic cardiovascular disease, such as coronary artery disease, congestive heart failure, and cardiac arrhythmias, have a strong influence on each other, and systemic inflammation has been considered as the main linkage between them.,On the other hand, airflow limitation may markedly affect lung mechanics in terms of static and dynamic hyperinflation, especially in pulmonary emphysema, and they can in turn influence cardiac performance as well.,Skeletal mass depletion, which is a common feature in COPD especially in pulmonary emphysema patients, may have also a role in cardiovascular function of these patients, irrespective of lung damage.,We reviewed the emerging evidence that highlights the role of lung mechanics and muscle mass impairment on ventricular volumes, stroke volume, and stroke work at rest and on exercise in the presence of pulmonary emphysema.,Patients with emphysema may differ among COPD population even in terms of cardiovascular function.

It is generally known that positive pressure ventilation is associated with impaired venous return and decreased right ventricular output, in particular in patients with a low right atrial pressure and relative hypovolaemia.,Altered lung mechanics have been suggested to impair right ventricular output in COPD, but this relation has never been firmly established in spontaneously breathing patients at rest or during exercise, nor has it been determined whether these cardiopulmonary interactions are influenced by right atrial pressure.,Twenty-one patients with COPD underwent simultaneous measurements of intrathoracic, right atrial and pulmonary artery pressures during spontaneous breathing at rest and during exercise.,Intrathoracic pressure and right atrial pressure were used to calculate right atrial filling pressure.,Dynamic changes in pulmonary artery pulse pressure during expiration were examined to evaluate changes in right ventricular output.,Pulmonary artery pulse pressure decreased up to 40% during expiration reflecting a decrease in stroke volume.,The decline in pulse pressure was most prominent in patients with a low right atrial filling pressure.,During exercise, a similar decline in pulmonary artery pressure was observed.,This could be explained by similar increases in intrathoracic pressure and right atrial pressure during exercise, resulting in an unchanged right atrial filling pressure.,We show that in spontaneously breathing COPD patients the pulmonary artery pulse pressure decreases during expiration and that the magnitude of the decline in pulmonary artery pulse pressure is not just a function of intrathoracic pressure, but also depends on right atrial pressure.

Chronic obstructive pulmonary disease (COPD) is highly prevalent and significantly affects the daily functioning of patients.,Self-management strategies, including increasing physical activity, can help people with COPD have better health and a better quality of life.,Digital mobile health (mHealth) techniques have the potential to aid the delivery of self-management interventions for COPD.,We developed an mHealth intervention (Self-Management supported by Assistive, Rehabilitative, and Telehealth technologies-COPD [SMART-COPD]), delivered via a smartphone app and an activity tracker, to help people with COPD maintain (or increase) physical activity after undertaking pulmonary rehabilitation (PR).,This study aimed to determine the feasibility and acceptability of using the SMART-COPD intervention for the self-management of physical activity and to explore the feasibility of conducting a future randomized controlled trial (RCT) to investigate its effectiveness.,We conducted a randomized feasibility study.,A total of 30 participants with COPD were randomly allocated to receive the SMART-COPD intervention (n=19) or control (n=11).,Participants used SMART-COPD throughout PR and for 8 weeks afterward (ie, maintenance) to set physical activity goals and monitor their progress.,Questionnaire-based and physical activity-based outcome measures were taken at baseline, the end of PR, and the end of maintenance.,Participants, and health care professionals involved in PR delivery, were interviewed about their experiences with the technology.,Overall, 47% (14/30) of participants withdrew from the study.,Difficulty in using the technology was a common reason for withdrawal.,Participants who completed the study had better baseline health and more prior experience with digital technology, compared with participants who withdrew.,Participants who completed the study were generally positive about the technology and found it easy to use.,Some participants felt their health had benefitted from using the technology and that it assisted them in achieving physical activity goals.,Activity tracking and self-reporting were both found to be problematic as outcome measures of physical activity for this study.,There was dissatisfaction among some control group members regarding their allocation.,mHealth shows promise in helping people with COPD self-manage their physical activity levels. mHealth interventions for COPD self-management may be more acceptable to people with prior experience of using digital technology and may be more beneficial if used at an earlier stage of COPD.,Simplicity and usability were more important for engagement with the SMART-COPD intervention than personalization; therefore, the intervention should be simplified for future use.,Future evaluation will require consideration of individual factors and their effect on mHealth efficacy and use; within-subject comparison of step count values; and an opportunity for control group participants to use the intervention if an RCT were to be carried out.,Sample size calculations for a future evaluation would need to consider the high dropout rates.

The 1-min sit-to-stand (1-min STS) test and handgrip strength test have been proposed as simple tests of functional exercise performance in chronic obstructive pulmonary disease (COPD) patients.,We assessed the long-term (5-year) predictive performance of the 1-min sit-to-stand and handgrip strength tests for mortality, health-related quality of life (HRQoL) and exacerbations in COPD patients.,In 409 primary care patients, we found the 1-min STS test to be strongly associated with long-term morality (hazard ratio per 3 more repetitions: 0.81, 95% CI 0.65 to 0.86) and moderately associated with long-term HRQoL.,Neither test was associated with exacerbations.,Our results suggest that the 1-min STS test may be useful for assessing the health status and long-term prognosis of COPD patients.,This study was registered at http://www.clinicaltrials.gov/ (NCT00706602, 25 June 2008).

Smoking represents a significant risk factor for many chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD).,To identify dysregulation of specific proteins and pathways in bronchoalveolar lavage (BAL) cells associated with smoking, isobaric tags for relative and absolute quantitation (iTRAQ)-based shotgun proteomics analyses were performed on BAL cells from healthy never-smokers and smokers with normal lung function from the Karolinska COSMIC cohort.,Multivariate statistical modeling, multivariate correlations with clinical data, and pathway enrichment analysis were performed.,Smoking exerted a significant impact on the BAL cell proteome, with more than 500 proteins representing 15 molecular pathways altered due to smoking.,The majority of these alterations occurred in a gender-independent manner.,The phagosomal- and leukocyte trans endothelial migration (LTM) pathways significantly correlated with FEV1/FVC as well as the percentage of CD8+ T-cells and CD8+CD69+ T-cells in smokers.,The correlations to clinical parameters in healthy never-smokers were minor.,The significant correlations of proteins in the phagosome- and LTM pathways with activated cytotoxic T-cells (CD69+) and the level of airway obstruction (FEV1/FVC) in smokers, both hallmarks of COPD, suggests that these two pathways may play a role in the molecular events preceding the development of COPD in susceptible smokers.,Both pathways were found to be further dysregulated in COPD patients from the same cohort, thereby providing further support to this hypothesis.,Given that not all smokers develop COPD in spite of decades of smoking, it is also plausible that some of the molecular pathways associated with response to smoking exert protective mechanisms to smoking-related pathologies in resilient individuals.,ClinicalTrials.gov identifier NCT02627872; Retrospectively registered on December 9, 2015.,The online version of this article (10.1186/s12931-017-0695-6) contains supplementary material, which is available to authorized users.

Toll-like receptors (TLRs) participate in the defence against bacterial infections that are common in patients with Chronic Obstructive Pulmonary Disease (COPD).,We studied all tagging SNPs in TLR2 and TLR4 and their associations with the level and change over time of both FEV1 and sputum inflammatory cells in moderate-to-severe COPD.,Nine TLR2 SNPs and 17 TLR4 SNPs were genotyped in 110 COPD patients.,Associations of SNPs with lung function and inflammatory cells in induced sputum were analyzed cross-sectionally with linear regression and longitudinally with linear mixed-effect models.,Two SNPs in TLR2 (rs1898830 and rs11938228) were associated with a lower level of FEV1 and accelerated decline of FEV1 and higher numbers of sputum inflammatory cells.,None of the TLR4 SNPs was associated with FEV1 level.,Eleven out of 17 SNPs were associated with FEV1 decline, including rs12377632 and rs10759931, which were additionally associated with higher numbers of sputum inflammatory cells at baseline and with increase over time.,This is the first longitudinal study showing that tagging SNPs in TLR2 and TLR4 are associated with the level and decline of lung function as well as with inflammatory cell numbers in induced sputum in COPD patients, suggesting a role in the severity and progression of COPD.

Objectives of this study were to evaluate the prevalence of thoracic pain in patients with chronic obstructive pulmonary disease (COPD) and its relationship with Forced Expiratory Volume in the first second (FEV1), static hyperinflation, dyspnoea, functional exercise capacity, disease-specific health status, anxiety, and depression.,This cross-sectional observational study included patients with COPD entering pulmonary rehabilitation.,Participants underwent spirometry, plethysmography, and measurement of single breath diffusion capacity.,Pain was assessed using a multidimensional, structured pain interview.,In addition, dyspnoea severity (Modified Medical Research Council Dyspnoea Scale (mMRC)), functional exercise capacity (six-minute walking distance (6MWD)), disease-specific health status (COPD Assessment Test (CAT)), and symptoms of anxiety and depression (Hospital Anxiety Depression Scale (HADS)) were recorded.,55 of the included 67 participants reported chronic pain (82.1 %).,53.7 % had thoracic pain.,After considering multiple comparisons, only younger age and worse CAT scores were related with the presence of thoracic pain (p = 0.01).,There were no relationships between thoracic pain and FEV1, static lung hyperinflation, diffusion capacity, mMRC score, 6MWD, anxiety or depression.,Thoracic pain is highly prevalent in COPD patients and is related to impaired disease-specific health status, but there is no relationship with FEV1, static hyperinflation, dyspnoea severity or functional exercise capacity.

To systematically investigate the prevalence of pain, factors related with pain and pain management interventions in patients with chronic obstructive pulmonary disease (COPD).,Systematic review and meta-analysis.,PubMed (MEDLINE), EMBASE, CINAHL and PsychINFO from 1966 to December 2013.,Studies were included if they presented clinical data on pain or symptom burden in patients with COPD, or pain as a domain of quality of life (QoL).,All types of study designs were included.,Of the 1571 articles that were identified, 39 met the inclusion criteria and were included in this review.,Fourteen studies focused on pain and symptom burden (including pain) in patients with COPD and 25 studies focused on QoL using a questionnaire that included a separate pain domain.,Reported pain prevalence in high-quality studies ranged from 32 to 60%.,Included studies report that pain is more prevalent in patients with COPD compared to participants from the general population.,Comorbidity, nutritional status, QoL and several symptoms were related to pain.,None of the included studies reported a significant relationship between lung function and pain prevalence or severity.,However, studies investigating pain in patients with moderate COPD reported higher pain prevalence compared to studies in patients with severe of very severe COPD.,Although literature on this topic is limited and shows substantial heterogeneity, pain seems to be a significant problem in patients with COPD and is related to several other symptoms, comorbidity and QoL.,Data synthesis suggests that pain is more prevalent in patients with moderate COPD compared to patients with severe or very severe COPD.,Further research is needed and should focus on determining a more accurate pain prevalence, investigating the relationship between pain prevalence, disease severity and comorbidity and explore implementation and efficacy of pain management interventions in patients with COPD.

COPD is characterised by tissue destruction and inflammation.,Given the lack of curative treatments and the progressive nature of the disease, new treatments for COPD are highly relevant.,In vitro cell culture and animal studies have demonstrated that mesenchymal stromal cells (MSCs) have the capacity to modify immune responses and to enhance tissue repair.,These properties of MSCs provided a rationale to investigate their potential for treatment of a variety of diseases, including COPD.,Preclinical models support the hypothesis that MSCs may have clinical efficacy in COPD.,However, although clinical trials have demonstrated the safety of MSC treatment, thus far they have not provided evidence for MSC efficacy in the treatment of COPD.,In this review, we discuss the rationale for MSC-based cell therapy in COPD, the main findings from in vitro and in vivo preclinical COPD model studies, clinical trials in patients with COPD and directions for further research.

Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation.

Some COPD patients are more susceptible to exacerbations than others.,Mechanisms underlying these differences in susceptibility are not well understood.,We hypothesized that altered cell mediated immune responses may underlie a propensity to suffer from frequent exacerbations in COPD.,Peripheral blood mononuclear cells (PBMCs) were obtained from 24 stable COPD patients, eight frequent exacerbators (≥3 diary-card exacerbations/year) and 16 infrequent exacerbators (< 3 diary-card exacerbations/year).,Detailed multi-parameter flow cytometry was used to study differences in innate and adaptive systemic immune function between frequent and infrequently exacerbating COPD patients.,The 24 COPD patients had a mean (SD) age of 76.3 (9.4) years and FEV1 1.43 (0.60)L, 53.3 (18.3)% predicted.,PBMCs of frequent exacerbators (FE) contained lower frequencies of CD4+ T central memory cells (CD4+ Tcm) compared to infrequent exacerbators (IE) (FE = 18.7 %; IE = 23.9 %; p = 0.035).,This observation was also apparent in absolute numbers of CD4+ Tcm cells (FE = 0.17 × 10^6/mL; IE = 0.25 × 10^6/mL; p = 0.035).,PBMCs of FE contained a lower frequency of CD8+ T effector memory cells expressing HLA-DR (Human Leukocyte Antigen - D Related) compared to IE COPD patients (FE = 22.7 %; IE = 31.5 %; p = 0.007).,Differences in the adaptive systemic immune system might associate with exacerbation susceptibility in the ‘frequent exacerbator’ COPD phenotype.,These differences include fewer CD4+ T central memory cells and CD8+ T effector memory cells.,Not applicable.

