a stringlengths 138 8.15k | b stringlengths 138 8.15k | label int64 1 1 |
|---|---|---|
Little is known regarding the relationship between balance impairments and physical activity in COPD.,There has been no study investigating the relationship between balance and objectively measured physical activity.,Here we investigated the association between balance and physical activity measured by an activity monitor in elderly COPD patients.,Twenty-two outpatients with COPD (mean age, 72±7 years; forced expiratory volume in 1 second, 53%±21% predicted) and 13 age-matched healthy control subjects (mean age, 72±6 years) participated in the study.,We assessed all 35 subjects’ balance (one-leg standing test [OLST] times, Short Physical Performance Battery total scores, standing balance test scores, 4 m gait speed, and five-times sit-to-stand test [5STST]) and physical activity (daily steps and time spent in moderate-to-vigorous physical activity per day [MV-PA]).,Possible confounders were assessed in the COPD group.,The between-group differences in balance test scores and physical activity were analyzed.,A correlation analysis and multivariate regression analysis were conducted in the COPD group.,The COPD patients exhibited significant reductions in OLST times (P=0.033), Short Physical Performance Battery scores (P=0.013), 4 m gait speed (P<0.001), five-times sit-to-stand times (P=0.002), daily steps (P=0.003), and MV-PA (P=0.022) compared to the controls; the exception was the standing balance test scores.,The correlation and multivariate regression analyses revealed significant independent associations between OLST times and daily steps (P<0.001) and between OLST times and MV-PA (P=0.014) in the COPD group after adjusting for possible confounding factors.,Impairments in balance and reductions in physical activity were observed in the COPD group.,Deficits in balance are independently associated with physical inactivity. | Decreased physical activity is associated with higher mortality in subjects with COPD.,The aim of this study was to assess clinical characteristics and physical activity levels (PALs) in subjects with COPD.,Seventy-three subjects with COPD (67 ± 7 yrs, 44 female) with one-second forced expiratory volume percentage (FEV1%) predicted values of 43 ± 16 were included.,The ratio of total energy expenditure (TEE) and resting metabolic rate (RMR) was used to define the physical activity level (PAL) (PAL = TEE/RMR).,TEE was assessed with an activity monitor (ActiReg), and RMR was measured by indirect calorimetry.,Walking speed (measured over 30-meters), maximal quadriceps muscle strength, fat-free mass and systemic inflammation were measured as clinical characteristics.,Hierarchical linear regression was applied to investigate the explanatory values of the clinical correlates to PAL.,The mean PAL was 1.47 ± 0.19, and 92% of subjects were classified as physically very inactive or sedentary.,The walking speed was 1.02 ± 0.23 m/s, the quadriceps strength was 31.3 ± 11.2 kg, and the fat-free mass index (FFMI) was 15.7 ± 2.3 kg/m2, identifying 42% of subjects as slow walkers, 21% as muscle-weak and 49% as FFM-depleted.,The regression model explained 45.5% (p < 0.001) of the variance in PAL.,The FEV1% predicted explained the largest proportion (22.5%), with further improvements in the model from walking speed (10.1%), muscle strength (7.0%) and FFMI (3.0%).,Neither age, gender nor systemic inflammation contributed to the model.,Apart from lung function, walking speed and muscle strength are important correlates of physical activity.,Further explorations of the longitudinal effects of the factors characterizing the most inactive subjects are warranted. | 1 |
The objective of this study was to compare the cost-effectiveness of the fixed-dose combination (FDC) of tiotropium + olodaterol Respimat® FDC with tiotropium alone for patients with chronic obstructive pulmonary disease (COPD) in the Italian health care setting using a newly developed patient-level Markov model that reflects the current understanding of the disease.,While previously published models have largely been based around a cohort approach using a Markov structure and GOLD stage stratification, an individual-level Markov approach was selected for the new model.,Using patient-level data from the twin TOnado trials assessing Tiotropium + olodaterol Respimat® FDC versus tiotropium, outcomes were modelled based on the trough forced expiratory volume (tFEV1) of over 1000 patients in each treatment arm, tracked individually at trial visits through the 52-week trial period, and after the trial period it was assumed to decline at a constant rate based on disease stage.,Exacerbation risk was estimated based on a random-effects logistic regression analysis of exacerbations in UPLIFT.,Mortality by age and disease stage was estimated from an analysis of TIOSPIR trial data.,Cost of bronchodilators and other medications, routine management, and costs of treatment for moderate and severe exacerbations for the Italian setting were included.,A cost-effectiveness analysis was conducted over a 15-year time horizon from the perspective of the Italian National Health Service.,Aggregating total costs and quality-adjusted life years (QALYs) for each treatment cohort over 15 years and comparing tiotropium + olodaterol Respimat® FDC with tiotropium alone, resulted in mean incremental costs per patient of €1167 and an incremental cost-effectiveness ratio (ICER) of €7518 per additional QALY with tiotropium + olodaterol Respimat® FDC.,The lung function outcomes observed for tiotropium + olodaterol Respimat® FDC in TOnado drove the results in terms of slightly higher mean life-years (12.24 versus 12.07) exacerbation-free months (11.36 versus 11.32) per patient and slightly fewer moderate and severe exacerbations per patient-year (0.411 versus 0.415; 0.21 versus 0.24) versus tiotropium.,Probabilistic sensitivity analyses showed tiotropium + olodaterol Respimat® FDC to be the more cost-effective treatment in 95.2% and 98.4% of 500 simulations at thresholds of €20,000 and €30,000 per QALY respectively.,Tiotropium + olodaterol Respimat® FDC is a cost-effective bronchodilator in the maintenance treatment of COPD for the Italian health care system. | The efficacy and safety of once-daily tiotropium + olodaterol (T+O) maintenance treatment was demonstrated in the large, multinational, replicate, randomized, Phase III, Tonado® 1 (NCT01431274) and 2 (NCT01431287) studies in patients with moderate to very severe COPD.,However, there may be racial differences in the effects of T+O on lung function in patients with COPD.,In this Tonado® subgroup analysis, we assessed efficacy and safety of T+O in Japanese participants.,Versus the overall population, the 413 Japanese patients randomized and treated were slightly older, with more men, lower body mass index, lower baseline St George’s Respiratory Questionnaire (SGRQ) scores, fewer current smokers, but with higher pack-year smoking history.,A lower proportion of Japanese patients used inhaled corticosteroids, short-acting muscarinic antagonists, or short- or long-acting β-adrenergic agonists at baseline, but use of long-acting muscarinic antagonists was higher.,At Week 24, mean improvements with T+O 5/5 μg in forced expiratory volume in 1 second area under the curve from 0-3 hours response were 151 mL versus olodaterol and 134 mL versus tiotropium 5 μg; mean improvements with T+O 2.5/5 μg were 87 mL versus olodaterol and 70 mL versus tiotropium 2.5 μg.,Mean improvements with T+O 5/5 μg in trough forced expiratory volume in 1 second were 131 mL versus olodaterol and 108 mL versus tiotropium 5 μg; mean improvements with T+O 2.5/5 μg were 60 mL versus olodaterol and 47 mL versus tiotropium 2.5 μg.,SGRQ scores improved from baseline to a greater extent with both doses of T+O versus monotherapies.,Responses were similar in the overall population.,Adverse-event incidence was generally balanced across treatment groups.,Consistent with results from the overall population, T+O 5/5 μg was superior to each monotherapy for lung function and SGRQ in the Japanese sub-population of patients with COPD in Tonado®. | 1 |
The benefits of pharmacotherapy with tiotropium HandiHaler 18 μg for patients with chronic obstructive pulmonary disease (COPD) have been previously demonstrated.,However, few data exist regarding the treatment of moderate disease (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II).,To determine whether tiotropium improves lung function/patient-reported outcomes in patients with GOLD stage II COPD naive to maintenance therapy.,A randomised 24-week double-blind placebo-controlled trial of tiotropium 18 μg once daily (via HandiHaler) was performed in maintenance therapy-naive patients with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7 and post-bronchodilator FEV1 ⩾50 and <80%.,A total of 457 patients were randomised (238 tiotropium, 219 placebo; mean age 62 years; FEV1 1.93 l (66% predicted)).,Tiotropium was superior to placebo in mean change from baseline in post-dose FEV1 area under the curve from 0 to 3 h (AUC0-3h) at week 24 (primary endpoint): 0.19 vs.,−0.03 l (least-squares mean difference 0.23 l, P<0.001).,FVC AUC0-3h, trough and peak FEV1 and FVC were significantly improved with tiotropium versus placebo (P<0.001).,Compared with placebo, tiotropium provided numerical improvements in physical activity (P=NS).,Physician’s Global Assessment (health status) improved (P=0.045) with less impairment on the Work Productivity and Activity Impairment questionnaire (P=0.043) at week 24.,The incidence of exacerbations, cough, bronchitis and dyspnoea was lower with tiotropium than placebo.,Tiotropium improved lung function and patient-reported outcomes in maintenance therapy-naive patients with GOLD stage II COPD, suggesting benefits in initiating maintenance therapy early. | Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD).,The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.,In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.,At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints).,Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint).,All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.,Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk.,Aclidinium/formoterol may be an effective treatment for patients with COPD.,ClinicalTrials.gov: NCT01462942.,The online version of this article (doi:10.1186/1471-2466-14-178) contains supplementary material, which is available to authorized users. | 1 |
The purpose of this study was to update our network meta-analysis in order to compare the efficacy of indacaterol 75 μg with that of a fixed-dose combination of formoterol and budesonide (FOR/BUD) and a fixed-dose combination salmeterol and fluticasone (SAL/FP) for the treatment of chronic obstructive pulmonary disease (COPD) based on evidence identified previously in addition to two new randomized clinical trials.,Fifteen randomized, placebo-controlled clinical trials including COPD patients were evaluated: indacaterol 75 μg once daily (n = 2 studies), indacaterol 150 μg once daily (n = 5), indacaterol 300 μg once daily (n = 4), FOR/BUD 9/160 μg twice daily (n = 2), FOR/BUD 9/320 μg twice daily (n = 2), SAL/FP 50/500 μg twice daily (n = 4), and SAL/FP 50/250 μg twice daily (n = 1).,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.,Outcomes of interest were trough forced expiratory volume in 1 second (FEV1) and transitional dyspnea index at 12 weeks.,Based on the results without adjustment for covariates, indacaterol 75 μg resulted in a greater improvement in FEV1 at 12 weeks compared with FOR/BUD 9/160 μg (difference in change from baseline 0.09 L [95% credible interval 0.04-0.13]) and FOR/BUD 9/320 μg (0.07 L [0.03-0.11]) and was comparable with SAL/FP 50/250 μg (0.00 L [−0.07-0.07]) and SAL/FP 50/500 μg (0.01 L [−0.04-0.05]).,For transitional dyspnea index, data was available only for indacaterol 75 μg versus SAL/FP 50/500 μg (−0.49 points [−1.87-0.89]).,Based on results of a network meta-analysis with and without covariates, indacaterol 75 μg is expected to be at least as efficacious as FOR/BUD (9/320 μg and 9/160 μg) and comparable with SAL/FP (50/250 μg and 50/500 μg) in terms of lung function.,In terms of breathlessness (transitional dyspnea index) at 12 weeks, the results are inconclusive given the limited data. | 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. | 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. | Chronic obstructive pulmonary disease (COPD) is widely underdiagnosed, but the most effective approach for identifying these patients is unknown.,The aim of this study was to summarise and compare the effectiveness of different case finding approaches for undiagnosed COPD in primary care.,A systematic review of primary studies of any design evaluating case finding strategies for COPD in primary care among individuals aged ⩾35 years with no prior diagnosis was conducted.,Medline, Embase and other bibliographic databases were searched from 1997 to 2013, and methodological quality was assessed using standard tools.,Results were described and meta-analysis of the uptake and yield from different approaches was performed where there was sufficient homogeneity.,Three randomised controlled trials (RCTs), 1 controlled trial and 35 uncontrolled studies were identified that assessed the identification of new cases of COPD through systematic case finding.,A range of approaches were used including pre-screening with questionnaires (n=13) or handheld flow meters (n=5) or direct invitation to diagnostic spirometry (n=30).,Overall, any approach identified more undiagnosed COPD compared with usual care.,Targeting those at higher risk (e.g., smokers) and pre-screening (e.g., using questionnaires) is likely to increase the yield.,However, studies were heterogeneous and were limited by a lack of comparison groups, inadequate reporting and diversity in the definition of COPD, which limited our ability to draw firm conclusions.,There is extensive heterogeneity among studies evaluating case finding strategies for COPD, with few RCTs.,Well-conducted RCTs comparing case finding approaches are needed to identify the most effective target population, recruitment strategy and screening tests, using a clinical definition of COPD, and addressing the limitations highlighted in this review.,There is also a need to evaluate the impact of case finding on clinical care and patient outcomes. | 1 |
Epidemiological studies have shown that ambient air pollution is closely associated with increased respiratory inflammation and decreased lung function.,Particulate matters (PMs) are major components of air pollution that damages lung cells.,However, the mechanisms remain to be elucidated.,This study examines the effects of PMs on intercellular adhesion molecule-1 (ICAM-1) expression and the related mechanisms in vitro and in vivo.,The cytotoxicity, reactive oxygen species (ROS) generation, and monocyte adherence to A549 cells were more severely affected by treatment with O-PMs (organic solvent-extractable fraction of SRM1649b) than with W-PMs (water-soluble fraction of SRM1649b).,We observed a significant increase in ICAM-1 expression by O-PMs, but not W-PMs.,O-PMs also induced the phosphorylation of AKT, p65, and STAT3.,Pretreating A549 cells with N-acetyl cysteine (NAC), an antioxidant, attenuated O-PMs-induced ROS generation, the phosphorylation of the mentioned kinases, and the expression of ICAM-1.,Furthermore, an AKT inhibitor (LY294002), NF-κB inhibitor (BAY11-7082), and STAT3 inhibitor (Stattic) significantly down-regulated O-PMs-induced ICAM-1 expression as well as the adhesion of U937 cells to epithelial cells.,Interleukin-6 (IL-6) was the most significantly changed cytokine in O-PMs-treated A549 cells according to the analysis of the cytokine antibody array.,The IL-6 receptor inhibitor tocilizumab (TCZ) and small interfering RNA for IL-6 significantly reduced ICAM-1 secretion and expression as well as the reduction of the AKT, p65, and STAT3 phosphorylation in O-PMs-treated A549 cells.,In addition, the intratracheal instillation of PMs significantly increased the levels of the ICAM-1 and IL-6 in lung tissues and plasma in WT mice, but not in IL-6 knockout mice.,Pre-administration of NAC attenuated those PMs-induced adverse effects in WT mice.,Furthermore, patients with chronic obstructive pulmonary disease (COPD) had higher plasma levels of ICAM-1 and IL-6 compared to healthy subjects.,These results suggest that PMs increase ICAM-1 expression in pulmonary epithelial cells in vitro and in vivo through the IL-6/AKT/STAT3/NF-κB signaling pathway.,The online version of this article (10.1186/s12989-018-0240-x) contains supplementary material, which is available to authorized users. | Research on the association between chronic bronchitis and chronic obstructive pulmonary disease (COPD) exacerbations has led to discordant results.,Furthermore, the impact of chronic bronchitis on mortality in COPD subjects is unclear.,Within the Rotterdam Study, a population-based cohort study of subjects aged ≥45 years, chronic bronchitis was defined as having a productive cough for ≥3 months per year for two consecutive years.,Linear, logistic regression and Cox proportional hazard models were adjusted for age, sex and pack-years.,Out of 972 included COPD subjects, 752 had no chronic phlegm production (CB−) and 220 had chronic phlegm production, of whom 172 met the definition of chronic bronchitis (CB+).,CB+ subjects were older, more frequently current smokers and had more pack-years than CB− subjects.,During a median 6.5 years of follow-up, CB+ subjects had greater decline in lung function (−38 mL·year−1, 95% CI −61.7-−14.6; p=0.024).,CB+ subjects had an increased risk of frequent exacerbations (OR 4.0, 95% CI 2.7-5.9; p<0.001).,In females, survival was significantly worse in CB+ subjects compared to CB− subjects.,Regarding cause-specific mortality, CB+ subjects had an increased risk of respiratory mortality (hazard ratio 2.16, 95% CI 1.12-4.17; p=0.002).,COPD subjects with chronic bronchitis have an increased risk of exacerbations and respiratory mortality compared to COPD subjects without chronic phlegm production.,Chronic bronchitis increases the risk of exacerbations and mortality among patients with COPDhttp://ow.ly/o1fq30bFf9Q | 1 |
Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation. | Supplemental Digital Content is available in the text,This study compares the prevalence rates of comorbidities between chronic obstructive pulmonary disease (COPD) and non-COPD control patients reported in literature.,Literature was searched in several electronic databases.,After the selection of studies by following précised eligibility criteria, meta-analyses of odds ratios (ORs) were carried out with subgroup and sensitivity analyses under random effects model.,Eleven studies (47,695,183 COPD and 47,924,876 non-COPD control patients’ data) were used for meta-analysis.,Average age of COPD patients was 66.66 ± 8.72 years of whom 55.4 ± 11.9% were males.,The prevalence of cardiovascular comorbidities [OR 1.90, 95% confidence interval (95% CI) 1.59-2.28; P < .00001], cerebrovascular comorbidities (OR 1.84, 95% CI 1.47-2.31; P < .00001), hypertension (OR 1.45, 95% CI 1.31-1.61; P < .00001), diabetes mellitus (OR 1.22, 95% CI 1.07-1.38; P = .003), neurological and psychiatric disorders (OR 1.78, 95% CI 1.48-2.14; P < .00001), gut and renal disorders (OR 1.96, 95% CI 1.43-2.68; P < .00001), musculoskeletal disorders (OR 1.51, 95% CI 1.27-1.78; P < .00001), non-COPD respiratory comorbidities (OR 2.81, 95% CI 2.52-3.14; P < .00001), and cancer (OR 1.67, 95% CI 1.25-2.23; P = .0005) were significantly higher in COPD patients than in non-COPD controls.,COPD is associated with significantly higher comorbidities than in other diseases that should be taken into consideration in COPD control strategies. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities.,The main cause is smoking tobacco, but other factors have been identified.,Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli.,The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both.,Comorbidities include ischaemic heart disease, diabetes, and lung cancer.,Bronchodilators constitute the mainstay of treatment: β2 agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids).,Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification.,Future research should be directed towards the development of agents that notably affect the course of disease. | Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression.,A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs).,PQTLs consistently replicated between the two cohorts.,Features of pQTLs were compared to previously reported expression QTLs (eQTLs).,Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests.,We identified 527 highly significant (p < 8 X 10−10) pQTLs in 38 (43%) of blood proteins tested.,Most pQTL SNPs were novel with low overlap to eQTL SNPs.,The pQTL SNPs explained >10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC).,Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes.,Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins.,The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates.,Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema.,In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms.,Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group. | 1 |
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. | Objective To examine the effect of β blockers in the management of chronic obstructive pulmonary disease (COPD), assessing their effect on mortality, hospital admissions, and exacerbations of COPD when added to established treatment for COPD.,Design Retrospective cohort study using a disease specific database of COPD patients (TARDIS) linked to the Scottish morbidity records of acute hospital admissions, the Tayside community pharmacy prescription records, and the General Register Office for Scotland death registry.,Setting Tayside, Scotland (2001-2010),Population 5977 patients aged >50 years with a diagnosis of COPD.,Main outcome measures Hazard ratios for all cause mortality, emergency oral corticosteroid use, and respiratory related hospital admissions calculated through Cox proportional hazard regression after correction for influential covariates.,Results Mean follow-up was 4.35 years, mean age at diagnosis was 69.1 years, and 88% of β blockers used were cardioselective.,There was a 22% overall reduction in all cause mortality with β blocker use.,Furthermore, there were additive benefits of β blockers on all cause mortality at all treatment steps for COPD.,Compared with controls (given only inhaled therapy with either short acting β agonists or short acting antimuscarinics), the adjusted hazard ratio for all cause mortality was 0.28 (95% CI 0.21 to 0.39) for treatment with inhaled corticosteroid, long acting β agonist, and long acting antimuscarinic plus β blocker versus 0.43 (0.38 to 0.48) without β blocker.,There were similar trends showing additive benefits of β blockers in reducing oral corticosteroid use and hospital admissions due to respiratory disease. β blockers had no deleterious impact on lung function at all treatment steps when given in conjunction with either a long acting β agonist or antimuscarinic agent,Conclusions β blockers may reduce mortality and COPD exacerbations when added to established inhaled stepwise therapy for COPD, independently of overt cardiovascular disease and cardiac drugs, and without adverse effects on pulmonary function. | 1 |
We investigated a large population of patients with chronic obstructive pulmonary disease (COPD) to determine their frequency of medication use and patterns of pharmacotherapy.,Medical and pharmacy claims data were retrospectively analyzed from 19 health plans (>7.79 million members) across the US.,Eligible patients were aged ≥40 years, continuously enrolled during July 2004 to June 2005, and had at least one inpatient or at least two outpatient claims coded for COPD.,As a surrogate for severity of illness, COPD patients were stratified by complexity of illness using predefined International Classification of Diseases, Ninth Revision, Clinical Modification, Current Procedural Terminology, Fourth Edition, and Healthcare Common Procedure Coding System codes.,A total of 42,565 patients with commercial insurance and 8507 Medicare patients were identified.,Their mean age was 54.7 years and 74.8 years, and 48.7% and 46.9% were male, respectively.,In total, 66.3% of commercial patients (n = 28,206) were not prescribed any maintenance COPD pharmacotherapy (59.1% no medication; 7.2% inhaled short-acting β2-agonist only).,In the Medicare population, 70.9% (n = 6031) were not prescribed any maintenance COPD pharmacotherapy (66.0% no medication; 4.9% short-acting β2-agonist only).,A subset of patients classified as high-complexity were similarly undertreated, with 58.7% (5358/9121) of commercial and 68.8% (1616/2350) of Medicare patients not prescribed maintenance COPD pharmacotherapy.,Only 18.0% and 9.8% of diagnosed smokers in the commercial and Medicare cohorts had a claim for a smoking cessation intervention and just 16.6% and 23.5%, respectively, had claims for an influenza vaccination.,This study highlights a high degree of undertreatment of COPD in both commercial and Medicare patients, with most patients receiving no maintenance pharmacotherapy or influenza vaccination. | Chronic obstructive pulmonary disease (COPD) exacerbations are associated with systemic consequences.,Data from a 4-year trial (Understanding Potential Long-term Impacts on Function with Tiotropium [UPLIFT®], n = 5,992) were used to determine risk for nonlower respiratory serious adverse events (NRSAEs) following an exacerbation.,Patients with ≥1 exacerbation were analyzed.,NRSAE incidence rates (incidence rate [IR], per 100 patient-years) were calculated for the 30 and 180 days before and after the first exacerbation.,NRSAEs were classified by diagnostic terms and organ classes.,Maentel-Haenszel rate ratios (RR) (pre- and postexacerbation onset) along with 95% confidence intervals (CI) were computed.,A total of 3,960 patients had an exacerbation.,The mean age was 65 years, forced expiratory volume in 1 s (FEV1) was 38% predicted, and 74% were men.,For all NRSAEs, the IRs 30 days before and after an exacerbation were 20.2 and 65.2 with RR (95% CI) = 3.22 (2.40-4.33).,The IRs for the 180-day periods were 13.2 and 31.0 with RR (95% CI) = 2.36 (1.93-2.87).,The most common NRSAEs by organ class for both time periods were cardiac, respiratory system (other), and gastrointestinal.,All NRSAEs as well as cardiac events were more common after the first exacerbation, irrespective of whether the patient had cardiac disease at baseline.,The findings confirm that, after exacerbations, serious adverse events in other organ systems are more frequent, particularly those that are cardiac in nature. | 1 |
Chronic obstructive pulmonary disease (COPD) is a preventable and treatable lung disease characterized by airflow limitation that is not fully reversible.,In a significant proportion of patients with COPD, reduced lung elastic recoil combined with expiratory flow limitation leads to lung hyperinflation during the course of the disease.,Development of hyperinflation during the course of COPD is insidious.,Dynamic hyperinflation is highly prevalent in the advanced stages of COPD, and new evidence suggests that it also occurs in many patients with mild disease, independently of the presence of resting hyperinflation.,Hyperinflation is clinically relevant for patients with COPD mainly because it contributes to dyspnea, exercise intolerance, skeletal muscle limitations, morbidity, and reduced physical activity levels associated with the disease.,Various pharmacological and nonpharmacological interventions have been shown to reduce hyperinflation and delay the onset of ventilatory limitation in patients with COPD.,The aim of this review is to address the more recent literature regarding the pathogenesis, assessment, and management of both static and dynamic lung hyperinflation in patients with COPD.,We also address the influence of biological sex and obesity and new developments in our understanding of hyperinflation in patients with mild COPD and its evolution during progression of the disease. | Chronic obstructive pulmonary disease (COPD) is characterized by poorly reversible airflow limitation.,The pathological hallmarks of COPD are inflammation of the peripheral airways and destruction of lung parenchyma or emphysema.,The functional consequences of these abnormalities are expiratory airflow limitation and dynamic hyperinflation, which then increase the elastic load of the respiratory system and decrease the performance of the respiratory muscles.,These pathophysiologic features contribute significantly to the development of dyspnea, exercise intolerance and ventilatory failure.,Several treatments may palliate flow limitation, including interventions that modify the respiratory pattern (deeper, slower) such as pursed lip breathing, exercise training, oxygen, and some drugs.,Other therapies are aimed at its amelioration, such as bronchodilators, lung volume reduction surgery or breathing mixtures of helium and oxygen.,Finally some interventions, such as inspiratory pressure support, alleviate the threshold load associated to flow limitation.,The degree of flow limitation can be assessed by certain spirometry indexes, such as vital capacity and inspiratory capacity, or by other more complexes indexes such as residual volume/total lung capacity or functional residual capacity/total lung capacity.,Two of the best methods to measure flow limitation are to superimpose a flow-volume loop of a tidal breath within a maximum flow-volume curve, or to use negative expiratory pressure technique.,Likely this method is more accurate and can be used during spontaneous breathing.,A definitive definition of dynamic hyperinflation is lacking in the literature, but serial measurements of inspiratory capacity during exercise will document the trend of end-expiratory lung volume and allow establishing relationships with other measurements such as dyspnea, respiratory pattern, exercise tolerance, and gas exchange. | 1 |
During our medical training, we learned that oxygen administration in patients with chronic obstructive pulmonary disease (COPD) induces hypercapnia through the 'hypoxic drive' mechanism and can be dangerous.,This mindset frequently results in the reluctance of clinicians to administer oxygen to hypoxemic patients with COPD.,However, this fear is not based on evidence in the literature.,Here, we will review the impact and pathophysiology of oxygen-induced hypercapnia in patients with acute exacerbation of COPD and recommend a titrated oxygen management. | Objectives To compare standard high flow oxygen treatment with titrated oxygen treatment for patients with an acute exacerbation of chronic obstructive pulmonary disease in the prehospital setting.,Design Cluster randomised controlled parallel group trial.,Setting Ambulance service in Hobart, Tasmania, Australia.,Participants 405 patients with a presumed acute exacerbation of chronic obstructive pulmonary disease who were treated by paramedics, transported, and admitted to the Royal Hobart Hospital during the trial period; 214 had a diagnosis of chronic obstructive pulmonary disease confirmed by lung function tests in the previous five years.,Interventions High flow oxygen treatment compared with titrated oxygen treatment in the prehospital (ambulance/paramedic) setting.,Main outcome measure Prehospital or in-hospital mortality.,Results In an intention to treat analysis, the risk of death was significantly lower in the titrated oxygen arm compared with the high flow oxygen arm for all patients (high flow oxygen n=226; titrated oxygen n=179) and for the subgroup of patients with confirmed chronic obstructive pulmonary disease (high flow n=117; titrated n=97).,Overall mortality was 9% (21 deaths) in the high flow oxygen arm compared with 4% (7 deaths) in the titrated oxygen arm; mortality in the subgroup with confirmed chronic obstructive pulmonary disease was 9% (11 deaths) in the high flow arm compared with 2% (2 deaths) in the titrated oxygen arm.,Titrated oxygen treatment reduced mortality compared with high flow oxygen by 58% for all patients (relative risk 0.42, 95% confidence interval 0.20 to 0.89; P=0.02) and by 78% for the patients with confirmed chronic obstructive pulmonary disease (0.22, 0.05 to 0.91; P=0.04).,Patients with chronic obstructive pulmonary disease who received titrated oxygen according to the protocol were significantly less likely to have respiratory acidosis (mean difference in pH 0.12 (SE 0.05); P=0.01; n=28) or hypercapnia (mean difference in arterial carbon dioxide pressure −33.6 (16.3) mm Hg; P=0.02; n=29) than were patients who received high flow oxygen.,Conclusions Titrated oxygen treatment significantly reduced mortality, hypercapnia, and respiratory acidosis compared with high flow oxygen in acute exacerbations of chronic obstructive pulmonary disease.,These results provide strong evidence to recommend the routine use of titrated oxygen treatment in patients with breathlessness and a history or clinical likelihood of chronic obstructive pulmonary disease in the prehospital setting.,Trial registration Australian New Zealand Clinical Trials Register ACTRN12609000236291. | 1 |
Airway inflammation, especially neutrophilic airway inflammation, is a cardinal pathophysiologic feature in chronic obstructive pulmonary disease (COPD) patients.,The ideal biomarkers characterizing the inflammation might have important potential clinical applications in disease assessment and therapeutic intervention.,Sputum myeloperoxidase (MPO) is recognized as a marker of neutrophil activity.,The purpose of this meta-analysis is to determine whether sputum MPO levels could reflect disease status or be regulated by regular medications for COPD.,Studies were identified by searching PubMed, Embase, the Cochrane Database, CINAHL and http://www.controlled-trials.com for relevant reports published before September 2012.,Observational studies comparing sputum MPO in COPD patients and healthy subjects or asthmatics, or within the COPD group, and studies comparing sputum MPO before and after treatment were all included.,Data were independently extracted by two investigators and analyzed using STATA 10.0 software.,A total of 24 studies were included in the meta-analysis.,Sputum MPO levels were increased in stable COPD patients when compared with normal controls, and this increase was especially pronounced during exacerbations as compared with MPO levels during the stable state.,Theophylline treatment was able to reduce MPO levels in COPD patients, while glucocorticoid treatment failed to achieve the same result.,Sputum MPO might be a promising biomarker for guiding COPD management; however, further investigations are needed to confirm this. | Oxidative stress is an important feature in the pathogenesis of COPD.,Targeting oxidative stress with antioxidants or boosting the endogenous levels of antioxidants is likely to be beneficial in the treatment of COPD.,Antioxidant agents such as thiol molecules (glutathione and mucolytic drugs, such as N-acetyl-L-cysteine and N-acystelyn), dietary polyphenols (curcumin, resveratrol, green tea, catechins/quercetin), erdosteine, and carbocysteine lysine salt, all have been reported to control nuclear factor-kappaB (NF-κ B) activation, regulation of glutathione biosynthesis genes, chromatin remodeling, and hence inflammatory gene expression.,Specific spin traps such as α-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a superoxide dismutase mimetic M40419 have also been reported to inhibit cigarette smoke-induced inflammatory responses in vivo.,Since a variety of oxidants, free radicals, and aldehydes are implicated in the pathogenesis of COPD, it is possible that therapeutic administration of multiple antioxidants will be effective in the treatment of COPD.,Various approaches to enhance lung antioxidant capacity and clinical trials of antioxidant compounds in COPD are discussed. | 1 |
