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Ferroptosis is a necrotic form of regulated cell death (RCD) mediated by phospholipid peroxidation in association with free iron-mediated Fenton reactions.,Disrupted iron homeostasis resulting in excessive oxidative stress has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD).,Here, we demonstrate the involvement of ferroptosis in COPD pathogenesis.,Our in vivo and in vitro models show labile iron accumulation and enhanced lipid peroxidation with concomitant non-apoptotic cell death during cigarette smoke (CS) exposure, which are negatively regulated by GPx4 activity.,Treatment with deferoxamine and ferrostatin-1, in addition to GPx4 knockdown, illuminate the role of ferroptosis in CS-treated lung epithelial cells.,NCOA4-mediated ferritin selective autophagy (ferritinophagy) is initiated during ferritin degradation in response to CS treatment.,CS exposure models, using both GPx4-deficient and overexpressing mice, clarify the pivotal role of GPx4-regulated cell death during COPD.,These findings support a role for cigarette smoke-induced ferroptosis in the pathogenesis of COPD.,Altered iron homeostasis resulting in excessive oxidative stress has been implicated in smoke-induced lung diseases.,Here the authors show that ferroptosis of lung epithelial cells, potentially resulting from excessive ferritinophagy, is involved in the pathogenesis of COPD. | Chronic obstructive pulmonary disease (COPD) is predicted to become the third most common cause of death and the fifth most common cause of disability in the world by 2020.,Recently, variants in the hypoxia-inducible factor 1α (HIF1A), cholinergic receptor, neuronal nicotinic, alpha polypeptide-5, and iron-responsive element-binding protein 2 gene (IREB2) genes were found to be associated with COPD.,This study aims to identify whether the variations in these genes are related to COPD in the Hainan population of the People’s Republic of China.,We genotyped 12 single nucleotide polymorphisms in a case-control study with 200 COPD cases and 401 controls from Hainan, People’s Republic of China.,Odds ratios and 95% confidence intervals were estimated using the chi-squared (χ2) test, genetic model analysis, haplotype analysis, and stratification analysis.,In the genetic model analysis, we found that the genotype T/T of rs13180 of IREB2 decreased the COPD risk by 0.52-fold (P=0.025).,But in the further stratification analysis, we failed to find the association between the selected single nucleotide polymorphisms with COPD risk in Han population.,In addition, the haplotype analysis of HIF1A gene also was not found to be the possible haplotype associated with COPD risk.,Our results support that IREB2 rs13180 is associated with COPD in Hainan population.,And this is the first time the HIF1A polymorphisms in COPD in a Chinese population has been reported, although we failed to find any significant result. | 1 |
Real-world prescription pathways leading to triple therapy (TT) (inhaled corticosteroid [ICS] plus long-acting β2-agonist bronchodilator [LABA] plus long-acting muscarinic antagonist) differ from Global initiative for chronic Obstructive Lung Disease [GOLD] and National Institute for Health and Care Excellence treatment recommendations.,This study sets out to identify COPD patients without asthma receiving TT, and determine the pathways taken from diagnosis to the first prescription of TT.,This was a historical analysis of COPD patients without asthma from the Optimum Patient Care Research Database (387 primary-care practices across the UK) from 2002 to 2010.,Patient disease severity was classified using GOLD 2013 criteria.,Data were analyzed to determine prescribing of TT before, at, and after COPD diagnosis; the average time taken to receive TT; and the impact of lung function grade, modified Medical Research Council dyspnea score, and exacerbation history on the pathway to TT.,During the study period, 32% of patients received TT.,Of these, 19%, 28%, 37%, and 46% of patients classified as GOLD A, B, C, and D, respectively, progressed to TT after diagnosis (P<0.001).,Of all patients prescribed TT, 25% were prescribed TT within 1 year of diagnosis, irrespective of GOLD classification (P=0.065).,The most common prescription pathway to TT was LABA plus ICS.,It was observed that exacerbation history did influence the pathway of LABA plus ICS to TT.,Real life UK prescription data demonstrates the inappropriate prescribing of TT and confirms that starting patients on ICS plus LABA results in the inevitable drift to overuse of TT.,This study highlights the need for dissemination and implementation of COPD guidelines to physicians, ensuring that patients receive the recommended therapy. | Exacerbations of chronic obstructive pulmonary disease (COPD) are natural events in the progression of the disease, and are characterised by acute worsening of symptoms, especially dyspnoea.,These heterogeneous events follow increased airway inflammation, often due to infection, and lead to decreased airflow and increased lung hyperinflation relative to stable COPD.,Although exacerbation frequency generally increases as COPD progresses, some patients experience frequent exacerbations (≥2 per year) independently of disease severity.,Exacerbations, especially frequent exacerbations, are associated with impaired health-related quality of life, reduced physical activity and poor disease prognosis.,The cornerstone of pharmacotherapy for stable COPD is long-acting bronchodilators, including the long-acting β2-agonists (LABAs) and long-acting anti-muscarinic agents (LAMAs) alone or combined with inhaled corticosteroids (ICS).,While ICS treatment can potentially reduce the risk of exacerbations, clinical studies have demonstrated the efficacy of LABAs and LAMAs in reducing COPD symptoms, primarily by reducing lung hyperinflation secondary to reduced airway resistance.,Sustained reduction in lung hyperinflation may in turn lessen dyspnoea during an exacerbation.,Indeed, recent studies suggest that bronchodilators may also reduce the incidence of, or prevent, exacerbations.,Using data from recent studies, this review explores the evidence and possible mechanisms through which bronchodilators may prevent exacerbations. | 1 |
The aim of this study was to compare potential differences between the perception that COPD patients have of their disease and the perception that physicians have of how the disease affects their patients.,Surveys in COPD patients and physicians caring for COPD patients were conducted in Spain, Italy, and Germany.,Online questionnaires mirrored to explore the same domains, were administered to patients and physicians.,Physicians were asked to respond to the questionnaire taking a recently seen patient who represents the majority of COPD patients usually managed, as a reference.,Patients with COPD completed a survey containing the same questions offered to the physicians (Medical Investigation of Respiratory COPD Perception [MIRROR] survey).,Comparisons between the responses of patients and general practitioners (GPs) and between patients and pulmonologists (PULs) were run separately using the chi-square, Fisher’s exact, or Student’s t-tests.,A total of 334 COPD patients, 333 GPs, and 333 PULs participated in the surveys.,The typical perception that PULs have of the COPD patient was that of an older man with more severe disease and less likely to be a smoker, than the included COPD patients.,COPD was regarded as a major health problem by patients and physicians, but its impact on overall quality of life among more severe patients was less strongly perceived by physicians than by patients.,Instead, physicians paid more attention to domains related to clinical features (cough, phlegm, and dyspnea), while underestimating COPD impact on leisure and social activities.,The majority of patients stated not being completely frank with their doctors during visits.,Both GPs and PULs seemed to recognize this issue but underestimated its extent.,To improve the doctor-patient communication, a more frank reporting by the patients of their symptoms and feelings and an increased awareness of physicians about the impact on nonconventional domains that patients perceive as importantly affected by COPD should be encouraged. | Chronic obstructive pulmonary disease (COPD) is a very prevalent and invalidating disease.,The aim of this study was to analyze the burden borne by informal caregivers of patients with COPD.,We used the Survey on Disabilities, Personal Autonomy, and Dependency Situations (Encuesta sobre Discapacidad, Autonomía personal y Situaciones de Dependencia [EDAD]-2008) to obtain information on the characteristics of disabled individuals with COPD and their caregivers in Spain.,Additionally, statistical multivariate analyses were performed to analyze the impact that an increase in dependence would have on the problems for which caregivers provide support, in terms of health, professional, and leisure/social dimensions.,A total of 461,884 individuals with one or more disabilities and with COPD were identified, and 220,892 informal caregivers were estimated.,Results showed that 35% of informal caregivers had health-related problems due to the caregiving provided; 83% had leisure/social-related problems; and among caregivers of working age, 38% recognized having profession-related problems.,The probability of a problem arising was significantly associated with the degree of dependence of the patient receiving care.,Caregivers of patients with great dependence showed a 39% higher probability of presenting health-related problems, 27% more professional problems, and 23% more leisure problems compared with those with nondependent patients.,The results show the large impact on society in terms of the welfare of informal caregivers of patients with COPD.,A higher level of dependence was associated with more severe problems in caregivers, in all dimensions. | 1 |
We tested the role of endothelial dysfunction in the development of COPD/emphysema.,We found that restoration of lung endothelial cells and blockade of endothelial-derived leucine-rich α-2-glycoprotein perturbs the pathogenesis of COPD/emphysema.,Chronic obstructive pulmonary disease (COPD) is marked by airway inflammation and airspace enlargement (emphysema) leading to airflow obstruction and eventual respiratory failure.,Microvasculature dysfunction is associated with COPD/emphysema.,However, it is not known if abnormal endothelium drives COPD/emphysema pathology and/or if correcting endothelial dysfunction has therapeutic potential.,Here, we show the centrality of endothelial cells to the pathogenesis of COPD/emphysema in human tissue and using an elastase-induced murine model of emphysema.,Airspace disease showed significant endothelial cell loss, and transcriptional profiling suggested an apoptotic, angiogenic, and inflammatory state.,This alveolar destruction was rescued by intravenous delivery of healthy lung endothelial cells.,Leucine-rich α-2-glycoprotein-1 (LRG1) was a driver of emphysema, and deletion of Lrg1 from endothelial cells rescued vascular rarefaction and alveolar regression.,Hence, targeting endothelial cell biology through regenerative methods and/or inhibition of the LRG1 pathway may represent strategies of immense potential for the treatment of COPD/emphysema. | De novo lymphatic vessel formation has recently been observed in lungs of patients with moderate chronic obstructive pulmonary disease (COPD).,However, the distribution of lymphatic vessel changes among the anatomical compartments of diseased lungs is unknown.,Furthermore, information regarding the nature of lymphatic vessel alterations across different stages of COPD is missing.,This study performs a detailed morphometric characterization of lymphatic vessels in major peripheral lung compartments of patients with different severities of COPD and investigates the lymphatic expression of molecules involved in immune cell trafficking.,Peripheral lung resection samples obtained from patients with mild (GOLD stage I), moderate-severe (GOLD stage II-III), and very severe (GOLD stage IV) COPD were investigated for podoplanin-immunopositive lymphatic vessels in distinct peripheral lung compartments: bronchioles, pulmonary blood vessels and alveolar walls.,Control subjects with normal lung function were divided into never smokers and smokers.,Lymphatics were analysed by multiple morphological parameters, as well as for their expression of CCL21 and the chemokine scavenger receptor D6.,The number of lymphatics increased by 133% in the alveolar parenchyma in patients with advanced COPD compared with never-smoking controls (p < 0.05).,In patchy fibrotic lesions the number of alveolar lymphatics increased 20-fold from non-fibrotic parenchyma in the same COPD patients.,The absolute number of lymphatics per bronchiole and artery was increased in advanced COPD, but numbers were not different after normalization to tissue area.,Increased numbers of CCL21- and D6-positive lymphatics were observed in the alveolar parenchyma in advanced COPD compared with controls (p < 0.01).,Lymphatic vessels also displayed increased mean levels of immunoreactivity for CCL21 in the wall of bronchioles (p < 0.01) and bronchiole-associated arteries (p < 0.05), as well as the alveolar parenchyma (p < 0.001) in patients with advanced COPD compared with never-smoking controls.,A similar increase in lymphatic D6 immunoreactivity was observed in bronchioles (p < 0.05) and alveolar parenchyma (p < 0.01).,This study shows that severe stages of COPD is associated with increased numbers of alveolar lymphatic vessels and a change in lymphatic vessel phenotype in major peripheral lung compartments.,This novel histopathological feature is suggested to have important implications for distal lung immune cell traffic in advanced COPD. | 1 |
COPD is a major global cause of mortality and morbidity.,PINNACLE-4 evaluated the efficacy and safety of GFF MDI (glycopyrrolate/formoterol fumarate metered dose inhaler) in patients from Asia, Europe, and the USA with moderate-to-very severe COPD.,In this double-blind, placebo-controlled, Phase III study, patients were randomized to treatment with GFF MDI 18/9.6 μg, glycopyrrolate (GP) MDI 18 μg, formoterol fumarate (FF) MDI 9.6 μg, or placebo MDI (all twice daily) for 24 weeks.,Lung function, patient-reported outcomes (symptoms and health-related quality of life), and safety were assessed.,Of the 1,756 patients randomized, 1,740 patients were included in the intent-to-treat population (mean age 64.2 years, 74.1% male, and 40.2% Asian).,GFF MDI significantly improved morning predose trough FEV1 at Week 24 (primary endpoint) vs placebo MDI, GP MDI, and FF MDI (least squares mean differences: 165, 59, and 72 mL, respectively; all P<0.0001).,GFF MDI also significantly improved other lung function endpoints vs placebo MDI, GP MDI, and FF MDI and patient-reported outcomes vs placebo MDI and GP MDI.,A larger proportion of patients treated with GFF MDI achieved the minimum clinically important difference in Transition Dyspnea Index score vs GP MDI and placebo MDI and in St George’s Respiratory Questionnaire score vs placebo MDI.,Adverse event rates were similar across treatment groups.,These results demonstrated the efficacy of GFF MDI in patients with moderate-to-very severe COPD.,GFF MDI was well tolerated, with a safety profile commensurate with long-acting bronchodilators. | We report the results of the first direct comparison of the once-daily fixed-dose long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) combinations umeclidinium/vilanterol (UMEC/VI) and tiotropium/olodaterol (TIO/OLO) in patients with COPD.,This was a randomized, two-period crossover open-label study in symptomatic patients with COPD [age 40 years or older, postbronchodilator forced expiratory volume in 1 s (FEV1) of 70% or less and 50% or more of predicted normal values, and modified Medical Research Council Dyspnoea Scale score of 2 or greater] not receiving inhaled corticosteroid therapy.,Patients were randomized to receive UMEC/VI (62.5/25 µg once daily) via a multidose dry powder inhaler (ELLIPTA) followed by TIO/OLO (5/5 µg once daily) via a soft mist inhaler (Respimat), each for 8 weeks with an interim 3-week washout or vice versa.,The primary end point was the change from baseline in trough FEV1 at week 8 with a noninferiority margin of − 50 mL in the per-protocol (PP) population.,The incidence of adverse events was also assessed.,In total, 236 patients (mean age 64.4 years, 60% male) were included in the intent-to-treat population and 227 were included in the PP population.,UMEC/VI treatment was noninferior in the PP population and superior in the intent-to-treat population to TIO/OLO treatment with regard to trough FEV1 at week 8 [FEV1 change from baseline 180 mL vs 128 mL; difference 52 mL (95% confidence interval 28-77 mL); p < 0.001].,Patients receiving UMEC/VI had twofold increased odds of experiencing a clinically meaningful increase (100 mL or more) from baseline in trough FEV1 at week 8 compared with patients receiving TIO/OLO (odds ratio 2.05; 95% confidence interval 1.34-3.14).,Adverse events occurred in 25% of patients in the UMEC/VI group and in 31% of patients in the TIO/OLO group.,In this first direct comparison of two once-daily fixed-dose LAMA/LABA combinations, superiority was observed for the primary end point of trough FEV1 at week 8 with UMEC/VI compared with TIO/OLO in patients with symptomatic COPD.,Both treatments had similar safety profiles.,These findings confirm the results of previous indirect LAMA/LABA comparisons, and show that an efficacy gradient exists within the LAMA/LABA class.,ClinicalTrials.gov identifier NCT02799784.,GlaxoSmithKline.,The online version of this article (doi:10.1007/s12325-017-0626-4) contains supplementary material, which is available to authorized users. | 1 |
