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This retrospective, observational study of a routine clinical practice reports the feasibility and efficiency of home-based pulmonary rehabilitation (PR), including transcutaneous neuromuscular electrical stimulation (NMES) or usual endurance physical exercise (UEPE), on exercise tolerance, anxiety/depression, and health-related quality of life (HRQoL) in patients with COPD.,Seventy-one patients with COPD participated in home-based PR with NMES (Group NMES [GNMES]), while 117 patients participated in home-based PR with the UEPEs (Group UEPE [GUEPE]).,NMES was applied for 30 minutes twice a day, every day.,The endurance exercises in GUEPE began with a minimum 10-minute session at least 5 days a week, with the goal being 30-45 minutes per session.,Three upper and lower limb muscle strengthening exercises lasting 10-15 minutes were also proposed to both the groups for daily practice.,Moreover, PR in both the groups included a weekly 90-minute session based on an educational needs assessment.,The sessions comprised endurance physical exercise for GUEPE, NMES for GNMES, resumption of physical daily living activities, therapeutic patient education, and psychosocial support to facilitate health behavior changes.,Before and after PR, functional mobility and physical exercise capacity, anxiety, depression, and HRQoL were evaluated at home.,The study revealed that NMES significantly improved functional mobility (−18.8% in GNMES and −20.6% in GUEPE), exercise capacity (+20.8% in GNMES and +21.8% in GUEPE), depression (−15.8% in GNMES and −30.1% in GUEPE), and overall HRQoL (−7.0% in GNMES and −18.5% in GUEPE) in the patients with COPD, regardless of the group (GNMES or GUEPE) or severity of airflow obstruction.,Moreover, no significant difference was observed between the groups with respect to these data (P>0.05).,Home-based PR including self-monitored NMES seems feasible and effective for severely disabled COPD patients with severe exercise intolerance. | Exercise tolerance testing is an integral part of the pulmonary rehabilitation (PR) management of patients with chronic obstructive pulmonary disease (COPD).,The 6-minute stepper test (6MST) is a new, well-tolerated, reproducible exercise test, which can be performed without any spatial constraints.,The aim of this study was to compare the results of the 6MST to those obtained during a 6-minute walk test (6MWT) and cardiopulmonary exercise testing (CPET) in a cohort of COPD patients.,Ninety-one COPD patients managed by outpatient PR and assessed by 6MST, 6MWT, and CPET were retrospectively included in this study.,Correlations between the number of steps on the 6MST, the distance covered on the 6MWT, oxygen consumption, and power at the ventilatory threshold and at maximum effort during CPET were analyzed before starting PR, and the improvement on the 6MST and 6MWT was compared after PR.,The number of steps on the 6MST was significantly correlated with the distance covered on the 6MWT (r=0.56; P<0.0001), the power at maximum effort (r=0.46; P<0.0001), and oxygen consumption at maximum effort (r=0.39; P<0.005).,Performances on the 6MST and 6MWT were significantly improved after PR (570 vs 488 steps, P=0.001 and 448 vs 406 m, respectively; P<0.0001).,Improvements of the 6MST and 6MWT after PR were significantly correlated (r=0.34; P=0.03).,The results of this study show that the 6MST is a valid test to evaluate exercise tolerance in COPD patients.,The use of this test in clinical practice appears to be particularly relevant for the assessment of patients managed by home PR. | 1 |
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends triple therapy (long-acting muscarinic receptor antagonists, long-acting beta-2 agonists, and inhaled corticosteroids) for patients with only the most severe COPD.,Data on the proportion of COPD patients on triple therapy and their characteristics are sparse and dated.,Objective 1 of this study was to estimate the proportion of all, and all treated, COPD patients receiving triple therapy.,Objective 2 was to characterize those on triple therapy and assess the concordance of triple therapy use with GOLD guidelines.,This retrospective study used claims from the IMS PharMetrics Plus database from 2009 to 2013.,Cohort 1 was selected to assess Objective 1 only; descriptive analyses were conducted in Cohort 2 to answer Objective 2.,A validated claims-based algorithm and severity and frequency of exacerbations were used as proxies for COPD severity.,Of all 199,678 patients with COPD in Cohort 1, 7.5% received triple therapy after diagnosis, and 25.5% of all treated patients received triple therapy.,In Cohort 2, 30,493 COPD patients (mean age =64.7 years) who initiated triple therapy were identified.,Using the claims-based algorithm, 34.5% of Cohort 2 patients were classified as having mild disease (GOLD 1), 40.8% moderate (GOLD 2), 22.5% severe (GOLD 3), and 2.3% very severe (GOLD 4).,Using exacerbation severity and frequency, 60.6% of patients were classified as GOLD 1/2 and 39.4% as GOLD 3/4.,In this large US claims database study, one-quarter of all treated COPD patients received triple therapy.,Although triple therapy is recommended for the most severe COPD patients, spirometry is infrequently assessed, and a majority of the patients who receive triple therapy may have only mild/moderate disease.,Any potential overprescribing of triple therapy may lead to unnecessary costs to the patient and health care system. | 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. | 1 |
Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone.,The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.,In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair®/Pressair®)*.,Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV1 (FDCs versus formoterol).,Secondary endpoints were change from baseline in St.,George’s Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24.,Safety and tolerability were also assessed.,At study end, improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001).,Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC.,Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively.,All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies.,Treatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo.,Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD.,Clinicaltrials.gov NCT01437397.,*Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the US as Pressair® and Genuair® within all other licensed territories.,The online version of this article (doi:10.1186/s12931-014-0123-0) contains supplementary material, which is available to authorized users. | 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. | 1 |
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. | Epidemiological research into the role of traffic pollution on chronic respiratory and allergic disease has focused primarily on children.,Studies in adults, in particular those based on objective outcomes such as bronchial hyperresponsiveness, skin sensitisation, and lung function, are limited.,We have used an existing cohort of 2644 adults aged 18-70 living in Nottingham, UK, for whom baseline health and demographic data were collected in 1991 and computed two markers of exposure to traffic: distance between the home and nearest main road and modelled outdoor nitrogen dioxide (NO2) concentration at the home location.,Using multiple regression techniques, we analysed cross-sectional associations with bronchial hyperresponsiveness, FEV1, spirometry-defined COPD, skin test positivity, total IgE and questionnaire-reported wheeze, asthma, eczema and hayfever in 2599 subjects, and longitudinal associations with decline in FEV1 in 1329 subjects followed-up nine years later in 2000.,There were no significant cross-sectional associations between home proximity to the roadside or NO2 level on any of the outcomes studied (adjusted OR of bronchial hyperresponsiveness in relation to living ≤150 m vs >150 m from a road = 0.92, 95% CI 0.68 to 1.24).,Furthermore, neither exposure was associated with a significantly greater decline in FEV1 over time (adjusted mean difference in ΔFEV1 for living ≤150 m vs >150 m of a road = 10.03 ml, 95% CI, -33.98 to 54.04).,This study found no evidence to suggest that living in close proximity to traffic is a major determinant of asthma, allergic disease or COPD in adults. | 1 |
The aim of this study was to assess the current evidence for long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combinations (FDCs) in the treatment of COPD.,A systematic literature search of randomized controlled trials published in English up to September 2017 of LABA/LAMA FDCs vs LABA or LAMA or LABA/inhaled corticosteroid (ICS) FDCs in COPD patients was performed using PubMed, Embase, Scopus, and Google Scholar.,Outcomes including forced expiratory volume in 1 second (FEV1), Transition Dyspnea Index (TDI) scores, St George’s Respiratory Questionnaire (SGRQ) scores, exacerbations, exercise tolerance (endurance time [ET]), inspiratory capacity (IC), and rescue medication use were evaluated.,In total, 27 studies were included in the review.,LABA/LAMA FDCs significantly improved lung function (FEV1) at 12 weeks compared with LABA or LAMA or LABA/ICS.,These effects were maintained over time.,Significant improvements with LABA/LAMA FDCs vs each evaluated comparator were also observed in TDI and SGRQ scores, even if significant differences between different LABA/LAMA FDCs were detected.,Only the LABA/LAMA FDC indacaterol/glycopyrronium has shown superiority vs LAMA and LABA/ICS for reducing exacerbation rates, while olodaterol/tiotropium and indacaterol/glycopyrronium have been shown to improve ET and IC vs the active comparators.,Rescue medication use was significantly reduced by LABA/LAMA FDCs vs the evaluated comparators.,LABA/LAMA FDCs were safe, with no increase in the risk of adverse events with LABA/LAMA FDCs vs the monocomponents.,Evidence supporting the efficacy of LABA/LAMA FDCs for COPD is heterogeneous, particularly for TDI and SGRQ scores, exacerbation rates, ET, and IC.,So far, indacaterol/glycopyrronium is the LABA/LAMA FDC that has the strongest evidence for superiority vs LABA, LAMA, and LABA/ICS FDCs across the evaluated outcomes.,LABA/LAMA FDCs were safe; however, more data should be collected in a real-world setting to confirm their safety. | Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities.,COPD exacerbations and comorbidities contribute to the overall severity in individual patients.,Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age.,Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations.,However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide.,This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale.,Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases.,All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases.,In this review, we focus on the major comorbidities that affect COPD patients.,We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs.,We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity. | 1 |
Chronic obstructive pulmonary disease (COPD) is an underdiagnosed condition sharing risk factors with lung cancer.,Lung cancer screening may provide an opportunity to improve COPD diagnosis.,Using Pan-Canadian Early Detection of Lung Cancer (PanCan) study data, the present study sought to determine the following: 1) What is the prevalence of COPD in a lung cancer screening population?,2) Can a model based on clinical and screening low-dose CT scan data predict the likelihood of COPD?,The single arm PanCan study recruited current or former smokers age 50-75 who had a calculated risk of lung cancer of at least 2% over 6 years.,A baseline health questionnaire, spirometry, and low-dose CT scan were performed.,CT scans were assessed by a radiologist for extent and distribution of emphysema.,With spirometry as the gold standard, logistic regression was used to assess factors associated with COPD.,Among 2514 recruited subjects, 1136 (45.2%) met spirometry criteria for COPD, including 833 of 1987 (41.9%) of those with no prior diagnosis, 53.8% of whom had moderate or worse disease.,In a multivariate model, age, current smoking status, number of pack-years, presence of dyspnea, wheeze, participation in a high-risk occupation, and emphysema extent on LDCT were all statistically associated with COPD, while the overall model had poor discrimination (c-statistic = 0.627 (95% CI of 0.607 to 0.650).,The lowest and the highest risk decile in the model predicted COPD risk of 27.4 and 65.3%.,COPD had a high prevalence in a lung cancer screening population.,While a risk model had poor discrimination, all deciles of risk had a high prevalence of COPD, and spirometry could be considered as an additional test in lung cancer screening programs.,(Clinical Trial Registration: ClinicalTrials.gov, number NCT00751660, registered September 12, 2008),The online version contains supplementary material available at 10.1186/s12890-020-01344-y. | Abnormal apoptotic events in chronic obstructive pulmonary disease (COPD) subvert cellular homeostasis and may play a primary role in its pathogenesis.,However, studies in human subjects are limited.,p53 and bcl2 protein expression was measured by western blot on lung tissue specimens from 43 subjects (23 COPD smokers and 20 non-COPD smokers), using beta-actin as internal control.,Additionally, p53 and bcl2 expression patterns were evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded lung tissue sections from the same individuals.,Western blot analysis showed statistically significant increased p53 protein levels in COPD smokers in comparison with non-COPD smokers (p = 0.038), while bcl2 protein levels were not statistically different between the two groups.,Lung immunohistochemistry showed increased ratio of positive p53-stained type II pneumocytes/total type II pneumocytes in COPD smokers compared to non-COPD smokers (p = 0.01), whereas the p53 staining ratio in alveolar macrophages and in lymphocyte-like cells did not differ statistically between the two groups.,On the other hand, bcl2 expression did not differ between the two groups in all three cell types.,The increased expression of pro-apoptotic p53 in type II pneumocytes of COPD patients not counterbalanced by the anti-apoptotic bcl2 could reflect increased apoptosis in the alveolar epithelium of COPD patients.,Our results confirm previous experiments and support the hypothesis of a disturbance in the balance between the pro- and anti-apoptotic mediators in COPD. | 1 |
Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous.,We sought to investigate the sputum cellular, mediator, and microbiome profiles of both asthma and COPD exacerbations.,Patients with severe asthma or moderate-to-severe COPD were recruited prospectively to a single center.,Sputum mediators were available in 32 asthmatic patients and 73 patients with COPD assessed at exacerbation.,Biologic clusters were determined by using factor and cluster analyses on a panel of sputum mediators.,Patterns of clinical parameters, sputum mediators, and microbiome communities were assessed across the identified clusters.,The asthmatic patients and patients with COPD had different clinical characteristics and inflammatory profiles but similar microbial ecology.,Three exacerbation biologic clusters were identified.,Cluster 1 was COPD predominant, with 27 patients with COPD and 7 asthmatic patients exhibiting increased blood and sputum neutrophil counts, proinflammatory mediators (IL-1β, IL-6, IL-6 receptor, TNF-α, TNF receptors 1 and 2, and vascular endothelial growth factor), and proportions of the bacterial phylum Proteobacteria.,Cluster 2 had 10 asthmatic patients and 17 patients with COPD with increased blood and sputum eosinophil counts, type 2 mediators (IL-5, IL-13, CCL13, CCL17, and CCL26), and proportions of the bacterial phylum Bacteroidetes.,Cluster 3 had 15 asthmatic patients and 29 patients with COPD with increased type 1 mediators (CXCL10, CXCL11, and IFN-γ) and proportions of the phyla Actinobacteria and Firmicutes.,A biologic clustering approach revealed 3 subgroups of asthma and COPD exacerbations, each with different percentages of patients with overlapping asthma and COPD.,The sputum mediator and microbiome profiles were distinct between clusters. | Exhaled, endogenous particles are formed from the epithelial lining fluid in small airways, where surfactant protein A (SP-A) plays an important role in pulmonary host defense.,Based on the knowledge that chronic obstructive pulmonary disease (COPD) starts in the small airway epithelium, we hypothesized that chronic inflammation modulates peripheral exhaled particle SP-A and albumin levels.,The main objective of this explorative study was to compare the SP-A and albumin contents in exhaled particles from patients with COPD and healthy subjects and to determine exhaled particle number concentrations.,Patients with stable COPD ranging from moderate to very severe (n = 13), and healthy non-smoking subjects (n = 12) were studied.,Subjects performed repeated breath maneuvers allowing for airway closure and re-opening, and exhaled particles were optically counted and collected on a membrane using the novel PExA® instrument setup.,Immunoassays were used to quantify SP-A and albumin.,COPD patients exhibited significantly lower SP-A mass content of the exhaled particles (2.7 vs.,3.9 weight percent, p = 0.036) and lower particle number concentration (p<0.0001) than healthy subjects.,Albumin mass contents were similar for both groups.,Decreased levels of SP-A may lead to impaired host defense functions of surfactant in the airways, contributing to increased susceptibility to COPD exacerbations.,SP-A in exhaled particles from small airways may represent a promising non-invasive biomarker of disease in COPD patients. | 1 |
Some patients share characteristics of both COPD and asthma.,As yet, there is no gold standard to identify patients with the so-called asthma-COPD overlap syndrome (ACOS).,To describe the differences between ACOS patients and the remaining COPD patients, and to compare the clinical characteristics of patients diagnosed with ACOS by two different criteria: previous diagnosis of asthma before the age of 40 years; and the diagnostic criteria of the Spanish guidelines of COPD.,Multicenter, observational, cross-sectional study performed in 3,125 COPD patients recruited in primary care and specialized outpatient clinics.,Patients with COPD and a history of asthma before the age of 40 years were diagnosed with ACOS and compared to the remaining COPD patients.,Subsequently, ACOS patients were subdivided based on whether they fulfilled the Spanish guidelines of the COPD diagnostic criteria or not, and they were compared.,ACOS was diagnosed in 15.9% of the patients.,These patients had different basal characteristics compared to the remaining COPD patients, including a higher frequency of women and more exacerbations despite lower tobacco exposure and better lung function.,They were more likely to have features of asthma, such as a positive bronchodilator test, higher peripheral eosinophilia, and higher total immunoglobulin E.,Within the ACOS group, only one-third fulfilled the diagnostic criteria of the Spanish guidelines of COPD; these individuals were not significantly different from the remaining ACOS patients, except for having more exacerbations and poorer lung function.,ACOS patients diagnosed on the basis of a previous diagnosis of asthma differed from the remaining COPD patients, but they were similar to ACOS patients diagnosed according to more restrictive criteria, suggesting that a history of asthma before the age of 40 years could be a useful criterion to suspect ACOS in a patient with COPD. | Objective To investigate the occurrence of pneumonia and pneumonia related events in patients with chronic obstructive pulmonary disease (COPD) treated with two different fixed combinations of inhaled corticosteroid/long acting β2 agonist.,Design Observational retrospective pairwise cohort study matched (1:1) for propensity score.,Setting Primary care medical records data linked to Swedish hospital, drug, and cause of death registry data for years 1999-2009.,Participants Patients with COPD diagnosed by a physician and prescriptions of either budesonide/formoterol or fluticasone/salmeterol.,Main outcome measures Yearly pneumonia event rates, admission to hospital related to pneumonia, and mortality.,Results 9893 patients were eligible for matching (2738 in the fluticasone/salmeterol group; 7155 in the budesonide/formoterol group), yielding two matched cohorts of 2734 patients each.,In these patients, 2115 (39%) had at least one recorded episode of pneumonia during the study period, with 2746 episodes recorded during 19 170 patient years of follow up.,Compared with budesonide/formoterol, rate of pneumonia and admission to hospital were higher in patients treated with fluticasone/salmeterol: rate ratio 1.73 (95% confidence interval 1.57 to 1.90; P<0.001) and 1.74 (1.56 to 1.94; P<0.001), respectively.,The pneumonia event rate per 100 patient years for fluticasone/salmeterol versus budesonide/formoterol was 11.0 (10.4 to 11.8) versus 6.4 (6.0 to 6.9) and the rate of admission to hospital was 7.4 (6.9 to 8.0) versus 4.3 (3.9 to 4.6).,The mean duration of admissions related to pneumonia was similar for both groups, but mortality related to pneumonia was higher in the fluticasone/salmeterol group (97 deaths) than in the budesonide/formoterol group (52 deaths) (hazard ratio 1.76, 1.22 to 2.53; P=0.003).,All cause mortality did not differ between the treatments (1.08, 0.93 to 1.14; P=0.59).,Conclusions There is an intra-class difference between fixed combinations of inhaled corticosteroid/long acting β2 agonist with regard to the risk of pneumonia and pneumonia related events in the treatment of patients with COPD.,Trial registration Clinical Trials.gov NCT01146392. | 1 |
As chronic obstructive pulmonary disease (COPD) is a heterogeneous disease it is unlikely that all patients will benefit equally from a given therapy.,Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, has been shown to improve lung function in moderate and severe COPD but its effect on exacerbations in unselected populations was inconclusive.,This led to the question of whether a responsive subset existed that could be investigated further.,The datasets of two previous replicate, randomized, double-blind, placebo-controlled, parallel-group studies (oral roflumilast 500 μg or placebo once daily for 52 weeks) that were inconclusive regarding exacerbations were combined in a post-hoc, pooled analysis to determine whether roflumilast reduced exacerbations in a more precisely defined patient subset.,The pooled analysis included 2686 randomized patients.,Roflumilast significantly decreased exacerbations by 14.3% compared with placebo (p = 0.026).,Features associated with this reduction were: presence of chronic bronchitis with or without emphysema (26.2% decrease, p = 0.001), presence of cough (20.9% decrease, p = 0.006), presence of sputum (17.8% decrease, p = 0.03), and concurrent use of inhaled corticosteroids (ICS; 18.8% decrease, p = 0.014).,The incidence of adverse events was similar with roflumilast and placebo (81.5% vs 80.1%), but more patients in the roflumilast group had events assessed as likely or definitely related to the study drug (21.5% vs 8.3%).,This post-hoc, pooled analysis showed that roflumilast reduced exacerbation frequency in a subset of COPD patients whose characteristics included chronic bronchitis with/without concurrent ICS.,These observations aided the design of subsequent phase 3 studies that prospectively confirmed the reduction in exacerbations with roflumilast treatment.,ClinicalTrials.gov identifiers: NCT00076089 and NCT00430729. | The GOLD classification of COPD severity introduces a stage 0 (at risk) comprising individuals with productive cough and normal lung function.,The aims of this study were to investigate total mortality risks in GOLD stages 0-4 with special focus on stage 0, and furthermore to assess the influence of symptoms of chronic bronchitis on mortality risks in GOLD stages 1-4.,Between 1974 and 1992, a total of 22 044 middle-aged individuals participated in a health screening, which included a spirometry as well as recording of respiratory symptoms and smoking habits.,Individuals with comorbidity at baseline (diabetes, stroke, cancer, angina pectoris, or heart infarction) were excluded from the analyses.,Hazard ratios (HR 95% CI) of total mortality were analyzed in GOLD stages 0-4 with individuals with normal lung function and without symptoms of chronic bronchitis as a reference group.,HR:s in smoking individuals with symptoms of chronic bronchitis within the stages 1-4 were calculated with individuals with the same GOLD stage but without symptoms of chronic bronchitis as reference.,The number of deaths was 3674 for men and 832 for women based on 352 324 and 150 050 person-years respectively.,The proportion of smokers among men was 50% and among women 40%.,Self reported comorbidity was present in 4.6% of the men and 6.6% of the women.,Among smoking men, Stage 0 was associated with an increased mortality risk, HR; 1.65 (1.32-2.08), of similar magnitude as in stage 2, HR; 1.41 (1.31-1.70).,The hazard ratio in stage 0 was significantly higher than in stage 1 HR; 1.13 (0.98-1.29).,Among male smokers with stage 1; HR: 2.04 (1.34-3.11), and among female smokers with stage 2 disease; HR: 3.16 (1.38-7.23), increased HR:s were found in individuals with symptoms of chronic bronchitis as compared to those without symptoms of chronic bronchitis.,Symptoms fulfilling the definition of chronic bronchitis were associated with an increased mortality risk among male smokers with normal pulmonary function (stage 0) and also with an increased risk of death among smoking individuals with mild to moderate COPD (stage 1 and 2). | 1 |
Indacaterol is a once-daily long-acting inhaled β2-agonist indicated for maintenance treatment of moderate-to-severe chronic obstructive pulmonary disease (COPD).,The large inter-patient and inter-study variability in forced expiratory volume in 1 second (FEV1) with bronchodilators makes determination of optimal doses difficult in conventional dose-ranging studies.,We considered alternative methods of analysis.,We utilized a novel modelling approach to provide a robust analysis of the bronchodilatory dose response to indacaterol.,This involved pooled analysis of study-level data to characterize the bronchodilatory dose response, and nonlinear mixed-effects analysis of patient-level data to characterize the impact of baseline covariates.,The study-level analysis pooled summary statistics for each steady-state visit in 11 placebo-controlled studies.,These study-level summaries encompassed data from 7476 patients at indacaterol doses of 18.75-600 μg once daily, and showed that doses of 75 μg and above achieved clinically important improvements in predicted trough FEV1 response.,Indacaterol 75 μg achieved 74% of the maximum effect on trough FEV1, and exceeded the midpoint of the 100-140 mL range that represents the minimal clinically important difference (MCID; ≥120 mL vs placebo), with a 90% probability that the mean improvement vs placebo exceeded the MCID.,Indacaterol 150 μg achieved 85% of the model-predicted maximum effect on trough FEV1 and was numerically superior to all comparators (99.9% probability of exceeding MCID).,Indacaterol 300 μg was the lowest dose that achieved the model-predicted maximum trough response.,The patient-level analysis included data from 1835 patients from two dose-ranging studies of indacaterol 18.75-600 μg once daily.,This analysis provided a characterization of dose response consistent with the study-level analysis, and demonstrated that disease severity, as captured by baseline FEV1, significantly affects the dose response, indicating that patients with more severe COPD require higher doses to achieve optimal bronchodilation.,Comprehensive assessment of the bronchodilatory dose response of indacaterol in COPD patients provided a robust confirmation that 75 μg is the minimum effective dose, and that 150 and 300 μg are expected to provide optimal bronchodilation, particularly in patients with severe disease. | 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. | 1 |
COPD is a leading cause of morbidity and mortality, yet it remains largely under-diagnosed.,Case-finding is encouraged by many professionals, but there is a lack of information on the patients’ views and perspectives.,Semistructured interviews were conducted with adults, aged 40 years or older with a history of smoking, who were eligible and invited for case-finding for COPD as a part of a large UK primary care trial.,Patients, including those who consented or declined participation and those with and without COPD after screening, were interviewed.,Interviews were transcribed and analyzed using the framework method.,The 43 interviews revealed the following two main categories of themes: patients’ views on COPD case-finding and barriers to case-finding.,Overall, case-finding was deemed important and beneficial.,Participants highlighted the need for screening activities to be convenient for patients but perceived that general practitioners (GPs) lacked the time and accessing appointments was difficult.,Desire for a health check among symptomatic patients facilitated participation in case-finding.,Psychological barriers to engagement included denial of ill health or failure to recognize symptoms, fear of the “test”, and lung symptoms being low on the hierarchy of patient health complaints.,Mechanical barriers included providing care for another person (and therefore being too busy), being unable to access GP appointments, and lacking feedback of spirometry results or communication of the diagnosis.,Patient engagement with case-finding may be limited by denial or lack of recognition of symptoms and physical barriers to attendance.,Increasing public awareness of COPD risk factors and early symptoms may enhance case-finding. | Up to 436,000 adult Danes suffer from chronic obstructive pulmonary disease (COPD), with only one third diagnosed at this time.,The Danish National Board of Health recommends early detection of COPD, focusing on smokers/ex-smokers over 35 years of age with at least one lung symptom.,A governmental prevention committee has suggested that the municipalities, in addition to general practice, should be a potential arena responsible for early detection of COPD.,We undertook a pilot study to investigate the feasibility and effectiveness of early detection of COPD in municipalities following the recommendations of the Danish National Board of Health.,The Municipality of Esbjerg offered spirometry to Danish citizens at risk of COPD without a previous diagnosis of the disease, following the National Board of Health’s recommendations.,Citizens with evidence of airway obstruction (forced expiratory volume in one second [FEV1]/forced vital capacity [FVC] <70%) were advised to visit their general practitioner for diagnosis.,These citizens were followed up by telephone interview 3 months later.,Of 152 citizens sampled (50% females, mean age 58 years, 51% smokers) 51.3% had evidence of airway obstruction, with 87% being mild to moderate in terms of severity.,Seven of ten citizens (71%) then visited their general practitioner, with 85% of these being diagnosed with COPD.,The number of smokers embarking on smoking cessation or quitting smoking increased following COPD screening, with the highest frequency in participants with evidence of airway obstruction.,In addition to early detection of COPD in general practice, early detection of airway obstruction in defined risk populations in Danish municipalities seems feasible and effective for identifying new patients with COPD.,However, additional research is needed in larger samples to confirm the results of the present study. | 1 |
To explore the associations between sleep hypoventilation (SH) and daytime arterial pressures of carbon dioxide (PaCO2), sleep stages, and sleep apneas/hypopneas (AHI) in subjects with chronic obstructive pulmonary disease (COPD).,SH has previously been found in COPD-subjects with chronic hypercapnic respiratory failure (CHRF) using supplementary oxygen (LTOT), and has been proposed as a possible predictor for CHRF.,A prospectively designed observational study in a pulmonary rehabilitation hospital of 100 (39 male) stable COPD inpatients with a mean forced expiratory volume in 1 second (FEV1) of 1.1 L (42% of predicted) and a mean age of 64 years, using polysomnography with transcutaneous measurement of carbon dioxide pressure increase (ΔPtcCO2).,SH as defined by the American Academy of Sleep Medicine (AASM) was found in 15 of the subjects, seven of whom used LTOT.,However, six had SH despite being normocapnic during the daytime (only one on LTOT).,Subjects with SH had a greater ΔPtcCO2 increase from nonrapid eye movement (NREM) to rapid eye movement (REM) sleep stages compared to non-SH subjects (mean [standard deviation] between-groups difference =0.23(0.20) kPa, P<0.0005).,Subjects with apnea/hypopnea index ≥15 (overlap, N=27) did not differ from those with COPD alone (AHI <5, N=25) in sleep ΔPtcCO2 or daytime PaCO2.,A regression model with the variables FEV1, LTOT, and sleep maximum ΔPtcCO2 explained 56% of the variance in daytime PaCO2 (F(3, 94) =40.37, P<0.001).,In stable COPD, SH as defined by the AASM was found both in normocapnic, non-LTOT subjects and in hypercapnic, LTOT-using subjects.,Between-sleep-stage increase in ΔPtcCO2 was higher in subjects with SH.,Overlap subjects did not differ from simple COPD subjects in sleep ΔPtcCO2 or daytime PaCO2. | To assess the distribution of high-sensitivity cardiac troponin T (hs-cTnT) concentrations in stable chronic obstructive pulmonary disease (COPD), and whether hs-cTnT is associated with pulmonary function.,Prospectively designed, cross-sectional study.,Outpatient clinic of Norwegian teaching hospital and community-based setting.,Sample of 101 stable COPD patients from the hospital's outpatient clinic and 120 individuals derived from a random general population sample.,Ratio of hs-cTnT in stable COPD patients compared with references from the general population.,Change in ratio of hs-cTnT per unit increase of relevant covariables.,The crude geometric means of circulating hs-cTnT in the cases and the references were 7.75 and 3.01 ng/l, respectively (p <0.001); that is, a relative ratio of 2.57 (95% CI 2.05 to 3.23).,After adjustment for relevant confounders, this ratio was moderately attenuated to 1.65 (1.31-2.08).,In the total study cohort, as well as among stable COPD patients, we found a significant positive association between hs-cTnT and interleukin-6 concentrations (p <0.001) and the presence of pathologic Q waves (p=0.023).,Among stable COPD patients, one quartile increase in forced expiratory volume 1 was associated with a 39% decrease in hs-cTnT and patient category (Global Initiative of Obstructive Lung Disease classification 2011) was positively associated with hs-cTnT (p trend <0.001) after multivariate adjustment.,Stable COPD is independently associated with higher hs-cTnT compared with randomly drawn subjects from the general population.,In patients with stable COPD, higher hs-cTnT seems to be associated with immune activation and the severity of the disease. | 1 |
The risk of dying of lung cancer is up to eightfold higher in patients with COPD than in age- and gender-matched controls.,The aim of this study was to investigate the factors associated with lung cancer in a large cohort of COPD patients from primary care centers.,To analyze whether age, gender, socioeconomic factors, comorbidity, and medication affect the risk of lung cancer in COPD, we used a COPD cohort of primary care patients.,Data from primary care medical records and mandatory Swedish national registers were collected and linked in this population-based, retrospective observational registry study (NCT01146392).,Of the total cohort, 19,894 patients were included in the study.,Five hundred and ninety-four lung cancer cases were diagnosed, corresponding to 3.0% of the studied population.,In a multivariate analysis, the risk of lung cancer was lower if the COPD patients had a concurrent asthma diagnosis (HR: 0.54, CI: 0.41-0.71), while the risk of lung cancer increased with increasing age.,A decreased lung cancer risk was observed in an exposure-dependent manner in patients who were prescribed inhaled corticosteroids (HR: 0.52, CI: 0.37-0.73), while the opposite was found for the use of acetylsalicylic acid (HR: 1.58, CI: 1.15-2.16).,In this large population-based cohort, a concurrent asthma diagnosis and use of inhaled corticosteroids were independently related to decreased risk of lung cancer in COPD patients, while the use of acetylsalicylic acid was associated with an increased risk.,The findings of the present study should be seen as hypothesis generating and need to be confirmed in prospective studies. | Inhaled corticosteroids (ICS) have been associated with decreased lung cancer risk.,However, they have been associated with pulmonary infections (tuberculosis [TB] and pneumonia) in patients with chronic obstructive pulmonary disease (COPD).,TB and pneumonia have increased lung cancer risk.,The association between post-ICS pulmonary infections and lung cancer remains unclear.,We conducted a retrospective cohort study from 2003 to 2010 using the Taiwan National Health Insurance Research Database.,Among the 1,089,955 patients with COPD, we identified 8813 new users of ICS prescribed for a period of 3 months or more and 35,252 non-ICS users who were randomly matched for sex, age and date of ICS use from 2003 to 2005.,Cox proportional hazard regression was used to estimate the hazard ratio (HR) of pulmonary infections in patients with/without ICS use.,The HRs for lung cancer in ICS users with sequential lung infections were as follows; 2.42 (95 % confidence interval [CI], 1.28-4.58) for individuals with TB, 2.37 (95 % CI, 1.01-5.54) for TB and pneumonia, and 1.17(95 % CI, 0.69-1.98) for those with pneumonia.,For non-ICS users with pulmonary infections, the HRs were 1.68 (95 % CI, 0.78-3.65) for individual with TB and pneumonia, 1.42 (95 % CI, 0.89-2.26) for TB, and 0.95 (95 % CI, 0.62-1.46) for individuals with pneumonia.,COPD patients with TB /or pneumonia who used ICS had increased risk of lung cancer.,Because the overall prognosis of lung cancer remains poor, screening tests are recommended for patients with these conditions. | 1 |
Inhaled corticosteroids (ICS) are commonly used to treat COPD and are associated with increased risk of pneumonia.,The aim of this study was to assess if accumulated use of ICS is associated with a dose-dependent risk of a positive airway culture with Pseudomonas aeruginosa in patients with COPD.,We conducted a multiregional epidemiological cohort study including Danish COPD patients followed in outpatient clinics during 2010-2017.,ICS use was categorised based on accumulated prescriptions redeemed 365 days prior to cohort entry.,Cox proportional hazard regression model was used to estimate the risk of acquiring P. aeruginosa.,Propensity score matched models were used as sensitivity analyses.,A total of 21 408 patients were included in the study, of which 763 (3.6%) acquired P. aeruginosa during follow-up.,ICS use was associated with a dose-dependent risk of P. aeruginosa (low ICS dose: HR 1.38, 95% CI 1.03 to 1.84, p=0.03; moderate ICS dose: HR 2.16, 95% CI 1.63 to 2.85, p<0.0001; high ICS dose: HR 3.58, 95% CI 2.75 to 4.65, p<0.0001; reference: no ICS use).,A propensity matched model confirmed the results (high ICS dose compared with no/low/moderate ICS dose: HR 2.05, 95% CI 1.76 to 2.39, p p<0.0001).,Use of ICS in patients with COPD followed in Danish outpatient clinics was associated with a substantially increased and dose-dependent risk of acquiring P. aeruginosa.,Caution should be taken when administering high doses of ICS in severely ill patients with COPD.,These results should be confirmed in comparable cohorts and other settings. | Observational studies suggest that immunoglobulin treatment may reduce the frequency of acute exacerbations of COPD (AECOPD).,To inform the design of a future randomised control trial (RCT) of intravenous immunoglobulin (IVIG) treatment efficacy for AECOPD prevention.,A pilot RCT was conducted.,We recruited patients with COPD hospitalized for AECOPD, or from ambulatory clinics with one severe, or two moderate AECOPD in the previous year regardless of their serum IgG level.,Patients were allocated in a 1:1 ratio with balanced randomisation to monthly IVIG or normal saline for 1 year.,The primary outcome was feasibility defined as pre-specified accrual, adherence, and follow-up rates.,Secondary outcomes included safety, tolerance, AECOPD rates, time to first AECOPD, quality of life, and healthcare costs.,Seventy patients were randomized (37 female; mean age 67.7; mean FEV1 35.1%).,Recruitment averaged 4.5±0.9 patients per month (range 0-8), 34 (49%) adhered to at least 80% of planned treatments, and four (5.7%) were lost to follow-up.,There were 35 serious adverse events including seven deaths and one thromboembolism.,None was related to IVIG.,There were 56 and 48 moderate and severe AECOPD in the IVIG vs control groups.,In patients with at least 80% treatment adherence, median time to first moderate or severe AECOPD was 275 vs 114 days, favoring the IVIG group (HR 0.76, 95% CI 0.3-1.92).,The study met feasibility criteria for recruitment and retention, but adherence was low.,A trend toward more robust treatment efficacy in adherent patients supports further study, but future trials must address treatment adherence.,NCT0290038, registered 24 February 2016, https://clinicaltrials.gov/ct2/show/NCT02690038 and NCT03018652, registered January 12, 2017, https://clinicaltrials.gov/ct2/show/NCT03018652. | 1 |