The aims of this systematic review were to determine which blood-based molecules have been evaluated as possible biomarkers to diagnose chronic obstructive pulmonary disease (COPD) exacerbations (AECOPD) and to ascertain the quality of these biomarker publications.,Patients of interest were those that have been diagnosed with COPD.,MEDLINE, EMBASE, and CINAHL databases were searched systematically through February 2015 for publications relating to AECOPD diagnostic biomarkers.,We used a modified guideline for the REporting of tumor MARKer Studies (mREMARK) to assess study quality.,Additional components of quality included the reporting of findings in a replication cohort and the use of receiver-operating characteristics area-under-the curve statistics in evaluating performance. 59 studies were included, in which the most studied biomarkers were C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α).,CRP showed consistent elevations in AECOPD compared to control subjects, while IL-6 and TNF-α had variable statistical significance and results. mREMARK scores ranged from 6 to 18 (median score of 13). 12 articles reported ROC analyses and only one study employed a replication cohort to confirm biomarker performance.,Studies of AECOPD diagnostic biomarkers remain inconsistent in their reporting, with few studies employing ROC analyses and even fewer demonstrating replication in independent cohorts.

We sought to assess whether the effects of mesenchymal stromal cells (MSC) on lung inflammation and remodeling in experimental emphysema would differ according to MSC source and administration route.,Emphysema was induced in C57BL/6 mice by intratracheal (IT) administration of porcine pancreatic elastase (0.1 UI) weekly for 1 month.,After the last elastase instillation, saline or MSCs (1×105), isolated from either mouse bone marrow (BM), adipose tissue (AD) or lung tissue (L), were administered intravenously (IV) or IT.,After 1 week, mice were euthanized.,Regardless of administration route, MSCs from each source yielded: 1) decreased mean linear intercept, neutrophil infiltration, and cell apoptosis; 2) increased elastic fiber content; 3) reduced alveolar epithelial and endothelial cell damage; and 4) decreased keratinocyte-derived chemokine (KC, a mouse analog of interleukin-8) and transforming growth factor-β levels in lung tissue.,In contrast with IV, IT MSC administration further reduced alveolar hyperinflation (BM-MSC) and collagen fiber content (BM-MSC and L-MSC).,Intravenous administration of BM- and AD-MSCs reduced the number of M1 macrophages and pulmonary hypertension on echocardiography, while increasing vascular endothelial growth factor.,Only BM-MSCs (IV > IT) increased the number of M2 macrophages.,In conclusion, different MSC sources and administration routes variably reduced elastase-induced lung damage, but IV administration of BM-MSCs resulted in better cardiovascular function and change of the macrophage phenotype from M1 to M2.

Within the chronic obstructive pulmonary disease (COPD) spectrum, lung emphysema presents, as a primarily histopathologic feature, the destruction of pulmonary parenchyma and, accordingly, an increase in the airflow obstruction distal to the terminal bronchiole.,Notwithstanding the significant advances in prevention and treatment of symptoms, no effective or curative therapy has been accomplished.,In this context, cellular therapy with stem cells (SCs) arises as a new therapeutic approach, with a wide application potential.,The purpose of this study is to evaluate the safety of SCs infusion procedure in patients with advanced COPD (stage IV dyspnea).,After selection, patients underwent clinical examination and received granulocyte colony-stimulating factor, immediately prior to the bone marrow harvest.,The bone marrow mononuclear cells (BMMC) were isolated and infused into a peripheral vein.,The 12-month follow-up showed a significant improvement in the quality of life, as well as a clinical stable condition, which suggest a change in the natural process of the disease.,Therefore, the proposed methodology in this study for BMMC cell therapy in sufferers of advanced COPD was demonstrated to be free of significant adverse effects.,Although a larger sample and a greater follow-up period are needed, it is possible to infer that BMMC cell therapy introduces an unprecedented change in the course or in the natural history of emphysema, inhibiting or slowing the progression of disease.,This clinical trial was registered with ClinicalTrials.gov (NCT01110252) and was approved by the Brazilian National Committee of Ethics in Research (registration no.,14764, CONEP report 233/2009).

Reports have suggested a reduction in exacerbations of chronic obstructive pulmonary disease (COPD) during the coronavirus disease 2019 (COVID-19) pandemic, particularly hospital admissions for severe exacerbations.,However, the magnitude of this reduction varies between studies.,Electronic databases were searched from January 2020 to May 2021.,Two independent reviewers screened titles and abstracts and, when necessary, full text to determine if studies met inclusion criteria.,A modified version of the Newcastle-Ottawa Scale was used to assess study quality.,A narrative summary of eligible studies was synthesised, and meta-analysis was conducted using a random effect model to pool the rate ratio and 95% confidence intervals (95% CI) for hospital admissions.,Exacerbation reduction was compared against the COVID-19 Containment and Health Index.,A total of 13 of 745 studies met the inclusion criteria and were included in this review, with data from nine countries.,Nine studies could be included in the meta-analysis.,The pooled rate ratio of hospital admissions for COPD exacerbations during the pandemic period was 0.50 (95% CI 0.44-0.57).,Findings on the rate of community-treated exacerbations were inconclusive.,Three studies reported a significant decrease in the incidence of respiratory viral infections compared with the pre-pandemic period.,There was not a significant relationship between exacerbation reduction and the COVID-19 Containment and Health Index (rho = 0.20, p = 0.53).,There was a 50% reduction in admissions for COPD exacerbations during the COVID-19 pandemic period compared to pre-pandemic times, likely associated with a reduction in respiratory viral infections that trigger exacerbations.,Future guidelines should consider including recommendations on respiratory virus infection control measures to reduce the burden of COPD exacerbations beyond the pandemic period.

Coronavirus disease 2019 (COVID-19) is an evolving infectious disease that dramatically spread all over the world in the early part of 2020.,No studies have yet summarized the potential severity and mortality risks caused by COVID-19 in patients with chronic obstructive pulmonary disease (COPD), and we update information in smokers.,We systematically searched electronic databases from inception to March 24, 2020.,Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.,Study quality was assessed using a modified version of the Newcastle-Ottawa Scale.,We synthesized a narrative from eligible studies and conducted a meta-analysis using a random-effects model to calculate pooled prevalence rates and 95% confidence intervals (95%CI).,In total, 123 abstracts were screened and 61 full-text manuscripts were reviewed.,A total of 15 studies met the inclusion criteria, which included a total of 2473 confirmed COVID-19 patients.,All studies were included in the meta-analysis.,The crude case fatality rate of COVID-19 was 7.4%.,The pooled prevalence rates of COPD patients and smokers in COVID-19 cases were 2% (95% CI, 1%-3%) and 9% (95% CI, 4%-14%) respectively.,COPD patients were at a higher risk of more severe disease (risk of severity = 63%, (22/35) compared to patients without COPD 33.4% (409/1224) [calculated RR, 1.88 (95% CI, 1.4-2.4)].,This was associated with higher mortality (60%).,Our results showed that 22% (31/139) of current smokers and 46% (13/28) of ex-smokers had severe complications.,The calculated RR showed that current smokers were 1.45 times more likely [95% CI: 1.03-2.04] to have severe complications compared to former and never smokers.,Current smokers also had a higher mortality rate of 38.5%.,Although COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD.,Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate.,Effective preventive measures are required to reduce COVID-19 risk in COPD patients and current smokers.

To integrate evidence from randomised controlled trials (RCTs) and observational studies on the efficacy of inhaled treatments for chronic obstructive pulmonary disease using network meta-analyses.,Systematic searches MEDLINE and Embase based on predetermined criteria.,Network meta-analyses of RCTs investigated efficacy on exacerbations (long-term: ≥20 weeks of treatment; short-term: <20 weeks), lung function (≥12 weeks), health-related quality of life, mortality and adverse events.,Qualitative comparisons of efficacies between RCTs and observational studies.,212 RCTs and 19 observational studies were included.,Compared with combined long-acting beta-adrenoceptor agonists and long-acting muscarinic antagonists (LABA+LAMA), triple therapy (LABA+LAMA+inhaled corticosteroid) was significantly more effective at reducing exacerbations (long-term 0.85 (95% CI: 0.78 to 0.94; short-term 0.67 (95% CI: 0.49 to 0.92)) and mortality (0.72 (95% CI: 0.59 to 0.89)) but was also associated with increased pneumonia (1.35 (95% CI: 1.10 to 1.67)).,No differences in lung function (0.02 (95% CI: −0.10 to 0.14)), health-related quality of life (−1.12 (95% CI: −3.83 to 1.59)) or other adverse events (1.02 (95% CI: 0.96 to 1.08)) were found.,Most of the observational evidence trended in the same direction as pooled RCT data.,Further evidence, especially pragmatic trials, are needed to fully understand the characteristics of patient subgroups who may benefit from triple therapy and for those whom the extra risk of adverse events, such as pneumonia, may outweigh any benefits.,CRD42018088013.

Recently, two “fixed triple” single-inhaler combinations of an inhaled corticosteroid (ICS), a long-acting β2-agonist (LABA), and a long-acting muscarinic antagonist (LAMA) have become available for patients with COPD.,This review presents the clinical evidence that led to the approval of these triple therapies, discusses the role of ICS in patients with COPD, and presents data on the relative efficacy of “fixed triple” (ICS/LAMA/LABA) therapy vs LAMA, ICS/LABA, and LAMA/LABA combinations, and summarizes studies in which ICS/LABAs were combined with LAMAs to form “open triple” combinations.,Of the five main fixed triple studies completed so far, three evaluated the efficacy and safety of an extrafine formulation of beclometasone dipropionate, formoterol fumarate, and glycopyrronium; the other two studies evaluated fluticasone furoate, vilanterol, and umeclidinium.,Overall, compared to LAMA, ICS/LABA, or LAMA/LABA, triple therapy decreased the risk of exacerbations and improved lung function and health status, with a favorable benefit-to-harm ratio.,Furthermore, triple therapy showed a promising signal in terms of improved survival.,The evidence suggests that triple therapy is the most effective treatment in moderate/severe symptomatic patients with COPD at risk of exacerbations, with marginal if any risk of side effects including pneumonia.,Ongoing studies are examining the role of triple therapy in less severe symptomatic patients with COPD and asthma-COPD overlap.

Using a composite endpoint, pooled data from two 12-week Phase III placebo-controlled trials (GOLDEN 3, NCT02347761; GOLDEN 4, NCT02347774) were analyzed to determine whether glycopyrrolate inhalation solution (25 mcg and 50 mcg) administered twice daily (BID) via the eFlow® Closed System nebulizer (GLY) reduced the risk of clinically important deterioration (CID) in patients with moderate-to-very-severe COPD.,CID was defined as ≥100-mL decrease from baseline in post-bronchodilator trough forced expiratory volume in one second (FEV1), or ≥4-unit increase in baseline St.,George’s Respiratory Questionnaire (SGRQ) total score, or moderate/severe exacerbation.,The relative treatment effect of GLY versus placebo on the odds of CID (any and by component endpoints) was expressed as the odds ratio (OR) and 95% confidence interval (CI).,Subgroups categorized by age (<65/≥65 years), sex, smoking status (current/former), long-acting beta agonist (LABA) use, FEV1 (<50%/≥50%), and peak inspiratory flow rate (PIFR) (<60 L/min/≥60 L/min) were analyzed.,Compared to placebo, GLY 25 mcg and 50 mcg BID over 12 weeks significantly reduced the risk of CID by 50% (OR: 0.50 [0.37-0.68]) and 40% (OR: 0.60 [0.44-0.80]), respectively.,Subjects treated with GLY 25 mcg BID were 59% less likely to experience CID in FEV1 (OR: 0.41 [0.27-0.62]) and 48% less likely to perceive CID in health status (OR: 0.52 [0.37-0.73]).,Statistically significant reductions were also observed at the higher dose.,The incidence of moderate/severe exacerbations was low and comparable among the cohorts.,GLY 25 mcg BID was significantly more effective than placebo (p<0.05) in preventing CID irrespective of age, smoking status, LABA use, COPD severity, or PIFR.,Subjects <65 years (OR 0.45 [0.29-0.68]) and those with PIFR <60 L/min (OR 0.36 [0.20-0.67]) exhibited the largest benefit.,Nebulized GLY over 12 weeks significantly reduced the risk of CID and provided greater short-term stability in patients with moderate-to-very-severe COPD.

Chronic obstructive pulmonary disease (COPD) is common in older people, with an estimated prevalence of 10% in the US population aged ≥75 years.,Inhaled medications are the cornerstone of treatment for COPD and are typically administered by one of three types of devices, ie, pressurized metered dose inhalers, dry powder inhalers, and nebulizers.,However, age-related pulmonary changes may negatively influence the delivery of inhaled medications to the small airways.,In addition, physical and cognitive impairment, which are common in elderly patients with COPD, pose special challenges to the use of handheld inhalers in the elderly.,Health care providers must take time to train patients to use handheld inhalers and must also check that patients are using them correctly on a regular basis.,Nebulizers should be considered for patients unable to use handheld inhalers properly.,What follows is a review of issues associated with COPD and its treatment in the elderly patient.