Telemedicine is changing traditional nursing care, and entails nurses performing advanced and complex care within a new clinical environment, and monitoring patients at a distance.,Telemedicine practice requires complex disease management, advocating that the nurses’ reasoning and decision-making processes are supported.,Computerised decision support systems are being used increasingly to assist reasoning and decision-making in different situations.,However, little research has focused on the clinical reasoning of nurses using a computerised decision support system in a telemedicine setting.,Therefore, the objective of the study is to explore the process of telemedicine nurses’ clinical reasoning when using a computerised decision support system for the management of patients with chronic obstructive pulmonary disease.,The factors influencing the reasoning and decision-making processes were investigated.,In this ethnographic study, a combination of data collection methods, including participatory observations, the think-aloud technique, and a focus group interview was employed.,Collected data were analysed using qualitative content analysis.,When telemedicine nurses used a computerised decision support system for the management of patients with complex, unstable chronic obstructive pulmonary disease, two categories emerged: “the process of telemedicine nurses’ reasoning to assess health change” and “the influence of the telemedicine setting on nurses’ reasoning and decision-making processes”.,An overall theme, termed “advancing beyond the system”, represented the connection between the reasoning processes and the telemedicine work and setting, where being familiar with the patient functioned as a foundation for the nurses’ clinical reasoning process.,In the telemedicine setting, when supported by a computerised decision support system, nurses’ reasoning was enabled by the continuous flow of digital clinical data, regular video-mediated contact and shared decision-making with the patient.,These factors fostered an in-depth knowledge of the patients and acted as a foundation for the nurses’ reasoning process.,Nurses’ reasoning frequently advanced beyond the computerised decision support system recommendations.,Future studies are warranted to develop more accurate algorithms, increase system maturity, and improve the integration of the digital clinical information with clinical experiences, to support telemedicine nurses’ reasoning process. | An essential element in the treatment of patients with chronic obstructive pulmonary disease (COPD) is rehabilitation, of which supervised training is an important part.,However, not all individuals with severe COPD can participate in the rehabilitation provided by hospitals and municipal training centres due to distance to the training venues and transportation difficulties.,The aim of the study was to assess the feasibility of an individualized home-based training and counselling programme via video conference to patients with severe COPD after hospitalization including assessment of safety, clinical outcomes, patients’ perceptions, organisational aspects and economic aspects.,The design was a pre- and post-test intervention study.,Fifty patients with severe COPD were included.,The telemedicine training and counselling included three weekly supervised exercise sessions by a physiotherapist and up to two supervised counselling and training sessions in energy conservation techniques by an occupational therapist.,The telemedicine videoconferencing equipment was a computer containing a screen, a microphone, an on/off switch and a volume control.,Thirty seven (74%) participants completed the programme, with improvements in health status assessed by the Clinical COPD Questionnaire and physical performance assessed by a sit-to-stand test and a timed-up-and-go test.,There were no cases of patient fall or emergency contact with a general practitioner during the telemedicine training sessions.,The study participants believed the telemedicine training and counselling was essential for getting started with being physically active in a secure manner.,The business case showed that under the current financing system, the reimbursement to the hospital was slightly higher than the hospital expenditures.,Thus, the business case for the hospital was positive.,The organizational analysis indicated that the perceptions of the staff were that the telemedicine service had improved the continuity of the rehabilitation programme for the patients and enabled the patients’ everyday lives to be included in the treatment.,This study showed that home-based supervised training and counselling via video conference is safe and feasible and that telemedicine can help to ensure more equitable access to supervised training in patients with severe COPD.,Clinical Trials NCT02085187 (Date of registration 10.03.2014). | 1 |
Asthma and chronic obstructive pulmonary disease (COPD) are common chronic airway diseases.,Overlap in the clinical features of these 2 diseases is observed in many cases, and thus, the concept of asthma-COPD overlap (ACO) has recently been proposed.,However, the definition of ACO and the clinical significance remains to be determined.,We evaluated the prevalence and risk of acute exacerbation in ACO among Korean COPD patients as defined by modified Spanish criteria and American Thoracic Society (ATS) Roundtable criteria.,The prevalence of ACO was 47.7% (660/1383) by modified Spanish criteria and 1.9% (26/1383) by ATS Roundtable criteria.,ACO, regardless of criteria, did not significant affect the exacerbation risk during at least 1-year follow-up period.,Substantial discrepancies were found in the prevalence and outcome of ACO according to different diagnostic criteria, which would compromise implementation of ACO before the definition is established. | Small airway changes and dysfunction contribute importantly to airway obstruction in chronic obstructive pulmonary disease (COPD), which is currently treated with inhaled corticosteroids (ICS) and long-acting bronchodilators at Global initiative for Obstructive Lung Disease (GOLD) grades 2-4.,This retrospective matched cohort analysis compared effectiveness of a representative small-particle ICS (extrafine beclomethasone) and larger-particle ICS (fluticasone) in primary care patients with COPD.,Smokers and ex-smokers with COPD ≥40 years old initiating or stepping-up their dose of extrafine beclomethasone or fluticasone were matched 1:1 for demographic characteristics, index prescription year, concomitant therapies, and disease severity during 1 baseline year.,During 2 subsequent years, we evaluated treatment change and COPD exacerbations, defined as emergency care/hospitalization for COPD, acute oral corticosteroids, or antibiotics for lower respiratory tract infection.,Mean patient age was 67 years, 57%-60% being male.,For both initiation (n=334:334) and step-up (n=189:189) patients, exacerbation rates were comparable between extrafine beclomethasone and fluticasone cohorts during the 2 year outcome period.,Odds of treatment stability (no exacerbation or treatment change) were significantly greater for patients initiating extrafine beclomethasone compared with fluticasone (adjusted odds ratio 2.50; 95% confidence interval, 1.32-4.73).,Median ICS dose exposure during 2 outcome years was significantly lower (P<0.001) for extrafine beclomethasone than fluticasone cohorts (315 μg/day versus 436 μg/day for initiation, 438 μg/day versus 534 μg/day for step-up patients).,We observed that small-particle ICS at significantly lower doses had comparable effects on exacerbation rates as larger-particle ICS at higher doses, whereas initiation of small-particle ICS was associated with better odds of treatment stability during 2-years’ follow-up. | 1 |
The role of statins as anti-inflammatory drugs in chronic obstructive pulmonary disease (COPD) is controversial.,This study aimed to determine the efficacy of statins used with or without corticosteroids in COPD patients.,This was a retrospective cohort study and used the two million outpatients and inpatients in Taiwan’s Longitudinal Health Insurance Database covering 2000 to 2015.,A total of 92,460 patients were identified in this study.,We divided COPD patients into four groups by auditing each patient’s medication (statins used or not; corticosteroids used or not) and used Cox regression to analyze and compare the effects of statins in COPD patients with or without corticosteroids.,In terms of all COPD patients, our findings were consistent with previous studies showing that statins decreased COPD-related hospitalization and mortality rates.,However, the beneficial effects were only observed in younger patients or those not taking corticosteroids in further analysis.,Statins significantly decreased hospitalization and mortality rates in the non-corticosteroids groups.,The hazard ratios increased with age and were not statistically significant for patients > 70 years old.,Statins did not significantly decrease ED visits, hospitalization, and mortality in corticosteroids groups.,Statins decreased hospitalization and mortality rates in COPD patients not taking corticosteroids but were not efficacious in patients on corticosteroids therapy.,Furthermore, the beneficial effects of statins gradually decreased with patient age.,Based on the findings, statins used in COPD patients may need to consider the patient age and corticosteroids used or not. | Statins have, due to their anti-inflammatory properties, been suggested to potentially improve chronic obstructive pulmonary disease (COPD) outcomes.,We aimed to investigate the effect of statins on time to first exacerbation and all-cause mortality in high-risk COPD outpatients.,All outpatients with COPD seen at the Department of Respiratory Medicine, Copenhagen University Hospital Amager and Hvidovre, Denmark in 2016 were identified and followed for 3.5 years in this retrospective, registry-based cohort study of time to first acute exacerbation of COPD (AECOPD) or death.,AECOPD was defined as a rescue course of oral corticosteroid and/or hospital admission.,The association was estimated using time-varying crude and multivariable Cox proportional hazard regression.,The cohort comprised 950 COPD outpatients, mean (SD) age 71 (11) years, and FEV1 44% predicted (IQR 33%; 57%).,The annual exacerbation rate was 0.88 (1.68) and 211 patients (22%) had a history of hospital admission for AECOPD in the 12 months prior to index date.,Three hundred and ninety-three patients (41.4%) were defined as statin users, with 131 (33.3%) having filled the first prescription for statin after index date.,Statin use was not associated with reduced risk of AECOPD.,When stratifying for moderate and severe exacerbations in a sub-analysis in the same model, statin use did not have an increased HR for exacerbation of either severity (HR = 1.02 (95% CI 0.85to 1.24; p = 0.811) and HR = 1.07 (95% CI 0.89 to 1.29; p = 0.492) respectively).,Statin use was not associated with all-cause mortality (HR 1.05 (95% CI, 0.75 to 1.47, p = 0.777)).,We did not find any association between statin use and risk of AECOPD or all-cause mortality.,The result adds to the evidence that an aggressive approach with statin treatment upfront is not beneficial in COPD, unless prescribed according to current guidelines for cardiovascular diseases. | 1 |
Objective To evaluate the safety of benzodiazepines and opioids in patients with very severe chronic obstructive pulmonary disease (COPD).,Design Population based longitudinal consecutive cohort study.,Setting Centres prescribing long term oxygen therapy in Sweden.,Patients 2249 patients starting long term oxygen therapy for COPD in Sweden between 2005 and 2009 in the national Swedevox Register.,Main outcome measures Effects of benzodiazepines and opioids on rates of admission to hospital and mortality, adjusted for age, sex, arterial blood gases, body mass index (BMI), performance status, previous admissions, comorbidities, and concurrent drugs.,Results 1681 (76%) patients were admitted to hospital, and 1129 (50%) died under observation.,No patient was lost to follow-up.,Benzodiazepines and opioids were not associated with increased admission: hazard ratio 0.98 (95% confidence interval, 0.87 to 1.10) and 0.98 (0.86 to 1.10), respectively.,Benzodiazepines were associated with increased mortality (1.21, 1.05 to 1.39) with a dose response trend.,Opioids also had a dose response relation with mortality: lower dose opioids (≤30 mg oral morphine equivalents a day) were not associated with increased mortality (1.03, 0.84 to 1.26) in contrast with higher dose opioids (1.21, 1.02 to 1.44).,Concurrent benzodiazepines and opioids in lower doses were not associated with increased admissions (0.86, 0.53 to 1.42) or mortality (1.25, 0.78 to 1.99).,Associations were not modified by being naive to the drugs or by hypercapnia.,Conclusions Lower dose opioids are not associated with increased admissions or deaths in patients with COPD and might be safe for symptom reduction in severe respiratory disease. | Several studies investigated the association of anemia with health related quality of life (HRQL) in patients with chronic disease.,However, there is little evidence regarding the association of anemia with HRQL in patients with chronic obstructive pulmonary disease (COPD).,This is a post-hoc analysis of a study which enrolled a population of adults aged 35-79 randomly selected from residents of Erie and Niagara Counties, NY, between 1996 and 2000.,In addition to demographic information and physical measurements, we obtained spirometry data and hemoglobin levels.,We used modified Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria to define COPD, and World Health Organization (WHO) criteria to define anemia.,To assess HRQL we used the Short Form-36 (SF-36) to assess physical functioning (PF), physical component summary (PCS) measures and mental component summary (MCS) measures.,In the entire study population (n = 2704), respondents with anemia had lower scores on the physical functioning domain [45.4 (SD10.9) vs.,49.2 (SD 9.1); p < 0.0001].,Among patients with COPD (n = 495) the PF scores (39.9 vs.,45.4) and the PCS (41.9 vs.,45.9) were significantly lower in individuals with anemia compared to those without.,In multiple regression analysis, the association between hemoglobin and PCS was positive (regression coefficient 0.02, p = 0.003).,There was no significant association of hemoglobin with PF scores or the mental component summary measure after adjusting for covariates in patients with COPD.,In patients with moderate to very severe COPD anemia may be associated with worse HRQL.,However, co-morbidities may explain part or all of this association in these patients. | 1 |
It is desirable to facilitate the use of an affordable, reliable, and portable spirometer, for earlier diagnosis of COPD in China, particularly in rural areas.,The aim of this study was to assess the agreement of a handheld “disposable pneumotachograph” (D-PNEU) spirometer with the gold standard spirometer and to evaluate its diagnostic accuracy of spirometric classification of airflow obstruction.,A total of 241 adult Chinese subjects ranging from healthy to those with mixed levels of pulmonary disease performed spirometry in a conventional body plethysmograph, and using a D-PNEU device in randomized order.,The three best spirometric tests were recorded for comparative analysis.,A Bland-Altman graph was created to assess the agreement between devices.,Using FEV1/FVC <70% as the “gold standard” for obstruction, the accuracy of classifying the severity of airway obstruction for all subjects was assessed.,For the specific individuals (n=159) able to exhale for at least 6 seconds, the accuracy of classifying airway obstruction was further assessed.,For this purpose, a receiver operating characteristic curve was used to determine an optimal cutoff point of FEV1/FEV6 ratio obtained by the D-PNEU device, which matched the global definition of FEV1/FVC <70% by the traditional spirometer.,The Bland-Altman analysis showed that the between-device agreement for key airflow metrics was within clinically acceptable limits.,The D-PNEU device had 87.1% accuracy in the classification of severity of obstruction in all 241 subjects, when using FEV1/FVC<70% as the “gold standard” for both devices.,The D-PNEU device had 93.7% accuracy in the 159 individuals able to exhale for at least 6 seconds, when a cutoff point of FEV1/FEV6 was 74%.,A disposable handheld spirometry device is capable of accurately identifying and quantifying airway obstruction in patients deemed to be at risk, however, caution should be exercised and all available brands should be tested. | Spirometry is commonly accepted as the gold standard for the diagnosis of COPD, but the reality remains that quality assured spirometry is not or cannot be provided universally around the globe.,Adding PEF measurement to a screening questionnaire may rule out airflow limitation compatible with COPD rationalizing spirometry testing.,We conducted a cross-sectional survey in a sample of individuals 40-80 yrs. old in Dubai, UAE.,They were invited to answer a short socio-demographic questionnaire including a report on current, past history of smoking, and had PEF measured, then they conducted spirometry to identify airflow limitation compatible with COPD.,Overall, 525 (91.0%) participants performed PEF and spirometry (68% male, with a mean age of 59 years, 17% UAE Nationals), 24% reported smoking of different sorts.,Overall, 68 participants (12.9%, 95% C.I.,10.3% to 16.1%) had airflow limitation compatible with COPD.,PEFR alone identified 141participants with airflow limitation compatible with COPD, with specificity of 80% and sensitivity of 73.5%.,PEFR could be an easy, cheap, and non-biased tool to assist with the case-finding of COPD before confirmation with spirometry. | 1 |
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. | Purpose.,This study aimed to examine whether plasma levels of cathepsin S or its inhibitor, cystatin C, may serve as biomarkers for COPD.,Patients and Methods.,We measured anthropometrics and performed pulmonary function tests and chest CT scans on 94 patients with COPD and 31 subjects with productive cough but no airflow obstruction (“at risk”; AR).,In these subjects and in 52 healthy nonsmokers (NS) and 66 healthy smokers (HS) we measured plasma concentrations of cathepsin S and cystatin C using an ELISA.,Data were analyzed using simple and logistic regression and receiver operating characteristic analyses.,Results.,Cathepsin S and cystatin C plasma levels were significantly higher in the COPD and AR groups than in the NS and HS groups (p < 0.01).,Among the COPD patients and AR subjects, plasma cathepsin S levels and cathepsin S/cystatin C ratios, but not cystatin C levels, were negatively related to severe airflow limitation (% FEV1 predicted < 50%; p = 0.005) and severe emphysema as assessed by low attenuation area (LAA) score on chest CT scans (LAA ≥ 8.0; p = 0.001).,Conclusion.,Plasma cathepsin S and cathepsin S/cystatin C ratios may serve as potential biomarkers for COPD. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD), characterized by acute deterioration in symptoms, may be due to bacterial or viral infections, environmental exposures, or unknown factors.,Exacerbation frequency may be a stable trait in COPD patients, which could imply genetic susceptibility.,Observing the genes, networks, and pathways that are up- and down-regulated in COPD patients with differing susceptibility to exacerbations will help to elucidate the molecular signature and pathogenesis of COPD exacerbations.,Gene expression array and plasma biomarker data were obtained using whole-blood samples from subjects enrolled in the Treatment of Emphysema With a Gamma-Selective Retinoid Agonist (TESRA) study.,Linear regression, weighted gene co-expression network analysis (WGCNA), and pathway analysis were used to identify signatures and network sub-modules associated with the number of exacerbations within the previous year; other COPD-related phenotypes were also investigated.,Individual genes were not found to be significantly associated with the number of exacerbations.,However using network methods, a statistically significant gene module was identified, along with other modules showing moderate association.,A diverse signature was observed across these modules using pathway analysis, marked by differences in B cell and NK cell activity, as well as cellular markers of viral infection.,Within two modules, gene set enrichment analysis recapitulated the molecular signatures of two gene expression experiments; one involving sputum from asthma exacerbations and another involving viral lung infections.,The plasma biomarker myeloperoxidase (MPO) was associated with the number of recent exacerbations.,A distinct signature of COPD exacerbations may be observed in peripheral blood months following the acute illness.,While not predictive in this cross-sectional analysis, these results will be useful in uncovering the molecular pathogenesis of COPD exacerbations.,The online version of this article (doi:10.1186/s12920-014-0072-y) contains supplementary material, which is available to authorized users. | 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 |
There is a need for agents that suppress inflammation and progression of chronic obstructive pulmonary disease. p38 mitogen-activated protein kinase (p38 MAPK) has been associated with this disorder, and several inhibitors of this cascade are in clinical trials for its treatment, but their efficacy and utility are unknown.,This study evaluated the relationship between p38 MAPK activation and susceptibility to cigarette smoke (CS)-induced emphysema, and whether its inhibition ameliorated the lung inflammation and injury in murine models of cigarette smoke exposure.,In acute and chronic CS exposure, the activation and expression of p38 MAPK in the lungs, as well as lung inflammation and injury (proteinase production, apoptosis, and oxidative DNA damage), were compared between two mouse strains: C57BL/6 (emphysema-susceptible) and NZW (emphysema-resistant).,The selective p38 MAPK inhibitor SB203580 (45 mg/kg) was administrated intra-peritoneally to C57BL/6 mice, to examine whether it ameliorated cigarette smoke-induced lung inflammation and injury.,Acute CS-induced lung inflammation (neutrophil infiltration, mRNA expressions of TNF-α and MIP-2), proteinase expression (MMP-12 mRNA), apoptosis, and oxidative DNA damage were significantly lower in NZW than C57BL/6 mice. p38 MAPK was significantly activated and up-regulated by both acute and chronic CS exposure in C57BL/6 but not NZW mice. mRNA expression of p38 MAPK was also upregulated in C57BL/6 by chronic CS exposure and tended to be constitutively suppressed in NZW mice.,SB203580 significantly attenuated lung inflammation (neutrophil infiltration, mRNA expressions of TNF-α and MIP-2, protein levels of KC, MIP-1α, IL-1β, and IL-6), proteinase expression (MMP-12 mRNA), oxidative DNA damage, and apoptosis caused by acute CS exposure.,Cigarette smoke activated p38 MAPK only in mice that were susceptible to cigarette smoke-induced emphysema.,Its selective inhibition ameliorated lung inflammation and injury in a murine model of cigarette smoke exposure. p38 MAPK pathways are a possible molecular target for the treatment of chronic obstructive pulmonary disease. | Although culture-independent techniques have shown that the lungs are not sterile, little is known about the lung microbiome in chronic obstructive pulmonary disease (COPD).,We used pyrosequencing of 16S amplicons to analyze the lung microbiome in two ways: first, using bronchoalveolar lavage (BAL) to sample the distal bronchi and air-spaces; and second, by examining multiple discrete tissue sites in the lungs of six subjects removed at the time of transplantation.,We performed BAL on three never-smokers (NS) with normal spirometry, seven smokers with normal spirometry (“heathy smokers”, HS), and four subjects with COPD (CS).,Bacterial 16 s sequences were found in all subjects, without significant quantitative differences between groups.,Both taxonomy-based and taxonomy-independent approaches disclosed heterogeneity in the bacterial communities between HS subjects that was similar to that seen in healthy NS and two mild COPD patients.,The moderate and severe COPD patients had very limited community diversity, which was also noted in 28% of the healthy subjects.,Both approaches revealed extensive membership overlap between the bacterial communities of the three study groups.,No genera were common within a group but unique across groups.,Our data suggests the existence of a core pulmonary bacterial microbiome that includes Pseudomonas, Streptococcus, Prevotella, Fusobacterium, Haemophilus, Veillonella, and Porphyromonas.,Most strikingly, there were significant micro-anatomic differences in bacterial communities within the same lung of subjects with advanced COPD.,These studies are further demonstration of the pulmonary microbiome and highlight global and micro-anatomic changes in these bacterial communities in severe COPD patients. | 1 |
Pulmonary function measures reflect respiratory health and predict mortality, and are used in the diagnosis of chronic obstructive pulmonary disease (COPD).,We tested genome-wide association with the forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in 48,201 individuals of European ancestry, with follow-up of top associations in up to an additional 46,411 individuals.,We identified new regions showing association (combined P<5×10−8) with pulmonary function, in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1, and KCNE2.,Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function. | There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD).,The only known genetic risk factor is severe deficiency of α1-antitrypsin, which is present in 1-2% of individuals with COPD.,We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study.,The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population.,Logistic regression models with adjustments of covariates were used to analyze the case-control populations.,Family-based association analyses were conducted for a diagnosis of COPD and lung function in the family populations.,Two SNPs at the α-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study.,They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48×10−10, (rs8034191) and 5.74×10−10 (rs1051730).,Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations.,The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%.,The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels.,Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; doi:10.1371/journal.pgen.1000429).,The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD.,CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer. | 1 |
Rationale: Whether pharmacological therapy alters decline in FEV1 in chronic obstructive pulmonary disease remains controversial.,Because pharmacotherapy improves health status, exacerbation rate, and symptoms, it may be unethical to complete placebo-controlled long-term studies aimed at modifying FEV1 decline.,Objectives: We conducted a systematic review of placebo-controlled pharmacological trials lasting ≥1 year to address the question of whether therapy alters FEV1 decline.,Methods: A literature search for randomized trials that included repeated spirometry with at least one active and one placebo arm was conducted.,Articles were excluded if study duration was <1 year, <3 spirometric measurements, or <100 subjects per arm.,Study design was assessed using the Jadad score.,To combine studies and find the estimated effect, we used random effects methodology to account for both within-study and between-study variation.,Measurements and Main Results: There were 33,051 patients in the analysis (active component, n = 21,941; placebo, n = 11,110 in nine studies).,The active treatment arms demonstrated a 5.0 ml/yr reduction (95% confidence interval, 0.8-9.1 ml/yr; P < 0.001) in the rate of FEV1 decline compared with the placebo arms.,The relative FEV1 differences between active and placebo arms were within the range of differences reported for health status and for the exacerbation rate in the same studies.,Conclusions: In chronic obstructive pulmonary disease, pharmacotherapy ameliorates rate of lung function decline.,The relative benefit observed is within the range of those reported for health status and exacerbations in the same studies.,Guidelines should be adjusted according to these findings. | One‐way endobronchial valves (EBV) insertion to reduce pulmonary air trapping has been used as therapy for chronic obstructive pulmonary disease (COPD) patients.,However, local inflammation may result and can contribute to worsening of clinical status in these patients.,We hypothesized that combined EBV insertion and intrabronchial administration of mesenchymal stromal cells (MSCs) would decrease the inflammatory process, thus mitigating EBV complications in severe COPD patients.,This initial study sought to investigate the safety of this approach.,For this purpose, a phase I, prospective, patient‐blinded, randomized, placebo‐controlled design was used.,Heterogeneous advanced emphysema (Global Initiative for Chronic Lung Disease [GOLD] III or IV) patients randomly received either allogeneic bone marrow‐derived MSCs (108 cells, EBV+MSC) or 0.9% saline solution (EBV) (n = 5 per group), bronchoscopically, just before insertion of one‐way EBVs.,Patients were evaluated 1, 7, 30, and 90 days after therapy.,All patients completed the study protocol and 90‐day follow‐up.,MSC delivery did not result in acute administration‐related toxicity, serious adverse events, or death.,No significant between‐group differences were observed in overall number of adverse events, frequency of COPD exacerbations, or worsening of disease.,Additionally, there were no significant differences in blood tests, lung function, or radiological outcomes.,However, quality‐of‐life indicators were higher in EBV + MSC compared with EBV.,EBV + MSC patients presented decreased levels of circulating C‐reactive protein at 30 and 90 days, as well as BODE (Body mass index, airway Obstruction, Dyspnea, and Exercise index) and MMRC (Modified Medical Research Council) scores.,Thus, combined use of EBV and MSCs appears to be safe in patients with severe COPD, providing a basis for subsequent investigations using MSCs as concomitant therapy.,Stem Cells Translational Medicine 2017;6:962-969 | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by a progressive airflow limitation and is associated with a chronic inflammatory response in both airways and lungs. microRNAs (miRNAs) are often highly conserved between species and have an intricate role within homeostatic conditions and immune responses.,Also, miRNAs are dysregulated in smoking-associated diseases.,We investigated the miRNA profile of 523 miRNAs by stem-loop RT-qPCR in lung tissue and cell-free bronchoalveolar lavage (BAL) supernatant of mice exposed to air or cigarette smoke (CS) for 4 or 24 weeks.,After 24 weeks of CS exposure, 31 miRNAs were differentially expressed in lung tissue and 78 in BAL supernatant.,Next, we correlated the miRNA profiling data to inflammation in BAL and lung, obtained by flow cytometry or ELISA.,In addition, we surveyed for overlap with newly assessed miRNA profiles in bronchial biopsies and with previously assessed miRNA profiles in lung tissue and induced sputum supernatant of smokers with COPD.,Several miRNAs showed concordant differential expression between both species including miR-31*, miR-155, miR-218 and let-7c.,Thus, investigating miRNA profiling data in different compartments and both species provided accumulating insights in miRNAs that may be relevant in CS-induced inflammation and the pathogenesis of COPD. | A core feature of chronic obstructive pulmonary disease (COPD) is the accelerated decline in forced expiratory volume in one second (FEV1).,The recent Groningen and Leiden Universities study of Corticosteroids in Obstructive Lung Disease (GLUCOLD) study suggested that particular phenotypes of COPD benefit from fluticasone±salmeterol by reducing the rate of FEV1 decline, yet the underlying mechanisms are unknown.,Whole-genome gene expression profiling using the Affymetrix Gene ST array (V.1.0) was performed on 221 bronchial biopsies available from 89 COPD patients at baseline and after 6 and 30 months of fluticasone±salmeterol and placebo treatment in GLUCOLD.,Linear mixed effects modelling revealed that the expression of 138 genes decreased, whereas the expression of 140 genes significantly upregulated after both 6 and 30 months of treatment with fluticasone±salmeterol versus placebo.,A more pronounced treatment-induced change in the expression of 50 and 55 of these 278 genes was associated with a lower rate of decline in FEV1 and Saint George Respiratory Questionnaire, respectively.,Genes decreasing with treatment were involved in pathways related to cell cycle, oxidative phosphorylation, epithelial cell signalling, p53 signalling and T cell signalling.,Genes increasing with treatment were involved in pathways related to focal adhesion, gap junction and extracellular matrix deposition.,Finally, the fluticasone-induced gene expression changes were enriched among genes that change in the airway epithelium in smokers with versus without COPD in an independent data set.,The present study suggests that gene expression in biological pathways of COPD is dynamic with treatment and reflects disease activity.,This study opens the gate to targeted and molecular phenotype-driven therapy of COPD. | 1 |
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. | While tobacco smoking is the main risk factor for chronic obstructive pulmonary disease (COPD) only a fraction of smokers go on to develop the disease.,We investigated the relationship between the insertion (I) - deletion (D) polymorphisms in the Angiotensin converting enzyme (ACE) gene and the risk of developing COPD in smokers by determining the distribution of the ACE genotypes (DD, ID and II) in 151 life-long male smokers. 74 of the smokers had developed COPD (62 ± 2 years; FEV1 44 ± 6 % reference) whereas the rest retained normal lung function (56 ± 2 yrs; FEV1 95 ± 3 % reference).,In addition, we genotyped 159 males recruited randomly from the general population.,The prevalence of the DD genotype was highest (p = 0.01) in the smokers that developed COPD and its presence was associated with a 2-fold increase in the risk for COPD (OR 2.2; IC95% 1.1 to 5.5).,Surprisingly, the 151 individuals in the smoking population did not demonstrate Hardy-Weinberg equilibrium unlike the 159 recruited from the general population.,Our results suggest that ACE polymorphisms are associated with both the smoking history of an individual and their risk of developing COPD. | 1 |
Over the past 20 years, the Global Initiative for Asthma (GINA) has regularly published and annually updated a global strategy for asthma management and prevention that has formed the basis for many national guidelines.,However, uptake of existing guidelines is poor.,A major revision of the GINA report was published in 2014, and updated in 2015, reflecting an evolving understanding of heterogeneous airways disease, a broader evidence base, increasing interest in targeted treatment, and evidence about effective implementation approaches.,During development of the report, the clinical utility of recommendations and strategies for their practical implementation were considered in parallel with the scientific evidence.,This article provides a summary of key changes in the GINA report, and their rationale.,The changes include a revised asthma definition; tools for assessing symptom control and risk factors for adverse outcomes; expanded indications for inhaled corticosteroid therapy; a framework for targeted treatment based on phenotype, modifiable risk factors, patient preference, and practical issues; optimisation of medication effectiveness by addressing inhaler technique and adherence; revised recommendations about written asthma action plans; diagnosis and initial treatment of the asthma−chronic obstructive pulmonary disease overlap syndrome; diagnosis in wheezing pre-school children; and updated strategies for adaptation and implementation of GINA recommendations.,This paper summarises key changes in the GINA global strategy report, a practical new resource for asthma carehttp://ow.ly/ObvYi | 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 |
To determine the influence of iterative reconstruction (IR) on quantitative computed tomography (CT) measurements of emphysema, air trapping, and airway wall and lumen dimensions, compared to filtered back-projection (FBP).,Inspiratory and expiratory chest CTs of 75 patients (37 male, 38 female; mean age 64.0 ± 5.7 years) were reconstructed using FBP and IR.,CT emphysema, CT air trapping and airway dimensions of a segmental bronchus were quantified using several commonly used quantification methods.,The two algorithms were compared using the concordance correlation coefficient (p c) and Wilcoxon signed rank test.,Only the E/I-ratioMLD as a measure of CT air trapping and airway dimensions showed no significant differences between the algorithms, whereas all CT emphysema and the other CT air trapping measures were significantly different at IR when compared to FBP (P < 0.001).,The evaluated IR algorithm significantly influences quantitative CT measures in the assessment of emphysema and air trapping.,However, the E/I-ratioMLD as a measure of CT air trapping, as well as the airway measurements, is unaffected by this reconstruction method.,Quantitative CT of the lungs should be performed with careful attention to the CT protocol, especially when iterative reconstruction is introduced.,• New techniques in CT allow numerous quantitative measurements of lung function.,• Iterative reconstruction influences quantitative CT measurements of emphysema and air trapping.,• Expiratory-to-inspiratory ratio of mean lung density and airway measurements are unaffected by iterative reconstruction.,• Quantitative lung-CT should be performed with careful attention to the CT protocol. | Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease that is characterized by chronic airflow limitation.,Unraveling of this heterogeneity is challenging but important, because it might enable more accurate diagnosis and treatment.,Because spirometry cannot distinguish between the different contributing pathways of airflow limitation, and visual scoring is time-consuming and prone to observer variability, other techniques are sought to start this phenotyping process.,Quantitative computed tomography (CT) is a promising technique, because current CT technology is able to quantify emphysema, air trapping, and large airway wall dimensions.,This review focuses on CT quantification techniques of COPD disease components and their current status and role in phenotyping COPD. | 1 |