Microspirometry may be useful as the second stage of a screening pathway among patients reporting respiratory symptoms.,We assessed sensitivity and specificity of the Vitalograph® lung monitor compared with post-bronchodilator confirmatory spirometry (ndd Easy on-PC) among primary care chronic obstructive pulmonary disease (COPD) patients within the Birmingham COPD cohort.,We report a case-control analysis within 71 general practices in the UK.,Eligible patients were aged ≥40 years who were either on a clinical COPD register or reported chronic respiratory symptoms on a questionnaire.,Participants performed pre- and post-bronchodilator microspirometry, prior to confirmatory spirometry.,Out of the 544 participants, COPD was confirmed in 337 according to post-bronchodilator confirmatory spirometry.,Pre-bronchodilator, using the LLN as a cut-point, the lung monitor had a sensitivity of 50.5% (95% CI 45.0%, 55.9%) and a specificity of 99.0% (95% CI 96.6%, 99.9%) in our sample.,Using a fixed ratio of FEV1/FEV6 < 0.7 to define obstruction in the lung monitor, sensitivity increased (58.8%; 95% CI 53.0, 63.8) while specificity was virtually identical (98.6%; 95% CI 95.8, 99.7).,Within our sample, the optimal cut-point for the lung monitor was FEV1/FEV6 < 0.78, with sensitivity of 82.8% (95% CI 78.3%, 86.7%) and specificity of 85.0% (95% CI 79.4%, 89.6%).,Test performance of the lung monitor was unaffected by bronchodilation.,The lung monitor could be used in primary care without a bronchodilator using a simple ratio of FEV1/FEV6 as part of a screening pathway for COPD among patients reporting respiratory symptoms. | Chronic obstructive pulmonary disease (COPD) is one of the main contributors to the global burden of disease.,The aim of this systematic review was to quantify the disease burden of COPD in China and to determine the risk factors of the disease.,The number of studies included in the review was 47 with an average quality assessment score of 7.70 out of 10.,Reported COPD prevalence varied between 1.20% and 8.87% in different provinces/cities across China.,The prevalence rate of COPD was higher among men (7.76%) than women (4.07%).,The disease was more prevalent in rural areas (7.62%) than in urban areas (6.09%).,The diagnostic rate of COPD patients in China varied from 23.61% to 30.00%.,The percentage of COPD patients receiving outpatient treatment was around 50%, while the admission rate ranged between 8.78% and 35.60%.,Tobacco exposure and biomass fuel/solid fuel usage were documented as two important risk factors of COPD.,COPD ranked among the top three leading causes of death in China.,The direct medical cost of COPD ranged from 72 to 3,565 USD per capita per year, accounting for 33.33% to 118.09% of local average annual income.,The most commonly used scales for the assessment of quality of life (QoL) included Saint George Respiratory Questionnaire, Airways Questionnaire 20, SF-36, and their revised versions.,The status of QoL was worse among COPD patients than in non-COPD patients, and COPD patients were at higher risks of depression.,The COPD burden in China was high in terms of economic burden and QoL.,In view of the high smoking rate and considerable concerns related to air pollution and smog in China, countermeasures need to be taken to improve disease prevention and management to reduce disease burdens raised by COPD. | 1 |
The prescription of physical activity for hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) can be complicated by the presence of comorbidities.,The current research aimed to synthesize the relevant literature on the benefits of exercise for people with multimorbidities who experience an AECOPD, and ask: What are the parameters and outcomes of exercise in AECOPD and in conditions that are common comorbidities as reported by systematic reviews (SRs)?,An SR was performed using the Cochrane Collaboration protocol.,Nine electronic databases were searched up to July 2011.,Articles were included if they (1) described participants with AECOPD, chronic obstructive pulmonary disease (COPD), or one of eleven common comorbidities, (2) were an SR, (3) examined aerobic training (AT), resistance training (RT), balance training (BT), or a combination thereof, (4) included at least one outcome of fitness, and (5) compared exercise training versus control/sham.,This synthesis examined 58 SRs of exercise training in people with AECOPD, COPD, or eleven chronic conditions commonly associated with COPD.,Meta-analyses of endurance (aerobic or exercise capacity, 6-minute walk distance - 6MWD) were shown to significantly improve in most conditions (except osteoarthritis, osteoporosis, and depression), whereas strength was shown to improve in five of the 13 conditions searched: COPD, older adults, heart failure, ischemic heart disease, and diabetes.,Several studies of different conditions also reported improvements in quality of life, function, and control or prevention outcomes.,Meta-analyses also demonstrate that exercise training decreases the risk of mortality in older adults, and those with COPD or ischemic heart disease.,The most common types of training were AT and RT.,BT and functional training were commonly applied in older adults.,The quality of the SRs for most conditions was moderate to excellent (>65%) as evaluated by AMSTAR scores.,In summary, this synthesis showed evidence of significant benefits from exercise training in AECOPD, COPD, and conditions that are common comorbidities.,A broader approach to exercise and activity prescription in pulmonary rehabilitation may induce therapeutic benefits to ameliorate clinical sequelae associated with AECOPD and comorbidities such as the inclusion of BT and functional training. | Chronic obstructive pulmonary disease (COPD) remains a major public health problem that affects the quality of life of patients, however smoking cessation may emeliorate the functional effects of COPD and alter patient quality of life.,The aim of this study was to validate the Clinical COPD Questionnaire (CCQ) into Greek and with such to evaluate the quality of life in patients with different stages of COPD, as also assess their quality of life before and after smoking cessation.,The internal validity of questionnaire was high (Cronbach's a = 0.92).,The reliability of equivalent types in 16 stabilized patients also was high (ICC = 0.99).,In general the domains within the CCQ were strongly correlated with each other, while each domain in separate was strongly correlated with the overall CCQ score (r2 = 0.953, r2 = 0.915 and r2 = 0.842 in regards to the functional, symptomatic and mental domain, respectively).,The CCQ scores were also correlated with FEV1, (r2 = -0.252, p < 0.001), FEV1/FVC, (r2 = -0.135, p < 0.001) as also with the quality of life questionnaire SF-12 (r2 = -0.384, p < 0.001).,Smoking cessation also lead to a significant reduction in CCQ score and increase in the SF-12 score.,The self administered CCQ indicates satisfactory validity, reliability and responsiveness and may be used in clinical practice to assess patient quality of life.,Moreover the CCQ indicated the health related quality of life gains attributable to smoking cessation among COPD patients, projecting smoking cessation as a key target in COPD patient management. | 1 |