Chronic bronchitis is a disease of the bronchi that is manifested by cough and sputum expectoration occurring on most days for at least 3 months of the year and for at least 2 consecutive years when other respiratory or cardiac causes for the chronic productive cough are excluded.,The disease is caused by an interaction between noxious inhaled agents (eg, cigarette smoke, industrial pollutants, and other environmental pollutants) and host factors (eg, genetic and respiratory infections) that results in chronic inflammation in the walls and lumen of the airways.,As the disease advances, progressive airflow limitation occurs, usually in association with pathologic changes of emphysema.,This condition is called COPD.,When a stable patient experiences a sudden clinical deterioration with increased sputum volume, sputum purulence, and/or worsening of shortness of breath, this is referred to as an acute exacerbation of chronic bronchitis as long as conditions other than acute tracheobronchitis are ruled out.,The purpose of this review is to present the evidence for the diagnosis and treatment of cough due to chronic bronchitis, and to make recommendations that will be useful for clinical practice.,Recommendations for this section of the review were obtained from data using a National Library of Medicine (PubMed) search dating back to 1950, performed in August 2004, of the literature published in the English language.,The search was limited to human studies, using the search terms “cough,” “chronic bronchitis,” and “COPD.”,The most effective way to reduce or eliminate cough in patients with chronic bronchitis and persistent exposure to respiratory irritants, such as personal tobacco use, passive smoke exposure, and workplace hazards is avoidance.,Therapy with a short-acting inhaled β-agonist, inhaled ipratropium bromide, and oral theophylline, and a combined regimen of inhaled long-acting β-agonist and an inhaled corticosteroid may improve cough in patients with chronic bronchitis, but there is no proven benefit for the use of prophylactic antibiotics, oral corticosteroids, expectorants, postural drainage, or chest physiotherapy.,For the treatment of an acute exacerbation of chronic bronchitis, there is evidence that inhaled bronchodilators, oral antibiotics, and oral corticosteroids (or in severe cases IV corticosteroids) are useful, but their effects on cough have not been systematically evaluated.,Therapy with expectorants, postural drainage, chest physiotherapy, and theophylline is not recommended.,Central cough suppressants such as codeine and dextromethorphan are recommended for short-term symptomatic relief of coughing.,Chronic bronchitis due to cigarette smoking or other exposures to inhaled noxious agents is one of the most common causes of chronic cough in the general population.,The most effective way to eliminate cough is the avoidance of all respiratory irritants.,When cough persists despite the removal of these inciting agents, there are effective agents to reduce or eliminate cough. | 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. | 1 |
Sputum and blood eosinophil counts predict corticosteroid effects in COPD patients.,Bacterial infection causes increased airway neutrophilic inflammation.,The relationship of eosinophil counts with airway bacterial load in COPD patients is uncertain.,We tested the hypothesis that bacterial load and eosinophil counts are inversely related.,COPD patients were seen at stable state and exacerbation onset.,Sputum was processed for quantitative polymerase chain reaction detection of the potentially pathogenic microorganisms (PPM) H. influenzae, M. catarrhalis and S. pneumoniae.,PPM positive was defined as total load ≥1 × 104copies/ml.,Sputum and whole blood were analysed for differential cell counts.,At baseline, bacterial counts were not related to blood eosinophils, but sputum eosinophil % was significantly lower in patients with PPM positive compared to PPM negative samples (medians: 0.5% vs.,1.25% respectively, p = 0.01).,Patients with PPM positive samples during an exacerbation had significantly lower blood eosinophil counts at exacerbation compared to baseline (medians: 0.17 × 109/L vs.,0.23 × 109/L respectively, p = 0.008), while no blood eosinophil change was observed with PPM negative samples.,These findings indicate an inverse relationship between bacterial infection and eosinophil counts.,Bacterial infection may influence corticosteroid responsiveness by altering the profile of neutrophilic and eosinophilic inflammation.,The online version of this article (doi:10.1186/s12931-017-0570-5) contains supplementary material, which is available to authorized users. | 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. | 1 |
Dyspnea is a distressing, debilitating, and near-ubiquitous symptom affecting patients with COPD.,In addition to the functional consequences of dyspnea, which include activity limitation and reduced exercise tolerance, it is important to consider its psychological impact on patients with COPD, such as onset of depression or anxiety.,Moreover, the anticipation of dyspnea itself can have a significant effect on patients’ emotions and behavior, with patients frequently self-limiting physical activity to avoid what has become the hallmark symptom of COPD.,Dyspnea is, therefore, a key target for COPD treatments.,Pharmacologic treatments can optimize respiratory mechanics, provide symptom relief, and reduce patients’ increased inspiratory neural drive to breathe.,However, it is important to acknowledge the value of non-pharmacologic interventions, such as pulmonary rehabilitation and patient self-management education, which have proven to be invaluable tools for targeting the affective components of dyspnea.,Furthermore, it is important to encourage maintenance of physical activity to optimize long-term patient outcomes.,Here, we review the physiological and psychological consequences of activity-related dyspnea in COPD, assess the efficacy of modern management strategies in improving this common respiratory symptom, and discuss key unmet clinical and research needs that warrant further immediate attention. | The Visual Simplified Respiratory Questionnaire (VSRQ) was designed to assess health-related quality of life (HRQoL) in patients with chronic obstructive pulmonary disease (COPD).,It contains eight items: dyspnea, anxiety, depressed mood, sleep, energy, daily activities, social activities and sexual life.,Psychometric properties were assessed during a clinical trial that evaluated the impact of tiotropium on HRQoL of COPD patients.,These included the determination of structure, internal consistency reliability, concurrent validity with the St George’s Respiratory Questionnaire (SGRQ), test - retest reliability, clinical validity and responsiveness to change over two weeks.,Minimal important difference (MID) was calculated; cumulative response curves (CRC) were based on the dyspnea item.,Psychometric analyses showed that VSRQ structure was unidimensional.,The questionnaire demonstrated good internal consistency reliability (Cronbach’s alpha = 0.84), good concurrent validity with SGRQ (Spearman = −0.70) and clinical validity, good test-retest reproducibility (ICC = 0.77), and satisfactory responsiveness (standardized response mean = 0.57; Guyatt’s statistic = 0.63).,MID was 3.4; CRC median value of the ‘minimally improved’ patients was 3.5.,In conclusion, VSRQ brevity and satisfactory psychometric properties make it a good candidate for large studies to assess HRQoL in COPD patients.,Further validation is needed to extend its use in clinical practice. | 1 |
Increasing age is associated with poor prognosis in patients with COPD.,This analysis from the replicate Phase III OTEMTO® and TONADO® studies examined the efficacy and safety of tiotropium, a long-acting anticholinergic, combined with olodaterol, a long-acting β2-agonist, compared to monotherapies and placebo in patients with COPD aged 40 years to <65 years, 65 years to <75 years, 75 years to <85 years, and ≥85 years.,In these double-blind, parallel-group, active-controlled, multicenter, randomized studies, patients received tiotropium + olodaterol 2.5/5 μg or 5/5 μg, tiotropium 5 μg or 2.5 μg (TONADO only), olodaterol 5 μg (TONADO only), or placebo (OTEMTO only).,This analysis used the approved doses of tiotropium + olodaterol 5/5 μg, tiotropium 5 μg, and olodaterol 5 μg.,Primary end points at 12 weeks (OTEMTO) or 24 weeks (TONADO) included St George’s Respiratory Questionnaire (SGRQ) total score, forced expiratory volume in 1 second (FEV1) area under the curve from 0 hour to 3 hours (AUC0-3) response, and trough FEV1 response.,A total of 1,621 patients were randomized (40 years to <65 years, n=749; 65 years to <75 years, n=674; 75 years to <85 years, n=186; ≥85 years, n=12) in OTEMTO and 5,162 patients (40 years to <65 years, n=2,654; 65 years to <75 years, n=1,967; 75 to <85 years, n=528; ≥85 years, n=13) in TONADO.,FEV1 AUC0-3 and trough FEV1 responses improved with tiotropium + olodaterol 5/5 μg at 12 weeks and 24 weeks compared to monotherapies or placebo for all age groups.,SGRQ scores generally improved with tiotropium + olodaterol 5/5 μg after 12 weeks in OTEMTO and improved after 24 weeks in all age groups in TONADO.,In all age groups receiving tiotropium + olodaterol 5/5 μg compared to monotherapies or placebo, transition dyspnea index scores generally improved, while rescue medication usage improved.,No differences were noted in relative responses to treatment or safety when using tiotropium + olodaterol 5/5 μg compared to monotherapies or placebo across all age groups. | Olodaterol is a long-acting β2-agonist with a 24-hour bronchodilator profile.,Two replicate, randomized, double-blind, placebo-controlled, parallel-group, Phase III trials were performed as part of a comprehensive clinical program to investigate the long-term safety and efficacy of olodaterol in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) receiving usual-care background therapy.,Patients received olodaterol 5 μg or 10 μg or placebo once daily for 48 weeks.,Coprimary end points were forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 3 hours (AUC0-3) response (change from baseline), and trough FEV1 response at 12 weeks.,Secondary end points included additional lung function assessments, use of rescue medications, FEV1 AUC response from 0 to 12 hours, and Patient Global Rating over 48 weeks.,Overall, 624 and 642 patients were evaluated in studies 1222.11 and 1222.12, respectively.,In both studies, olodaterol 5 μg and 10 μg significantly improved the FEV1 AUC0-3 response (P<0.0001) and trough FEV1 (study 1222.11, P<0.0001; study 1222.12, P<0.05, post hoc) at week 12, with an incidence of adverse events comparable with that of placebo.,Secondary end points supported the efficacy of olodaterol.,These studies demonstrate the long-term efficacy and safety of once-daily olodaterol 5 μg and 10 μg in patients with moderate to very severe COPD continuing with usual-care maintenance therapy. | 1 |
The clinical benefit of continued supervised maintenance exercise programs following pulmonary rehabilitation in COPD remains unclear.,This systematic review aimed to synthesize the available evidence on the efficacy of supervised maintenance exercise programs compared to usual care following pulmonary rehabilitation completion on health care use and mortality.,Electronic databases (MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials, Web of Science, and PEDro) and trial registers (ClinicalTrials.gov and Current Controlled Trials) were searched for randomized trials comparing supervised maintenance exercise programs with usual care following pulmonary rehabilitation completion.,Primary outcomes were respiratory-cause hospital admissions, exacerbations requiring treatment with antibiotics and/or systemic corticosteroids, and mortality.,Eight trials (790 COPD patients) met the inclusion criteria, six providing data for meta-analysis.,Continued supervised maintenance exercise compared to usual care following pulmonary rehabilitation completion significantly reduced the risk of experiencing at least one respiratory-cause hospital admission (risk ratio 0.62, 95% confidence interval [CI] 0.47-0.81, P<0.001).,Meta-analyses also suggested that supervised maintenance exercise leads to a clinically important reduction in the rate of respiratory-cause hospital admissions (rate ratio 0.72, 95% CI 0.50-1.05, P=0.09), overall risk of an exacerbation (risk ratio 0.79, 95% CI 0.52-1.19, P=0.25), and mortality (risk ratio 0.57, 95% CI 0.17-1.92, P=0.37).,In the first systematic review of the area, current evidence demonstrates that continued supervised maintenance exercise compared to usual care following pulmonary rehabilitation reduces health care use in COPD.,The variance in the quality of the evidence included in this review highlights the need for this evidence to be followed up with further high-quality randomized trials. | To assess the effect of telehealthcare compared with usual practice in patients with chronic obstructive pulmonary disease (COPD).,A cluster-randomised trial with 26 municipal districts that were randomly assigned either to an intervention group whose members received telehealthcare in addition to usual practice or to a control group whose members received usual practice only (13 districts in each arm).,Twenty-six municipal districts in the North Denmark Region of Denmark.,Patients who fulfilled the Global Initiative for COPD guidelines and one of the following criteria: COPD Assessment Test score ≥10; or Medical Research Dyspnoea Council Scale ≥3; or Modified Medical Research Dyspnoea Council Scale ≥2; or ≥2 exacerbations during the past 12 months.,Health-related quality of life (HRQoL) assessed by the physical component summary (PCS) and mental component summary (MCS) scores of the Short Form 36-Item Health Survey, Version 2.,Data were collected at baseline and at 12 month follow-up and analysed according to the intention-to-treat principle with complete cases, n=574 (258 interventions; 316 controls) and imputed data, n=1225 (578 interventions, 647 controls) using multilevel modelling.,In the intention-to-treat analysis (n=1225), the raw mean difference in PCS from baseline to 12 month follow-up was −2.6 (SD 12.4) in the telehealthcare group and −2.8 (SD 11.9) in the usual practice group.,The raw mean difference in MCS scores in the same period was −4.7 (SD 16.5) and −5.3 (SD 15.5) for telehealthcare and usual practice, respectively.,The adjusted mean difference in PCS and MCS between groups at 12 months was 0.1 (95% CI −1.4 to 1.7) and 0.4 (95% CI −1.7 to 2.4), respectively.,The overall sample and all subgroups demonstrated no statistically significant differences in HRQoL between telehealthcare and usual practice.,NCT01984840; Results. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) have increased susceptibility to respiratory tract infection, which contributes to disease progression and mortality, but mechanisms of increased susceptibility to infection remain unclear.,The aim of this study was to determine whether glucose concentrations were increased in airway samples (nasal lavage fluid, sputum, and bronchoalveolar lavage fluid) from patients with stable COPD and to determine the effects of viral infection on sputum glucose concentrations and how airway glucose concentrations relate to bacterial infection.,We measured glucose concentrations in airway samples collected from patients with stable COPD and smokers and nonsmokers with normal lung function.,Glucose concentrations were measured in patients with experimentally induced COPD exacerbations, and these results were validated in patients with naturally acquired COPD exacerbations.,Relationships between sputum glucose concentrations, inflammatory markers, and bacterial load were examined.,Sputum glucose concentrations were significantly higher in patients with stable COPD compared with those in control subjects without COPD.,In both experimental virus-induced and naturally acquired COPD exacerbations, sputum and nasal lavage fluid glucose concentrations were increased over baseline values.,There were significant correlations between sputum glucose concentrations and sputum inflammatory markers, viral load, and bacterial load.,Airway samples with higher glucose concentrations supported more Pseudomonas aeruginosa growth in vitro.,Airway glucose concentrations are increased in patients with stable COPD and further increased during COPD exacerbations.,Increased airway glucose concentrations might contribute to bacterial infections in both patients with stable and those with exacerbated COPD.,This has important implications for the development of nonantibiotic therapeutic strategies for the prevention or treatment of bacterial infection in patients with COPD. | Respiratory virus infections are commonly associated with COPD exacerbations, but little is known about the mechanisms linking virus infection to exacerbations.,Pathogenic mechanisms in stable COPD include oxidative and nitrosative stress and reduced activity of histone deacetylase-2 (HDAC2), but their roles in COPD exacerbations is unknown.,We investigated oxidative and nitrosative stress (O&NS) and HDAC2 in COPD exacerbations using experimental rhinovirus infection.,Nine subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease stage II), 10 smokers, and 11 nonsmokers were successfully infected with rhinovirus.,Markers of O&NS-associated cellular damage, and inflammatory mediators and proteases were measured in sputum, and HDAC2 activity was measured in sputum and bronchoalveolar macrophages.,In an in vitro model, monocyte-derived THP-1 cells were infected with rhinovirus and nitrosylation and activity of HDAC2 was measured.,Rhinovirus infection induced significant increases in airways inflammation and markers of O&NS in subjects with COPD.,O&NS markers correlated with virus load and inflammatory markers.,Macrophage HDAC2 activity was reduced during exacerbation and correlated inversely with virus load, inflammatory markers, and nitrosative stress.,Sputum macrophage HDAC2 activity pre-infection was inversely associated with sputum virus load and inflammatory markers during exacerbation.,Rhinovirus infection of monocytes induced nitrosylation of HDAC2 and reduced HDAC2 activity; inhibition of O&NS inhibited rhinovirus-induced inflammatory cytokines.,O&NS, airways inflammation, and impaired HDAC2 may be important mechanisms of virus-induced COPD exacerbations.,Therapies targeting these mechanisms offer potential new treatments for COPD exacerbations. | 1 |
Chronic obstructive pulmonary disease (COPD) outpatients account for a large burden of usual care by respirologists.,EPOCONSUL is the first national clinical audit conducted in Spain on the medical care for COPD patients delivered in outpatient respiratory clinics.,We aimed to evaluate the clinical interventions and the degree of adherence to recommendations in outpatients of current COPD clinical practice guidelines.,This is an observational study with prospective recruitment (May 2014-May 2015) of patients with a COPD diagnosis as seen in outpatient respiratory clinics.,The information collected was historical in nature as for the clinical data of the last and previous consultations, and the information concerning hospital resources was concurrent.,A total of 17,893 clinical records of COPD patients in outpatient respiratory clinics from 59 Spanish hospitals were evaluated.,Of the 5,726 patients selected, 4,508 (78.7%) were eligible.,Overall, 12.1% of COPD patients did not fulfill a diagnostic spirometry criteria.,Considerable variability existed in the available resources and work organization of the hospitals, although the majority were university hospitals with respiratory inpatient units.,There was insufficient implementation of clinical guidelines in preventive and educational matters.,In contrast, quantitative evaluation of dyspnea grade (81.9%) and exacerbation history (70.9%) were more frequently performed.,Only 12.4% had COPD severity calculated according to the Body mass index, airflow Obstruction, Dyspnoea and Exercise capacity (BODE) index.,Phenotype characteristics according to Spanish National Guideline for COPD were determined in 46.3% of the audited patients, and the risk evaluation according to Global initiative for chronic Obstructive Lung Disease was estimated only in 21.9%.,The EPOCONSUL study reports the current situation of medical care for COPD patients in outpatient clinics in Spain, revealing its variability, strengths, and weaknesses.,This information has to be accounted for by health managers to define corrective strategies and maximize good clinical practice. | To estimate the potential cost savings by following the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline recommendations in patients being treated for chronic obstructive pulmonary disease (COPD) with the combination of long-acting β2-agonist (LABA), long-acting muscarinic antagonist (LAMA) or inhaled corticosteroids (ICS).,The Geisinger Health System (GHS) database was utilized to identify subjects between January 1, 2004 to March 12, 2007.,The index date was based on the first prescription of a LAMA plus LABA, LAMA plus LABA/ICS, or LABA plus ICS.,Patients were included in the study if they: had a COPD diagnosis; had data representative of treatment 12 months prior to and 12 months post index date; were 40 years of age or over; had no prior diagnosis for asthma; and had pulmonary function test (PFT) data.,We examined the baseline characteristics of these patients along with their healthcare resource utilization.,Based on PFT data within 30 days of the index date, a subgroup was classified as adhering or non-adhering to GOLD guidelines.,A total of 364 subjects could be classified as adhering or non-adherent to current GOLD guidelines based on their PFT results.,The adherent subgroup received COPD medications consistent with current GOLD guidelines.,Of the LAMA plus LABA cohort, 25 patients adhered and 39 patients were non-adherent to current GOLD guidelines.,In the cohort of LABA plus ICS, 74 patients were adherent and 180 patients non-adherent to current GOLD guidelines.,In the cohort of LAMA plus LABA/ICS, 21 patients were adherent and 25 patients non-adherent to current GOLD guidelines.,GOLD adherence was associated with mean total cost of all services savings of $5,889 for LAMA plus LABA, $3,330 for LABA + ICS, and $10,217 for LAMA plus LABA/ICS cohorts.,Staging of COPD with a PFT and adherence to current GOLD guidelines was associated with lower costs in subjects with moderate to severe COPD.,Appropriate use of LAMA plus LABA, LABA plus ICS, and LAMA plus LABA/ICS has economic as well as clinical benefits for patients and payers. | 1 |
The Spanish Guidelines for COPD (GesEPOC) describe four clinical phenotypes: non-exacerbator (NE), asthma-COPD overlap syndrome (ACO), frequent exacerbator with emphysema (EE), and exacerbator with chronic bronchitis (ECB).,The objective of this study was to determine the frequency of COPD phenotypes, their clinical characteristics, and the availability of diagnostic tools to classify COPD phenotypes in clinical practice.,This study was an epidemiological, cross-sectional, and multi-centered study.,Patients ≥40 years old with a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio of <0.7 and who were smokers or former smokers (with at least 10 pack-years) were included.,The availability of diagnostic tools to classify COPD phenotypes was assessed by an ad hoc questionnaire.,A total of 647 patients (294 primary care [PC], 353 pulmonology centers) were included.,Most patients were male (80.8%), with a mean age (SD) of 68.2 (9.2) years, mean post-bronchodilator FEV1 was 53.2% (18.9%) and they suffered a mean of 2.2 (2.1) exacerbations in the last year.,NE was the most frequent phenotype (47.5%) found, followed by ECB (29.1%), EE (17.0%), and ACO (6.5%).,Significant differences between the four phenotypes were found regarding age; sex; body mass index; FEV1; body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE)/body mass index, airflow obstruction, dyspnea and exacerbations (BODEx) index; modified Medical Research Council dyspnea scale; respiratory symptoms; comorbidi-ties; hospitalizations; and exacerbations in the last year.,Physicians considered that >80% of the diagnostic tools needed to classify COPD phenotypes were available, with the exception of computed tomography (26.9%) and carbon monoxide transfer test (13.5%) in PC, and sputum eosinophilia count in PC and pulmonology centers (40.4% and 49.4%, respectively).,In Spanish clinical practice, almost half of the patients with COPD presented with NE phenotype.,The prevalence of ACO according to the Spanish consensus definition was very low.,In general, physicians indicated that they had the necessary tools for diagnosing COPD phenotypes. | Using sputum neutrophils as the primary measure, and other inflammation biomarkers, this study evaluated the anti-inflammatory effects of the combination salmeterol 50 mcg and fluticasone propionate 250 mcg (SFC 250) in Japanese patients with chronic obstructive pulmonary disease (COPD).,Patients were treated in a randomized, double-blind, parallel group, placebo-controlled trial with SFC 250 twice daily (n=26) or placebo (n=26) for 12 weeks.,At the start and end of treatment, inflammation biomarkers (sputum and serum), lung function, and health status (COPD Assessment Test [CAT] questionnaire) were measured.,Although a numerical decrease in differential neutrophil count was observed from baseline, SFC 250 did not significantly reduce sputum neutrophils compared with placebo, nor were there significant changes from baseline in the other biomarkers (sputum or serum), lung function, or CAT, versus placebo.,Squamous epithelial cell contamination in some sputum samples rendered them unacceptable for analysis, which reduced the sample size to n=19 (SFC 250) and n=10 (placebo).,However, inclusion of contaminated samples did not affect the overall trend of the outcome.,Ad hoc bootstrap statistical analysis showed a 27.9% (SFC 250) and 1.3% (placebo) decrease in sputum neutrophils.,Sputum IL-8 decreased by 43.2% after SFC 250 but increased by 48.3% with placebo.,Responder analyses showed 42% of patients had ≥20% decrease in neutrophils from baseline; and 47% of patients had a ≥200 pg/mL change in sputum IL-8 following SFC 250 versus 20% after placebo; both changes are considered clinically relevant.,This study provides additional information about inflammation in Japanese COPD patients and is the first to study the anti-inflammatory effects of SFC 250 in this context and population.,In the primary analysis, SFC 250 did not produce significant changes from baseline in sputum neutrophil levels or other sputum or serum inflammatory markers compared with placebo.,Secondary ad hoc statistical analysis showed that SFC 250 reduced the number of sputum neutrophils and IL-8 compared with placebo. | 1 |
Pulmonary surfactant protein D (SP-D) is considered as a candidate biomarker for the functional integrity of the lung and for disease progression, which can be detected in serum.,The origin of SP-D in serum and how serum concentrations are related to pulmonary concentrations under inflammatory conditions is still unclear.,In a cross-sectional study comprising non-smokers (n = 10), young - (n = 10), elderly smokers (n = 20), and smokers with COPD (n = 20) we simultaneously analysed pulmonary and serum SP-D levels with regard to pulmonary function, exercise, repeatability and its quaternary structure by native gel electrophoresis.,Statistical comparisons were conducted by ANOVA and post-hoc testing for multiple comparisons; repeatability was assessed by Bland-Altman analysis.,In COPD, median (IQR) pulmonary SP-D levels were lower (129(68) ng/ml) compared to smokers (young: 299(190), elderly: 296(158) ng/ml; p < 0.01) and non-smokers (967(708) ng/ml; p < 0.001).,The opposite was observed in serum, with higher concentrations in COPD (140(89) ng/ml) as compared to non-smokers (76(47) ng/ml; p < 0.01).,SP-D levels were reproducible and correlated with the degree of airway obstruction in all smokers.,In addition, smoking lead to disruption of the quaternary structure.,Pulmonary and serum SP-D levels are stable markers influenced by smoking and related to airflow obstruction and disease state.,Smaller subunits of pulmonary SP-D and the rapid increase of serum SP-D levels in COPD due to exercise support the translocation hypothesis and its use as a COPD biomarker.,no interventional trial | Many of the systemic manifestations of chronic obstructive pulmonary disease (COPD) are mediated through increased systemic levels of inflammatory proteins.,We assessed the long term repeatability of Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) over one year and examined the relationships between these systemic markers in COPD.,Fifty-eight stable COPD patients completed a baseline and one-year visit.,Serum IL-6, plasma CRP, and plasma TNF-α were measured.,Repeatability was expressed by intraclass correlation coefficient (Ri) and the Bland-Altman method.,Pearson correlations were used to determine the relationships between the systemic markers at both visits.,There was moderate repeatability with a very high degree of statistical significance (p ≤ 0.001) between the two visits for all the systemic biomarkers (IL-6, CRP, and TNF-α).,CRP was significantly associated with IL-6 at both visits (r = 0.55, p = 0.0001, r = 0.51, p = 0.0002, respectively).,There were no other significant associations between the systemic markers at either of the visits.,Systemic inflammatory biomarkers IL-6, CRP, and TNF-α were moderately repeatable over a twelve month period in COPD patients.,We have also shown that a robust and repeatable association between IL-6 and CRP exists. | 1 |
Pulmonary rehabilitation is known to improve function and quality of life for people with chronic obstructive pulmonary disease (COPD).,However, little research has been conducted on the influence of culture on experiences of pulmonary rehabilitation.,This study examined factors influencing uptake of pulmonary rehabilitation by Māori with COPD in New Zealand.,Grounded theory nested within kaupapa Māori methodology.,Transcripts were analyzed from interviews and focus groups with 15 Māori and ten New Zealand non-Māori invited to attend pulmonary rehabilitation for COPD.,Māori participants had either attended a mainstream hospital-based program, a community-based program designed “by Māori, for Māori”, or had experienced both.,Several factors influencing uptake of pulmonary rehabilitation were common to all participants regardless of ethnicity: 1) participants’ past experiences (eg, of exercise; of health care systems), 2) attitudes and expectations, 3) access issues (eg, time, transport, and conflicting responsibilities), and 4) initial program experiences.,These factors were moderated by the involvement of family and peers, interactions with health professionals, the way information on programs was presented, and by new illness events.,For Māori, however, several additional factors were also identified relating to cultural experiences of pulmonary rehabilitation.,In particular, Māori participants placed high value on whakawhanaungatanga: the making of culturally meaningful connections with others.,Culturally appropriate communication and relationship building was deemed so important by some Māori participants that when it was absent, they felt strongly discouraged to attend pulmonary rehabilitation.,Only the more holistic services offered a program in which they felt culturally safe and to which they were willing to return for ongoing rehabilitation.,Lack of attention to cultural factors in the delivery of pulmonary rehabilitation may be a barrier to its uptake by indigenous, minority ethnic groups, such as New Zealand Māori.,Indigenous-led or culturally responsive health care interventions for COPD may provide a solution to this issue. | In this narrative review, we put self-management in the context of a 50-year history of research about how patients with COPD respond to their illness.,We review a definition of self-management, and emphasize that self-management should be combined with disease management and the chronic care model in order to be effective.,Reviewing the empirical status of self-management in COPD, we conclude that self-management is part and parcel of modern, patient-oriented biopsychosocial care.,In pulmonary rehabilitation programs, self-management is instrumental in improving patients’ functional status and quality of life.,We conclude by emphasizing how studying the way persons with COPD make sense of their illness helps in refining self-management, and thereby patient-reported outcomes in COPD. | 1 |
Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous.,We sought to investigate the sputum cellular, mediator, and microbiome profiles of both asthma and COPD exacerbations.,Patients with severe asthma or moderate-to-severe COPD were recruited prospectively to a single center.,Sputum mediators were available in 32 asthmatic patients and 73 patients with COPD assessed at exacerbation.,Biologic clusters were determined by using factor and cluster analyses on a panel of sputum mediators.,Patterns of clinical parameters, sputum mediators, and microbiome communities were assessed across the identified clusters.,The asthmatic patients and patients with COPD had different clinical characteristics and inflammatory profiles but similar microbial ecology.,Three exacerbation biologic clusters were identified.,Cluster 1 was COPD predominant, with 27 patients with COPD and 7 asthmatic patients exhibiting increased blood and sputum neutrophil counts, proinflammatory mediators (IL-1β, IL-6, IL-6 receptor, TNF-α, TNF receptors 1 and 2, and vascular endothelial growth factor), and proportions of the bacterial phylum Proteobacteria.,Cluster 2 had 10 asthmatic patients and 17 patients with COPD with increased blood and sputum eosinophil counts, type 2 mediators (IL-5, IL-13, CCL13, CCL17, and CCL26), and proportions of the bacterial phylum Bacteroidetes.,Cluster 3 had 15 asthmatic patients and 29 patients with COPD with increased type 1 mediators (CXCL10, CXCL11, and IFN-γ) and proportions of the phyla Actinobacteria and Firmicutes.,A biologic clustering approach revealed 3 subgroups of asthma and COPD exacerbations, each with different percentages of patients with overlapping asthma and COPD.,The sputum mediator and microbiome profiles were distinct between clusters. | There is now convincing evidence that the airway epithelium drives the pathogenesis of COPD.,A major aspect of this is the disease-related reduction in barrier function that is potentiated by dysregulation of tight junction (TJ) protein complexes.,However, a significant number of studies using in vitro smoke exposure models have not observed alterations in barrier permeability.,We have previously shown that zinc (Zn) is an influential cytoprotective factor for the airway epithelium, and its depletion by cigarette smoke produces disease-related modifications consistent with inflammatory changes in COPD.,We hypothesized that Zn deficiency is a significant co-stimulus with cigarette smoke extract (CSE) for potentiating the leaky barrier phenotype exhibited in COPD.,We employed an ex vivo model of differentiated human airway epithelium exposed to Zn depletion and CSE to determine the contribution of Zn in maintaining normal epithelial permeability.,Western blot analysis demonstrated a significant downregulation of the TJ proteins such as ZO-1 (−1.93-fold, P<0.05) and Claudin-1 (−3.37-fold, P<0.01) with the combination exposure.,Assessment of barrier function via paracellular ionic conductance and tracer permeability also showed that Zn depletion was an important factor, which potentiated an increase in epithelial permeability (P<0.001 for both) compared to Zn depletion or CSE exposures in isolation.,Visual inspection of the epithelium using transmission electron microscopy revealed a marked reduction in junction complexes between the adjacent airway epithelial cells treated with a combination of Zn depletion and CSE.,These observations identify Zn deficiency as a significant codeterminant with CSE as a factor leading to an increase in airway epithelial permeability.,Hence, as Zn dyshomeostasis has been reported in the airway epithelium exposed to chronic cigarette smoke and inflammation, targeting these phenomena may represent a promising strategy to ameliorate the leaky barrier phenotype that is synonymous with COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is among the leading causes of morbidity and mortality worldwide.,Glucocorticoids are currently the most applicable anti-inflammatory treatment for COPD.,However, a subset of COPD subjects is relatively insensitive to this treatment.,Fenspiride, a non-corticosteroid anti-inflammatory drug, has been described to have beneficial effects in patients with COPD, although the mechanism of its action is not well known.,The effect of fenspiride on contractile activity of bronchial smooth muscle was studied in a rat model of COPD induced by long-term exposure of the animals to nitrogen dioxide (NO2).,Contractile activity of bronchial smooth muscle was evaluated in vitro.,Isometric contraction of bronchial preparations was measured following electrical stimulation.,Fenspiride administration to rats during the acute stage of COPD (15 days of NO2 exposure) prevented the bronchial constriction induced by NO2.,The bronchodilator effect of a low-dose of fenspiride (0.15 mg/kg) was mediated by interaction with the nerve endings of capsaicin-sensitive C-fibers.,Interaction of fenspiride with C-fibers was shown to prevent initiation of neurogenic inflammation, as evidenced by lack of COPD-like structural changes in the lungs.,The bronchodilator effect of a high-dose of fenspiride (15 mg/kg) was mediated not only by the afferent component, but also involved a direct relaxing effect on smooth muscle cells.,The anti-inflammatory and bronchodilator effects of a low-dose of fenspiride may be used for prevention of COPD development in individuals from high-risk cohorts exposed to aggressive environmental factors. | In asthma, higher chymase positive mast cell (MC-C) numbers are associated with less airway obstruction.,In COPD, the distribution of MC-C and tryptase positive mast cells (MC-T) in central and peripheral airways, and their relation with lung function, is unknown.,We compared MC-T and MC-C distributions in COPD and controls without airflow limitation, and determined their relation with lung function.,Lung tissue sections from 19 COPD patients (median [interquartile range] FEV1% predicted 56 [23-75]) and 10 controls were stained for tryptase and chymase.,Numbers of MC-T and MC-C were determined in different regions of central and peripheral airways and percentage of degranulation was determined.,COPD patients had lower MC-T numbers in the subepithelial area of central airways than controls.,In COPD, MC-T numbers in the airway wall and more specifically in the epithelium and subepithelial area of peripheral airways correlated positively with FEV1/VC (Spearman's rho (rs) 0.47, p = 0.05 and rs 0.48, p = 0.05, respectively); MC-C numbers in airway smooth muscle of peripheral airways correlated positively with FEV1% predicted (rs 0.57, p = 0.02).,Both in COPD patients and controls the percentage of degranulated MC-T and MC-C mast cells was higher in peripheral than in central airways (all p < 0.05), but this was not different between the groups.,More MC-T and MC-C in peripheral airways correlate with better lung function in COPD patients.,It is yet to determine whether this reflects a protective association of mast cells with COPD pathogenesis, or that other explanations are to be considered. | 1 |