The well-recognized individual heterogeneity within COPD patients has led to a growing interest in greater personalization in the approach of these patients.,Thus, the treatable traits strategy has been proposed as a further step towards precision medicine in the management of chronic airway disease, both in stable phase and acute exacerbations.,The aim of this paper is to perform a critical review on the treatable traits strategy and propose a guide to approach COPD patients in the light of this new concept.,An innovative stepwise approach is proposed - a multidisciplinary model based on two distinct phases, with the potential to be implemented in both primary care and hospital settings.,The first phase is the initial and focused assessment of a selected subset of treatable traits, which should be addressed in all COPD patients in both settings (primary care and hospital).,As some patients may present with advanced disease at diagnosis or may progress despite this initial treatment requiring a more specialized assessment, they should progress to a second phase, in which a broader approach is recommended.,Beyond stable COPD, we explore how the treatable traits strategy may be applied to reduce the risk of future exacerbations and improve the management of COPD exacerbations.,Since many treatable traits have already been related to exacerbation risk, the strategy proposed here represents an opportunity to be proactive.,Although it still lacks prospective validation, we believe this is the way forward for the future of the COPD approach. | Microorganisms, particularly bacteria, are frequently found in the lower airways of COPD patients, both in stable state and during exacerbations.,The host-pathogen relationship in COPD is a complex, dynamic process characterised by frequent changes in pathogens, their strains and loads, and subsequent host immune responses.,Exacerbations are detrimental events in the course of COPD and evidence suggests that 70% may be caused by microorganisms.,When considering bacterial exacerbations, recent findings based on molecular typing have demonstrated that the acquisition of new strains of bacteria or antigenic changes in pre-existing strains are the most important triggers for exacerbation onset.,Even in clinically stable COPD patients the presence of microorganisms in their lower airways may cause harmful effects and induce chronic low-grade airway inflammation leading to increased exacerbation frequency, an accelerated decline in lung function and impaired health-related quality of life.,Besides intraluminal localisation in the distal airways, bacteria can be found in the bronchial walls and parenchymal lung tissue of COPD patients.,Therefore, the isolation of pathogenic bacteria in stable COPD should be considered as a form of chronic infection rather than colonisation.,This new approach may have important implications for the management of patients with COPD. | 1 |
Airway epithelium integrity is essential to maintain its role of mechanical and functional barrier.,Recurrent epithelial injuries require a complex mechanism of repair to restore its integrity.,In chronic obstructive pulmonary disease (COPD), an abnormal airway epithelial repair may participate in airway remodeling.,The objective was to determine if airway epithelial wound repair of airway epithelium is abnormal in COPD.,Patients scheduled for lung resection were prospectively recruited.,Demographic, clinical data and pulmonary function tests results were recorded.,Emphysema was visually scored and histological remodeling features were noted.,Primary bronchial epithelial cells (BEC) were extracted and cultured for wound closure assay.,We determined the mean speed of wound closure (MSWC) and cell proliferation index, matrix metalloprotease (MMP)-2, MMP-9 and cytokines levels in supernatants of BEC 18 hours after cell wounding.,In a subset of patients, bronchiolar epithelial cells were also cultured for wound closure assay for MSWC analyze.,13 COPD and 7 non COPD patients were included.,The severity of airflow obstruction and the severity of emphysema were associated with a lower MSWC in BEC (p = 0.01, 95% CI [0.15-0.80]; p = 0.04, 95% CI [−0.77;-0.03] respectively).,Cell proliferation index was decreased in COPD patients (19 ± 6% in COPD vs 27 ± 3% in non COPD, p = 0.04).,The severity of COPD was associated with a lower level of MMP-2 (7.8 ± 2 105 AU in COPD GOLD D vs 12.8 ± 0.13 105 AU in COPD GOLD A, p = 0.04) and a lower level of IL-4 (p = 0.03, 95% CI [0.09;0.87]).,Moreover, higher levels of IL-4 and IL-2 were associated with a higher MSWC (p = 0.01, 95% CI [0.17;0.89] and p = 0.02, 95% CI [0.09;0.87] respectively).,Clinical characteristics and smoking history were not associated with MSWC, cell proliferation index or MMP and cytokines levels.,Finally, we showed an association of the MSWC of bronchial and corresponding bronchiolar epithelial cells obtained from the same patients (p = 0.02, 95% CI [0.12;0.89]).,Our results showed an abnormal bronchial epithelial wound closure process in severe COPD.,Further studies are needed to elucidate the contribution and the regulation of this mechanism in the complex pathophysiology of COPD.,The online version of this article (doi:10.1186/s12931-014-0151-9) contains supplementary material, which is available to authorized users. | The Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is a chloride channel that primarily resides in airway epithelial cells.,Decreased CFTR expression and/or function lead to impaired airway surface liquid (ASL) volume homeostasis, resulting in accumulation of mucus, reduced clearance of bacteria, and chronic infection and inflammation.,Expression of CFTR and the cigarette smoke metal content were assessed in lung samples of controls and COPD patients with established GOLD stage 4.,CFTR protein and mRNA were quantified by immunohistochemistry and quantitative RT-PCR, respectively.,Metals present in lung samples were quantified by ICP-AES.,The effect of cigarette smoke on down-regulation of CFTR expression and function was assessed using primary human airway epithelial cells.,The role of leading metal(s) found in lung samples of GOLD 4 COPD patients involved in the alteration of CFTR was confirmed by exposing human bronchial epithelial cells 16HBE14o- to metal-depleted cigarette smoke extracts.,We found that CFTR expression is reduced in the lungs of GOLD 4 COPD patients, especially in bronchial epithelial cells.,Assessment of metals present in lung samples revealed that cadmium and manganese were significantly higher in GOLD 4 COPD patients when compared to control smokers (GOLD 0).,Primary human airway epithelial cells exposed to cigarette smoke resulted in decreased expression of CFTR protein and reduced airway surface liquid height.,16HBE14o-cells exposed to cigarette smoke also exhibited reduced levels of CFTR protein and mRNA.,Removal and/or addition of metals to cigarette smoke extracts before exposure established their role in decrease of CFTR in airway epithelial cells.,CFTR expression is reduced in the lungs of patients with severe COPD.,This effect is associated with the accumulation of cadmium and manganese suggesting a role for these metals in the pathogenesis of COPD. | 1 |
Inhaled therapy is key to the management of chronic obstructive pulmonary disease (COPD).,New drugs and inhalers have recently been launched or will soon become available, and the expiry of patent protection covering several currently used inhaled bronchodilators and corticosteroids will be accompanied by the development of bioequivalent, generic inhaled drugs.,Consequently, a broader availability of branded and generic compounds will increase prescription opportunities.,Given the time course of COPD, patients are likely to switch drugs and inhalers in daily practice.,Switching from one device to another, if not accompanied by appropriate training for the patient, can be associated with poor clinical outcomes and increased use of health care resources.,In fact, while it seems reasonable to prescribe generic inhaled drugs to reduce costs, inadequate use of inhaler devices, which is often associated with a poor patient-physician or patient-pharmacist relationship, is one of the most common reasons for failure to achieve COPD treatment outcomes.,Further research is needed to quantify, as in asthma, the impact of inappropriate switching of inhalers in patients with COPD and show the outcomes related to the effect of using the same device for delivering inhaled medications. | Investigate long-term effects 4 years after the end of a 1-year self-management program (SMP) with 30 hours of education and 16 hours of physical activity in patients with chronic obstructive pulmonary disease (COPD).,Prospective observational outcome study.,SMP focused on improving disease related self-care skills.,Main outcome measures were health-related quality of life, HRQoL, (St Georges Respiratory Questionnaire, SGRQ total) and exercise capacity (6-minute walk test, 6MWT).,Thirty patients participated, 47% women.,Baseline mean age was 67 years and mean pre-bronchodilator FEV1 (forced expiratory volume in 1 second) percentage predicted was 41.3.,HRQoL showed a statistical significant improvement during the 1-year intervention.,Four years after the end of the program SGRQ total was similar to baseline value, 1.4 points (95% CI: −3.6 to 6.3, P = 0.580).,Also 6MWT was similar to baseline value at the same test point, −10 m (95% CI: −27 to 8, P = 0.262), and 63% reported having continued to exercise regularly a minimum of three times per week during the follow-up period.,The participants in a 1-year self-management program with additional training had maintained their pre-intervention level of HRQoL and exercise capacity 4 years after the end of the program.,Two out of three participants had continued to exercise regularly. | 1 |
Cigarette smoking (CS), the main risk factor for COPD (chronic obstructive pulmonary disease) in developed countries, decreases alveolar macrophages (AM) clearance of both apoptotic cells and bacterial pathogens.,This global deficit of AM engulfment may explain why active smokers have worse outcomes of COPD exacerbations, episodes characterized by airway infection and inflammation that carry high morbidity and healthcare cost.,When administered as intravenous supplementation, the acute phase-reactant alpha-1 antitrypsin (A1AT) reduces the severity of COPD exacerbations in A1AT deficient (AATD) individuals and of bacterial pneumonia in murine models, but the effect of A1AT on AM scavenging functions has not been reported.,Apoptotic cell clearance (efferocytosis) was measured in human AM isolated from patients with COPD, in primary rat AM or differentiated monocytes exposed to CS ex vivo, and in AM recovered from mice exposed to CS.,A1AT (100 μg/mL, 16 h) significantly ameliorated efferocytosis (by ~50%) in AM of active smokers or AM exposed ex vivo to CS.,A1AT significantly improved AM global engulfment, including phagocytosis, even when cells were simultaneously challenged with apoptotic and Fc-coated (bacteria-like) targets.,The improved efferocytosis in A1AT-treated macrophages was associated with inhibition of tumor necrosis factor-α converting enzyme (TACE) activity, decreased mannose receptor shedding, and markedly increased abundance of efferocytosis receptors (mannose- and phosphatidyl serine receptors and the scavenger receptor B2) on AM plasma membrane.,Directed airway A1AT treatment (via inhalation of a nebulized solution) restored in situ airway AM efferocytosis after CS exposure in mice.,The amelioration of CS-exposed AM global engulfment may render A1AT as a potential therapy for COPD exacerbations. | Eosinophilic airway inflammation is observed in 10-30% of COPD subjects.,Whether increased eosinophils or impairment in their clearance by macrophages is associated with the severity and frequency of exacerbations is unknown.,We categorised 103 COPD subjects into 4 groups determined by the upper limit of normal for their cytoplasmic macrophage red hue (<6%), an indirect measure of macrophage efferocytosis of eosinophils, and area under the curve sputum eosinophil count (≥3%/year).,Eosinophil efferocytosis by monocyte-derived macrophages was studied in 17 COPD subjects and 8 normal controls.,There were no differences in baseline lung function, health status or exacerbation frequency between the groups: A-low red hue, high sputum eosinophils (n = 10), B-high red hue, high sputum eosinophils (n = 16), C-low red hue, low sputum eosinophils (n = 19) and D- high red hue, low sputum eosinophils (n = 58).,Positive bacterial culture was lower in groups A (10%) and B (6%) compared to C (44%) and D (21%) (p = 0.01).,The fall in FEV1 from stable to exacerbation was greatest in group A (ΔFEV1 [95 % CI] -0.41 L [-0.65 to -0.17]) versus group B (-0.16 L [-0.32 to -0.011]), C (-0.11 L [-0.23 to -0.002]) and D (-0.16 L [-0.22 to -0.10]; p = 0.02).,Macrophage efferocytosis of eosinophils was impaired in COPD versus controls (86 [75 to 92]% versus 93 [88 to 96]%; p = 0.028); was most marked in group A (71 [70 to 84]%; p = 0.0295) and was inversely correlated with exacerbation frequency (r = -0.63; p = 0.006).,Macrophage efferocytosis of eosinophils is impaired in COPD and is related to the severity and frequency of COPD exacerbations. | 1 |
In respiratory disorders, patient- and physician-perceived satisfaction with the maintenance inhaler device is an important factor driving treatment compliance and outcomes.,We examine inhaler preferences in asthma and COPD from patient and physician perspectives, particularly focusing on the relative importance of individual device attributes and patient characteristics guiding inhaler choice.,Real-world data from >7,300 patients with asthma, COPD, or asthma-COPD overlap syndrome (ACOS) consulting for routine care were derived from respiratory Disease Specific Programs conducted in Europe, USA, Japan, and China.,Outcome variables included current pattern of inhaled maintenance therapy and device type, physician preference, patient-reported device attribute importance, and satisfaction.,The most commonly prescribed inhalers for maintenance therapy of asthma, COPD, and ACOS were dry powder inhalers (62.8%-88.5% of patients) and pressurized metered dose inhalers (18.9%-35.3% of patients).,One-third of physicians stated no preference for maintenance device when prescribing treatment, and less than one-third of patients reported being “extremely satisfied” with any attribute of their device.,Instructions being “simple and easy to follow” was the inhaler attribute most commonly selected as important.,For approximately one-third of patients across all groups, “ease of use/suitability of inhaler device” was a reason for the prescribing decision, as stated by the physician.,Device characteristics were more likely to impact the prescribing decision in older patients (in asthma and COPD; P<0.01) and those with worse disease severity (in COPD; P<0.001).,A relatively high proportion of physicians had no preference for inhaler type across asthma, COPD, and ACOS.,Simplicity of use was the most important inhaler attribute from a patient’s perspective.,Physicians appeared to place most importance on ease of use and device suitability when selecting inhalers for older patients and those with more severe disease, particularly in COPD. | Background: Two studies were undertaken to characterize the maximal effort inhalation profiles of healthy subjects and patients with asthma or chronic obstructive pulmonary disease (COPD) through a moderate-resistance dry powder inhaler (DPI).,Correlations between inhaler-specific inhalation characteristics and inhaler-independent lung function parameters were investigated.,Methods: Healthy subjects (n = 15), patients with mild, moderate, or severe asthma (n = 45), and patients with mild, moderate, severe, or very-severe COPD (n = 60) were included in the studies.,Inhalation pressure drop versus time profiles were recorded using an instrumented ELLIPTA® DPI or bespoke resistor component with equivalent resistivity.,Inhaler-independent lung function assessments included pharyngometry, spirometry, plethysmography, and diffusion.,Results: For the inhaler-specific inhalation profiles, the mean maximal effort peak inspiratory flow rates (PIFRs) varied across the subgroups from 65.8-110.6 L/min (range: 41.6-142.9).,Peak pressure drop, PIFR, inhaled volume, and average inhalation flow rate (primary endpoints) did not differ markedly between healthy subjects and patients with asthma or mild COPD.,Moderate, severe, and very-severe COPD patients demonstrated lower mean peak pressure drops, PIFRs and inhaled volumes, which tended to decrease with increasing COPD severity.,Severe and very-severe COPD patients demonstrated shorter mean inhalation times compared with all other participants.,Inhaler-independent lung function parameters were consistent with disease severity, and statistically significant (p < 0.05) strong correlations (R > 0.7) with components of the inhaler-specific inhalation profiles were observed in the COPD cohort; correlations in the asthma cohort tended to be weaker.,Conclusions: All participants achieved a maximal effort PIFR ≥ 41.6 L/min through the moderate resistance of the ELLIPTA inhaler.,Patients with asthma achieved similar inhalation profiles to healthy subjects, but increasing COPD severity tended to reduce a patient's inhalation capability.,Correlation analyses suggest that some lung function parameters may be a useful indicator of ability to inhale efficiently through a moderate-resistance DPI, such as the ELLIPTA inhaler. | 1 |
The DYNAGITO study was a Phase IIIb, randomized, double-blind, multicenter, active-controlled, parallel-group, 52-week study designed to determine the efficacy and safety of tiotropium and olodaterol combination therapy (TIO+OLO 5/5 μg) versus tiotropium monotherapy (TIO 5 μg) for reducing moderate-to-severe exacerbations of COPD.,This is a prespecified analysis of the DYNAGITO data in Japanese patients.,Enrolled patients had a diagnosis of COPD with at least one moderate-to-severe exacerbation in the previous 12 months.,Of the total 7,880 treated patients in the DYNAGITO study, 461 (TIO+OLO 5/5 μg: n=226, TIO 5 μg: n=235) were Japanese.,The primary endpoint was the annualized rate of moderate-to-severe COPD exacerbations.,The key secondary endpoint was the time to first moderate-to-severe COPD exacerbation, and other secondary endpoints included the annualized rate of exacerbations leading to hospitalization, time to first COPD exacerbation leading to hospitalization, and all-cause mortality.,Safety data were analyzed descriptively.,Combination therapy with TIO+OLO resulted in a 29% lower rate of moderate-to-severe COPD exacerbations relative to TIO monotherapy (rate ratio 0.71; 99% CI: 0.46, 1.10; p=0.0434).,The risk of a first moderate-to-severe COPD exacerbation was 19% lower with TIO+OLO combination therapy than with TIO monotherapy (HR 0.81; 99% CI: 0.57, 1.17; p=0.1379), although this difference was not statistically significant.,The annualized rate of COPD exacerbations requiring hospitalization was 14% lower in the TIO+OLO arm than in the TIO arm (rate ratio 0.86; 95% CI: 0.52, 1.42; p=0.5654).,The adverse event incidence was balanced between treatment arms.,In a prespecified subgroup analysis of Japanese patients in the DYNAGITO study, combination therapy with TIO+OLO was more effective than TIO in reducing exacerbations.,Both treatments were well tolerated. | 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. | 1 |
Lung clearance index (LCI), derived from multiple-breath washout (MBW), is a well-established assessment of ventilation inhomogeneity in cystic fibrosis but has not been widely applied in other conditions characterized by heterogeneous airways disease, such as COPD.,The aim of this study was to evaluate the sensitivity, repeatability, and practicality of LCI in patients with COPD.,Fifty-four COPD patients completed MBW using nitrogen as the washout tracer gas (MBWN2, measured using an Exhalyzer™ device), spirometry, and plethysmography.,Twenty patients repeated MBWN2, MBWSF6 (using a separate Innocor™ gas analyzer to measure washout of the exogenous trace sulphur hexafluoride), and spirometry at a second visit ≥24 hours later.,Mean (SD) COPD LCI measured by nitrogen washout (LCIN2) was 12.1 (2.2); mean (SD) LCI Z-score 5.8 (2.0).,LCIN2 increased across Global Initiative for Obstructive Lung Disease stages 1 to 3 and was abnormal (Z-score >1.65) in all COPD patients, including those with forced expiratory volume in 1 second (FEV1) ≥80% predicted.,LCI was repeatable (median intra-test coefficient of variation 4.1%) and reproducible (limits of agreement −1.8 to 1.6) after mean of 16 days.,Functional residual capacity (FRC) measurements were significantly greater using nitrogen than SF6 or plethysmography: mean FRC measured by nitrogen washout (FRCN2) 139% predicted versus FRC measured by plethysmography 125% predicted, p<0.0001.,LCI is most suitable as a measure of early airways disease in COPD in those with well-preserved FEV1, with similar repeatability and limitations to that observed in cystic fibrosis.,Using the Exhalyzer system to perform MBWN2, however, appeared to substantially over-read FRC.,This discrepancy needs addressing before FRCN2 measurements made using this device can be reliably deployed. | Wnt signaling pathways are tightly controlled under a physiological condition, under which they play key roles in many biological functions, including cell fate specification and tissue regeneration.,Increasing lines of evidence recently demonstrated that a dysregulated activation of Wnt signaling, particularly the Wnt/β-catenin signaling, was involved in the pathogenesis of chronic pulmonary diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).,In this respect, Wnt signaling interacts with other cellular signaling pathways to regulate the initiation and pathogenic procedures of airway inflammation and remodeling, pulmonary myofibroblast proliferation, epithelial-to-mesenchymal transition (EMT), and development of emphysema.,Intriguingly, Wnt/β-catenin signaling is activated in IPF; an inhibition of this signaling leads to an alleviation of pulmonary inflammation and fibrosis in experimental models.,Conversely, Wnt/β-catenin signaling is inactivated in COPD tissues, and its reactivation results in an amelioration of airspace enlargement with a restored alveolar epithelial structure and function in emphysema models.,These studies thus imply distinct mechanisms of Wnt/β-catenin signaling in the pathogenesis of these two chronic pulmonary diseases, indicating potential targets for COPD and IPF treatments.,This review article aims to summarize the involvement and pathogenic roles of Wnt signaling pathways in the COPD and IPF, with a focus on the implication of Wnt/β-catenin signaling as underlying mechanisms and therapeutic targets in these two incurable diseases. | 1 |
The TORRACTO® study evaluated the effects of tiotropium/olodaterol versus placebo on endurance time during constant work-rate cycling and constant speed shuttle walking in patients with chronic obstructive pulmonary disease (COPD) after 12 weeks of treatment.,The effects of once-daily tiotropium/olodaterol (2.5/5 and 5/5 μg) on endurance time during constant work-rate cycle ergometry (CWRCE) after 6 and 12 weeks of treatment were compared with placebo in patients with COPD in a randomized, double-blind, placebo-controlled, parallel-group clinical trial.,Endurance time during the endurance shuttle walk test (ESWT) after 6 and 12 weeks of treatment was also evaluated in a subset of patients.,A total of 404 patients received treatment, with 165 participating in the ESWT substudy.,A statistically significant improvement in endurance time during CWRCE was observed after 12 weeks (primary endpoint) with tiotropium/olodaterol 5/5 µg [14% (p = 0.02)] but not with tiotropium/olodaterol 2.5/5 µg [9% (p = 0.14)] versus placebo.,In the ESWT substudy, a trend to improvement in endurance time during ESWT after 12 weeks (key secondary endpoint) was observed with tiotropium/olodaterol 5/5 µg [21% (p = 0.055)] and tiotropium/olodaterol 2.5/5 µg [21% (p = 0.056)] versus placebo.,Tiotropium/olodaterol 5/5 µg improved endurance time during cycle ergometry versus placebo, with a strong tendency to also improve walking endurance time.,[ClinicalTrials.gov identifier: NCT01525615.] | 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 |
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. | In patients with COPD progressive dyspnoea leads to a sedentary lifestyle.,To date, no studies exist investigating the effects of Nordic Walking in patients with COPD.,Therefore, the aim was to determine the feasibility of Nordic Walking in COPD patients at different disease stages.,Furthermore we aimed to determine the short- and long-term effects of Nordic Walking on COPD patients' daily physical activity pattern as well as on patients exercise capacity.,Sixty COPD patients were randomised to either Nordic Walking or to a control group.,Patients of the Nordic Walking group (n = 30; age: 62 ± 9 years; FEV1: 48 ± 19% predicted) underwent a three-month outdoor Nordic Walking exercise program consisting of one hour walking at 75% of their initial maximum heart rate three times per week, whereas controls had no exercise intervention.,Primary endpoint: daily physical activities (measured by a validated tri-axial accelerometer); secondary endpoint: functional exercise capacity (measured by the six-minute walking distance; 6MWD).,Assessment time points in both groups: baseline, after three, six and nine months.,After three month training period, in the Nordic Walking group time spent walking and standing as well as intensity of walking increased (Δ walking time: +14.9 ± 1.9 min/day; Δ standing time: +129 ± 26 min/day; Δ movement intensity: +0.40 ± 0.14 m/s2) while time spent sitting decreased (Δ sitting time: -128 ± 15 min/day) compared to baseline (all: p < 0.01) as well as compared to controls (all: p < 0.01).,Furthermore, 6MWD significantly increased compared to baseline (Δ 6MWD: +79 ± 28 meters) as well as compared to controls (both: p < 0.01).,These significant improvements were sustained six and nine months after baseline.,In contrast, controls showed unchanged daily physical activities and 6MWD compared to baseline for all time points.,Nordic Walking is a feasible, simple and effective physical training modality in COPD.,In addition, Nordic Walking has proven to positively impact the daily physical activity pattern of COPD patients under short- and long-term observation.,Nordic Walking improves daily physical activities in COPD: a randomised controlled trial - ISRCTN31525632 | 1 |
The study aimed to determine the relationship between throat microbiome and COPD.,Sixty-five Chinese males (n=20, smokers without COPD; n=45 smokers with COPD) were included.,Nonmetric multidimensional scaling indicated differences of microbiome between COPD and controls, but no difference was observed between COPD patients with differing degrees of lung function or disease severity.,Rarefaction analyses suggested that operational taxonomic units (OTUs, species-level) richness decreased in COPD.,The dominant taxa between COPD and controls were similar, but the proportions of taxonomic distribution were different.,The dominant phyla were Bacteroidetes, Proteobacteria, Firmicutes and Fusobacteria.,The dominant genera were Haemophilus, Leptotrichia, Porphyromonas, Fusobacterium, Veillonella, Streptococcus, Neisseria and Prevotella.,Two dominant OTUs, otu3 (Veillonella_dispar) and otu4 (Streptococcus_unclassified), were identified.,Otu3 and its father-level taxa, which were negatively correlated with predicted percent of forced expiratory volume in a second (FEV1%pred), were increased in COPD.,By contrast, otu4 and its father-level taxa, which were positively correlated with FEV1%pred, were decreased in COPD.,Otu4 also showed a slight potential as a COPD biomarker.,To conclude, the throat microbiome was different between smokers with or without COPD, which is similar to findings from the lower respiratory tract.,This study may strengthen our understanding of the relationship between microbiomes of different airway sites and COPD. | Nontypeable Haemophilus influenzae colonizes and infects the airways of adults with chronic obstructive pulmonary disease, the fourth most common cause of death worldwide.Thus, H. influenzae, an exclusively human pathogen, has adapted to survive in the hostile environment of the human airways.To characterize proteins expressed by H. influenzae in the airways, a prototype strain was grown in pooled human sputum to simulate conditions in the human respiratory tract.The proteins from whole bacterial cell lysates were solubilized with a strong buffer and then quantitatively cleaned with an optimized precipitation/on-pellet enzymatic digestion procedure.Proteomic profiling was accomplished by Nano-flow liquid chromatography/mass spectroscopy with low void volume and high separation efficiency with a shallow, long gradient.,A total of 1402 proteins were identified with high confidence, including 170 proteins that were encoded by genes that are annotated as conserved hypothetical proteins.Thirty-one proteins were present in greater abundance in sputum-grown conditions at a ratio of > 1.5 compared to chemically defined media.These included 8 anti-oxidant and 5 stress-related proteins, suggesting that expression of antioxidant activity and stress responses is important for survival in the airways.Four proteins involved in uptake of divalent anions and 9 proteins that function in uptake of various molecules were present in greater abundance in sputum-grown conditions.,Proteomic expression profiling of H. influenzae grown in pooled human sputum revealed increased expression of antioxidant, stress-response proteins and cofactor and nutrient uptake systems compared to media grown cells.These observations suggest that H. influenzae adapts to the oxidative and nutritionally limited conditions of the airways in adults with chronic obstructive pulmonary disease by increasing expression of molecules necessary for survival in these conditions. | 1 |
To determine the prevalence of COPD in Taiwan and to document the disease characteristics and associated risk factors.,We conducted a random cross-sectional national survey of adults older than 40 years in Taiwan.,Respiratory health screening questions identified subjects with diagnosed COPD or whose reported symptoms also fulfilled an epidemiological case definition; these were eligible to complete the survey, which also included indices of symptom severity and disability and questions on comorbidities, medical treatments, smoking habits, and occupations potentially harmful to respiratory health.,Subjects with diagnosed COPD were subdivided by smoking status.,Subjects who fulfilled the case definition of COPD and smoked were designated as “possible COPD”.,Participants who did not fit the case definition of COPD were asked only about their personal circumstances and smoking habits.,Data from these groups were analyzed and compared.,Of the 6,600 participants who completed the survey, 404 (6.1%) fulfilled the epidemiological case definition of COPD: 137 with diagnosed COPD and 267 possible COPD.,The most common comorbidities of COPD were hypertension or cardiovascular diseases (36.1%).,Subjects with definite COPD had significantly higher COPD Assessment Test scores than the possible COPD group (14.6±8.32 vs 12.6±6.49, P=0.01) and significantly more comorbid illnesses (P=0.01).,The main risk factors contributing to health care utilization in each COPD cohort were higher COPD Assessment Test scores (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.04-1.26), higher modified Medical Research Council Breathlessness Scale scores (OR 1.97, 95% CI 1.11-3.51), and having more than one comorbidity (OR 5.19, 95% CI 1.05-25.61).,With estimated prevalence of 6.1% in the general population, COPD in Taiwan has been underdiagnosed.,Symptoms and comorbidities were independent risk factors for health care utilization in subjects with definite or possible COPD.,There is an urgent need to raise awareness of the importance of early evaluation and prompt treatment for subjects with chronic airway symptoms. | There are limited data on the risk of pulmonary disease in patients with diabetes.,The aim of this study was to evaluate and compare the incidence of asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, pneumonia, and lung cancer in patients with and without a diagnosis of diabetes.,We conducted a retrospective, longitudinal cohort study using the electronic records of a large health plan in northern California.,Age and sex data were available for all cohort members (n = 1,811,228).,Data on confounders were available for a subcohort that responded to surveys (n = 121,886), among whom Cox proportional hazards regression models were fit.,Age- and sex-adjusted incidence rates and 95% CIs were calculated for members with and without diabetes in the full cohort and the subcohort.,No difference was observed for lung cancer, but the incidence of asthma, COPD, fibrosis, and pneumonia was significantly higher in those members with a diagnosis of diabetes.,These differences remained significant in regression models adjusted for age, sex, race/ethnicity, smoking, BMI, education, alcohol consumption, and outpatient visits (asthma hazard ratio [HR] 1.08 [95% CI 1.03-1.12], COPD HR 1.22 [1.15-1.28], pulmonary fibrosis HR 1.54 [1.31-1.81], and pneumonia HR 1.92 [1.84-1.99]).,The risk of pneumonia and COPD increased significantly with increasing A1C.,Individuals with diabetes are at increased risk of several pulmonary conditions (asthma, COPD, fibrosis, and pneumonia) but not lung cancer.,This increased risk may be a consequence of declining lung function in patients with diabetes. | 1 |
Frequent exacerbations which are both costly and potentially life-threatening are a major concern to patients with chronic obstructive pulmonary disease (COPD), despite the availability of several treatment options.,This study aimed to assess the lifetime costs and outcomes associated with alternative treatment regimens for patients with severe COPD in the UK setting.,A Markov cohort model was developed to predict lifetime costs, outcomes, and cost-effectiveness of various combinations of a long-acting muscarinic antagonist (LAMA), a long-acting beta agonist (LABA), an inhaled corticosteroid (ICS), and roflumilast in a fully incremental analysis.,Patients willing and able to take ICS, and those refusing or intolerant to ICS were analyzed separately.,Efficacy was expressed as relative rate ratios of COPD exacerbation associated with alternative treatment regimens, taken from a mixed treatment comparison.,The analysis was conducted from the UK National Health Service (NHS) perspective.,Parameter uncertainty was explored using one-way and probabilistic sensitivity analysis.,Based on the results of the fully incremental analysis a cost-effectiveness frontier was determined, indicating those treatment regimens which represent the most cost-effective use of NHS resources.,For ICS-tolerant patients the cost-effectiveness frontier suggested LAMA as initial treatment.,Where patients continue to exacerbate and additional therapy is required, LAMA + LABA/ICS can be a cost-effective option, followed by LAMA + LABA/ICS + roflumilast (incremental cost-effectiveness ratio [ICER] versus LAMA + LABA/ICS: £16,566 per quality-adjusted life-year [QALY] gained).,The ICER in ICS-intolerant patients, comparing LAMA + LABA + roflumilast versus LAMA + LABA, was £13,764/QALY gained.,The relative rate ratio of exacerbations was identified as the primary driver of cost-effectiveness.,The treatment algorithm recommended in UK clinical practice represents a costeffective approach for the management of COPD.,The addition of roflumilast to the standard of care regimens is a clinical and cost-effective treatment option for patients with severe COPD, who continue to exacerbate despite existing bronchodilator therapy. | To estimate patient- and episode-level direct costs of chronic obstructive pulmonary disease (COPD) among commercially insured patients in the US.,In this retrospective claims-based analysis, commercial enrollees with evidence of COPD were grouped into five mutually exclusive cohorts based on the most intensive level of COPD-related care they received in 2006, ie, outpatient, urgent outpatient (outpatient care in addition to a claim for an oral corticosteroid or antibiotic within seven days), emergency department (ED), standard inpatient admission, and intensive care unit (ICU) cohorts.,Patient- level COPD-related annual health care costs, including patient- and payer-paid costs, were compared among the cohorts.,Adjusted episode-level costs were calculated.,Of the 37,089 COPD patients included in the study, 53% were in the outpatient cohort, 37% were in the urgent outpatient cohort, 3% were in the ED cohort, and the standard admission and ICU cohorts together comprised 6%.,Mean (standard deviation, SD) annual COPD-related health care costs (2008 US$) increased across the cohorts (P < 0.001), ranging from $2003 ($3238) to $43,461 ($76,159) per patient.,Medical costs comprised 96% of health care costs for the ICU cohort.,Adjusted mean (SD) episode-level costs were $305 ($310) for an outpatient visit, $274 ($336) for an urgent outpatient visit, $327 ($65) for an ED visit, $9745 ($2968) for a standard admission, and $33,440 for an ICU stay.,Direct costs of COPD-related care for commercially insured patients are driven by hospital stays with or without ICU care.,Exacerbation prevention resulting in reduced need for inpatient care could lower costs. | 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. | The 2013 GOLD classification system for COPD distinguishes four stages: A (low symptoms, low exacerbation risk), B (high symptoms, low risk), C (low symptoms, high risk) and D (high symptoms, high risk).,Assessment of risk is based on exacerbation history and airflow obstruction, whatever results in a higher risk grouping.,The previous system was solely based on airflow obstruction.,Earlier studies compared the predictive performance of new and old classification systems with regards to mortality and exacerbations.,The objective of this study was to compare the ability of both classifications to predict the number of future (total and severe) exacerbations and mortality in a different patient population, and to add an outcome measure to the comparison: lung function decline.,Patient-level data from the UPLIFT trial were used to analyze 4-year survival in a Weibull model, with GOLD stages at baseline as covariates.,A generalized linear model was used to compare the numbers of exacerbations (total and severe) per stage.,Analyses were repeated with stages C and D divided into substages depending on lung function and exacerbation history.,Lung function decline was analysed in a repeated measures model.,Mortality increased from A to D, but there was no difference between B and C.,For the previous GOLD stages 2-4, survival curves were clearly separated.,Yearly exacerbation rates were: 0.53, 0.72 and 0.80 for stages 2-4; and 0.35, 0.45, 0.58 and 0.74 for A-D.,Annual rates of lung function decline were: 47, 38 and 26 ml for stages 2-4 and 44, 48, 38 and 39 for stages A-D.,With regards to model fit, the new system performed worse at predicting mortality and lung function decline, and better at predicting exacerbations.,Distinguishing between the sub-stages of high-risk led to substantial improvements.,The new classification system is a modest step towards a phenotype approach.,It is probably an improvement for the prediction of exacerbations, but a deterioration for predicting mortality and lung function decline.,ClinicalTrials.gov NCT00144339 (September 2, 2005).,The online version of this article (doi:10.1186/1471-2466-14-163) contains supplementary material, which is available to authorized users. | 1 |