Training in correct inhaler use, ideally in person or by video demonstration, can minimize errors but is rarely provided in clinics.,This open-label, low-intervention study evaluated critical error rates with dry-powder inhalers (DPIs), before and after training, in patients with chronic obstructive pulmonary disease.,Patients prescribed an inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) (ELLIPTA, Turbuhaler, or DISKUS), long-acting muscarinic antagonist (LAMA)/LABA (ELLIPTA or Breezhaler), or LAMA-only DPI (ELLIPTA, HandiHaler, or Breezhaler) were enrolled.,Critical errors were assessed before training (Visit 1 [V1]; primary endpoint) and 6 weeks thereafter (Visit 2 [V2]; secondary endpoint).,Logistic regression models were used to calculate odds ratios (ORs) for between-group comparisons.,The intent-to-treat population comprised 450 patients.,At V1, fewer patients made ≥1 critical error with ELLIPTA (10%) versus other ICS/LABA DPIs (Turbuhaler: 40%, OR 4.66, P=0.005; DISKUS: 26%, OR 2.48, P=0.114) and other LAMA or LAMA/LABA DPIs (HandiHaler: 34%, OR 3.50, P=0.026; Breezhaler: 33%, OR 3.94, P=0.012).,Critical error rates with the primary ICS/LABA DPI were not significantly different between ELLIPTA ICS/LABA (10%) and ICS/LABA plus LAMA groups (12-25%).,Critical errors with the primary ICS/LABA DPI occurred less frequently with ELLIPTA ICS/LABA with or without LAMA (11%) versus Turbuhaler ICS/LABA with or without LAMA (39%, OR 3.99, P<0.001) and DISKUS ICS/LABA with or without LAMA (26%, OR 2.18, P=0.069).,Simulating single-inhaler versus multiple-inhaler triple therapy, critical error rates were lower with ELLIPTA fluticasone furoate/vilanterol (FF/VI; 10%) versus ELLIPTA FF/VI plus LAMA (22%), considering errors with either DPI (OR 2.50, P=0.108).,At V2, critical error rates decreased for all DPIs/groups, reaching zero only for ELLIPTA.,Between-group comparisons were similar to V1.,Fewer patients made critical errors with ELLIPTA versus other ICS/LABA, and LAMA or LAMA/LABA DPIs.,The effect of “verbal” training highlights its importance for reducing critical errors with common DPIs. | The aim of this study is to summarize the evidence on the dose-response relationship between body mass index (BMI) and mortality in patients with chronic obstructive pulmonary disease (COPD).,We performed a systemic literature search in PubMed, Embase, and Web of Science for relevant studies that were published until June 2015.,A random effects meta-analysis was used to estimate the pooled relative risks (RRs) of all-cause mortality in COPD patients with normal weight compared with those who were underweight, overweight, or obese.,In addition, a dose-response meta-analysis was conducted to explore the dose-response relationship between BMI and all-cause mortality in COPD patients.,A total of 17 observational studies involving 30,182 COPD patients among 285,960 participants were included.,Compared with the reference category, the RRs of underweight, overweight, and obese individuals were 1.40 (95% confidence interval (CI), 1.20-1.63), 0.80 (95% CI, 0.67-0.96), and 0.77 (95% CI, 0.62-0.95), respectively.,A significant nonlinear relationship between BMI and mortality of COPD patients was found by using a random effects model.,COPD patients with BMI of <21.75 kg/m2 had a higher risk of death.,Moreover, an increase in the BMI resulted in a decrease in the risk of death.,The risk of death was lowest when BMI was 30 kg/m2 (RR = 0.69; 95% CI, 0.53-0.89).,The BMI was not associated with all-cause mortality when BMI was >32 kg/m2.,Our findings indicate that overweight is associated with a lower risk of all-cause mortality among patients with COPD whereas underweight is associated with a higher risk of all-cause mortality in these patients.,However, there is limited evidence to support the association between obesity and the risk of all-cause mortality in patients with COPD. | 1 |
Coronavirus disease 2019 (COVID‐19) caused by infection with severe acute respiratory syndrome coronavirus 2 was first detected in Wuhan, China, in late 2019 and continues to spread worldwide.,Persistent questions remain about the relationship between the severity of COVID‐19 and comorbid diseases, as well as other chronic pulmonary conditions.,In this systematic review and meta‐analysis, we aimed to examine in detail whether the underlying chronic obstructive pulmonary diseases (COPD), asthma and chronic respiratory diseases (CRDs) were associated with an increased risk of more severe COVID‐19.,A comprehensive literature search was performed using five international search engines.,In the initial search, 722 articles were identified.,After eliminating duplicate records and further consideration of eligibility criteria, 53 studies with 658,073 patients were included in the final analysis.,COPD was present in 5.2% (2191/42,373) of patients with severe COVID‐19 and in 1.4% (4203/306,151) of patients with non‐severe COVID‐19 (random‐effects model; OR = 2.58, 95% CI = 1.99-3.34, Z = 7.15, p < 0.001).,CRD was present in 8.6% (3780/44,041) of patients with severe COVID‐19 and in 5.7% (16,057/280,447) of patients with non‐severe COVID‐19 (random‐effects model; OR = 2.14, 95% CI = 1.74-2.64, Z = 7.1, p < 0.001).,Asthma was present in 2.3% (1873/81,319) of patients with severe COVID‐19 and in 2.2% (11,796/538,737) of patients with non‐severe COVID‐19 (random‐effects model; OR = 1.13, 95% CI = 0.79-1.60, Z = 0.66, p = 0.50).,In conclusion, comorbid COPD and CRD were clearly associated with a higher severity of COVID‐19; however, no association between asthma and severe COVID‐19 was identified.,See relatedEditorial | We aimed to investigate the relationship between clinical characteristics, outcomes and the severity of severe acute respiratory syndrome coronavirus 2 pneumonia.,We performed a systematic review and meta-analysis using PubMed, Embase, and Cochrane Library databases to assess the clinical characteristics and outcomes of confirmed COVID-19 cases and compared severe (ICU) and nonsevere (non-ICU) groups.,We included 12 cohort studies including 2,445 patients with COVID-19.,Compared with nonsevere (non-ICU) patients, severe (ICU) disease was associated with a smoking history (P = .003) and comorbidities including chronic obstructive pulmonary disease (OR = 5.08, P < .001), diabetes (OR = 3.17, P < .001), hypertension (OR = 2.40, P < .001), coronary heart disease (OR = 2.66, P < .001), cerebrovascular diseases (OR = 2.68, P = .008), and malignancy (OR=2.21, P = .040).,We found significant differences between the 2 groups for fever, dyspnea, decreased lymphocyte and platelet counts, and increased leukocyte count, C-creative protein, procalcitonin, lactose dehydrogenase, aspartate aminotransferase, alanine aminotransferase, creatinine kinase, and creatinine levels (P < .05).,Significant differences were also observed for multiple treatments (P < .05).,Patients in the severe (ICU) group were more likely to have complications and had a much higher mortality rate and lower discharge rate than those with nonsevere (non-ICU) disease (P < .05).,Investigation of clinical characteristics and outcomes of severe cases of COVID-19 will contribute to early prediction, accurate diagnosis, and treatment to improve the prognosis of patients with severe illness. | 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.] | Chronic obstructive pulmonary disease (COPD) constitutes a growing health care problem worldwide.,Integrated disease management (IDM) of mild to moderate COPD patients has been demonstrated to improve exercise capacity and health status after one year, but long-term results are currently lacking in primary care.,Long-term data from the Bocholtz study, a controlled clinical trial comparing the effects of IDM versus usual care on health status in 106 primary care COPD patients during 24 months of follow-up, were analyzed using the Clinical COPD Questionnaire (CCQ).,In addition, the Kroonluchter IDM implementation program has treated 216 primary care patients with mild to moderate COPD since 2006.,Longitudinal six-minute walking distance (6MWD) results for patients reaching 24 months of follow-up were analyzed using paired-sample t-tests.,In prespecified subgroup analyses, the differential effects of baseline CCQ score, Medical Research Council (MRC) dyspnea score, and 6MWD were investigated.,In the Bocholtz study, subjects were of mean age 64 years, with an average postbronchodilator forced expiratory volume in one second (FEV1) of 63% predicted and an FEV1/forced vital capacity (FVC) ratio of 0.56.,No significant differences existed between groups at baseline.,CCQ improved significantly and in a clinically relevant manner by 0.4 points over 24 months; effect sizes were doubled in patients with CCQ > 1 at baseline and tripled in patients with MRC dyspnea score >2.,In the Kroonluchter cohort, 56 subjects completed follow-up, were of mean age 69 years, with an FEV1/FVC ratio of 0.59, while their postbronchodilator FEV1 of 65% predicted was somewhat lower than in the total group.,6MWD improved significantly and in a clinically relevant manner up to 93 m at 12 months and was sustained at 83 m over 24 months; this effect occurred faster in patients with MRC dyspnea score >2.,In patients with baseline 6MWD < 400 m the improvement remained >100 m at 24 months.,In this study, IDM improved and sustained health status and exercise capacity in primary care COPD patients during two years of follow-up.,Improvements in health status are consistently higher in patients with CCQ > 1 at baseline, being strongest in patients with baseline MRC dyspnea score >2.,Improvements in exercise capacity remain highest in patients with 6MWD < 400 m at baseline and seem to occur earlier in patients with MRC dyspnea score >2. | 1 |