Chronic obstructive pulmonary disease (COPD) is a major global cause of morbidity and mortality, projected to become the 3rd cause of disease mortality worldwide by 2020.,COPD is characterized by persistent and not fully reversible airflow limitation that is usually progressive and is associated with an abnormal chronic inflammatory response of the lung to noxious agents including cigarette smoke.,Currently available therapeutic strategies aim to ease COPD symptoms but cannot prevent its progress or regenerate physiological lung structure or function.,The urgently needed new approaches for the treatment of COPD include stem cell therapies among which transplantation of mesenchymal stem cells derived from Wharton’s jelly (WJ-MSCs) emerges as a promising therapeutic strategy because of the unique properties of these cells.,The present review discusses the main biological properties of WJ-MSCs pertinent to their potential application for the treatment of COPD in the context of COPD pathomechanisms with emphasis on chronic immune inflammatory processes that play key roles in the development and progression of COPD. | Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by chronic airway inflammation and emphysema, and is caused by exposure to noxious particles or gases, e.g. cigarette smoke.,Smoking and oxidative stress lead to accelerated formation and accumulation of advanced glycation end products (AGEs), causing local tissue damage either directly or by binding the receptor for AGEs (RAGE).,This study assessed the association of AGEs or RAGE in plasma, sputum, bronchial biopsies and skin with COPD and lung function, and their variance between these body compartments.,Healthy smoking and never-smoking controls (n = 191) and COPD patients (n = 97, GOLD stage I-IV) were included.,Autofluorescence (SAF) was measured in the skin, AGEs (pentosidine, CML and CEL) and sRAGE in blood and sputum by ELISA, and in bronchial biopsies by immunohistochemistry. eQTL analysis was performed in bronchial biopsies.,COPD patients showed higher SAF values and lower plasma sRAGE levels compared to controls and these values associated with decreased lung function (p <0.001; adjusting for relevant covariates).,Lower plasma sRAGE levels significantly and independently predicted higher SAF values (p < 0.001).,One SNP (rs2071278) was identified within a region of 50 kB flanking the AGER gene, which was associated with the gene and protein expression levels of AGER and another SNP (rs2071278) which was associated with the accumulation of AGEs in the skin.,In COPD, AGEs accumulate differentially in body compartments, i.e. they accumulate in the skin, but not in plasma, sputum and bronchial biopsies.,The association between lower sRAGE and higher SAF levels supports the hypothesis that the protective mechanism of sRAGE as a decoy-receptor is impaired in COPD.,The online version of this article (doi:10.1186/s12931-016-0363-2) contains supplementary material, which is available to authorized users. | 1 |
Randomized, controlled trials comparing long-acting muscarinic antagonist (LAMA) efficacy in COPD are limited.,This network meta-analysis (NMA) assessed the relative efficacy of tiotropium 18 µg once-daily (OD) and newer agents (aclidinium 400 µg twice-daily, glycopyrronium 50 µg OD, and umeclidinium 62.5 µg OD).,A systematic literature review identified randomized, controlled trials of adult COPD patients receiving LAMAs.,A NMA within a Bayesian framework examined change from baseline in trough forced expiratory volume in 1 second (FEV1), transitional dyspnea index focal score, St George’s Respiratory Questionnaire score, and rescue medication use.,Twenty-four studies (n=21,311) compared LAMAs with placebo/each other.,Aclidinium, glycopyrronium, tiotropium, and umeclidinium, respectively, demonstrated favorable results versus placebo, for change from baseline (95% credible interval) in 12-week trough FEV1 (primary endpoint: 101.40 mL [77.06-125.60]; 117.20 mL [104.50-129.90]; 114.10 mL [103.10-125.20]; 136.70 mL [104.20-169.20]); 24-week trough FEV1 (128.10 mL [84.10-172.00]; 135.80 mL [123.10-148.30]; 106.40 mL [95.45-117.30]; 115.00 mL [74.51-155.30]); 24-week St George’s Respiratory Questionnaire score (−4.60 [−6.76 to −2.54]; −3.14 [−3.83 to −2.45]; −2.43 [−2.92 to −1.93]; −4.69 [−7.05 to −2.31]); 24-week transitional dyspnea index score (1.00 [0.41-1.59]; 1.01 [0.79-1.22]; 0.82 [0.62-1.02]; 1.00 [0.49-1.51]); and 24-week rescue medication use (data not available; −0.41 puffs/day [−0.62 to −0.20]; −0.52 puffs/day [−0.74 to −0.30]; −0.30 puffs/day [−0.81 to 0.21]).,For 12-week trough FEV1, differences in change from baseline (95% credible interval) were −12.8 mL (−39.39 to 13.93), aclidinium versus tiotropium; 3.08 mL (−7.58 to 13.69), glycopyrronium versus tiotropium; 22.58 mL (−11.58 to 56.97), umeclidinium versus tiotropium; 15.90 mL (−11.60 to 43.15), glycopyrronium versus aclidinium; 35.40 mL (−5.06 to 76.07), umeclidinium versus aclidinium; and 19.50 mL (−15.30 to 54.38), umeclidinium versus glycopyrronium.,Limitations included inhaler-related factors and safety; longer-term outcomes were not considered.,The new LAMAs studied had at least comparable efficacy to tiotropium, the established class standard.,Choice should depend on physician’s and patient’s preference. | Exercise training improves exercise tolerance in chronic obstructive pulmonary disease (COPD).,Tiotropium 18 μg once daily induces sustained bronchodilation throughout the day and reduces hyperinflation, one of the pathophysiological factors contributing to exertional dyspnea in COPD patients.,To determine whether tiotropium enhances the effects of exercise training in patients with COPD.,Multicenter, 25 week randomized, double-blind, placebo-controlled, parallel-group study.,Twelve Italian Pulmonary Units practicing pulmonary rehabilitation.,Two hundred thirty four COPD patients (196 males; mean age: 67.4 ± 7.6; forced expiratory volume at 1 second (FEV1): 41.4 ± 13.0% predicted) were randomised to tiotropium 18 μg or placebo inhalation capsules taken once daily.,Both groups underwent a 8 week pulmonary rehabilitation program (PR) consisting of 3 exercise training session per week.,Baseline, at the end of PR and after 12 weeks, patients completed pulmonary function testing, six minute walking test (6MWT), the Baseline and Transition Dyspnea Index (BDI and TDI), and the St.,George’s Respiratory Questionnaire (SGRQ).,Relative to placebo, tiotropium had larger trough and post-study drug FEV1 responses on all test days.,At the end of and 12 weeks following PR, patients on tiotropium showed no statistically significant differences in 6MWT compared to patients on placebo.,Compared to the period immediately prior to PR, the mean improvement in 6MWT was only 29.7 meters (7.1%) for the combined cohort.,Mean TDI focal scores at the end of PR were 3.60 for tiotropium and 2.25 for placebo (p < 0.01).,At 12 weeks after PR, TDI focal scores were 2.71 for tiotropium and 2.11 for placebo (p = 0.16).,Reduction in all four SGRQ component scores, indicating an improvement in health-related quality of life, was observed for the tiotropium group over the duration of the study compared to placebo but the differences were not statistically significant.,During the study period, there were fewer exacerbations and exacerbation days in the tiotropium group.,Although significant improvements were observed with perceived dyspnea, compared to placebo, the addition of tiotropium to pulmonary rehabilitation did not improve the 6MWT. | 1 |
Patients diagnosed with chronic obstructive pulmonary disease (COPD) in China are commonly prescribed ipratropium plus theophylline (I+T) therapy.,Studies have shown that an inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) combination is also efficacious in reducing symptoms and exacerbations.,This study evaluated the efficacy and tolerability of adding budesonide/formoterol (BUD/FORM) to I+T in Chinese patients with severe COPD.,A randomized, parallel-group, open-label, multicenter phase IV study (Clinical Trials.gov identifier: NCT01415518) was conducted in China.,Patients received either BUD/FORM (160/4.5 µg; two inhalations twice daily [bid] via Turbuhaler®) + I (20 µg per inhalation, two inhalations four times daily) + T (100 mg bid) or I+T alone for 12 weeks.,The primary efficacy variable was change from baseline in predose forced expiratory volume in 1 s (FEV1).,A total of 584 patients were randomized equally between treatment groups.,At the end of the study, the BUD/FORM plus I+T group displayed significant improvements in predose FEV1 versus the I+T group (between-group difference 6.9%; 95% confidence interval [CI]: 4.3, 9.6; p < 0.0001).,Forced vital capacity, inspiratory capacity, peak expiratory flow and health-related quality of life (HRQoL) scores were significantly improved (all p < 0.0001) and exacerbation frequency was reduced (43.5% reduction; rate ratio 0.565, 95% CI 0.325, 0.981; p = 0.0425) with BUD/FORM plus I+T versus I+T alone.,Patients with severe COPD in China treated with BUD/FORM plus I+T showed significant improvements in lung function and HRQoL and a reduction in exacerbations compared with I+T alone.,Both treatments were well tolerated and no safety concerns were noted.,The reviews of this paper are available via the supplemental material section. | Many patients with chronic obstructive pulmonary disease (COPD) are treated with twice daily (BID) inhaled corticosteroids (ICS).,This study evaluated whether daily PM mometasone furoate administered via a dry powder inhaler (MF-DPI) was equally effective compared to twice daily dosing.,In a 52-week, randomized, double-blind, placebo-controlled study, 911 subjects with moderate-to-severe COPD managed without ICS received MF-DPI 800 μg QD PM, MF-DPI 400 μg BID, or placebo.,The change from baseline in postbronchodilator forced expiratory volume in 1 second (FEV1), total COPD symptom scores, and health status as well as the percentage of subjects with a COPD exacerbation were assessed.,Adverse events were recorded.,Mometasone furoate administered via a dry powder inhaler 800 μg QD PM and 400 μg BID significantly increased postbronchodilator FEV1 from baseline (50 mL and 53 mL, respectively, versus a 19 mL decrease for placebo; P < 0.001).,The percentage of subjects exacerbating was significantly lower in the pooled MF-DPI groups than in the placebo group (P = 0.043).,Subjects receiving MF-DPI 400 μg BID reported a statistically significant (19%) reduction in COPD symptom scores compared with placebo (P < 0.001).,Health status as measured with St.,George's Respiratory Questionnaire (SGRQ) improved significantly in all domains (Total, Activity, Impacts, and Symptoms) in the pooled MF-DPI groups versus placebo (P ≤ 0.031).,MF-DPI treatment was well tolerated.,Once-daily MF-DPI improved lung function and health status in subjects with moderate-to-severe COPD and was comparable to BID MF-DPI. | 1 |
There is little data surrounding the survival of patients with chronic obstructive pulmonary disease (COPD) who are admitted to the critical care unit with exacerbation of symptoms.,We conducted a study to measure the in-hospital and intensive care unit (ICU) outcomes of patients admitted with COPD exacerbation, and identified the related prognostic factors.,We performed a retrospective cohort study of patients who were admitted to the adult ICU between January 2006 and July 2011 for COPD exacerbation in King Abdulaziz National Guard Hospital, Al-Hasa, Saudi Arabia.,During the study period, a total of 119 patients were admitted to the ICU with acute respiratory failure attributed to COPD exacerbation.,The mean age was 72 ± 13 years, and 44 (37%) were females.,The main cause of respiratory failure was infection, which occurred in 102 (86%) patients.,Thirty-nine (33%) of the admitted patients were mechanically ventilated, and the median duration was 2.6 (1-42) days.,The median lengths of the ICU and hospital stays were 3 (1-40) and 9 (2-43) days, respectively.,The ICU mortality was 6%, and hospital mortality was 11%.,Low Glasgow Coma Scale on admission, intubation, duration of mechanical ventilation, current smoking, tracheostomy, cardiopulmonary arrest, and the development of acute renal failure were associated with higher hospital mortality.,Early ICU and hospital mortality is low for COPD patients who have been admitted to the ICU with exacerbation.,Low Glasgow Coma Scale scores on admission, intubation, prolonged use of mechanical ventilation, and the development of acute renal failure were identified as risk factors associated with increased hospital mortality. | Chronic obstructive lung disease (COPD) exacerbations are a significant cause of morbidity and mortality.,Data regarding factors which causes or prevents exacerbations is very limited.,The aim of this systematic review is to summarize the results from available studies to identify potential risk factors for hospital admission and/or re-admission among patients experiencing COPD exacerbations.,We undertook a systematic review of the literature.,Potential studies were identified by searching the electronic databases: PubMed, EMBASE, BIOSIS, CINAHL, PsycINFO, Cochrane library, reference lists in trial reports, and other relevant articles.,Seventeen articles that met the predefined inclusion criteria were identified.,Heterogeneity of study designs, risk factors and outcomes restrict the result to only a systematic review and precluded a formal meta-analysis.,In this review, three predictive factors: previous hospital admission, dyspnea and oral corticosteroids were all found to be significant risk factors of readmissions and variables including using long term oxygen therapy, having low health status or poor health related quality of life and not having routine physical activity were all associated with an increased risk of both admission and readmission to hospital.,There are a number of potential modifiable factors that are independently associated with a higher risk of COPD exacerbation requiring admission/readmission to the hospital.,Identifying these factors and the development of targeted interventions could potentially reduce the number and severity of such exacerbations. | 1 |
Asthma and chronic obstructive pulmonary disease (COPD) are both highly prevalent conditions that can coexist in the same individual: the so-called ‘asthma -COPD overlap’ (ACO).,Its prevalence and prognosis vary widely depending on how ACO is defined in each publication, the severity of bronchial obstruction of patients included and the treatment they are receiving.,Although there is a lack of evidence about the biology of ACO, the overlap of both diseases should express a mixture of a Th1 inflammatory pattern (characteristic of COPD) and a Th2 signature (characteristic of asthma).,In this review we support a novel algorithm for ACO diagnosis proposed by the Spanish Respiratory Society (SEPAR), based on a sequential evaluation that considers: (a) the presence of chronic airflow limitation in a smoker or ex-smoker patient ⩾35 years old; (b) a current diagnosis of asthma; and (c) the existence of a very positive bronchodilator test (PBT; ⩾15% and ⩾400 ml) or the presence of eosinophilia in blood (⩾300 eosinophils/μl).,This algorithm can identify those patients who may benefit from a treatment with inhaled corticosteroids (ICSs) and maybe from biological drugs in a near future.,In addition, it is easily applicable in clinical practice.,The major disadvantage is that it groups patients with very different characteristics under the ACO’s umbrella.,In view of this heterogeneity, we recommend a strategy of defining specific and measurable therapeutic objectives for every single patient and identifying the traits that can be treated to achieve those objectives. | Azithromycin (AZM) reduces pulmonary inflammation and exacerbations in patients with COPD having emphysema.,The antimicrobial effects of AZM on the lower airway microbiome are not known and may contribute to its beneficial effects.,Here we tested whether AZM treatment affects the lung microbiome and bacterial metabolites that might contribute to changes in levels of inflammatory cytokines in the airways.,20 smokers (current or ex-smokers) with emphysema were randomised to receive AZM 250 mg or placebo daily for 8 weeks.,Bronchoalveolar lavage (BAL) was performed at baseline and after treatment.,Measurements performed in acellular BAL fluid included 16S rRNA gene sequences and quantity; 39 cytokines, chemokines and growth factors and 119 identified metabolites.,The response to lipopolysaccharide (LPS) by alveolar macrophages after ex-vivo treatment with AZM or bacterial metabolites was assessed.,Compared with placebo, AZM did not alter bacterial burden but reduced α-diversity, decreasing 11 low abundance taxa, none of which are classical pulmonary pathogens.,Compared with placebo, AZM treatment led to reduced in-vivo levels of chemokine (C-X-C) ligand 1 (CXCL1), tumour necrosis factor (TNF)-α, interleukin (IL)-13 and IL-12p40 in BAL, but increased bacterial metabolites including glycolic acid, indol-3-acetate and linoleic acid.,Glycolic acid and indol-3-acetate, but not AZM, blunted ex-vivo LPS-induced alveolar macrophage generation of CXCL1, TNF-α, IL-13 and IL-12p40.,AZM treatment altered both lung microbiota and metabolome, affecting anti-inflammatory bacterial metabolites that may contribute to its therapeutic effects.,NCT02557958. | 1 |
The stigma of non-communicable respiratory diseases (NCRDs), whether perceived or otherwise, can be an important element of a patient’s experience of his/her illness and a contributing factor to poor psychosocial, treatment and clinical outcomes.,This systematic review examines the evidence regarding the associations between stigma-related experiences and patient outcomes, comparing findings across a range of common NCRDs.,Electronic databases and manual searches were conducted to identify original quantitative research published to December 2015.,Articles focussing on adult patient samples diagnosed with asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, lung cancer or mesothelioma, and included a measurement of stigma-related experience (i.e. perceived stigma, shame, blame or guilt), were eligible for inclusion.,Included articles were described for study characteristics, outcome scores, correlates between stigma-related experiences and patient outcomes and methodological rigor.,Twenty-five articles were eligible for this review, with most (n = 20) related to lung cancer.,No articles for cystic fibrosis were identified.,Twenty unique scales were used, with low to moderate stigma-related experiences reported overall.,The stigma-related experiences significantly correlated with all six patient-related domains explored (psychosocial, quality of life, behavioral, physical, treatment and work), which were investigated more widely in COPD and lung cancer samples.,No studies adequately met all criteria for methodological rigor.,The inter-connectedness of stigma-related experiences to other aspects of patient experiences highlight that an integrated approach is needed to address this important issue.,Future studies should adopt more rigorous methodology, including streamlining measures, to provide robust evidence. | Supplemental Digital Content is available in the text,Presently, there is no recommendation on how to assess functional status of chronic obstructive pulmonary disease (COPD) patients.,This study aimed to summarize and systematically evaluate these measures.,Studies on measures of COPD patients’ functional status published before the end of January 2015 were included using a search filters in PubMed and Web of Science, screening reference lists of all included studies, and cross-checking against some relevant reviews.,After title, abstract, and main text screening, the remaining was appraised using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) 4-point checklist.,All measures from these studies were rated according to best-evidence synthesis and the best-rated measures were selected.,A total of 6447 records were found and 102 studies were reviewed, suggesting 44 performance-based measures and 14 patient-reported measures.,The majority of the studies focused on internal consistency, reliability, and hypothesis testing, but only 21% of them employed good or excellent methodology.,Their common weaknesses include lack of checks for unidimensionality, inadequate sample sizes, no prior hypotheses, and improper methods.,On average, patient-reported measures perform better than performance-based measures.,The best-rated patient-reported measures are functional performance inventory (FPI), functional performance inventory short form (FPI-SF), living with COPD questionnaire (LCOPD), COPD activity rating scale (CARS), University of Cincinnati dyspnea questionnaire (UCDQ), shortness of breath with daily activities (SOBDA), and short-form pulmonary functional status scale (PFSS-11), and the best-rated performance-based measures are exercise testing: 6-minute walk test (6MWT), endurance treadmill test, and usual 4-meter gait speed (usual 4MGS).,Further research is needed to evaluate the reliability and validity of performance-based measures since present studies failed to provide convincing evidence.,FPI, FPI-SF, LCOPD, CARS, UCDQ, SOBDA, PFSS-11, 6MWT, endurance treadmill test, and usual 4MGS performed well and are preferable to assess functional status of COPD patients. | 1 |
The economic burden of COPD has not been well studied in China.,This study investigated the total costs caused by COPD and the influencing factors for the high economic burden in urban areas of China.,A cross-sectional study was carried out among 678 COPD patients in four cities in China in 2011.,The average annual direct medical costs (DMCs), direct nonmedical costs (DNMCs), and indirect costs (ICs) on COPD were measured by median and mean (± standard deviation).,Logistic regression model was used to explore factors related to high total costs on COPD.,The median annual DMCs, DNMCs, and ICs per COPD patient were RMB 5565 Yuan (US$ 862), 0 Yuan (US$ 0), and 0 Yuan (US$ 0), respectively, and the mean annual DMCs, DNMCs, and ICs per COPD patient were RMB 11968 (±22422) Yuan [US$ 1853 (±3472)], 539 (±2092) Yuan [US$ 83 (±324)], and 2087 (±8110) Yuan [US$ 323 (±1256)], respectively.,The annual DMCs, DNMCs, and ICs for diagnosed COPD patients were RMB 195.70 billion Yuan (US$ 30.30 billion), 8.78 billion Yuan (US$ 1.36 billion), and 34.10 billion Yuan (US$ 5.28 billion), respectively, in China.,Hospitalization accounted for 56.7% of the total costs.,High economic burden was significantly related to age, acute exacerbations, and disease severity in COPD patients.,COPD posed a heavy economic burden in China.,Measures to delay the disease progression and to reduce the risks of acute exacerbation and hospitalization will help substantially lower the costs for COPD care. | Despite the availability of national and international guidelines, evidence suggests that chronic obstructive pulmonary disease (COPD) treatment is not always prescribed according to recommendations.,This study evaluated the current management of patients with COPD using a large UK primary-care database.,This analysis used electronic patient records and patient-completed questionnaires from the Optimum Patient Care Research Database.,Data on current management were analyzed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group and presence or absence of a concomitant asthma diagnosis, in patients with a COPD diagnosis at ≥35 years of age and with spirometry results supportive of the COPD diagnosis.,A total of 24,957 patients were analyzed, of whom 13,557 (54.3%) had moderate airflow limitation (GOLD Stage 2 COPD).,The proportion of patients not receiving pharmacologic treatment for COPD was 17.0% in the total COPD population and 17.7% in the GOLD Stage 2 subset.,Approximately 50% of patients in both cohorts were receiving inhaled corticosteroids (ICS), either in combination with a long-acting β2-agonist (LABA; 26.7% for both cohorts) or a LABA and a long-acting muscarinic antagonist (LAMA; 23.2% and 19.9%, respectively).,ICS + LABA and ICS + LABA + LAMA were the most frequently used treatments in GOLD Groups A and B.,Of patients without concomitant asthma, 53.7% of the total COPD population and 50.2% of the GOLD Stage 2 subset were receiving ICS.,Of patients with GOLD Stage 2 COPD and no exacerbations in the previous year, 49% were prescribed ICS.,A high proportion of GOLD Stage 2 COPD patients were symptomatic on their current management (36.6% with modified Medical Research Council score ≥2; 76.4% with COPD Assessment Test score ≥10).,COPD is not treated according to GOLD and National Institute for Health and Care Excellence recommendations in the UK primary-care setting.,Some patients receive no treatment despite experiencing symptoms.,Among those on treatment, most receive ICS irrespective of severity of airflow limitation, asthma diagnosis, and exacerbation history.,Many patients on treatment continue to have symptoms. | 1 |
Chronic obstructive pulmonary disease (COPD) is mainly induced by the increased content of particulate matter 2.5 (PM2.5) in the atmosphere.,This study aimed to evaluate the effects of betulinic acid derivative on lung inflammation in a mouse model of chronic obstructive pulmonary disease induced by particulate matter 2.5.,The mice were given a PM2.5 (25 μl) suspension for 7 days by the intranasal route to establish a COPD model.,The content of TNF-α and IL-6 in the BALF samples was measured by commercially available ELISA kits.,The PM2.5-induced higher LDH and ACP levels were significantly alleviated in mouse lung tissues by treatment with betulinic acid derivative.,Treatment with betulinic acid derivative also suppressed PM2.5-induced increase in AKP and ALB levels in mouse lung tissues.,Betulinic acid derivative reversed PM2.5-mediated suppression of SOD activity and elevation of NOS level in mouse BALF.,Moreover, the PM2.5-induced excessive NO and MDA levels in mouse BALF were significantly reduced (P<0.05) by treatment with betulinic acid derivative.,Treatment with betulinic acid derivative improved TNF-α and IL-6 levels in BALF induced by PM2.5 exposure.,Betulinic acid derivative inhibited PM2.5-induced acute inflammatory exudate, alveolar septae damage, and inflammatory cell infiltration in lungs of mice.,In the mouse model of PM2.5-induced COPD, betulinic acid derivative reduced the degree of lung inflammation and downregulated inflammatory mediators.,These findings support the need for further in vivo studies and clinical evaluation of betulinic acid derivative in patients with COPD. | A multitude of epidemiological studies have shown that ambient fine particulate matter 2.5 (diameter < 2.5um; PM2.5) was associated with increased morbidity and mortality of chronic obstructive pulmonary disease (COPD).,However, the underlying associated mechanisms have not yet been elucidated.,We conducted this study to investigate the role of PM2.5 in the development of COPD and associated mechanisms.,We firstly conducted a cross-sectional study in Chinese han population to observe PM2.5 effects on COPD morbidity.,Then, in vitro, we incubated human bronchial epithelial cells to different concentrations of PM2.5 for 24 h.,The expression levels of IL-6 and IL-8 were detected by ELISA and the levels of MMPs, TGF-β1, fibronectin and collagen was determined by immunoblotting.,In vivo, we subjected C57BL/6 mice to chronic prolonged exposure to PM2.5 for 48 weeks to study the influence of PM2.5 exposure on lung function, pulmonary structure and inflammation.,We found that the effect of PM2.5 on COPD morbidity was associated with its levels and that PM2.5 and cigarette smoke could have a synergistic impact on COPD development and progression.,Both vitro and vivo studies demonstrated that PM2.5 exposure could induce pulmonary inflammation, decrease lung function, and cause emphysematous changes.,Furthermore, PM2.5 could markedly aggravated cigarette smoke-induced changes.,In short, we found that prolonged chronic exposure to PM2.5 resulted in decreased lung function, emphysematous lesions and airway inflammation.,Most importantly, long-term PM2.5 exposure exacerbateed cigarette smoke-induced changes in COPD. | 1 |
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. | Chronic obstructive pulmonary disease (COPD) is a progressive and irreversible chronic inflammatory disease of the lung.,The nature of the immune reaction in COPD raises the possibility that IL-17 and related cytokines may contribute to this disorder.,This study analyzed the expression of IL-17A and IL-17F as well as the phenotype of cells producing them in bronchial biopsies from COPD patients.,Bronchoscopic biopsies of the airway were obtained from 16 COPD subjects (GOLD stage 1-4) and 15 control subjects.,Paraffin sections were used for the investigation of IL-17A and IL-17F expression in the airways by immunohistochemistry, and frozen sections were used for the immunofluorescence double staining of IL-17A or IL-17F paired with CD4 or CD8.,In order to confirm the expression of IL-17A and IL-17F at the mRNA level, a quantitative RT-PCR was performed on the total mRNA extracted from entire section or CD8 positive cells selected by laser capture microdissection.,IL-17F immunoreactivity was significantly higher in the bronchial biopsies of COPD patients compared to control subjects (P < 0.0001).,In the submucosa, the absolute number of both IL-17A and IL-17F positive cells was higher in COPD patients (P < 0.0001).,After adjusting for the total number of cells in the submucosa, we still found that more cells were positive for both IL-17A (P < 0.0001) and IL-17F (P < 0.0001) in COPD patients compared to controls.,The mRNA expression of IL-17A and IL-17F in airways of COPD patients was confirmed by RT-PCR.,The expression of IL-17A and IL-17F was co-localized with not only CD4 but also CD8, which was further confirmed by RT-PCR on laser capture microdissection selected CD8 positive cells.,These findings support the notion that Th17 cytokines could play important roles in the pathogenesis of COPD, raising the possibility of using this mechanism as the basis for novel therapeutic approaches. | 1 |
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised many questions about the management of patients with chronic obstructive pulmonary disease (COPD) and whether modifications of their therapy are required.,It has raised questions about recognizing and differentiating coronavirus disease (COVID-19) from COPD given the similarity of the symptoms.,The Global Initiative for Chronic Obstructive Lung Disease (GOLD) Science Committee used established methods for literature review to present an overview of the management of patients with COPD during the COVID-19 pandemic.,It is unclear whether patients with COPD are at increased risk of becoming infected with SARS-CoV-2.,During periods of high community prevalence of COVID-19, spirometry should only be used when it is essential for COPD diagnosis and/or to assess lung function status for interventional procedures or surgery.,Patients with COPD should follow basic infection control measures, including social distancing, hand washing, and wearing a mask or face covering.,Patients should remain up to date with appropriate vaccinations, particularly annual influenza vaccination.,Although data are limited, inhaled corticosteroids, long-acting bronchodilators, roflumilast, or chronic macrolides should continue to be used as indicated for stable COPD management.,Systemic steroids and antibiotics should be used in COPD exacerbations according to the usual indications.,Differentiating symptoms of COVID-19 infection from chronic underlying symptoms or those of an acute COPD exacerbation may be challenging.,If there is suspicion for COVID-19, testing for SARS-CoV-2 should be considered.,Patients who developed moderate-to-severe COVID-19, including hospitalization and pneumonia, should be treated with evolving pharmacotherapeutic approaches as appropriate, including remdesivir, dexamethasone, and anticoagulation.,Managing acute respiratory failure should include appropriate oxygen supplementation, prone positioning, noninvasive ventilation, and protective lung strategy in patients with COPD and severe acute respiratory distress syndrome.,Patients who developed asymptomatic or mild COVID-19 should be followed with the usual COPD protocols.,Patients who developed moderate or worse COVID-19 should be monitored more frequently and accurately than the usual patients with COPD, with particular attention to the need for oxygen therapy. | Chronic Obstructive Pulmonary Disease (COPD) and Non-Alcoholic Fatty Liver Disease (NAFLD) both independently increase cardiovascular risk.,We hypothesized that NAFLD might increase the incidence of cardiovascular disease and death in COPD patients.,The relationship between NAFLD, incident cardiovascular events, and death was assessed in a prospective cohort of COPD patients with 5-year follow-up.,Noninvasive algorithms combining biological parameters (FibroMax®) were used to evaluate steatosis, non-alcoholic steatohepatitis (NASH) and liver fibrosis.,Univariate and multivariate Cox regression models were used to assess the hazard for composite outcome at the endpoint (death or cardiovascular event) for each liver pathology.,In 111 COPD patients, 75% exhibited liver damage with a prevalence of steatosis, NASH and fibrosis of 41%, 37% and 61%, respectively.,During 5-year follow-up, 31 experienced at least one cardiovascular event and 7 died.,In univariate analysis, patients with liver fibrosis had more cardiovascular events and higher mortality (Hazard ratio [95% CI]: 2.75 [1.26; 6.03]) than those with no fibrosis; this remained significant in multivariate analysis (Hazard ratio [95% CI]: 2.94 [1.18; 7.33]).,We also found that steatosis and NASH were not associated with increased cardiovascular events or mortality.,To conclude, early assessment of liver damage might participate to improve cardiovascular outcomes in COPD patients. | 1 |
Despite the availability of guideline recommendations, diagnostic confusion between COPD and asthma appears common, and often it is very difficult to decide whether the obstruction is caused by asthma or COPD in a patient with airway obstruction.,However, there are well-defined features that help in differentiating asthma from COPD in the presence of fixed airflow obstruction.,Nonetheless, the presentations of asthma and COPD can converge and mimic each other, making it difficult to give these patients a diagnosis of either condition.,The association of asthma and COPD in the same patient has been designated mixed asthma-COPD phenotype or overlap syndrome.,However, since the absence of a clear definition and the inclusion of patients with different characteristics under this umbrella term, it may not facilitate treatment decisions, especially in the absence of clinical trials addressing this heterogeneous population.,We are realizing that neither asthma nor COPD are single diseases, but rather syndromes consisting of several endotypes and phenotypes, consequently comprising a spectrum of diseases that must be recognized and adequately treated with targeted therapy.,Therefore, we must treat patients by personalizing therapy on the basis of those treatable traits present in each subject. | Chronic obstructive pulmonary disease (COPD) symptoms in the morning, including dyspnea and sputum production, affect patients’ quality of life and limit their ability to carry out even simple morning activities.,It is now emerging that these symptoms are associated with increased risk of exacerbations and work absenteeism, suggesting that they have a more profound impact on patients than previously thought.,The development of validated patient-reported outcome (PRO) questionnaires to capture patients’ experience of COPD symptoms in the morning is, therefore, vital for establishing effective and comprehensive management strategies.,Although it is well established that long-acting bronchodilators are effective in improving COPD symptoms, the limited available data on their impact on morning symptoms and activities have been obtained with non-validated PRO questionnaires.,In this review, we discuss the impact of COPD symptoms in the morning and available tools used to evaluate them, and highlight specific gaps that need to be addressed to develop standardized instruments able to meet regulatory requirement.,We also present available evidence on the effect of pharmacological therapies on morning symptoms. | 1 |
Skeletal muscle atrophy and dysfunction are common complications in the chronic obstructive pulmonary disease (COPD).,However, the underlying molecular mechanism remains elusive.,Serum response factor (SRF) is a transcription factor which is critical in myocyte differentiation and growth.,In this study, we established a mouse COPD model induced by cigarette smoking (CS) exposure for 24 weeks, with apparent pathophysiological changes, including increased airway resistance, enlarged alveoli, and skeletal muscle atrophy.,Levels of upstream regulators of SRF, striated muscle activator of Rho signaling (STARS), and ras homolog gene family, member A (RhoA) were decreased in quadriceps muscle of COPD mice.,Meanwhile, the nucleic location of SRF was diminished along with its cytoplasmic accumulation.,There was a downregulation of the target muscle-specific gene, Igf1.,These results suggest that the CS is one of the major causes for COPD pathogenesis, which induces the COPD-associated skeletal muscle atrophy which is closely related to decreasing SRF nucleic translocation, consequently downregulating the SRF target genes involved in muscle growth and nutrition.,The STARS/RhoA signaling pathway might contribute to this course by impacting SRF subcellular distribution. | The adaptor protein p66Shc regulates intracellular oxidant levels through the modulation of a forkhead-related transcription factor (FOXO3a).,The genetic ablation of p66Shc (p66Shc-/-) renders mice resistant to oxidative stress and p53-dependent apoptosis.,We investigated whether p66Shc ablation in mice modifies lung cellular and molecular responses to cigarette smoke (CS) exposure.,No differences between wild type (WT) and p66Shc-/- mice were observed in terms of inflammation and oxidant burden after acute CS exposure; however,p66Shc ablation modifies specific features of chronic inflammation induced by repeated exposure to CS.,Unlike WT mice, p66Shc-/- mice did not develop emphysema, showing protection toward oxidative damage to DNA and apoptosis as revealed by a trivial 8-hydroxyguanosine staining and faint TUNEL and caspase-3 positivity on alveolar epithelial cells.,Unexpectedly, CS exposure in p66Shc-/- mice resulted in respiratory bronchiolitis with fibrosis in surrounded alveoli.,Respiratory bronchiolitis was characterized by peribronchiolar infiltrates of lymphocytes and histiocytes, accumulation of ageing pigmented macrophages within and around bronchioles, and peribronchiolar fibrosis.,The blockage of apoptosis interferes with the macrophage “clearance” from alveolar spaces, favouring the accumulation of aging macrophages into alveoli and the progressive accumulation of iron pigment in long-lived senescent cells.,The presence of areas of interstitial and alveolar fibrosis in peripheral parenchyma often accompanied the bronchiolar changes.,Macrophages from smoking p66Shc-/- mice elaborate M2 cytokines (i.e., IL-4 and IL-13) and enzymes (i.e., chitinase and arginase I), which can promote TGF-beta expression, collagen deposition, and fibrosis in the surrounding areas.,We demonstrate here that resistance to oxidative stress and p53-dependent apoptosis can modify tissue responses to CS caused by chronic inflammation without influencing early inflammatory response to CS exposure. | 1 |