QVA149 is a once-daily (o.d.) inhaled dual bronchodilator containing a fixed-dose combination of the long-acting β2-agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium for the treatment of COPD.,The QUANTIFY study compared QVA149 with a free-dose bronchodilator combination of tiotropium plus formoterol (TIO+FOR) in improving health-related quality of life (HRQoL) of patients with COPD.,This multicentre, blinded, triple-dummy, parallel-group, non-inferiority study randomised patients aged ≥40 years with moderate-to-severe COPD (post-bronchodilator forced expiratory volume in 1 s (FEV1) ≥30% to <80% predicted) to QVA149 110/50 µg o.d. or TIO 18 µg o.d.,+ FOR 12 µg twice daily (1:1) for 26 weeks.,The primary endpoint was to demonstrate non-inferiority in HRQoL assessed using St George's Respiratory Questionnaire-COPD (SGRQ-C).,The prespecified non-inferiority margin was 4 units.,Secondary endpoints included Transition Dyspnoea Index (TDI) score, pre-dose FEV1, forced vital capacity (FVC) and safety.,Of the 934 patients randomised (QVA149=476 and TIO+FOR=458), 87.9% completed the study.,At week 26, non-inferiority was met for SGRQ-C (QVA149 vs TIO+FOR; difference: -0.69 units; 95% CI −2.31 to 0.92; p=0.399).,A significantly higher percentage of patients achieved a clinically relevant ≥1 point improvement in TDI total score with QVA149 (49.6%) versus TIO+FOR (42.4%; p=0.033).,QVA149 significantly increased pre-dose FEV1 (+68 mL, 95% CI 37 mL to 100 mL; p<0.001) and FVC (+74 mL, 95% CI 24 mL to 125 mL; p=0.004) compared with TIO+FOR at week 26.,The incidence of adverse events was comparable between both treatments (QVA149=43.7% and TIO+FOR=42.6%).,QVA149 is non-inferior to TIO+FOR in improving HRQoL, with clinically meaningful and significant improvements in breathlessness and lung function in patients with COPD.,NCT01120717. | Chronic obstructive pulmonary disease (COPD) represents a significant cause of global morbidity and mortality, with a substantial economic impact.,Recent changes in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidance refined the classification of patients for treatment using a combination of spirometry, assessment of symptoms, and/or frequency of exacerbations.,The aim of treatment remains to reduce existing symptoms while decreasing the risk of future adverse health events.,Long-acting bronchodilators are the mainstay of therapy due to their proven efficacy.,GOLD guidelines recommend combining long-acting bronchodilators with differing mechanisms of action if the control of COPD is insufficient with monotherapy, and recent years have seen growing interest in the additional benefits that combination of long-acting muscarinic antagonists (LAMAs), typified by tiotropium, with long-acting β2-agonists (LABAs), such as formoterol and salmeterol.,Most studies have examined free combinations of currently available LAMAs and LABAs, broadly showing a benefit in terms of lung function and other patient-reported outcomes, although evidence is limited at present.,Several once- or twice-daily fixed-dose LAMA/LABA combinations are under development, most involving newly developed monotherapy components.,This review outlines the existing data for LAMA/LABA combinations in the treatment of COPD, summarizes the ongoing trials, and considers the evidence required to inform the role of LAMA/LABA combinations in treatment of this disease. | 1 |
The high incidence of chronic obstructive pulmonary disease (COPD), one of the most prevalent diseases worldwide, has attracted growing attention.,Cigarette smoking is considered a major contributory factor in the pathogenesis and progression of COPD due to the tremendous oxidative burden that it causes, which induces an oxidant/antioxidant imbalance.,Excessive oxidation induced by the excessive generation of mitochondrial reactive oxygen species disturbs the antioxidant systems and plays an important role in triggering and promoting chronic inflammation of airways.,Given that mitochondria is one of the main sites of reactive oxygen species production by the oxidative phosphorylation process, oxidative stress may affect mitochondrial function by changing its structure and morphology and by affecting a series of mitochondrial proteins.,In particular, PTEN-induced putative kinase 1/Parkin and p62 play critical roles in mitophagy.,During the process, the Akt ubiquitin E3 ligase is an important mediator associated with cigarette smoke exposure-induced pulmonary endothelial cell death and dysfunction.,Thus, understanding the underlying mechanisms of the signaling pathway may provide important information regarding the therapeutic treatment of COPD by application of alternative PTEN-induced putative kinase 1 targets or ubiquitin E3 ligase. | Chronic Obstructive Pulmonary disease (COPD) is an inflammatory syndrome that represents an increasing health problem, especially in the elderly population.,Drug therapies are symptomatic and inadequate to contrast disease progression and mortality.,Thus, there is an urgent need to clarify the molecular mechanisms responsible for this condition in order to identify new biomarkers and therapeutic targets.,Processes including oxidant/antioxidant, protease/antiprotease, and proliferative/antiproliferative balance and control of inflammatory response become dysfunctional during aging as well as in COPD.,Recently it was suggested that Sirtuin 1 (SIRT1), an antiaging molecule involved in the response to oxidative stress and chronic inflammation, is implicated in both development and progression of COPD.,The present review focuses on the involvement of SIRT1 in the regulation of redox state, inflammation, and premature senescence, all crucial characteristics of COPD phenotypes.,Recent evidence corroborating the statement of the “aging theory for COPD” was also discussed. | 1 |
31-77% of patients with COPD have vitamin D deficiency and insufficiency, with results being highly variable between studies.,Vitamin D may also correlate with disease characteristics.,To find out the prevalence of vitamin D deficiency and insufficiency in patients with COPD admitted for exacerbation and a risk factors for lower vitamin D levels among comorbidities and COPD characteristics.,152 patients were studied for vitamin D serum levels (25(OH)D).,All of them were also assessed for diabetes mellitus (DM) and metabolic syndrome (MS).,Data were gathered also for smoking status and exacerbations in last year.,All patients completed CAT and mMRC questionnaires and underwent spirometry.,A total of 83,6% of patients have reduced levels of vitamin D. 42,8% (65/152) have vitamin D insufficiency (defined as 25-50 nmol/L) and 40,8% (62/152) have vitamin D deficiency (<25 nmol/L).,The mean level of 25(OH)D for all patients is 31,97 nmol/L (95%CI 29,12-34,68).,Vitamin D deficiency and insufficiency are more prevalent in females vs. males (97,7 vs 77,8%; p = 0.003).,The prevalence and severity of vitamin D deficiency and insufficiency in this study is significantly higher when compared to an unselected Bulgarian population (prevalence 75,8%; mean level 38,75 nmol/L).,Vitamin D levels correlate with quality of life (measured by the mMRC scale) and lung function (FVC, FEV1, FEV6, FEF2575, FEV3, but not with FEV1/FVC ratio and PEF), it does not correlate with the presence of arterial hypertension, DM, MS and number of moderate, severe and total exacerbations.,Vitamin D deficiency is a risk factor for longer hospital stay.,The patients with COPD admitted for exacerbation are a risk group for vitamin D deficiency and insufficiency, which is associated with worse disease characteristics. | Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) is associated with rapid decline in lung function, poorer health-related quality-of-life outcomes, and frequent exacerbations, compared to COPD alone.,Although the numbers of patients with ACOS have increased, there is little established evidence regarding diagnostic criteria and treatment options.,Thus, the aim of our study was to clarify the clinical, physiological, and radiological features of patients with ACOS.,We examined a total of 100 patients with COPD and 40 patients with ACOS, who were selected based on clinical criteria.,All patients underwent baseline testing, including a COPD assessment test, pulmonary function tests, and multidetector row computed tomography imaging.,Percentage of low attenuation volume, percentage of wall area, and percentage of total cross-sectional area of pulmonary vessels less than 5 mm2 (%CSA <5) were determined using multidetector row computed tomography.,ACOS patients were administered a fixed dose of budesonide/formoterol (160/4.5 μg, two inhalations; twice daily) for 12 weeks, after which the ACOS patients underwent multidetector row computed tomography to measure the same parameters.,At baseline, the ACOS patients and COPD patients had a similar degree of airflow limitation, vital capacity, and residual volume.,ACOS patients had higher COPD assessment test scores, percentage of wall area, and %CSA <5 than COPD patients.,Compared to baseline, budesonide/formoterol treatment significantly increased the forced expiratory volume in 1 second and decreased the degree of airway wall thickness (percentage of wall area) as well as pulmonary microvascular density (%CSA <5) in ACOS patients.,Our results suggest that ACOS is characterized by an airway lesion-dominant phenotype, in contrast to COPD.,Higher %CSA <5 might be a characteristic feature of ACOS. | 1 |
Lung macrophage subpopulations have been identified based on size.,We investigated characteristics of small and large macrophages in the alveolar spaces and lung interstitium of COPD patients and controls.,Alveolar and interstitial cells were isolated from lung resection tissue from 88 patients.,Macrophage subpopulation cell-surface expression of immunological markers and phagocytic ability were assessed by flow cytometry.,Inflammatory related gene expression was measured.,Alveolar and interstitial macrophages had subpopulations of small and large macrophages based on size and granularity.,Alveolar macrophages had similar numbers of small and large cells; interstitial macrophages were mainly small.,Small macrophages expressed significantly higher cell surface HLA-DR, CD14, CD38 and CD36 and lower CD206 compared to large macrophages.,Large alveolar macrophages showed lower marker expression in COPD current compared to ex-smokers.,Small interstitial macrophages had the highest pro-inflammatory gene expression levels, while large alveolar macrophages had the lowest.,Small alveolar macrophages had the highest phagocytic ability.,Small alveolar macrophage CD206 expression was lower in COPD patients compared to smokers.,COPD lung macrophages include distinct subpopulations; Small interstitial and small alveolar macrophages with more pro-inflammatory and phagocytic function respectively, and large alveolar macrophages with low pro-inflammatory and phagocytic ability. | Non-typeable Haemophilus influenza (NTHi) infection is common in COPD.,Corticosteroids can have limited therapeutic effects in COPD patients.,NTHi causes corticosteroid insensitive cytokine production from COPD alveolar macrophages.,We investigated the mechanisms by which NTHi causes corticosteroid insensitive inflammatory responses, and the effects of NTHi exposure on COPD macrophage polarisation.,Alveolar macrophages from COPD patients and controls were exposed to NTHi in conjunction with the corticosteroid dexamethasone and/or the p38 MAPK inhibitor BIRB-796.,Cytokine release, GR phosphorylation and modulation and macrophage phenotype were analysed.,Dexamethasone significantly inhibited NTHi induced TNF-α, IL-6 and IL-10 from COPD macrophages but, CXCL8 was not suppressed.,BIRB-796 combined with dexamethasone caused significantly greater inhibition of all cytokines than either drug alone (p < 0.05 all comparisons).,NTHi caused phosphorylation of GR S226 reducing GR nuclear localisation, an effect regulated by p38 MAPK.,NTHi altered macrophage polarisation by increasing IL-10 and decreasing CD36, CD206, CD163 and HLA-DR.,NTHi exposure causes p38 MAPK dependent GR phosphorylation associated with decreased GR function in COPD alveolar macrophages.,Combining a p38 MAPK inhibitor with corticosteroids can enhance anti-inflammatory effects during NTHi exposure of COPD alveolar macrophages.,NTHi causes macrophage polarisation that favours bacterial persistence.,The online version of this article (doi:10.1186/s12931-017-0539-4) contains supplementary material, which is available to authorized users. | 1 |
Few studies have investigated the 24-hour symptom profile in patients with COPD or how symptoms during the 24-hour day are inter-related.,This observational study assessed the prevalence, severity and relationship between night-time, early morning and daytime COPD symptoms and explored the relationship between 24-hour symptoms and other patient-reported outcomes.,The study enrolled patients with stable COPD in clinical practice.,Baseline night-time, early morning and daytime symptoms (symptom questionnaire), severity of airflow obstruction (FEV1), dyspnoea (modified Medical Research Council Dyspnoea Scale), health status (COPD Assessment Test), anxiety and depression levels (Hospital Anxiety and Depression Scale), sleep quality (COPD and Asthma Sleep Impact Scale) and physical activity level (sedentary, moderately active or active) were recorded.,The full analysis set included 727 patients: 65.8% male, mean ± standard deviation age 67.2 ± 8.8 years, % predicted FEV1 52.8 ± 20.5%.,In each part of the 24-hour day, >60% of patients reported experiencing ≥1 symptom in the week before baseline.,Symptoms were more common in the early morning and daytime versus night-time (81.4%, 82.7% and 63.0%, respectively).,Symptom severity was comparable for each period assessed.,Overall, in the week before baseline, 56.7% of patients had symptoms throughout the whole 24-hour day (3 parts of the day); 79.9% had symptoms in ≥2 parts of the 24-hour day.,Symptoms during each part of the day were inter-related, irrespective of disease severity (all p < 0.001).,Early morning and daytime symptoms were associated with the severity of airflow obstruction (p < 0.05 for both).,Night-time, early morning and daytime symptoms were all associated with worse dyspnoea, health status and sleep quality, and higher anxiety and depression levels (all p < 0.001 versus patients without symptoms in each corresponding period).,In each part of the 24-hour day, there was also an association between symptoms and a patient’s physical activity level (p < 0.05 for each period).,More than half of patients experienced COPD symptoms throughout the whole 24-hour day.,There was a significant relationship between night-time, early morning and daytime symptoms.,In each period, symptoms were associated with worse patient-reported outcomes, suggesting that improving 24-hour symptoms should be an important consideration in the management of COPD.,The online version of this article (doi:10.1186/s12931-014-0122-1) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) is characterized by irreversible, progressive obstruction of lung airflow.,Dyspnea (shortness of breath [SOB]) is the COPD symptom which most negatively impacts patients’ daily activities.,To assess how SOB affects daily activities, 37 items were drafted through focus group discussions and cognitive interviews with COPD patients to develop a patient-reported outcome instrument: the Shortness of Breath with Daily Activities questionnaire (SOBDA).,Psychometric analysis was conducted to reduce the number of items and evaluate the measurement properties of the final SOBDA.,Prospective, observational study of 334 COPD patients, recruited from 24 pulmonology and internal medicine clinics in the United States.,The 37-item SOBDA was administered to patients each evening for 28 days using an electronic diary.,Patients answered every item and rated their level of SOB experienced that day during specific activities.,Item selection was conducted by examining item characteristics, dimensionality, and Rasch model analysis results.,The decision to delete an item was based on psychometric evidence, content validity, and expert clinical input.,The final SOBDA instrument was evaluated for internal consistency, reproducibility, convergent validity, known-groups validity, and responsiveness.,Twenty-four items from the 37-item pool were removed following the item selection process: nine items were removed due to high item-to-item correlations; five due to floor effects; three due to infrequent activity; one due to gender bias; two due to low factor loadings; three due to unordered response options; and one due to expert’s discretion.,Internal consistency and reproducibility of the final SOBDA were demonstrated by Cronbach Alpha = 0.87, and intra-class correlation coefficient = 0.91.,Convergent validity was demonstrated by high correlation with the CRQ-SAS (0.60) and SGRQ-C (0.61).,Known groups validity was demonstrated by significant difference between ratings of the mMRC and clinical global rating of severity.,Evaluation of the ability to detect change was not performed owing to too few responders at the end of the study.,Through the empirical item reduction process, 13 items were selected from the 37-item pool generated during qualitative development.,The final 13-item SOBDA is a reliable and valid instrument for use in clinical trials. | 1 |
Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma.,In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017.,Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex.,Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases.,We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs.,In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9-584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990.,Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia.,The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically.,Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8-7·2] of all deaths), behind cardiovascular diseases and neoplasms.,Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578-4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%.,However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%).,In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD.,In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes.,Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world.,Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions.,Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men.,Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region.,Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990.,Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis.,Bill & Melinda Gates Foundation. | COPD is currently the fourth cause of morbidity and mortality in the developed world.,Patients with COPD experience a progressive deterioration and disability, which lead to a worsening in their health-related quality of life (HRQoL).,The aim of this work is to assess the Health-Related Quality of Life (HRQoL) of patients with stable COPD followed in primary care and to identify possible predictors of disease.,It is a multicenter, epidemiological, observational, descriptive study.,Subjects of both sexes, older than 40 years and diagnosed of COPD at least 12 months before starting the study were included.,Sociodemographic data, severity of disease, comorbidity, and use of health resources in the previous 12 months were collected.,All patients were administered a generic quality-of-life questionnaire, the SF-12, that enables to calculate two scores, the physical (PCS-12) and the mental (MCS-12) component summary scores.,10,711 patients were evaluated (75.6% men, 24.4% women), with a mean age of 67.1 years (SD 9.66).,The mean value of FEV1 was 35.9 ± 10.0%.,Mean PCS-12 and MCS-12 scores were 36.0 ± 9.9 and 48.3 ± 10.9, respectively.,Compared to the reference population, patients with COPD had a reduction of PCS-12, even in mild stages of the disease.,The correlation with FEV1 was higher for PCS-12 (r = 0.38) than for MCS-12 (r = 0.12).,Predictors for both HRQoL components were sex, FEV1, use of oxygen therapy, and number of visits to emergency rooms and hospital admissions.,Other independent predictors of PCS-12 were age, body mass index and educational level.,Patients with stable COPD show a reduction of their HRQoL, even in mild stages of the disease.,The factors determining the HRQoL include sex, FEV1, use of oxygen therapy, and number of visits to emergency rooms and hospital admissions. | 1 |
A multidimensional assessment of COPD was recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) in 2013 and revised in 2017.,We examined the ability of the GOLD 2017 and the new 16 subgroup (1A-4D) classifications to predict clinical outcomes, including exacerbation and mortality, and compared them with the GOLD 2013 classifications.,Patients with COPD were recruited from January 2006 to December 2017.,The predictive abilities of grades 1-4 and groups A-D were examined through a logistic regression analysis with receiver operating curve estimations and area under the curve (AUC).,A total of 553 subjects with COPD were analyzed.,The mortality rate was 48.6% during a median follow-up period of 5.2 years.,Both the GOLD 2017 and the 2013 group A-D classifications had good predictive ability for total and severe exacerbations, for which the AUCs were 0.79 vs 0.77 and 0.79 vs 0.78, respectively.,The AUCs for the GOLD 2017 groups A-D, grades 1-4, and the GOLD 2013 group A-D classifications were 0.70, 0.66, and 0.70 for all-cause mortality and 0.73, 0.71, and 0.74 for respiratory cause mortality, respectively.,Combining the spirometric staging with the grouping for the GOLD 2017 subgroups (1A-4D), the all-cause mortality rate for group B and D patients was significantly increased from subgroups 1B-4B (27.7%, 50.6%, 53.3%, and 69.2%, respectively) and groups 1D-4D (55.0%, 68.8%, 82.1%, and 90.5%, respectively).,The AUCs of subgroups (1A-4D) were 0.73 and 0.77 for all-cause and respiratory mortality, respectively; the new classification was determined more accurate than the GOLD 2017 for predicting mortality (P<0.0001).,The GOLD 2017 classification performed well by identifying individuals at risk of exacerbation, but its predictive ability for mortality was poor among COPD patients.,Combining the spirometric staging with the grouping increased the predictive ability for all-cause and respiratory mortality.,We validate the ability of the GOLD 2017 and 16 subgroup (1A-4D) classifications to predict clinical outcome for COPD patients.,The GOLD 2017 classification performed well by identifying individuals at risk of exacerbation, but its predictive ability for mortality was poor.,The new 16 subgroup (1A-4D) classification combining the spirometric 1-4 staging and the A-D grouping increased the predictive ability for mortality and was better than the GOLD 2017 for predicting all-cause and respiratory mortality among COPD patients. | 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 |
Several composite markers have been proposed for risk assessment in chronic obstructive pulmonary disease (COPD).,However, choice of parameters and score complexity restrict clinical applicability.,Our aim was to provide and validate a simplified COPD risk index independent of lung function.,The PROMISE study (n=530) was used to develop a novel prognostic index.,Index performance was assessed regarding 2-year COPD-related mortality and all-cause mortality.,External validity was tested in stable and exacerbated COPD patients in the ProCOLD, COCOMICS and COMIC cohorts (total n=2988).,Using a mixed clinical and statistical approach, body mass index (B), severe acute exacerbations of COPD frequency (AE), modified Medical Research Council dyspnoea severity (D) and copeptin (C) were identified as the most suitable simplified marker combination. 0, 1 or 2 points were assigned to each parameter and totalled to B-AE-D or B-AE-D-C.,It was observed that B-AE-D and B-AE-D-C were at least as good as BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity), ADO (age, dyspnoea, airflow obstruction) and DOSE (dyspnoea, obstruction, smoking, exacerbation) indices for predicting 2-year all-cause mortality (c-statistic: 0.74, 0.77, 0.69, 0.72 and 0.63, respectively; Hosmer-Lemeshow test all p>0.05).,Both indices were COPD specific (c-statistic for predicting COPD-related 2-year mortality: 0.87 and 0.89, respectively).,External validation of B-AE-D was performed in COCOMICS and COMIC (c-statistic for 1-year all-cause mortality: 0.68 and 0.74; c-statistic for 2-year all-cause mortality: 0.65 and 0.67; Hosmer-Lemeshow test all p>0.05).,The B-AE-D index, plus copeptin if available, allows a simple and accurate assessment of COPD-related risk.,The B-AE-D indices allow a simple and accurate assessment of COPD-related risk in the absence of lung functionhttp://ow.ly/XFBox | Forced expiratory volume in one second (FEV1) is used to diagnose and establish a prognosis in chronic obstructive pulmonary disease (COPD).,Using multi-dimensional scores improves this predictive capacity.Two instruments, the BODE-index (Body mass index, Obstruction, Dyspnea, Exercise capacity) and the HADO-score (Health, Activity, Dyspnea, Obstruction), were compared in the prediction of mortality among COPD patients.,This is a prospective longitudinal study.,During one year (2003 to 2004), 543 consecutively COPD patients were recruited in five outpatient clinics and followed for three years.,The endpoints were all-causes and respiratory mortality.,In the multivariate analysis of patients with FEV1 < 50%, no significant differences were observed in all-cause or respiratory mortality across HADO categories, while significant differences were observed between patients with a lower BODE (less severe disease) and those with a higher BODE (greater severity).,Among patients with FEV1 ≥ 50%, statistically significant differences were observed across HADO categories for all-cause and respiratory mortality, while differences were observed across BODE categories only in all-cause mortality.,HADO-score and BODE-index were good predictors of all-cause and respiratory mortality in the entire cohort.,In patients with severe COPD (FEV1 < 50%) the BODE index was a better predictor of mortality whereas in patients with mild or moderate COPD (FEV1 ≥ 50%), the HADO-score was as good a predictor of respiratory mortality as the BODE-index.,These differences suggest that the HADO-score and BODE-index could be used for different patient populations and at different healthcare levels, but can be used complementarily. | 1 |
Objective: To explore the feasibility of disease-specific clinical pathways when used in primary care.,Design: A mixed-method sequential exploratory design was used.,First, merging and exploring quality interview data across two cases of collaboration between the specialist care and primary care on the introduction of clinical pathways for four selected chronic diseases.,Secondly, using quantitative data covering a population of 214,700 to validate and test hypothesis derived from the qualitative findings.,Setting: Primary care and specialist care collaborating to manage care coordination.,Results: Primary-care representatives expressed that their patients often have complex health and social needs that clinical pathways guidelines seldom consider.,The representatives experienced that COPD, heart failure, stroke and hip fracture, frequently seen in hospitals, appear in low numbers in primary care.,The quantitative study confirmed the extensive complexity among home healthcare nursing patients and demonstrated that, for each of the four selected diagnoses, a homecare nurse on average is responsible for preparing reception of the patient at home after discharge from hospital, less often than every other year.,Conclusions: The feasibility of disease-specific pathways in primary care is limited, both from a clinical and organisational perspective, for patients with complex needs.,The low prevalence in primary care of patients with important chronic conditions, needing coordinated care after hospital discharge, constricts transferring tasks from specialist care.,Generic clinical pathways are likely to be more feasible and efficient for patients in this setting.Key pointsClinical pathways in hospitals apply to single-disease guidelines, while more than 90% of the patients discharged to community health care for follow-up have multimorbidity.,Primary care has to manage the health care of the patient holistically, with all his or her complex needs.Patients most frequently admitted to hospitals, i.e. patients with COPD, heart failure, stroke and hip fracture are infrequent in primary care and represent a minority among patients in need of coordinated community health care.In primary care, the low rate of receiving patients discharged from hospitals of major chronic diseases hampers maintenance of required specific skills, thus constricting the transfer of tasks to primary care.,Generic clinical pathways are suggested to be more feasible than disease-specific pathways for most patients with complex needs.,Clinical pathways in hospitals apply to single-disease guidelines, while more than 90% of the patients discharged to community health care for follow-up have multimorbidity.,Primary care has to manage the health care of the patient holistically, with all his or her complex needs.,Patients most frequently admitted to hospitals, i.e. patients with COPD, heart failure, stroke and hip fracture are infrequent in primary care and represent a minority among patients in need of coordinated community health care.,In primary care, the low rate of receiving patients discharged from hospitals of major chronic diseases hampers maintenance of required specific skills, thus constricting the transfer of tasks to primary care.,Generic clinical pathways are suggested to be more feasible than disease-specific pathways for most patients with complex needs. | Chronic obstructive pulmonary disease (COPD) is a common cause of suffering and death.,Evidence-based management of COPD by general practitioners (GPs) is crucial for decreasing the impact of the disease.,Efficient strategies include early diagnosis, smoking cessation and multimodal treatment.,To describe knowledge about and skills for managing COPD in GPs in Sweden.,Prior to COPD education (the PRIMAIR Study), GPs at primary health care centers (PHCCs) in Stockholm replied to 13 written, patient-case based, multiple choice and free-text questions about COPD.,Their knowledge and practical management skills were assessed by assigned points that were analyzed with non-parametric tests.,Overall, 250 GPs at 34 PHCCs replied (89% response rate).,Total mean score was 9.9 (maximum 26).,Scores were highest on ‘management of smoking cessation’, ‘follow-up after exacerbation’ and ‘diagnostic procedures’.,Spirometry was used frequently, although interpretation skills were suboptimal.,‘Management of maintenance therapy’, ‘management of multimorbidity’ and ‘interprofessional cooperation’ had mediocre scores.,Scores were unrelated to whether there was a nurse-led asthma/COPD clinic at the PHCC.,Swedish GPs’ knowledge of COPD and adherence to current guidelines seem insufficient.,A nurse-led asthma/COPD clinic at the PHCC does not correlate with sufficient COPD skills in the GPs.,The relevance of this study to participants’ actual clinical practice and usefulness of easy-to-access clinical guides are interesting topics for future investigation.,To identify problem areas, we suggest using questionnaires prior to educational interventions.,General practitioners (GPs) play a crucial role in providing evidence-based care for patients with chronic obstructive pulmonary disease (COPD) who are treated in primary care.,Swedish GPs’ knowledge about COPD and adherence to current guidelines seem insufficient.,Areas in greatest need of improvement are spirometry interpretation, management of maintenance therapy, management of multimorbidity in patients with COPD and interprofessional cooperation. | 1 |
Severe exacerbations of COPD are commonly associated with hyperglycaemia, which predicts adverse outcomes.,Metformin is a well-established anti-hyperglycaemic agent in diabetes mellitus, possibly augmented with anti-inflammatory effects, but its effects in COPD are unknown.,We investigated accelerated metformin therapy in severe COPD exacerbations, primarily to confirm or refute an anti-hyperglycaemic effect, and secondarily to explore its effects on inflammation and clinical outcome.,This was a multicentre, randomised, double-blind, placebo-controlled trial testing accelerated metformin therapy in non-diabetic patients, aged ≥35 years, hospitalised for COPD exacerbations.,Participants were assigned in a 2:1 ratio to 1 month of metformin therapy, escalated rapidly to 2 g/day, or matched placebo.,The primary end point was mean in-hospital blood glucose concentration.,Secondary end points included the concentrations of fructosamine and C reactive protein (CRP), and scores on the COPD Assessment Test and Exacerbations of Chronic Pulmonary Disease Tool.,52 participants (mean (±SD) age 67±9 years) were randomised (34 to metformin, 18 to placebo).,All were included in the primary end point analysis.,The mean blood glucose concentrations in the metformin and placebo groups were 7.1±0.9 and 8.0±3.3 mmol/L, respectively (difference −0.9 mmol/L, 95% CI −2.1 to +0.3; p=0.273).,No significant between-group differences were observed on any of the secondary end points.,Adverse reactions, particularly gastrointestinal effects, were more common in metformin-treated participants.,Metformin did not ameliorate elevations in blood glucose concentration among non-diabetic patients admitted to hospital for COPD exacerbations, and had no detectable effect on CRP or clinical outcomes.,ISRCTN66148745 and NCT01247870. | Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability internationally.,Alveolar hypoxia and consequent hypoxemia increase in prevalence as disease severity increases.,Ventilation/perfusion mismatch resulting from progressive airflow limitation and emphysema is the key driver of this hypoxia, which may be exacerbated by sleep and exercise.,Uncorrected chronic hypoxemia is associated with the development of adverse sequelae of COPD, including pulmonary hypertension, secondary polycythemia, systemic inflammation, and skeletal muscle dysfunction.,A combination of these factors leads to diminished quality of life, reduced exercise tolerance, increased risk of cardiovascular morbidity, and greater risk of death.,Concomitant sleep-disordered breathing may place a small but significant subset of COPD patients at increased risk of these complications.,Long-term oxygen therapy has been shown to improve pulmonary hemodynamics, reduce erythrocytosis, and improve survival in selected patients with severe hypoxemic respiratory failure.,However, the optimal treatment for patients with exertional oxyhemoglobin desaturation, isolated nocturnal hypoxemia, or mild-to-moderate resting daytime hypoxemia remains uncertain. | 1 |
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. | Chronic obstructive pulmonary disease (COPD) is a leading cause of disability and mortality.,Caring for patients with COPD, particularly those with advanced disease who experience frequent exacerbations, places a significant burden on health care budgets, and there is a global need to reduce the financial and personal burden of COPD.,Evolving scientific evidence on the natural history and clinical course of COPD has fuelled a fundamental shift in our approach to the disease.,The emergence of data highlighting the heterogeneity in rate of lung function decline has altered our perception of disease progression in COPD and our understanding of appropriate strategies for the management of stable disease.,These data have demonstrated that early, effective, and prolonged bronchodilation has the potential to slow the rate of decline in lung function and to reduce the frequency of exacerbations that contribute to functional decline.,The goals of therapy for COPD are no longer confined to controlling symptoms, reducing exacerbations, and maintaining quality of life, and slowing disease progression is now becoming an achievable aim.,A challenge for the future will be to capitalize on these observations by improving the identification and diagnosis of patients with COPD early in the course of their disease, so that effective interventions can be introduced before the more advanced, disabling, and costly stages of the disease.,Here we critically review emerging data that underpin the advances in our understanding of the clinical course and management of COPD, and evaluate both current and emerging pharmacologic options for effective maintenance treatment. | 1 |