Acute exacerbations of chronic obstructive pulmonary disease (COPD) are associated with a significant mortality, health and economic burden.,Their diagnosis, assessment and management remain suboptimal and unchanged for decades.,Recent clinical and translational studies revealed that the significant heterogeneity in mechanisms and outcomes of exacerbations could be resolved by grouping them etiologically.,This is anticipated to lead to a better understanding of the biological processes that underlie each type of exacerbation and to allow the introduction of precision medicine interventions that could improve outcomes.,This review summarises novel data on the diagnosis, phenotyping, targeted treatment and prevention of COPD exacerbations. | COPD may impact food-related activities, such as grocery shopping, cooking, and eating.,Decreased food intake may result in an unhealthy diet, and in malnutrition, which is highly prevalent in patients with COPD.,Malnutrition is known to negatively impact clinical outcome and quality of life.,In this qualitative study, we aimed to explore strategies used to overcome food-related challenges, ie, dietary resilience, and whether these led to a healthy diet.,Furthermore, we aimed to identify the key themes of motivation for dietary resilience in patients with severe COPD.,In October 2015 to April 2016, 12 patients with severe COPD starting a pulmonary rehabilitation program were interviewed.,Qualitative description and thematic analysis were performed.,All participants mentioned the use of strategies to overcome challenges.,Key themes of motivation for dietary resilience were identified as “wanting to be as healthy as possible”, “staying independent”, and “promoting a sense of continuity and duty”.,Two out of 12 participants met the criteria for a healthy diet.,Our study showed a variety of motivational factors and strategies reported by patients with severe COPD to overcome food-related challenges.,However, the majority (n=10) of the participants did not meet the criteria for a healthy diet.,The identified key themes can be used to develop education to support patients with severe COPD to improve their diet. | 1 |
Although subtypes of chronic obstructive pulmonary disease are recognized, it is unknown what happens to these subtypes over time.,Our objectives were to assess the stability of cluster-based subtypes in patients with stable disease and explore changes in clusters over 1 year.,Multiple correspondence and cluster analysis were used to evaluate data collected from 543 stable patients included consecutively from 5 respiratory outpatient clinics.,Four subtypes were identified.,Three of them, A, B, and C, had marked respiratory profiles with a continuum in severity of several variables, while the fourth, subtype D, had a more systemic profile with intermediate respiratory disease severity.,Subtype A was associated with less dyspnea, better health-related quality of life and lower Charlson comorbidity scores, and subtype C with the most severe dyspnea, and poorer pulmonary function and quality of life, while subtype B was between subtypes A and C.,Subtype D had higher rates of hospitalization the previous year, and comorbidities.,After 1 year, all clusters remained stable.,Generally, patients continued in the same subtype but 28% migrated to another cluster.,Together with movement across clusters, patients showed changes in certain characteristics (especially exercise capacity, some variables of pulmonary function and physical activity) and changes in outcomes (quality of life, hospitalization and mortality) depending on the new cluster they belonged to.,Chronic obstructive pulmonary disease clusters remained stable over 1 year.,Most patients stayed in their initial subtype cluster, but some moved to another subtype and accordingly had different outcomes. | The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.,The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada.,Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified.,The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.,The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively.,The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th.,The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first.,Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.,The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation.,Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality. | 1 |
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised many questions about the management of patients with chronic obstructive pulmonary disease (COPD) and whether modifications of their therapy are required.,It has raised questions about recognizing and differentiating coronavirus disease (COVID-19) from COPD given the similarity of the symptoms.,The Global Initiative for Chronic Obstructive Lung Disease (GOLD) Science Committee used established methods for literature review to present an overview of the management of patients with COPD during the COVID-19 pandemic.,It is unclear whether patients with COPD are at increased risk of becoming infected with SARS-CoV-2.,During periods of high community prevalence of COVID-19, spirometry should only be used when it is essential for COPD diagnosis and/or to assess lung function status for interventional procedures or surgery.,Patients with COPD should follow basic infection control measures, including social distancing, hand washing, and wearing a mask or face covering.,Patients should remain up to date with appropriate vaccinations, particularly annual influenza vaccination.,Although data are limited, inhaled corticosteroids, long-acting bronchodilators, roflumilast, or chronic macrolides should continue to be used as indicated for stable COPD management.,Systemic steroids and antibiotics should be used in COPD exacerbations according to the usual indications.,Differentiating symptoms of COVID-19 infection from chronic underlying symptoms or those of an acute COPD exacerbation may be challenging.,If there is suspicion for COVID-19, testing for SARS-CoV-2 should be considered.,Patients who developed moderate-to-severe COVID-19, including hospitalization and pneumonia, should be treated with evolving pharmacotherapeutic approaches as appropriate, including remdesivir, dexamethasone, and anticoagulation.,Managing acute respiratory failure should include appropriate oxygen supplementation, prone positioning, noninvasive ventilation, and protective lung strategy in patients with COPD and severe acute respiratory distress syndrome.,Patients who developed asymptomatic or mild COVID-19 should be followed with the usual COPD protocols.,Patients who developed moderate or worse COVID-19 should be monitored more frequently and accurately than the usual patients with COPD, with particular attention to the need for oxygen therapy. | Few data are available in regards to the prevalence of pulmonary hypertension (PH) in the broad spectrum of COPD.,This study was aimed at assessing the prevalence of PH in a cohort of COPD patients across the severity of airflow limitation, and reporting the hemodynamic characteristics at rest and during exercise.,We performed a retrospective analysis on COPD patients who underwent right-heart catheterization in our center with measurements obtained at rest (n=139) and during exercise (n=85).,PH was defined as mean pulmonary artery pressure (mPAP) ≥25 mmHg and pulmonary capillary wedge pressure <15 mmHg.,Exercise-induced PH (EIPH) was defined by a ratio of ΔmPAP/Δcardiac output >3.,PH was present in 25 patients (18%).,According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, PH prevalence in GOLD 2 was 7% (3 patients); 25% (14 patients) in GOLD 3; and 22% (8 patients) in GOLD 4.,Severe PH (mPAP ≥35 mmHg) was identified in four patients (2.8%).,Arterial partial oxygen pressure was the outcome most strongly associated with PH (r=−0.29, P<0.001).,EIPH was observed in 60 patients (71%) and had a similar prevalence in both GOLD 2 and 3, and was present in all GOLD 4 patients.,Patients with PH had lower cardiac index during exercise than patients without PH (5.0±1.2 versus 6.7±1.4 L/min/m2, respectively; P=0.001).,PH has a similar prevalence in COPD patients with severe and very-severe airflow limitation, being associated with the presence of arterial hypoxemia.,In contrast, EIPH is highly prevalent, even in moderate COPD, and might contribute to limiting exercise tolerance. | 1 |