Indacaterol/glycopyrronium (IND/GLY) is approved for maintenance treatment of adult patients with COPD.,This post hoc analysis explored the efficacy and safety of IND/GLY versus salmeterol/fluticasone (SFC) in symptomatic (Global Initiative for Chronic Obstructive Lung Disease [GOLD] B and GOLD D) patients with moderate-to-severe COPD.,Data from LANTERN and ILLUMINATE studies were pooled and analyzed.,In both studies, symptomatic COPD patients were randomized to once-daily IND/GLY 110 μg/50 μg or twice-daily SFC 50 μg/500 μg.,End points were pre-dose trough forced expiratory volume in one second (FEV1), standardized area under the curve for FEV1 from 0 to 12 hours (FEV1 AUC0-12 hours), peak FEV1, peak forced vital capacity (FVC), pre-dose trough FVC, Transition Dyspnea Index (TDI) total score, St George’s Respiratory Questionnaire total score, rescue medication use and safety.,A total of 1,263 patients were classified as either GOLD B (n=809) or GOLD D (n=454).,At week 26, IND/GLY demonstrated statistically significant improvement in all lung function parameters versus SFC in patients in both the GOLD B and GOLD D subgroups.,TDI total score and rescue medication use were significantly improved with IND/GLY versus SFC in the overall population and in the GOLD B (TDI total score only) and GOLD D (rescue medication only) subgroups.,IND/GLY also reduced the rate of exacerbations in the pooled population.,Overall safety profile was comparable with a higher incidence of pneumonia in the SFC-treated group.,In this pooled analysis, IND/GLY demonstrated superior efficacy compared with SFC in patients in the GOLD B and GOLD D subgroups and supported its use in symptomatic COPD patients. | NVA237 is a once-daily dry-powder formulation of the long-acting muscarinic antagonist glycopyrronium bromide in development for the treatment of chronic obstructive pulmonary disease (COPD).,The glycopyrronium bromide in COPD airways clinical study 1 (GLOW1) evaluated the efficacy, safety and tolerability of NVA237 in patients with moderate-to-severe COPD.,Patients with COPD with a smoking history of ≥ 10 pack-years, post-bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and ≥ 30% predicted normal and FEV1/forced vital capacity < 0.70 were enrolled.,Patients were randomized to double-blind treatment with NVA237 50 μg once daily or placebo for 26 weeks with inhaled/intranasal corticosteroids or H1 antagonists permitted in patients stabilized on them prior to study entry.,The primary outcome measure was trough FEV1 at Week 12.,A total of 822 patients were randomized to NVA237 (n = 552) or placebo (n = 270).,Least squares mean (± standard error) trough FEV1 at Week 12 was significantly higher in patients receiving NVA237 (1.408 ± 0.0105 L), versus placebo (1.301 ± 0.0137 L; treatment difference 108 ± 14.8 mL, p < 0.001).,Significant improvements in trough FEV1 were apparent at the end of Day 1 and sustained through Week 26.,FEV1 was significantly improved in the NVA237 group versus placebo throughout the 24-hour periods on Day 1 and at Weeks 12 and 26, and at all other visits and timepoints.,Transition dyspnoea index focal scores and St.,George's Respiratory Questionnaire scores were significantly improved with NVA237 versus placebo at Week 26, with treatment differences of 1.04 (p < 0.001) and-2.81 (p = 0.004), respectively.,NVA237 significantly reduced the risk of first moderate/severe COPD exacerbation by 31% (p = 0.023) and use of rescue medication by 0.46 puffs per day (p = 0.005), versus placebo.,NVA237 was well tolerated and had an acceptable safety profile, with a low frequency of cardiac and typical antimuscarinic adverse effects.,Once-daily NVA237 was safe and well tolerated and provided rapid, sustained improvements in lung function, improvements in dyspnoea, and health-related quality of life, and reduced the risk of exacerbations and the use of rescue medication.,ClinicalTrials.gov: NCT01005901 | 1 |
Two replicate, multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase III studies investigated the long-term efficacy and safety of once-daily olodaterol via Respimat® versus placebo and formoterol over 48 weeks in patients with moderate to very severe chronic obstructive pulmonary disease receiving usual-care background therapy.,Patients received once-daily olodaterol 5 or 10 μg, twice-daily formoterol 12 μg, or placebo.,Co-primary end points were forced expiratory volume in 1 second (FEV1) area under the curve from 0-3 hours response, FEV1 trough response, and Mahler transition dyspnea index total score after 24 weeks; secondary end points included St George’s Respiratory Questionnaire.,Overall, 904 (Study 1222.13) and 934 (Study 1222.14) patients received treatment.,Olodaterol significantly improved FEV1 area under the curve from 0-3 hours versus placebo in both studies (with olodaterol 5 μg, 0.151 L and 0.129 L; with olodaterol 10 μg, 0.165 L and 0.154 L; for all comparisons P<0.0001) and FEV1 trough responses versus placebo (0.053-0.085 L; P<0.01), as did formoterol.,Primary analysis revealed no significant difference in transition dyspnea index focal score for any active treatment versus placebo.,Post hoc analysis using pattern mixture modeling (accounting for discontinuations) demonstrated statistical significance for olodaterol versus placebo.,St George’s Respiratory Questionnaire total score was significantly improved with olodaterol, but not formoterol, versus placebo.,No safety signals were identified from adverse-event or other safety data.,Once-daily olodaterol 5 μg and 10 μg is efficacious in patients with moderate to very severe chronic obstructive pulmonary disease on usual-care maintenance therapy, with a satisfactory safety profile. | The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD).,In two double-blind, 52-week studies, ACCLAIM/COPD I (n = 843) and II (n = 804), patients were randomised to inhaled aclidinium 200 μg or placebo once-daily.,Patients were required to have a post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of ≤70% and FEV1 <80% of the predicted value.,The primary endpoint was trough FEV1 at 12 and 28 weeks.,Secondary endpoints were health status measured by St George's Respiratory Questionnaire (SGRQ) and time to first moderate or severe COPD exacerbation.,At 12 and 28 weeks, aclidinium improved trough FEV1 versus placebo in ACCLAIM/COPD I (by 61 and 67 mL; both p < 0.001) and ACCLAIM/COPD II (by 63 and 59 mL; both p < 0.001).,More patients had a SGRQ improvement ≥4 units at 52 weeks with aclidinium versus placebo in ACCLAIM/COPD I (48.1% versus 39.5%; p = 0.025) and ACCLAIM/COPD II (39.0% versus 32.8%; p = 0.074).,The time to first exacerbation was significantly delayed by aclidinium in ACCLAIM/COPD II (hazard ratio [HR] 0.7; 95% confidence interval [CI] 0.55 to 0.92; p = 0.01), but not ACCLAIM/COPD I (HR 1.0; 95% CI 0.72 to 1.33; p = 0.9).,Adverse events were minor in both studies.,Aclidinium is effective and well tolerated in patients with moderate to severe COPD.,ClinicalTrials.gov: NCT00363896 (ACCLAIM/COPD I) and NCT00358436 (ACCLAIM/COPD II). | 1 |
Chronic obstructive pulmonary disease (COPD) imposes a substantial burden on individuals with the disease, which can include a range of symptoms (breathlessness, cough, sputum production, wheeze, chest tightness) of varying severities.,We present an overview of the biomedical literature describing reported relationships between COPD symptoms and disease burden in terms of quality of life, health status, daily activities, physical activity, sleep, comorbid anxiety, and depression, as well as risk of exacerbations and disease prognosis.,In addition, the substantial variability of COPD symptoms encountered (morning, daytime, and nighttime) is addressed and their implications for disease burden considered.,The findings from this narrative review, which mainly focuses on real-world and observational studies, demonstrate the impact of COPD symptoms on the burden of disease and that improved recognition and understanding of their impact is central to alleviating this burden. | Daily diaries are often used to collect data on disease activity, but are burdensome and compliance may be poor.,Their use in chronic obstructive pulmonary disease (COPD) and impact on the prevention and treatment of exacerbations is poorly researched.,We investigated diary-keeping in COPD and ascertained items that best predicted emergency attendances for exacerbations.,Participants in the active limb of a clinical trial in COPD kept daily diaries rating breathlessness, cough, sputum, physical activity, and use of reliever medication.,Data on 55 participants, 67% of whom were female, showed that overall compliance with diary-keeping was 62%.,Participants educated to primary school level only had lower compliance (P = 0.05).,Twenty patients had at least one emergency attendance, in whom the relative risk of an acute exacerbation for an increase in item score rose from six days prior to hospitalization, most sharply in the last two days.,Even for optimal combinations of items, the positive predictive value was poor, the best combination being cough, activity level, and inhaler use.,Good compliance can be achieved using daily diaries in COPD, although this is worse in those with a poor educational level.,Diary-keeping is not accurate in predicting acute exacerbations, but could be substantially simplified without loss of efficiency. | 1 |
Expression of β2-microglobulin (β2M) is involved in fibrosis progression in kidney, liver, and heart.,In this case-controlled retrospective study, we investigated the role of β2M in the development of pulmonary fibrosis in patients with chronic obstructive pulmonary disease (COPD).,Analysis of 450 COPD patients revealed that patients with decreased pulmonary diffusing capacity (DLCO) had increased β2M serum levels.,Compared to patients with lower β2M serum levels, patients with increased β2M levels exhibited increased alveolar wall/septal thickening and lung tissue β2M expression.,In addition, patients with increased β2M levels had increased lung expression of TGF-β1, Smad4, and a-SMA.,Animal experiments showed that increased β2M expression resulted in epithelial-mesenchymal transition (EMT), alveolar wall/septal thickening, and pulmonary fibrosis in a rat COPD model.,Together, these results indicate that β2M serum levels may serve as a new indicator for assessment of pulmonary diffusion function and pulmonary fibrosis severity in clinical practice and may provide a potential target for treatment of pulmonary fibrosis in the future. | Epithelial-mesenchymal transition (EMT) is a process associated with airway remodeling in chronic obstructive pulmonary disease (COPD), which leads to progressive pulmonary destruction.,Panax ginseng is a traditional herbal medicine that has been shown to improve pulmonary function and exercise capacity in patients with COPD.,Ginsenoside Rg1 is one of the main active components and was shown to inhibit oxidative stress and inflammation.,The present study investigated the hypothesis that ginsenoside Rg1 attenuates EMT in COPD rats induced by cigarette smoke (CS) and human bronchial epithelial (HBE) cells exposed to cigarette smoke extract (CSE).,Our data showed that CS or CSE exposure increased expression of the mesenchymal marker α-smooth muscle actin (α-SMA) and decreased expression of the epithelial marker epithelial cadherin (E-cad) in both lung tissues and HBE cells, which was markedly suppressed by ginsenoside Rg1.,Importantly, CS-induced upregulation of TGF-β1/Smad pathway components, including TGF-β1, TGF-βR1, phospho-Smad2, and phospho-Smad3, was also inhibited by ginsenoside Rg1.,Additionally, ginsenoside Rg1 mimicked the effect of SB525334, a TGF-βR1-Smad2/3 inhibitor, on suppression of EMT in CSE-induced HBE cells.,Collectively, we concluded that ginsenoside Rg1 alleviates CS-induced pulmonary EMT, in both COPD rats and HBE cells, via inhibition of the TGF-β1/Smad pathway. | 1 |
To establish the dose−response for pharmacodynamics (bronchodilatation), safety and pharmacokinetics for a nebulized formulation of the long acting muscarinic antagonist glycopyrrolate (EP-101) with a high efficiency nebulizer in patients with chronic obstructive pulmonary disease (COPD).,Patients with moderate to severe COPD (GOLD II/III), with reversible lung function, were enrolled into this randomized, double-blind, placebo-controlled, six period crossover study (n = 42).,Patients received single doses of EP-101 (12.5-400 μg) and placebo via a high efficiency nebulizer (eFlow® PARI nebulizer), with washout between treatments.,Plasma pharmacokinetics were assessed in a subset of patients (n = 11).,All treatments were well tolerated with similar adverse event rates reported with placebo and at all doses.,There were no clinically relevant changes in heart rate, systolic and diastolic blood pressure or in ECG parameters including QTc interval.,Following treatment with EP-101 at all doses there was a rapid bronchodilator response within 5 min.,Significant improvements in mean change from baseline FEV1 at 24 h were reported at doses ≥50 μg compared with placebo, with a clear dose−response relationship.,Mean changes in FEV1 were 0.10 l (95% CI 0.06, 0.14) and 0.12 l (95% CI 0.08, 0.16) for 100 μg and 200 μg, respectively.,Single doses of EP-101 ranging from 12.5 μg to 400 μg were well tolerated.,EP-101 delivered by high efficiency nebulizer device produced a rapid onset of bronchodilatation with clinically meaningful improvements in lung function maintained over a 24 h period at all doses >50 μg. | Arformoterol tartrate (arformoterol, 15 μg bid) is a nebulized long-acting β2-agonist approved for maintenance treatment of COPD.,This was a multicenter, double-blind, randomized, placebo-controlled study.,Patients (aged ≥ 40 years with baseline FEV1 ≤ 65% predicted, FEV1 > 0.50 L, FEV1/FVC ≤ 70%, and ≥ 15 pack-year smoking history) received arformoterol (n = 420) or placebo (n = 421) for 1 year.,The primary assessment was time from randomization to respiratory death or first COPD exacerbation-related hospitalization.,Among 841 patients randomized, 103 had ≥ 1 primary event (9.5% vs 15.0%, for arformoterol vs placebo, respectively).,Patients who discontinued treatment for any reason (39.3% vs 49.9%, for arformoterol vs placebo, respectively) were followed for up to 1 year postrandomization to assess for primary events.,Fewer patients receiving arformoterol than placebo experienced COPD exacerbation-related hospitalizations (9.0% vs 14.3%, respectively).,Twelve patients (2.9%) receiving arformoterol and 10 patients (2.4%) receiving placebo died during the study.,Risk for first respiratory serious adverse event was 50% lower with arformoterol than placebo (P = .003).,Numerically more patients on arformoterol (13; 3.1%) than placebo (10; 2.4%) experienced cardiac serious adverse events; however, time-to-first cardiac serious adverse event was not significantly different.,Improvements in trough FEV1 and FVC were greater with arformoterol (least-squares mean change from baseline vs placebo: 0.051 L, P = .030 and 0.075 L, P = .018, respectively).,Significant improvements in quality of life (overall St.,George’s Hospital Respiratory Questionnaire and Clinical COPD Questionnaire) were observed with arformoterol vs placebo (P < .05).,Arformoterol demonstrated an approximately 40% lower risk of respiratory death or COPD exacerbation-related hospitalization over 1 year vs placebo.,Arformoterol was well-tolerated and improved lung function vs placebo.,ClinicalTrials.gov; No.: NCT00909779; URL: www.clinicaltrials.gov | 1 |
COPD is a progressive disease characterized by exacerbations and a decline in health status and lung function.,Clinically important deterioration (CID) is a composite endpoint used to evaluate treatment efficacy.,This analysis evaluated the impact of a direct switch to once-daily indacaterol/glycopyrronium 110/50 µg (IND/GLY) from previous monotherapy with a long-acting β2-agonist (LABA) or long-acting muscarinic antagonist (LAMA) or with an LABA and an inhaled corticosteroid (LABA + ICS) on reducing CID.,CRYSTAL was a 12-week, prospective, multicenter, randomized, open-label study conducted in clinical practice settings.,Three definitions of CID (D1-D3) were used, including: 1) ≥100 mL decrease in trough forced expiratory volume in 1 second (FEV1), 2) ≥1 point decrease in transition dyspnea index (TDI) and/or ≥0.4 points increase in clinical COPD questionnaire score (CCQ), or 3) an acute moderate/severe exacerbation (AECOPD).,In D1 and D2, either TDI or CCQ was evaluated along with FEV1 and AECOPD, whereas in D3, all 4 parameters were included.,ClinicalTrials.gov number: NCT01985334.,Of the 2,159 patients analyzed, 1,622 switched to IND/GLY and 537 continued their baseline treatments.,The percentage of patients with a CID was significantly lower after a direct switch to IND/GLY versus LABA or LAMA using all 3 CID definitions (D1: odds ratio [OR] 0.41 [95% CI: 0.30-0.55]; D2: OR 0.41 [95% CI: 0.31-0.55]; D3: OR 0.39 [95% CI: 0.29-0.52]).,Compared with LABA + ICS, IND/GLY also reduced the risk of CID (D1: OR 0.76 [95% CI: 0.56-1.02]; D2: OR 0.75 [95% CI: 0.56-1.00]; D3: OR 0.67 [95% CI: 0.51-0.89]).,In this analysis, IND/GLY reduced the risk of a CID in moderate COPD patients after direct switch from LABA + ICS or LABA or LAMA in real-life clinical practice. | The aim of the study was to examine the longitudinal change in quality of life components of patients with chronic obstructive pulmonary disease (COPD).,In the Hokkaido COPD Cohort Study, 261 subjects were appropriately treated and followed over 5 years with a 74% follow-up rate at the end.,The longitudinal changes in St George’s Respiratory Questionnaire (SGRQ) scores were annually evaluated with forced expiratory volume in 1 second (FEV1).,The subjects were classified into the rapid decliners, slow decliners, and sustainers based on ΔFEV1/year.,The activity component of SGRQ generally deteriorated over time, and its annual decline was the greatest in the rapid decliners (<25th percentile).,In contrast, the symptom component improved significantly year by year in the sustainers (>75 percentile), and it did not deteriorate even in the rapid decliners.,Of the baseline data, predictors for worsening of the activity component were older age and lower body mass index.,Larger reversibility was related to symptom component improvement.,Of the follow-up data, ΔFEV1/year was the best predictor for worsening of the components of SGRQ.,Continuous smoking was another factor for worsening of the activity component.,For the symptom component, a history of exacerbation by admission definition was the determinant of its deterioration, whereas use of beta agonists was related to improvement.,The longitudinal changes of quality of life and their determinants are markedly different and independent between its components.,The activity component of SGRQ generally deteriorated over years, while the symptom component rather improved in some patients with COPD under appropriate treatment. | 1 |
Severe chronic obstructive pulmonary disease (COPD) is often associated with secondary pulmonary hypertension (PH), which worsens prognosis.,PH can be lowered by oxygen, but also by inhaled nitric oxide (NO), which has the potential to improve the health status of these patients.,NO is an important mediator in vascular reactions in the pulmonary circulation.,Oral compounds can act through NO-mediated pathways, but delivering pulsed inhaled NO (iNO) directly to the airways and pulmonary vasculature could equally benefit patients.,Therefore, a proof-of-concept study was performed to quantify pulmonary blood vessel caliber changes after iNO administration using computed tomography (CT)-based functional respiratory imaging (FRI).,Six patients with secondary PH due to COPD received “pulsed” iNO in combination with oxygen for 20 minutes via a nasal cannula.,Patients underwent a high-resolution CT scan with contrast before and after iNO.,Using FRI, changes in volumes of blood vessels and associated lobes were quantified.,Oxygen saturation and blood pressure were monitored and patients were asked about their subjective feelings.,Pulmonary blood vessel volume increased by 7.06%±5.37% after iNO.,A strong correlation (Ω20=0.32, P=0.002) was obtained between ventilation and observed vasodilation, suggesting that using the pulsed system, iNO is directed toward the ventilated zones, which consequently experience more vasodilation.,Patients did not develop oxygen desaturation, remained normotensive, and perceived an improvement in their dyspnea sensation.,Inhalation of pulsed NO with oxygen causes vasodilation in the pulmonary circulation of COPD patients, mainly in the well-ventilated areas.,A high degree of heterogeneity was found in the level of vasodilation.,Patients tend to feel better after the treatment.,Chronic use trials are warranted. | Chronic bronchitis (CB) has been related to poor outcomes in Chronic Obstructive Pulmonary Disease (COPD).,From a clinical standpoint, we have shown that subjects with CB in a group with moderate to severe airflow obstruction were younger, more likely to be current smokers, male, Caucasian, had worse health related quality of life, more dyspnea, and increased exacerbation history compared to those without CB.,We sought to further refine our clinical characterization of chronic bronchitics in a larger cohort and analyze the CT correlates of CB in COPD subjects.,We hypothesized that COPD patients with CB would have thicker airways and a greater history of smoking, acute bronchitis, allergic rhinitis, and occupational exposures compared to those without CB.,We divided 2703 GOLD 1-4 subjects in the Genetic Epidemiology of COPD (COPDGene®) Study into two groups based on symptoms: chronic bronchitis (CB+, n = 663, 24.5%) and no chronic bronchitis (CB-, n = 2040, 75.5%).,Subjects underwent extensive clinical characterization, and quantitative CT analysis to calculate mean wall area percent (WA%) of 6 segmental airways was performed using VIDA PW2 (http://www.vidadiagnostics.com).,Square roots of the wall areas of bronchi with internal perimeters 10 mm and 15 mm (Pi10 and Pi15, respectively), % emphysema, %gas trapping, were calculated using 3D Slicer (http://www.slicer.org).,There were no differences in % emphysema (11.4 ± 12.0 vs.,12.0 ± 12.6%, p = 0.347) or % gas trapping (35.3 ± 21.2 vs.,36.3 ± 20.6%, p = 0.272) between groups.,Mean segmental WA% (63.0 ± 3.2 vs.,62.0 ± 3.1%, p < 0.0001), Pi10 (3.72 ± 0.15 vs.,3.69 ± 0.14 mm, p < 0.0001), and Pi15 (5.24 ± 0.22 vs.,5.17 ± 0.20, p < 0.0001) were greater in the CB + group.,Greater percentages of gastroesophageal reflux, allergic rhinitis, histories of asthma and acute bronchitis, exposures to dusts and occupational exposures, and current smokers were seen in the CB + group.,In multivariate binomial logistic regression, male gender, Caucasian race, a lower FEV1%, allergic rhinitis, history of acute bronchitis, current smoking, and increased airway wall thickness increased odds for having CB.,Histories of asthma, allergic rhinitis, acute bronchitis, current smoking, a lower FEV1%, Caucasian race, male gender, and increased airway wall thickness are associated with CB.,These data provide clinical and radiologic correlations to the clinical phenotype of CB. | 1 |
Inefficient clearance of copious respiratory secretion is a cause of non-invasive positive pressure ventilation (NPPV) failure, especially in chronic respiratory patients with community-acquired-pneumonia (CAP) and impaired consciousness.,We postulated that in such a clinical scenario, when intubation and conventional mechanical ventilation (CMV) are strongly recommended, the suction of secretions with fiberoptic bronchoscopy (FBO) may increase the chance of NPPV success.,The objective of this pilot study was, firstly, to verify the safety and effectiveness of early FBO during NPPV and, secondly, to compare the hospital outcomes of this strategy versus a CMV-based strategy in patients with decompensated chronic obstructive pulmonary disease (COPD) due to CAP who are not appropriate candidates for NPPV because of inefficient mucous clearance and hypercapnic encephalopathy (HE).,This is a 12-month prospective matched case-control study performed in one respiratory semi-intensive care unit (RSICU) with expertise in NPPV and in one intensive care unit (ICU).,Fifteen acutely decompensated COPD patients with copious secretion retention and HE due to CAP undergoing NPPV in RSICU, and 15 controls (matched for arterial blood gases, acute physiology and chronic health evaluation score III, Kelly-Matthay scale, pneumonia extension and severity) receiving CMV in the ICU were studied.,Two hours of NPPV significantly improved arterial blood gases, Kelly and cough efficiency scores without FBO-related complications.,NPPV avoided intubation in 12/15 patients (80%).,Improvement in arterial blood gases was similar in the two groups, except for a greater PaO2/fraction of inspired oxygen ratio with CMV.,The rates of overall and septic complications, and of tracheostomy were lower in the NPPV group (20%, 20%, and 0%) versus the CMV group (80%, 60%, and 40%; P < 0.05).,Hospital mortality, duration of hospitalisation and duration of ventilation were similar in the two groups.,In patients with decompensated COPD due to CAP who are candidates for CMV because of HE and inability to clear copious secretions, NPPV with early therapeutic FBO performed by an experienced team is a feasible, safe and effective alternative strategy. | We hypothesized that the use of intrapulmonary percussive ventilation (IPV), a technique designed to improve mucus clearance, could prove effective in avoiding further deterioration in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) with mild respiratory acidosis.,The study was performed in a medical intensive care unit of a university hospital.,Thirty-three patients with exacerbations of COPD with a respiratory frequency ≥ 25/min, a PaCO2 > 45 Torr and 7.35 ≤ pH ≤ 7.38 were included in the study.,Patients were randomly assigned to receive either standard treatment (control group) or standard treatment plus IPV (IPV group).,The IPV group underwent two daily sessions of 30 minutes performed by a chest physiotherapist through a full face mask.,The therapy was considered successful when both worsening of the exacerbation and a decrease in pH to under 7.35, which would have required non-invasive ventilation, were avoided.,Thirty minutes of IPV led to a significant decrease in respiratory rate, an increase in PaO2 and a decrease in PaCO2 (p < 0.05).,Exacerbation worsened in 6 out of 17 patients in the control group versus 0 out of 16 in the IPV group (p < 0.05).,The hospital stay was significantly shorter in the IPV group than in the control group (6.8 ± 1.0 vs.,7.9 ± 1.3 days, p < 0.05).,IPV is a safe technique and may prevent further deterioration in patients with acute exacerbations of COPD with mild respiratory acidosis. | 1 |
Current pharmacological therapies for COPD improve quality of life and symptoms and reduce exacerbations.,Given the progressive nature of COPD, it is arguably more important to understand whether the available therapies are able to delay clinical deterioration; the concept of “clinically important deterioration” (CID) has therefore been developed.,We evaluated the efficacy of the single-inhaler triple combination beclometasone dipropionate, formoterol fumarate, and glycopyrronium (BDP/FF/G), using data from three large 1-year studies.,The studies compared BDP/FF/G to BDP/FF (TRILOGY), tiotropium (TRINITY), and indacaterol/glycopyrronium (IND/GLY; TRIBUTE).,All studies recruited patients with symptomatic COPD, FEV1 <50%, and an exacerbation history.,We measured the time to first CID and to sustained CID, an endpoint combining FEV1, St George’s Respiratory Questionnaire (SGRQ), moderate-to-severe exacerbations, and death.,The time to first CID was based on the first occurrence of any of the following: a decrease of ≥100 mL from baseline in FEV1, an increase of ≥4 units from baseline in SGRQ total score, the occurrence of a moderate/severe COPD exacerbation, or death.,The time to sustained CID was defined as: a CID in FEV1 and/or SGRQ total score maintained at all subsequent visits, an exacerbation, or death.,Extrafine BDP/FF/G significantly extended the time to first CID vs BDP/FF (HR 0.61, P<0.001), tiotropium (0.72, P<0.001), and IND/GLY (0.82, P<0.001), and significantly extended the time to sustained CID vs BDP/FF (HR 0.64, P<0.001) and tiotropium (0.80, P<0.001), with a numerical extension vs IND/GLY.,In patients with symptomatic COPD, FEV1 <50%, and an exacerbation history, extrafine BDP/FF/G delayed disease deterioration compared with BDP/FF, tiotropium, and IND/GLY.,The studies are registered in ClinicalTrials.gov: TRILOGY, NCT01917331; TRINITY, NCT01911364; TRIBUTE, NCT02579850. | Minimizing the risk of disease progression and exacerbations is the key goal of COPD management, as these are well-established indicators of poor COPD prognosis.,We developed a novel composite end point assessing three important aspects (lung function, health status, and exacerbations) of worsening in COPD.,The objective was to determine whether dual bronchodilation with umeclidinium/vilanterol (UMEC/VI) reduces clinically important deteriorations (CIDs) in COPD versus placebo or bronchodilator monotherapy.,This study is a post hoc analysis of two 24-week trials comparing UMEC/VI 62.5/25 µg with UMEC 62.5 µg, VI 25 µg, or placebo (Study A; NCT01313650), or UMEC/VI 62.5/25 µg with tiotropium (TIO) 18 µg (Study B; NCT01777334) in patients with symptomatic COPD, without a history of frequent exacerbations.,Deterioration was assessed as the time to a first CID, a composite measure defined as a decrease of ≥100 mL in trough forced expiratory volume in 1 second or ≥4-unit increase in St George’s Respiratory Questionnaire total score or an on-treatment moderate-to-severe COPD exacerbation.,In Study A, fewer patients experienced a first CID with UMEC/VI (44%) versus UMEC (50%), VI (56%), and placebo (75%).,The risk of a first CID was reduced with UMEC/VI (hazard ratio [HR]: 0.37 [95% confidence interval, CI: 0.30, 0.45]), UMEC (HR: 0.46 [95% CI: 0.38, 0.56]), and VI (HR: 0.55 [95% CI: 0.45, 0.66]; all P<0.001) versus placebo, and with UMEC/VI versus UMEC (HR: 0.80 [95% CI: 0.65, 0.97]; P<0.05) and versus VI (HR: 0.67 [95% CI: 0.55, 0.81]; P<0.001).,In Study B, fewer patients experienced a first CID with UMEC/VI (41%) versus TIO (59%).,UMEC/VI reduced the risk of a first composite CID by 43% versus TIO (HR: 0.57 [95% CI: 0.47, 0.69]; P<0.001).,This exploratory analysis, using a new assessment of clinical deterioration in COPD, revealed that a majority of symptomatic patients with low exacerbation risk experienced a deterioration during the 24-week study periods.,UMEC/VI reduces the risk of a first CID versus placebo or bronchodilator monotherapy. | 1 |
COPD is a progressive condition involving chronic inflammation and parenchymal destruction with resulting airflow limitation.,COPD is associated with worsening airflow limitation over time and increased frequency of COPD exacerbations, leading to increased mortality and morbidity.,The effects of COPD extend beyond the lungs, as multiple comorbidities may occur with COPD, including cardiovascular disease, diabetes mellitus, osteoporosis, depression, and pneumonia.,COPD exacerbations are associated with a rapid worsening of baseline symptoms that requires prompt management and may necessitate hospitalization in the case of a severe episode.,Patients with COPD exacerbations require urgent management of symptoms to prevent further worsening, and preventative steps may be taken to help reduce the number and frequency of future exacerbations.,Roflumilast is a potent and selective inhibitor of the enzyme phosphodiesterase-4 that targets the systemic inflammation associated with COPD.,Roflumilast has a variety of anti-inflammatory effects including decreasing inflammatory mediators and the expression of cell surface markers and inhibition of apoptosis.,Several clinical trials evaluating roflumilast in the treatment of COPD have demonstrated significant improvements from baseline versus placebo in lung function, including increases in mean pre- and postbronchodilator forced expiratory volume in 1 second and forced vital capacity.,Data suggest that roflumilast reduces moderate to severe exacerbations with the benefit most well established in patients with severe disease.,Given this evidence, roflumilast, as part of a combination regimen with long-acting bronchodilators, appears to be a reasonable treatment option for patients with severe to very severe COPD associated with chronic bronchitis and a history of exacerbations. | To quantify the relationship between severity of chronic obstructive pulmonary disease (COPD) as expressed by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and the annual exacerbation frequency in patients with COPD.,We performed a systematic literature review to identify randomized controlled trials and cohort studies reporting the exacerbation frequency in COPD patients receiving usual care or placebo.,Annual frequencies were determined for total exacerbations defined by an increased use of health care (event-based), total exacerbations defined by an increase of symptoms, and severe exacerbations defined by a hospitalization.,The association between the mean forced expiratory volume in one second (FEV1)% predicted of study populations and the exacerbation frequencies was estimated using weighted log linear regression with random effects.,The regression equations were applied to the mean FEV1% predicted for each GOLD stage to estimate the frequency per stage.,Thirty-seven relevant studies were found, with 43 reports of total exacerbation frequency (event-based, n = 19; symptom-based, n = 24) and 14 reports of frequency of severe exacerbations.,Annual event-based exacerbation frequencies per GOLD stage were estimated at 0.82 (95% confidence interval 0.46-1.49) for mild, 1.17 (0.93-1.50) for moderate, 1.61 (1.51-1.74) for severe, and 2.10 (1.51-2.94) for very severe COPD.,Annual symptom-based frequencies were 1.15 (95% confidence interval 0.67-2.07), 1.44 (1.14-1.87), 1.76 (1.70-1.88), and 2.09 (1.57-2.82), respectively.,For severe exacerbations, annual frequencies were 0.11 (95% confidence interval 0.02-0.56), 0.16 (0.07-0.33), 0.22 (0.20-0.23), and 0.28 (0.14-0.63), respectively.,Study duration or type of study (cohort versus trial) did not significantly affect the outcomes.,This study provides an estimate of the exacerbation frequency per GOLD stage, which can be used for health economic and modeling purposes. | 1 |
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and health care expenditure worldwide.,Relaxation of airway smooth muscle with inhaled bronchodilators is the cornerstone of treatment for stable COPD, with inhaled corticosteroids reserved for those with a history of exacerbations.,Tiotropium has occupied center stage in COPD treatment for over 10 years and improves lung function, quality of life, exercise endurance, and reduces the risk of COPD exacerbation.,Long-acting β2-agonists (LABAs) improve lung function, reduce dynamic hyperinflation, increase exercise tolerance, health-related quality of life, and reduce acute exacerbation of COPD.,The combination of long-acting muscarinic antagonists (LAMAs) and LABAs is thought to leverage different pathways to induce bronchodilation using submaximal drug doses, increasing the benefits and minimizing receptor-specific side effects.,Umeclidinium/vilanterol is the first combination of LAMA/LABA to be approved for use in stable COPD in USA and Europe.,Additionally, indacaterol/glycopyrronium and aclidinium/formoterol have been approved in Europe and in numerous locations outside USA.,Several other agents are in the late stages of development, most of which offer once-daily dosing.,The benefits of new LAMA/LABA combinations include improved pulmonary function, dyspnea, and health-related quality of life, and in some cases, reduced exacerbations.,These evolving treatments will provide new opportunities and challenges in the management of COPD. | Observational studies using case-control designs have showed an increased risk of pneumonia associated with inhaled corticosteroid (ICS)-containing medications in patients with chronic obstructive pulmonary disease (COPD).,New-user observational cohort designs may minimize biases associated with previous case-control designs.,To estimate the association between ICS and pneumonia among new users of ICS relative to inhaled long-acting bronchodilator (LABD) monotherapy.,Pneumonia events in COPD patients ≥45 years old were compared among new users of ICS medications (n = 11,555; ICS, ICS/long-acting β2-agonist [LABA] combination) and inhaled LABD monotherapies (n = 6,492; LABA, long-acting muscarinic antagonists) using Cox proportional hazards models, with propensity scores to adjust for confounding.,Setting: United Kingdom electronic medical records with linked hospitalization and mortality data (2002-2010).,New users were censored at earliest of: pneumonia event, death, changing/discontinuing treatment, or end of follow-up.,Outcomes: severe pneumonia (primary) and any pneumonia (secondary).,Following adjustment, new use of ICS-containing medications was associated with an increased risk of pneumonia hospitalization (n = 322 events; HR = 1.55, 95% CI: 1.14, 2.10) and any pneumonia (n = 702 events; HR = 1.49, 95% CI: 1.22, 1.83).,Crude incidence rates of any pneumonia were 48.7 and 30.9 per 1000 person years among the ICS-containing and LABD cohorts, respectively.,Excess risk of pneumonia with ICS was reduced when requiring ≥1 month or ≥ 6 months of new use.,There was an apparent dose-related effect, with greater risk at higher daily doses of ICS.,There was evidence of channeling bias, with more severe patients prescribed ICS, for which the analysis may not have completely adjusted.,The results of this new-user cohort study are consistent with published findings; ICS were associated with a 20-50% increased risk of pneumonia in COPD, which reduced with exposure time.,This risk must be weighed against the benefits when prescribing ICS to patients with COPD. | 1 |