The causal association between depression, anxiety, and health-related quality of life (HRQoL) in chronic obstructive pulmonary disease (COPD) is unclear.,We therefore conducted a systematic review of prospective cohort studies that measured depression, anxiety, and HRQoL in COPD.,Electronic databases (Medline, Embase, Cumulative Index to Nursing and Allied Health Literature [CINAHL], British Nursing Index and Archive, PsycINFO and Cochrane database) were searched from inception to June 18, 2013.,Studies were eligible for inclusion if they: used a nonexperimental prospective cohort design; included patients with a diagnosis of COPD confirmed by spirometry; and used validated measures of depression, anxiety, and HRQoL.,Data were extracted and pooled using random effects models.,Six studies were included in the systematic review; of these, three were included in the meta-analysis for depression and two were included for the meta-analysis for anxiety.,Depression was significantly correlated with HRQoL at 1-year follow-up (pooled r=0.48, 95% confidence interval 0.37-0.57, P<0.001).,Anxiety was also significantly correlated with HRQoL at 1-year follow-up (pooled r=0.36, 95% confidence interval 0.23-0.48, P<0.001).,Anxiety and depression predict HRQoL in COPD.,However, this longitudinal analysis does not show cause and effect relationships between depression and anxiety and future HRQoL.,Future studies should identify psychological predictors of poor HRQoL in well designed prospective cohorts with a view to isolating the mediating role played by anxiety disorder and depression. | There is good evidence for the positive benefits of pulmonary rehabilitation (PR) in the prevention of hospital admissions, lower mortality, and improved health-related quality of life.,There is also increasing evidence about the impact of PR on mental health and, in particular, mood disorders.,We aimed to identify how depression in chronic obstructive pulmonary disease (COPD) patients in Victoria, Australia, is being managed in PR, to identify the prevalence of depressive symptoms among COPD patients who attend PR, and to determine whether patients with depressive symptoms or anxiety symptoms dropped out of PR early.,Of 61 PR clinics, 44 were invited and 22 agreed to participate.,Telephone interviews were conducted to see how depression and anxiety in COPD patients were being recognized and managed in these clinics.,A total of 294 questionnaires were distributed to patients by clinic coordinators to determine the prevalence of anxiety/depression, as measured by the Hospital Anxiety and Depression Scale.,Coordinators were contacted to provide information on whether respondents dropped out of rehabilitation early or continued with their treatment at 2-4 months post program.,Seven clinics were not aware of local guidelines on assessment/treatment/management of mood.,Four clinics did not use any screening tools or other aids in the recognition and management of depression and/or anxiety.,Overall, eight clinics participating in this study requested advice on suitable screening tools.,The patient survey indicated that the mean depression score on the Hospital Anxiety and Depression Scale was 5.0 (standard deviation 3.0, range 1-13).,The mean anxiety score was 5.5 (standard deviation 3.4, range 0-18).,There was no evidence of a link between failure to complete rehabilitation and depression or anxiety scores, as only three of 105 patients failed to complete their rehabilitation.,Discussion: Awareness of management guidelines for depression and anxiety in COPD patients was variable across the clinics recruited into our study.,We found no link between compliance with rehabilitation and depression, but our sample had limitations.,Future research needs to investigate how best to encourage more use of available guidelines regarding integrating psychological and psychosocial support to supplement the exercise and education that are currently offered routinely by all PR clinics studied in Victoria, Australia. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary inflammation, airways obstruction and emphysema, and is a risk factor for cardiovascular disease (CVD).,However, the contribution of these individual COPD components to this increased risk is unknown.,Therefore, the aim of this study was to determine the contribution of emphysema in the presence or absence of pulmonary inflammation to the increased risk of CVD, using a mouse model for atherosclerosis.,Because smoke is a known risk factor for both COPD and CVD, emphysema was induced by intratracheal instillation of porcine pancreatic elastase (PPE).,Hyperlipidemic APOE*3-Leiden mice were intratracheally instilled with vehicle, 15 or 30 µg PPE and after 4 weeks, mice received a Western-type diet (WTD).,To study the effect of emphysema combined with pulmonary inflammation on atherosclerosis, mice received 30 µg PPE and during WTD feeding, mice were intranasally instilled with vehicle or low-dose lipopolysaccharide (LPS; 1 µg/mouse, twice weekly).,After 20 weeks WTD, mice were sacrificed and emphysema, pulmonary inflammation and atherosclerosis were analysed.,Intratracheal PPE administration resulted in a dose-dependent increase in emphysema, whereas atherosclerotic lesion area was not affected by PPE treatment.,Additional low-dose intranasal LPS administration induced a low-grade systemic IL-6 response, as compared to vehicle.,Combining intratracheal PPE with intranasal LPS instillation significantly increased the number of pulmonary macrophages and neutrophils.,Plasma lipids during the study were not different.,LPS instillation caused a limited, but significant increase in the atherosclerotic lesion area.,This increase was not further enhanced by PPE.,This study shows for the first time that PPE-induced emphysema both in the presence and absence of pulmonary inflammation does not affect atherosclerotic lesion development. | Systemic effects of chronic obstructive pulmonary disease (COPD) significantly contribute to severity and mortality of the disease.,We aimed to develop a COPD/emphysema model exhibiting systemic manifestations of the disease.,Female NMRI mice were treated 5 times intratracheally with porcine pancreatic elastase (emphysema) or phosphate-buffered saline (control).,Emphysema severity was quantified histologically by mean linear intercept, exercise tolerance by treadmill running distance, diaphragm dysfunction using isolated muscle strips, pulmonary hypertension by measuring right ventricular pressure, and neurohumoral activation by determining urinary norepinephrine concentration.,Mean linear intercept was higher in emphysema (260.7 ± 26.8 μm) than in control lungs (24.7 ± 1.7 μm).,Emphysema mice lost body weight, controls gained weight.,Running distance was shorter in emphysema than in controls.,Diaphragm muscle length was shorter in controls compared to emphysema.,Fatigue tests of muscle strips revealed impaired relaxation in emphysema diaphragms.,Maximum right ventricular pressure and norepinephrine were elevated in emphysema compared to controls.,Linear correlations were observed between running distance changes and intercept, right ventricular weight, norepinephrine, and diaphragm length.,The elastase mouse model exhibited severe emphysema with consecutive exercise limitation, and neurohumoral activation.,The model may deepen our understanding of systemic aspects of COPD. | 1 |
The optimal use of various therapeutic combinations for moderate/severe chronic obstructive pulmonary disease (COPD) is unclear.,The GLISTEN trial compared the efficacy of two long-acting anti-muscarinic antagonists (LAMA), when combined with an inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA).,This randomised, blinded, placebo-controlled trial in moderate/severe COPD patients compared once-daily glycopyrronium (GLY) 50 µg, once-daily tiotropium (TIO) 18 µg or placebo (PLA), when combined with salmeterol/fluticasone propionate (SAL/FP) 50/500 µg twice daily.,The primary objective was to determine the non-inferiority of GLY+SAL/FP versus TIO+SAL/FP on trough FEV1 after 12 weeks.,An important secondary objective was whether addition of GLY to SAL/FP was better than SAL/FP alone.,773 patients (mean FEV1 57.2% predicted) were randomised; 84.9% completed the trial.,At week 12, GLY+SAL/FP demonstrated non-inferiority to TIO+SAL/FP for trough FEV1: least square mean treatment difference (LSMdiff) −7 mL (SE 17.4) with a lower limit for non-inferiority of −60 mL.,There was significant increase in week 12 trough FEV1 with GLY+SAL/FP versus PLA+SAL/FP (LSMdiff 101 mL, p<0.001).,At 12 weeks, GLY+SAL/FP produced significant improvement in St George's Respiratory Questionnaire total score versus PLA+SAL/FP (LSMdiff −2.154, p=0.02).,GLY+SAL/FP demonstrated significant rescue medication reduction versus PLA+SAL/FP (LSMdiff −0.72 puffs/day, p<0.001).,Serious adverse events were similar for GLY+SAL/FP, TIO+SAL/FP and PLA+SAL/FP with an incidence of 5.8%, 8.5% and 5.8%, respectively.,GLY+SAL/FP showed comparable improvements in lung function, health status and rescue medication to TIO+SAL/FP.,Importantly, addition of GLY to SAL/FP demonstrated significant improvements in lung function, health status and rescue medication compared to SAL/FP.,NCT01513460. | There is an ongoing debate on whether patients with chronic obstructive pulmonary disease (COPD) seen in real-life clinical settings are represented in randomized controlled trials (RCTs) of COPD.,It is thought that the stringent inclusion and exclusion criteria of RCTs may prevent the participation of patients with specific characteristics or risk factors.,We surveyed a database of patients recruited into 35 placebo-controlled tiotropium RCTs and also conducted a systematic literature review of large-scale observational studies conducted in patients with a documented diagnosis of COPD between 1990 and 2013.,Patient demographics and comorbidities with a high prevalence in patients with COPD were compared between the two patient populations at baseline.,Using the Medical Dictionary for Regulatory Activities (MedDRA; v 14.0), patient comorbidities in the pooled tiotropium RCTs were classified according to system organ class, pharmacovigilance (PV) endpoints, and Standardised MedDRA Queries to enable comparison with the observational studies.,We identified 24,555 patients in the pooled tiotropium RCTs and 61,361 patients among the 13 observational studies that met our search criteria.,The Global initiative for chronic Obstructive Lung Disease (GOLD) staging of patients in the RCTs differed from that in observational studies: the proportion of patients with GOLD stages I+II disease ranged from 40.0% to 51.5% in the RCTs but 24.5% to 44.1% in the observational studies; for GOLD stage III or IV disease these ranges were 7.2%-45.8% (RCTs) and 13.7-42.1% (observational studies).,The comorbidities with the highest prevalence reported in the RCTs and observational studies were: hypertension (39.4%-40.0% vs 40.1%-60.6%), other ischemic heart disease (12.3%-14.2% vs 12.5%-41.0%), diabetes (10.3%-10.9% vs 4.0%-38.9%), depression (8.5%-9.5% vs 17.0%-20.6%), and cardiac arrhythmia (7.8%-11.4% vs 11.3%-15.8%).,The clinical profile of COPD patients treated in the tiotropium trial program appears to be largely in the range of clinical characteristics, including cardiovascular comorbidities, reported for “real-life patients.”,The tiotropium RCTs tended to include patients with more severe disease than the observational studies. | 1 |
COPD is one of the most debilitating diseases.,Frailty syndrome and advanced age may decrease the acceptance of illness, quality of life, and worsen health conditions in these patients, as well as lead to an increase in health care expenses.,The aim of the study was to assess how the level of frailty affects the acceptance of illness in elderly patients with COPD.,We also aimed to evaluate the associations between sociodemographic and clinical factors and the level of acceptance of illness, anxiety, and frailty in this group of patients.,The study included 102 COPD patients with a mean age of 63.2 (standard deviation =6.5) years and grades I (3%), II (37%), III (52%), and IV (8%) by Global Initiative for Chronic Obstructive Lung Disease.,The Polish versions of the Acceptance of Illness Scale and Tilburg frailty indicator were used.,Frailty syndrome was found in 77 (75.5%) patients, with an average score of 7.42 (standard deviation =2.24).,Coexisting diseases such as hypertension (46.07%), coronary artery disease (32.35%), heart failure (28.43%), diabetes (18.63%), and heart arrhythmia (9.8%) were found among the subjects.,The overall level of acceptance of illness was 20.6 (standard deviation =7.62).,A lower level of acceptance of illness was associated with a higher level of frailty, especially in the physical and social domain.,Elderly patients with severe COPD are more prone to frailty and decreased acceptance of their disease in comparison to patients with other chronic diseases.,Assessment and management of frailty in the care of older COPD patients are likely to improve risk stratification significantly and help personalize management, leading to better patient outcomes. | The chronic obstructive pulmonary disease (COPD) assessment test (CAT) is a short questionnaire that has facilitated health status measurements in subjects with COPD.,However, it remains controversial as to whether the CAT can be used as a suitable substitute for the St George’s Respiratory Questionnaire (SGRQ).,This study investigated the reliability and score distributions of the CAT and SGRQ and evaluated which factors contributed to health status for each questionnaire.,A total of 109 consecutive subjects with stable COPD from a single center were enrolled in this study.,Each subject completed pulmonary function tests, exercise tests, and the following self-administered questionnaires: the Baseline Dyspnea Index, the Hospital Anxiety and Depression Scale, the CAT, and SGRQ.,Internal consistencies of CAT and SGRQ total scores were both excellent (Cronbach’s α coefficients =0.890 and 0.933).,Statistically significant correlations were observed between CAT and SGRQ total scores (R=0.668, P<0.001).,Correlations of CAT scores with parameters related to pulmonary function, dyspnea, exercise performance, and psychological factors were inferior to correlations with those parameters with SGRQ total scores.,Both multiple regression analyses and principal component analyses revealed that there were slight differences between SGRQ total scores and CAT scores.,The CAT is similar to SGRQ in terms of discriminating health status.,However, we demonstrated that what is assessed by the CAT may differ slightly from what is measured by SGRQ. | 1 |
Individuals with respiratory disease are being increasingly exposed to wildfire smoke as populations encroach further into forested regions and climate change continues to bring higher temperatures with lower rainfall.,Frequent exposures have significant potential to accelerate conditions such as chronic obstructive pulmonary disease (COPD) which is characterised by an exaggerated inflammatory response to environmental stimuli.,Here we employ models of human airway epithelium exposed to wildfire smoke-extract (WFSE) to examine modulation in airway epithelial cell (AEC) survival, fragility and barrier function.,Submerged cultures of small airway epithelial cells (SAEC) and differentiated air-liquid interface (ALI) cultures of primary bronchial AEC (bAEC) were treated for 1-24 h with 1-10% WFSE generated from plant species found in the Australian bushland.,Autophagy (LC3-II and Sequestosome), apoptosis (Poly-(ADP)-Ribose Polymerase (PARP) cleavage) and tight junction proteins were measured using western blot.,Barrier function was assessed via permeability of fluorescein tracers and measuring trans-epithelial electrical resistance.,The production of IL-6 was assessed using ELISA.,Primary epithelial models exposed to WFSE exhibited a significant blockade in autophagy as evidenced by an increase in LC3-II coupled with a concomitant elevation in Sequestosome abundance.,These exposures also induced significant PARP cleavage indicative of apoptotic changes.,ALI cultures of bAEC treated with 5% WFSE demonstrated barrier dysfunction with significant increases in paracellular molecular permeability and ionic conductance, and a reduction in the abundance of the tight junction proteins ZO-1 and Claudin-1.,These cultures also exhibited increased IL-6 secretion consistent with the aberrant and pro-inflammatory repair response observed in the COPD airways.,Further, blocks in autophagy and barrier disruption were significantly elevated in response to WFSE in comparison to similar exposures with cigarette smoke-extract.,WFSE inhibits autophagic flux and induces barrier dysfunction in the airway epithelium.,As autophagy is a central regulator of cellular repair, viability, and inflammation, targeting the block in autophagic flux may ameliorate the consequences of wildfire smoke-exposure for individuals with pre-existing respiratory conditions.,The online version of this article (10.1186/s12931-018-0945-2) contains supplementary material, which is available to authorized users. | Chronic infections are associated with exacerbation in patients with chronic obstructive pulmonary disease (COPD).,The major objective of the management of these patients is the prevention and effective treatment of exacerbations.,Patients that have increased sputum production, associated with purulence and worsening shortness of breath, are the ones that will benefit from antibiotic therapy.,It is important to give the appropriate antibiotic therapy to prevent treatment failure, relapse, and the emergence of resistant pathogens.,In some patients, systemic corticosteroids are also indicated to improve symptoms.,In order to identify which patients are more likely to benefit from these therapies, clinical guidelines recommend stratifying patients based on their risk factor associated with poor outcome or recurrence.,It has been identified that patients with more severe disease, recurrent infection and presence of purulent sputum are the ones that will be more likely to benefit from this therapy.,Another approach related to disease prevention could be the use of prophylactic antibiotics during steady state condition.,Some studies have evaluated the continuous or the intermittent use of antibiotics in order to prevent exacerbations.,Due to increased bacterial resistance to antibiotics and the presence of side effects, several antibiotics have been developed to be nebulized for both treatment and prevention of acute exacerbations.,There is a need to design long-term studies to evaluate these interventions in the natural history of the disease.,The purpose of this publication is to review our understanding of the role of bacterial infection in patients with COPD exacerbation, the role of antibiotics, and future interventions. | 1 |
As of 11 July, 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic has infected over 12.7 million people around the world and caused more than 560,000 deaths [1].,Given the devastating impact that COVID-19 can have on the lung, it is natural to fear for patients with underlying COPD.,Estimating their excess risk for contracting COVID-19 and, in particular, its more severe respiratory manifestations has been a challenging exercise in this pandemic for various reasons.,First, the reporting on cases has concentrated on hospitalised and intensive care unit (ICU) patients, rather than on mild, outpatient cases.,This is in part also due to the variability in testing strategies across the world, where some nations with stricter testing requirements and scarce testing resources have focused on testing only those requiring hospitalisation.,COPD patients have increased risk of severe pneumonia and poor outcomes when they develop COVID-19.,This may be related to poor underlying lung reserves or increased expression of ACE-2 receptor in small airways.https://bit.ly/37dSB8l | The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) a pandemic [1].,COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,COVID-19 displays symptoms ranging from mild to severe (pneumonia) that can lead to death in some individuals [2-4].,As of 18 April 2020, there have been 2 280 945 cases of COVID-19 worldwide and 156 354 deaths [5].,SARS-CoV-2 uses the angiotensin-converting enzyme II (ACE-2) as the cellular entry receptor [6].,While the virus can infect individuals of any age, to date, most of the severe cases have been described in those >55 years of age and with significant comorbidities, such as COPD [7].,Here, we determined whether patients with COPD have increased expression of ACE-2 in bronchial epithelial cells in the lower respiratory tract.,Smokers and those with COPD have increased airway expression of ACE-2, which is the entry receptor for the COVID-19 virus.,This may explain the increased risk of severe COVID-19 in these subpopulations and highlight the importance of smoking cessation.https://bit.ly/3bC29es | 1 |
The long-acting muscarinic antagonist (LAMA) umeclidinium (UMEC) and the combination of UMEC with the long-acting β2-agonist (LABA) vilanterol (UMEC/VI) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD) in the US and EU.,They are not indicated for the treatment of asthma.,In this 52-week, double-blind, placebo-controlled, parallel-group safety study (GSK study DB2113359; NCT01316887), patients were randomized 2:2:1 to UMEC/VI 125/25 mcg, UMEC 125 mcg, or placebo.,Study endpoints included adverse events (AEs), clinical chemistry and hematology parameters, vital signs, 12-lead, and 24-hour Holter electrocardiograms.,COPD exacerbations and rescue medication use were assessed as safety parameters; lung function was also evaluated.,The incidence of on-treatment AEs, serious AEs (SAEs), and drug-related AEs was similar between treatment groups (AEs: 52-58%; SAEs: 6-7%; drug-related AEs: 12-13%).,Headache was the most common AE in each treatment group (8-11%).,AEs associated with the LAMA and LABA pharmacologic classes occurred at a low incidence across treatment groups.,No clinically meaningful effects on vital signs or laboratory assessments were reported for active treatments versus placebo.,The incidences of atrial arrhythmias with UMEC/VI 125/25 mcg were similar to placebo; for UMEC 125 mcg, the incidences of ectopic supraventricular beats, sustained supraventricular tachycardia, and ectopic supraventricular rhythm were ≥2% greater than placebo.,With active treatments, COPD exacerbations were fewer (13-15% of patients reporting ≥1 exacerbation) and on average less rescue medication was required (1.6-2.2 puffs/day) versus placebo (24% reporting ≥1 exacerbation, 2.6 puffs/day).,Both active treatments improved lung function versus placebo.,UMEC/VI 125/25 mcg and UMEC 125 mcg were well tolerated over 12 months in patients with COPD. | Relationships between improvements in lung function and other clinical outcomes in chronic obstructive pulmonary disease (COPD) are not documented extensively.,We examined whether changes in trough forced expiratory volume in 1 second (FEV1) are correlated with changes in patient-reported outcomes.,Pooled data from three indacaterol studies (n = 3313) were analysed.,Means and responder rates for outcomes including change from baseline in Transition Dyspnoea Index (TDI), St.,George's Respiratory Questionnaire (SGRQ) scores (at 12, 26 and 52 weeks), and COPD exacerbation frequency (rate/year) were tabulated across categories of ΔFEV1.,Also, generalised linear modelling was performed adjusting for covariates such as baseline severity and inhaled corticosteroid use.,With increasing positive ΔFEV1, TDI and ΔSGRQ improved at all timepoints, exacerbation rate over the study duration declined (P < 0.001).,Individual-level correlations were 0.03-0.18, but cohort-level correlations were 0.79-0.95.,At 26 weeks, a 100 ml increase in FEV1 was associated with improved TDI (0.46 units), ΔSGRQ (1.3-1.9 points) and exacerbation rate (12% decrease).,Overall, adjustments for baseline covariates had little impact on the relationship between ΔFEV1 and outcomes.,These results suggest that larger improvements in FEV1 are likely to be associated with larger patient-reported benefits across a range of clinical outcomes.,ClinicalTrials.gov NCT00393458, NCT00463567, and NCT00624286 | 1 |
The Minimal Clinically Important Difference (MCID) assesses what change on a measurement tool can be considered minimal clinically relevant.,Although the recall period can influence questionnaire scores, it is unclear if it influences the MCID.,This study is the first to examine longitudinally the impact of the recall period of an anchor question and its design on the MCID of COPD health status tools using the COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ) and the St.,George’s Respiratory Questionnaire (SGRQ).,Moderate to very severe COPD patients without respiratory co-morbidities were recruited during 3-week Pulmonary Rehabilitation (PR).,CAT, CCQ and SGRQ were completed at baseline, discharge, 3, 6, 9 and 12 months.,A 15-point Global Rating of Change scale (GRC) was completed at each follow-up.,A five-point GRC was used as second anchor at 12 months.,Mean change scores of a subset of patients indicating a minimal improvement on each of the anchor questions were considered the MCID.,The MCID estimates over different time periods were compared with one another by evaluating the degree of overlap of Confidence Intervals (CI) adjusted for dependency.,In total 451 patients were included (57.9 ± 6.6 years, 65% male, 50/39/11% GOLD II/III/IV), of which 309 completed follow-up.,Baseline health status scores were 20.2 ± 7.3 (CAT), 2.9 ± 1.2 (CCQ) and 50.7 ± 17.3 (SGRQ).,MCID estimates for improvement ranged − 3.1 to − 1.4 for CAT, − 0.6 to − 0.3 for CCQ, and − 10.3 to − 7.6 for SGRQ.,Absolute higher - though not significant - MCIDs were observed for CAT and CCQ directly after PR.,Significantly absolute lower MCID estimates were observed for CAT (difference − 1.4: CI -2.3 to − 0.5) and CCQ (difference − 0.2: CI -0.3 to −0.1) using a five-point GRC.,The recall period of a 15-point anchor question seemed to have limited impact on the MCID for improvement of CAT, CCQ and SGRQ during PR; although a 3-week MCID estimate directly after PR might lead to absolute higher values.,However, the design of the anchor question was likely to influence the MCID of CAT and CCQ.,RIMTCORE trial #DRKS00004609 and #12107 (Ethik-Kommission der Bayerischen Landesärztekammer).,The online version of this article (10.1186/s12955-018-0950-7) contains supplementary material, which is available to authorized users. | Health status provides valuable information, complementary to spirometry and improvement of health status has become an important treatment goal in COPD management.,We compared the usefulness and validity of the COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ), two simple questionnaires, in comparison with the St.,George Respiratory Questionnaire (SGRQ).,We administered the CAT, CCQ and SGRQ in patients with COPD stage I-IV during three visits.,Spirometry, 6 MWT, MRC scale, BODE index, and patients perspectives on questionnaires were recorded in all visits.,Standard Error of Measurement (SEM) was used to calculate the Minimal Clinical Important Difference (MCID) of all questionnaires.,We enrolled 90 COPD patients.,Cronbach's alpha for both CAT and CCQ was high (0.86 and 0.89, respectively).,Patients with severe COPD reported worse health status compared to milder subgroups.,CAT and CCQ correlated significantly (rho =0.64, p < 0.01) and both with the SGRQ (rho = 0.65; CAT and rho = 0.77; CCQ, p < 0.01).,Both questionnaires exhibited a weak correlation with lung function (rho = −0.35;CAT and rho = −0.41; CCQ, p < 0.01).,Their reproducibility was high; CAT: ICC = 0.94 (CI 0.92-0.96), total CCQ ICC = 0.95 (0.92-0.96) and SGRQ = 0.97 (CI 0.95-0.98).,The MCID calculated using the SEM method showed results similar to previous studies of 3.76 for the CAT, 0.41 for the CCQ and 4.84 for SGRQ.,Patients suggested both CAT and CCQ as easier tools than SGRQ in terms of complexity and time considerations.,More than half of patients preferred CCQ instead of CAT.,The CAT and CCQ have similar psychometric properties with a slight advantage for CCQ based mainly on patients’ preference and are both valid and reliable questionnaires to assess health status in COPD patients. | 1 |
Comparative effects on physical activity of mono and dual bronchodilators remain unclear in patients with treatment-naïve chronic obstructive pulmonary disease (COPD).,We sought to compare the changes in physical activity before and after tiotropium and tiotropium/olodaterol treatment in treatment-naïve COPD patients.,A prospective, multicenter, randomized, open-labeled, and parallel interventional study was conducted.,Eighty Japanese patients with treatment-naïve COPD were randomized to receive either tiotropium or tiotropium/olodaterol treatment for 12 weeks.,Spirometry and dyspnea index were assessed, and COPD assessment test (CAT) and the 6-minute walk distance (6MWD) were conducted before and after treatment.,Evaluation of physical activity was assessed by a triaxle accelerometer over a 2-week period before and after treatment.,There were no differences in the mean age (69.8 vs 70.4 years), body mass index (BMI) (22.5 vs 22.6 kg/m2) and mean % forced expiratory volume in 1 second (%FEV1) at baseline (61.5 vs 62.6%) between the two groups.,Changes in FEV1 (mean±standard error, 242.8±28.8 mL) and transient dyspnea index (TDI) (2.4±0.3 points) before and after tiotropium/olodaterol treatment were greater than with tiotropium treatment (104.1±31.9 mL, p<0.01 and 1.5±0.3, p=0.02, respectively).,Changes in the duration of physical activity with 1.0-1.5 metabolic equivalents (METs) estimated in the sedentary position following tiotropium/olodaterol treatment (−38.7±14.7 min) tended to be reduced more than with tiotropium treatment (−4.6±10.6 min) (p=0.06), although those with ≥2.0 METs numerically increased with both treatments (+10.8±7.6 min for tiotropium/olodaterol vs +8.3±7.6 min for tiotropium, p=0.82).,Tiotropium/olodaterol treatment reduced the duration of physical activity with 1.0-1.5 METs (regression coefficient, −43.6 [95% CI −84.1, −3.1], p=0.04) in a multiple regression model adjusted for cofounding factors such as age, FEV1, total CAT scores, 6MWD, and TDI.,This is the first study to report the impact of dual bronchodilator on physical activity in treatment-naïve COPD patients of Japanese with low BMI. | The Phase IV, 8-week, randomized, double-blind, placebo-controlled ACTIVATE study (NCT02424344) evaluated the effect of aclidinium/formoterol (AB/FF) 400/12 μg twice daily on lung hyperinflation, exercise capacity, and physical activity in patients with moderate-to-severe COPD.,Patients received AB/FF (n=134) or placebo (n=133) (1:1) via the Genuair™/Pressair® dry powder inhaler for 8 weeks.,From Weeks 5 to 8, all patients participated in behavioral intervention (BI; daily messages providing step goals).,The primary end point was trough functional residual capacity (FRC) at Week 4.,Exercise endurance time and physical activity were assessed at Week 4 (pharmacotherapy only) and at Week 8 (8 weeks of pharmacotherapy plus 4 weeks of BI).,Other end points included post-dose FRC, residual volume, and inspiratory capacity (IC) at rest and during exercise.,After 4 weeks, trough FRC improved with AB/FF versus placebo but did not reach significance (125 mL; P=0.0690).,However, post-dose FRC, residual volume, and IC at rest improved significantly with AB/FF at Week 4 versus placebo (all P<0.0001).,AB/FF significantly improved exercise endurance time and IC at isotime versus placebo at Week 4 (P<0.01 and P<0.0001, respectively) and Week 8 (P<0.05 and P<0.0001, respectively).,AB/FF achieved higher step counts (P<0.01) with fewer inactive patients (P<0.0001) at Week 4 versus placebo.,Following BI, AB/FF maintained improvements in physical activity at Week 8 and nonsignificant improvements were observed with placebo.,AB/FF 400/12 μg demonstrated improvements in lung hyperinflation, exercise capacity, and physical activity versus placebo that were maintained following the addition of BI.,A 4-week period of BI might be too short to augment the improvements of physical activity observed with AB/FF. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of worsening of symptoms, leading to substantial morbidity and mortality.,COPD exacerbations are associated with increased airway and systemic inflammation and physiological changes, especially the development of hyperinflation.,They are triggered mainly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation.,Some patients are particularly susceptible to exacerbations, and show worse health status and faster disease progression than those who have infrequent exacerbations.,Several pharmacological interventions are effective for the reduction of exacerbation frequency and severity in COPD such as inhaled steroids, long-acting bronchodilators, and their combinations.,Non-pharmacological therapies such as pulmonary rehabilitation, self-management, and home ventilatory support are becoming increasingly important, but still need to be studied in controlled trials.,The future of exacerbation prevention is in assessment of optimum combinations of pharmacological and non-pharmacological therapies that will result in improvement of health status, and reduction of hospital admission and mortality associated with COPD. | Acute exacerbations contribute to the morbidity and mortality associated with chronic obstructive pulmonary disease (COPD).,This proof-of-concept study evaluates whether intermittent pulsed moxifloxacin treatment could reduce the frequency of these exacerbations.,Stable patients with COPD were randomized in a double-blind, placebo-controlled trial to receive moxifloxacin 400 mg PO once daily (N = 573) or placebo (N = 584) once a day for 5 days.,Treatment was repeated every 8 weeks for a total of six courses.,Patients were repeatedly assessed clinically and microbiologically during the 48-week treatment period, and for a further 24 weeks' follow-up.,At 48 weeks the odds ratio (OR) for suffering an exacerbation favoured moxifloxacin: per-protocol (PP) population (N = 738, OR 0.75, 95% confidence interval (CI) 0.565-0.994, p = 0.046), intent-to-treat (ITT) population (N = 1149, OR 0.81, 95% CI 0.645-1.008, p = 0.059), and a post-hoc analysis of per-protocol (PP) patients with purulent/mucopurulent sputum production at baseline (N = 323, OR 0.55, 95% CI 0.36-0.84, p = 0.006).,There were no significant differences between moxifloxacin and placebo in any pre-specified efficacy subgroup analyses or in hospitalization rates, mortality rates, lung function or changes in St George's Respiratory Questionnaire (SGRQ) total scores.,There was, however, a significant difference in favour of moxifloxacin in the SGRQ symptom domain (ITT: -8.2 vs -3.8, p = 0.009; PP: -8.8 vs -4.4, p = 0.006).,Moxifloxacin treatment was not associated with consistent changes in moxifloxacin susceptibility.,There were more treatment-emergent, drug related adverse events with moxifloxacin vs placebo (p < 0.001) largely due to gastrointestinal events (4.7% vs 0.7%).,Intermittent pulsed therapy with moxifloxacin reduced the odds of exacerbation by 20% in the ITT population, by 25% among the PP population and by 45% in PP patients with purulent/mucopurulent sputum at baseline.,There were no unexpected adverse events and there was no evidence of resistance development.,ClinicalTrials.gov number, NCT00473460 (ClincalTrials.gov). | 1 |
Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity worldwide, with high and growing prevalence.,Its underdiagnosis and hence under-treatment is a general feature across all countries.,This is particularly true for the mild or early stages of the disease, when symptoms do not yet interfere with daily living activities and both patients and doctors are likely to underestimate the presence of the disease.,A diagnosis of COPD requires spirometry in subjects with a history of exposure to known risk factors and symptoms.,Postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity <0.7 or less than the lower limit of normal confirms the presence of airflow limitation, the severity of which can be measured by FEV1% predicted: stage 1 defines COPD with mild airflow limitation, which means postbronchodilator FEV1 ≥80% predicted.,In recent years, an elegant series of studies has shown that “exclusive reliance on spirometry, in patients with mild airflow limitation, may result in underestimation of clinically important physiologic impairment”.,In fact, exercise tolerance, diffusing capacity, and gas exchange can be impaired in subjects at a mild stage of airflow limitation.,Furthermore, growing evidence indicates that smokers without overt abnormal spirometry have respiratory symptoms and undergo therapy.,This is an essential issue in COPD.,In fact, on one hand, airflow limitation, even mild, can unduly limit the patient’s physical activity, with deleterious consequences on quality of life and even survival; on the other hand, particularly in younger subjects, mild airflow limitation might coincide with the early stage of the disease.,Therefore, we thought that it was worthwhile to analyze further and discuss this stage of “mild COPD”.,To this end, representatives of scientific societies from five European countries have met and developed this document to stimulate the attention of the scientific community on COPD with “mild” airflow limitation.,The aim of this document is to highlight some key features of this important concept and help the practicing physician to understand better what is behind “mild” COPD.,Future research should address two major issues: first, whether mild airflow limitation represents an early stage of COPD and what the mechanisms underlying the evolution to more severe stages of the disease are; and second, not far removed from the first, whether regular treatment should be considered for COPD patients with mild airflow limitation, either to prevent progression of the disease or to encourage and improve physical activity or both. | Chronic obstructive pulmonary disease (COPD) is a common disease worldwide.,This study aimed to investigate the health status of patients with newly diagnosed COPD.,A total of 45 healthy controls and 218 patients with newly diagnosed COPD were recruited.,Pulmonary function test (PFT) values, COPD assessment test (CAT) scores, exacerbation history, and demographics were recorded.,Forced expiratory volume in 1 s percent (FEV1%) predicted was significantly decreased and the CAT score was significantly increased in patients with COPD compared with healthy controls (P <0.001).,Among the COPD patients, the most commonly reported respiratory symptoms were cough (86.7%), sputum (80.3%), and dyspnea (45%).,A total of 86.2% patients were in the moderate or severe stage (spirometric classification) of COPD, and 71.5% were in Group C or Group D (combined assessment).,A total of 33.9% of the patients had 2 or more exacerbations in the previous year.,Nearly half of the patients (45.4%) had a high CAT score of ≥10.,Patients with a history of more exacerbations had a higher CAT score.,Most COPD patients were symptomatic and appeared to have moderate to severe airflow limitation or a high risk of exacerbation before definitely being diagnosed with COPD using the PFT. | 1 |