Nutritional status is a well-recognized prognostic indicator in chronic obstructive pulmonary disease (COPD); however, very little is known about the relationship between lung function and saturated fat intake.,We used data from the cross-sectional National Health and Nutrition Examination Surveys (NHANES) to assess the relationship between saturated fatty acid (SFA) intake and lung function in the general US adult population.,Adults in NHANES (2007-2012) with pre-bronchodilator spirometry measurements and dietary SFA intake were included.,Primary outcomes were lung function including forced expiratory volume in one second (FEV1), FEV1, forced vital capacity (FVC), FEV1/FVC ratio, percent predicted FEV1 and percent predicted FVC.,Multivariable regression models in the general population as well as those with spirometry-defined airflow obstruction were used to assess the relationship between lung function measurements and dietary SFA intake after adjustment for confounders. 11,180 eligible participants were included in this study.,Univariate analysis revealed a statistically significant positive association between total SFA intake and lung function outcomes; however, these relationships were attenuated after adjustment for covariates.,A secondary analysis of individuals with spirometry-defined airflow obstruction (FEV1/FVC < 0.7) revealed that a lower intake of SFA was associated with reduced FEV1 (β = −126.4, p = 0.04 for quartile 1 vs. quartile 4), FVC (β = −165.8. p = 0.01 for quartile 1 vs. quartile 4), and percent predicted FVC (β = −3.3. p = 0.04 for quartile 1 vs. quartile 4), after adjustment for relevant confounders.,No associations were observed for the FEV1/FVC ratio and percent predicted FEV1.,It is possible that characteristics such as food source and fatty acid chain length may influence associations between saturated fatty acid intake and health outcomes. | Early preclinical diagnosis of COPD is urgent.,We proposed that fatty acid composition of red blood cells may serve as a prognostic test for the complications in the chronic respiratory diseases.,Fatty acid composition of the erythrocyte membranes in patients with chronic respiratory diseases (chronic bronchitis, CB, and stable chronic obstructive pulmonary disease, COPD) was studied.,It was established that modification of the fatty acid composition in the erythrocyte membranes was unidirectional in both groups of patients.,Patients with CB and stable COPD (group A, GOLD 1) (15 subjects in each group) were studied in clinic.,The activity of the inflammatory process was evaluated by the phagocytic activity of neutrophils, cytokine levels and cytokine receptors in the blood serum (TNFα, sTNF-RI, bFGF, TGF-β, IL-8).,Fatty acid (FA) composition of the erythrocyte membranes was analyzed by gas liquid chromatography.,Statistical data processing was performed by the methods of descriptive statistics with Statistica 6.0.,In both groups (CB and COPD), a significant accumulation of the saturated FAs (14:0, 15:0, 18:0) was established.,The amount of the arachidonic acid (20:4n-6) was increased by 13% (р < 0.05) in CB patients and by 41% (р < 0.001) in COPD patients, as compared with healthy persons.,The elevated level of the PUFA n-6 in the erythrocytes membranes in patients with chronic respiratory diseases confirms that proinflammatory (leukotriene B4) and bronchospasm (prostaglandin D2) mediator substrates is increased.,The level of the eicosapentaenoic acid (20:5n-3) was decreased by 32% (р < 0.05) in CB patients and 2-fold (р < 0.001) in COPD patients.,The observed increase in the 20:4n-6/20:5n-3 ratio - 1.5-fold (р < 0.001) in CB patients and 3-fold in COPD patients - can be a specific marker of the adverse course of the respiratory pathology and the chronic inflammatory development.,Chronic respiratory disease development is associated with the disturbance of the fatty acid composition in erythrocyte membranes and disbalance of the ratio between precursor of pro- and antiinflammatory eicosanoids. | 1 |
Gas trapping quantified on chest CT scans has been proposed as a surrogate for small airway disease in COPD.,We sought to determine if measurements using paired inspiratory and expiratory CT scans may be better able to separate gas trapping due to emphysema from gas trapping due to small airway disease.,Smokers with and without COPD from the COPDGene Study underwent inspiratory and expiratory chest CT scans.,Emphysema was quantified by the percent of lung with attenuation < −950HU on inspiratory CT.,Four gas trapping measures were defined: (1) Exp−856, the percent of lung < −856HU on expiratory imaging; (2) E/I MLA, the ratio of expiratory to inspiratory mean lung attenuation; (3) RVC856-950, the difference between expiratory and inspiratory lung volumes with attenuation between −856 and −950 HU; and (4) Residuals from the regression of Exp−856 on percent emphysema.,In 8517 subjects with complete data, Exp−856 was highly correlated with emphysema.,The measures based on paired inspiratory and expiratory CT scans were less strongly correlated with emphysema.,Exp−856, E/I MLA and RVC856-950 were predictive of spirometry, exercise capacity and quality of life in all subjects and in subjects without emphysema.,In subjects with severe emphysema, E/I MLA and RVC856-950 showed the highest correlations with clinical variables.,Quantitative measures based on paired inspiratory and expiratory chest CT scans can be used as markers of small airway disease in smokers with and without COPD, but this will require that future studies acquire both inspiratory and expiratory CT scans. | COPD is a heterogeneous disease characterized by airflow obstruction and diagnosed by lung function.,CT imaging is emerging as an important, noninvasive tool in phenotyping COPD.,However, the use of CT imaging in defining the disease heterogeneity above lung function is not fully known.,Seventy-five patients with COPD (58 men, 17 women) were studied with CT imaging and with measures of airway inflammation.,Airway physiology and health status were also determined.,The presence of emphysema (EM), bronchiectasis (BE), and bronchial wall thickening (BWT) was found in 67%, 27%, and 27% of subjects, respectively.,The presence of EM was associated with lower lung function (mean difference % FEV1, −20%; 95% CI, −28 to −11; P < .001).,There was no difference in airway inflammation, exacerbation frequency, or bacterial load in patients with EM alone or with BE and/or BWT ± EM.,The diffusing capacity of the lung for carbon monoxide/alveolar volume ratio was the most sensitive and specific parameter in identifying EM (area under the receiver operator characteristic curve, 0.87; 95% CI, 0.79-0.96).,Physiologic cluster analysis identified three clusters, two of which were EM predominant and the third characterized by a heterogeneous combination of EM and BE.,The application of CT imaging can be useful as a tool in the multidimensional approach to phenotyping patients with COPD. | 1 |
•COPD is a risk factor for lung cancer beyond their shared aetiology.,•Both are driven by oxidative stress.,•Both are linked to cellular aging, senescence and telomere shortening.,•Both have been linked to genetic predisposition.,•Both show altered epigenetic regulation of gene expression.,COPD is a risk factor for lung cancer beyond their shared aetiology.,Both are driven by oxidative stress.,Both are linked to cellular aging, senescence and telomere shortening.,Both have been linked to genetic predisposition.,Both show altered epigenetic regulation of gene expression.,Both COPD and lung cancer are major worldwide health concerns owing to cigarette smoking, and represent a huge, worldwide, preventable disease burden.,Whilst the majority of smokers will not develop either COPD or lung cancer, they are closely related diseases, occurring as co-morbidities at a higher rate than if they were independently triggered by smoking.,Lung cancer and COPD may be different aspects of the same disease, with the same underlying predispositions, whether this is an underlying genetic predisposition, telomere shortening, mitochondrial dysfunction or premature aging.,In the majority of smokers, the burden of smoking may be dealt with by the body’s defense mechanisms: anti-oxidants such as superoxide dismutases, anti-proteases and DNA repair mechanisms.,However, in the case of both diseases these fail, leading to cancer if mutations occur or