Acute COPD exacerbations account for much of the rising disability and costs associated with COPD, but data on predictive risk factors are limited.,The goal of the current study was to develop a robust, clinically based model to predict frequent exacerbation risk.,Patients identified from the Optimum Patient Care Research Database (OPCRD) with a diagnostic code for COPD and a forced expiratory volume in 1 second/forced vital capacity ratio <0.7 were included in this historical follow-up study if they were ≥40 years old and had data encompassing the year before (predictor year) and year after (outcome year) study index date.,The data set contained potential risk factors including demographic, clinical, and comorbid variables.,Following univariable analysis, predictors of two or more exacerbations were fed into a stepwise multivariable logistic regression.,Sensitivity analyses were conducted for subpopulations of patients without any asthma diagnosis ever and those with questionnaire data on symptoms and smoking pack-years.,The full predictive model was validated against 1 year of prospective OPCRD data.,The full data set contained 16,565 patients (53% male, median age 70 years), including 9,393 patients without any recorded asthma and 3,713 patients with questionnaire data.,The full model retained eleven variables that significantly predicted two or more exacerbations, of which the number of exacerbations in the preceding year had the strongest association; others included height, age, forced expiratory volume in 1 second, and several comorbid conditions.,Significant predictors not previously identified included eosinophilia and COPD Assessment Test score.,The predictive ability of the full model (C statistic 0.751) changed little when applied to the validation data set (n=2,713; C statistic 0.735).,Results of the sensitivity analyses supported the main findings.,Patients at risk of exacerbation can be identified from routinely available, computerized primary care data.,Further study is needed to validate the model in other patient populations.

Real-world prescription pathways leading to triple therapy (TT) (inhaled corticosteroid [ICS] plus long-acting β2-agonist bronchodilator [LABA] plus long-acting muscarinic antagonist) differ from Global initiative for chronic Obstructive Lung Disease [GOLD] and National Institute for Health and Care Excellence treatment recommendations.,This study sets out to identify COPD patients without asthma receiving TT, and determine the pathways taken from diagnosis to the first prescription of TT.,This was a historical analysis of COPD patients without asthma from the Optimum Patient Care Research Database (387 primary-care practices across the UK) from 2002 to 2010.,Patient disease severity was classified using GOLD 2013 criteria.,Data were analyzed to determine prescribing of TT before, at, and after COPD diagnosis; the average time taken to receive TT; and the impact of lung function grade, modified Medical Research Council dyspnea score, and exacerbation history on the pathway to TT.,During the study period, 32% of patients received TT.,Of these, 19%, 28%, 37%, and 46% of patients classified as GOLD A, B, C, and D, respectively, progressed to TT after diagnosis (P<0.001).,Of all patients prescribed TT, 25% were prescribed TT within 1 year of diagnosis, irrespective of GOLD classification (P=0.065).,The most common prescription pathway to TT was LABA plus ICS.,It was observed that exacerbation history did influence the pathway of LABA plus ICS to TT.,Real life UK prescription data demonstrates the inappropriate prescribing of TT and confirms that starting patients on ICS plus LABA results in the inevitable drift to overuse of TT.,This study highlights the need for dissemination and implementation of COPD guidelines to physicians, ensuring that patients receive the recommended therapy.

Viral infection is a common trigger for acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,The aim of this study is to investigate the expression of cytokines in AECOPD.,Patients with AECOPD requiring hospitalization were recruited.,Meanwhile healthy volunteers of similar age that accepted routine check-ups and showed no clinical symptoms of inflammatory diseases were also recruited.,Induced sputum and serum were collected.,Induced sputum of participants was processed and tested for thirteen viruses and bacteria.,Forty cytokines were assayed in serum using the Quantibody Human Inflammation Array 3 (Ray Biotech, Inc.).,The most common virus detected in virus positive AECOPD (VP) was influenza A (16%).,No virus was found in controls.,Circulating levels of IL-6, TNF-α, and MCP-1 were elevated in VP and coinfection subjects (p < 0.05), while the levels of 37 other cytokines showed no difference, compared with virus negative groups and controls (p > 0.05).,Additionally, VP patients were less likely to have received influenza vaccination.,VP patients had a systemic inflammation response involving IL-6, TNF-α, and MCP-1 which may be due to virus-induced activation of macrophages.,There are important opportunities for further investigating AECOPD mechanisms and for the development of better strategies in the management and prevention of virus-related AECOPD.

Chronic exposure to high levels of ozone induces emphysema and chronic inflammation in mice.,We determined the recovery from ozone-induced injury and whether an antioxidant, N-acetylcysteine (NAC), could prevent or reverse the lung damage.,Mice were exposed to ozone (2.5 ppm, 3 hours/12 exposures, over 6 weeks) and studied 24 hours (24h) or 6 weeks (6W) later.,Nac (100 mg/kg, intraperitoneally) was administered either before each exposure (preventive) or after completion of exposure (therapeutic) for 6 weeks.,After ozone exposure, there was an increase in functional residual capacity, total lung volume, and lung compliance, and a reduction in the ratio of forced expiratory volume at 25 and 50 milliseconds to forced vital capacity (FEV25/FVC, FEV50/FVC).,Mean linear intercept (Lm) and airway hyperresponsiveness (AHR) to acetylcholine increased, and remained unchanged at 6W after cessation of exposure.,Preventive NAC reduced the number of BAL macrophages and airway smooth muscle (ASM) mass.,Therapeutic NAC reversed AHR, and reduced ASM mass and apoptotic cells.,Emphysema and lung function changes were irreversible up to 6W after cessation of ozone exposure, and were not reversed by NAC.,The beneficial effects of therapeutic NAC may be restricted to the ASM.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a significant cause of mortality of COPD patients, and pose a huge burden on healthcare.,One of the major causes of AECOPD is airway bacterial (e.g. nontypeable Haemophilus influenzae [NTHi]) infection.,However, the mechanisms underlying bacterial infections during AECOPD remain poorly understood.,As neutrophilic inflammation including increased release of human neutrophil elastase (HNE) is a salient feature of AECOPD, we hypothesized that HNE impairs airway epithelial defense against NTHi by degrading airway epithelial host defense proteins such as short palate, lung, and nasal epithelium clone 1 (SPLUNC1).,Recombinant human SPLUNC1 protein was incubated with HNE to confirm SPLUNC1 degradation by HNE.,To determine if HNE-mediated impairment of host defense against NTHi was SPLUNC1-dependent, SPLUNC1 protein was added to HNE-treated primary normal human airway epithelial cells.,The in vivo function of SPLUNC1 in NTHi defense was investigated by infecting SPLUNC1 knockout and wild-type mice intranasally with NTHi.,We found that: (1) HNE directly increased NTHi load in human airway epithelial cells; (2) HNE degraded human SPLUNC1 protein; (3) Recombinant SPLUNC1 protein reduced NTHi levels in HNE-treated human airway epithelial cells; (4) NTHi levels in lungs of SPLUNC1 knockout mice were increased compared to wild-type mice; and (5) SPLUNC1 was reduced in lungs of COPD patients.,Our findings suggest that SPLUNC1 degradation by neutrophil elastase may increase airway susceptibility to bacterial infections.,SPLUNC1 therapy likely attenuates bacterial infections during AECOPD.

The percentage of neutrophils in sputum are increased in COPD patients, and may therefore be a biomarker of airway inflammation.,We studied the relationships between sputum neutrophils and FEV1, health status, exacerbation rates, systemic inflammation and emphysema, and long term variability at 1 year.,Sputum samples were obtained from 488 COPD patients within the ECLIPSE cohort. 359 samples were obtained at baseline, and 297 after 1 year. 168 subjects provided samples at both visits.,Serum interleukin-6 (IL-6), IL-8, surfactant protein D and C-reactive protein levels were measured by immunoassays.,Low-dose CT scans evaluated emphysema.,Sputum neutrophil % increased with GOLD stage.,There was a weak association between % sputum neutrophils and FEV1 % predicted (univariate r2 = 0.025 and 0.094 at baseline and year 1 respectively, p < 0.05 after multivariate regression).,Similar weak but significant associations were observed between neutrophil % and health status measured using the St Georges Respiratory Questionairre.,There were no associations between neutrophils and exacerbation rates or emphysema.,Associations between sputum neutrophils and systemic biomarkers were non-significant or similarly weak.,The mean change over 1 year in neutrophil % was an increase of 3.5%.,Sputum neutrophil measurements in COPD are associated weakly with FEV1 % predicted and health status.,Sputum neutrophil measurements were dissociated from exacerbation rates, emphysema and systemic inflammation.

Chronic obstructive pulmonary disease (COPD) is one of the most common causes of mortality and a major contributor to morbidity.,Longitudinal clinical practice data yielding information on the characteristics of the disease, its natural course, and management are limited.,To investigate and describe the COPD population from a nationwide perspective during an 11-year period (1999-2009) with a focus on management, co-morbidity, and mortality.,This observational retrospective epidemiological study linked electronic medical records data from patients with COPD in primary care to mandatory Swedish hospital, drug and Cause of Death registry data from 1999 to 2009 (PATHOS).,A total of 21,361 patients with a COPD diagnosis were included (mean age 68.0 years, 53% females).,The proportion of patients diagnosed in primary care increased from 59% in 1999 to 81% in 2009 and the mean age at diagnosis decreased from 73 to 66 years.,The number of exacerbations decreased from 3.0 to 1.3 and COPD-related hospitalisations decreased from 1.02 to 0.20 per patient per year.,Prescriptions of long-acting muscarinic antagonists and fixed combinations of inhaled corticosteroid/long-acting β2-agonist inhalers increased from 0% to 36% and 37%, respectively.,The most common co-morbidities were hypertension, heart failure, ischaemic heart disease, and diabetes.,Overall life expectancy was 8.3±6.8 years shorter in patients with COPD than in the general population, and all-cause mortality was 3.5 times higher.,Management of COPD in Sweden has improved during the 11-year study period.,Despite this, patients with COPD have a substantially reduced life expectancy than the general population.

Patient-reported outcomes (PRO) questionnaires are being increasingly used in COPD clinical studies.,The challenge facing investigators is to determine what change is significant, ie what is the minimal clinically important difference (MCID).,This study aimed to identify the MCID for the clinical COPD questionnaire (CCQ) in terms of patient referencing, criterion referencing, and by the standard error of measurement (SEM).,Patients were ≥40 years of age, diagnosed with COPD, had a smoking history of >10 pack-years, and were participating in a randomized, controlled clinical trial comparing intravenous and oral prednisolone in patients admitted with an acute exacerbation of COPD.,The CCQ was completed on Days 1-7 and 42.,A Global Rating of Change (GRC) assessment was taken to establish the MCID by patient referencing.,For criterion referencing, health events during a period of 1 year after Day 42 were included in this analysis.,210 patients were recruited, 168 completed the CCQ questionnaire on Day42.,The MCID of the CCQ total score, as indicated by patient referencing in terms of the GRC, was 0.44.,The MCID of the CCQ in terms of criterion referencing for the major outcomes was 0.39, and calculation of the SEM resulted in a value of 0.21.,This investigation, which is the first to determine the MCID of a PRO questionnaire via more than one approach, indicates that the MCID of the CCQ total score is 0.4.

Chronic obstructive pulmonary disease (COPD) is caused by exposure to toxic particles, such as coal fly ash (CFA), diesel-exhaust particle (DEP), and cigarette smoke (CS), leading to chronic bronchitis, mucus production, and a subsequent lung dysfunction.,This study, using a mouse model of COPD, aimed to evaluate the effect of herbal combinational medication of Glycyrrhiza glabra (GG), Agastache rugosa (AR) containing glycyrrhizic acid (GA), and tilianin (TN) as active ingredients.,GA, a major active component of GG, possesses a range of pharmacological and biological activities including anti-inflammatory, anti-allergic, anti-oxidative.,TN is a major flavonoid that is present in AR.,It has been reported to have anti-inflammatory effects of potential utility as an anti-COPD agent.,The COPD in the mice model was induced by a challenge with CFA and DEP.,BALB/c mice received CFA and DEP alternately three times for 2 weeks to induce COPD.,The herbal mixture of GG, AR, and TN significantly decreased the number of neutrophils in the lungs and bronchoalveolar lavage (BAL) fluid.,It also significantly reduced the production of C-X-C motif chemokine ligand 2 (CXCL-2), IL-17A, CXCL-1, TNF-α, symmetric dimethylarginine (SDMA) in BALF and CXCL-2, IL-17A, CXCL-1, MUC5AC, transient receptor potential vanilloid-1 (TRPV1), IL-6, COX-2, NOS-II, and TNF-α mRNA expression in the lung tissue.,Notably, a combination of GG and AR was more effective at regulating such therapeutic targets than GG or AR alone.,The histolopathological lung injury was alleviated by treatment with the herbal mixture and their active ingredients (especially TN).,In this study, the herbal combinational mixture more effectively inhibited neutrophilic airway inflammation by regulating the expression of inflammatory cytokines and CXCL-2 by blocking the IL-17/STAT3 pathway.,Therefore, a herbal mixture of GG and AR may be a potential therapeutic agent to treat COPD.

Corticosteroid resistance is a major barrier to the effective treatment of chronic obstructive pulmonary disease (COPD).,Oxidative stress from cigarette smoke and chronic inflammation is likely to induce this corticosteroid insensitivity.,Quercetin is a polyphenol that has been reported to be an active oxygen scavenger as well as a functional adenosine monophosphate-activated protein kinase (AMPK) activator.,The aim of this study was to investigate the effect of quercetin on corticosteroid responsiveness in COPD cells.,Corticosteroid sensitivity was examined in human monocytic U937 cells exposed to cigarette smoke extract (CSE) and peripheral blood mononuclear cells (PBMC) collected from patients with COPD.,Corticosteroid sensitivity was determined as the dexamethasone concentration causing 40% inhibition of tumor necrosis factor alpha-induced CXCL8 production (Dex-IC40) in the presence or absence of quercetin.,In U937 cells, treatment with quercetin activated AMPK and induced expression of nuclear factor erythroid 2-related factor 2, and consequently reversed CSE-induced corticosteroid insensitivity.,PBMC from patients with COPD showed corticosteroid insensitivity compared with those from healthy volunteers, and treatment with quercetin restored corticosteroid sensitivity.,In conclusion, quercetin restores corticosteroid sensitivity, and has the potential to be a novel treatment in combination with corticosteroids in COPD.