To estimate the prevalence of both cardiometabolic and other co‐morbidities in patients with COVID‐19, and to estimate the increased risk of severity of disease and mortality in people with co‐morbidities.,Medline, Scopus and the World Health Organization website were searched for global research on COVID‐19 conducted from January 2019 up to 23 April 2020.,Study inclusion was restricted to English language publications, original articles that reported the prevalence of co‐morbidities in individuals with COVID‐19, and case series including more than 10 patients.,Eighteen studies were selected for inclusion.,Data were analysed using random effects meta‐analysis models.,Eighteen studies with a total of 14 558 individuals were identified.,The pooled prevalence for co‐morbidities in patients with COVID‐19 disease was 22.9% (95% CI: 15.8 to 29.9) for hypertension, 11.5% (9.7 to 13.4) for diabetes, and 9.7% (6.8 to 12.6) for cardiovascular disease (CVD).,For chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), cerebrovascular disease and cancer, the pooled prevalences were all less than 4%.,With the exception of cerebrovascular disease, all the other co‐morbidities presented a significantly increased risk for having severe COVID‐19.,In addition, the risk of mortality was significantly increased in individuals with CVD, COPD, CKD, cerebrovascular disease and cancer.,In individuals with COVID‐19, the presence of co‐morbidities (both cardiometabolic and other) is associated with a higher risk of severe COVID‐19 and mortality.,These findings have important implications for public health with regard to risk stratification and future planning. | Currently there is limited knowledge on medical comorbidities and COVID-19; we conducted a systematic review and meta-analysis to evaluate the impact of various morbidities on serious events in COVID 19.,PubMed, Cochrane Central Register of Clinical Trials were searched on April 28, 2020, to extract published articles that reported the outcomes of COVID-19 patients.,The search terms were “coronavirus” and “clinical characteristics”.,ICU admission, mechanical ventilation, ARDS, Pneumonia, death was considered serious events.,The comorbidities assessed in the study were Hypertension (HTN), Diabetes mellitus (DM), Cardiovascular diseases (CVD), Chronic obstructive pulmonary disease (COPD) and Chronic Kidney disease (CKD).,Subsequently, comparisons between comorbidity patient group and the non-comorbidity patient groups, in terms of serious events were made using the pooled estimates of odd’s ratio (OR),We identified 688 published results and 16 studies with 3994 patients were included in the systematic review.,Serious events were seen in 526(13.16%) patients.,Presence of hypertension with OR 2.95, diabetes mellitus with OR 3.07, Cardio vascular disease with OR 4.58, COPD with OR 6.66 and Chronic kidney disease with OR 5.32 had significant association in patients with COVID 19 on having serious events.,Presence of diabetes mellitus (OR 2.78)) had a significant impact on death in COVID 19 patients with a p-value 0.004.,Presence of medical comorbidities in COVID-19 leads to higher risk of developing serious events i.e.,ICU admission, mechanical intubation and mortality.,The presence of Diabetes mellitus has a significant impact on mortality rate in COVID-19 patients.,•Medical comorbidities in COVID-19 leads to higher morbidity and higher mortality rate.,•Patient with Comorbidities are likely to have high risk of severe events.,•Diabetes mellitus has a significant impact on mortality rate in COVID-19 patients.,Medical comorbidities in COVID-19 leads to higher morbidity and higher mortality rate.,Patient with Comorbidities are likely to have high risk of severe events.,Diabetes mellitus has a significant impact on mortality rate in COVID-19 patients. | 1 |
In deciding on the treatment plan for patients with chronic obstructive pulmonary disease (COPD), the burden of COPD as experienced by patients should be the core focus.,It is therefore important for daily practice to develop a tool that can both assess the burden of COPD and facilitate communication with patients in clinical practice.,This paper describes the development of an integrated tool to assess the burden of COPD in daily practice.,A definition of the burden of COPD was formulated by a Dutch expert team.,Interviews showed that patients and health-care providers agreed on this definition.,We found no existing instruments that fully measured burden of disease according to this definition.,However, the Clinical COPD Questionnaire meets most requirements, and was therefore used and adapted.,The adapted questionnaire is called the Assessment of Burden of COPD (ABC) scale.,In addition, the ABC tool was developed, of which the ABC scale is the core part.,The ABC tool is a computer program with an algorithm that visualises outcomes and provides treatment advice.,The next step in the development of the tool is to test the validity and effectiveness of both the ABC scale and tool in daily practice. | Chronic Obstructive Pulmonary Disease (COPD) is a disease state characterized by airflow limitation that is not fully reversible and usually progressive.,Current guidelines, among which the Dutch, have so far based their management strategy mainly on lung function impairment as measured by FEV1, while it is well known that FEV1 has a poor correlation with almost all features of COPD that matter to patients.,Based on this discrepancy the GOLD 2011 update included symptoms and impact in their treatment algorithm proposal.,Health status measures capture both symptoms and impact and could therefore be used as a standardized way to capture the information a doctor could otherwise only collect by careful history taking and recording.,We hypothesize that a treatment algorithm that is based on a simple validated 10 item health status questionnaire, the Clinical COPD Questionnaire (CCQ), improves health status (as measured by SGRQ) and classical COPD outcomes like exacerbation frequency, patient satisfaction and health care utilization compared to usual care based on guidelines.,This hypothesis will be tested in a randomized controlled trial (RCT) following 330 patients for two years.,During this period general practitioners will receive treatment advices every four months that are based on the patient’s health status (in half of the patients, intervention group) or on lung function (the remaining half of the patients, usual care group).,During the design process, the selection of outcomes and the development of the treatment algorithm were challenging.,This is discussed in detail in the manuscript to facilitate researchers in designing future studies in this changing field of implementation research.,Netherlands Trial Register, NTR2643 | 1 |
Lung fibroblasts are involved in extracellular matrix homeostasis, which is mainly regulated by transforming growth factor-beta (TGF-β), and are therefore crucial in lung tissue repair and remodeling.,Abnormal repair and remodeling has been observed in lung diseases like COPD.,As miRNA levels can be influenced by TGF-β, we hypothesized that TGF-β influences miRNA expression in lung fibroblasts, thereby affecting their function.,We investigated TGF-β1-induced miRNA expression changes in 9 control primary parenchymal lung fibroblasts using miRNA arrays.,TGF-β1-induced miRNA expression changes were validated and replicated in an independent set of lung fibroblasts composted of 10 controls and 15 COPD patients using qRT-PCR.,Ago2-immunoprecipitation followed by mRNA expression profiling was used to identify the miRNA-targetomes of unstimulated and TGF-β1-stimulated primary lung fibroblasts (n = 2).,The genes affected by TGF-β1-modulated miRNAs were identified by comparing the miRNA targetomes of unstimulated and TGF-β1-stimulated fibroblasts.,Twenty-nine miRNAs were significantly differentially expressed after TGF-β1 stimulation (FDR<0.05).,The TGF-β1-induced miR-455-3p and miR-21-3p expression changes were validated and replicated, with in addition, lower miR-455-3p levels in COPD (p<0.05).,We identified 964 and 945 genes in the miRNA-targetomes of unstimulated and TGF-β1-stimulated lung fibroblasts, respectively.,The TGF-β and Wnt pathways were significantly enriched among the Ago2-IP enriched and predicted targets of miR-455-3p and miR-21-3p.,The miR-455-3p target genes HN1, NGF, STRADB, DLD and ANO3 and the miR-21-3p target genes HHEX, CHORDC1 and ZBTB49 were consistently more enriched after TGF-β1 stimulation.,Two miRNAs, miR-455-3p and miR-21-3p, were induced by TGF-β1 in lung fibroblasts.,The significant Ago2-IP enrichment of targets of these miRNAs related to the TGF-β and/or Wnt pathways (NGF, DLD, HHEX) in TGF-β1-stimulated fibroblasts suggest a role for these miRNAs in lung diseases by affecting lung fibroblast function. | Chronic obstructive pulmonary disease (COPD), a major cause of death and morbidity worldwide, is characterized by expiratory airflow limitation that is not fully reversible, deregulated chronic inflammation, and emphysematous destruction of the lungs.,Despite the fact that COPD is a steadily growing global healthcare problem, the conventional therapies remain palliative, and regenerative approaches for disease management are not available yet.,We aim to provide an overview of key reviews, experimental, and clinical studies addressing lung emphysema development and repair mechanisms published in the past decade.,Novel aspects discussed herein include integral revision of the literature focused on lung microflora changes in COPD, autoimmune component of the disease, and environmental risk factors other than cigarette smoke.,The time span of studies on COPD, including emphysema, chronic bronchitis, and asthmatic bronchitis, covers almost 200 years, and several crucial mechanisms of COPD pathogenesis are described and studied.,However, we still lack the holistic understanding of COPD development and the exact picture of the time-course and interplay of the events during stable, exacerbated, corticosteroid-treated COPD states, and transitions in-between.,Several generally recognized mechanisms will be discussed shortly herein, ie, unregulated inflammation, proteolysis/antiproteolysis imbalance, and destroyed repair mechanisms, while novel topics such as deviated microbiota, air pollutants-related damage, and autoimmune process within the lung tissue will be discussed more extensively.,Considerable influx of new data from the clinic, in vivo and in vitro studies stimulate to search for novel concise explanation and holistic understanding of COPD nowadays. | 1 |
Background: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD).,It represents a collaborative effort on the part of a panel of expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thoracic Society.,Methods: Comprehensive evidence syntheses were performed on all relevant studies that addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts.,The evidence was appraised, rated, and graded, and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.,Results: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations: 1) a strong recommendation for the use of long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance; 2) a conditional recommendation for the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year; 3) a conditional recommendation for ICS withdrawal for patients with COPD receiving triple therapy (ICS/LABA/LAMA) if the patient has had no exacerbations in the past year; 4) no recommendation for or against ICS as an additive therapy to long-acting bronchodilators in patients with COPD and blood eosinophilia, except for those patients with a history of one or more exacerbations in the past year requiring antibiotics or oral steroids or hospitalization, for whom ICS is conditionally recommended as an additive therapy; 5) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and 6) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy.,Conclusions: The task force made recommendations regarding the pharmacologic treatment of COPD based on currently available evidence.,Additional research in populations that are underrepresented in clinical trials is needed, including studies in patients with COPD 80 years of age and older, those with multiple chronic health conditions, and those with a codiagnosis of COPD and asthma. | We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy.,Three studies of ≥1-year duration met the inclusion criteria.,Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%).,At baseline, 57-75% of patients had ≥2% blood eosinophils.,Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level.,For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001).,No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively).,In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo).,No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ.,Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations. | 1 |
Cigarette smoke is a major effector of chronic obstructive pulmonary disease (COPD), and Th17 cells and dendritic cells (DCs) involve in the pathogenesis of COPD.,Previous studies have demonstrated the anti-inflammatory effects of macrolides.,However, the effects of macrolides on the cigarette smoke extract- (CSE-) induced immune response are unclear.,Accordingly, in this study, we evaluated the effects of erythromycin (EM) on CSE-exposed DCs polarizing naïve CD4+ T cells into Th17 cells.,DCs were generated from bone marrow-derived mononuclear cells isolated from male BALB/c mice and divided into five groups: control DC group, CSE-exposed DC group, CD40-antibody-blocked CSE-exposed DC group, and EM-treated CSE-exposed DC group.,The function of polarizing CD4+ T cells into Th17 cells induced by all four groups of DCs was assayed based on the mixed lymphocyte reaction (MLR) of naïve CD4+ T cells.,CD40 expression in DCs in the CSE-exposed group increased significantly compared with that in the control group (P < 0.05).,The Th17 cells in the CSE-exposed DC/MLR group increased significantly compared with those in the control DC/MLR group (P < 0.05).,Moreover, Th17 cells in the CD40-blocked CSE-exposed DC/MLR group and EM-treated CSE-exposed DC/MLR group were reduced compared with those in the CSE-exposed DC/MLR group (P < 0.05).,Thus, these findings suggested that EM suppressed the CSE-exposed DC-mediated polarization of CD4+ T cells into Th17 cells and that this effect may be mediated through inhibition of the CD40/CD40L pathway. | Objective.,To study the effects of low-dose and long-term treatment with erythromycin on IL-17 and IL-23, in peripheral blood and induced sputum, in patients with stable chronic obstructive pulmonary disease (COPD).,Methods.,Patients were randomly divided into placebo-treated group, group A (12 months of additive treatment with erythromycin, N = 18), and group B (6 months of additive treatment with erythromycin followed by 6 months of follow-up, N = 18).,Inflammatory cells in induced sputum, pulmonary function, and the 6-minute walk distance (6MWD) were analyzed.,Concentrations of IL-17 and IL-23 in peripheral blood and sputum were measured using enzyme-linked immunosorbent assays.,Results.,After treatment, sputum and peripheral blood concentrations of IL-17 and IL-23 significantly decreased in groups A and B compared with placebo-treated group.,There were no significant differences after erythromycin withdrawal at months 9 and 12 in group B compared with placebo-treated group.,An increase in 6MWD was observed after treatment.,Conclusions.,Erythromycin was beneficial and reduced airway inflammation in COPD patients.,Underlying mechanisms may involve inhibition of IL-17 and IL-23 mediated airway inflammation.,COPD patients treated with erythromycin for 6 months experienced improved exercise capacity.,Finally, treatment for 12 months may be more effective than treatment for 6 months. | 1 |
Ensifentrine is an inhaled first-in-class dual inhibitor of phosphodiesterase (PDE) 3 and 4.,In a four-week randomized, double-blind, placebo-controlled, parallel-group study in patients with chronic obstructive pulmonary disease (COPD), nebulized ensifentrine 0.75 to 6mg twice daily significantly improved bronchodilation and symptoms, with all doses being well tolerated.,Here, we report data for a number of prespecified exploratory and post hoc endpoints from this study that help to further profile the effect of ensifentrine on symptoms.,Eligible patients were males or females aged 40-75 years with COPD, post-bronchodilator forced expiratory volume in 1 second 40-80% predicted.,Other than being clinically stable for at least four weeks prior to entry, there were no symptomatic inclusion or exclusion criteria.,The outcome measures reported in this manuscript are the Evaluating Respiratory Symptoms [E-RS™:COPD] questionnaire total score and subscales (breathlessness, cough/sputum and chest symptoms) at Weeks 1-4, Transition Dyspnea Index (TDI) focal score at Weeks 2 and 4, and St George’s Respiratory Questionnaire - COPD Specific (SGRQ-C) total score and domain data (symptoms, activity and impacts) at Week 4.,There was a gradual improvement versus placebo with all ensifentrine doses for all three E-RS™:COPD subscales from Week 1 to Week 4, with the greatest ensifentrine effect on the breathlessness subscale, and all four doses superior to placebo from Week 2 onwards (p<0.05).,For TDI focal score, all ensifentrine doses were superior to placebo at Weeks 2 and 4 (p<0.05).,In the individual SGRQ-C domains at Week 4, ensifentrine had the greatest effect on the symptoms domain, with ensifentrine 6mg superior to placebo (p<0.05).,In these analyses, ensifentrine demonstrated a notable early and meaningful effect on dyspnea, with this effect observed across two different assessment tools. | Many patients with chronic obstructive pulmonary disease (COPD) still experience daily symptoms, exacerbations, and accelerated lung function decline, even when receiving maximal combined treatment with inhaled long-acting bronchodilators and corticosteroids.,Novel treatment options are needed for these patients.,Phosphodiesterases (PDEs) are enzymes that impact a range of cellular functions by modulating levels of cyclic nucleotides, and there is evidence to suggest that combined inhibition of PDE3 and PDE4 can have additive (or perhaps synergistic) effects.,This study investigated the efficacy and safety of ensifentrine, a first-in-class dual inhibitor of PDE 3 and 4, in patients with COPD.,This randomised, double-blind, placebo-controlled, parallel-group, dose-ranging study recruited patients with COPD, post-bronchodilator forced expiratory volume in 1 s (FEV1) 40-80% predicted and FEV1/forced vital capacity ratio ≤ 0.7.,Patients were randomised equally to inhale nebulised ensifentrine 0.75, 1.5, 3 or 6 mg or placebo, all twice daily.,Primary outcome: placebo-adjusted difference in peak FEV1 (assessed over 3 h) at Week 4.,The study took place between July 2017 and February 2018.,Of 405 patients randomly assigned to medication, 375 (92.6%) completed the study.,For peak FEV1 at Week 4, all four ensifentrine doses were superior to placebo (p ≤ 0.0001) with least squares mean differences of 146 (95% CI 75-216), 153 (83-222), 200 (131-270) and 139 (69-210) mL for ensifentrine 0.75, 1.5, 3 and 6 mg, respectively.,Respiratory symptoms (assessed using the Evaluating Respiratory Symptoms questionnaire) were also significantly improved with all ensifentrine doses at Week 4.,Adverse events were reported by 33.3, 44.4, 35.4 and 36.3% patients with ensifentrine 0.75, 1.5, 3 and 6 mg, respectively, and 39.2% with placebo.,In this four-week Phase IIb study, all four ensifentrine doses significantly improved bronchodilation and symptoms, with a dose-ranging effect from 0.75 to 3 mg twice daily, and all doses well tolerated.,The study supports the continuing development of ensifentrine in COPD.,EudraCT 2016-005205-40, registered 30 May 2017. | 1 |
Smoking effects on physiological and gross pathology in chronic obstructive pulmonary disease (COPD) are relatively well described.,However, there is little known in COPD about the detailed interrelationships between lung function and inflammatory profiles in different airway compartments from the same individual and whether airway inflammation in these different compartments differs in ex- and current smokers with established COPD.,We compared sputum, bronchoalveolar (BAL), and airway wall inflammatory profiles in current versus ex-smokers and related this to smoking intensity and lung function in 17 current and 17 ex-smokers with mild to moderate COPD.,Current smokers had more sputum mast cells (% differential and absolute numbers), whereas ex-smokers had increased sputum neutrophils.,In BAL, there was a significant increase in eosinophils in current smokers, but ex-smokers had significantly increased neutrophils, lymphocytes, and epithelial cells.,There were no cell profile differences observed in airway biopsies between current and ex-smokers and there were no correlations between the individual inflammatory cell populations in any of the airway compartments.,In current smokers only, smoking intensity was negatively correlated with lung function, and associated with a reduction in overall cellularity of both sputum and BAL.,Airway inflammation persists in ex-smokers with COPD, but differs from COPD current smokers.,The impact of smoking appears to vary in different airway compartments and any direct relationships between cellularity and lung function tended to be negative, ie, worse lung function indicated the presence of fewer cells. | 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 |
Cachectic patients with chronic obstructive pulmonary disease (COPD) may benefit from nutritional support.,This double‐blind, randomized, controlled trial evaluated the safety and efficacy of targeted medical nutrition (TMN) vs. an isocaloric comparator in pre‐cachectic and cachectic patients with COPD.,Patients aged ≥50 years with moderate‐to‐severe COPD and involuntary weight loss or low body mass index (16-18 kg/m2) were randomized 1:1 to receive TMN (~230 kcal; 2 g omega‐3 fatty acids; 10 μg 25‐hydroxy‐vitamin D3) or isocaloric comparator twice daily for 12 weeks (ClinicalTrials.gov Identifier: NCT02442908).,Primary safety endpoints comprised adverse events and changes in vital signs, laboratory parameters, and concomitant medications.,Secondary efficacy endpoints included changes in weight, body composition, exercise tolerance, metabolic biomarkers, and systemic inflammation.,Forty‐five patients were randomized to receive TMN (n = 22; mean 69.2 years) or isocaloric comparator (n = 23; mean 69.7 years).,TMN was well tolerated.,Adverse events were similar in number and type in both groups.,Compliance to both products was good (TMN, 79%; comparator, 77%).,Both groups gained weight, but the TMN group gained comparatively more fat mass (P = 0.0013).,Reductions in systolic blood pressure (P = 0.0418) and secondary endpoints of triglycerides (P = 0.0217) and exercise‐induced fatigue (P = 0.0223) and dyspnoea (P = 0.0382), and increases in high‐density lipoprotein cholesterol (P = 0.0254), were observed in the TMN vs. the comparator group by week 12.,Targeted medical nutrition containing high‐dose omega‐3 fatty acids, vitamin D, and high‐quality protein is well tolerated with a good safety profile and has positive effects on blood pressure and blood lipids and on exercise‐induced fatigue and dyspnoea.,Therefore, this TMN could be clinically beneficial in the nutritional and metabolic support of pre‐cachectic and cachectic patients with COPD. | Patient centred outcomes, such as health status, are important in Chronic Obstructive Pulmonary Disease (COPD).,Extensive questionnaires on health status have good measurement properties, but are not suitable for use in primary care.,The newly developed, short Clinical COPD Questionnaire, CCQ, was therefore validated against the St George's Respiratory Questionnaire (SGRQ).,111 patients diagnosed by general practitioners as having COPD completed the questionnaires twice, 2-3 months apart, without systematic changes in treatment.,Within this sample of patients with "clinical COPD" a subgroup of patients with spirometry verified COPD was identified.,All analyses was performed on both groups.,The mean FEV1 (% predicted) was 58.1% for all patients with clinical COPD and 52.4% in the group with verified COPD (n = 83).,Overall correlations between SGRQ and CCQ were strong for all patients with clinical COPD (0.84) and the verified COPD subgroup (0.82).,The concordance intra-class correlation between SGRQ and CCQ was 0.91 (p < 0.05).,Correlations between CCQ and SGRQ were moderate to good, regardless of COPD severity.,The CCQ is a valid and reliable instrument for assessments of health status on the group level in patients treated for COPD in primary care but its reliability may not be sufficient for the monitoring of individual patients. | 1 |
Chronic obstructive pulmonary disease (COPD) and lung cancer, closely related to smoking, are major lung diseases affecting millions of individuals worldwide.,The generated gas mixture of smoking is proved to contain about 4,500 components such as carbon monoxide, nicotine, oxidants, fine particulate matter, and aldehydes.,These components were considered to be the principle factor driving the pathogenesis and progression of pulmonary disease.,A large proportion of lung cancer patients showed a history of COPD, which demonstrated that there might be a close relationship between COPD and lung cancer.,In the early stages of smoking, lung barrier provoked protective response and DNA repair are likely to suppress these changes to a certain extent.,In the presence of long-term smoking exposure, these mechanisms seem to be malfunctioned and lead to disease progression.,The infiltration of inflammatory cells to mucosa, submucosa, and glandular tissue caused by inhaled cigarette smoke is responsible for the destruction of matrix, blood supply shortage, and epithelial cell death.,Conversely, cancer cells have the capacity to modulate the proliferation of epithelial cells and produce of new vascular networks.,Comprehension understanding of mechanisms responsible for both pathologies is necessary for the prevention and treatment of COPD and lung cancer.,In this review, we will summarize related articles and give a glance of possible mechanism between cigarette smoking induced COPD and lung cancer. | Patients with chronic obstructive pulmonary disease (COPD) exhibit dominant features of chronic bronchitis, emphysema, and/or asthma, with a common phenotype of airflow obstruction.,COPD pulmonary physiology reflects the sum of pathological changes in COPD, which can occur in large central airways, small peripheral airways, and the lung parenchyma.,Quantitative or high-resolution computed tomography is used as a surrogate measure for assessment of disease progression.,Different biological or molecular markers have been reported that reflect the mechanistic or pathogenic triad of inflammation, proteases, and oxidants and correspond to the different aspects of COPD histopathology.,Similar to the pathogenic triad markers, genetic variations or polymorphisms have also been linked to COPD-associated inflammation, protease-antiprotease imbalance, and oxidative stress.,Furthermore, in recent years, there have been reports identifying aging-associated mechanistic markers as downstream consequences of the pathogenic triad in the lungs from COPD patients.,For this review, the authors have limited their discussion to a review of mechanistic markers and genetic variations and their association with COPD histopathology and disease status. | 1 |
As of 11 July, 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic has infected over 12.7 million people around the world and caused more than 560,000 deaths [1].,Given the devastating impact that COVID-19 can have on the lung, it is natural to fear for patients with underlying COPD.,Estimating their excess risk for contracting COVID-19 and, in particular, its more severe respiratory manifestations has been a challenging exercise in this pandemic for various reasons.,First, the reporting on cases has concentrated on hospitalised and intensive care unit (ICU) patients, rather than on mild, outpatient cases.,This is in part also due to the variability in testing strategies across the world, where some nations with stricter testing requirements and scarce testing resources have focused on testing only those requiring hospitalisation.,COPD patients have increased risk of severe pneumonia and poor outcomes when they develop COVID-19.,This may be related to poor underlying lung reserves or increased expression of ACE-2 receptor in small airways.https://bit.ly/37dSB8l | The global burden of chronic obstructive pulmonary disease (COPD) continues to grow in part due to better outcomes in other major diseases and in part because a substantial portion of the worldwide population continues to be exposed to inhalant toxins.,However, a disproportionate burden of COPD occurs in people of low socioeconomic status (SES) due to differences in health behaviors, sociopolitical factors, and social and structural environmental exposures.,Tobacco use, occupations with exposure to inhalant toxins, and indoor biomass fuel (BF) exposure are more common in low SES populations.,Not only does SES affect the risk of developing COPD and etiologies, it is also associated with worsened COPD health outcomes.,Effective interventions in these people are needed to decrease these disparities.,Efforts that may help lessen these health inequities in low SES include 1) better surveillance targeting diagnosed and undiagnosed COPD in disadvantaged people, 2) educating the public and those involved in health care provision about the disease, 3) improving access to cost-effective and affordable health care, and 4) markedly increasing the efforts to prevent disease through smoking cessation, minimizing use and exposure to BF, and decreasing occupational exposures.,COPD is considered to be one the most preventable major causes of death from a chronic disease in the world; therefore, effective interventions could have a major impact on reducing the global burden of the disease, especially in socioeconomically disadvantaged populations. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) can be categorized as having frequent (FE) or infrequent (IE) exacerbations depending on whether they respectively experience two or more, or one or zero exacerbations per year.,Although most patients do not change category from year to year, some will, and the factors associated with this behaviour have not been examined.,1832 patients completing two year follow-up in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study were examined at baseline and then yearly.,Exacerbations were defined by health care utilisation.,Patient characteristics compared between those patients who did or did not change exacerbation category from year 1 to year 2.,Between years 1 and 2, 221 patients (17%) changed from IE to FE and 210 patients (39%) from FE to IE.,More severe disease was associated with changing from IE to FE and less severe disease from FE to IE.,Over the preceding year, small falls in FEV1 and 6-minute walking distance were associated with changing from IE to FE, and small falls in platelet count associated with changing from FE to IE.,No parameter clearly predicts an imminent change in exacerbation frequency category.,SCO104960, clinicaltrials.gov identifier NCT00292552 | To evaluate the influence of heart disease on clinical characteristics, quality of life, use of health resources, and costs of patients with COPD followed at primary care settings under common clinical practice conditions.,Epidemiologic, observational, and descriptive study (EPIDEPOC study).,Patients ≥ 40 years of age with stable COPD attending primary care settings were included.,Demographic, clinical characteristics, quality of life (SF-12), seriousness of the disease, and treatment data were collected.,Results were compared between patients with or without associated heart disease.,A total of 9,390 patients with COPD were examined of whom 1,770 (18.8%) had heart disease and 78% were males.,When comparing both patient groups, significant differences were found in the socio-demographic characteristics, health profile, comorbidities, and severity of the airway obstruction, which was greater in patients with heart disease.,Differences were also found in both components of quality of life, physical and mental, with lower scores among those patients with heart disease.,Higher frequency of primary care and pneumologist visits, emergency-room visits and number of hospital admissions were observed among patients with heart diseases.,The annual total cost per patient was significantly higher in patients with heart disease; 2,937 ± 2,957 vs. 1,749 ± 2,120, p < 0.05.,Variables that were showed to be independently associated to COPD in subjects with hearth conditions were age, being inactive, ex-smokers, moderate physical exercise, body mass index, concomitant blood hypertension, diabetes, anxiety, the SF-12 physical and mental components and per patient per year total cost.,Patients with COPD plus heart disease had greater disease severity and worse quality of life, used more healthcare resources and were associated with greater costs compared to COPD patients without known hearth disease. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by varying trajectories of decline.,Information regarding the prognostic value of preventing short-term clinically important deterioration (CID) in lung function, health status, or first moderate/severe exacerbation as a composite endpoint of worsening is needed.,We evaluated post hoc the link between early CID and long-term adverse outcomes.,CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV1), ≥4-unit increase in St George’s Respiratory Questionnaire (SGRQ) score from baseline, and/or a moderate/severe exacerbation during enrollment in two 3-year studies.,Presence of CID was assessed at 6 months for the principal analysis (TORCH) and 12 months for the confirmatory analysis (ECLIPSE).,Association between presence (+) or absence (-) of CID and long-term deterioration in FEV1, SGRQ, future risk of exacerbations, and all-cause mortality was assessed.,In total, 2870 (54%; TORCH) and 1442 (73%; ECLIPSE) patients were CID+.,At 36 months, in TORCH, CID+ patients (vs CID-) had sustained clinically significant worsening of FEV1 (- 117 mL; 95% confidence interval [CI]: - 134, - 100 mL; P < 0.001) and SGRQ score (+ 6.42 units; 95% CI: 5.40, 7.45; P < 0.001), and had higher risk of exacerbations (hazard ratio [HR]: 1.61 [95% CI: 1.50, 1.72]; P < 0.001) and all-cause mortality (HR: 1.41 [95% CI: 1.15, 1.72]; P < 0.001).,Similar risks post-CID were observed in ECLIPSE.,A CID within 6-12 months of follow-up was consistently associated with increased long-term risk of exacerbations and all-cause mortality, and predicted sustained meaningful loss in FEV1 and health status amongst survivors.,NCT00268216; NCT00292552.,The online version of this article (10.1186/s12931-018-0928-3) contains supplementary material, which is available to authorized users. | 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 |
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. | The purpose of this study was to analyze the distribution of chronic obstructive pulmonary disease (COPD) in terms of time, place, and person among inpatients at the Mid Western Regional Hospital (MWRH) in Nepal.,A descriptive cross-sectional study was carried out by analyzing trends using secondary data for the fiscal years 2006-2009 in the inpatient department of the MWRH.,The majority of patients admitted for treatment of COPD were women (60%) and from higher ethnic groups (having a comparative advantage in terms of social and economic status), with a greater prevalence among those aged 60-69 years (37% of overall cases).,The incidence of COPD increased in consecutive years, with the highest load during the winter months.,The cases were most concentrated in places with easiest access to the hospital.,COPD was found in higher proportions among women, those aged 60-69 years, and upper caste groups, during the cold months, and among residents of areas near the hospital in the mid-western region of Nepal.,It is recommended that further detailed research and health education regarding COPD be carried out to reduce its burden and associated losses. | 1 |