Patients with asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) and cardiovascular diseases (CVDs) share common risk factors.,However, the association between ACOS and the incidence of CVDs has not been reported.,This study investigated the relationship between CVDs and ACOS in the general population.,Data were obtained from Taiwan’s National Health Insurance Research Database for the period 2000 to 2010.,The ACOS cohort comprised patients (n=5814) who had received a diagnosis of asthma and COPD.,The non-ACOS cohort comprised patients who had not received a diagnosis of asthma or COPD and were matched to the ACOS cohort (2:1) by age, sex and index date (n=11 625).,The cumulative incidence of CVDs-coronary artery disease (CAD), cardiac dysrhythmia (CD) and heart failure (HF)-was calculated.,Cox proportional regression analysis was employed to examine the relationship between ACOS and CVDs.,After adjustment for multiple confounding factors-age, sex, comorbidities and medications-patients with ACOS were associated with a significantly higher risk of CVDs; the adjusted HRs (aHRs; 95% CI) for CAD, CD and HF were 1.62 (1.50 to 1.76), 1.44 (1.30 to 1.61) and 1.94 (1.73 to 2.19), respectively, whereas those of beta-blockers treatment for CAD, CD and HF were 1.19 (0.92 to 1.53), 0.90 (0.56 to 1.45) and 0.82 (0.49 to 1.38).,The aHR of atenolol treatment for CD was 1.72 (1.01 to 2.93).,The aHRs (95% CIs) of ACOS without acute exacerbation of COPD (AE-COPD) for CAD, CD and HF were 1.85 (1.70 to 2.01), 1.57 (1.40 to 1.77) and 2.07 (1.82 to 2.35), respectively.,ACOS was associated with higher CVD risk, even without the presence of previous comorbidities or AE-COPD.,No significant differences in CVD events were observed in the ACOS cohort using beta-blockers, except for those using atenolol for treating CD. | Pulmonary hyperinflation has the potential for significant adverse effects on cardiovascular function in COPD.,The aim of this study was to investigate the relationship between dynamic hyperinflation and cardiovascular response to maximal exercise in COPD patients.,We studied 48 patients (16F; age 68 yrs ± 8; BMI 26 ± 4) with COPD.,All patients performed spirometry, plethysmography, lung diffusion capacity for carbon monoxide (TLco) measurement, and symptom-limited cardiopulmonary exercise test (CPET).,The end-expiratory lung volume (EELV) was evaluated during the CPET.,Cardiovascular response was assessed by change during exercise in oxygen pulse (ΔO2Pulse) and double product, i.e. the product of systolic blood pressure and heart rate (DP reserve), and by the oxygen uptake efficiency slope (OUES), i.e. the relation between oxygen uptake and ventilation.,Patients with a peak exercise EELV (%TLC) ≥ 75% had a significantly lower resting FEV1/VC, FEF50/FIF50 ratio and IC/TLC ratio, when compared to patients with a peak exercise EELV (%TLC) < 75%.,Dynamic hyperinflation was strictly associated to a poor cardiovascular response to exercise: EELV (%TLC) showed a negative correlation with ΔO2Pulse (r = - 0.476, p = 0.001), OUES (r = - 0.452, p = 0.001) and DP reserve (r = - 0.425, p = 0.004).,Furthermore, according to the ROC curve method, ΔO2Pulse and DP reserve cut-off points which maximized sensitivity and specificity, with respect to a EELV (% TLC) value ≥ 75% as a threshold value, were ≤ 5.5 mL/bpm (0.640 sensitivity and 0.696 specificity) and ≤ 10,000 Hg · bpm (0.720 sensitivity and 0.783 specificity), respectively.,The present study shows that COPD patients with dynamic hyperinflation have a poor cardiovascular response to exercise.,This finding supports the view that in COPD patients, dynamic hyperinflation may affect exercise performance not only by affecting ventilation, but also cardiac function. | 1 |
This observational study with tiotropium Respimat® was performed in a real-life setting to investigate its effectiveness with regard to physical functioning and tolerability.,Patients with chronic obstructive pulmonary disease (COPD; n = 1,230; mean age, 65.5 years) received tiotropium 5 μg once daily via Respimat® Soft Inhaler for 6 weeks in an open-label observational study.,At baseline and week 6, patients completed the Physical Function subdomain [PF-10] of the Short Form (SF) 36 questionnaire.,Improvement in standardized PF-10 score of ≥10 points was achieved by 61.5% of patients.,Mean (SD) standardized PF-10 scores improved by 13.4 (15.9) points, from 49.0 (24.5) to 62.3 points (23.5; P < 0.001).,Results in smokers (n = 435) were not significantly different to those in nonsmokers.,The general condition of patients improved during treatment.,Adverse events were reported by 4.0% of patients and were chiefly respiratory symptoms and dry mouth.,In COPD patients receiving tiotropium Respimat® in daily practice, physical function improved rapidly within 6 weeks of treatment, irrespective of smoking status. | Although medical treatment of COPD has advanced, nonadherence to medication regimens poses a significant barrier to optimal management.,Underuse, overuse, and improper use continue to be the most common causes of poor adherence to therapy.,An average of 40%-60% of patients with COPD adheres to the prescribed regimen and only 1 out of 10 patients with a metered dose inhaler performs all essential steps correctly.,Adherence to therapy is multifactorial and involves both the patient and the primary care provider.,The effect of patient instruction on inhaler adherence and rescue medication utilization in patients with COPD does not seem to parallel the good results reported in patients with asthma.,While use of a combined inhaler may facilitate adherence to medications and improve efficacy, pharmacoeconomic factors may influence patient’s selection of both the device and the regimen.,Patient’s health beliefs, experiences, and behaviors play a significant role in adherence to pharmacological therapy.,This manuscript reviews important aspects associated with medication adherence in patients with COPD and identifies some predictors of poor adherence. | 1 |
Chronic obstructive pulmonary disease (COPD) is a multifactorial clinical condition, characterized by chronic progressive (or worsening) respiratory symptoms, structural pulmonary abnormalities, and impaired lung function, and is often accompanied by multiple, clinically significant comorbid disorders.,In 2017, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) issued a new report on COPD prevention, diagnosis and management, aiming at personalizing the maintenance therapeutic approach of the stable disease, based on the patients’ symptoms and history of exacerbations (ABCD assessment approach).,Our objective was to evaluate the implementation of GOLD suggestions in everyday clinical practice in Greece.,This was a cross-sectional observational study.,Sixty-five different variables (demographics, vital sign measurements, COPD-related medical history parameters, comorbidities, vaccination data, COPD severity based on spirometry measurements, COPD stage based on the ABCD assessment approach, COPD treatments) were collected from 3615 nation-wide COPD patients (Greece).,The mean age at the time of initial COPD diagnosis was 63.8 (± 10.2).,Almost 60% of the subjects were classified into group B, while the remaining patients were falling into groups A (18%) and D (21%), and only a small minority of patients belonged to Group C, according to the ABCD assessment approach.,The compliance of respiratory physicians to the GOLD 2017 therapeutic suggestions is problematic, especially when it comes to COPD patients belonging to Group A.,Our data provide valuable information regarding the demographic and medical profile of COPD patients in Greece, the domains which the revised ABCD assessment approach may show some clinical significance on, and the necessity for medical practitioners dealing with COPD patients to adhere closer to international recommendations for the proper management of the disease.,The online version contains supplementary material available at 10.1186/s12890-021-01576-6. | The combination of aclidinium bromide, a long-acting anticholinergic, and formoterol fumarate, a long-acting beta2-agonist (400/12 μg twice daily) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease (COPD), and is approved in the European Union as a maintenance treatment.,The effect of this combination on symptoms of COPD and exacerbations is less well established.,We examined these outcomes in a pre-specified analysis of pooled data from two 24-week, double-blind, parallel-group, active- and placebo-controlled, multicentre, randomised Phase III studies (ACLIFORM and AUGMENT).,Patients ≥40 years with moderate to severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <70 % and FEV1 ≥30 % but <80 % predicted normal) were randomised (ACLIFORM: 2:2:2:2:1; AUGMENT: 1:1:1:1:1) to twice-daily aclidinium/formoterol 400/12 μg or 400/6 μg, aclidinium 400 μg, formoterol 12 μg or placebo via Genuair™/Pressair®.,Dyspnoea (Transition Dyspnoea Index; TDI), daily symptoms (EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [E-RS] questionnaire), night-time and early-morning symptoms, exacerbations (Healthcare Resource Utilisation [HCRU] and EXACT definitions) and relief-medication use were assessed.,The pooled intent-to-treat population included 3394 patients.,Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 (all p < 0.05).,Over 24 weeks, significant improvements in E-RS total score, overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with aclidinium/formoterol 400/12 μg versus placebo and both monotherapies (all p < 0.05).,The rate of moderate or severe HCRU exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg compared with placebo (p < 0.05) but not monotherapies; the rate of EXACT-defined exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg versus placebo (p < 0.01) and aclidinium (p < 0.05).,Time to first HCRU or EXACT exacerbation was longer with aclidinium/formoterol 400/12 μg compared with placebo (all p < 0.05) but not the monotherapies.,Relief-medication use was reduced with aclidinium/formoterol 400/12 μg versus placebo and aclidinium (p < 0.01).,Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo, aclidinium and formoterol in patients with moderate to severe COPD.,Furthermore, aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo.,NCT01462942 and NCT01437397 (ClinicalTrials.gov),The online version of this article (doi:10.1186/s12931-015-0250-2) contains supplementary material, which is available to authorized users. | 1 |
Cigarette smoke is a major risk factor for chronic obstructive pulmonary disease (COPD), an inflammatory lung disorder.,COPD is characterized by an increase in CD8+ T cells within the central and peripheral airways.,We hypothesized that the CD8+ T cells in COPD patients have increased Toll-like receptor (TLR) expression compared to control subjects due to the exposure of cigarette smoke in the airways.,Endobronchial biopsies and peripheral blood were obtained from COPD patients and control subjects.,TLR4 and TLR9 expression was assessed by immunostaining of lung tissue and flow cytometry of the peripheral blood.,CD8+ T cells isolated from peripheral blood were treated with or without cigarette smoke condensate (CSC) as well as TLR4 and TLR9 inhibitors.,PCR and western blotting were used to determine TLR4 and TLR9 expression, while cytokine secretion from these cells was detected using electrochemiluminescence technology.,No difference was observed in the overall expression of TLR4 and TLR9 in the lung tissue and peripheral blood of COPD patients compared to control subjects.,However, COPD patients had increased TLR4 and TLR9 expression on lung CD8+ T cells.,Exposure of CD8+ T cells to CSC resulted in an increase of TLR4 and TLR9 protein expression.,CSC exposure also caused the activation of CD8+ T cells, resulting in the production of IL-1β, IL-6, IL-10, IL-12p70, TNFα and IFNγ.,Furthermore, inhibition of TLR4 or TLR9 significantly attenuated the production of TNFα and IL-10.,Our results demonstrate increased expression of TLR4 and TLR9 on lung CD8+ T cells in COPD.,CD8+ T cells exposed to CSC increased TLR4 and TLR9 levels and increased cytokine production.,These results provide a new perspective on the role of CD8+ T cells in COPD. | Tobacco smoking has been considered the most important risk factor for chronic obstructive pulmonary disease (COPD) development.,However, not all smokers develop COPD and other environmental and genetic susceptibility factors underlie disease pathogenesis.,Recent studies have indicated that the impairment of TLR signaling might play a crucial role in the development of emphysema.,For this purpose we investigated the prevalence and any possible associations of common TLR polymorphisms (T L R2-R753Q, T L R4-D299G, and T L R4-T399I) in a group of 240 heavy smokers (>20 pack years), without overt atherosclerosis disease, of whom 136 had developed COPD and 104 had not.,The presence of T L R4-T399I polymorphism was associated with a 2.4-fold increased risk for COPD development (P = .044), but not with disease stage or frequency of exacerbations.,Considering that infections contribute to COPD and emphysema pathogenesis, our findings possibly indicate that dysfunctional polymorphisms of innate immune genes can affect the development of COPD in smokers.,Although this finding warrants further investigation, it highlights the importance of impaired innate immunity towards COPD development. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) commonly suffer from acute exacerbations (AECOPD) and display varying disease severity.,However, there is no available biomarker for the classification of AECOPD.,This study is aimed at investigating the sputum cellular profiles to classify patients with AECOPD.,A total of 83 patients with AECOPD and 26 healthy controls were recruited.,Their demographic and clinical characteristics were recorded, and their lung function was examined.,The phenotypes of sputum inflammatory cells were characterised, and the concentrations of sputum and serum amyloid-A (SAA), C-reactive protein (CRP), interleukin-6 (IL-6), and matrix metalloproteinase-9 (MMP-9) were measured.,Based on the sputum inflammatory cell profiles, individual patients were categorized into one of the four subgroups with inflammatory eosinophilic, neutrophilic, paucigranulocytic, and mixed granulocytic AECOPD.,Most AECOPD patients were reevaluated within 12-14 months after discharge.,There were 10 (12%) eosinophilic, 36 (43%) neutrophilic, 5 (6%) mixed granulocytic, and 32 (39%) paucigranulocytic AECOPD patients.,The patients with mixed granulocytic or neutrophilic AECOPD had a higher BODE score, more sputum inflammatory cells, lower lung function, and longer hospital stay, accompanied by higher concentrations of sputum MMP-9, IL-6 and CRP, and serum SAA, IL-6 and CRP.,Notably, 83% of patients with neutrophilic AECOPD displayed evidence of bacterial infection and many of them responded poorly to standard therapies.,In addition, patients with mixed granulocytic or neutrophilic stable COPD remained at lower lung functions and higher levels of inflammation.,Patients with AECOPD display heterogeneous inflammation, and the profiles of sputum inflammatory cells may be used as valuable biomarkers for the classification of AECOPD patients. | Chronic obstructive pulmonary disease is a common condition and a major cause of mortality.,COPD is characterized by irreversible airflow obstruction.,The physiological abnormalities observed in COPD are due to a combination of emphysema and obliteration of the small airways in association with airway inflammation.,The predominant cells involved in this inflammatory response are CD8+ lymphocytes, neutrophils, and macrophages.,Although eosinophilic airway inflammation is usually considered a feature of asthma, it has been demonstrated in large and small airway tissue samples and in 20%-40% of induced sputum samples from patients with stable COPD.,This airway eosinophilia is increased in exacerbations.,Thus, modifying eosinophilic inflammation may be a potential therapeutic target in COPD.,Eosinophilic airway inflammation is resistant to inhaled corticosteroid therapy, but does respond to systemic corticosteroid therapy, and the degree of response is related to the intensity of the eosinophilic inflammation.,In COPD, targeting treatment to normalize the sputum eosinophilia reduced the number of hospital admissions.,Whether controlling eosinophilic inflammation in COPD patients with an airway eosinophilia will modify disease progression and possibly alter mortality is unknown, but warrants further investigation. | 1 |
To compare efficacy of indacaterol to that of fixed-dose combination (FDC) formoterol and budesonide (FOR/BUD) and FDC salmeterol and fluticasone (SAL/FP) for the treatment of chronic obstructive pulmonary disease (COPD) based on the available randomized clinical trials (RCTs).,Fifteen placebo-controlled RCTs were included that evaluated: indacaterol 150 μg (n = 5 studies), indacaterol 300 μg (n = 4), FOR/BUD 9/160 μg (n = 2), FOR/BUD 9/320 μg (n = 3), SAL/FP 50/500 μg (n = 5), and SAL/FP 50/250 μg (n = 1).,Outcomes of interest were trough forced expiratory volume in 1 second (FEV1), total scores for St.,George’s Respiratory Questionnaire (SGRQ), and transition dyspnea index (TDI).,All trials were analyzed simultaneously using a Bayesian network meta-analysis and relative treatment effects between all regimens were obtained.,Treatment-by-covariate interactions were included where possible to improve the similarity of the trials.,Indacaterol 150 μg resulted in a higher change from baseline (CFB) in FEV1 at 12 weeks compared to FOR/BUD 9/160 μg (difference in CFB 0.11 L [95% credible intervals: 0.08, 0.13]) and FOR/BUD 9/320 μg (0.09 L [0.06, 0.11]) and was comparable to SAL/FP 50/250 μg (0.02 L [−0.04, 0.08]) and SAL/FP 50/500 μg (0.03 L [0.00, 0.06]).,Similar results were observed for indacaterol 300 μg at 12 weeks and indacaterol 150/300 μg at 6 months.,Indacaterol 150 μg demonstrated comparable improvement in SGRQ total score at 6 months versus FOR/BUD (both doses), and SAL/FP 50/500 μg (−2.16 point improvement [−4.96, 0.95]).,Indacaterol 150 and 300 μg demonstrated comparable TDI scores versus SAL/FP 50/250 μg (0.21 points (−0.57, 0.99); 0.39 [−0.39, 1.17], respectively) and SAL/FP 50/500 μg at 6 months.,Indacaterol monotherapy is expected to be at least as good as FOR/BUD (9/320 and 9/160 μg) and comparable to SAL/FP (50/250 and 50/500 μg) in terms of lung function.,Indacaterol is also expected to be comparable to FOR/BUD (9/320 and 9/160 μg) and SAL/FP 50/500 μg in terms of health status and to SAL/FP (50/250 and 50/500 μg) in terms of breathlessness. | Little is known about factors that determine health status decline in clinical trials of COPD.,To examine health status changes over 3 years in the TORCH study of salmeterol+fluticasone propionate (SFC) vs. salmeterol alone, fluticasone propionate alone or placebo.,St George's Respiratory Questionnaire (SGRQ) was administered at baseline then every 6 months.,Data from 4951 patients in 28 countries were available.,SFC produced significant improvements over placebo in all three SGRQ domains during the study: (Symptoms -3.6 [95% CI -4.8, -2.4], Activity -2.8 [95% CI -3.9, -1.6], Impacts -3.2 [95% CI -4.3, -2.1]) but the pattern of change over time differed between domains.,SGRQ deteriorated faster in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages III & IV relative to GOLD stage II (p < 0.001).,There was no difference in the relationship between deterioration in SGRQ Total score and forced expiratory volume in one second (FEV1) decline (as % predicted) in men and women.,Significantly faster deterioration in Total score relative to FEV1 % predicted was seen in older patients (≥ 65 years) and there was an age-related change in Total score that was independent of change in FEV1.,The relationship between deterioration in FEV1 and SGRQ did not differ in different world regions, but patients in Asia-Pacific showed a large improvement in score that was unrelated to FEV1 change.,In addition to treatment effects, health status changes in clinical trials may be influenced by demographic and disease-related factors.,Deterioration in health status appears to be fastest in older persons and those with severe airflow limitation.,ClinicalTrials.gov: NCT00268216 | 1 |
Depression and anxiety are very common in people with chronic obstructive pulmonary disease (COPD) and are associated with excess morbidity and mortality.,Patients prefer non-drug treatments and clinical guidelines promote non-pharmacological interventions as first line therapy for depression and anxiety in people with long term conditions.,However the comparative effectiveness of psychological and lifestyle interventions among COPD patients is not known.,We assessed whether complex psychological and/or lifestyle interventions are effective in reducing symptoms of anxiety and depression in patients with COPD.,We then determined what types of psychological and lifestyle interventions are most effective.,Systematic review of randomised controlled trials of psychological and/or lifestyle interventions for adults with COPD that measured symptoms of depression and/or anxiety.,CENTRAL, Medline, Embase, PsychINFO, CINAHL, ISI Web of Science and Scopus were searched up to April 2012.,Meta-analyses using random effects models were undertaken to estimate the average effect of interventions on depression and anxiety.,Thirty independent comparisons from 29 randomised controlled trials (n = 2063) were included in the meta-analysis.,Overall, psychological and/or lifestyle interventions were associated with small reductions in symptoms of depression (standardised mean difference −0.28, 95% confidence interval −0.41 to −0.14) and anxiety (standardised mean difference −0.23, 95% confidence interval −0.38 to −0.09).,Multi-component exercise training was the only intervention subgroup associated with significant treatment effects for depression (standardised mean difference −0.47, 95% confidence interval −0.66 to −0.28), and for anxiety (standardised mean difference −0.45, 95% confidence interval −0.71 to −0.18).,Complex psychological and/or lifestyle interventions that include an exercise component significantly improve symptoms of depression and anxiety in people with COPD.,Furthermore, multi-component exercise training effectively reduces symptoms of anxiety and depression in all people with COPD regardless of severity of depression or anxiety, highlighting the importance of promoting physical activity in this population. | Background: COPD pathology involves not only the lungs but also extrapulmonary abnormalities.,Osteoporosis is one of the most important abnormalities because it may cause vertebral compression fractures and deteriorate pulmonary function.,COPD patients have many risk factors for osteoporosis, such as low BMI, decreased activity, systemic inflammation, and use of corticosteroids.,Some of these factors have been shown to deteriorate with COPD exacerbations.,We previously demonstrated the correlation between emphysema and osteoporosis and between emphysema progression and COPD exacerbations.,Thus, the hypothesis that exacerbation causes osteoporosis progression in COPD patients was investigated.,Methods: Forty-two COPD patients not on osteoporosis treatment for over 2 years were recruited.,During follow-up, exacerbations had been prospectively recorded.,Thoracic vertebral bone mineral density (BMD) was measured using chest CT, and the annual change in BMD was calculated.,The change was compared between patients with and without a history of exacerbations.,Results: The decrease in thoracic vertebral BMD was greater in patients with than in those without a history of exacerbations (median ABMD mg/ml year: −3.78 versus −0.30, p = 0.02).,Moreover, multivariate regression analysis showed that exacerbations and baseline Pa02 were independent predictors of the BMD decrease (R2 = 0.20, p = 0.007, and R2 = 0.09, p = 0.03, respectively) after adjustment for baseline age, smoking status, and airflow limitation.,Conclusions: This is the first longitudinal study to demonstrate that COPD exacerbations are independently associated with osteoporosis progression.,Osteoporosis progression should be evaluated in COPD patients, especially in those with a history of frequent exacerbations. | 1 |
Objective evaluation of the physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD) is important.,We validated a triaxial accelerometer, Active Style Pro HJA-750C® (HJA), and evaluated the necessary conditions for obtaining reproducible data.,The PA measured by HJA was compared with that measured by two already validated accelerometers in 11 patients with COPD (age: 76.6 ± 6.9, FEV1% predicted: 57.6 ± 18.6).,Then, the influence of weather and holidays on the PA and the required number of days to obtain repeatability were examined in 21 patients with COPD (age: 73.0 ± 8.0, FEV1% predicted: 58.7 ± 19.0).,The PA values measured by HJA and those by DynaPort Move Monitor® (DMM) or Actimarker® (AM) were significantly correlated at all intensities (p=0.024 at ≥4.0 METs by DMM and p < 0.0001 at the rest) except at ≥4.0 METs by AM, though the values measured by HJA were higher than those by AM which was reported to underestimate PA.,The durations of PA on rainy days were significantly shorter than those on nonrainy days, but those on holidays were not different from those on weekdays.,The values of ICC for 3, 4, or 5 days were higher than 0.8 at all intensities.,The PA measured by HJA was correlated with the dyspnea scale FVC and age and tended to correlate with FEV1.,The HJA was validated for evaluating the PA in patients with COPD.,This trial is registered with UMIN000016363. | The relationship between physical activity, disease severity, health status and prognosis in patients with COPD has not been systematically assessed.,Our aim was to identify and summarise studies assessing associations between physical activity and its determinants and/or outcomes in patients with COPD and to develop a conceptual model for physical activity in COPD.,We conducted a systematic search of four databases (Medline, Embase, CINAHL and Psychinfo) prior to November 2012.,Teams of two reviewers independently selected articles, extracted data and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess quality of evidence.,86 studies were included: 59 were focused on determinants, 23 on outcomes and 4 on both.,Hyperinflation, exercise capacity, dyspnoea, previous exacerbations, gas exchange, systemic inflammation, quality of life and self-efficacy were consistently related to physical activity, but often based on cross-sectional studies and low-quality evidence.,Results from studies of pharmacological and non-pharmacological treatments were inconsistent and the quality of evidence was low to very low.,As outcomes, COPD exacerbations and mortality were consistently associated with low levels of physical activity based on moderate quality evidence.,Physical activity was associated with other outcomes such as dyspnoea, health-related quality of life, exercise capacity and FEV1 but based on cross-sectional studies and low to very low quality evidence.,Physical activity level in COPD is consistently associated with mortality and exacerbations, but there is poor evidence about determinants of physical activity, including the impact of treatment. | 1 |
Chronic obstructive pulmonary disease (COPD) is now the fourth leading cause of death in the world, and it continues to increase in developing countries.,The World Health Organization expects COPD to be the third most common cause of death in the world by 2020.,Effective and continuous postdischarge care can help patients to maintain good health.,The use of electronic health records (EHRs) as an element of community health care is new technology in China.,The aim of this study was to develop and evaluate a Web-based coaching program using EHRs for physical function and health-related quality of life for patients with COPD in China.,A randomized controlled trial was conducted from 2008 to 2015 at two hospitals.,The control group received routine care and the intervention group received routine care with the addition of the Web-based coaching program using EHRs.,These were used to manage patients’ demographic and clinical variables, publish relevant information, and have communication between patients and health care providers.,Participants were not blinded to group assignment.,The effects of the intervention were evaluated by lung function, including percent of forced expiratory volume in 1 second (FEV1%), percent of forced vital capacity (FVC%), peak expiratory flow (PEF), maximum midexpiratory flow; St George’s Respiratory Questionnaire (SGRQ); Modified Medical Research Council Dyspnea Scale (MMRC); and 6-Minute Walk Test (6MWT).,Data were collected before the program, and at 1, 3, 6, and 12 months after the program.,Of the 130 participants, 120 (92.3%) completed the 12-month follow-up program.,There were statistically significant differences in lung function (FEV1%: F1,4=5.47, P=.002; FVC%: F1,4=3.06, P=.02; PEF: F1,4=12.49, P<.001), the total score of SGRQ (F1,4=23.30, P<.001), symptoms of SGRQ (F1,4=12.38, P<.001), the activity of SGRQ (F1,4=8.35, P<.001), the impact of SGRQ (F1,4=12.26, P<.001), MMRC (F1,4=47.94, P<.001), and 6MWT (F1,4=35.54, P<.001) between the two groups with the variation of time tendency.,The Web-based coaching program using EHRs in China appears to be useful for patients with COPD when they are discharged from hospital into the community.,It promotes the sharing of patients’ medical information by hospital and community nurses, and achieves dynamic management and follow-up analysis for patients’ disease.,In addition, this program can postpone the decreasing rate of lung function, improve quality of life, decrease dyspnea, and increase physical capacity. | With the limited reach of pulmonary rehabilitation (PR) and low levels of daily physical activity in chronic obstructive pulmonary disease (COPD), a need exists to increase daily exercise.,This study evaluated telephone health-mentoring targeting home-based walking (tele-rehab) compared to usual waiting time (usual care) followed by group PR.,People with COPD were randomized to tele-rehab (intervention) or usual care (controls).,Tele-rehab delivered by trained nurse health-mentors supported participants’ home-based walking over 8-12 weeks.,PR, delivered to both groups simultaneously, included 8 weeks of once-weekly education and self-management skills, with separate supervised exercise.,Data were collected at three time-points: baseline (TP1), before (TP2), and after (TP3) PR.,The primary outcome was change in physical capacity measured by 6-minute walk distance (6MWD) with two tests performed at each time-point.,Secondary outcomes included changes in self-reported home-based walking, health-related quality of life, and health behaviors.,Of 65 recruits, 25 withdrew before completing PR.,Forty attended a median of 6 (4) education sessions.,Seventeen attended supervised exercise (5±2 sessions).,Between TP1 and TP2, there was a statistically significant increase in the median 6MWD of 12 (39.1) m in controls, but no change in the tele-rehab group.,There were no significant changes in 6MWD between other time-points or groups, or significant change in any secondary outcomes.,Participants attending supervised exercise showed a nonsignificant improvement in 6MWD, 12.3 (71) m, while others showed no change, 0 (33) m.,The mean 6MWD was significantly greater, but not clinically meaningful, for the second test compared to the first at all time-points.,Telephone-mentoring for home-based walking demonstrated no benefit to exercise capacity.,Two 6-minute walking tests at each time-point may not be necessary.,Supervised exercise seems essential in PR.,The challenge of incorporating exercise into daily life in COPD is substantial. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is currently the fifth leading cause of death worldwide.,Neutrophilic inflammation is prominent, worsened during infective exacerbations and is refractory to glucocorticosteroids (GCs).,Deregulated neutrophilic inflammation can cause excessive matrix degradation through proteinase release.,Gelatinase and azurophilic granules within neutrophils are a major source of matrix metalloproteinase (MMP)-9 and neutrophil elastase (NE), respectively, which are elevated in COPD.,Secreted MMP-9 and NE activity in BALF were stratified according to GOLD severity stages.,The regulation of secreted NE and MMP-9 in isolated blood neutrophils was investigated using a pharmacological approach.,In vivo release of MMP-9 and NE in mice exposed to cigarette smoke (CS) and/or the TLR agonist lipopolysaccharide (LPS) in the presence of dexamethasone (Dex) was investigated.,Neutrophil activation as assessed by NE release was increased in severe COPD (36-fold, GOLD II vs.,IV).,MMP-9 levels (8-fold) and activity (21-fold) were also elevated in severe COPD, and this activity was strongly associated with BALF neutrophils (r = 0.92, p<0.001), but not macrophages (r = 0.48, p = 0.13).,In vitro, release of NE and MMP-9 from fMLP stimulated blood neutrophils was insensitive to Dex and attenuated by the PI3K inhibitor, wortmannin.,In vivo, GC resistant neutrophil activation (NE release) was only seen in mice exposed to CS and LPS.,In addition, GC refractory MMP-9 expression was only associated with neutrophil activation.,As neutrophils become activated with increasing COPD severity, they become an important source of NE and MMP-9 activity, which secrete proteinases independently of TIMPs.,Furthermore, as NE and MMP-9 release was resistant to GC, targeting of the PI3K pathway may offer an alternative pathway to combating this proteinase imbalance in severe COPD. | Cigarette smoking is the main risk factor for the development of chronic obstructive pulmonary disease (COPD), a major cause of morbidity and mortality worldwide.,Despite this, the cellular and molecular mechanisms that contribute to COPD pathogenesis are still poorly understood.,The objective of this study was to assess IL-1 α and β expression in COPD patients and to investigate their respective roles in perpetuating cigarette smoke-induced inflammation.,Functional studies were pursued in smoke-exposed mice using gene-deficient animals, as well as blocking antibodies for IL-1α and β.,Here, we demonstrate an underappreciated role for IL-1α expression in COPD.,While a strong correlation existed between IL-1α and β levels in patients during stable disease and periods of exacerbation, neutrophilic inflammation was shown to be IL-1α-dependent, and IL-1β- and caspase-1-independent in a murine model of cigarette smoke exposure.,As IL-1α was predominantly expressed by hematopoietic cells in COPD patients and in mice exposed to cigarette smoke, studies pursued in bone marrow chimeric mice demonstrated that the crosstalk between IL-1α+ hematopoietic cells and the IL-1R1+ epithelial cells regulates smoke-induced inflammation.,IL-1α/IL-1R1-dependent activation of the airway epithelium also led to exacerbated inflammatory responses in H1N1 influenza virus infected smoke-exposed mice, a previously reported model of COPD exacerbation.,This study provides compelling evidence that IL-1α is central to the initiation of smoke-induced neutrophilic inflammation and suggests that IL-1α/IL-1R1 targeted therapies may be relevant for limiting inflammation and exacerbations in COPD. | 1 |
With increasing choice of medications and devices for asthma and chronic obstructive pulmonary disease (COPD) treatment, comparative evidence may inform treatment decisions.,This systematic literature review assessed clinical and economic evidence for using a single combination inhaler versus multiple inhalers to deliver the same medication for patients with asthma or COPD.,In 2016, Embase, PubMed and the Cochrane library were searched for publications reporting studies in asthma or COPD comparing a single-inhaler combination medicine with multiple inhalers delivering the same medication.,Publications included English-language articles published since 1996 and congress abstracts since 2013.,Clinical, economic and adherence endpoints were assessed.,Of 2031 abstracts screened, 18 randomized controlled trials (RCTs) in asthma and four in COPD, nine retrospective and three prospective observational studies in asthma, and four observational studies in COPD were identified.,Of these, five retrospective and one prospective study in asthma, and two retrospective studies in COPD reported greater adherence with a single inhaler than multiple inhalers.,Nine observational studies reported significantly (n=7) or numerically (n=2) higher rates of adherence with single- versus multiple-inhaler therapy.,Economic analyses from retrospective and prospective studies showed that use of single-inhaler therapies was associated with reduced healthcare resource use (n=6) and was cost-effective (n=5) compared with multiple-inhaler therapies.,Findings in 18 asthma RCTs and one prospective study reporting lung function, and six RCTs reporting exacerbation rates, showed no significant differences between a single inhaler and multiple inhalers.,This was in contrast to several observational studies reporting reductions in healthcare resource use or exacerbation events with single-inhaler treatment, compared with multiple inhalers.,Retrospective and prospective studies showed that single-inhaler use was associated with decreased healthcare resource utilization and improved cost-effectiveness compared with multiple inhalers.,Lung function and exacerbation rates were mostly comparable in the RCTs, possibly due to study design. | 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. | 1 |
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death by disease worldwide and has a 30-day readmission rate of 22.6%.,In 2015, COPD was added to the Medicare Hospital Readmission Reductions Program.,The objective of this paper was to survey the current medical technologies for remote patient monitoring (RPM) tools that forecast COPD exacerbations in order to reduce COPD readmissions.,We searched literature and digital health news to find commercially available RPM devices focused on predicting COPD exacerbations.,These technologies were reviewed and compared according to four criteria: forecasting ability, cost, ease of use, and appearance.,A rating system was developed to facilitate the evaluation process.,As of June 2019, a list of handheld and hands-free devices was compiled.,We compared features and found substantial variations.,Devices that ranked higher on all criteria tended to have a high or unlisted price.,Commonly mass-marketed devices like the pulse oximeter and spirometer surprisingly fulfilled the least criteria.,The COPD RPM technologies with most technological promise and compatibility with daily living appear to have high or unlisted prices.,Consumers and providers need better access to product information to make informed decisions. | Objective To test the effectiveness of telemonitoring integrated into existing clinical services such that intervention and control groups have access to the same clinical care.,Design Researcher blind, multicentre, randomised controlled trial.,Setting UK primary care (Lothian, Scotland).,Participants Adults with at least one admission for chronic obstructive pulmonary disease (COPD) in the year before randomisation.,We excluded people who had other significant lung disease, who were unable to provide informed consent or complete the study, or who had other significant social or clinical problems.,Interventions Participants were recruited between 21 May 2009 and 28 March 2011, and centrally randomised to receive telemonitoring or conventional self monitoring.,Using a touch screen, telemonitoring participants recorded a daily questionnaire about symptoms and treatment use, and monitored oxygen saturation using linked instruments.,Algorithms, based on the symptom score, generated alerts if readings were omitted or breached thresholds.,Both groups received similar care from existing clinical services.,Main outcome measures The primary outcome was time to hospital admission due to COPD exacerbation up to one year after randomisation.,Other outcomes included number and duration of admissions, and validated questionnaire assessments of health related quality of life (using St George’s respiratory questionnaire (SGRQ)), anxiety or depression (or both), self efficacy, knowledge, and adherence to treatment.,Analysis was intention to treat.,Results Of 256 patients completing the study, 128 patients were randomised to telemonitoring and 128 to usual care; baseline characteristics of each group were similar.,The number of days to admission did not differ significantly between groups (adjusted hazard ratio 0.98, 95% confidence interval 0.66 to 1.44).,Over one year, the mean number of COPD admissions was similar in both groups (telemonitoring 1.2 admissions per person (standard deviation 1.9) v control 1.1 (1.6); P=0.59).,Mean duration of COPD admissions over one year was also similar between groups (9.5 days per person (standard deviation 19.1) v 8.8 days (15.9); P=0.88).,The intervention had no significant effect on SGRQ scores between groups (68.2 (standard deviation 16.3) v 67.3 (17.3); adjusted mean difference 1.39 (95% confidence interval −1.57 to 4.35)), or on other questionnaire outcomes.,Conclusions In participants with a history of admission for exacerbations of COPD, telemonitoring was not effective in postponing admissions and did not improve quality of life.,The positive effect of telemonitoring seen in previous trials could be due to enhancement of the underpinning clinical service rather than the telemonitoring communication.,Trial registration ISRCTN96634935.,Funding: The trial was funded by an NHS applied research programme grant from the Chief Scientist Office of the Scottish government (ARPG/07/03).,The funder had no role in study design and the collection, analysis, and interpretation of data and the writing of the article and the decision to submit it for publication.,NHS Lothian supported the telemonitoring service and the clinical services. | 1 |