The aetiology of acute exacerbations of COPD (AECOPD) is incompletely understood.,Understanding the relationship between chronic bacterial airway infection and viral exposure may explain the incidence and seasonality of these events.,In this prospective, observational cohort study (NCT01360398), patients with COPD aged 40-85 years underwent sputum sampling monthly and at exacerbation for detection of bacteria and viruses.,Results are presented for subjects in the full cohort, followed for 1 year.,Interactions between exacerbation occurrence and pathogens were investigated by generalised estimating equation and stratified conditional logistic regression analyses.,The mean exacerbation rate per patient-year was 3.04 (95% CI 2.63 to 3.50).,At AECOPD, the most common bacterial species were non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis, and the most common virus was rhinovirus.,Logistic regression analyses (culture bacterial detection) showed significant OR for AECOPD occurrence when M. catarrhalis was detected regardless of season (5.09 (95% CI 2.76 to 9.41)).,When NTHi was detected, the increased risk of exacerbation was greater in high season (October-March, OR 3.04 (1.80 to 5.13)) than low season (OR 1.22 (0.68 to 2.22)).,Bacterial and viral coinfection was more frequent at exacerbation (24.9%) than stable state (8.6%).,A significant interaction was detected between NTHi and rhinovirus presence and AECOPD risk (OR 5.18 (1.92 to 13.99); p=0.031).,AECOPD aetiology varies with season.,Rises in incidence in winter may be driven by increased pathogen presence as well as an interaction between NTHi airway infection and effects of viral infection.,Results, NCT01360398.

Chronic obstructive pulmonary disease (COPD) is related to an abnormal chronic inflammatory response of the lung to mainly cigarette smoke (CS) and the disease risk is increased in aged individuals.,The source of this chronic inflammation is due to the repeated and progressive activation of immune cells.,We hypothesize that in a chronic CS-induced mouse model, the predisposition to COPD pathogenesis in aged mice is characterized by an elevated immune response compared to young animals.,We measured several characteristics of COPD in young and old mice (2 and 12 months of age) exposed to CS for 3 months.,CS-exposed aged mice exhibited increased lung compliance (0.061 ± 0.008 vs.,0.055 ± 0.006 ml/cm H2O, p < 0.01), emphysema development (35.36 ± 0.71 vs.,25.31 ± 0.005 μm; p < 0.01) and airway remodeling (2.15 ± 0.37 vs.,1.09 ± 0.64 μm3/μm2; p < 0.01) compared to control animals, which was not seen in CS-exposed young mice.,Quantification of lung tissue inflammation revealed a significantly greater volume of inducible bronchus-associated lymphoid tissue structures in aged mice after CS exposure (5.94 ± 2.89 vs.,2.37 ± 1.69 μm3/μm2; p < 0.01).,Our results indicate that age-induced lung inflammation is further elevated after CS exposure in old mice, potentially via an age-induced change in immune cell susceptibility to CS thereby accelerating the pathophysiological hallmarks of COPD.

Chronic obstructive pulmonary disease (COPD) is a progressive and irreversible disease responsible for the deaths of 3 million people worldwide in 2005, and predicted to be the third leading cause of death worldwide by 2030.,Many COPD models developed to date have followed a Markov structure, in which patients or populations can move between defined health states over successive time periods or cycles.,In COPD, health states are typically based on disease severity defined solely by lung function, as described by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.,These current modelling methods may restrict the ability to reflect the disease progression/clinical pathway or clinical practice.,Given these limitations in previous COPD models, the authors aimed to develop a more flexible model that could improve on the description of the clinical disease pathway.,The overall objective of this model was to inform the development of policies, guidelines or cost-effectiveness analyses.,A second objective was to validate the model in relation to existing epidemiology studies of COPD.,A patient simulation model was developed in Microsoft Excel™.,The predictability of the model was tested by populating it with data from natural history of disease studies as well as with clinical trial data.,Each patient moves through the model with demographic characteristics randomly generated from a set distribution.,These characteristics determine the risk of clinical events occurring in the model.,The validation with these studies found the model to have generally good predictive ability, yielding in this way a good degree of external validity.,The micro-simulation model is a flexible approach for modelling COPD that allows consideration of complex COPD treatment pathways.,The model was found to be generally robust in terms of predicting clinical outcomes of published studies when tested against other studies.,It has significant potential as a tool for supporting future COPD treatment positioning decisions as well as to inform the development of policies, guidelines or cost-effectiveness analyses.

The poor recognition and related underdiagnosis of COPD contributes to an underestimation of mortality in subjects with COPD.,Data derived from population studies can advance our understanding of the true burden of COPD.,The objective of this report was to evaluate the impact of COPD on mortality and its predictors in a cohort of subjects with and without COPD recruited during the twenty first century.,All subjects with COPD (n = 993) defined according to the GOLD spirometric criteria, FEV1/FVC < 0.70, and gender- and age-matched subjects without airway obstruction, non-COPD (n = 993), were identified in a clinical follow-up survey of the Obstructive Lung Disease in Northern Sweden (OLIN) Studies cohorts in 2002-2004.,Mortality was observed until the end of year 2007.,Baseline data from examination at recruitment were used in the risk factor analyses; age, smoking status, lung function (FEV1 % predicted) and reported heart disease.,The mortality was significantly higher among subjects with COPD, 10.9%, compared to subjects without COPD, 5.8% (p < 0.001).,Mortality was associated with higher age, being a current smoker, male gender, and COPD.,Replacing COPD with FEV1 % predicted in the multivariate model resulted in the decreasing level of FEV1 being a significant risk factor for death, while heart disease was not a significant risk factor for death in any of the models.,In this cohort COPD and decreased FEV1 were significant risk factors for death when adjusted for age, gender, smoking habits and reported heart disease.

Chronic obstructive pulmonary disease (COPD) is a known risk factor for lung cancer and a leading cause of mortality in the U.S., but its impact may not be fully appreciated, especially among low-income populations in the southeast where COPD prevalence and lung cancer incidence are elevated.,We conducted a prospective study among 26,927 low-income adults age 40-79 in the Southern Community Cohort Study who had a Center for Medicare and Medicaid Services (CMS) encounter prior to enrollment and were followed for a median of over 6 years.,Using a validated algorithm for assessing COPD from CMS claims data, we estimated COPD prevalence and potential misreporting.,From Cox proportional hazard models, we computed overall and lung cancer-specific mortality according to COPD status.,The overall prevalence of CMS-diagnosed COPD was 16%, but was twice as high among whites as blacks.,Only 35% of these individuals, however, self-reported having COPD, with underreporting significantly greater for blacks than whites.,Smoking-adjusted all-cause mortality was increased by 1.7-fold and lung cancer mortality by 2.3-fold among those with a CMS COPD diagnosis, with similar patterns in blacks and whites, but no excess was found among those self-reporting COPD and without CMS confirmation.,The prevalence of COPD in this low-income population may be greater than previously recognized and misreporting is common.,COPD is associated with elevated lung cancer mortality, even among those not self-reporting the condition.

Recent guidelines for chronic obstructive pulmonary disease (COPD) state that COPD is both preventable and treatable.,To gain a more positive outlook on the disease it is interesting to investigate factors associated with good, self-rated health and quality of life in subjects with self-reported COPD in the population.,In a cross-sectional study design, postal survey questionnaires were sent to a stratified, random population in Sweden in 2004 and 2008.,The prevalence of subjects (40-84 years) who reported having COPD was 2.1% in 2004 and 2.7% in 2008.,Data were analyzed for 1475 subjects.,Regression models were used to analyze the associations between health measures (general health status, the General Health Questionnaire, the EuroQol five-dimension questionnaire) and influencing factors.,The most important factor associated with good, self-rated health and quality of life was level of physical activity.,Odds ratios for general health varied from 2.4 to 7.7 depending on degree of physical activity, where subjects with the highest physical activity level reported the best health and also highest quality of life.,Social support and absence of economic problems almost doubled the odds ratios for better health and quality of life.,In this population-based public health survey, better self-rated health status and quality of life in subjects with self-reported COPD was associated with higher levels of physical activity, social support, and absence of economic problems.,The findings indicated that of possible factors that could be influenced, promoting physical activity and strengthening social support are important in maintaining or improving the health and quality of life in subjects with COPD.,Severity of the disease as a possible confounding effect should be investigated in future population studies.

Supplemental Digital Content is available in the text,Nowadays, there is growing recognition that chronic obstructive pulmonary disease (COPD) may have influence on lung cancer.,However, coexisted COPD related to prognosis of lung cancer is still elusive.,We conducted this meta-analysis to examine the association between COPD and 5-year overall survival (OS) and postoperative pulmonary complications of patients with lung cancer.,A comprehensive computer-based online search was conducted using PubMed, Embase, Medline, and the Cochrane Library for articles published before September 30, 2017.,We identified 29 eligible studies, which included 70,111 patients in the related literature.,Twenty-two of the 29 studies provided hazard ratio for OS (1.18, 95% confidence interval: 1.11-1.25; P < .001), it suggested that the presence of COPD indicated poor survival for the patients with lung cancer.,In subgroup analysis, the relationship between COPD and OS occurrence remained statistically prominent in the subgroups stratified by study designs, COPD diagnosis timing, lung cancer surgery, cancer stage, and origins of patients.,The presence of COPD increased the risk of bronchopleural fistula, pneumonia, prolonged air leakage, and prolonged mechanical ventilation.,The present meta-analysis suggested that coexisting COPD is associated with poor survival outcomes in patients with lung cancer and higher rates of postoperative pulmonary complications.

This study was conducted in order to investigate the differences in the respiratory physiology of patients with chronic obstructive pulmonary disease (COPD), asthma-COPD overlap syndrome (ACOS), and asthma with airflow limitation (asthma FL+).,The medical records for a series of all stable patients with persistent airflow limitation due to COPD, ACOS, or asthma were retrospectively reviewed and divided into the COPD group (n=118), the ACOS group (n=32), and the asthma FL+ group (n=27).,All the patients underwent chest high-resolution computed tomography (HRCT) and pulmonary function tests, including respiratory impedance.,The low attenuation area score on chest HRCT was significantly higher in the COPD group than in the ACOS group (9.52±0.76 vs 5.09±1.16, P<0.01).,The prevalence of bronchial wall thickening on chest HRCT was significantly higher in the asthma FL+ group than in the COPD group (55.6% vs 25.0%, P<0.01).,In pulmonary function, forced expiratory volume in 1 second (FEV1) and peak expiratory flow rate were significantly higher in the asthma FL+ group than in the ACOS group (76.28%±2.54% predicted vs 63.43%±3.22% predicted, P<0.05 and 74.40%±3.16% predicted vs 61.08%±3.54% predicted, P<0.05, respectively).,Although residual volume was significantly lower in the asthma FL+ group than in the COPD group (112.05%±4.34% predicted vs 137.38%±3.43% predicted, P<0.01) and the ACOS group (112.05%±4.34% predicted vs148.46%±6.25% predicted, P<0.01), there were no significant differences in functional residual capacity or total lung capacity.,The increase in FEV1 in response to short-acting β2-agonists was significantly greater in the ACOS group than in the COPD group (229±29 mL vs 72±10 mL, P<0.01) and the asthma FL+ group (229±29 mL vs 153±21 mL, P<0.05).,Regarding respiratory impedance, resistance at 5 Hz and resistance at 20 Hz, which are oscillatory parameters of respiratory resistance, were significantly higher in the asthma FL+ group than in the COPD group at the whole-breath (4.29±0.30 cmH2O/L/s vs 3.41±0.14 cmH2O/L/s, P<0.01 and 3.50±0.24 cmH2O/L/s vs 2.68±0.10 cmH2O/L/s, P<0.01, respectively), expiratory, and inspiratory phases.,Although persistent airflow limitation occurs in patients with COPD, ACOS, and asthma FL+, they may have distinct characteristics of the respiratory physiology and different responsiveness to bronchodilators.

Chronic obstructive pulmonary disease (COPD) exacerbations are associated with high disease burden and costs, especially in the case of hospitalizations.,The overall number of hospital admissions due to exacerbations of COPD has increased.,It is remarkable that re-admissions account for a substantial part of these hospitalizations.,This pilot study investigates the use of case management to reduce re-admissions due to COPD.,COPD patients with more than one hospitalization per year due to an exacerbation were included.,The participants (n = 10) were closely monitored and intensively coached for 20 weeks after hospitalization.,The case manager provided care in a person-focused manner.,The case manager informed and supported the patient, took action when relapse threatened, coordinated and connected primary and secondary care.,Data of 12 months before and after start of the intervention were compared.,Primary outcome was the difference in number of hospitalizations.,Secondary outcomes were health-related quality of life (measured by the Clinical COPD Questionnaire, CCQ) and dyspnoea (measured by the MRC Dyspnoea Scale).,The incidence rate of hospitalizations was found to be 2.25 times higher (95% confidence interval [CI] 1.3-3.9; P = 0.004) 12 months before compared with 12 months after the start of case management.,COPD patients had a mean CCQ score of 3.3 (95% CI 2.8-3.8) before and 2.4 (95% CI 1.9-2.8) after 20 weeks of case management; a difference of 1.0 (95% CI 0.4-1.6; P = 0.001).,The mean MRC scores showed no significant differences before (4.3; 95% CI 3.7-4.9) and after the case management period (3.9; 95% CI 3.2-4.6); a difference of 0.4 (95% CI − 0.1 to 0.9; P = 0.114).,This pilot study shows that the number of COPD hospital re-admissions decreased significantly after the introduction of a case manager.,Moreover, there was an improvement in patient-reported health-related quality of life.,The online version of this article (10.1186/s13104-017-2946-5) contains supplementary material, which is available to authorized users.

Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation.

Current in-hospital management of exacerbations of COPD is suboptimal, and patient outcomes are poor.,The primary aim of this study was to evaluate whether implementation of a care pathway (CP) for COPD improves the 6 months readmission rate.,Secondary outcomes were the 30 days readmission rate, mortality, length of stay and adherence to guidelines.,An international cluster randomized controlled trial was performed in Belgium, Italy and Portugal.,General hospitals were randomly assigned to an intervention group where a CP was implemented or a control group where usual care was provided.,The targeted population included patients with COPD exacerbation.,Twenty-two hospitals were included, whereof 11 hospitals (n=174 patients) were randomized to the intervention group and 11 hospitals (n=168 patients) to the control group.,The CP had no impact on the 6 months readmission rate.,However, the 30 days readmission rate was significantly lower in the intervention group (9.7%; 15/155) compared to the control group (15.3%; 22/144) (odds ratio =0.427; 95% confidence interval 0.222-0.822; P=0.040).,Performance on process indicators was significantly higher in the intervention group for 2 of 24 main indicators (8.3%).,The implementation of this in-hospital CP for COPD exacerbation has no impact on the 6 months readmission rate, but it significantly reduces the 30 days readmission rate.

Exacerbations, a leading cause of hospitalization in patients with chronic obstructive pulmonary disease (COPD), affect the quality of life and prognosis.,Treatment recommendations as provided in the evidence-based guidelines are not consistently followed, partly due to absence of simplified task-oriented approach to care.,In this study, we describe the development and implementation of a clinical pathway (CP) and evaluate its effectiveness in the management of COPD exacerbation.,We developed a CP and evaluated its effectiveness in a non-randomized prospective study with historical controls on patients admitted for exacerbation of COPD to Universiti Kebangsaan Malaysia Medical Centre (UKMMC).,Consecutive patients who were admitted between June 2009 and December 2010 were prospectively recruited into the CP group.,Non-CP historical controls were obtained from case records of patients admitted between January 2008 and January 2009.,Clinical outcomes were evaluated by comparing the length of stay (LOS), complication rates, readmissions, and mortality rates.,Ninety-five patients were recruited in the CP group and 98 patients were included in the non-CP historical group.,Both groups were comparable with no significant differences in age, sex and severity of COPD (p = 0.641).,For clinical outcome measures, patients in the CP group had shorter length of stay than the non-CP group (median (IQR): 5 (4-7) days versus 7 (7-9) days, p < 0.001) and 24.1% less complications (14.7% versus 38.8%, p < 0.001).,We did not find any significant differences in readmission and mortality rates.,The implementation of CP -reduced the length of stay and complication rates of patients hospitalized for acute exacerbation of COPD.

The Continuing to Confront COPD International Patient Survey aimed to estimate the prevalence and burden of COPD globally and to update findings from the Confronting COPD International Survey conducted in 1999-2000.,Chronic obstructive pulmonary disease (COPD) patients in 12 countries worldwide were identified through systematic screening of population samples.,Telephone and face-to-face interviews were conducted between November 2012 and May 2013 using a structured survey that incorporated validated patient-reported outcome instruments.,Eligible patients were adults aged 40 years and older who were taking regular respiratory medications or suffered with chronic respiratory symptoms and reported either 1) a physician diagnosis of COPD/emphysema, 2) a physician diagnosis of chronic bronchitis, or 3) a symptom-based definition of chronic bronchitis.,The burden of COPD was measured with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) Dyspnea Scale.,Of 106,876 households with at least one person aged ≥40 years, 4,343 respondents fulfilled the case definition of COPD and completed the full survey.,COPD prevalence ranged from 7% to 12%, with most countries falling within the range of 7%-9%.,In all countries, prevalence increased with age, and in all countries except the US was greater among men (range 6%-14%) than among women (range 5%-11%).,A significant disease burden was observed when considering COPD symptoms or health status, and showed wide variations across countries.,Prevalence of moderate-to-severe dyspnea (mMRC scale ≥2) ranged from 27% to 61%, and mean CAT score ranged from 16.0 to 24.8, indicating medium-to-high impairment.,This survey, representing 12 countries, showed similar rates of estimated COPD prevalence across countries that were higher than those reported a decade ago in the original Confronting COPD International Survey.,A significant burden of COPD was demonstrated by symptoms and health care-resource use, similar to that reported in the original survey.

A nebulized formulation of formoterol, Perforomist®, 20 μg/2 ml, has been available since 2007 for the maintenance treatment of chronic obstructive pulmonary disease (COPD).,We review the safety and efficacy data obtained during its development.,In a dose-finding study, formoterol inhalation solution (FFIS) was similar to the formoterol originator, Foradil® 12 μg DPI (FA) in patients with COPD.,In a 12-week efficacy study, FFIS manifested a rapid onset of action and FEV1 peak, AUC0-12, and trough levels similar to FA.,No loss of efficacy, tachyphylaxis, was observed over 12 weeks of regular administration.,In placebo-controlled studies in COPD patients receiving maintenance tiotropium, the addition of FFIS significantly augmented bronchodilation over the 6-week treatment duration, signifying that nebulized formoterol can further improve lung function in patients who are receiving tiotropium without an observed increase in adverse reactions.,The safety profile of FFIS during 12-week and 1-year studies revealed adverse events that were similar to those of placebo and FA.,Cardiac rhythm studies, including frequent ECGs and Holter monitoring, did not indicate any increase in rate or rhythm disturbances greater than placebo or FA.,We conclude that maintenance use of Perforomist® is appropriate for patients with COPD who require or prefer a nebulizer for management of their disease.

The potential benefits of statins for the prevention of exacerbations in patients with COPD remains controversial.,No previous studies have investigated the impact of statins on clinical outcomes in COPD patients with frequent exacerbations.,This study aimed to evaluate the association between the use of statins and the risk of subsequent hospitalized exacerbations in COPD frequent exacerbators.,We conducted a population-based cohort study using the Taiwan National Health Insurance Research Database.,139,223 COPD patients with a first hospitalized exacerbation between 2004 and 2012 were analyzed.,Among them, 35,482 had a second hospitalized exacerbation within a year after the first exacerbation, and were defined as frequent exacerbators. 1:4 propensity score matching was used to create matched samples of statin users and non-users.,The competing risk regression analysis model was used to evaluate the association between statin use and exacerbation risk.,The use of statins was associated with a significantly reduced risk in subsequent hospitalized exacerbations in COPD patients after their first hospitalized exacerbation (adjusted subdistribution hazard ration [SHR], 0.89; 95% CI, 0.85-0.93, P<0.001).,In frequent exacerbators, the SHR for subsequent hospitalized exacerbations in statins users was 0.88 (95% CI, 0.81-0.94, P=0.001).,Subgroup analysis among frequent exacerbators demonstrated that the use of statins only provided a protective effect against subsequent hospitalized exacerbations in male patients aged 75 years and older, with coexisting diabetes mellitus, hypertension or cardiovascular disease, and no protective effect was observed in those with lung cancer or depression.,Current use of statins was associated with a greater protective effect for reducing subsequent hospitalized exacerbation.,The use of statins was associated with a significant reduction in the risk of hospitalized exacerbations in COPD patients after a first hospitalized exacerbation and in specified COPD frequent exacerbators.

Alterations in the composition of the lung microbiome associated with adverse clinical outcomes, known as dysbiosis, have been implicated with disease severity and exacerbations in COPD.,To characterise longitudinal changes in the lung microbiome in the AERIS study (Acute Exacerbation and Respiratory InfectionS in COPD) and their relationship with associated COPD outcomes.,We surveyed 584 sputum samples from 101 patients with COPD to analyse the lung microbiome at both stable and exacerbation time points over 1 year using high-throughput sequencing of the 16S ribosomal RNA gene.,We incorporated additional lung microbiology, blood markers and in-depth clinical assessments to classify COPD phenotypes.,The stability of the lung microbiome over time was more likely to be decreased in exacerbations and within individuals with higher exacerbation frequencies.,Analysis of exacerbation phenotypes using a Markov chain model revealed that bacterial and eosinophilic exacerbations were more likely to be repeated in subsequent exacerbations within a subject, whereas viral exacerbations were not more likely to be repeated.,We also confirmed the association of bacterial genera, including Haemophilus and Moraxella, with disease severity, exacerbation events and bronchiectasis.,Subtypes of COPD have distinct bacterial compositions and stabilities over time.,Some exacerbation subtypes have non-random probabilities of repeating those subtypes in the future.,This study provides insights pertaining to the identification of bacterial targets in the lung and biomarkers to classify COPD subtypes and to determine appropriate treatments for the patient.,Results, NCT01360398.

Rationale: The IMPACT (Informing the Pathway of Chronic Obstructive Pulmonary Disease Treatment) trial demonstrated a significant reduction in all-cause mortality (ACM) risk with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus UMEC/VI in patients with chronic obstructive pulmonary disease (COPD) at risk of future exacerbations.,Five hundred seventy-four patients were censored in the original analysis owing to incomplete vital status information.,Objectives: Report ACM and impact of stepping down therapy, following collection of additional vital status data.,Methods: Patients were randomized 2:2:1 to FF/UMEC/VI 100/62.5/25 μg, FF/VI 100/25 μg, or UMEC/VI 62.5/25 μg following a run-in on their COPD therapies.,Time to ACM was prespecified.,Additional vital status data collection and subsequent analyses were performed post hoc.,Measurements and Main Results: We report vital status data for 99.6% of the intention-to-treat population (n = 10,355), documenting 98 (2.36%) deaths on FF/UMEC/VI, 109 (2.64%) on FF/VI, and 66 (3.19%) on UMEC/VI.,For FF/UMEC/VI, the hazard ratio for death was 0.72 (95% confidence interval, 0.53-0.99; P = 0.042) versus UMEC/VI and 0.89 (95% confidence interval, 0.67-1.16; P = 0.387) versus FF/VI.,Independent adjudication confirmed lower rates of cardiovascular and respiratory death and death associated with the patient’s COPD.,Conclusions: In this secondary analysis of an efficacy outcome from the IMPACT trial, once-daily single-inhaler FF/UMEC/VI triple therapy reduced the risk of ACM versus UMEC/VI in patients with symptomatic COPD and a history of exacerbations.

A single inhaler containing inhaled corticosteroid (ICS)/long-acting beta-agonist (LABA)/long-acting muscarinic antagonist (LAMA) is a more convenient way of delivering triple therapy in patients with COPD.,Single triple therapy has been shown to be superior at reducing exacerbations and improving quality of life compared to LABA/LAMA, especially in patients with a prior history of frequent exacerbations and blood eosinophilia, who have ICS responsive disease.,The corollary is that patients with infrequent exacerbations who are noneosinophilic may be safely de-escalated from triple therapy to LABA/LAMA without loss of control.,Pointedly, there is a substantially increased risk of pneumonia associated with the triple therapy containing fluticasone furoate but not beclometasone dipropionate or budesonide.,Since triple therapy is also better than ICS/LABA at reducing exacerbations and improving lung function, symptoms, and quality of life, this brings into question the rationale for using ICS/LABA.,Hence, we propose a simplified pragmatic decision process based on symptoms, prior to exacerbation history, and blood eosinophils to select which patients should be given a single triple inhaler or LABA/LAMA.,Differences in patient preference of inhaler device, formulations and drugs will also determine which triple inhaler prescribers elect to use.

COPD is an abnormal inflammatory response characterized by decreased expression of TLR2 in patients, which is suggested to induce invasive pulmonary aspergillosis (IPA).,MicroRNAs (miRNAs) have been shown to play important roles in the pathogenesis of human respiratory system disorders.,Therefore, the aim of this study was to identify the miRNAs involved in the regulation of TLR2 signaling in COPD.,miRNA microarray analysis was performed to screen for the dysregulated miRNAs in alveolar macrophages (AMs) isolated from COPD rats.,The interaction between these miRNAs and TLR2 gene was predicted using miRBase and validated using dual luciferase assay.,Based on the analysis, a novel miR-344b-1-3p was identified as a novel modulator of TLR2 gene.,Then, the mechanism through which miR-344b-1-3p regulated TLR2 expression was explored using cigarette smoke extract (CSE)-pretreated NR8383 cells.,Moreover, by subjecting CSE-pretreated NR8383 cells to Pam3CSK4, the effect of miR-344b-1-3p on NF-κB activity and other important mediators of COPD, including IRAK-1, ERK, TNF-α, IL-1β, and MIP-2, was also assessed.,COPD rat model was successfully induced by smoke inhalation.,Among the 11 upregulated miRNAs in AMs from COPD rats, miR-344b-1-3p was predicted to be a novel miRNA targeting TLR2 gene.,In the CSE pretreated NR8383 cells exposed to Pam3CSK4, miR-344b-1-3p inhibition increased the expression levels of TLR2, TNF-α, and IL-1β and decreased the expression levels of MIP-2.,In addition, the phosphorylation of IRAK-1, IκBα, and IRK was augmented by miR-344b-1-3p inhibition.,Findings outlined in this study suggest that miR-344b-1-3p was an effective modulator of TLR2 gene, which can be employed as a promising therapeutic and preventive target of IPA in COPD patients.