COPD if damage to the cell and proteins becomes too great.,Alternatively COPD could be a driving factor in lung cancer, by increasing oxidative stress and the resulting DNA damage, chronic exposure to pro-inflammatory cytokines, repression of the DNA repair mechanisms and increased cellular proliferation.,Understanding the mechanisms that drive these processes in primary cells from patients with these diseases along with better disease models is essential for the development of new treatments. | Genotoxic stress, such as by exposure to bromodeoxyuridine (BrdU) and cigarette smoke, induces premature cell senescence.,Recent evidence indicates that cellular senescence of various types of cells is accelerated in COPD patients.,However, whether the senescence of airway epithelial cells contributes to the development of airway diseases is unknown.,The present study was designed to test the hypothesis that premature senescence of airway epithelial cells (Clara cells) impairs repair processes and exacerbates inflammation after airway injury.,C57/BL6J mice were injected with the Clara-cell-specific toxicant naphthalene (NA) on days 0, 7, and 14, and each NA injection was followed by a daily dose of BrdU on each of the following 3 days, during which regenerating cells were allowed to incorporate BrdU into their DNA and to senesce.,The p38 MAPK inhibitor SB202190 was injected 30 minutes before each BrdU dose.,Mice were sacrificed at different times until day 28 and lungs of mice were obtained to investigate whether Clara cell senescence impairs airway epithelial regeneration and exacerbates airway inflammation.,NCI-H441 cells were induced to senesce by exposure to BrdU or the telomerase inhibitor MST-312.,Human lung tissue samples were obtained from COPD patients, asymptomatic smokers, and nonsmokers to investigate whether Clara cell senescence is accelerated in the airways of COPD patients, and if so, whether it is accompanied by p38 MAPK activation.,BrdU did not alter the intensity of the airway epithelial injury or inflammation after a single NA exposure.,However, after repeated NA exposure, BrdU induced epithelial cell (Clara cell) senescence, as demonstrated by a DNA damage response, p21 overexpression, increased senescence-associated β-galactosidase activity, and growth arrest, which resulted in impaired epithelial regeneration.,The epithelial senescence was accompanied by p38 MAPK-dependent airway inflammation.,Senescent NCI-H441 cells impaired epithelial wound repair and secreted increased amounts of pro-inflammatory cytokines in a p38 MAPK-dependent manner.,Clara cell senescence in COPD patients was accelerated and accompanied by p38 MAPK activation.,Senescence of airway epithelial cells impairs repair processes and exacerbates p38 MAPK-dependent inflammation after airway injury, and it may contribute to the pathogenesis of COPD. | 1 |
Accurate assessment of a patient’s risk of recurrence and treatment response is an important prerequisite of personalized therapy in lung cancer.,This study extends a previously described non-small cell lung cancer prognostic model by the addition of chemotherapy and co-morbidities through the use of linked SEER-Medicare data.,Data on 34,203 lung adenocarcinoma and 26,967 squamous cell lung carcinoma patients were used to determine the contribution of Chronic Obstructive Pulmonary Disease (COPD) to prognostication in 30 treatment combinations.,A Cox model including COPD was estimated on 1,000 bootstrap samples, with the resulting model assessed on ROC, Brier Score, Harrell’s C, and Nagelkerke’s R2 metrics in order to evaluate improvements in prognostication over a model without COPD.,The addition of COPD to the model incorporating cancer stage, age, gender, race, and tumor grade was shown to improve prognostication in multiple patient groups.,For lung adenocarcinoma patients, there was an improvement on the prognostication in the overall patient population and in patients without receiving chemotherapy, including those receiving surgery only.,For squamous cell carcinoma, an improvement on prognostication was seen in both the overall patient population and in patients receiving multiple types of chemotherapy.,COPD condition was able to stratify patients receiving the same treatments into significantly (log-rank p<0.05) different prognostic groups, independent of cancer stage.,Combining patient information on COPD, cancer stage, age, gender, race, and tumor grade could improve prognostication and prediction of treatment response in individual non-small cell lung cancer patients.,This model enables refined prognosis and estimation of clinical outcome of comprehensive treatment regimens, providing a useful tool for personalized clinical decision-making. | Recent studies suggest that coexistence of chronic obstructive pulmonary disease (COPD) might be independently related to a worse prognosis for lung cancer.,However, because data on the substantial prevalence of COPD and its severity in Asian lung cancer patients remain limited, clinical impact of prevalence and severity of COPD among the population has not been fully evaluated.,Furthermore, patients with COPD often have comorbidities.,Thus, whether the decision-making process for therapeutic management of lung cancer patients might be independently affected by COPD remains elusive.,Clinical impact of prevalence and severity of COPD were evaluated in 270 Japanese patients with newly diagnosed lung cancer who were sequentially registered and underwent bronchoscopy from August 2010 to July 2012 at Nagoya University hospital.,Furthermore, to explore whether or not the severity of airflow obstruction might affect the decision to propose thoracic surgery with curative intent, we evaluated data from patients with lung cancer at stage 1A to 3A who underwent spirometry and bronchoscopy.,The prevalence rate of COPD was 54.4% among Japanese patients with lung cancer who underwent bronchoscopy.,The incidence of Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1 and 2 was significantly higher than that of GOLD grade 3.,Although COPD-related comorbidities were not independent factors for proposing thoracic surgery, the number of thoracic surgeries performed was significantly less in the COPD group than the non-COPD group.,Multivariate analysis showed that more severe airway obstruction, advanced clinical staging, and higher age, were independent factors associated with the decision on thoracic surgery.,We demonstrated a high prevalence of COPD among Japanese lung cancer patients.,Based on the knowledge that severity of COPD is one of the most important factors in the therapeutic decision, comprehensive assessment of COPD at bronchoscopy might allow us to implement the optimum management for lung cancer patients. | 1 |
Polypharmacy of respiratory medications is commonly observed in patients with chronic obstructive pulmonary disease (COPD).,The aims of this study were to investigate determinants of polypharmacy and to study the consistency of actual respiratory drug use with current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in pulmonary rehabilitation candidates with COPD.,Data were extracted from the records of all patients with a diagnosis of COPD referred for pulmonary rehabilitation to CIRO+ between 2005 and 2009.,Use of respiratory medications, self-reported COPD exacerbations, lung function, blood gases, exercise capacity, Medical Research Council (MRC) dyspnea grade, and St George’s Respiratory Questionnaire (SGRQ) were recorded as part of assessment of health status.,In total, 1859 COPD patients of mean age (± standard deviation) 64.3 ± 9.7 years and with a forced expiratory volume in one second (FEV1) of 44.7% ± 18.2% were included.,On average, patients used 3.5 ± 1.5 respiratory medications; this number increased with increasing GOLD stage, MRC score, and SGRQ scores.,FEV1 (% predicted), SGRQ, and number of recent exacerbations were independent determinants of polypharmacy.,Use of long-acting bronchodilators and inhaled corticosteroids was substantial and comparable in all GOLD stages.,Use of corticosteroids was not restricted to patients with frequent exacerbations.,Polypharmacy of respiratory medications is common in COPD patients with persistent symptoms.,In addition to severity of disease, health status is an independent predictor of polypharmacy.,Actual drug use in COPD patients referred for pulmonary rehabilitation is partially inconsistent with current GOLD guidelines. | Exercise training improves exercise tolerance in chronic obstructive pulmonary disease (COPD).,Tiotropium 18 μg once daily induces sustained bronchodilation throughout the