The Glittre-ADL test (TGlittre) is a valid and reliable test for the evaluation of functional capacity and involves multiple physical activities of daily living (PADL), which are known to be troublesome to patients with Chronic Obstructive Pulmonary Disease (COPD).,However, it is still unknown if this test is also able to reflect the functional performance of patients with COPD.,To investigate whether the TGlittre reflects the functional performance of COPD patients and whether the necessary time to complete the TGlittre and the PADL varies according to disease severity.,Thirty-eight patients with COPD (age 65, SD=7 years; forced expiratory volume in the first second 41.3, SD=15.2% predicted) underwent anthropometric and lung function assessments and were submitted to the TGlittre and PADL measurement.,TGlittre performance correlated significantly (p<0.05) with PADL variables, such as time sitting (r=0.50), walking (r=-0.46), number of steps taken (r=-0.53), walking movement intensity (r=-0.66), walking energy expenditure (r=-0.50), and total energy expenditure (r=-0.33).,TGlittre performance was not significantly different in patients among the Global Initiative for COPD (GOLD) spirometric stages, but walking and sitting time were significantly lower and greater, respectively, in severe and very severe patients compared to those with moderate disease (p<0.05).,The performance on the TGlittre correlates with walking and sitting time and other real life PADL measurements.,The severity of the disease is associated with the differences in the level of physical activity in daily life more than in functional capacity. | Sleep problems are common in patients with chronic obstructive pulmonary disease (COPD), but the validity of patient-reported outcome measures (PROMs) that measure sleep dysfunction has not been evaluated.,We have reviewed the literature to identify disease-specific and non-disease-specific sleep PROMs that have been validated for use in COPD patients.,The review also examined the psychometric properties of identified sleep outcome measures and extracted point and variability estimates of sleep instruments used in COPD studies.,The online EMBASE, MEDLINE, PsycINFO, and SCOPUS databases for all years to May 2014 were used to source articles for the review.,The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.,Criteria from the Medical Outcomes Trust Scientific Advisory Committee guidelines were used to evaluate the psychometric properties of all sleep PROMs identified.,One COPD-specific and six non-COPD-specific sleep outcome measures were identified and 44 papers met the review selection criteria.,We only identified one instrument, the COPD and Asthma Sleep Impact Scale, which was developed specifically for use in COPD populations.,Ninety percent of the identified studies used one of two non-disease-specific sleep scales, ie, the Pittsburgh Sleep Quality Index and/or the Epworth Sleep Scale, although neither has been tested for reliability or validity in people with COPD.,The results highlight a need for existing non-disease-specific instruments to be validated in COPD populations and also a need for new disease-specific measures to assess the impact of sleep problems in COPD. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) with frequent exacerbations (ExCOPD) are commonly treated with inhaled corticosteroids (ICS) and are at risk of infections caused by potential pathogenic bacteria (PPB) including Pseudomonas aeruginosa (PsA).,To investigate the association between the use of ICS and PsA infection among ExCOPD.,Case-control study with longitudinal follow-up that recruited ExCOPD after a hospitalisation due to exacerbation between 2012 and 2020.,Patients with isolation of PsA (COPD-PsA) in sputum either during admission or follow-up were compared with those with other or no PPB.,Clinical, functional characteristics, DDD, use of ICS and survival were evaluated.,Cox regression analysis was performed to evaluate the risk factors associated to PsA infection and mortality.,358 patients (78% male, mean age 73±9 years) were enrolled and followed up for a median of 4 years (IQR=3-8). 173 patients (48.3%) had at least a positive culture for PsA.,COPD-PsA had more frequent exacerbations, more severe airflow limitation and higher mortality (69.4% vs 46.5%, p<0.001).,There were no differences in the use of ICS between groups but the dose of ICS was significantly higher among COPD-PsA (median of 500 µg fluticasone propionate equivalents (IQR=250-1000) vs 400 µg (IQR=200-1000), p=0.007).,Blood eosinophil count (BEC) was not different between ICS users and non-users.,In multivariate analysis, the dose of ICS was an independent risk factor for PsA infection and mortality but not ICS use.,ICS dose, but not its use, could be a risk factor for PsA infection in patients with severe COPD regardless of BEC. | The respiratory microbiome is altered in COPD patients but its relationship with core components of the disease, such as the severity of airflow limitation, the frequency of exacerbations or the circulating levels of eosinophils, is unclear.,Cross-sectional study comprising 72 clinically stable COPD patients (mean age 68 [SD 7.9] years; FEV1 48.7 [SD 20.1]% of reference) who provided spontaneous sputum samples for 16S rRNA gene amplification and sequencing.,The microbiome composition was analysed with QIIME.,We observed that: (1) more severe airflow limitation was associated with reduced relative abundance (RA) of Treponema and an increase in Pseudomonas; (2) patients with ≥2 exacerbations the previous year showed a significantly different bacterial community with respect to non-exacerbators (p = 0.014), with changes in 13 genera, including an increase of Pseudomonas, and finally, (3) peripheral eosinophils levels ≥2% were associated with more diverse microbiome [Chao1 224.51 (74.88) vs 277.39 (78.92) p = 0.006; Shannon 3.94 (1.05) vs 4.54 (1.06) p = 0.020], and a significant increase in the RAs of 20 genera.,The respiratory microbiome in clinically stable COPD patients varies significantly according to the severity of airflow limitation, previous history of exacerbations and circulating eosinophils levels.,The online version of this article (10.1186/s12890-019-0867-x) contains supplementary material, which is available to authorized users. | 1 |
The burden of symptoms and risk of exacerbations are the main drivers of the overall assessment of the Chronic Obstructive Pulmonary Disease (COPD) and the adequate treatment approaches per current Global Initiative for Chronic Obstructive Lung Disease (GOLD).,Physical activity has emerged as both functional outcome and non-pharmacological intervention in COPD patients, despite the lack of standardized measures or guidelines in clinical practice.,This study aimed to explore in more depth the 24-h respiratory symptoms, the physical activity level (PAL) and the relationship between these two determinants in stable COPD patients.,This was a multinational, multicenter, observational, cross-sectional study conducted in ten European countries and Israel.,Dedicated questionnaires for each part of the day (morning, daytime, night) were used to assess respiratory symptoms.,PAL was evaluated with self- and interview-reported tools [EVS (exercise as vital sign) and YPAS (Yale Physical Activity Survey)], and physician’s judgement.,Patients were stratified in ABCD groups by 2013 and 2017 GOLD editions using the questionnaires currently recommended: modified Medical Research Council dyspnea scale and COPD Assessment Test.,The study enrolled 2190 patients (mean age: 66.9 years; male: 70.0%; mean % predicted FEV1: 52.6; GOLD groups II-III: 84.5%; any COPD treatment: 98.9%).,Most patients (> 90%) reported symptoms in any part of the 24-h day, irrespective of COPD severity.,PAL evaluations showed discordant results between patients and physicians: 32.9% of patients considered themselves completely inactive, while physicians judged 11.9% patients as inactive.,By YPAS, the overall study population spent an average of 21.0 h/week performing physical activity, and 68.4% of patients were identified as sedentary.,In any GOLD ABCD group, the percentage of inactive patients was high.,Our study found negative, weak correlations between respiratory symptoms and self-reported PAL (p < 0.001).,Despite regular treatment, the majority of stable COPD patients with moderate to severe disease experienced daily variable symptoms.,Physical activity level was low in this COPD cohort, and yet overestimated by physicians.,With evidence indicating the negative consequences of inactivity, its adequate screening, a more active promotion and regular assessment of physical activity are urgently needed in COPD patients for better outcomes.,NCT03031769, retrospectively registered, 23 Jan 2017.,The online version of this article (10.1186/s12931-019-1053-7) contains supplementary material, which is available to authorized users. | Persons with Chronic Obstructive Pulmonary Disease (COPD), performing some level of regular physical activity, have a lower risk of both COPD-related hospital admissions and mortality.,COPD patients of all stages seem to benefit from exercise training programs, thereby improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue.,Physical inactivity, which becomes more severe with increasing age, is a point of concern in healthy older adults.,COPD might worsen this scenario, but it is unclear to what degree.,This literature review aims to present the extent of the impact of COPD on objectively-measured daily physical activity (DPA).,The focus is on the extent of the impact that COPD has on duration, intensity, and counts of DPA, as well as whether the severity of the disease has an additional influence on DPA.,A literature review was performed in the databases PubMed [MEDLINE], Picarta, PEDRO, ISI Web of Knowledge and Google scholar.,After screening, 11 studies were identified as being relevant for comparison between COPD patients and healthy controls with respect to duration, intensity, and counts of DPA.,Four more studies were found to be relevant to address the subject of the influence the severity of the disease may have on DPA.,The average percentage of DPA of COPD patients vs. healthy control subjects for duration was 57%, for intensity 75%, and for activity counts 56%.,Correlations of DPA and severity of the disease were low and/or not significant.,From the results of this review, it appears that patients with COPD have a significantly reduced duration, intensity, and counts of DPA when compared to healthy control subjects.,The intensity of DPA seems to be less affected by COPD than duration and counts.,Judging from the results, it seems that severity of COPD is not strongly correlated with level of DPA.,Future research should focus in more detail on the relation between COPD and duration, intensity, and counts of DPA, as well as the effect of disease severity on DPA, so that these relations become more understandable. | 1 |
Incidence and prognosis for severe asthma-COPD overlap is poorly characterized.,We investigated incidence and long-term outcome for patients with asthma-COPD overlap compared to asthma and COPD alone.,A total of 57,053 adults (aged 50-64 years) enrolled in the Danish Diet, Cancer, and Health cohort (1993-1997) were followed in the National Patients Registry for admissions for asthma (DJ45-46) and COPD (DJ40-44) and vital status.,Asthma-COPD overlap was defined as at least one hospital admission for asthma and one for COPD (different time points), and incident asthma-COPD overlap as at least one of the diagnoses occurring after enrollment into the Diet, Cancer, and Health cohort.,A total of 1,845 (3.2%) and 4,037 (7.1%) participants had admissions for asthma and COPD, respectively, with 662 (1.2%) participants with asthma-COPD overlap.,Incidence rate of asthma-COPD overlap per 1,000 person-years was higher in women (0.73) than in men (0.54) (P<0.02).,Mortality rate was higher in asthma-COPD overlap (25.9 per 1,000 person-years) compared with COPD (23.1, P<0.05) and asthma (7.9, P<0.001) alone.,Compared to COPD alone, mortality was higher in women with asthma-COPD overlap (19.6 and 25.5, respectively; P<0.01), and the excess mortality rate for asthma-COPD overlap patients was most prominent for younger age groups (12.9 compared to 7.2 and 4.6 for COPD and asthma alone, respectively; P<0.01).,This large population-based study revealed a higher incidence of severe asthma-COPD overlap in women compared to men, and furthermore that all-cause mortality is higher in women and younger subjects with asthma-COPD overlap compared with those with asthma or COPD alone. | The joint distribution of asthma and chronic obstructive pulmonary disease (COPD) has not been well described.,This study aims at determining the prevalence of self-reported physician diagnoses of asthma, COPD and of the asthma-COPD overlap syndrome and to assess whether these conditions share a common set of risk factors.,A screening questionnaire on respiratory symptoms, diagnoses and risk factors was administered by mail or phone to random samples of the general Italian population aged 20-44 (n = 5163) 45-64 (n = 2167) and 65-84 (n = 1030) in the frame of the multicentre Gene Environment Interactions in Respiratory Diseases (GEIRD) study.,A physician diagnosis of asthma or COPD (emphysema/chronic bronchitis/COPD) was reported by 13% and 21% of subjects aged <65 and 65-84 years respectively.,Aging was associated with a marked decrease in the prevalence of diagnosed asthma (from 8.2% to 1.6%) and with a marked increase in the prevalence of diagnosed COPD (from 3.3% to 13.3%).,The prevalence of the overlap of asthma and COPD was 1.6% (1.3%-2.0%), 2.1% (1.5%-2.8%) and 4.5% (3.2%-5.9%) in the 20-44, 45-64 and 65-84 age groups.,Subjects with both asthma and COPD diagnoses were more likely to have respiratory symptoms, physical impairment, and to report hospital admissions compared to asthma or COPD alone (p<0.01).,Age, sex, education and smoking showed different and sometimes opposite associations with the three conditions.,Asthma and COPD are common in the general population, and they coexist in a substantial proportion of subjects.,The asthma-COPD overlap syndrome represents an important clinical phenotype that deserves more medical attention and further research. | 1 |
To assess the effect of telehealthcare compared with usual practice in patients with chronic obstructive pulmonary disease (COPD).,A cluster-randomised trial with 26 municipal districts that were randomly assigned either to an intervention group whose members received telehealthcare in addition to usual practice or to a control group whose members received usual practice only (13 districts in each arm).,Twenty-six municipal districts in the North Denmark Region of Denmark.,Patients who fulfilled the Global Initiative for COPD guidelines and one of the following criteria: COPD Assessment Test score ≥10; or Medical Research Dyspnoea Council Scale ≥3; or Modified Medical Research Dyspnoea Council Scale ≥2; or ≥2 exacerbations during the past 12 months.,Health-related quality of life (HRQoL) assessed by the physical component summary (PCS) and mental component summary (MCS) scores of the Short Form 36-Item Health Survey, Version 2.,Data were collected at baseline and at 12 month follow-up and analysed according to the intention-to-treat principle with complete cases, n=574 (258 interventions; 316 controls) and imputed data, n=1225 (578 interventions, 647 controls) using multilevel modelling.,In the intention-to-treat analysis (n=1225), the raw mean difference in PCS from baseline to 12 month follow-up was −2.6 (SD 12.4) in the telehealthcare group and −2.8 (SD 11.9) in the usual practice group.,The raw mean difference in MCS scores in the same period was −4.7 (SD 16.5) and −5.3 (SD 15.5) for telehealthcare and usual practice, respectively.,The adjusted mean difference in PCS and MCS between groups at 12 months was 0.1 (95% CI −1.4 to 1.7) and 0.4 (95% CI −1.7 to 2.4), respectively.,The overall sample and all subgroups demonstrated no statistically significant differences in HRQoL between telehealthcare and usual practice.,NCT01984840; Results. | Although a number of studies have suggested that the use of Telemonitoring (TM) in patients with Chronic Obstructive Pulmonary Disease (COPD) can be useful and efficacious, its real utility in detecting Acute Exacerbation (AE) signaling the need for prompt treatment is not entirely clear.,The current study aimed to investigate the benefits of a TM system in managing AE in advanced-stage COPD patients to improve their Health-Related Quality of Life (HRQL) and to reduce utilization of healthcare services.,A 12-month Randomised Controlled Trial (RCT) was conducted in the Veneto region (Italy).,Adult patients diagnosed with Class III-IV COPD in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification were recruited and provided a TM system to alert the clinical staff via a trained operator whenever variations in respiratory parameters fell beyond the individual’s normal range.,The study’s primary endpoint was HRQL, measured by the Italian version of the two Short Form 36-item Health Survey (SF36v2).,Its secondary endpoints were: scores on the Hospital Anxiety and Depression Scale (HADS); the number and duration of hospitalizations; the number of readmissions; the number of appointments with a pulmonary specialist; the number of visits to the emergency department; and the number of deaths.,Three hundred thirty-four patients were enrolled and randomized into two groups for a 1 year period.,At its conclusion, changes in the SF36 Physical and Mental Component Summary scores did not significantly differ between the TM and control groups [(-2.07 (8.98) vs -1.91 (7.75); p = 0.889 and -1.08 (11.30) vs -1.92 (10.92); p = 0.5754, respectively].,Variations in HADS were not significantly different between the two groups [0.85 (3.68) vs 0.62 (3.6); p = 0.65 and 0.50 (4.3) vs 0.72 (4.5); p = 0.71].,The hospitalization rate for AECOPD and/or for any cause was not significantly different in the two groups [IRR = 0.89 (95% CI 0.79-1,04); p = 0.16 and IRR = 0.91 (95% CI 0,75 - 1.04); p = 0.16, respectively].,The readmission rate for AECOPD and/or any cause was, however, significantly lower in the TM group with respect to the control one [IRR = 0.43 (95% CI 0.19-0.98); p = 0.01 and 0.46 (95% CI 0.24-0.89); p = 0.01, respectively].,Study results showed that in areas where medical services are well established, TM does not significantly improve HRQL in patients with COPD who develop AE.,Although not effective in reducing hospitalizations, TM can nevertheless facilitate continuity of care during hospital-to-home transition by reducing the need for early readmission.,Retrospectively registered on January 2012, ClinicalTrials.gov Identifier: NCT01513980. | 1 |
Exacerbations of COPD (ECOPD) are a frequent cause of hospitalization that seemed to ameliorate during the COVID outbreak.,We aimed to evaluate the clinical characteristics of COPD-related hospital admissions and mortality in relation to the presence of COVID-19.,We conducted a case-control study of patients admitted in four teaching hospitals throughout Spain between March 15 and April 30, 2020.,Hospital admissions of respiratory cause with and without PCR-proven SARS-CoV-2 infection in patients with COPD were evaluated.,Baseline and episode-related clinical characteristics were analyzed.,Logistic regression analysis was performed to evaluate the risk for mortality.,During the study period, 2101 patients were admitted for respiratory worsening, 1200 (57.1%) with COVID-19.,A total of 228 (10.8%) were admitted due to COPD worsening, of whom 52 (22.8%) tested positive for COVID-19.,COPD patients with COVID-19, when compared to those without COVID-19, were more frequently males with better lung function (FEV1 postbronchodilator 71% vs 46% respectively, p<0.001) and had higher mortality (44.9% vs 13.6% respectively, p<0.001) despite similar age, comorbidities, total days of hospitalization and admission to intensive care unit.,COVID-19 and eosinopenia were the strongest risk factors for mortality in the multivariate analysis in the overall COPD population.,Inhaled corticosteroid use was not associated to mortality.,Hospitalizations for ECOPD without COVID-19 were more frequent than COPD with COVID-19 during the first outbreak, but the latter were associated with higher mortality and low eosinophil counts that warrant further analysis. | Early descriptions of patients admitted to hospital during the COVID-19 pandemic showed a lower prevalence of asthma and chronic obstructive pulmonary disease (COPD) than would be expected for an acute respiratory disease like COVID-19, leading to speculation that inhaled corticosteroids (ICSs) might protect against infection with severe acute respiratory syndrome coronavirus 2 or the development of serious sequelae.,We assessed the association between ICS and COVID-19-related death among people with COPD or asthma using linked electronic health records (EHRs) in England, UK.,In this observational study, we analysed patient-level data for people with COPD or asthma from primary care EHRs linked with death data from the Office of National Statistics using the OpenSAFELY platform.,The index date (start of follow-up) for both cohorts was March 1, 2020; follow-up lasted until May 6, 2020.,For the COPD cohort, individuals were eligible if they were aged 35 years or older, had COPD, were a current or former smoker, and were prescribed an ICS or long-acting β agonist plus long-acting muscarinic antagonist (LABA-LAMA) as combination therapy within the 4 months before the index date.,For the asthma cohort, individuals were eligible if they were aged 18 years or older, had been diagnosed with asthma within 3 years of the index date, and were prescribed an ICS or short-acting β agonist (SABA) only within the 4 months before the index date.,We compared the outcome of COVID-19-related death between people prescribed an ICS and those prescribed alternative respiratory medications: ICSs versus LABA-LAMA for the COPD cohort, and low-dose or medium-dose and high-dose ICSs versus SABAs only in the asthma cohort.,We used Cox regression models to estimate hazard ratios (HRs) and 95% CIs for the association between exposure categories and the outcome in each population, adjusted for age, sex, and all other prespecified covariates.,We calculated e-values to quantify the effect of unmeasured confounding on our results.,We identified 148 557 people with COPD and 818 490 people with asthma who were given relevant respiratory medications in the 4 months before the index date.,People with COPD who were prescribed ICSs were at increased risk of COVID-19-related death compared with those prescribed LABA-LAMA combinations (adjusted HR 1·39 [95% CI 1·10-1·76]).,Compared with those prescribed SABAs only, people with asthma who were prescribed high-dose ICS were at an increased risk of death (1·55 [1·10-2·18]), whereas those given a low or medium dose were not (1·14 [0·85-1·54]).,Sensitivity analyses showed that the apparent harmful association we observed could be explained by relatively small health differences between people prescribed ICS and those not prescribed ICS that were not recorded in the database (e value lower 95% CI 1·43).,Our results do not support a major role for regular ICS use in protecting against COVID-19-related death among people with asthma or COPD.,Observed increased risks of COVID-19-related death can be plausibly explained by unmeasured confounding due to disease severity.,UK Medical Research Council. | 1 |
The article addresses the strategic role of workforce preparation in the process of adoption of Systems Medicine as a driver of biomedical research in the new health paradigm.,It reports on relevant initiatives, like CASyM, fostering Systems Medicine at EU level.,The chapter focuses on the BioHealth Computing Program as a reference for multidisciplinary training of future systems-oriented researchers describing the productive interactions with the Synergy-COPD project. | Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory process of the lung inducing persistent airflow limitation.,Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy.,Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate.,In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators.,Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles.,Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization.,These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients. | 1 |
Only a few studies have evaluated the radiologic features of pre-existing structural abnormalities where lung cancer may develop.,This study aimed to analyze the computed tomography (CT) images of lung areas where new cancer developed in chronic obstructive pulmonary disease (COPD) patients.,We conducted a multicenter, longitudinal cohort study, called the Keio COPD Comorbidity Research, to assess the incidence of lung cancer.,Emphysema and interstitial abnormalities were evaluated in 240 COPD patients who had baseline CT scans applicable for further digital analyses.,For patients who developed lung cancer during the 3-year follow-up period, the local spherical lung density of the precancerous area was individually quantified.,Lung cancer was newly diagnosed in 21 participants (2.3% per year).,The percent-age of low attenuation area in patients who developed lung cancer was higher than that of the other patients (20.0% vs 10.4%, P=0.014).,The presence of emphysema (odds ratio [OR] 4.2, 95% confidence interval [CI] 1.0-29.0, P=0.049) or interstitial lung abnormalities (OR 15.6, 95% CI 4.4-65.4, P<0.0001) independently increased the risk for lung cancer.,Compared with the density of the entire lung, the local density of the precancerous area was almost the same in patients with heterogeneous emphysema, but it was higher in most patients with interstitial abnormalities.,The presence of emphysema or interstitial abnormalities or a combination of both were independent predictors of lung cancer development in COPD patients.,Furthermore, lung cancer most often developed in non-emphysematous areas or in interstitial abnormalities. | Computed tomography (CT) is widely used for evaluation of lung diseases.,To evaluate the value of CT measurement of pulmonary artery for diagnosis of chronic obstructive pulmonary disease (COPD) and its comorbidity pulmonary hypertension (PH), we retrospectively reviewed the CT of 221 patients with COPD and 115 control patients without cardiovascular or lung disease.,Patients with COPD were divided into PH (COPD-PH) and non-PH according to systolic pulmonary artery pressure.,Main pulmonary artery (MPA), right pulmonary artery (RPA) and left pulmonary artery branches, and ascending aorta (AAo) and descending aorta (DAo) diameters were measured.,Meanwhile, the ratios of MPA/AAo and MPA/DAo were calculated.,MPA, RPA, and left pulmonary artery diameters were significantly larger in COPD than those in the controls, and this augment was more obvious in COPD-PH.,AAo and DAo diameters did not vary obviously between groups, while MPA/AAo and MAP/DAo increased significantly in COPD and PH.,MPA could be helpful for COPD diagnosis (MPA diameter ≥27.5 mm, sensitivity 54%, and specificity 80%), and RPA could be applied for COPD-PH diagnosis (RPA diameter ≥23.4 mm, sensitivity 67%, and specificity 76%).,There was a marked correlation between MPA/DAo and systolic pulmonary artery pressure (r=0.594, P<0.001).,Therefore, chest CT could be a simple and effective modality for diagnostic evaluation of COPD and its comorbidity, PH. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is one of the top leading causes of death and disability, and its management is focused on reducing risk factors, relieving symptoms, and preventing exacerbations.,The study aim was to describe COPD prescribing patterns in Greece by using existing health administrative data for outpatients.,This is a retrospective cross-sectional study based on prescriptions collected by the largest social insurance fund, during the first and last trimester of 2012.,Selection criteria were the prescription of specific active substances and a COPD diagnosis.,Extracted information included active substance, strength, pharmaceutical form and number of packages prescribed, diagnosis, time of dispensing, as well as insurees’ age, gender, percentage of co-payment and social security unique number.,Statistical analysis included descriptive statistics and logistic regression.,174,357 patients received medicines for COPD during the study period.,Patients were almost equally distributed between male and female, and age above 55 years was strongly correlated with COPD.,Most patients received a long-acting beta agonist plus inhaled corticosteroid combination (LABA +ICS), followed by long-acting muscarinic agonist (LAMA). 63% patients belonging in the 35-54 age received LABA+ICS.,LAMA was prescribed more frequently among males and was strongly correlated with COPD.,The study provides big data analysis of Greek COPD prescribing patterns.,It highlights the need for appropriate COPD classification in primary care illustrating the role of electronic prescribing in ensuring appropriate prescribing.,Moreover, it indicates possible gender differences in treatment response or disease severity, and the impact of statutory co-payments on prescribing. | 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. | 1 |
Asthma and chronic obstructive pulmonary disease are inflammatory lung disorders responsible for significant morbidity and mortality worldwide.,While the importance of allergic responses in asthma is well known, respiratory viral and bacterial infections and pollutants especially cigarette smoke are important factors in the pathogenesis of both diseases.,Corticosteroid treatment remains the first preference of treatment in either disease, however these therapies are not always completely effective, and are associated with side effects and steroid resistance.,Due to such limitations, development of new treatments represents a major goal for both the pharmaceutical industry and academic researchers.,There are now excellent reasons to promote NF-κB signalling intermediates and Rel family proteins as potential therapeutic targets for both asthma and chronic obstructive pulmonary disease.,This notion is supported by the fact that much of the underlying inflammation of both diseases independent of stimuli, is mediated at least in part, by NF-κB mediated signalling events in several cell types.,Also, a range of inhibitors of NF-κB signalling intermediates are now available, including DNA oligonucleotides and DNA-peptide molecules that act as NF-κB decoy sequences, small molecule inhibitors such as IKK-β inhibitors, and proteasome inhibitors affecting NF-κB signalling, that have either shown promise in animal models or have begun clinical trials in other disorders.,This review will focus on the role of NF-κB in both diseases, will discuss its suitability as a target, and will highlight recent key studies that support the potential of NF-κB as a therapeutic target in these two important inflammatory lung diseases. | Macrophages are among the most abundant cells in the respiratory tract, and they can have strikingly different phenotypes within this environment.,Our knowledge of the different phenotypes and their functions in the lung is sketchy at best, but they appear to be linked to the protection of gas exchange against microbial threats and excessive tissue responses.,Phenotypical changes of macrophages within the lung are found in many respiratory diseases including asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis.,This paper will give an overview of what macrophage phenotypes have been described, what their known functions are, what is known about their presence in the different obstructive and restrictive respiratory diseases (asthma, COPD, pulmonary fibrosis), and how they are thought to contribute to the etiology and resolution of these diseases. | 1 |
Exacerbations of COPD are managed differently, but whether treatment of one exacerbation predicts the likelihood of subsequent events is unknown.,We examined whether the treatment given for exacerbations predicted subsequent outcomes.,This was a post-hoc analysis of 17,135 patients with COPD from TIOtropium Safety and Performance In Respimat® (TIOSPIR®).,Patients treated with tiotropium with one or more moderate to severe exacerbations on study were analyzed using descriptive statistics, logistic and Cox regression analysis, and Kaplan-Meier plots.,Of 8,061 patients with moderate to severe exacerbation(s), demographics were similar across patients with exacerbations treated with antibiotics and/or steroids or hospitalization.,Exacerbations treated with systemic corticosteroids alone or in combination with antibiotics had the highest risk of subsequent exacerbation (HR: 1.21, P=0.0004 and HR: 1.33, P<0.0001, respectively), and a greater risk of having a hospitalized (severe) exacerbation (HR: 1.59 and 1.63, P<0.0001, respectively) or death (HR: 1.50, P=0.0059 and HR: 1.47, P=0.0002, respectively) compared with exacerbations treated with antibiotics alone.,Initial hospitalization led to the highest risk of subsequent hospitalization (all-cause or COPD related [severe exacerbation], HR: 3.35 and 4.31, P<0.0001, respectively) or death (all-cause or COPD related, HR: 3.53 and 5.54, P<0.0001, respectively) versus antibiotics alone.,These data indicate that the way exacerbations are treated initially is a useful guide to the patient’s subsequent clinical course.,Factors that clinicians consider when making treatment choices require further clarification. | To characterize the distribution of BMI in a population-based sample of COPD patients and to evaluate the impact of obesity on their health status, exercise tolerance, systemic inflammation and comorbidity.,A population-based sample of 3,797 subjects aged 40-80 years from the EPI-SCAN study was selected.,Subjects were categorized according their body mass index (BMI) as underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2) or obese (BMI≥30.0 kg/m2).,Subjects were evaluated with post-bronchodilator spirometry and 6-minute walk tests.,Smoking habits, respiratory symptoms, generic and specific quality of life, daily physical activities, comorbidities and systemic inflammatory biomarkers were recorded.,The prevalence of obesity or being overweight was higher in the 382 COPD patients than in the subjects without airflow limitation (29.4%, 95%CI 24.8-33.9% vs.,24.3, 95%CI 22.9-25.8; and 44.7%, 95%CI 39.7-49.6% vs.,43.0%, 95%CI 41.3-44.6, respectively; p = 0.020).,In the COPD subgroup, obese subjects presented more dyspnea and less chronic cough, chronic bronchitis or chronic phlegm than normal-weight patients, as well as a worse health status.,Moreover, reduced exercise tolerance and higher plasmatic C-reactive protein levels were found in the obese patients, who also presented a greater prevalence of cardiovascular disease (adjusted odds ratio 4.796, 95%CI 1.806-12.736, p = 0.002).,In a population-based sample, obesity is more prevalent in COPD patients than in subjects without airflow limitation.,Furthermore, obesity affects the clinical manifestations, quality of life and exercise tolerance of COPD patients, and it may contribute to a phenotype characterized by increased systemic inflammation and greater frequency of cardiovascular comorbidity. | 1 |
COPD self-management is a complex behavior influenced by many factors.,Despite scientific evidence that better disease outcomes can be achieved by enhancing self-management, many COPD patients do not respond to self-management interventions.,To move toward more effective self-management interventions, knowledge of characteristics associated with activation for self-management is needed.,The purpose of this study was to identify key patient and disease characteristics of activation for self-management.,An explorative cross-sectional study was conducted in primary and secondary care in patients with COPD.,Data were collected through questionnaires and chart reviews.,The main outcome was activation for self-management, measured with the 13-item Patient Activation Measure (PAM).,Independent variables were sociodemographic variables, self-reported health status, depression, anxiety, illness perception, social support, disease severity, and comorbidities.,A total of 290 participants (age: 67.2±10.3; forced expiratory volume in 1 second predicted: 63.6±19.2) were eligible for analysis.,While poor activation for self-management (PAM-1) was observed in 23% of the participants, only 15% was activated for self-management (PAM-4).,Multiple linear regression analysis revealed six explanatory determinants of activation for self-management (P<0.2): anxiety (β: −0.35; −0.6 to −0.1), illness perception (β: −0.2; −0.3 to −0.1), body mass index (BMI) (β: −0.4; −0.7 to −0.2), age (β: −0.1; −0.3 to −0.01), Global Initiative for Chronic Obstructive Lung Disease stage (2 vs 1 β: −3.2; −5.8 to −0.5; 3 vs 1 β: −3.4; −7.1 to 0.3), and comorbidities (β: 0.8; −0.2 to 1.8), explaining 17% of the variance.,This study showed that only a minority of COPD patients is activated for self-management.,Although only a limited part of the variance could be explained, anxiety, illness perception, BMI, age, disease severity, and comorbidities were identified as key determinants of activation for self-management.,This knowledge enables health care professionals to identify patients at risk of inadequate self-management, which is essential to move toward targeting and tailoring of self-management interventions.,Future studies are needed to understand the complex causal mechanisms toward change in self-management. | To unpack and interpret descriptions of experiences of social relationships during pulmonary rehabilitation (PR) for people living with chronic obstructive pulmonary disease (COPD).,Inspired by interpretive phenomenology, individual qualitative interviews were conducted twice with 18 persons from COPD rehabilitation units in two general hospitals.,Qualitative content analysis was performed.,Analysis of the interviews revealed the overarching theme of belonging.,The participants emphasised social integration in rehabilitation groups as well as support from peers and health-care personnel as important dimensions of social relationships with regard to PR.,Active participation in and engagement with the groups provided opportunities for patients to share their knowledge, encouraged mutual trust, and support and increased self-confidence, and motivation for self-care and further social participation.,Integration in the groups and perceived support during PR made coping and adaptation easier and had a positive effect on quality of life.,Patients' perspectives on PR were strongly influenced by certain facets of social relationships, such as social integration and social support.,Patients', peers' and health-care professionals' strategies to promote social support and social integration should be further explored in the future, both in different contexts and for longer periods of time. | 1 |