Sirtuin-1 (SIRT1) and SIRT6, NAD+-dependent Class III protein deacetylases, are putative anti-aging enzymes, down-regulated in patients with chronic obstructive pulmonary disease (COPD), which is characterized by the accelerated ageing of the lung and associated with increased oxidative stress.,Here, we show that oxidative stress (hydrogen peroxide) selectively elevates microRNA-34a (miR-34a) but not the related miR-34b/c, with concomitant reduction of SIRT1/-6 in bronchial epithelial cells (BEAS2B), which was also observed in peripheral lung samples from patients with COPD.,Over-expression of a miR-34a mimic caused a significant reduction in both mRNA and protein of SIRT1/-6, whereas inhibition of miR-34a (antagomir) increased these sirtuins.,Induction of miR-34a expression with H2O2 was phosphoinositide-3-kinase (PI3K) dependent as it was associated with PI3Kα activation as well as phosphatase and tensin homolog (PTEN) reduction.,Importantly, miR-34a antagomirs increased SIRT1/-6 mRNA levels, whilst decreasing markers of cellular senescence in airway epithelial cells from COPD patients, suggesting that this process is reversible.,Other sirtuin isoforms were not affected by miR-34a.,Our data indicate that miR-34a is induced by oxidative stress via PI3K signaling, and orchestrates ageing responses under oxidative stress, therefore highlighting miR-34a as a new therapeutic target and biomarker in COPD and other oxidative stress-driven aging diseases.

Mortality rate is high in patients with chronic obstructive pulmonary disease (COPD).,Our aim was to investigate long-term mortality and associated risk factors in COPD patients previously hospitalized for a COPD exacerbation.,A total of 256 patients from the Nordic countries were followed for 8.7 ± 0.4 years after the index hospitalization in 2000-2001.,Prior to discharge, the St George’s Respiratory Questionnaire was administered and data on therapy and comorbidities were obtained.,Information on long-term mortality was obtained from national registries in each of the Nordic countries.,In total, 202 patients (79%) died during the follow up period, whereas 54 (21%) were still alive.,Primary cause of death was respiratory (n = 116), cardiovascular (n = 43), malignancy (n = 28), other (n = 10), or unknown (n = 5).,Mortality was related to older age, with a hazard risk ratio (HRR) of 1.75 per 10 years, lower forced expiratory volume in 1 second (FEV1) (HRR 0.80), body mass index (BMI) <20 kg/m2 (HRR 3.21), and diabetes (HRR 3.02).,Older age, lower BMI, and diabetes were related to both respiratory and cardiovascular mortality.,An association was also found between lower FEV1 and respiratory mortality, whereas mortality was not significantly associated with therapy, anxiety, or depression.,Almost four out of five patients died within 9 years following an admission for COPD exacerbation.,Increased mortality was associated with older age, lower lung function, low BMI, and diabetes, and these factors should be taken into account when making clinical decisions about patients who have been admitted to hospital for a COPD exacerbation.

Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability internationally.,Alveolar hypoxia and consequent hypoxemia increase in prevalence as disease severity increases.,Ventilation/perfusion mismatch resulting from progressive airflow limitation and emphysema is the key driver of this hypoxia, which may be exacerbated by sleep and exercise.,Uncorrected chronic hypoxemia is associated with the development of adverse sequelae of COPD, including pulmonary hypertension, secondary polycythemia, systemic inflammation, and skeletal muscle dysfunction.,A combination of these factors leads to diminished quality of life, reduced exercise tolerance, increased risk of cardiovascular morbidity, and greater risk of death.,Concomitant sleep-disordered breathing may place a small but significant subset of COPD patients at increased risk of these complications.,Long-term oxygen therapy has been shown to improve pulmonary hemodynamics, reduce erythrocytosis, and improve survival in selected patients with severe hypoxemic respiratory failure.,However, the optimal treatment for patients with exertional oxyhemoglobin desaturation, isolated nocturnal hypoxemia, or mild-to-moderate resting daytime hypoxemia remains uncertain.

Chronic obstructive pulmonary disease (COPD), the most common chronic respiratory disease worldwide, not only leads to the decline of pulmonary function and quality of life consecutively, but also has become a major economic burden on individuals, families, and society in China.,The purpose of this meta-analysis was to explore the risk factors for developing COPD in the Chinese population that resides in China and to provide a theoretical basis for the early prevention of COPD.,A total of 2457 cross-sectional, case-control, and cohort studies published related to risk factors for COPD in China were searched.,Based on the inclusion and exclusion criteria, 20 articles were selected.,Stata 11.0 was used for meta-analysis.,After merging the data, the pooled effect and 95% confidence intervals (CIs) were calculated to assess the association between risk factors and COPD.,Heterogeneity between studies was assessed using I2 and Cochran’s Q tests.,Begg’s test was used to assess publication bias.,Exposure to particulate matter less than 2.5 μm in diameter (PM2.5) (pooled effect = 1.73; 95%CI: 1.16~2.58; P <0.01), smoking history (pooled effect = 2.58; 95%CI: 2.00~3.32; P <0.01), passive smoking history (pooled effect = 1.39; 95%CI: 1.03~1.87; P = 0.03), male sex(pooled effect = 1.70; 95%CI: 1.31~2.22; P <0.01), body mass index (BMI) <18.5 kg/m2 (pooled effect = 1.73; 95%CI: 1.32~2.25; P <0.01), exposure to biomass burning emissions (pooled effect = 1.65; 95%CI: 1.32~2.06; P <0.01), childhood respiratory infections (pooled effect = 3.44; 95%CI: 1.33~8.90; P = 0.01), residence (pooled effect = 1.24; 95%CI: 1.09~1.42; P <0.01), and a family history of respiratory diseases (pooled effect = 2.04; 95%CI: 1.53~2.71; P <0.01) were risk factors for COPD in the Chinese population.,Early prevention of COPD could be accomplished by quitting smoking, reducing exposure to air pollutants and biomass burning emissions, maintaining body mass index between 18.5 kg/m2 and 28 kg/m2, protecting children from respiratory infections, adopting active treatments to children with respiratory diseases, and conducting regular screening for those with family history of respiratory diseases.

The objective of this study is to assess whether statin use is associated with beneficial effects on COPD outcomes.,We conducted a systematic review and meta-analysis of all available studies describing the association between statin use and COPD mortality, exacerbations and cardiovascular events.,Medline, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched, with no restrictions.,The hazard ratio (HR) with 95% confidence interval (CI) was estimated.,Fifteen studies with a total of 238,459 patients were included.,Nine articles provided data on all-cause mortality (124,543 participants), and they gave a HR of 0.62 (95% CI 0.52 to 0.73).,Three studies provided data on cancer mortality (90,077 participants), HR 0.83 (0.65 to 1.08); four studies on COPD mortality (88,767 participants), HR 0.48 (0.23 to 0.99); and three studies on cardiovascular mortality (90,041 participants), HR 0.93 (0.50 to 1.72).,Six articles provided data on COPD exacerbation with or without hospitalization (129,796 participants), HR 0.64 (0.55 to 0.75).,Additionally, the use of statins was associated with a significant reduction risk of myocardial infarction, but not for stroke.,Our systematic review showed a clear benefit of statins in patients with COPD.

Although COPD among non-smokers (NS-COPD) is common, little is known about this phenotype.,We compared NS-COPD subjects with smoking COPD (S-COPD) patients in a rural Indian population using a variety of clinical, physiological, radiological, sputum cellular and blood biomarkers.,Two hundred ninety subjects (118 healthy, 79 S-COPD, 93 NS-COPD) performed pre- and post-bronchodilator spirometry and were followed for 2 years to study the annual rate of decline in lung function.,Body plethysmography, impulse oscillometry, inspiratory-expiratory HRCT, induced sputum cellular profile and blood biomarkers were compared between 49 healthy, 45 S-COPD and 55 NS-COPD subjects using standardized methods.,Spirometric response to oral corticosteroids was measured in 30 female NS-COPD patients.,Compared to all male S-COPD subjects, 47% of NS-COPD subjects were female, were younger by 3.2 years, had greater body mass index, a slower rate of decline in lung function (80 vs 130 mL/year), more small airways obstruction measured by impulse oscillometry (p < 0.001), significantly less emphysema (29% vs 11%) on CT scans, lower values in lung diffusion parameters, significantly less neutrophils in induced sputum (p < 0.05) and tended to have more sputum eosinophils.,Hemoglobin and red cell volume were higher and serum insulin lower in S-COPD compared to NS-COPD.,Spirometric indices, symptoms and quality of life were similar between S-COPD and NS-COPD.,There was no improvement in spirometry in NS-COPD patients after 2 weeks of an oral corticosteroid.,Compared to S-COPD, NS-COPD is seen in younger subjects with equal male-female predominance, is predominantly a small-airway disease phenotype with less emphysema, preserved lung diffusion and a slower rate of decline in lung function.

The diagnostic criteria of asthma-COPD overlap syndrome (ACOS) are controversial.,Emphysema is characteristic of COPD and usually does not exist in typical asthma patients.,Emphysema in patients with asthma suggests the coexistence of COPD.,Quantitative computed tomography (CT) allows repeated evaluation of emphysema noninvasively.,We investigated the value of quantitative CT measurements of emphysema in the diagnosis of ACOS.,This study included 404 participants; 151 asthma patients, 125 COPD patients, and 128 normal control subjects.,All the participants underwent pulmonary function tests and a high-resolution CT scan.,Emphysema measurements were taken with an Airway Inspector software.,The asthma patients were divided into high and low emphysema index (EI) groups based on the percentage of low attenuation areas less than −950 Hounsfield units.,The characteristics of asthma patients with high EI were compared with those having low EI or COPD.,The normal value of percentage of low attenuation areas less than −950 Hounsfield units in Chinese aged >40 years was 2.79%±2.37%.,COPD patients indicated more severe emphysema and more upper-zone-predominant distribution of emphysema than asthma patients or controls.,Thirty-two (21.2%) of the 151 asthma patients had high EI.,Compared with asthma patients with low EI, those with high EI were significantly older, more likely to be male, had more pack-years of smoking, had more upper-zone-predominant distribution of emphysema, and had greater airflow limitation.,There were no significant differences in sex ratios, pack-years of smoking, airflow limitation, or emphysema distribution between asthma patients with high EI and COPD patients.,A greater number of acute exacerbations were seen in asthma patients with high EI compared with those with low EI or COPD.,Asthma patients with high EI fulfill the features of ACOS, as described in the Global Initiative for Asthma and Global Initiative for Chronic Obstructive Lung Disease guidelines.,Quantitative CT measurements of emphysema may help in diagnosing ACOS.

Antibiotic treatment is one of the major pharmacologic treatments for acute exacerbation of chronic obstructive pulmonary disease (AECOPD).,However, the choice of antibiotic depends on the local resistance pattern.,A multicenter, randomized, controlled trial was done in patients with AECOPD to compare the efficacy of levofloxacin with that of cefuroxime axetil.,Patients with AECOPD and without radiographic evidence of pneumonia were enrolled and randomized to either levofloxacin 500 mg daily or cefuroxime 250 mg twice daily in the mildmoderate exacerbation group, or 500 mg twice daily in the severe exacerbation group, for seven days.,Clinical efficacy and microbiologic response were evaluated 5-7 days after the last dose.,Treatment was clinically successful in 90.4% of patients in the levofloxacin group, and in 90.6% of patients in the cefuroxime group (95% confidence interval −9.40 to 10.91), within a noninferiority margin of 10%.,The microbiologic response appeared to be higher in the levofloxacin group, but the difference was not statistically significant.,The safety profile was similar in both groups.,Levofloxacin is not inferior to cefuroxime with regard to clinical efficacy in treating AECOPD.

Bronchodilators represent the hallmark of symptomatic treatment of Chronic Obstructive Pulmonary Disease (COPD).,There are four categories of bronchodilators: anticholinergics, methylxanthines, short-acting β2-agonists, and long-acting β2-agonists such as formoterol.,Significant research has been performed to investigate the efficacy, safety and tolerability of formoterol in the therapeutic field of COPD.,Formoterol exhibits a rapid onset of bronchodilation similar to that observed with salbutamol, yet its long bronchodilatory duration is comparable to salmeterol.,In addition, formoterol presents with a clear superiority in lung function improvement compared with either ipratropium bromide or oral theophylline, while its efficacy improves when administered in combination with ipratropium.,Formoterol has been shown to better reduce dynamic hyperinflation, which is responsible for exercise intolerance and dyspnea in COPD patients, compared with other bronchodilators, whereas it exerts synergistic effect with tiotropium.,Moreover, formoterol reduces exacerbations, increases days free of use of rescue medication and improves patients’ quality of life and disease symptoms.,Formoterol has a favorable safety profile and is better tolerated than theophylline.,Collectively, data extracted from multicenter clinical trials support formoterol as a valid therapeutic option in the treatment of COPD.

CD8 cells may contribute towards an autoimmune process in COPD.,Down regulation of T cell receptor (TCR) signalling molecules occurs in autoimmune diseases with consequent T cell dysfunction.,We hypothesise that TCR signalling is abnormal in COPD pulmonary CD8 cells.,Micro-array gene expression analysis of blood and pulmonary COPD CD8 samples was performed and compared to pulmonary CD8 cells from smoker controls (S).,We focused on the TCR signalling pathway, with validation of key findings using polymerase chain reaction and immunofluorescence.,TCR signalling molecules in COPD pulmonary CD8 cells were down regulated compared to blood CD8 cells (CD247: fold change (FC) −2.43, Q = 0.001; LCK: FC −2.25, Q = 0.01).,Micro-array analysis revealed no significant differences between COPD and S pulmonary CD8 cells.,However, PCR revealed significantly lower gene expression levels of CD247 (FC −1.79, p = 0.04) and LCK (FC −1.77, p = 0.01) in COPD compared to S pulmonary CD8 cells.,CD247 down regulation in COPD CD8 cells was confirmed by immunofluorescent staining of bronchoalveolar lavage cells: Significantly fewer COPD CD8 cells co-expressed CD247 compared to healthy non-smoker CD8 cells (mean 88.9 vs 75.2%, p<0.05) There is down regulation of TCR signalling molecules in COPD pulmonary CD8 cells.,This may cause T cell dysfunction.