Research on the association between chronic bronchitis and chronic obstructive pulmonary disease (COPD) exacerbations has led to discordant results.,Furthermore, the impact of chronic bronchitis on mortality in COPD subjects is unclear.,Within the Rotterdam Study, a population-based cohort study of subjects aged ≥45 years, chronic bronchitis was defined as having a productive cough for ≥3 months per year for two consecutive years.,Linear, logistic regression and Cox proportional hazard models were adjusted for age, sex and pack-years.,Out of 972 included COPD subjects, 752 had no chronic phlegm production (CB−) and 220 had chronic phlegm production, of whom 172 met the definition of chronic bronchitis (CB+).,CB+ subjects were older, more frequently current smokers and had more pack-years than CB− subjects.,During a median 6.5 years of follow-up, CB+ subjects had greater decline in lung function (−38 mL·year−1, 95% CI −61.7-−14.6; p=0.024).,CB+ subjects had an increased risk of frequent exacerbations (OR 4.0, 95% CI 2.7-5.9; p<0.001).,In females, survival was significantly worse in CB+ subjects compared to CB− subjects.,Regarding cause-specific mortality, CB+ subjects had an increased risk of respiratory mortality (hazard ratio 2.16, 95% CI 1.12-4.17; p=0.002).,COPD subjects with chronic bronchitis have an increased risk of exacerbations and respiratory mortality compared to COPD subjects without chronic phlegm production.,Chronic bronchitis increases the risk of exacerbations and mortality among patients with COPDhttp://ow.ly/o1fq30bFf9Q | Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases.,We sought to determine, in terms of their sputum cellular and mediator profiles, the extent to which they represent distinct or overlapping conditions supporting either the “British” or “Dutch” hypotheses of airway disease pathogenesis.,We compared the clinical and physiological characteristics and sputum mediators between 86 subjects with severe asthma and 75 with moderate-to-severe COPD.,Biological subgroups were determined using factor and cluster analyses on 18 sputum cytokines.,The subgroups were validated on independent severe asthma (n = 166) and COPD (n = 58) cohorts.,Two techniques were used to assign the validation subjects to subgroups: linear discriminant analysis, or the best identified discriminator (single cytokine) in combination with subject disease status (asthma or COPD).,Discriminant analysis distinguished severe asthma from COPD completely using a combination of clinical and biological variables.,Factor and cluster analyses of the sputum cytokine profiles revealed 3 biological clusters: cluster 1: asthma predominant, eosinophilic, high TH2 cytokines; cluster 2: asthma and COPD overlap, neutrophilic; cluster 3: COPD predominant, mixed eosinophilic and neutrophilic.,Validation subjects were classified into 3 subgroups using discriminant analysis, or disease status with a binary assessment of sputum IL-1β expression.,Sputum cellular and cytokine profiles of the validation subgroups were similar to the subgroups from the test study.,Sputum cytokine profiling can determine distinct and overlapping groups of subjects with asthma and COPD, supporting both the British and Dutch hypotheses.,These findings may contribute to improved patient classification to enable stratified medicine. | 1 |
Despite the frequency and negative impact of low physical activity among patients with chronic obstructive pulmonary disease (COPD), little is known about how it persists and remits over time or the factors predicting new states of low physical activity.,The aim of the study was to determine the probability of a transition between states of low and nonlow physical activity in a cohort of patients with stable COPD followed for 2 years.,We also investigated different potentially modifiable factors to determine whether they can predict new states of low physical activity.,We prospectively included 137 patients with stable COPD (mean age 66.9 ± 8.3 years).,Physical activity was measured at baseline and at 1 and 2 years of follow up.,Low physical activity was defined according to energy expenditure by cut-off points from the Fried frailty model.,The likelihood of annual transition towards new states and recovery was calculated.,We evaluated demographic, frailty, nonrespiratory, and respiratory variables as potential predictors, using generalized estimating equations.,At baseline, 37 patients (27%) presented with low physical activity.,During the study period, a total of 179 annual transitions were identified with nonlow physical activity at the beginning of the year; 17.5% transitioned to low physical activity.,In contrast, 34.3% of the 67 transitions that started with low physical activity recovered.,Predictors of transition to new states of low physical activity were dyspnea ⩾2 (odds ratio = 3.21; 95% confidence interval: 1.20-8.61) and poor performance on the five sit-to-stand test (odds ratio = 4.75; 95% confidence interval: 1.30-17.47).,The change between levels of low and nonlow physical activity is dynamic, especially for recovery.,Annual transitions toward new states of low physical activity are likely among patients with dyspnea or poor performance on the five sit-to-stand test.,The reviews of this paper are available via the supplemental material section. | 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 |
Polymorphonuclear neutrophils have in recent years attracted new attention due to their ability to release neutrophil extracellular traps (NETs).,These web-like extracellular structures deriving from nuclear chromatin have been depicted in ambiguous roles between antimicrobial defence and host tissue damage.,NETs consist of DNA strands of varying thickness and are decorated with microbicidal and cytotoxic proteins.,Their principal structure has in recent years been characterised at molecular and ultrastructural levels but many features that are of direct relevance to cytotoxicity are still incompletely understood.,These include the extent of chromatin decondensation during NET formation and the relative amounts and spatial distribution of the microbicidal components within the NET.,In the present work, we analyse the structure of NETs found in induced sputum of patients with acutely exacerbated chronic obstructive pulmonary disease (COPD) using confocal laser microscopy and electron microscopy.,In vitro induced NETs from human neutrophils serve for purposes of comparison and extended analysis of NET structure.,Results demonstrate that COPD sputa are characterised by the pronounced presence of NETs and NETotic neutrophils.,We provide new evidence that chromatin decondensation during NETosis is most extensive and generates substantial amounts of double-helix DNA in ‘beads-on-a-string’ conformation.,New information is also presented on the abundance and location of neutrophil elastase (NE) and citrullinated histone H3 (citH3).,NE occurs in high densities in nearly all non-fibrous constituents of the NETs while citH3 is much less abundant.,We conclude from the results that (i) NETosis is an integral part of COPD pathology; this is relevant to all future research on the etiology and therapy of the disease; and that (ii) release of ‘beads-on-a-string’ DNA studded with non-citrullinated histones is a common feature of in vivo NETosis; this is of relevance to both the antimicrobial and the cytotoxic effects of NETs. | Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory lung disease which may be complicated by development of co-morbidities including metabolic disorders.,Metabolic disorders commonly associated with this disease contribute to lung function impairment and mortality.,Systemic inflammation appears to be a major factor linking COPD to metabolic alterations.,Adipose tissue seems to interfere with systemic inflammation in COPD patients by producing a large number of proteins, known as “adipokines”, involved in various processes such as metabolism, immunity and inflammation.,There is evidence that adiponectin is an important modulator of inflammatory processes implicated in airway pathophysiology.,Increased serum levels of adiponectin and expression of its receptors on lung tissues of COPD patients have recently highlighted the importance of the adiponectin pathway in this disease.,Further, in vitro studies have demonstrated an anti-inflammatory activity for this adipokine at the level of lung epithelium.,This review focuses on mechanisms by which adiponectin is implicated in linking COPD with metabolic disorders. | 1 |
Exacerbations of COPD are defined clinically by worsening of chronic respiratory symptoms.,Chronic respiratory symptoms are common in the general population.,There are no data on the frequency of exacerbation-like events in individuals without spirometric evidence of COPD.,To determine the occurrence of ‘exacerbation-like’ events in individuals without airflow limitation, their associated risk factors, healthcare utilisation and social impacts.,We analysed the cross-sectional data from 5176 people aged 40 years and older who participated in a multisite, population-based study on lung health.,The study cohort was stratified into spirometrically defined COPD (post-bronchodilator FEV1/FVC < 0.7) and non-COPD (post bronchodilator FEV1/FVC ≥ 0.7 and without self-reported doctor diagnosis of airway diseases) subgroups and then into those with and without respiratory ‘exacerbation-like’ events in the past year.,Individuals without COPD had half the frequency of ‘exacerbation-like’ events compared with those with COPD.,In the non-COPD group, the independent associations with ‘exacerbations’ included female gender, presence of wheezing, the use of respiratory medications and self-perceived poor health.,In the non-COPD group, those with exacerbations were more likely than those without exacerbations to have poorer health-related quality of life (12-item Short-Form Health Survey), miss social activities (58.5% vs 18.8%), miss work for income (41.5% vs 17.3%) and miss housework (55.6% vs 16.5%), p<0.01 to <0.0001.,Events similar to exacerbations of COPD can occur in individuals without COPD or asthma and are associated with significant health and socioeconomic outcomes.,They increase the respiratory burden in the community and may contribute to the false-positive diagnosis of asthma or COPD. | Never smokers comprise a substantial proportion of patients with COPD.,Their characteristics and possible risk factors in this population are not yet well defined.,We analyzed data from 14 countries that participated in the international, population-based Burden of Obstructive Lung Disease (BOLD) study.,Participants were aged ≥ 40 years and completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors.,A diagnosis of COPD was based on the postbronchodilator FEV1/FVC ratio, according to current GOLD (Global Initiative for Obstructive Lung Disease) guidelines.,In addition to this, the lower limit of normal (LLN) was evaluated as an alternative threshold for the FEV1/FVC ratio.,Among 4,291 never smokers, 6.6% met criteria for mild (GOLD stage I) COPD, and 5.6% met criteria for moderate to very severe (GOLD stage II+) COPD.,Although never smokers were less likely to have COPD and had less severe COPD than ever smokers, never smokers nonetheless comprised 23.3% (240/1,031) of those classified with GOLD stage II+ COPD.,This proportion was similar, 20.5% (171/832), even when the LLN was used as a threshold for the FEV1/FVC ratio.,Predictors of COPD in never smokers include age, education, occupational exposure, childhood respiratory diseases, and BMI alterations.,This multicenter international study confirms previous evidence that never smokers comprise a substantial proportion of individuals with COPD.,Our data suggest that, in addition to increased age, a prior diagnosis of asthma and, among women, lower education levels are associated with an increased risk for COPD among never smokers. | 1 |
Given the dearth of COPD self-management interventions that specifically acknowledge multi-morbidity in primary care, we aimed to activate COPD patients through personalised self-management support that recognised the implications of co-morbidities.,This single-group experimental study included patients aged 40−84 with a spirometry diagnosis of COPD and at least one co-morbidity.,A self-management education programme for COPD in the context of multi-morbidity, based on the Health Belief Model, was tailored and delivered to participants by general practice nurses in face-to-face sessions.,At 6 months’ follow-up, there was significant improvement in patient activation (p < 0.001), COPD-related quality of life (p = 0.012), COPD knowledge (p < 0.001) and inhaler device technique (p = 0.001), with no significant change in perception of multi-morbidity (p = 0.822) or COPD-related multi-morbidity (0.084).,The programme improved patients’ self-efficacy for their COPD as well as overall health behaviour.,The findings form an empirical basis for further testing the programme in a large-scale randomised controlled trial. | The complexity of breathlessness in advanced disease requires a diversity of measures ideally tailored to the individual patient needs.,‘Breathlessness services’ have been systematically developed and tested to provide specific interventions and support for patients and their carers.,The aim of this article is (1) to identify and describe components of breathlessness services and (2) to describe the clinical model of one specific service in more detail.,This article is based on a systematic review evaluating randomized controlled trials (RCTs) and quasi-RCTs which examine the effectiveness of services aiming to improve breathlessness of patients with advanced disease.,The Munich Breathlessness Service (MBS) is described in detail as an example of a recently set-up specialist service.,Five service models were identified which were tested in six RCTs.,Services varied regarding structure and composition with face-to-face meetings, some with additional telephone contacts.,Service duration was median 6 weeks (range 2-12 weeks).,Involved professions were nurses, various therapists and, in two models, also physicians.,The breathing-thinking-functioning model was targeted by various service components.,The MBS is run by a multi-professional team mainly with physicians and physiotherapists.,Patients are seen weekly over 5-6 weeks with an individualized management plan.,Breathlessness services are a new model for patients with advanced disease integrating symptom management and early access to palliative care. | 1 |
The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally. | Ventilation/perfusion (V/P) single-photon emission computed tomography (SPECT) is recognized as a diagnostic method with potential beyond the diagnosis of pulmonary embolism.,V/P SPECT identifies functional impairment in diseases such as heart failure (HF), pneumonia, and chronic obstructive pulmonary disease (COPD).,The development of hybrid SPECT/computed tomography (CT) systems, combining functional with morphological imaging through the addition of low-dose CT (LDCT), may be useful in COPD, as these patients are prone to lung cancer and other comorbidities.,The aim of this study was to investigate the added value of LDCT among healthy smokers and patients with stable COPD, when examined with V/P SPECT/CT hybrid imaging.,Sixty-nine subjects, 55 with COPD (GOLD I-IV) and 14 apparently healthy smokers, were examined with V/P SPECT and LDCT hybrid imaging.,Spirometry was used to verify COPD grade.,Only one apparently healthy smoker and three COPD patients had a normal or nearly normal V/P SPECT.,All other patients showed various degrees of airway obstruction, even when spirometry was normal.,The same interpretation was reached on both modalities in 39% of the patients.,LDCT made V/P SPECT interpretation more certain in 9% of the patients and, in 52%, LDCT provided additional diagnoses.,LDCT better characterized the type of emphysema in 12 patients.,In 19 cases, tumor-suspected changes were reported.,Three of these 19 patients (ie, 4.3% of all subjects) were in the end confirmed to have lung cancer.,The majority of LDCT findings were not regarded as clinically significant.,V/P SPECT identified perfusion patterns consistent with decompensated left ventricular HF in 14 COPD patients.,In 16 patients (23%), perfusion defects were observed.,HF and perfusion defects were not recognized with LDCT.,In COPD patients and long-time smokers, hybrid imaging had added value compared to V/P SPECT alone, by identifying patients with lung malignancy and more clearly identifying emphysema.,V/P SPECT visualizes comorbidities to COPD not seen with LDCT, such as pulmonary embolism and left ventricular HF. | 1 |
Several composite markers have been proposed for risk assessment in chronic obstructive pulmonary disease (COPD).,However, choice of parameters and score complexity restrict clinical applicability.,Our aim was to provide and validate a simplified COPD risk index independent of lung function.,The PROMISE study (n=530) was used to develop a novel prognostic index.,Index performance was assessed regarding 2-year COPD-related mortality and all-cause mortality.,External validity was tested in stable and exacerbated COPD patients in the ProCOLD, COCOMICS and COMIC cohorts (total n=2988).,Using a mixed clinical and statistical approach, body mass index (B), severe acute exacerbations of COPD frequency (AE), modified Medical Research Council dyspnoea severity (D) and copeptin (C) were identified as the most suitable simplified marker combination. 0, 1 or 2 points were assigned to each parameter and totalled to B-AE-D or B-AE-D-C.,It was observed that B-AE-D and B-AE-D-C were at least as good as BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity), ADO (age, dyspnoea, airflow obstruction) and DOSE (dyspnoea, obstruction, smoking, exacerbation) indices for predicting 2-year all-cause mortality (c-statistic: 0.74, 0.77, 0.69, 0.72 and 0.63, respectively; Hosmer-Lemeshow test all p>0.05).,Both indices were COPD specific (c-statistic for predicting COPD-related 2-year mortality: 0.87 and 0.89, respectively).,External validation of B-AE-D was performed in COCOMICS and COMIC (c-statistic for 1-year all-cause mortality: 0.68 and 0.74; c-statistic for 2-year all-cause mortality: 0.65 and 0.67; Hosmer-Lemeshow test all p>0.05).,The B-AE-D index, plus copeptin if available, allows a simple and accurate assessment of COPD-related risk.,The B-AE-D indices allow a simple and accurate assessment of COPD-related risk in the absence of lung functionhttp://ow.ly/XFBox | Chronic obstructive pulmonary disease (COPD) is characterized by irreversible, progressive obstruction of lung airflow.,Dyspnea (shortness of breath [SOB]) is the COPD symptom which most negatively impacts patients’ daily activities.,To assess how SOB affects daily activities, 37 items were drafted through focus group discussions and cognitive interviews with COPD patients to develop a patient-reported outcome instrument: the Shortness of Breath with Daily Activities questionnaire (SOBDA).,Psychometric analysis was conducted to reduce the number of items and evaluate the measurement properties of the final SOBDA.,Prospective, observational study of 334 COPD patients, recruited from 24 pulmonology and internal medicine clinics in the United States.,The 37-item SOBDA was administered to patients each evening for 28 days using an electronic diary.,Patients answered every item and rated their level of SOB experienced that day during specific activities.,Item selection was conducted by examining item characteristics, dimensionality, and Rasch model analysis results.,The decision to delete an item was based on psychometric evidence, content validity, and expert clinical input.,The final SOBDA instrument was evaluated for internal consistency, reproducibility, convergent validity, known-groups validity, and responsiveness.,Twenty-four items from the 37-item pool were removed following the item selection process: nine items were removed due to high item-to-item correlations; five due to floor effects; three due to infrequent activity; one due to gender bias; two due to low factor loadings; three due to unordered response options; and one due to expert’s discretion.,Internal consistency and reproducibility of the final SOBDA were demonstrated by Cronbach Alpha = 0.87, and intra-class correlation coefficient = 0.91.,Convergent validity was demonstrated by high correlation with the CRQ-SAS (0.60) and SGRQ-C (0.61).,Known groups validity was demonstrated by significant difference between ratings of the mMRC and clinical global rating of severity.,Evaluation of the ability to detect change was not performed owing to too few responders at the end of the study.,Through the empirical item reduction process, 13 items were selected from the 37-item pool generated during qualitative development.,The final 13-item SOBDA is a reliable and valid instrument for use in clinical trials. | 1 |
This study explored the relationship between the fractional exhaled nitric oxide (FeNO) level and the efficacy of inhaled corticosteroid (ICS) in asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) patients with different disease severity.,A total of 127 ACOS patients with ACOS (case group) and 131 healthy people (control group) were enrolled in this study.,Based on the severity of COPD, the ACOS patients were divided into: mild ACOS; moderate ACOS; severe ACOS; and extremely severe ACOS groups.,We compared FeNO levels, pulmonary function parameters including percentage of forced expiratory volume in 1 second (FEV1) to predicted value (FEV1%pred), ratio of FEV1 to forced vital capacity (FEV1/FVC), inspiratory capacity to total lung capacity (IC/TLC) and residual volume to total lung capacity (RV/TLC), arterial blood gas parameters, including PH, arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2), total serum immunoglobulin E (IgE), induced sputum eosinophil (EOS), plasma surfactant protein A (SP-A), plasma soluble receptor for advanced glycation end products (sRAGE), sputum myeloperoxidase (MPO), sputum neutrophil gelatinase-associated lipocalin (NGAL) and Asthma Control Test (ACT) scores, and COPD Assessment Test (CAT) scores.,Compared with pre-treatment parameters, the FeNO levels, RV/TLC, PaCO2, total serum IgE, induced sputum EOS, plasma SP-A, sputum MPO, sputum NGAL, and CAT scores were significantly decreased after 6 months of ICS treatment, while FEV1%pred, FEV1/FVC, IC/TLC, PH, PaO2, plasma sRAGE, and ACT scores were significantly increased in ACOS patients with different disease severity after 6 months of ICS treatment.,This finding suggests that the FeNO level may accurately predict the efficacy of ICS in the treatment of ACOS patients. | Asthma-COPD overlap syndrome (ACOS) is a commonly encountered chronic airway disease.,However, ACOS is still a consensus-based clinical phenotype and the underlying inflammatory mechanisms are inadequately characterized.,To clarify the inflammatory mediatypical for ACOS, five biomarkers, namely interleukin (IL)-13, myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), chitinase-like protein (YKL-40), and IL-6, were selected.,This study hypothesized that sputum biomarkers relevant for airway inflammation in asthma (IL-13), COPD (MPO, NGAL), or in both asthma and COPD (YKL-40, IL-6) could be used to differentiate ACOS from COPD and asthma.,The aim of this study was to characterize the inflammatory profile and improve the recognition of ACOS.,Induced sputum levels of IL-13, MPO, NGAL, YKL-40, and IL-6 were measured by enzyme-linked immunosorbent assay/Luminex assay in a Finnish discovery cohort (n=90) of nonsmokers, smokers, and patients with asthma, COPD, and ACOS and validated in a Japanese cohort (n=135).,The classification accuracy of potential biomarkers was compared with area under the receiver operating characteristic curves.,Only sputum NGAL levels could differentiate ACOS from asthma (P<0.001 and P<0.001) and COPD (P<0.05 and P=0.002) in the discovery and replication cohorts, respectively.,Sputum NGAL levels were independently correlated with the percentage of pre-bronchodilator forced expiratory volume in 1 second predicted in multivariate analysis in the discovery and replication cohorts (P=0.001 and P=0.002, respectively).,In conclusion, sputum biomarkers reflecting both airway inflammation and remodeling of the tissue show potential in differentiation between asthma, COPD, and ACOS. | 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. | Induced and spontaneous sputum are used to evaluate the airways microbiota.,Whether the sputum types can be used interchangeably in microbiota research is unknown.,Our aim was to compare microbiota in induced and spontaneous sputum from COPD patients sampled during the same consultation.,COPD patients from Bergen, Norway, were followed between 2006/2010, examined during the stable state and exacerbations. 30 patients delivered 36 sample pairs.,DNA was extracted by enzymatic and mechanical lysis methods.,The V3-V4 region of the 16S rRNA gene was PCR-amplified and prepared for paired-end sequencing.,Illumina Miseq System was used for sequencing, and Quantitative Insights Into Microbial Ecology (QIIME) and Stata were used for bioinformatics and statistical analyses.,Approximately 4 million sequences were sorted into 1004 different OTUs and further assigned to 106 different taxa.,Pair-wise comparison of both taxonomic composition and beta-diversity revealed significant differences in one or both parameters in 1/3 of sample pairs.,Alpha-diversity did not differ.,Comparing abundances for each taxa identified, showed statistically significant differences between the mean abundances in induced versus spontaneous samples for 15 taxa when disease state was considered.,This included potential pathogens like Haemophilus and Moraxella.,When studying microbiota in sputum samples one should take into consideration how samples are collected and avoid the usage of both induced and spontaneous sputum in the same study. | 1 |
Inhaled drug delivery is the cornerstone treatment for asthma and chronic obstructive pulmonary disease (COPD).,However, use of inhaler devices can be challenging, potentially leading to critical errors in handling that can significantly reduce drug delivery to the lungs and effectiveness of treatment.,A systematic review was conducted to define ‘critical’ errors and their impact on health outcomes and resource use between 2004 and 2016, using key search terms for inhaler errors in asthma and COPD (Search-1) and associated health-economic and patient burden (Search-2).,Search-1 identified 62 manuscripts, 47 abstracts, and 5 conference proceedings (n = 114 total).,Search-2 identified 9 studies.,We observed 299 descriptions of critical error.,Age, education status, previous inhaler instruction, comorbidities and socioeconomic status were associated with worse handling error frequency.,A significant association was found between inhaler errors and poor disease outcomes (exacerbations), and greater health-economic burden.,We have shown wide variations in how critical errors are defined, and the evidence shows an important association between inhaler errors and worsened health outcomes.,Given the negative impact diminished disease outcomes impose on resource use, our findings highlight the importance of achieving optimal inhaler technique, and a need for a consensus on defining critical and non-critical errors.,The online version of this article (10.1186/s12931-017-0710-y) contains supplementary material, which is available to authorized users. | Poor adherence to inhaled therapy is common in patients with asthma and COPD.,An inhaler selection based on patients’ preference could be beneficial to adherence and treatment effectiveness.,Properly designed questionnaires can assess patients’ satisfaction with their medication devices.,The aim of this study was to estimate, using the Feeling of Satisfaction with Inhaler (FSI-10) questionnaire, the ease of use and satisfaction of patients regarding three different marketed dry powder inhalers (DPIs): Diskus® (DK), Elpenhaler® (EH), and Turbuhaler® (TH).,The FSI-10 is a self-completed questionnaire to assess patients’ opinions regarding ease of use, portability, and usability of devices, irrespective of the drug used.,We performed a 4-week, open, noninterventional, multicenter, parallel clinical study in 560 asthmatic and 561 COPD patients.,During the first visit, patients were classified into three groups according to the DPI they were already using.,Patients were regularly receiving their treatments (Seretide DK, Rolenium EH, and Symbicort TH) and agreed to complete the FSI-10 questionnaire in the second visit.,A total of 517 COPD and 523 asthma patients completed the study.,All DPIs tested received satisfactory results, while the EH obtained consistently higher scores in the FSI-10 in both COPD and asthma patients (44.7 and 44.1 vs 41.5 and 43 for TH, 40.8 and 41.4 for DK, P<0.001 and P<0.01, respectively).,TH was rated better than DK by asthma patients.,Patients suffering with severe COPD tended to express higher feeling of satisfaction than those with moderate or mild disease, irrespective of the device used.,All DPIs tested were highly acceptable by asthma and COPD patients of different ages; nevertheless, EH received significantly higher ratings in most of the questionnaire domains.,COPD patients in advanced stages of the disease generally expressed higher level of satisfaction with their devices. | 1 |
Pulmonary artery enlargement (PAE) is associated with exacerbations in Chronic Obstructive Pulmonary Disease (COPD) and with survival in moderate to severe patients.,The potential role of PAE in survival prediction has not been compared with other clinical and physiological prognostic markers.,In 188 patients with COPD, PA diameter was measured on a chest CT and the following clinical and physiological parameters registered: age, gender, smoking status, pack-years history, dyspnea, lung function, exercise capacity, Body Mass Index, BODE index and history of exacerbations in year prior to enrolment.,Proportional Cox regression analysis determined the best predictor of all cause survival.,During 83 months (±42), 43 patients died.,Age, pack-years history, smoking status, BMI, FEV1%, six minute walking distance, Modified Medical Research Council dyspnea scale, BODE index, exacerbation rate prior to enrollment, PA diameter and PAE (diameter≥30mm) were associated with survival.,In the multivariable analysis, age (HR: 1.08; 95%CI: 1.03-1.12, p<0.001) and PAE (HR: 2.78; 95%CI: 1.35-5.75, p = 0.006) were the most powerful parameters associated with all-cause mortality.,In this prospective observational study of COPD patients with mild to moderate airflow limitation, PAE was the best predictor of long-term survival along with age. | The COPD assessment test (CAT) score is a key component of the multifactorial assessment of COPD in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidelines of 2014.,Nevertheless, little is known regarding the differences among COPD categories in terms of clinical parameters such as pulmonary function or radiological findings.,Thus, our aims in this study were to evaluate the associations between CAT scores and pulmonary clinical parameters, and to investigate factors that could discriminate between a “less symptomatic group” (categories A and C) and a “more symptomatic group” (categories B and D) among stable COPD patients.,We enrolled 200 outpatients at Chiba University Hospital.,Study subjects were assessed by CAT, pulmonary function testing, and multidetector computed tomography (MDCT).,We assessed possible correlations between these indices.,CAT scores were negatively correlated with percentage of the forced expiratory volume in 1 second predicted value (FEV1 %predicted) and percentage of the diffusing capacity for carbon monoxide per liter of lung volume predicted value (DLCO/VA [%predicted]) results and positively correlated with low attenuation volume percentage (LAV%) and residual volume to total lung capacity ratios (RV/TLC).,In the “more symptomatic group” (category B or D), the mean DLCO/VA (%predicted) was significantly lower and the mean LAV% and RV/TLC was significantly higher than those in the “less symptomatic group” (category A or C), respectively.,Interestingly, those in category B had higher mean LAV% compared to those in category C.,CAT scores were significantly correlated with pulmonary function parameters and emphysematous changes on MDCT.,The new GOLD classification system would be a step toward a phenotypic approach, especially taking into account the degree of emphysema and hyperinflation. | 1 |
Although chronic obstructive pulmonary disease (COPD) is a major global health burden there is a lack of patient awareness of disease severity, particularly in relation to exacerbations.,We conducted a global patient survey using an innovative, internet-based methodology to gain insight into patient perceptions of COPD and exacerbations in a real-world sample typical of today’s working-age COPD population.,Two thousand patients with COPD (53%), chronic bronchitis (52%) and/or emphysema (22%) from 14 countries completed an online questionnaire developed by the authors.,The Medical Research Council (MRC) breathlessness scale was used to delineate symptom severity.,Over three quarters of patients (77%) had experienced an exacerbation, with 27% of MRC 1 and 2 patients and 52% of MRC 3, 4 and 5 patients requiring hospitalization as a result of an exacerbation.,While a majority of MRC 1 and 2 patients (51%) reported being back to normal within a few days of an exacerbation, 23% of MRC 3, 4 and 5 patients took several weeks to return to normal and 6% never fully recovered.,A high proportion of patients (39%) took a ‘wait and see’ approach to exacerbations.,Despite the high prevalence of exacerbations and their negative impact on quality of life, 73% of MRC 1 and 2 patients and 64% of MRC 3, 4 and 5 patients felt that they had control of their COPD.,However, 77% of all patients were worried about their long-term health, and 38% of MRC 1 and 2 patients and 59% of MRC 3, 4 and 5 patients feared premature death due to COPD.,To reduce the adverse effects of COPD on patients’ quality of life and address their fears for the future, we need better patient education and improved prevention and treatment of exacerbations. | This study was conducted to describe the different antibiotics that are used in the home management of chronic obstructive pulmonary disease (COPD) exacerbations and to estimate the failure rates following the initiation of the antibiotic.,A cohort study was conducted.,Patients enrolled in a COPD home management program were included in the analysis.,Failure rates were defined as an additional prescription of an antibiotic, an emergency room visit, or a hospitalization for a COPD exacerbation in the 30 days following the initiation of the antibiotic.,A total of 1180 episodes of antibiotic treatment were analyzed.,Overall, 348 episodes led to a failure (29.5%).,The most frequently used antibiotics were cefuroxime (45.9%) and ciprofloxacin (21.1%).,This project demonstrates that a wide range of antibiotics were prescribed to our population of COPD patients with a moderate to severe form of the disease.,Many treatment failures (about 30%) occurred in the 30-day period following the initiation of the home therapy with an antibiotic.,Clinicians should be aware of this high failure rate when managing mild exacerbations of COPD at home. | 1 |
Little is known about the microbiota shift induced by exacerbation in chronic obstructive pulmonary disease (COPD) patients.,The sputa microbiota of COPD patients was evaluated when clinically stable and during acute exacerbations of the disease.,Sputa microbiota was analyzed using 16S ribosomal RNA gene pyrosequencing and quantitative polymerase chain reaction-based pathogen detection.,Nine COPD patients were enrolled.,Pyrosequencing of 16S rRNA genes identified 2,267 unique bacterial operational taxonomic units.,Principal microbiota shifts during exacerbation were in either Proteobacteria, Firmicutes or Bacteroidetes.,Streptococcus and Moraxella levels were detected during exacerbation in severe (Global Initiative for Chronic Obstructive Lung Disease 3) COPD patients.,Most of the clinically-important genera found in the sputum with the pyrosequencing of 16S rRNA gene correlated with specific quantitative polymerase chain reactions for bacteria while respiratory viruses were nearly absent.,Sputum microbiotas of exacerbated COPD patients are complex.,This pilot study shows a clear shift in the microbiota of patients during exacerbation.,The nature of this shift varies from patient to patient in such a way that the treatment should be patient-specific.,Further studies are needed to establish the impact of microbial exacerbations on the pulmonary microbiota. | COPD is the third leading cause of death in the world and its global burden is predicted to increase further.,Even though the prevalence of COPD is well studied, only few studies examined the incidence of COPD in a prospective and standardized manner.,In a prospective population-based cohort study (Rotterdam Study) enrolling subjects aged ≥45, COPD was diagnosed based on a pre-bronchodilator obstructive spirometry (FEV1/FVC < 0.70).,In absence of an interpretable spirometry within the Rotterdam Study, cases were defined as having COPD diagnosed by a physician on the basis of clinical presentation and obstructive lung function measured by the general practitioner or respiratory physician.,Incidence rates were calculated by dividing the number of incident cases by the total number of person years of subjects at risk.,In this cohort of 14,619 participants, 1993 subjects with COPD were identified of whom 689 as prevalent ones and 1304 cases as incident ones.,The overall incidence rate (IR) of COPD was 8.9/1000 person-years (PY); 95 % Confidence Interval (CI) 8.4-9.4.,The IR was higher in males and in smokers.,The proportion of female COPD participants without a history of smoking was 27.2 %, while this proportion was 7.3 % in males.,The prevalence of COPD in the Rotterdam Study is 4.7 % and the overall incidence is approximately 9/1000 PY, with a higher incidence in males and in smokers.,The proportion of never-smokers among female COPD cases is substantial.,The online version of this article (doi:10.1007/s10654-016-0132-z) contains supplementary material, which is available to authorized users. | 1 |