COPD patients have high pulmonary and systemic oxidative stress that correlates with severity of disease.,Sulforaphane has been shown to induce expression of antioxidant genes via activation of a transcription factor, nuclear factor erythroid-2 related factor 2 (Nrf2).,This parallel, placebo-controlled, phase 2, randomized trial was conducted at three US academic medical centers.,Patients who met GOLD criteria for COPD and were able to tolerate bronchoscopies were randomly assigned (1:1:1) to receive placebo, 25 μmoles, or 150 μmoles sulforaphane daily by mouth for four weeks.,The primary outcomes were changes in Nrf2 target gene expression (NQ01, HO1, AKR1C1 and AKR1C3) in alveolar macrophages and bronchial epithelial cells.,Secondary outcomes included measures of oxidative stress and airway inflammation, and pulmonary function tests.,Between July 2011 and May 2013, 89 patients were enrolled and randomized.,Sulforaphane was absorbed in the patients as evident from their plasma metabolite levels.,Changes in Nrf2 target gene expression relative to baseline ranged from 0.79 to 1.45 and there was no consistent pattern among the three groups; the changes were not statistically significantly different from baseline.,Changes in measures of inflammation and pulmonary function tests were not different among the groups.,Sulforaphane was well tolerated at both dose levels.,Sulforaphane administered for four weeks at doses of 25 μmoles and 150 μmoles to patients with COPD did not stimulate the expression of Nrf2 target genes or have an effect on levels of other anti-oxidants or markers of inflammation.,Clinicaltrials.gov: NCT01335971. | Smoking tobacco is a leading cause of chronic obstructive pulmonary disease (COPD), but although the majority of COPD cases can be directly related to smoking, only a quarter of smokers actually develop the disease.,A potential reason for the disparity between smoking and COPD may involve an individual's ability to mount a protective adaptive response to cigarette smoke (CS).,Glutathione (GSH) is highly concentrated in the lung epithelial lining fluid (ELF) and protects against many inhaled oxidants.,The changes in GSH that occur with CS are not well investigated; therefore the GSH adaptive response that occurs with a commonly utilized CS exposure was examined in mice.,Mice were exposed to CS for 5 h after which they were rested in filtered air for up to 16 h.,GSH levels were measured in the ELF, bronchoalveolar lavage cells, plasma, and tissues.,GSH synthesis was assessed by measuring γ-glutamylcysteine ligase (GCL) activity in lung and liver tissue.,GSH levels in the ELF, plasma, and liver were decreased by as much as 50% during the 5 h CS exposure period whereas the lung GSH levels were unchanged.,Next, the time course of rebound in GSH levels after the CS exposure was examined.,CS exposure initially decreased ELF GSH levels by 50% but within 2 h GSH levels rebound to about 3 times basal levels and peaked at 16 h with a 6-fold increase and over repeat exposures were maintained at a 3-fold elevation for up to 2 months.,Similar changes were observed in tissue GCL activity which is the rate limiting step in GSH synthesis.,Furthermore, elevation in ELF GSH levels was not arbitrary since the CS induced GSH adaptive response after a 3d exposure period prevented GSH levels from dropping below basal levels.,CS exposures evoke a powerful GSH adaptive response in the lung and systemically.,These data suggests there may be a sensor that sets the ELF GSH adaptive response to prevent GSH levels from dipping below basal levels.,Factors that disrupt GSH adaptive responses may contribute to the pathophysiology of COPD. | 1 |
Exercise tolerance decreases as COPD progresses.,Pulmonary hypertension (PH) is common in COPD and may reduce performance further.,COPD patients with and without PH could potentially be identified by cardiopulmonary exercise test (CPET).,However, results from previous studies are diverging, and a unified conclusion is missing.,We hypothesized that CPET combined with arterial blood gases is useful to discriminate between COPD outpatients with and without PH.,In total, 93 COPD patients were prospectively included.,Pulmonary function tests, right heart catheterization, and CPET with blood gases were performed.,The patients were divided, by mean pulmonary artery pressure, into COPD-noPH (<25 mmHg) and COPD-PH (≥25 mmHg) groups.,Linear mixed models (LMMs) were fitted to estimate differences when repeated measurements during the course of exercise were considered and adjusted for gender, age, and airway obstruction.,Ventilatory and/or hypoxemic limitation was the dominant cause of exercise termination.,In LMM analyses, significant differences between COPD-noPH and COPD-PH were observed for PaO2, SaO2, PaCO2, ventilation, respiratory frequency, and heart rate.,PaO2 <61 mmHg (8.1 kPa) during unloaded pedaling, the only load level achieved by all the patients, predicted PH with a sensitivity of 86% and a specificity of 78%.,During CPET, low exercise performance and PaO2 strongly indicated PH in COPD patients. | Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms and pathological consequences.,Although primarily viewed as a respiratory disease, COPD has both pulmonary and extrapulmonary effects, which have an impact on many aspects of physical, emotional, and mental well-being.,Traditional assessment of COPD relies heavily on measuring lung function, specifically forced expiratory volume in 1 second (FEV1).,However, the evidence suggests that FEV1 is a relatively poor correlate of symptoms such as breathlessness and the impact of COPD on daily life.,Furthermore, many consequences of the disease, including anxiety and depression and the ability to perform daily activities, can only be described and reported reliably by the patient.,Thus, in order to provide a comprehensive view of the effects of interventions in clinical trials, it is essential that spirometry is accompanied by assessments using patient-reported outcome (PRO) instruments.,We provide an overview of patient-reported outcome concepts in COPD, such as breathlessness, physical functioning, and health status, and evaluate the tools used for measuring these concepts.,Particular attention is given to the newly developed instruments emerging in response to recent regulatory guidelines for the development and use of PROs in clinical trials.,We conclude that although data from the development and validation of these new PRO instruments are emerging, to build the body of evidence that supports the use of a new instrument takes many years.,Furthermore, new instruments do not necessarily have better discriminative or evaluative properties than older instruments.,The development of new PRO tools, however, is crucial, not only to ensure that key COPD concepts are being reliably measured but also that the relevant treatment effects are being captured in clinical trials.,In turn, this will help us to understand better the patient’s experience of the disease. | 1 |
The clinical and radiological presentation of chronic obstructive pulmonary disease (COPD) is heterogenous depending on the characterized sources of inflammation.,This study aimed to evaluate COPD phenotypes associated with specific dust exposure.,This study was designed to compare the characteristics, clinical outcomes and radiological findings between two prospective COPD cohorts representing two distinguishing regions in the Republic of Korea; COPD in Dusty Area (CODA) and the Korean Obstructive Lung Disease (KOLD) cohort.,A total of 733 participants (n = 186 for CODA, and n = 547 for KOLD) were included finally.,A multivariate analysis to compare lung function and computed tomography (CT) measurements of both cohort studies after adjusting for age, sex, education, body mass index, smoking status, and pack-year, Charlson comorbidity index, and frequency of exacerbation were performed by entering the level of FEV1(%), biomass exposure and COPD medication into the model in stepwise.,The mean wall area (MWA, %) became significantly lower in COPD patients in KOLD from urban and metropolitan area than those in CODA cohort from cement dust area (mean ± standard deviation [SD]; 70.2 ± 1.21% in CODA vs.,66.8 ± 0.88% in KOLD, p = 0.028) after including FEV1 in the model.,COPD subjects in KOLD cohort had higher CT-emphysema index (EI, 6.07 ± 3.06 in CODA vs.,20.0 ± 2.21 in KOLD, p < 0.001, respectively).,The difference in the EI (%) was consistently significant even after further adjustment of FEV1 (6.12 ± 2.88% in CODA vs.,17.3 ± 2.10% in KOLD, p = 0.002, respectively).,However, there was no difference in the ratio of mean lung density (MLD) between the two cohorts (p = 0.077).,Additional adjustment for biomass parameters and medication for COPD did not alter the statistical significance after entering into the analysis with COPD medication.,Higher MWA and lower EI were observed in COPD patients from the region with dust exposure.,These results suggest that the imaging phenotype of COPD is influenced by specific environmental exposure. | Severe exacerbations of COPD, ie, those leading to hospitalization, have profound clinical implications for patients and significant economic consequences for society.,The prevalence and burden of severe COPD exacerbations remain high, despite recognition of the importance of exacerbation prevention and the availability of new treatment options.,Severe COPD exacerbations are associated with high mortality, have negative impact on quality of life, are linked to cardiovascular complications, and are a significant burden on the health-care system.,This review identified risk factors that contribute to the development of severe exacerbations, treatment options (bronchodilators, antibiotics, corticosteroids [CSs], oxygen therapy, and ventilator support) to manage severe exacerbations, and strategies to prevent readmission to hospital.,Risk factors that are amenable to change have been highlighted.,A number of bronchodilators have demonstrated successful reduction in risk of severe exacerbations, including long-acting muscarinic antagonist or long-acting β2-agonist mono- or combination therapies, in addition to vaccination, mucolytic and antibiotic therapy, and nonpharmacological interventions, such as pulmonary rehabilitation.,Recognition of the importance of severe exacerbations is an essential step in improving outcomes for patients with COPD.,Evidence-based approaches to prevent and manage severe exacerbations should be implemented as part of targeted strategies for disease management. | 1 |
Current guidelines recommend spirometry to confirm a diagnosis of chronic obstructive pulmonary disease (COPD).,To investigate whether a self-reported diagnosis of COPD is associated with prior spirometry and whether a correct diagnosis of COPD is more likely when spirometry was performed.,We used data from the population-based Austrian Burden of Obstructive Lung Disease (BOLD) study.,Participants were aged >40 years and completed post-bronchodilator spirometry.,Reported COPD diagnosis and reported prior lung function test were based on questionnaire.,Persistent airflow limitation was defined as post-bronchodilator forced expiratory volume in one second/forced vital capacity ratio <0.7, corresponding with COPD Global initiative for chronic Obstructive Lung Disease (GOLD) grade I+, and GOLD grade II+ was also investigated.,A correct diagnosis of COPD was defined as a reported physician's diagnosis of COPD and the presence of persistent airflow limitation.,68 (5.4%) of 1,258 participants reported a prior physician's diagnosis of COPD.,Of these, only 17 (25.0%) reported a lung function test within the past 12 months and 46 (67.6%) at any time in the past.,The likelihood for a correct COPD GOLD grade I+ diagnosis was similar among subjects reporting a lung function test during the last 12 months (likelihood ratio 2.07, 95% CI 0.89 to 5.50) and those not reporting a lung function during the last 12 months (likelihood ratio 2.78, 95% CI 1.58 to 4.87).,Similar likelihood ratios were seen when GOLD grade II+ was investigated and when lung function was reported at any time in the past.,One-third of subjects with a reported diagnosis of COPD never had a lung function test.,When spirometry was reported, this did not increase the likelihood of a correct COPD diagnosis. | Using the COPD Diagnostic Questionnaire (CDQ) as a selection tool for spirometry could potentially improve the efficiency and accuracy of chronic obstructive pulmonary disease (COPD) diagnosis in at-risk patients.,To identify an optimal single cut point for the CDQ that divides primary care patients into low or high likelihood of COPD, with the latter group undergoing spirometry.,Former or current smokers aged 40-85 years with no prior COPD diagnosis were invited to a case-finding appointment with the practice nurse at various general practices in Sydney, Australia.,The CDQ was collected and pre- and post-bronchodilator spirometry was performed.,Cases with complete CDQ data and spirometry meeting quality standards were analysed (1,054 out of 1,631 patients).,CDQ cut points were selected from a receiver operating characteristic (ROC) curve.,The area under the ROC curve was 0.713.,A cut point of 19.5 had the optimal combination of sensitivity (63%) and specificity (70%) with two-thirds below this cut point.,A cut point of 14.5 corresponded to a sensitivity of 91%, specificity of 35% and negative predictive value of 96%, and 31% of patients below this cut point.,The CDQ can be used to select patients at risk of COPD for spirometry using one cut point.,We consider two possible cut points.,The 19.5 cut point excludes a higher proportion of patients from undergoing spirometry with the trade-off of more false negatives.,The 14.5 cut point has a high sensitivity and negative predictive value, includes more potential COPD cases but has a higher rate of false positives. | 1 |
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. | The BEACON study evaluated the efficacy and safety of QVA149, a once-daily dual bronchodilator containing a fixed-dose combination of the long-acting β2-agonist (LABA) indacaterol and long-acting muscarinic antagonist (LAMA) glycopyrronium (NVA237), in development for the treatment of patients with chronic obstructive pulmonary disease (COPD), compared with the free-dose concurrent administration of indacaterol plus glycopyrronium (IND+GLY).,In this multicenter, double-blind, parallel group study, patients with stage II or stage III COPD (Global initiative for chronic Obstructive Lung Disease [GOLD] 2010) were randomized (1:1) to once-daily QVA149 (110 μg indacaterol/50 μg glycopyrronium) or concurrent administration of indacaterol (150 μg) and glycopyrronium (50 μg) via the Breezhaler® device (Novartis AG, Basel, Switzerland) for 4 weeks.,The primary endpoint was to evaluate the noninferiority of QVA149 as compared with concurrent administration of IND+GLY, for trough forced expiratory volume in 1 second (FEV1) after 4 weeks of treatment.,The other assessments included FEV1 area under the curve from 0 to 4 hours (AUC0-4 hours) at day 1 and week 4, symptom scores, rescue medication use, safety, and tolerability over the 4-week study period.,Of 193 patients randomized, 187 (96.9%) completed the study.,Trough FEV1 at week 4 for QVA149 and IND+GLY was 1.46 L ± 0.02 and 1.46 L ± 0.18, respectively.,The FEV1 AUC0-4 hours at day 1 and week 4 were similar between the two treatment groups.,Both treatment groups had a similar reduction in symptom scores and rescue medication use for the 4-week treatment period.,Overall, 25.6% of patients in QVA149 group and 25.2% in the IND+GLY group experienced an adverse event, with the majority being mild-to-moderate in severity.,No deaths were reported during the study or during the 30 days follow-up period.,The BEACON study demonstrated that once-daily QVA149 provides an efficacy and safety profile similar to the concurrent administration of its monocomponents indacaterol and glycopyrronium. | 1 |
Purpose: Assess the clinical and economic consequences associated with an early versus late diagnosis in patients with COPD.,Patients and methods: In a retrospective, observational cohort study, electronic medical record data (2000-2014) were collected from Swedish primary care patients with COPD.,COPD indicators (pneumonia, other respiratory diseases, oral corticosteroids, antibiotics for respiratory infections, prescribed drugs for respiratory symptoms, lung function measurement) registered prior to diagnosis were applied to categorize patients into those receiving early (2 or less indicators) or late diagnosis (3 or more indicators registered >90 days preceding a COPD diagnosis).,Outcome measures included annual rate of and time to first exacerbation, mortality risk, prevalence of comorbidities and health care utilization.,Results: More patients with late diagnosis (n=8827) than with early diagnosis (n=3870) had a recent comorbid diagnosis of asthma (22.0% vs 3.9%; P<0.0001).,Compared with early diagnosis, patients with late diagnosis had a higher exacerbation rate (hazard ratio [HR] 1.89, 95% confidence interval [CI]: 1.83-1.96; P<0.0001) and shorter time to first exacerbation (HR 1.61, 95% CI: 1.54-1.69; P<0.0001).,Mortality was not different between groups overall but higher for late versus early diagnosis, after excluding patients with past asthma diagnosis (HR 1.10, 95% CI: 1.02-1.18; P=0.0095).,Late diagnosis was also associated with higher direct costs than early diagnosis.,Conclusion: Late COPD diagnosis is associated with higher exacerbation rate and increased comorbidities and costs compared with early diagnosis.,The study highlights the need for accurate diagnosis of COPD in primary care in order to reduce exacerbations and the economic burden of COPD. | Prediction models for exacerbations in patients with chronic obstructive pulmonary disease (COPD) are scarce.,Our aim was to develop and validate a new model to predict exacerbations in patients with COPD.,The derivation cohort consisted of patients aged 65 years or over, with a COPD diagnosis, who were followed up over 24 months.,The external validation cohort consisted of another cohort of COPD patients, aged 50 years or over.,Exacerbations of COPD were defined as symptomatic deterioration requiring pulsed oral steroid use or hospitalization.,Logistic regression analysis including backward selection and shrinkage were used to develop the final model and to adjust for overfitting.,The adjusted regression coefficients were applied in the validation cohort to assess calibration of the predictions and calculate changes in discrimination applying C-statistics.,The derivation and validation cohort consisted of 240 and 793 patients with COPD, of whom 29% and 28%, respectively, experienced an exacerbation during follow-up.,The final model included four easily assessable variables: exacerbations in the previous year, pack years of smoking, level of obstruction, and history of vascular disease, with a C-statistic of 0.75 (95% confidence interval [CI]: 0.69-0.82).,Predictions were well calibrated in the validation cohort, with a small loss in discrimination potential (C-statistic 0.66 [95% CI 0.61-0.71]).,Our newly developed prediction model can help clinicians to predict the risk of future exacerbations in individual patients with COPD, including those with mild disease. | 1 |
A multitude of epidemiological studies have shown that ambient fine particulate matter 2.5 (diameter < 2.5um; PM2.5) was associated with increased morbidity and mortality of chronic obstructive pulmonary disease (COPD).,However, the underlying associated mechanisms have not yet been elucidated.,We conducted this study to investigate the role of PM2.5 in the development of COPD and associated mechanisms.,We firstly conducted a cross-sectional study in Chinese han population to observe PM2.5 effects on COPD morbidity.,Then, in vitro, we incubated human bronchial epithelial cells to different concentrations of PM2.5 for 24 h.,The expression levels of IL-6 and IL-8 were detected by ELISA and the levels of MMPs, TGF-β1, fibronectin and collagen was determined by immunoblotting.,In vivo, we subjected C57BL/6 mice to chronic prolonged exposure to PM2.5 for 48 weeks to study the influence of PM2.5 exposure on lung function, pulmonary structure and inflammation.,We found that the effect of PM2.5 on COPD morbidity was associated with its levels and that PM2.5 and cigarette smoke could have a synergistic impact on COPD development and progression.,Both vitro and vivo studies demonstrated that PM2.5 exposure could induce pulmonary inflammation, decrease lung function, and cause emphysematous changes.,Furthermore, PM2.5 could markedly aggravated cigarette smoke-induced changes.,In short, we found that prolonged chronic exposure to PM2.5 resulted in decreased lung function, emphysematous lesions and airway inflammation.,Most importantly, long-term PM2.5 exposure exacerbateed cigarette smoke-induced changes in COPD. | In chronic obstructive pulmonary disease (COPD), oxidative stress regulates the inflammatory response of bronchial epithelium and monocytes/macrophages through kinase modulation and has been linked to glucocorticoid unresponsiveness.,Glycogen synthase-3β (GSK3β) inactivation plays a key role in mediating signaling processes upon reactive oxygen species (ROS) exposure.,We hypothesized that GSK3β is involved in oxidative stress-induced glucocorticoid insensitivity in COPD.,We studied levels of phospho-GSK3β-Ser9, a marker of GSK3β inactivation, in lung sections and cultured monocytes and bronchial epithelial cells of COPD patients, control smokers, and nonsmokers.,We observed increased levels of phospho-GSK3β-Ser9 in monocytes, alveolar macrophages, and bronchial epithelial cells from COPD patients and control smokers compared with nonsmokers.,Pharmacological inactivation of GSK3β did not affect CXCL8 or granulocyte-macrophage colony-stimulating factor (GM-CSF) expression but resulted in glucocorticoid insensitivity in vitro in both inflammatory and structural cells.,Further mechanistic studies in monocyte and bronchial epithelial cell lines showed that GSK3β inactivation is a common effector of oxidative stress-induced activation of the MEK/ERK-1/2 and phosphatidylinositol 3-kinase/Akt signaling pathways leading to glucocorticoid unresponsiveness.,In primary monocytes, the mechanism involved modulation of histone deacetylase 2 (HDAC2) activity in response to GSK3β inactivation.,In conclusion, we demonstrate for the first time that ROS-induced glucocorticoid unresponsiveness in COPD is mediated through GSK3β, acting as a ROS-sensitive hub. | 1 |
Rationale: Bronchoscopic lung volume reduction with Zephyr Valves improves lung function, exercise tolerance, and quality of life of patients with hyperinflated emphysema and little to no collateral ventilation.,Objectives:Post hoc analysis of patient-reported outcomes (PROs), including multidimensional measures of dyspnea, activity, and quality of life, in the LIBERATE (Lung Function Improvement after Bronchoscopic Lung Volume Reduction with Pulmonx Endobronchial Valves used in Treatment of Emphysema) study are reported.,Methods: A total of 190 patients with severe heterogeneous emphysema and little to no collateral ventilation in the target lobe were randomized 2:1 to the Zephyr Valve or standard of care.,Changes in PROs at 12 months in the two groups were compared: dyspnea with the Transitional Dyspnea Index (TDI), focal score; the Chronic Obstructive Pulmonary Disease Assessment Test (CAT; breathlessness on hill/stairs); Borg; the EXAcerbations of Chronic pulmonary disease Tool-PRO, dyspnea domain; activity with the TDI, magnitude of task/effort/functional impairment, CAT (limited activities), and the St.,George’s Respiratory Questionnaire (SGRQ), activity domain; and psychosocial status with the SGRQ, impacts domain, and CAT (confidence and energy).,Results: At 12 months, patients using the Zephyr Valve achieved statistically significant and clinically meaningful improvements in the SGRQ; CAT; and the TDI, focal score, compared with standard of care.,Improvements in the SGRQ were driven by the impacts and activity domains (P < 0.05 and P < 0.001, respectively).,Reduction in CAT was through improvements in breathlessness (P < 0.05), energy level (P < 0.05), activities (P < 0.001), and increased confidence when leaving home (P < 0.05).,The TDI measures of effort, task, and functional impairment were uniformly improved (P < 0.001).,The EXAcerbations of Chronic Pulmonary Disease Tool (EXACT)-PRO, dyspnea domain, was significantly improved in the Zephyr Valve group.,Improvements correlated with changes in residual volume and residual volume/TLC ratio.,Conclusions: Patients with severe hyperinflated emphysema achieving lung volume reductions with Zephyr Valves experience improvements in multidimensional scores for breathlessness, activity, and psychosocial parameters out to at least 12 months.,Clinical trial registered with www.clinicaltrials.gov (NCT01796392). | Chronic obstructive pulmonary disease (COPD) progresses very slowly and the majority of patients are therefore elderly.,COPD is characterized by an abnormal persistent inflammatory response to noxious environmental stimuli and there are increasing evidences for a close relationship between premature aging and chronic inflammatory diseases.,Thus, COPD is considered to be a disease of an accelerating aging.,In this review, we collected the evidence for roles of aging on pathogenesis of COPD and considered future therapeutic strategy for COPD based on this senescence hypothesis.,Since calorie restriction has been proved to extend lifespan, many efforts were made to clarify the molecular mechanism of aging.,Aging is defined as the progressive decline of homeostasis that occurs after the reproductive phase of life is complete, leading to an increasing risk of disease or death due to impaired DNA repair after damage by oxidative stress or telomere shortening as a result of repeated cell division.,During aging, pulmonary function progressively deteriorates; innate immunity is impaired and pulmonary inflammation increases, accompanied by structural changes, such as an enlargement of airspaces.,Noxious environmental gases, such as cigarette smoke, may worsen these aging-related events in the lung or accelerate aging of the lung due to reduction in anti-aging molecules and/or stimulation of aging molecules.,Aging signaling are complex but conserved in divert species, such as worm, fruit fry, rodent and humans.,Especially the insulin like growth factor (IGF-1) signaling was well documented.,Geroprotectors are therapeutics that affect the root cause of aging and age-related diseases, and thus prolong the life-span of animals.,Most of geroprotectors such as melatonin, metformin, rapamycin and resveratrol are anti-oxidant or anti-aging molecule regulators.,Therefore, geroprotection for the lung might be an attractive approach for the treatment of COPD by preventing premature aging of lung. | 1 |
Directly recorded patient experience of symptoms and health-related quality of life (HRQoL) can complement lung function and exacerbation rate data in chronic obstructive pulmonary disease (COPD) clinical studies.,The FULFIL study recorded daily symptoms and activity limitation together with additional patient-reported outcomes of dyspnea and HRQoL, as part of the prespecified analyses.,FULFIL co-primary endpoint data have been previously reported.,FULFIL was a phase III, 24-week, randomized, double-blind, double-dummy, multicenter study comparing once-daily single inhaler triple therapy [fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI)] 100 µg/62.5 µg/25 µg with twice-daily inhaled corticosteroid/long-acting β2-agonist therapy [budesonide/formoterol (BUD/FOR)] 400 µg/12 µg in patients with symptomatic COPD at risk of exacerbations.,A subset participated for 52 weeks.,Patient-reported assessments were: Evaluating Respiratory Symptoms in COPD™ (E-RS: COPD), St George’s Respiratory Questionnaire (SGRQ) for COPD, COPD Assessment Test (CAT), baseline and transitional dyspnea indices (TDI) and daily and global anchor questions for activity limitation.,FF/UMEC/VI showed greater reductions from baseline in 4-weekly mean E-RS: COPD total and all subscale scores compared with BUD/FOR; differences were statistically significant (P < 0.05) at each time period.,FF/UMEC/VI also demonstrated greater improvements from baseline at weeks 4 and 24 in SGRQ domain scores and TDI focal score compared with BUD/FOR.,At weeks 4 and 24, improvements greater than the minimal clinically important difference from baseline were observed in CAT score with FF/UMEC/VI, but not BUD/FOR; differences were statistically significant (P ≤ 0.003).,These findings demonstrate sustained daily symptom and HRQoL benefits of FF/UMEC/VI versus BUD/FOR.,The inclusion of the CAT may provide data that are readily generalizable to everyday clinical practice.,ClinicalTrials.gov number: NCT02345161.,GSK.,The online version of this article (10.1007/s12325-017-0650-4) contains supplementary material, which is available to authorized users. | Several small studies found night-time awakenings due to COPD symptoms were associated with decreased health status.,In this study, night-time awakenings in patients with COPD were examined and effects of tiotropium therapy evaluated.,This study was a post hoc, exploratory, pooled analysis of twin, multicenter, double-blind, randomized, placebo-controlled, parallel-group trials.,Patients with stable moderate-to-severe COPD were randomized to tiotropium HandiHaler® (n = 550) or placebo (n = 371) and followed for 13 weeks.,During a 2-week, pre-treatment baseline period and for 13 weeks on treatment, self-reported night-time awakenings due to COPD symptoms, rescue medication (albuterol) use, and morning and evening peak expiratory flow rate (PEFR) were recorded daily.,Nightly, COPD-related awakenings were scored: 0 = no awakenings; 1 = 1 awakening; 2 = 2-3 awakenings; or 3 = awake most of the night.,Health-related quality-of-life (HRQoL) and energy-fatigue questionnaires were completed at baseline and during treatment.,Patients were aged 65.2 ± 8.7 years (mean ± SD), with a mean pre-bronchodilator FEV1 of 36.1 ± 13.5 % predicted normal at baseline.,Data for night-time awakenings and albuterol use were available for 543 (99 %) patients on tiotropium and 352 (95 %) on placebo.,At baseline, 280 (51.5 %) patients on tiotropium and 179 (50.1 %) on placebo reported ≥1 COPD-related night-time awakening per week.,Over the 13-weeks’ treatment, tiotropium was associated with fewer night-time awakenings, with mean ± SE overall awakening scores per week of 0.356 ± 0.006 compared with 0.421 ± 0.007 for placebo (p < 0.001); means were significantly lower for tiotropium versus placebo in patients with baseline awakenings (p < 0.001), but not for those without baseline awakenings.,COPD-related night-time awakenings were associated with increased nocturnal rescue medication use and lower HRQoL ratings in both treatment arms.,Following start of treatment, tiotropium decreased patients’ use of rescue medication compared with placebo, and morning and evening adjusted means for PEFR were higher for tiotropium compared with placebo.,Tiotropium is associated with decreased COPD-related night-time awakenings.,Night-time awakenings are associated with increased nocturnal rescue medication use and may be a surrogate marker of symptom control in patients with COPD.,The online version of this article (doi:10.1186/s12931-016-0340-9) contains supplementary material, which is available to authorized users. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) are at risk of developing cardiac arrhythmias and elevated heart rate.,A theoretical mechanistic association based on the interaction of long-acting β2-agonists (LABAs) with adrenoreceptors in the heart and vasculature is assumed as a potential class-related risk.,Therefore, we performed a pooled analysis of Holter electrocardiogram (ECG) data from four 48-week, randomized, double-blind, placebo-controlled, parallel-group, Phase III clinical trials evaluating olodaterol (5 μg or 10 μg) or formoterol (12 µg) versus placebo.,We analyzed Holter ECG data from a representative subset of 775 patients with Global Initiative for Chronic Obstructive Lung Disease stage 2-4 COPD from four studies (1222.11-14) assessing olodaterol (5 μg and 10 μg) and formoterol (12 µg) versus placebo.,No statistically significant (P>0.3) or clinically relevant differences in the shift from baseline of premature supraventricular or ventricular beats were observed among the active treatment and the placebo groups.,Minor and transient differences were observed in the adjusted mean heart rate from baseline during treatment in all groups.,There was a numerically small but statistically significant increase for formoterol at Week 24, olodaterol 5 μg at Weeks 12 and 40, and olodaterol 10 μg at Week 40 (all less than 3.0 beats per minute).,Mean heart rates returned to a statistically non-significant change at Week 48 for all treatment groups.,No increase in major adverse cardiovascular events was observed.,Treatment with olodaterol or formoterol is not associated with arrhythmias or a persistent increase in heart rate as assessed by Holter ECG in patients with COPD.,ClinicalTrials.gov identifiers: NCT00782210 (1222.11); NCT00782509 (1222.12); NCT00793624 (1222.13); NCT00796653 (1222.14). | The novel long-acting β 2-agonist olodaterol demonstrated an acceptable safety profile in short-term phase II clinical studies.,This analysis of four randomized, double-blind, placebo-controlled, parallel-group, phase III studies (1222.11, NCT00782210; 1222.12, NCT00782509; 1222.13, NCT00793624; 1222.14, NCT00796653) evaluated the long-term safety of olodaterol once daily (QD) in a large cohort of patients with moderate to very severe (Global initiative for chronic Obstructive Lung Disease 2-4) chronic obstructive pulmonary disease (COPD).,The studies compared olodaterol (5 or 10 μg) QD via Respimat®, formoterol 12 μg twice daily (BID) via Aerolizer® (1222.13 and 1222.14), and placebo for 48 weeks.,Patients continued receiving background maintenance therapy, with ∼60% receiving concomitant cardiovascular therapy and 25% having a history of concomitant cardiac disease.,Pre-specified analyses of pooled data assessed the adverse events (AEs) and serious AEs in the whole population, and in subgroups with cardiac disease, along with in-depth electrocardiogram and Holter monitoring.,In total, 3104 patients were included in the safety analysis: 876 received olodaterol 5 μg, 883 received olodaterol 10 μg, 885 received placebos, and 460 received formoterol 12 μg BID.,Overall incidence of on-treatment AEs (71.2%), serious AEs (16.1%), and deaths (1.7%) were balanced across treatment groups.,Respiratory and cardiovascular AEs, including major adverse cardiac events, were reported at similar frequencies in placebo and active treatment groups.,The safety profiles of both olodaterol 5 μg (marketed and registered dose) and 10 μg QD delivered via Respimat® are comparable to placebo and formoterol BID in this population, with no safety signals identified. | 1 |
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. | Metabolic syndrome is a common extrapulmonary comorbidity in patients with chronic obstructive pulmonary disease (COPD).,However, the reported relationship of COPD with dyslipidemia, an important component of metabolic syndrome, is ambiguous.,The aim of this meta-analysis is to investigate the association between COPD and the serum levels of high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), total cholesterol (TC), and triglyceride (TG).,The PubMed and Embase databases were searched to find potential studies using the search terms of (“dyslipidemia” or “HDL” or “LDL” or “cholesterol” or “triglyceride”) and COPD.,We also performed subgroup analysis enrolling patients who were not receiving treatment for dyslipidemia.,Mean differences (MD) with 95% confidence intervals (CI) were estimated with random effects models.,A total of 11 studies comprising 615 cases and 471 controls were included in the study.,No significant differences were found in the HDL (MD = −2.55, 95% CI [−6.03, 0.93], P = 0.15), LDL (MD = −2.25, 95% CI [−13.36, 8.86], P = 0.69), TC (MD = −2.69, 95% CI [−13.30, 7.92], P = 0.62), and TG (MD = 6.90, 95% CI [−2.81, 16.60], P = 0.16) levels of the 2 groups.,However, subgroup analysis enrolling patients who were not receiving treatment for dyslipidemia showed that TG levels were higher in patients with stable COPD than in healthy individuals (MD = 16.35, 95% CI [5.90, 26.80], P = 0.002).,Excluding the impact of hypolipidemic treatment on serum lipid profile, TG levels were higher in patients with COPD than in healthy individuals.,This meta-analysis suggested that physicians should screen COPD patients for elevated TG levels to reduce the risk of cardiovascular morbidity and mortality. | 1 |
The aim of this study was to assess the degree of adherence for two standard regimens for administrating anticholinergic drugs (12 and 24 hours) in patients with chronic obstruction of the airflow and to establish whether the use of a once-daily dose improves the level of treatment adherence.,We used long-acting anticholinergics (LAMAs) as a study variable, and included the entire health area of Castile-La Mancha, numbering 2,100,998 inhabitants, as the study population.,We analyzed a total of 16,446 patients who had been prescribed a LAMA between January 1, 2013 and December 31, 2013.,The follow-up period, based on a centralized system of electronic prescription management, was extended until December 2014.,During 2013, the medication collected was 7.4%-10.7% higher than indicated by labeling.,This was very similar for all LAMAs, irrespective of the patient’s sex, the molecule, the device, and the drug dosage.,We did not observe seasonal variations in the consumption of LAMAs, nor did we detect differences between prescription drugs for once-daily (every 24 hours) versus twice-daily (every 12 hours) administration, between the different molecules, or between different types of inhalers for the same molecule.,The results were similar in 2014.,The principal conclusion of this study is that, in an area with a centralized management system of pharmacological prescriptions, adherence to treatment with LAMAs is very high, irrespective of the molecules or inhalation device.,We did not find that patients who used twice-daily medication had a lower adherence. | Glycopyrronium bromide (NVA237) is an inhaled long-acting muscarinic antagonist in development for treatment of COPD.,This study compared the efficacy and safety of once-daily (OD) and twice-daily (BID) glycopyrronium bromide regimens, using a novel model-based approach, in patients with moderate-to-severe COPD.,Double-blind, randomized, dose-finding trial with an eight-treatment, two-period, balanced incomplete block design.,Patients (smoking history ≥10 pack-years, post-bronchodilator FEV1 ≥30% and <80% predicted, FEV1/FVC <0.7) were randomized to one of 16 independent sequences for 28 days.,Primary endpoint: mean trough FEV1 at Day 28.,385 patients (mean age 61.2 years; mean post-bronchodilator FEV1 53% predicted) were randomized; 88.6% completed.,All OD and BID dosing regimens produced dose-dependent bronchodilation; at Day 28, increases in mean trough FEV1 versus placebo were statistically significant for all regimens, ranging from 51 mL (glycopyrronium bromide 12.5 μg OD) to 160 mL (glycopyrronium bromide 50 μg BID).,Pharmacodynamic steady-state was reached by Day 7.,There was a small separation (≤37 mL) between BID and OD dose-response curves for mean trough FEV1 at steady-state in favour of BID dosing.,Over 24 hours, separation between OD and BID regimens was even smaller (FEV1 AUC0-24h maximum difference for equivalent daily dose regimens: 8 mL).,Dose-response results for FEV1 at 12 hours, FEV1 AUC0-12h and FEV1 AUC0-4h at steady-state showed OD regimens provided greater improvement over placebo than BID regimens for total daily doses of 25 μg, 50 μg and 100 μg, while the reverse was true for OD versus BID regimens from 12-24 hours.,The 12.5 μg BID dose produced a marginally higher improvement in trough FEV1 versus placebo than 50 μg OD, however, the response at 12 hours over placebo was suboptimal (74 mL).,Glycopyrronium bromide was safe and well tolerated at all doses.,Glycopyrronium bromide 50 μg OD provides significant bronchodilation over a 24 hour period, and in terms of FEV1 AUC0-24h is not significantly different than the same total daily dose administered BID.,Importantly, OD dosing may confer better patient adherence.,The results are consistent with previous glycopyrronium bromide studies and support once-daily dosing of glycopyrronium bromide 50 μg in patients with moderate-to-severe COPD.,ClinicalTrials.gov: NCT01119950 | 1 |