Chronic pulmonary diseases are a major cause of morbidity and mortality and their impact is expected to increase in the future.,Respiratory viruses are the most common cause of acute respiratory infections and it is increasingly recognized that respiratory viruses are a major cause of acute exacerbations of chronic pulmonary diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis.,There is now increasing evidence that the host response to virus infection is dysregulated in these diseases and a better understanding of the mechanisms of abnormal immune responses has the potential to lead to the development of new therapies for virus-induced exacerbations.,The aim of this article is to review the current knowledge regarding the role of viruses and immune modulation in chronic pulmonary diseases and discuss avenues for future research and therapeutic implications.,The online version of this article (doi:10.1186/1741-7015-10-27) contains supplementary material, which is available to authorized users.

In chronic obstructive pulmonary disease (COPD) apoptotic bronchial epithelial cells are increased, and their phagocytosis by alveolar macrophages (AM) is decreased alongside bacterial phagocytosis.,Epithelial cellular lipids, including those exposed on uncleared apoptotic bodies, can become oxidized, and may be recognized and presented as non-self by antigen presenting cells.,CD1b is a lipid-presenting protein, previously only described in dendritic cells.,We investigated whether CD1b is upregulated in COPD AM, and whether lipid oxidation products are found in the airways of cigarette smoke (CS) exposed mice.,We also characterise CD1b for the first time in a range of macrophages and assess CD1b expression and phagocytic function in response to oxidised lipid.,Bronchoalveolar lavage and exhaled breath condensate were collected from never-smoker, current-smoker, and COPD patients and AM CD1b expression and airway 8-isoprostane levels assessed.,Malondialdehyde was measured in CS-exposed mouse airways by confocal/immunofluorescence.,Oxidation of lipids produced from CS-exposed 16HBE14o- (HBE) bronchial epithelial cells was assessed by spectrophotometry and changes in lipid classes assessed by mass spectrometry.,16HBE cell toxicity was measured by flow cytometry as was phagocytosis, CD1b expression, HLA class I/II, and mannose receptor (MR) in monocyte derived macrophages (MDM).,AM CD1b was significantly increased in COPD smokers (4.5 fold), COPD ex-smokers (4.3 fold), and smokers (3.9 fold), and AM CD1b significantly correlated with disease severity (FEV1) and smoking pack years.,Airway 8-isoprostane also increased in smokers and COPD smokers and ex-smokers.,Malondialdehyde was significantly increased in the bronchial epithelium of CS-exposed mice (MFI of 18.18 vs 23.50 for control).,Oxidised lipid was produced from CS-exposed bronchial epithelial cells (9.8-fold of control) and showed a different overall lipid makeup to that of control total cellular lipid.,This oxidised epithelial lipid significantly upregulated MDM CD1b, caused bronchial epithelial cell toxicity, and reduced MDM phagocytic capacity and MR in a dose dependent manner.,Increased levels of oxidised lipids in the airways of COPD patients may be responsible for reduced phagocytosis and may become a self-antigen to be presented by CD1b on macrophages to perpetuate disease progression despite smoking cessation.

Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammation and high oxidative stress.,Studies suggest that oxidized low density lipoprotein (ox-LDL) is involved in diseases associated with oxidative stress and inflammation.,However, no data on the possible relationship between COPD and ox-LDL are available.,This study compared serum levels of ox-LDL in 48 COPD patients and 32 health controls and correlated them with lung function, systematic inflammation, and oxidative stress.,Serum levels of ox-LDL, C-reactive protein (CRP), and oxidative stress (measured by reactive oxygen species, ROS) were analyzed using commercial kits.,Mean levels of serum ox-LDL were significantly higher in COPD patients than in controls (18.62 ± 7.56 versus 12.57 ± 5.90 mU/L, P < 0.05).,Serum levels of CRP and ROS were also significantly higher in COPD patients.,Serum levels of ox-LDL in COPD patients correlated inversely with FEV1% predicted, an index of lung function (r = −0.347, P = 0.016), while they correlated positively with CRP and ROS levels.,These results suggest that serum levels of ox-LDL are increased in COPD patients and that these levels are associated with lung function, inflammation, and oxidative stress in COPD.,Future studies are needed to determine whether and how ox-LDL plays a role in COPD.

Symptomatic relief is an important treatment goal for patients with COPD.,To date, no diary for evaluating respiratory symptoms in clinical trials has been developed and scientifically-validated according to FDA and EMA guidelines.,The EXACT - Respiratory Symptoms (E-RS) scale is a patient-reported outcome (PRO) measure designed to address this need.,The E-RS utilizes 11 respiratory symptom items from the existing and validated 14-item EXACT, which measures symptoms of exacerbation.,The E-RS total score quantifies respiratory symptom severity, and 3 domains assess breathlessness, cough and sputum, and chest symptoms.,This study examined the performance of the E-RS in each of 3 controlled trials with common and unique validation variables: one 6-month (N = 235, US) and two 3-month (N = 749; N = 597; international).,Subjects completed the E-RS as part of a daily eDiary.,Tests of reliability, validity, and responsiveness were conducted in each dataset.,In each study, RS-Total score was internally consistent (Cronbach α) (0.88, 0.92, 0.92) and reproducible (intra-class correlation) in stable patients (2 days apart: 0.91; 7 days apart: 0.71, 0.74).,RS-Total scores correlated significantly with the following criterion variables (Spearman’s rho; p < 0.01, all comparisons listed here): FEV1% predicted (−0.19, −0.14, −0.15); St.,George’s Respiratory Questionnaire (SGRQ) (0.65, 0.52, 0.51); Breathlessness, Cough, and Sputum Scale (BCSS) (0.89, 0.89); modified Medical Research Council dyspnoea scale (mMRC) (0.40); rescue medication use (0.43, 0.42); Functional Performance Inventory Short-Form (FPI-SF) (0.43); 6-minute walk distance (6-MWT) (−0.30, −0.14) and incremental shuttle walk (ISWT) (−0.18) tests.,Correlations between these variables and RS-Breathlessness, RS-Cough and Sputum, RS-Chest Symptoms scores supported subscale validity.,RS-Total, RS-Breathlessness, and RS-Chest Symptoms differentiated mMRC levels of breathlessness severity (p < 0.0001).,RS-Total and domain scores differentiated subjects with no rescue medication use and 3 or more puffs (p < 0.0001).,Sensitivity to changes in health status (SGRQ), symptoms (BCSS), and exercise capacity (6MWT, ISWT) were also shown and responder definitions using criterion- and distribution-based methods are proposed.,Results suggest the E-RS is a reliable, valid, and responsive measure of respiratory symptoms of COPD suitable for use in natural history studies and clinical trials.,MPEX: NCT00739648; AZ1: NCT00949975; AZ 2: NCT01023516,The online version of this article (doi:10.1186/s12931-014-0124-z) contains supplementary material, which is available to authorized users.

COPD is characterized by variability in exercise capacity and physical activity (PA), and acute exacerbations (AEs).,Little is known about the relationship between daily step count, a direct measure of PA, and the risk of AEs, including hospitalizations.,In an observational cohort study of 169 persons with COPD, we directly assessed PA with the StepWatch Activity Monitor, an ankle-worn accelerometer that measures daily step count.,We also assessed exercise capacity with the 6-minute walk test (6MWT) and patient-reported PA with the St.,George's Respiratory Questionnaire Activity Score (SGRQ-AS).,AEs and COPD-related hospitalizations were assessed and validated prospectively over a median of 16 months.,Mean daily step count was 5804±3141 steps.,Over 209 person-years of observation, there were 263 AEs (incidence rate 1.3±1.6 per person-year) and 116 COPD-related hospitalizations (incidence rate 0.56±1.09 per person-year).,Adjusting for FEV1 % predicted and prednisone use for AE in previous year, for each 1000 fewer steps per day walked at baseline, there was an increased rate of AEs (rate ratio 1.07; 95%CI = 1.003-1.15) and COPD-related hospitalizations (rate ratio 1.24; 95%CI = 1.08-1.42).,There was a significant linear trend of decreasing daily step count by quartiles and increasing rate ratios for AEs (P = 0.008) and COPD-related hospitalizations (P = 0.003).,Each 30-meter decrease in 6MWT distance was associated with an increased rate ratio of 1.07 (95%CI = 1.01-1.14) for AEs and 1.18 (95%CI = 1.07-1.30) for COPD-related hospitalizations.,Worsening of SGRQ-AS by 4 points was associated with an increased rate ratio of 1.05 (95%CI = 1.01-1.09) for AEs and 1.10 (95%CI = 1.02-1.17) for COPD-related hospitalizations.,Lower daily step count, lower 6MWT distance, and worse SGRQ-AS predict future AEs and COPD-related hospitalizations, independent of pulmonary function and previous AE history.,These results support the importance of assessing PA in patients with COPD, and provide the rationale to promote PA as part of exacerbation-prevention strategies.

Chronic obstructive pulmonary disease (COPD) is increasingly being recognized as a highly heterogeneous disorder, composed of varying pathobiology.,Accurate detection of COPD subtypes by image biomarkers are urgently needed to enable individualized treatment thus improving patient outcome.,We adapted the Parametric Response Map (PRM), a voxel-wise image analysis technique, for assessing COPD phenotype.,We analyzed whole lung CT scans of 194 COPD individuals acquired at inspiration and expiration from the COPDGene Study.,PRM identified the extent of functional small airways disease (fSAD) and emphysema as well as provided CT-based evidence that supports the concept that fSAD precedes emphysema with increasing COPD severity.,PRM is a versatile imaging biomarker capable of diagnosing disease extent and phenotype, while providing detailed spatial information of disease distribution and location.,PRMs ability to differentiate between specific COPD phenotypes will allow for more accurate diagnosis of individual patients complementing standard clinical techniques.

To determine the relationship between lung function impairment and quantitative computed tomography (CT) measurements of air trapping and emphysema in a population of current and former heavy smokers with and without airflow limitation.,In 248 subjects (50 normal smokers; 50 mild obstruction; 50 moderate obstruction; 50 severe obstruction; 48 very severe obstruction) CT emphysema and CT air trapping were quantified on paired inspiratory and end-expiratory CT examinations using several available quantification methods.,CT measurements were related to lung function (FEV1, FEV1/FVC, RV/TLC, Kco) by univariate and multivariate linear regression analysis.,Quantitative CT measurements of emphysema and air trapping were strongly correlated to airflow limitation (univariate r-squared up to 0.72, p < 0.001).,In multivariate analysis, the combination of CT emphysema and CT air trapping explained 68-83% of the variability in airflow limitation in subjects covering the total range of airflow limitation (p < 0.001).,The combination of quantitative CT air trapping and emphysema measurements is strongly associated with lung function impairment in current and former heavy smokers with a wide range of airflow limitation.,• CT helps to automatically assess lung disease in heavy smokers,• CT quantitatively measures emphysema and small airways disease in heavy smokers,• CT air trapping and CT emphysema are associated with lung function impairment

Reduced physical activity (PA) in patients with COPD is associated with a poor prognosis.,Increasing PA is a key therapeutic target, but thus far few strategies have been found effective in this patient group.,To investigate the effectiveness of a 12-week semiautomated telecoaching intervention on PA in patients with COPD in a multicentre European randomised controlled trial.,343 patients from six centres, encompassing a wide spectrum of disease severity, were randomly allocated to either a usual care group (UCG) or a telecoaching intervention group (IG) between June and December 2014.,This 12-week intervention included an exercise booklet and a step counter providing feedback both directly and via a dedicated smartphone application.,The latter provided an individualised daily activity goal (steps) revised weekly and text messages as well as allowing occasional telephone contacts with investigators.,PA was measured using accelerometry during 1 week preceding randomisation and during week 12.,Secondary outcomes included exercise capacity and health status.,Analyses were based on modified intention to treat.,Both groups were comparable at baseline in terms of factors influencing PA.,At 12 weeks, the intervention yielded a between-group difference of mean, 95% CI (lower limit - upper limit; ll-ul) +1469, 95% CI (971 to 1965) steps/day and +10.4, 95% CI (6.1 to 14.7) min/day moderate PA; favouring the IG (all p≤0.001).,The change in 6-min walk distance was significantly different (13.4, 95% CI (3.40 to 23.5) m, p<0.01), favouring the IG.,In IG patients, an improvement could be observed in the functional state domain of the clinical COPD questionnaire (p=0.03) compared with UCG.,Other health status outcomes did not differ.,The amount and intensity of PA can be significantly increased in patients with COPD using a 12-week semiautomated telecoaching intervention including a step counter and an application installed on a smartphone.,NCT02158065.

Accessible interventions to train patients with chronic obstructive pulmonary disease (COPD) are needed.,We designed urban trails of different intensities (low, moderate and high) in different types of public spaces (boulevard, beach and park).,We aimed to validate the trails’ design by assessing the physiological response to unsupervised walking trails of: (1) different intensities in COPD patients, and (2) same intensity from different public spaces in healthy adults.,On different days and under standardized conditions, 10 COPD patients walked the three intensity trails designed in a boulevard space, and 10 healthy subjects walked the three intensity trails in three different spaces.,We measured physiological response and energy expenditure using a gas analyzer.,We compared outcomes across trails intensity and/or spaces using mixed-effects linear regression.,In COPD patients, physiological response and energy expenditure increased significantly according to the trails intensity: mean (SD) peak V˙O2 15.9 (3.5), 17.4 (4.7), and 17.7 (4.4) mL/min/kg (p-trend = 0.02), and MET-min 60 (23), 64 (26), 72 (31) (p-trend<0.01) in low, moderate and high intensity trails, respectively.,In healthy subjects there were no differences in physiological response to walking trails of the same intensity across different spaces.,We validated the trails design for the training of COPD patients by showing that the physiological response to and energy expenditure on unsupervised walking these trails increased according to the predefined trails’ intensity and did not change across trails of the same intensity in different public space.,Walkable public spaces allow the design of trails that could be used for the training of COPD patients in the community.