Sputum eosinophilia occurs in approximately one-third of stable chronic obstructive pulmonary disease (COPD) patients and can predict exacerbation risk and response to corticosteroid treatments.,Sputum induction, however, requires expertise, may not always be successful, and does not provide point-of-care results.,Easily applicable diagnostic markers that can predict sputum eosinophilia in stable COPD patients have the potential to progress COPD management.,This study investigated the correlation and predictive relationship between peripheral blood and sputum eosinophils.,It also examined the repeatability of blood eosinophil counts.,Stable COPD patients (n=141) were classified as eosinophilic or noneosinophilic based on their sputum cell counts (≥3%), and a cross-sectional analysis was conducted comparing their demographics, clinical characteristics, and blood cell counts.,Receiver operating characteristic curve analysis was used to assess the predictive ability of blood eosinophils for sputum eosinophilia.,Intraclass correlation coefficient was used to examine the repeatability of blood eosinophil counts.,Blood eosinophil counts were significantly higher in patients with sputum eosinophilia (n=45) compared to those without (0.3×109/L vs 0.15×109/L; P<0.0001).,Blood eosinophils correlated with both the percentage (ρ=0.535; P<0.0001) and number of sputum eosinophils (ρ=0.473; P<0.0001).,Absolute blood eosinophil count was predictive of sputum eosinophilia (area under the curve =0.76, 95% confidence interval [CI] =0.67-0.84; P<0.0001).,At a threshold of ≥0.3×109/L (specificity =76%, sensitivity =60%, and positive likelihood ratio =2.5), peripheral blood eosinophil counts enabled identification of the presence or absence of sputum eosinophilia in 71% of the cases.,A threshold of ≥0.4×109/L had similar classifying ability but better specificity (91.7%) and higher positive likelihood ratio (3.7).,In contrast, ≥0.2×109/L offered a better sensitivity (91.1%) for ruling out sputum eosinophilia.,There was a good agreement between two measurements of blood eosinophil count over a median of 28 days (intraclass correlation coefficient =0.8; 95% CI =0.66-0.88; P<0.0001).,Peripheral blood eosinophil counts can help identify the presence or absence of sputum eosinophilia in stable COPD patients with a reasonable degree of accuracy. | Smoking effects on physiological and gross pathology in chronic obstructive pulmonary disease (COPD) are relatively well described.,However, there is little known in COPD about the detailed interrelationships between lung function and inflammatory profiles in different airway compartments from the same individual and whether airway inflammation in these different compartments differs in ex- and current smokers with established COPD.,We compared sputum, bronchoalveolar (BAL), and airway wall inflammatory profiles in current versus ex-smokers and related this to smoking intensity and lung function in 17 current and 17 ex-smokers with mild to moderate COPD.,Current smokers had more sputum mast cells (% differential and absolute numbers), whereas ex-smokers had increased sputum neutrophils.,In BAL, there was a significant increase in eosinophils in current smokers, but ex-smokers had significantly increased neutrophils, lymphocytes, and epithelial cells.,There were no cell profile differences observed in airway biopsies between current and ex-smokers and there were no correlations between the individual inflammatory cell populations in any of the airway compartments.,In current smokers only, smoking intensity was negatively correlated with lung function, and associated with a reduction in overall cellularity of both sputum and BAL.,Airway inflammation persists in ex-smokers with COPD, but differs from COPD current smokers.,The impact of smoking appears to vary in different airway compartments and any direct relationships between cellularity and lung function tended to be negative, ie, worse lung function indicated the presence of fewer cells. | 1 |
Smoking is the main risk factor for chronic obstructive pulmonary disease (COPD).,Women with COPD who smoke experienced a higher risk of hospitalization and worse decline of lung function.,Yet the mechanisms of these gender-related differences in clinical presentations in COPD remain unknown.,The aim of our study is to identify proteins and molecular pathways associated with COPD pathogenesis, with emphasis on elucidating molecular gender difference.,We employed shotgun isobaric tags for relative and absolute quantitation (iTRAQ) proteome analyses of bronchoalveolar lavage (BAL) cells from smokers with normal lung function (n = 25) and early stage COPD patients (n = 18).,Multivariate modeling, pathway enrichment analysis, and correlation with clinical characteristics were performed to identify specific proteins and pathways of interest.,More pronounced alterations both at the protein- and pathway- levels were observed in female COPD patients, involving dysregulation of the FcγR-mediated phagocytosis-lysosomal axis and increase in oxidative stress.,Alterations in pathways of the phagocytosis-lysosomal axis associated with a female-dominated COPD phenotype correlated well with specific clinical features: FcγR-mediated phagocytosis correlated with FEV1/FVC, the lysosomal pathway correlated with CT < −950 Hounsfield Units (HU), and regulation of actin cytoskeleton correlated with FEV1 and FEV1/FVC in female COPD patients.,Alterations observed in the corresponding male cohort were minor.,The identified molecular pathways suggest dysregulation of several phagocytosis-related pathways in BAL cells in female COPD patients, with correlation to both the level of obstruction (FEV1/FVC) and disease severity (FEV1) as well as emphysema (CT < −950 HU) in women.,No.: NCT02627872, retrospectively registered on December 9, 2015.,The online version of this article (10.1186/s12931-017-0699-2) contains supplementary material, which is available to authorized users. | Smoking represents a significant risk factor for many chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD).,To identify dysregulation of specific proteins and pathways in bronchoalveolar lavage (BAL) cells associated with smoking, isobaric tags for relative and absolute quantitation (iTRAQ)-based shotgun proteomics analyses were performed on BAL cells from healthy never-smokers and smokers with normal lung function from the Karolinska COSMIC cohort.,Multivariate statistical modeling, multivariate correlations with clinical data, and pathway enrichment analysis were performed.,Smoking exerted a significant impact on the BAL cell proteome, with more than 500 proteins representing 15 molecular pathways altered due to smoking.,The majority of these alterations occurred in a gender-independent manner.,The phagosomal- and leukocyte trans endothelial migration (LTM) pathways significantly correlated with FEV1/FVC as well as the percentage of CD8+ T-cells and CD8+CD69+ T-cells in smokers.,The correlations to clinical parameters in healthy never-smokers were minor.,The significant correlations of proteins in the phagosome- and LTM pathways with activated cytotoxic T-cells (CD69+) and the level of airway obstruction (FEV1/FVC) in smokers, both hallmarks of COPD, suggests that these two pathways may play a role in the molecular events preceding the development of COPD in susceptible smokers.,Both pathways were found to be further dysregulated in COPD patients from the same cohort, thereby providing further support to this hypothesis.,Given that not all smokers develop COPD in spite of decades of smoking, it is also plausible that some of the molecular pathways associated with response to smoking exert protective mechanisms to smoking-related pathologies in resilient individuals.,ClinicalTrials.gov identifier NCT02627872; Retrospectively registered on December 9, 2015.,The online version of this article (10.1186/s12931-017-0695-6) contains supplementary material, which is available to authorized users. | 1 |
COPD accounts for the highest rate of hospital admissions among major chronic diseases.,COPD hospitalizations are associated with impaired quality of life, high health care utilization, and poor prognosis and result in an economic and a social burden that is both substantial and increasing.,The aim of this study is to determine the efficacy of a comprehensive case management program (CCMP) in reducing length of stay (LOS) and risk of hospital admissions and readmissions in patients with COPD.,We retrospectively compared outcomes across five large hospitals in Vancouver, BC, Canada, following the implementation of a systems approach to the management of COPD patients who were identified in the hospital and followed up in the community for 90 days.,We compared numbers, rates, and intervals of readmission and LOS during 2 years of active program delivery compared to 1 year prior to program implementation.,A total of 1,564 patients with a clinical diagnosis of COPD were identified from 2,719 hospital admissions during the 3 years of study.,The disease management program reduced COPD-related hospitalizations by 30% and hospitalizations for all causes by 13.6%.,Similarly, the rate of readmission for all causes showed a significant decline, with hazard ratios (HRs) of 0.55 (year 1) and 0.51 (year 2) of intervention (P<0.001).,In addition, patients’ mean LOS (days) for COPD-related admissions declined significantly from 10.8 to 6.8 (P<0.05).,A comprehensive disease management program for COPD patients, including education, case management, and follow-up, was associated with significant reduction in hospital admissions and LOS. | Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients.,Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype.,This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes.,These patients are therefore a priority for research and treatment.,The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection.,Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment.,Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype.,This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.,The online version of this article (doi:10.1186/1741-7015-11-181) contains supplementary material, which is available to authorized users. | 1 |
Blood biomarkers are increasingly used to stratify high risk chronic obstructive pulmonary disease (COPD) patients; however, there are fewer studies that have investigated multiple biomarkers and replicated in multiple large well-characterized cohorts of susceptible current and former smokers.,We used two MSD multiplex panels to measure 9 cytokines and chemokines in 2123 subjects from COPDGene and 1117 subjects from SPIROMICS.,These biomarkers included: interleukin (IL)-2, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, eotaxin/CCL-11, eotaxin-3/CCL-26, and thymus and activation-regulated chemokine (TARC)/CCL-17.,Regression models adjusted for clinical covariates were used to determine which biomarkers were associated with the following COPD phenotypes: airflow obstruction (forced expiratory flow at 1 s (FEV1%) and FEV1/forced vital capacity (FEV1/FVC), chronic bronchitis, COPD exacerbations, and emphysema.,Biomarker-genotype associations were assessed by genome-wide association of single nucleotide polymorphisms (SNPs).,Eotaxin and IL-6 were strongly associated with airflow obstruction and accounted for 3-5% of the measurement variance on top of clinical variables.,IL-6 was associated with progressive airflow obstruction over 5 years and both IL-6 and IL-8 were associated with progressive emphysema over 5 years.,None of the biomarkers were consistently associated with chronic bronchitis or COPD exacerbations.,We identified one novel SNP (rs9302690 SNP) that was associated with CCL17 plasma measurements.,When assessing smoking related pulmonary disease, biomarkers of inflammation such as IL-2, IL-6, IL-8, and eotaxin may add additional modest predictive value on top of clinical variables alone.,COPDGene (ClinicalTrials.gov Identifier: NCT02445183).,Subpopulations and Intermediate Outcomes Measures in COPD Study (SPIROMICS) (ClinicalTrials.gov Identifier: NCT 01969344).,The online version of this article (10.1186/s12931-017-0662-2) contains supplementary material, which is available to authorized users. | Non-typeable Haemophilus influenza (NTHi) infection is common in COPD.,Corticosteroids can have limited therapeutic effects in COPD patients.,NTHi causes corticosteroid insensitive cytokine production from COPD alveolar macrophages.,We investigated the mechanisms by which NTHi causes corticosteroid insensitive inflammatory responses, and the effects of NTHi exposure on COPD macrophage polarisation.,Alveolar macrophages from COPD patients and controls were exposed to NTHi in conjunction with the corticosteroid dexamethasone and/or the p38 MAPK inhibitor BIRB-796.,Cytokine release, GR phosphorylation and modulation and macrophage phenotype were analysed.,Dexamethasone significantly inhibited NTHi induced TNF-α, IL-6 and IL-10 from COPD macrophages but, CXCL8 was not suppressed.,BIRB-796 combined with dexamethasone caused significantly greater inhibition of all cytokines than either drug alone (p < 0.05 all comparisons).,NTHi caused phosphorylation of GR S226 reducing GR nuclear localisation, an effect regulated by p38 MAPK.,NTHi altered macrophage polarisation by increasing IL-10 and decreasing CD36, CD206, CD163 and HLA-DR.,NTHi exposure causes p38 MAPK dependent GR phosphorylation associated with decreased GR function in COPD alveolar macrophages.,Combining a p38 MAPK inhibitor with corticosteroids can enhance anti-inflammatory effects during NTHi exposure of COPD alveolar macrophages.,NTHi causes macrophage polarisation that favours bacterial persistence.,The online version of this article (doi:10.1186/s12931-017-0539-4) contains supplementary material, which is available to authorized users. | 1 |
The risk of exacerbation in chronic obstructive pulmonary disease (COPD) depends on the severity of disease and other less well known factors.,Predictive models of exacerbation are more accurate than the forced expiratory volume in one second (FEV1).,The objective was to design a model that predicts the risk of exacerbation in COPD.,Retrospective cohort study with data from the electronic medical records of patients diagnosed with COPD in the province of Lleida (Spain).,A total of 2501 patients were followed during 3 years.,The dependent variable was acute exacerbation; independent variables were: clinical parameters, spirometry results, severity of disease, influenza and 23-valent pneumococcal immunisation, comorbidities, smoking and history of exacerbation.,The association of these variables with disease exacerbation was measured by the adjusted odds ratio using a logistic regression model.,Mean age at the start of the study was 68.38 years (SD = 11.60) and 74.97 % patients were men; severity of disease was considered mild in 50.82 % of patients, moderate in 35.31 %, severe in 9.44 % and very severe in 4.44 %.,During the three year study period up to 83.17 % of patients experienced at least one exacerbation.,Predictive factors in the model were age, gender, previous exacerbations, influenza and 23-valent pneumococcal immunisations, number of previous visits to the General Practice and severity (GOLD), with an area under the ROC curve (AUROC) of 0.70.,This model can identify patients at high risk of acute exacerbation.,Preventive measures and modification of treatment in these high-risk patients would improve survival. | Patients with COPD have high risk for osteoporosis and fractures.,Hip and vertebral fractures might impair mobility, and vertebral fractures further reduce lung function.,This review discusses the evidence of bone loss due to medical treatment opposed to disease severity and risk factors for COPD, and therapeutic options for the prevention and treatment of osteoporosis in these patients.,A review of the English-language literature was conducted using the MEDLINE database until June 2009.,Currently used bronchodilators probably lack adverse effect on bone.,Oral corticosteroids (OCS) increase bone resorption and decrease bone formation in a dose response relationship, but the fracture risk is increased more than reflected by bone densitometry.,Inhaled corticosteroids (ICS) have been associated with both increased bone loss and fracture risk.,This might be a result of confounding by disease severity, but high doses of ICS have similar effects as equipotent doses of OCS.,The life-style factors should be modified, use of regular OCS avoided and use of ICS restricted to those with evidenced effect and probably kept at moderate doses.,The health care should actively reveal risk factors, include bone densitometry in fracture risk evaluation, and give adequate prevention and treatment for osteoporosis. | 1 |
Background: Combination therapy with a long-acting bronchodilator and an inhaled corticosteroid (ICS) is recommended in patients with chronic obstructive pulmonary disease (COPD) who have frequent exacerbations.,The efficacy and tolerability of the combination of budesonide/formoterol have been demonstrated in patients with COPD when administered via the dry powder inhaler (DPI) in a 1-year study and when administered via the hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) in a 6-month study.,Objective: This study assessed the long-term efficacy and tolerability of budesonide/formoterol HFA pMDI in patients with moderate to very severe COPD.,Methods: This was a 12-month, randomized, double-blind, double-dummy, parallel-group, active- and placebo-controlled, multicentre study (NCT00206167) of 1964 patients aged ≥40 years with moderate to very severe COPD conducted from 2005 to 2007 at 237 sites in the US, Europe and Mexico.,After 2 weeks of treatment based on previous therapy (ICSs, short-acting bronchodilators allowed), patients received one of the following treatments twice daily: budesonide/formoterol pMDI 160/4.5 μg × two inhalations (320/9 μg); budesonide/formoterol pMDI 80/4.5 μg × two inhalations (160/9 μg); formoterol DPI 4.5 μg × two inhalations (9 μg); or placebo.,Main outcome measures: The co-primary efficacy variables were pre-dose forced expiratory volume in 1 second (FEV1) and 1-hour post-dose FEV1.,Results: Budesonide/formoterol 320/9 μg demonstrated greater improvements in pre-dose FEV1 versus formoterol (p = 0.008), and both budesonide/formoterol doses demonstrated greater improvements in 1-hour post-dose FEV1 versus placebo (p < 0.001).,The rate of COPD exacerbations was lower in both budesonide/formoterol groups compared with formoterol and placebo (p ≤ 0.004).,Both budesonide/formoterol doses were more effective than placebo (p ≤ 0.006) for controlling dyspnoea and improving health status (St George’s Respiratory Questionnaire).,All treatments were generally well tolerated.,The incidence of pneumonia was not different for active (3.4-4.0%) and placebo (5.0%) groups.,Conclusions: Budesonide/formoterol pMDI (320/9 μg and 160/9 μg) improved pulmonary function and reduced symptoms and exacerbations over 1 year in patients with moderate to very severe COPD.,Only budesonide/formoterol pMDI 320/9 μg demonstrated greater efficacy for both co-primary variables compared with formoterol DPI 9 μg.,Both budesonide/formoterol pMDI dosages were well tolerated relative to formoterol and placebo.,Supplementary material is available for this article at 10.2165/00003495-200969050-00004 and is accessible for authorized users. | Pooled data were analyzed to evaluate the safety and tolerability of indacaterol, a once-daily inhaled long-acting β2-agonist for chronic obstructive pulmonary disease (COPD).,Data were pooled from clinical studies of 3-12 months’ duration in patients with moderate-to-severe COPD receiving double-blind indacaterol 75 μg (n = 449), 150 μg (n = 2611), 300 μg (n = 1157), or 600 μg once daily (n = 547); formoterol 12 μg twice daily (n = 556); salmeterol 50 μg twice daily (n = 895); placebo (n = 2012); or tiotropium 18 μg once daily, given open label or blinded (n = 1214).,Outcomes were adverse events, serious adverse events and deaths, plasma potassium, blood glucose, and QTc interval and vital signs.,The commonest adverse events with indacaterol were COPD worsening, nasopharyngitis, and headache; most cases were mild or moderate and incidence was generally similar to placebo and other active treatments.,The risk of acute respiratory serious adverse events (leading to hospitalization, intubation, or death) was not significantly increased with any of the active treatments compared with placebo.,COPD exacerbation rates (analyzed in the intent-to-treat population) were significantly reduced with all active treatments versus placebo.,Hazard ratios versus placebo for major cardiovascular adverse events were <1 for all indacaterol doses.,Notable values for vital signs and measures of systemic β2-adrenoceptor activity were rare with indacaterol.,The number of deaths adjusted per patient-year was lower with indacaterol (all doses combined) than with placebo (relative risk 0.21 [95% confidence interval 0.07-0.660], P = 0.008).,Indacaterol has a good profile of safety and tolerability that is appropriate for the maintenance treatment of 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. | 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. | 1 |
Using data from the Continuing to Confront COPD International Physician and Patient Surveys, this paper describes physicians’ attitudes and beliefs regarding chronic obstructive pulmonary disease (COPD) prognosis, and compares physician and patient perceptions with respect to COPD.,In 12 countries worldwide, 4,343 patients with COPD were identified through systematic screening of population samples, and 1,307 physicians who regularly saw patients with COPD were sampled from in-country professional databases.,Both patients and physicians completed surveys about their COPD knowledge, beliefs, and perceptions; physicians answered further questions about diagnostic methods and treatment choices for COPD.,Most physicians (79%) responded that the long-term health outlook for patients with COPD has improved over the past decade, largely attributed to the introduction of better medications.,However, patient access to medication remains an issue in many countries, and some physicians (39%) and patients (46%) agreed/strongly agreed with the statement “there are no truly effective treatments for COPD”.,There was strong concordance between physicians and patients regarding COPD management practices, including the use of spirometry (86% of physicians and 76% of patients reporting they used/had undergone a spirometry test) and smoking cessation counseling (76% of physicians reported they counseled their smoking patients at every clinic visit, and 71% of smoking patients stated that they had received counseling in the past year).,However, the groups differed in their perception about the role of smoking in COPD, with 78% of physicians versus 38% of patients strongly agreeing with the statement “smoking is the cause of most cases of COPD”.,The Continuing to Confront COPD International Surveys demonstrate that while physicians and patients largely agreed about COPD management practices and the need for more effective treatments for COPD, a gap exists about the causal role of smoking in COPD. | Chronic obstructive pulmonary disease (COPD) is an obstructive and progressive airway disease associated with an important reduction in daily physical activity and psychological problems that contribute to the patient’s disability and poor health-related quality of life (HRQoL).,Nowadays, pulmonary rehabilitation (PR) plays an essential role in the management of symptomatic patients with COPD, by breaking the vicious circle of dyspnea-decreased activity-deconditioning-isolation.,Indeed the main benefits of comprehensive PR programs for patients with COPD include a decrease in symptoms (dyspnea and fatigue), improvements in exercise tolerance and HRQoL, reduction of health care utilization (particularly bed-days), as well as an increase in physical activity.,Several randomized studies and meta-analyses greatly established the benefits of PR, which additionally, is recommended in a number of influential guidelines.,This review aimed to highlight the impact of PR on COPD patients, focusing on the clinical usefulness of PR, which provides patients a good support for change. | 1 |
The study investigates which physical performance or muscle function/mass tests significantly correlate with objectively measured physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD) and could potentially serve to identify physically inactive COPD patients in routine clinical practice.,A cross-sectional, observational study was conducted in outpatients with moderate to very severe COPD.,PA was measured during one week with the StepWatch Activity Monitor®, an ankle-worn accelerometer, and expressed in steps per day.,Physical fitness and peripheral muscle function/mass were evaluated by the 4-meter gait speed (4MGS) test, the 6-minute walk distance (6MWD), the 30-second chair stand test (30sCST), the timed up and go test (TUGT), handgrip strength, arm muscle area, calf circumference, the fat-free mass index (FFMI), and ultrasound measurement of the quadriceps muscle.,Spearman’s rank correlation analysis and ROC analysis were performed.,The study population (N=111, 69% men, mean age 68 years) walked a mean of 8059 steps/day.,The daily step count strongly correlated with the 6MWD (rho=0.684, p<0.001) and moderately with the 4MGS (rho=0.464, p<0.001), the TUGT (rho= −0.463, p<0.001), and the 30sCST (rho=0.402, p<0.001).,The correlation with the FFMI was weak (rho=0.210, p=0.027), while the other parameters did not significantly correlate with the daily step count.,The 6MWD had the best discriminative power to identify patients with very low PA defined as <5000 steps/day (AUC=0.802 [95% CI: 0.720-0.884], p<0.001), followed by the TUGT, the 4MGS, and the 30sCST.,The 6MWD, the 4MGS, the TUGT, and the 30sCST are easy to perform in any clinical setting and may be used by clinicians in the screening of physically inactive COPD patients. | No current patient-centred instrument captures all dimensions of physical activity in chronic obstructive pulmonary disease (COPD).,Our objective was item reduction and initial validation of two instruments to measure physical activity in COPD.,Physical activity was assessed in a 6-week, randomised, two-way cross-over, multicentre study using PROactive draft questionnaires (daily and clinical visit versions) and two activity monitors.,Item reduction followed an iterative process including classical and Rasch model analyses, and input from patients and clinical experts.,236 COPD patients from five European centres were included.,Results indicated the concept of physical activity in COPD had two domains, labelled “amount” and “difficulty”.,After item reduction, the daily PROactive instrument comprised nine items and the clinical visit contained 14.,Both demonstrated good model fit (person separation index >0.7).,Confirmatory factor analysis supported the bidimensional structure.,Both instruments had good internal consistency (Cronbach's α>0.8), test-retest reliability (intraclass correlation coefficient ≥0.9) and exhibited moderate-to-high correlations (r>0.6) with related constructs and very low correlations (r<0.3) with unrelated constructs, providing evidence for construct validity.,Daily and clinical visit “PROactive physical activity in COPD” instruments are hybrid tools combining a short patient-reported outcome questionnaire and two activity monitor variables which provide simple, valid and reliable measures of physical activity in COPD patients.,Both PROactive hybrid tools are simple, valid, and reliable measures of physical activity in COPD patientshttp://ow.ly/LJqP8 | 1 |
The efficacy of inhaled salmeterol plus fluticasone propionate (SFC) in patients with severe or very severe COPD is well documented.,However, there are only limited data about the influence of GOLD severity staging on the effectiveness of SFC, particularly in patients with milder disease.,TORCH was a 3-year, double-blind, placebo-controlled trial of 6112 patients with moderate/severe COPD with pre-bronchodilator FEV1 < 60% predicted (mean age 65 years, 76% male, mean 44% predicted FEV1, 43% current smokers).,To understand the relative efficacy of SFC and its components by GOLD stages, we conducted a post-hoc analysis of the TORCH dataset using baseline post-bronchodilator FEV1 to segment patients into three groups: moderate COPD (GOLD stage II and above: ≥ 50%; n = 2156), severe COPD (GOLD stage III: 30% to < 50%; n = 3019) and very severe COPD (GOLD stage IV: < 30%; n = 937).,Compared with placebo, SFC improved post-bronchodilator FEV1: 101 ml (95% confidence interval [CI]: 71, 132) in GOLD stage II, 82 ml (95% CI: 60, 104) in GOLD stage III and 96 ml (95% CI: 54, 138) in GOLD stage IV patients, and reduced the rate of exacerbations: 31% (95% CI: 19, 40) in GOLD stage II, 26% (95% CI: 17, 34) in GOLD stage III and 14% (95% CI: -4, 29) in GOLD stage IV.,SFC improved health status to a greater extent than other treatments regardless of baseline GOLD stage.,Similarly, SFC reduced the risk of death by 33% (hazard ratio [HR] 0.67; 95% CI: 0.45, 0.98) for GOLD stage II, 5% (HR 0.95; 95% CI: 0.73, 1.24) for GOLD stage III, and 30% (HR 0.70; 95% CI: 0.47, 1.05) for GOLD stage IV.,The rates of adverse events were similar across treatment arms and increased with disease severity.,Overall, there was a higher incidence of pneumonia in the fluticasone propionate and SFC arms, compared with other treatments in all GOLD stages.,In the TORCH study, SFC reduced moderate-to-severe exacerbations and improved health status and FEV1 across GOLD stages.,Treatment with SFC may be associated with reduced mortality compared with placebo in patients with GOLD stage II disease.,The effects were similar to those reported for the study as a whole.,Thus, SFC is an effective treatment option for patients with GOLD stage II COPD.,Clinicaltrial.gov registration NCT00268216; Study number: SCO30003 | Influencing the progression of COPD has long been an elusive goal of drug therapy.,Directly or indirectly, this has again been investigated in two of the largest, long-term drug trials in COPD: Towards a Revolution in COPD Health (TORCH) and Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT®).,Neither trial achieved statistical significance in their respective primary outcomes; however, both make considerable contributions to understanding of how the progression of COPD may be influenced.,The objective of this article is to review the data from these different trials with a view to what can be learnt about the management of COPD.,The long-term improvements in lung function, health-related quality of life, and possibly survival from the use of long-acting bronchodilators in these trials suggest an influence on progression of the disease.,With the more optimistic view of benefits from drug treatment of COPD that these trials provide, a review of prescribing practices is warranted. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality.,COPD is typified by persistent, progressive airflow limitation and a range of respiratory and systemic symptoms such as breathlessness, coughing, wheezing, depression, anxiety, general fatigue, and sleeping difficulties.,Despite receiving treatment for COPD, many patients suffer from regular symptoms that affect their daily lives and lead to increased morbidity.,These symptoms vary in severity, frequency, and type, and can occur at any time throughout the 24-h day, with over half of patients with COPD experiencing symptoms in the morning, during the day, and at nighttime.,Despite the prevalence of symptoms, patient and physician perception of the impact of COPD symptoms on patients’ lives is not always in concordance.,Dual bronchodilator therapy with a long-acting muscarinic antagonist (LAMA) and long-acting beta agonist (LABA) has the potential to treat the symptoms of COPD in addition to improving lung function.,This review therefore examines the burden of symptoms experienced throughout the day by patients with COPD and the evidence for combined LAMA/LABA treatment in terms of symptom management.,As patients with COPD experience varying symptoms throughout the course of their disease, the role of tailoring treatment to the individual needs of the patient is also examined.,We conclude that the symptoms of COPD are troublesome, variable, can occur during all parts of the 24-h day, and have a substantial impact on patients’ health status and quality of life.,In order to provide effective, patient-orientated care, patients with COPD should be evaluated on the basis of lung function, the frequency of symptoms, and patient-perceived impact of symptoms on their lives.,Therapy should be chosen carefully based on individualized assessment, ensuring personalization to the individual needs of the patient. | The GOLD guidelines suggest that the presence of a post-bronchodilator forced expiratory volume in one second (FEV1) < 80% of the predicted value in combination with a FEV1/forced vital capacity (FVC) < 70% confirms the diagnosis of COPD.,Limited data exist regarding the accuracy of these criteria to distinguish between COPD and asthma.,The aim of this study therefore was to investigate the diagnostic value of post-bronchodilator lung function parameters in obstructive lung disease.,The pulmonary function tests of 43 (22 = COPD, 21 = asthma) patients with similar baseline characteristics were evaluated (baseline FEV1 were 55.7% ± 7.6%, and 59.3% ± 8.4% predicted for COPD and asthma, respectively).,Bronchodilator responsiveness (BDR) was calculated according to three recognized pulmonary function test criteria.,The first criteria, post-bronchodilator FEV1 < 80% of the predicted value in combination with a post-bronchodilator FEV1/FVC ratio of <70%, had an accuracy of 70% to diagnose COPD.,This combination was very sensitive (100%) in diagnosing COPD, but it was not specific (38%).,The second BDR criteria, defined as an increase of <12% and 200 mL of initial FEV1 and criterion number 3, an increase of < 9% of predicted FEV1, were less sensitive (55% and 59%, respectively), but more specific (81% and 76% respectively) to diagnose COPD.,Our findings suggest that the current recommended spirometric indices are not optimal in differentiating between COPD and asthma. | 1 |
TELOS compared budesonide (BD)/formoterol fumarate dihydrate (FF) metered dose inhaler (BFF MDI), formulated using innovative co-suspension delivery technology that enables consistent aerosol performance, with its monocomponents and budesonide/formoterol fumarate dihydrate dry powder inhaler (DPI) in patients with moderate to very severe chronic obstructive pulmonary disease (COPD), without a requirement for an exacerbation history.,In this phase III, double-blind, parallel-group, 24-week study (NCT02766608), patients were randomised to BFF MDI 320/10 µg (n=664), BFF MDI 160/10 µg (n=649), FF MDI 10 µg (n=648), BD MDI 320 µg (n=209) or open-label budesonide/formoterol DPI 400/12 µg (n=219).,Primary end-points were change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) and FEV1 area under the curve from 0-4 h (AUC0-4).,Time to first and rate of moderate/severe exacerbations were assessed.,BFF MDI 320/10 µg improved pre-dose trough FEV1 versus FF MDI (least squares mean (LSM) 39 mL; p=0.0018), and BFF MDI 320/10 µg and 160/10 µg improved FEV1 AUC0-4 versus BD MDI (LSM 173 mL and 157 mL, respectively; both p<0.0001) at week 24.,BFF MDI 320/10 µg and 160/10 µg improved time to first and rate of moderate/severe exacerbations versus FF MDI.,Treatments were well tolerated, with pneumonia incidence ranging from 0.5-1.4%.,BFF MDI improved lung function versus monocomponents and exacerbations versus FF MDI in patients with moderate to very severe COPD.,TELOS: co-suspension delivery technology budesonide/formoterol fumarate dihydrate in a metered dose inhaler improved lung function and time to first and rate of exacerbations versus monocomponents in patients with moderate to very severe COPDhttp://ow.ly/ffWo30lrJL6 | Background: Combination therapy with a long-acting bronchodilator and an inhaled corticosteroid (ICS) is recommended in patients with chronic obstructive pulmonary disease (COPD) who have frequent exacerbations.,The efficacy and tolerability of the combination of budesonide/formoterol have been demonstrated in patients with COPD when administered via the dry powder inhaler (DPI) in a 1-year study and when administered via the hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) in a 6-month study.,Objective: This study assessed the long-term efficacy and tolerability of budesonide/formoterol HFA pMDI in patients with moderate to very severe COPD.,Methods: This was a 12-month, randomized, double-blind, double-dummy, parallel-group, active- and placebo-controlled, multicentre study (NCT00206167) of 1964 patients aged ≥40 years with moderate to very severe COPD conducted from 2005 to 2007 at 237 sites in the US, Europe and Mexico.,After 2 weeks of treatment based on previous therapy (ICSs, short-acting bronchodilators allowed), patients received one of the following treatments twice daily: budesonide/formoterol pMDI 160/4.5 μg × two inhalations (320/9 μg); budesonide/formoterol pMDI 80/4.5 μg × two inhalations (160/9 μg); formoterol DPI 4.5 μg × two inhalations (9 μg); or placebo.,Main outcome measures: The co-primary efficacy variables were pre-dose forced expiratory volume in 1 second (FEV1) and 1-hour post-dose FEV1.,Results: Budesonide/formoterol 320/9 μg demonstrated greater improvements in pre-dose FEV1 versus formoterol (p = 0.008), and both budesonide/formoterol doses demonstrated greater improvements in 1-hour post-dose FEV1 versus placebo (p < 0.001).,The rate of COPD exacerbations was lower in both budesonide/formoterol groups compared with formoterol and placebo (p ≤ 0.004).,Both budesonide/formoterol doses were more effective than placebo (p ≤ 0.006) for controlling dyspnoea and improving health status (St George’s Respiratory Questionnaire).,All treatments were generally well tolerated.,The incidence of pneumonia was not different for active (3.4-4.0%) and placebo (5.0%) groups.,Conclusions: Budesonide/formoterol pMDI (320/9 μg and 160/9 μg) improved pulmonary function and reduced symptoms and exacerbations over 1 year in patients with moderate to very severe COPD.,Only budesonide/formoterol pMDI 320/9 μg demonstrated greater efficacy for both co-primary variables compared with formoterol DPI 9 μg.,Both budesonide/formoterol pMDI dosages were well tolerated relative to formoterol and placebo.,Supplementary material is available for this article at 10.2165/00003495-200969050-00004 and is accessible for authorized users. | 1 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.