miR-190a-5p expression alters dynamically in response to hypoxia.,However, the role of miR-190a-5p expression in hypoxia-induced pulmonary hypertension (PH) remains unclear.,We sought to correlate the miR-190a-5p expression levels with the severity, diagnosis, and prognosis of PH in relation to chronic obstructive pulmonary disease (COPD-PH).,Additionally, we evaluated the effect of miR-190a-5p through in vitro experiments on human pulmonary endothelial cells (HPECs) that were exposed to hypoxia and in vivo experiments using an animal model of hypoxia-induced PH.,Circulating miR-190a-5p levels were measured from 73 patients with PH and 32 healthy controls through quantitative real-time PCR.,The levels of miR-190a-5p and the expression of Krüppel-like factor 15 (KLF15) were analyzed in HPECs that were exposed to hypoxia, and the effects of antagomir-190a-5p in mice with chronic hypoxia-induced PH were tested.,Target gene analysis was performed by Western blot and luciferase assay.,The miR-190a-5p level was significantly higher in patients with COPD-PH than in the healthy controls.,Higher miR-190a-5p levels were associated with a greater severity of COPD-PH.,In vitro experiments on HPECs showed that exposure to hypoxia increased the miR-190a-5p levels significantly.,KLF15 was validated as a target of miR-190a-5p.,Transfection with miR-190a-5p mimicked inhibition of KLF15 expression in HPECs.,In the mouse model of PH, antagomir-190a-5p reduced right ventricular systolic pressure and enhanced the KLF15 expression levels in lung tissue.,miR-190a-5p regulates hypoxia-induced PH by targeting KLF15.,The circulating levels of miR-190a-5p correlate with the severity of COPD-PH, thereby confirming the diagnostic and prognostic value of this parameter in COPD-PH. | The adaptor protein p66Shc regulates intracellular oxidant levels through the modulation of a forkhead-related transcription factor (FOXO3a).,The genetic ablation of p66Shc (p66Shc-/-) renders mice resistant to oxidative stress and p53-dependent apoptosis.,We investigated whether p66Shc ablation in mice modifies lung cellular and molecular responses to cigarette smoke (CS) exposure.,No differences between wild type (WT) and p66Shc-/- mice were observed in terms of inflammation and oxidant burden after acute CS exposure; however,p66Shc ablation modifies specific features of chronic inflammation induced by repeated exposure to CS.,Unlike WT mice, p66Shc-/- mice did not develop emphysema, showing protection toward oxidative damage to DNA and apoptosis as revealed by a trivial 8-hydroxyguanosine staining and faint TUNEL and caspase-3 positivity on alveolar epithelial cells.,Unexpectedly, CS exposure in p66Shc-/- mice resulted in respiratory bronchiolitis with fibrosis in surrounded alveoli.,Respiratory bronchiolitis was characterized by peribronchiolar infiltrates of lymphocytes and histiocytes, accumulation of ageing pigmented macrophages within and around bronchioles, and peribronchiolar fibrosis.,The blockage of apoptosis interferes with the macrophage “clearance” from alveolar spaces, favouring the accumulation of aging macrophages into alveoli and the progressive accumulation of iron pigment in long-lived senescent cells.,The presence of areas of interstitial and alveolar fibrosis in peripheral parenchyma often accompanied the bronchiolar changes.,Macrophages from smoking p66Shc-/- mice elaborate M2 cytokines (i.e., IL-4 and IL-13) and enzymes (i.e., chitinase and arginase I), which can promote TGF-beta expression, collagen deposition, and fibrosis in the surrounding areas.,We demonstrate here that resistance to oxidative stress and p53-dependent apoptosis can modify tissue responses to CS caused by chronic inflammation without influencing early inflammatory response to CS exposure. | 1 |
The forced oscillation technique provides information concerning respiratory impedance, which comprises resistance and reactance of the respiratory system.,However, its relationship with morphological changes of the lungs in chronic obstructive pulmonary disease (COPD) remains unclear.,Respiratory impedance and spirometric data were evaluated in 98 patients with COPD and 49 reference subjects.,Wall thickness (WT) and airway intraluminal area (Ai) of third- to sixth-generation bronchi, and percentage low-attenuation area with less than −950 HU (%LAA) of lungs were measured using three-dimensional computed tomography.,COPD patients had higher respiratory impedance, decreased Ai, and increased %LAA compared with reference subjects.,Indices of respiratory resistance and reactance and forced expiratory volume in 1 second (FEV1) were correlated with Ai, and the association between percent predicted FEV1 and Ai was predominant in distal bronchi.,The difference in respiratory resistance between 5 Hz and 20 Hz (R5-R20) and FEV1/forced vital capacity ratio (FEV1/FVC) were correlated with WT.,The %LAA was correlated with the FEV1/FVC ratio and respiratory reactance.,Airway function measurements with the forced oscillation technique provide complementary information to spirometry in COPD. | 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. | 1 |
The rate of obesity is increasing in Asia, but the clinical impact of body mass index (BMI) on the outcome of chronic obstructive pulmonary disease (COPD) remains unknown.,We aimed to assess this impact while focusing on the risk of exacerbation, health-care utilization, and medical costs.,We examined 43,864 subjects registered in the Korean National Health and Nutrition Examination Survey (KNHANES) database from 2007 to 2012, and linked the data of COPD patients who had mild to moderate airflow obstruction (n = 1,320) to National Health Insurance (NHI) data.,COPD was confirmed by spirometry.,BMI was used to stratify patients into four categories: underweight (BMI <18.5 kg/m2), normal range (18.5-22.9 kg/m2), overweight (23-24.9 kg/m2), and obese (≥25 kg/m2).,Of the 1,320 patients with COPD with mild to moderate airflow obstruction, 27.8% had a BMI ≥25 kg/m2.,Compared with normal-weight patients, obese patients tended to experience fewer exacerbations (incidence rate ratio [IRR] 0.88; 95% CI 0.77-0.99; P = 0.04), although this association was not significant in a multivariable analysis.,COPD-related health-care utilization and medical expenses were higher among underweight patients than the other groups.,After adjustment, the risk of COPD-related hospitalization was highest among underweight and higher among overweight patients vs normal-weight patients (adjusted IRRs: 7.12, 1.00, 1.26, and 1.02 for underweight, normal, overweight, and obese groups, respectively; P = 0.01).,Decreased weight tends to negatively influence prognosis of COPD with mild to moderate airflow obstruction, whereas higher BMI was not significantly related to worse outcomes. | COPD often coexists with chronic conditions that may influence disease prognosis.,We investigated associations between chronic (co)morbidities and exacerbations in primary care COPD patients.,Retrospective cohort study based on 2012-2013 electronic health records from 179 Dutch general practices.,Comorbidities from patients with physician-diagnosed COPD were categorized according to International Classification of Primary Care (ICPC) codes.,Chi-squared tests, uni- and multivariable logistic, and Cox regression analyses were used to study associations with exacerbations, defined as oral corticosteroid prescriptions.,Fourteen thousand six hundred three patients with COPD could be studied (mean age 67 (SD 12) years, 53% male) for two years.,At baseline 12,826 (88%) suffered from ≥1 comorbidities, 3263 (22%) from ≥5.,The most prevalent comorbidities were hypertension (35%), coronary heart disease (19%), and osteoarthritis (18%).,Several comorbidities showed statistically significant associations with frequent (i.e., ≥2/year) exacerbations: heart failure (odds ratio [OR], 95% confidence interval: 1.72; 1.38-2.14), blindness & low vision (OR 1.46; 1.21-1.75), pulmonary cancer (OR 1.85; 1.28-2.67), depression 1.48; 1.14-1.91), prostate disorders (OR 1.50; 1.13-1.98), asthma (OR 1.36; 1.11-1.70), osteoporosis (OR 1.41; 1.11-1.80), diabetes (OR 0.80; 0.66-0.97), dyspepsia (OR 1.25; 1.03-1.50), and peripheral vascular disease (OR 1.20; 1.00-1.45).,From all comorbidity categories, having another chronic respiratory disease beside COPD showed the highest risk for developing a new exacerbation (Cox hazard ratio 1.26; 1.17-1.36).,Chronic comorbidities are highly prevalent in primary care COPD patients.,Several chronic comorbidities were associated with having frequent exacerbations and increased exacerbation risk. | 1 |
The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.,The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada.,Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified.,The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.,The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively.,The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th.,The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first.,Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.,The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation.,Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality. | The diagnosis and treatment of patients with chronic obstructive pulmonary disease (COPD) in Spain continues to present challenges, and problems are exacerbated when there is a lack of coordinated follow-up between levels of care.,This paper sets out the protocol for assessing the impact of an integrated management model for the care of patients with COPD.,The new model will be evaluated in terms of 1) improvement in the rational utilization of health-care services and 2) benefits reflected in improved health status and quality of life for patients.,A quasi-experimental study of the effectiveness of a COPD management model called COPD PROCESS.,The patients in the study cohorts will be residents of neighborhoods served by two referral hospitals in Barcelona, Spain.,One area comprises the intervention group (n = 32,248 patients) and the other the control group (n = 32,114 patients).,The study will include pre- and post-intervention assessment 18 months after the program goes into effect.,Analyses will be on two datasets: clinical and administrative data available for all patients, and clinical assessment information for a cohort of 440 patients sampled randomly from the intervention and control areas.,The main endpoints will be the hospitalization rates in the two health-care areas and quality-of-life measures in the two cohorts.,The COPD PROCESS model foresees the integrated multidisciplinary management of interventions at different levels of the health-care system through coordinated routine clinical practice.,It will put into practice diagnostic and treatment procedures that are based on current evidence, multidisciplinary consensus, and efficient use of available resources.,Care pathways in this model are defined in terms of patient characteristics, level of disease severity and the presence or absence of exacerbation.,The protocol covers the full range of care from primary prevention to treatment of complex cases. | 1 |
Chronic obstructive pulmonary disease (COPD) is a progressive disease and a composite endpoint could be an indicator of treatment effect on disease worsening.,This post-hoc analysis assessed whether indacaterol/glycopyrronium (IND/GLY) 110/50 μg once daily reduced the risk of clinically important deterioration (CID) versus salmeterol/fluticasone (SFC) 50/500 μg twice daily in moderate-to-very severe COPD patients from the FLAME study.,CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV1) or ≥ 4-unit increase in St.,George’s Respiratory Questionnaire (SGRQ) total score or a moderate-to-severe COPD exacerbation.,Changes from baseline in the rate of moderate and severe exacerbations, time to first moderate-to-severe exacerbation, and change from baseline in the SGRQ score, measured after Week 12 up to Week 52, were assessed by presence of early CID (CID+) or absence of CID (CID−) at Week 12.,IND/GLY significantly delayed the time to CID (hazard ratio [HR] (95% confidence interval [CI]), 0.72 [0.67-0.78]; P < 0.0001), and reduced the incidences of CID versus SFC.,Additionally, IND/GLY delayed the time to CID in all patient subgroups.,After 12 weeks until 52 weeks, CID+ patients had a significantly higher rate of moderate-to-severe exacerbations versus CID− patients (P < 0.0001); moreover, CID+ patients experienced moderate-to-severe exacerbations significantly earlier versus CID− patients (P < 0.0001).,CID+ patients had a comparable change in the SGRQ total score versus CID− patients.,IND/GLY reduced the risk of CID versus SFC.,CID had a significant impact on long-term exacerbation outcomes in patients with moderate-to-very severe COPD and a history of ≥1 exacerbations in the previous year.,Clinicaltrials.gov NCT01782326.,The online version of this article (10.1186/s12931-018-0830-z) contains supplementary material, which is available to authorized users. | 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 | 1 |
Chronic obstructive pulmonary disease (COPD) is an inflammatory disease characterized by a progressive and irreversible deterioration of lung function.,Exacerbations of COPD have prolonged negative effects on pulmonary function and a major impact on health status and outcomes.,NLRP3 inflammasome is a cardinal component of the inflammatory response, with marked evidence in stable and exacerbations of COPD.,The aim of our study was to evaluate the NLRP3 inflammasome activity during COPD exacerbation by using an in vitro model.,A549 cells were stimulated with different concentrations (10%, 4%, 2%) of cigarette smoke extract (CSE) with or without LPS (0.1μg/ml) for 24 hours.,Cell viability was assessed by using XTT test.,Levels of inflammatory cytokines (IL-8, MCP-1, and IL-1β) were measured by ELISA and the activity level of NLRP-3 was evaluated by flow cytometry.,Cells exposed to CSE present an increase in inflammatory cytokines (IL-8 and MCP-1) production in a dose-dependent manner.,Incubation with LPS to these cells results in higher levels of IL-8 and MCP-1 compared to stimulation of CSE alone.,NLRP3 inflammasome activity and IL-1β levels were significantly increased in cells exposed to both CSE and LPS compared to CSE alone.,NLRP3 inflammasome is upregulated in an in-vitro model of COPD and COPD exacerbation.,Our findings provide novel biomarkers for COPD exacerbation and may present new targets for future research. | 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. | 1 |
Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease.,For each patient, four of five treatments were administered once daily for 6 weeks, with a 21-day washout between treatments: tiotropium/olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg, olodaterol 5 µg or placebo, all via the Respimat inhaler.,Primary outcomes were inspiratory capacity prior to exercise and exercise endurance time during constant work-rate cycle ergometry to symptom limitation at 75% of peak incremental work rate after 6 weeks (2 h post-dose).,295 and 291 patients were treated in MORACTO 1 and 2, respectively.,Tiotropium/olodaterol 2.5/5 and 5/5 µg provided significant improvements in inspiratory capacity versus placebo and monotherapies (p<0.0001), and significant improvements in exercise endurance time versus placebo (p<0.0001).,Intensity of breathing discomfort was reduced following both doses of tiotropium/olodaterol versus placebo (p<0.0001).,Once-daily tiotropium/olodaterol yielded improvements in lung hyperinflation versus placebo and statistically significant improvements versus monotherapies.,Tiotropium/olodaterol also showed improvements in dyspnoea and exercise tolerance versus placebo but not consistently versus monotherapies.,T/O reduces lung hyperinflation in COPD versus T, O or placebo and increases exercise endurance versus placebohttp://ow.ly/ml3G307XW6a | 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. | 1 |
Expiratory flow limitation (EFL) is seen in some patients presenting with a COPD exacerbation; however, it is unclear how EFL relates to the clinical features of the exacerbation.,We hypothesized that EFL when present contributes to symptoms and duration of recovery during a COPD exacerbation.,Our aim was to compare changes in EFL with symptoms in subjects with and without flow-limited breathing admitted for a COPD exacerbation.,A total of 29 subjects with COPD were recruited within 48 hours of admission to West China Hospital for an acute exacerbation.,Daily measurements of post-bronchodilator spirometry, resistance, and reactance using the forced oscillation technique and symptom (Borg) scores until discharge were made.,Flow-limited breathing was defined as the difference between inspiratory and expiratory respiratory system reactance (EFL index) greater than 2.8 cmH2O·s·L−1.,The physiological predictors of symptoms during recovery were determined by mixed-effect analysis.,Nine subjects (31%) had flow-limited breathing on admission despite similar spirometry compared to subjects without flow-limited breathing.,Spirometry and resistance measures did not change between enrolment and discharge.,EFL index values improved in subjects with flow-limited breathing on admission, with resolution in four patients.,In subjects with flow-limited breathing on admission, symptoms were related to inspiratory resistance and EFL index values.,In subjects without flow-limited breathing, symptoms related to forced expiratory volume in 1 second/forced vital capacity.,In the whole cohort, EFL index values at admission was related to duration of stay (Rs=0.4, P=0.03).,The presence of flow-limited breathing as well as abnormal respiratory system mechanics contribute independently to symptoms during COPD exacerbations. | The skeletal muscles play an essential role in life, providing the mechanical basis for respiration and movement.,Skeletal muscle dysfunction is prevalent in all stages of chronic obstructive pulmonary disease (COPD), and significantly influences symptoms, functional capacity, health related quality of life, health resource usage and even mortality.,Furthermore, in contrast to the lungs, the skeletal muscles are potentially remedial with existing therapy, namely exercise-training.,This review summarizes clinical and laboratory observations of the respiratory and peripheral skeletal muscles (in particular the diaphragm and quadriceps), and current understanding of the underlying etiological processes.,As further progress is made in the elucidation of the molecular mechanisms of skeletal muscle dysfunction, new pharmacological therapies are likely to emerge to treat this important extra-pulmonary manifestation of COPD. | 1 |
Airway eosinophilic inflammation is a characteristic of asthmatic patients and of a sub group of COPD subjects.,Blood eosinophils are deemed as a good surrogate marker of sputum eosinophilic inflammation; however, controversial data have been published particularly in COPD.,The aim of our study was to compare blood and sputum eosinophils in COPD and asthmatic patients in “real life”.,Sputum was induced in stable patients with COPD or asthma with hypertonic saline solution and blood eosinophils were evaluated.,Frequency of comorbidities was recorded.,Correlations were performed stratifying patients by disease and comorbidities.,146 patients, 57 with COPD and 89 with asthma were evaluated.,Blood and sputum eosinophils expressed as percentages were correlated in COPD (rho = 0.40; p = 0.004), but the entity of correlation was lower compared with asthmatic subjects (rho = 0.71; p < 0.0001).,When blood eosinophils were expressed as counts the correlation was slightly lower than when expressed as percentages in COPD (rho = 0.35; p = 0.01) and in asthmatic patients (rho = 0.68; p < 0.0001).,In COPD patients older than 73 years or with blood eosinophils higher than the median value (210.6 eos/μl), or co-diagnosed with hypertension, ischemic heart disease or atrial fibrillation no correlation between blood and sputum eosinophils was found.,However, the effect of ischemic heart disease and atrial fibrillation could be driven by hypertension since most of these patients have this comorbidity.,Blood eosinophils correlated with sputum eosinophils to a lesser degree in COPD than in asthmatic patients.,Older age, high blood eosinophils and hypertension affected the correlation between blood and sputum eosinophils, more studies are needed to evaluate the role of other cardiac comobidities. | 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. | 1 |
After the development of the COPD Strategy of the National Health Service in Spain, all scientific societies, patient organisations, and central and regional governments formed a partnership to enhance care and research in COPD.,At the same time, the Spanish Society of Pneumology and Thoracic Surgery (SEPAR) took the initiative to convene the various scientific societies involved in the National COPD Strategy and invited them to participate in the development of the new Spanish guidelines for COPD (Guía Española de la EPOC; GesEPOC).,Probably the more innovative approach of GesEPOC is to base treatment of stable COPD on clinical phenotypes, a term which has become increasingly used in recent years to refer to the different clinical forms of COPD with different prognostic implications.,The proposed phenotypes are: (A) infrequent exacerbators with either chronic bronchitis or emphysema; (B) overlap COPD-asthma; (C) frequent exacerbators with emphysema predominant; and (D) frequent exacerbators with chronic bronchitis predominant.,The assessment of severity has also been updated with the incorporation of multidimensional indices.,The severity of the obstruction, as measured by forced expiratory volume in 1 second, is essential but not sufficient.,Multidimensional indices such as the BODE index have shown excellent prognostic value.,If the 6-minute walking test is not performed routinely, its substitution by the frequency of exacerbations (BODEx index) provides similar prognostic properties.,This proposal aims to achieve a more personalised management of COPD according to the clinical characteristics and multidimensional assessment of severity. | Persons with Chronic Obstructive Pulmonary Disease (COPD), performing some level of regular physical activity, have a lower risk of both COPD-related hospital admissions and mortality.,COPD patients of all stages seem to benefit from exercise training programs, thereby improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue.,Physical inactivity, which becomes more severe with increasing age, is a point of concern in healthy older adults.,COPD might worsen this scenario, but it is unclear to what degree.,This literature review aims to present the extent of the impact of COPD on objectively-measured daily physical activity (DPA).,The focus is on the extent of the impact that COPD has on duration, intensity, and counts of DPA, as well as whether the severity of the disease has an additional influence on DPA.,A literature review was performed in the databases PubMed [MEDLINE], Picarta, PEDRO, ISI Web of Knowledge and Google scholar.,After screening, 11 studies were identified as being relevant for comparison between COPD patients and healthy controls with respect to duration, intensity, and counts of DPA.,Four more studies were found to be relevant to address the subject of the influence the severity of the disease may have on DPA.,The average percentage of DPA of COPD patients vs. healthy control subjects for duration was 57%, for intensity 75%, and for activity counts 56%.,Correlations of DPA and severity of the disease were low and/or not significant.,From the results of this review, it appears that patients with COPD have a significantly reduced duration, intensity, and counts of DPA when compared to healthy control subjects.,The intensity of DPA seems to be less affected by COPD than duration and counts.,Judging from the results, it seems that severity of COPD is not strongly correlated with level of DPA.,Future research should focus in more detail on the relation between COPD and duration, intensity, and counts of DPA, as well as the effect of disease severity on DPA, so that these relations become more understandable. | 1 |
Cigarette smoking is the most commonly encountered and readily identifiable risk factor for COPD.,However, it is not clear which quantitative factors related to smoking influence the prognosis of COPD patients.,A total of 204 patients with a long-term history of smoking were enrolled into this study and followed up for 5 years.,Patients were divided into “death” or “survival” groups based on follow-up results and “quitting-smoking” or “continuing-smoking” groups based on whether they gave up smoking.,Patients in the death group had a longer smoking time, lower prevalence of quitting smoking, later onset of COPD symptoms, older age at quitting smoking, lower forced expiratory volume in one second (FEV1) % predicted, and lower ratio of FEV1/forced vital capacity.,Age, age at quitting smoking, and FEV1% predicted were independently associated with mortality from COPD.,Compared to the continuing-smoking group, the quitting-smoking group had a lower mortality rate, longer course of COPD, earlier onset of COPD symptoms, and lower residual volume percent predicted.,During the 5-year follow-up, 113 deaths were recorded (quitting-smoking group: n=92; 40 deaths; continuing-smoking group: n=112; 73 deaths).,The mortality risk remained significantly higher in the continuing-smoking group than the quitting-smoking group (log-rank test, 13.59; P=0.0002).,Smoking time may be related to the mortality rate from COPD.,Smoking cessation has the greatest capacity to influence the natural history of COPD. | Waste management, namely, collection, transport, sorting and processing, and disposal, is an issue of social concern owing to its environmental impact and effects on public health.,In fact, waste management activities are carried out according to procedures that can have various negative effects on the environment and, potentially, on human health.,The aim of our study was to assess the potential effects on respiratory health of this exposure in workers in the waste management and disposal field, as compared with a group of workers with no occupational exposure to outdoor pollutants.,The sample consisted of a total of 124 subjects, 63 waste collectors, and 61 office clerks.,Informed consent was obtained from all subjects before inclusion in the study.,The entire study population underwent pulmonary function assessments with spirometry and completed two validated questionnaires for the diagnosis of rhinitis and chronic bronchitis.,Statistical analyses were performed using STATA 13.,Spirometry showed a statistically significant reduction in the mean Tiffenau Index values in the exposed workers, as compared with the controls, after adjusting for the confounding factors of age, BMI, and smoking habit.,Similarly, the mean FEV1 values were lower in the exposed workers than in the controls, this difference being again statistically significant.,The FVC differences measured in the two groups were not found to be statistically significant.,We ran a cross-sectional study to investigate the respiratory health of a group of workers in the solid waste collection and disposal field as compared with a group of office workers.,In agreement with most of the data in the literature, our findings support the existence of a prevalence of respiratory deficits in waste disposal workers.,Our data suggest the importance of adopting preventive measures, such as wearing specific individual protection devices, to protect this particular category of workers from adverse effects on respiratory health. | 1 |
Since the early 1960s, a compelling body of evidence has accumulated to show that proteinases play critical roles in airspace enlargement in chronic obstructive pulmonary disease (COPD).,However, until recently the causative enzymes and their exact roles in pathologic processes in COPD have not been clear.,Recent studies of gene-targeted mice in murine models of COPD have confirmed roles for proteinases not only in airspace enlargement, but also in airway pathologies in COPD.,These studies have also shed light on the specific proteinases involved in COPD pathogenesis, and the mechanisms by which these proteinases injure the lung.,They have also identified important interactions between different classes of proteinases, and between proteinases and other molecules that amplify lung inflammation and injury.,This review will discuss the biology of proteinases and the mechanisms by which they contribute to the pathogenesis of COPD.,In addition, I will discuss the potential of proteinase inhibitors and anti-inflammatory drugs as new treatment strategies for COPD patients. | Patients with chronic obstructive pulmonary disease (COPD) can experience 'exacerbations' of their conditions.,An exacerbation is an event defined in terms of subjective descriptors or symptoms, namely dyspnoea, cough and sputum that worsen sufficiently to warrant a change in medical management.,There is a need for reliable markers that reflect the pathological mechanisms that underlie exacerbation severity and that can be used as a surrogate to assess treatment effects in clinical studies.,Little is known as to how existing study variables and suggested markers change in both the stable and exacerbation phases of COPD.,In an attempt to find the best surrogates for exacerbations, we have reviewed the literature to identify which of these markers change in a consistent manner with the severity of the exacerbation event.,We have searched standard databases between 1966 to July 2004 using major keywords and terms.,Studies that provided demographics, spirometry, potential markers, and clear eligibility criteria were included in this study.,Central tendencies and dispersions for all the variables and markers reported and collected by us were first tabulated according to sample size and ATS/ERS 2004 Exacerbation Severity Levels I to III criteria.,Due to the possible similarity of patients in Levels II and III, the data was also redefined into categories of exacerbations, namely out-patient (Level I) and in-patient (Levels II & III combined).,For both approaches, we performed a fixed effect meta-analysis on each of the reported variables.,We included a total of 268 studies reported between 1979 to July 2004.,These studies investigated 142,407 patients with COPD.,Arterial carbon dioxide tension and breathing rate were statistically different between all levels of exacerbation severity and between in out- and in-patient settings.,Most other measures showed weak relationships with either level or setting, or they had insufficient data to permit meta-analysis.,Arterial carbon dioxide and breathing rate varied in a consistent manner with exacerbation severity and patient setting.,Many other measures showed weak correlations that should be further explored in future longitudinal studies or assessed using suggested mathematical modelling techniques.,The online version of this article (doi:10.1186/1465-9921-7-74) contains supplementary material, which is available to authorized users. | 1 |
The development of chronic obstructive pulmonary disease, upon exposure to tobacco smoke, is the cumulative effect of defects in several genes.,With the aim of understanding the genetic structure that is characteristic of our patient population, we selected forty two single nucleotide polymorphisms of twenty genes based on previous studies and genotyped a total of 382 samples, which included 236 patients and 146 controls using Sequenom MassARRAY system.,Allele frequencies of rs2276109 (MMP12) and rs1800925 (IL13) differed significantly between patients and controls (p = 0.013 and 0.044 respectively).,Genotype analysis showed association of rs2276109 (MMP12) under additive and dominant models (p = 0.017, p = 0.012 respectively), rs1800925 (IL13) under additive model (p = 0.047) and under recessive model, rs1695 (GSTP1; p = 0.034), rs729631, rs975278, rs7583463 (SERPINE2; p = 0.024, 0.024 and 0.012 respectively), rs2568494, rs10851906 (IREB2; p = 0.026 and 0.041 respectively) and rs7671167 (FAM13A; p = 0.029).,The minor alleles of rs1695 (G), rs7671167 (T), rs729631 (G), rs975278 (A) and rs7583463 (A) showed significant negative association whereas those of rs2276109 (G), rs2568494 (A), rs10851906 (G) and rs1800469 (T; TGF-β) showed significant positive association with lung function under different genetic models.,Haplotypes carrying A allele of rs2276109, G allele of rs1695 showed negative correlation with lung function.,Haplotypes carrying major alleles of rs7671167 (C) of FAM13A and rs729631 (C), rs975278 (G), rs7583463 (C) of SERPINE2 had protective effect on lung function.,Haplotypes of IREB2 carrying major alleles of rs2568494 (G), rs2656069 (A), rs10851906 (A), rs965604 (C) and minor alleles of rs1964678 (T), rs12593229 (T) showed negative correlation with lung function.,In conclusion, our study replicated the results of most of the previous studies.,However, the positive correlation between the minor alleles of rs2568494 (A) and rs10851906 (G) of IREB2 and lung function needs further investigation. | 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). | 1 |
There is increasing recognition of asthma-COPD overlap syndrome (ACOS), which shares some features of both asthma and COPD; however, the prevalence and characteristics of ACOS are not well understood.,The aim of this study was to investigate the prevalence of ACOS among patients with COPD and its characteristics using a stepwise approach as stated in the recent report of the Global Initiative for Asthma (GINA) and the Global Initiative for Chronic Obstructive Lung Disease (GOLD).,This multicenter, cross-sectional, observational study enrolled outpatients who were receiving medical treatment for COPD.,Clinical data, including spirometry results, were retrieved from medical records.,For symptom assessment, patients were asked to complete the Clinical COPD questionnaire and the modified British Medical Research Council questionnaire.,Of the 1,008 patients analyzed, 167 (16.6%) had syndromic features of ACOS.,Of the total number of patients, 93 and 42 (9.2% and 4.2%) also had a predefined clinical variability of ≥12%/≥200 mL and ≥12%/≥400 mL in forced expiratory volume in 1 second (FEV1), respectively, and therefore were identified as having ACOS.,Conversely, the number of patients who had either syndromic or spirometric feature of ACOS was 595 (59.0%, ≥12%/≥200 mL FEV1 clinical variability), and 328 patients (32.5%, ≥12%/≥400 mL FEV1 clinical variability) had both the features.,Patients identified as having ACOS were of significantly younger age, had a shorter duration of COPD, lower number of pack-years, better lung function, milder dyspnea symptoms, and higher peripheral blood eosinophil values compared with patients with COPD alone.,The rate of exacerbations in the previous year was not significantly different between the ACOS and COPD groups.,Using a stepwise approach, as stated in the GINA/GOLD report, the proportions of patients identified as having ACOS were found to be 9.2% and 4.2% (depending on the FEV1 variability cutoff used) among the 1,008 outpatients medically treated for COPD in a real-life clinical setting. | In recent years, the so-called asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) has received much attention, not least because elderly individuals may present characteristics suggesting a diagnosis of both asthma and COPD.,At present, ACOS is described clinically as persistent airflow limitation combined with features of both asthma and COPD.,The aim of this paper is, therefore, to review the currently available literature focusing on symptoms and clinical characteristics of patients regarded as having ACOS.,Based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, a systematic literature review was performed.,A total of 11 studies met the inclusion criteria for the present review.,All studies dealing with dyspnea (self-reported or assessed by the Medical Research Council dyspnea scale) reported more dyspnea among patients classified as having ACOS compared to the COPD and asthma groups.,In line with this, ACOS patients have more concomitant wheezing and seem to have more cough and sputum production.,Compared to COPD-only patients, the ACOS patients were found to have lower FEV1% predicted and FEV1/FVC ratio in spite of lower mean life-time tobacco exposure.,Furthermore, studies have revealed that ACOS patients seem to have not only more frequent but also more severe exacerbations.,Comorbidity, not least diabetes, has also been reported in a few studies, with a higher prevalence among ACOS patients.,However, it should be acknowledged that only a limited number of studies have addressed the various comorbidities in patients with ACOS.,The available studies indicate that ACOS patients may have more symptoms and a higher exacerbation rate than patients with asthma and COPD only, and by that, probably a higher overall respiratory-related morbidity.,Similar to patients with COPD, ACOS patients seem to have a high occurrence of comorbidity, including diabetes.,Further research into the ACOS, not least from well-defined prospective studies, is clearly needed. | 1 |
Cardiovascular disease (CVD) is a common comorbidity associated with chronic obstructive pulmonary disease (COPD), but few studies have been conducted to identify CVD risk in COPD patients.,This study was to develop a predictive model of CVD in COPD patients based on the National Health and Nutrition Examination Survey (NHANES) database.,A total of 3,226 COPD patients were retrieved from NHANES 2007-2012, dividing into the training (n = 2351) and testing (n = 895) sets.,The prediction models were conducted using the multivariable logistic regression and random forest analyses, respectively.,Receiver operating characteristic (ROC) curves, area under the curves (AUC) and internal validation were used to assess the predictive performance of models.,The logistic regression model for predicting the risk of CVD was developed regarding age, gender, body mass index (BMI), high-density lipoprotein (HDL), glycosylated hemoglobin (HbA1c), family history of heart disease, and stayed overnight in the hospital due to illness last year, which the AUC of the internal validation was 0.741.,According to the random forest analysis, the important variables-associated with CVD risk were screened including smoking (NNAL and cotinine), HbA1c, HDL, age, gender, diastolic blood pressure, poverty income ratio, BMI, systolic blood pressure, and sedentary activity per day.,The AUC of the internal validation was 0.984, indicating the random forest model for predicting the CVD risk in COPD cases was superior to the logistic regression model.,The random forest model performed better predictive effectiveness for the cardiovascular risk among COPD patients, which may be useful for clinicians to guide the clinical practice. | Although cardiovascular disease (CVD) is a common comorbidity associated with chronic obstructive pulmonary disease (COPD), it is unknown how to improve prediction of cardiovascular (CV) risk in individuals with COPD.,Traditional CV risk scores have been tested in different populations but not uniquely in COPD.,The potential of alternative markers to improve CV risk prediction in individuals with COPD is unknown.,We aimed to determine the predictive value of conventional CVD risk factors in COPD and to determine if additional markers improve prediction beyond conventional factors.,Data from the Evaluation of the Role of Inflammation in Chronic Airways disease cohort, which enrolled 729 individuals with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II-IV COPD were used.,Linked hospital episode statistics and survival data were prospectively collected for a median 4.6 years of follow-up.,Five UK centres interested in COPD.,Population-based sample including 714 individuals with spirometry-defined COPD, smoked at least 10 pack years and who were clinically stable for >4 weeks.,Baseline measurements included aortic pulse wave velocity (aPWV), carotid intima-media thickness (CIMT), C reactive protein (CRP), fibrinogen, spirometry and Body mass index, airflow Obstruction, Dyspnoea and Exercise capacity (BODE) Index, 6 min walk test (6MWT) and 4 m gait speed (4MGS) test.,New occurrence (first event) of fatal or non-fatal hospitalised CVD, and all-cause and cause-specific mortality.,Out of 714 participants, 192 (27%) had CV hospitalisation and 6 died due to CVD.,The overall CV risk model C-statistic was 0.689 (95% CI 0.688 to 0.691). aPWV and CIMT neither had an association with study outcome nor improved model prediction.,CRP, fibrinogen, GOLD stage, BODE Index, 4MGS and 6MWT were associated with the outcome, independently of conventional risk factors (p<0.05 for all).,However, only 6MWT improved model discrimination (C=0.727, 95% CI 0.726 to 0.728).,Poor physical performance defined by the 6MWT improves prediction of CV hospitalisation in individuals with COPD.,ID 11101. | 1 |
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