Chronic obstructive pulmonary disease (COPD) is characterized by the destruction of alveolar walls, chronic inflammation and persistent respiratory symptoms.,There is no curative clinical treatment for COPD.,In this context, cell-based therapy is a promising therapeutic alternative for COPD.,Thus, in this open, controlled and randomized Phase I Clinical Trial, we aimed to assess the safety of the infusion of autologous bone marrow mononuclear cells (BMMC), adipose-derived mesenchymal stromal cells (ADSC) and, especially, the safety of concomitant infusion (co-infusion) of BMMC and ADSC as a new therapeutic alternative for COPD.,The rationale for co-infusion of BMMC and ADSC is based on the hypothesis of an additive or synergistic therapeutic effect resulting from this association.,To achieve the proposed objectives, twenty patients with moderate-to-severe COPD were randomly divided into four groups: control group - patients receiving conventional treatment; BMMC group - patients receiving only BMMC; ADSC group - patients receiving only ADSC, and co-infusion group - patients receiving the concomitant infusion of BMMC and ADSC.,Patients were assessed for pulmonary function, biochemical profile, and quality of life over a 12 months follow-up.,No adverse events were detected immediately after the infusion of BMMC, ADSC or co-infusion.,In the 12-month follow-up, no causal relationship was established between adverse events and cell therapy procedures.,Regarding the efficacy, the BMMC group showed an increase in forced expiratory volume (FEV1) and diffusing capacity for carbon monoxide (DLCO).,Co-infusion group showed a DLCO, and gas exchange improvement and a better quality of life.,The results obtained allow us to conclude that cell-based therapy with co-infusion of BMMC and ADSC is a safe procedure and a promising therapeutic for COPD.,However, additional studies with a greater number of patients are needed before randomized and controlled Phase III clinical trials can be implemented.

Chronic obstructive pulmonary disease (COPD) is emphysema and/or chronic bronchitis characterised by long-term breathing problems and poor airflow.,The prevalence of COPD has increased over the last decade and the drugs most commonly used to treat it, such as glucocorticoids and bronchodilators, have significant therapeutic effects; however, they also cause side effects, including infection and immunosuppression.,Here we reviewed the pathogenesis and progression of COPD and elaborated on the effects and mechanisms of newly developed molecular targeted COPD therapeutic drugs.,Among these new drugs, we focussed on thioredoxin (Trx).,Trx effectively prevents the progression of COPD by regulating redox status and protease/anti-protease balance, blocking the NF-κB and MAPK signalling pathways, suppressing the activation and migration of inflammatory cells and the production of cytokines, inhibiting the synthesis and the activation of adhesion factors and growth factors, and controlling the cAMP-PKA and PI3K/Akt signalling pathways.,The mechanism by which Trx affects COPD is different from glucocorticoid-based mechanisms which regulate the inflammatory reaction in association with suppressing immune responses.,In addition, Trx also improves the insensitivity of COPD to steroids by inhibiting the production and internalisation of macrophage migration inhibitory factor (MIF).,Taken together, these findings suggest that Trx may be the ideal drug for treating COPD.

Current treatment strategies to stratify exacerbation risk rely on history of ≥2 events in the previous year.,To understand year-to-year variability and factors associated with consistent exacerbations over time, we present a prospective analysis of the SPIROMICS cohort.,We analyzed SPIROMICS participants with COPD and three years of prospective data (n=1,105).,We classified participants according to yearly exacerbation frequency.,Stepwise logistic regression compared factors associated with individuals experiencing ≥1 AECOPD in every year for three years versus none.,During three years follow-up, 48·7% of participants experienced at least one AECOPD, while the majority (51·3%) experienced none.,Only 2·1% had ≥2 AECOPD in each year.,An inconsistent pattern (both years with and years without AECOPD) was common (41·3% of the group), particularly among GOLD stages 3 and 4 subjects (56·1%).,In logistic regression, consistent AECOPD (≥1 event per year for three years) as compared to no AECOPD were associated with higher baseline symptom burden assessed with the COPD Assessment Test, previous exacerbations, greater evidence of small airway abnormality by computed tomography, lower Interleukin-15 (IL-15) and elevated Interleukin-8 (IL-8).,Although AECOPD are common, the exacerbation status of most individuals varies markedly from year to year.,Among participants who experienced any AECOPD over three years, very few repeatedly experienced ≥2 events/year.,In addition to symptoms and history of exacerbations in the prior year, we identified several novel biomarkers associated with consistent exacerbations, including CT-defined small airway abnormality, IL-15 and IL-8.

The optimal use of various therapeutic combinations for moderate/severe chronic obstructive pulmonary disease (COPD) is unclear.,The GLISTEN trial compared the efficacy of two long-acting anti-muscarinic antagonists (LAMA), when combined with an inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA).,This randomised, blinded, placebo-controlled trial in moderate/severe COPD patients compared once-daily glycopyrronium (GLY) 50 µg, once-daily tiotropium (TIO) 18 µg or placebo (PLA), when combined with salmeterol/fluticasone propionate (SAL/FP) 50/500 µg twice daily.,The primary objective was to determine the non-inferiority of GLY+SAL/FP versus TIO+SAL/FP on trough FEV1 after 12 weeks.,An important secondary objective was whether addition of GLY to SAL/FP was better than SAL/FP alone.,773 patients (mean FEV1 57.2% predicted) were randomised; 84.9% completed the trial.,At week 12, GLY+SAL/FP demonstrated non-inferiority to TIO+SAL/FP for trough FEV1: least square mean treatment difference (LSMdiff) −7 mL (SE 17.4) with a lower limit for non-inferiority of −60 mL.,There was significant increase in week 12 trough FEV1 with GLY+SAL/FP versus PLA+SAL/FP (LSMdiff 101 mL, p<0.001).,At 12 weeks, GLY+SAL/FP produced significant improvement in St George's Respiratory Questionnaire total score versus PLA+SAL/FP (LSMdiff −2.154, p=0.02).,GLY+SAL/FP demonstrated significant rescue medication reduction versus PLA+SAL/FP (LSMdiff −0.72 puffs/day, p<0.001).,Serious adverse events were similar for GLY+SAL/FP, TIO+SAL/FP and PLA+SAL/FP with an incidence of 5.8%, 8.5% and 5.8%, respectively.,GLY+SAL/FP showed comparable improvements in lung function, health status and rescue medication to TIO+SAL/FP.,Importantly, addition of GLY to SAL/FP demonstrated significant improvements in lung function, health status and rescue medication compared to SAL/FP.,NCT01513460.

Past research has suggested significant relationships between symptoms and health outcomes among patients with COPD.,However, these studies have generally focused on a broad COPD sample and may have included those not receiving proper treatment.,As a result, the aim of this study was to document the burden of COPD symptoms among those who are currently treated with the standard-of-care (SOC) medications in both the US and Western Europe.,Data from the 2013 US (N=75,000) and 2011 (N=57,512)/2013 (N=62,000) European (France, Germany, Italy, Spain, and UK; 5EU) National Health and Wellness Survey (NHWS) were used.,The NHWS is a health survey administered to a demographically representative sample of the adult population in each country.,A total of 1,666 and 2,006 patients with self-reported physician diagnosis of COPD in the 5EU and US, respectively, were being treated with the appropriate SOC (based on self-reported medication use) and were included in the analyses.,Symptoms (eg, dyspnea, coughing, wheezing) were reported descriptively and summed to create a symptom score (with higher score indicating more frequent symptoms).,The relationships between the symptom score and patient outcomes (eg, health status using the Short Form-36 version 2 [SF-36v2], work productivity and activity impairment [WPAI], and self-reported health care resource use) were explored using regression modeling.,Nearly all patients (99.7% and 99.8% in the 5EU and US, respectively) reported experiencing symptoms and >80% reported experiencing at least one symptom “often”.,Increasing symptom scores were associated with poorer health status (unstandardized beta [b] =−0.87 and −0.78 for mental component summary and physical component summary, respectively, in the US and b =−0.67 and −0.79 in the 5EU, respectively; all P<0.05).,Increasing symptom scores were also associated with greater work impairment (b =0.09 and 0.06 for the US and 5EU, respectively), activity impairment (b =0.05 and 0.06, respectively), and health care resource utilization (eg, hospitalizations: b =0.05 and 0.06, respectively) (all P<0.05).,Approximately 70% of patients reported some level of non-adherence.,Greater non-adherence was significantly associated with more frequent symptoms, poorer health status, and greater work impairment and health care resource use (all P<0.05).,Patients with COPD who are using the appropriate SOC still experience symptoms, which have a significant effect on both humanistic and economic outcomes.

Previous studies of healthcare utilization for chronic obstructive pulmonary disease (COPD) have focused on time-trends in COPD visits or COPD treatments, or the effect of hospital volume on mortality.,Few data are available regarding outcomes after an ED visit (and subsequent hospitalization) for COPD, which are both very common in patients with COPD.,Our objective was to assess time-trends and predictors of emergency department and subsequent inpatient health care utilization and charges associated with COPD in the U.S.,We used the 2009-12 U.S.,Nationwide Emergency Department Sample (NEDS) to study the incidence of ED visits and subsequent hospitalizations with COPD as the primary diagnosis.,We used the 2012 NEDS data to study key patient/hospital factors associated with outcomes, including charges, hospitalization and dischage from hospital to home.,ED visits for COPD as the primary diagnosis increased from 1.02 million in 2009 to 1.04 in 2010 to 1.10 million in 2012 (0.79-0.82 % of all ED visits); respective charges were $2.13, $2.32, and $3.09 billion.,In 2012, mean ED charges/visit were $2,812, hospitalization charges/visit were $29,043 and the length of hospital stay was 4.3 days. 49 % were hospitalized after an ED visit.,Older age, higher median income, metropolitan residence and comorbidities (diabetes, hypertension, HF, hyperlipidemia, CHD, renal failure and osteoarthritis) were associated with higher risk whereas male sex, Medicaid or self pay insurance status, hospital location in Midwest, South or West U.S. were associated with lower risk of hospitalization.,65.4 % of all patients hospitalized for COPD from ED were discharged home.,Older age, comorbidities (diabetes, HF, CHD, renal failure, osteoarthritis) and metropolitan residence were associated with lower odds of discharge to home, whereas male sex, payer other than Medicare, Midwest, South or West U.S. hospital location were associated with higher odds.,Health care utilization and costs in patients with COPD are significant and increasing.,COPD constitutes a major public health burden in the U.S.,We identified risk factors for hospitalization, costs, and home discharge in patients with COPD that will allow future studies to investigate interventions to potentially reduce COPD-associated utilization.,The online version of this article (doi:10.1186/s12931-015-0319-y) contains supplementary material, which is available to authorized users.

In patients with chronic obstructive pulmonary disease (COPD), the extent of physical activity (PA) is correlated with disease severity and prognosis.,However, factors associated with low-level PA in elderly COPD patients are not known.,We assessed the levels of PA and clinical factors associated with low-level of PA in elderly COPD patients.,This was a secondary analysis of a multicenter, prospective study of 245 patients with COPD.,Among them, 160 patients with 65 years or more were included.,Three PA groups were defined with respect to daily activity time (low, moderate, and high).,Health related quality of life (HRQL) was measured using St.,George’s respiratory questionnaire (SGRQ) and 36-item short-form health survey.,Anxiety and depression status were assessed employing the hospital anxiety and depression scale (HADS).,Multivariate logistic regression was performed to identify independent predictors of low-level PA in elderly COPD patients.,Of all the 160 patients, 103 (64.4%) engaged in low-level PA.,Upon univariate analysis, a decreased exercise capacity (6-minute walk test < 250 m), an increased dyspnea (the modified medical research council [MMRC] dyspnea scale ≥ 2), a decreased HRQL (total SGRQ score), and a presence of depression (HADS-D ≥ 8) were significantly associated with low-level PA.,Upon multivariate analysis, an MMRC grade ≥ 2 (hazard ratio [HR], 2.550; p = 0.034), and HADS-D ≥ 8 (HR, 2.076; p = 0.045) were independently associated with low-level PA in elderly COPD patients.,Two-thirds of elderly patients with COPD reported low-level of PA.,More severe dyspnea and a presence of depression were independently associated with low-level PA in elderly COPD patients.

Diabetes damages major organ systems through disrupted glycemic control and increased inflammation.,The effects of diabetes on the lung have been of interest for decades, but the modest reduction in pulmonary function and its nonprogressive nature have limited its investigation.,A recent systematic review found that diabetes was associated with reductions in forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and diffusing capacity for carbon monoxide of the lung and increased FEV1/FVC.,They reported pooled results including few smokers.,This study will examine measures of pulmonary function in participants with extensive smoking exposure.,We examined pulmonary function in participants with a >10-pack-year history of smoking with and without diabetes with and without chronic obstructive pulmonary disease (COPD).,We measured pulmonary function, exercise capacity, and pulmonary-related quality of life in 10,129 participants in the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) Study.,Participants with diabetes were observed to have reduced pulmonary function after controlling for known risk factors and also significant reductions in exercise capacity and quality of life across functional stages of COPD.,Pulmonary function in patients with ≥10 pack-years of smoking and diabetes is reduced, and this decrease is associated with significant reductions in activity-related quality of life and exercise capacity.