day and reduces hyperinflation, one of the pathophysiological factors contributing to exertional dyspnea in COPD patients.,To determine whether tiotropium enhances the effects of exercise training in patients with COPD.,Multicenter, 25 week randomized, double-blind, placebo-controlled, parallel-group study.,Twelve Italian Pulmonary Units practicing pulmonary rehabilitation.,Two hundred thirty four COPD patients (196 males; mean age: 67.4 ± 7.6; forced expiratory volume at 1 second (FEV1): 41.4 ± 13.0% predicted) were randomised to tiotropium 18 μg or placebo inhalation capsules taken once daily.,Both groups underwent a 8 week pulmonary rehabilitation program (PR) consisting of 3 exercise training session per week.,Baseline, at the end of PR and after 12 weeks, patients completed pulmonary function testing, six minute walking test (6MWT), the Baseline and Transition Dyspnea Index (BDI and TDI), and the St.,George’s Respiratory Questionnaire (SGRQ).,Relative to placebo, tiotropium had larger trough and post-study drug FEV1 responses on all test days.,At the end of and 12 weeks following PR, patients on tiotropium showed no statistically significant differences in 6MWT compared to patients on placebo.,Compared to the period immediately prior to PR, the mean improvement in 6MWT was only 29.7 meters (7.1%) for the combined cohort.,Mean TDI focal scores at the end of PR were 3.60 for tiotropium and 2.25 for placebo (p < 0.01).,At 12 weeks after PR, TDI focal scores were 2.71 for tiotropium and 2.11 for placebo (p = 0.16).,Reduction in all four SGRQ component scores, indicating an improvement in health-related quality of life, was observed for the tiotropium group over the duration of the study compared to placebo but the differences were not statistically significant.,During the study period, there were fewer exacerbations and exacerbation days in the tiotropium group.,Although significant improvements were observed with perceived dyspnea, compared to placebo, the addition of tiotropium to pulmonary rehabilitation did not improve the 6MWT. | 1 |
Chronic obstructive pulmonary disease (COPD), characterized by irreversible airflow obstruction, is a major cause of morbidity and mortality worldwide.,However, geographic differences in the clinical characteristics of severe COPD patients have not been widely studied.,We recruited a total of 828 severe COPD cases from three continents.,Subjects in Poland were enrolled by the Institute of Tuberculosis and Lung Diseases in Warsaw; subjects in Korea participated at several university hospitals in Korea; and subjects in USA were enrolled at two clinics affiliated with academic medical centers.,All subjects were over the age of 30 with at least 10 pack-years of cigarette smoking history.,Cases manifested severe to very severe airflow obstruction with post-bronchodilator forced expiratory volume in 1 second (FEV1) <50% predicted and FEV1/forced vital capacity <0.7.,All subjects completed a detailed questionnaire and underwent standardized pre-bronchodilator and post-bronchodilator spirometry.,Subjects with known tuberculosis (TB)-associated lung parenchymal destruction were excluded.,Univariate and multivariate assessments of the impact of the country of origin on respiratory symptoms and respiratory illness were performed.,In both univariate and multivariate analyses, a history of TB (38.7%) and physician-diagnosed asthma (43.9%) were significantly more common in subjects with severe COPD from Korea than USA or Poland, while attacks of bronchitis (64.2%) were more common in subjects with severe COPD from Poland.,COPD subjects from Poland had more severe dyspnea (modified Medical Research Council 3.3±1.0) and more frequently reported symptoms of chronic bronchitis (52.2%).,A history of TB was also more common in Poland (10.8%) than in USA (0.3%) severe COPD patients.,Respiratory symptoms and other respiratory illnesses associated with severe COPD differed widely among three continents. | The Korea Chronic Obstructive Pulmonary Disorders Subgroup Study Team (Korea COPD Subgroup Study team, KOCOSS) is a multicenter observational study that includes 956 patients (mean age 69.9 ± 7.8 years) who were enrolled from 45 tertiary and university-affiliated hospitals from December 2011 to October 2014.,The initial evaluation for all patients included pulmonary function tests (PFT), 6-minute walk distance (6MWD), COPD Assessment Test (CAT), modified Medical Research Council (mMRC) dyspnea scale, and the COPD-specific version of St.,George’s Respiratory Questionnaire (SGRQ-C).,Here, we report the comparison of baseline characteristics between patients with early- (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage I and II/groups A and B) and late-stage COPD (GOLD stage III and IV/groups C and D).,Among all patients, the mean post-bronchodilator FEV1 was 55.8% ± 16.7% of the predicted value, and most of the patients were in GOLD stage II (520, 56.9%) and group B (399, 42.0%).,The number of exacerbations during one year prior to the first visit was significantly lower in patients with early COPD (0.4 vs.,0.9/0.1 vs.,1.2), as were the CAT score (13.9 vs.,18.3/13.5 vs.,18.1), mMRC (1.4 vs.,2.0/1.3 vs.1.9), and SGRQ-C total score (30.4 vs.,42.9/29.1 vs.,42.6) compared to late-stage COPD (all P < 0.001).,Common comorbidities among all patients were hypertension (323, 37.7%), diabetes mellitus (139, 14.8%), and depression (207, 23.6%).,The data from patients with early COPD will provide important information towards early detection, proper initial management, and design of future studies. | 1 |
Despite a number of important differences in the pathogenesis, course and prognosis of asthma and chronic obstructive pulmonary disease (COPD), these two entities also have common features with airway inflammation being one of them.,Airway remodeling is a characteristic feature of asthma, but data on the bronchial wall thickening in COPD patients are still scarce.,To assess the relation between the inflammatory cell count in the bronchoalveolar lavage fluid (BALF) and thickness of bronchial walls assessed by high resolution computed tomography (HRCT) in asthma and COPD patients.,The study was conducted in 9 patients with mild-to-moderate asthma (M/F 4/5, mean age 35 ± 10 years) and 11 patients with mild-to-moderate COPD (M/F 7/4, mean age 57 ± 9 years).,In all subjects lung function tests and HRCT scanning of the chest were performed.,External (D) and internal (L) diameters of the airways were assessed at five selected lung levels.,The lumen area (AL), wall area (WA), wall thickness (WT) and bronchial wall thickness (WT/D ratio) were calculated.,Eight patients with asthma and 8 patients with COPD underwent fiberoptic bronchoscopy and bronchoalveolar lavage (BAL).,Total and differential cell counts were assessed in the BAL fluid.,Mean FEV1% pred was 80 ± 19%, and 73 ± 20% in asthma and COPD patients, respectively (NS).,No significant differences in the total and differential cell counts in BALF were found in patients with asthma and COPD.,There were no significant differences in the airway diameter or airway wall thickness.,The mean inner airway diameter was 1.4 ± 0.3 and 1.2 ± 0.3 mm and the mean lumen area was 1.8 ± 0.7 and 1.6 ± 0.7 mm2 in asthma and COPD, respectively (NS).,Negative correlations between the eosinophil count in BALF and inner airway diameter (r = -0.7, P < 0.05) and lumen area (r = -0.7, P < 0.05) were found in asthmatics.,There was no significant relationship between the BALF cell count and airway wall thickness in COPD patients.,In mild-to-moderate asthma and COPD the airway diameter and thickness are similar.,In asthmatics, the airway diameter might be associated with eosinophil count in BAL fluid. | The reticular basement membrane (Rbm) in smokers and especially smokers with COPD is fragmented with "clefts" containing cells staining for the collagenase matrix-metalloproteinase-9 (MMP-9) and fibroblast protein, S100A4.,These cells are also present in the basal epithelium.,Such changes are likely hallmarks of epithelial mesenchymal transition (EMT).,We aimed to confirm the epithelial origin of these Rbm cells, and to exclude potential confounding by infiltrating inflammatory cells.,Endobronchial biopsy sections from 17 COPD current smokers, with documented Rbm splitting and cellularity were stained for neutrophil elastase (neutrophil marker), CD68 (macrophage/mature fibroblasts), CD4+/CD8+ T lymphocytes, CD19 (B-cells), CD11c (dendritic cells/inflammatory cells), and S100 (Langerhans cells).,The number of cells in the Rbm and epithelium staining for these "inflammatory" cell markers were then compared to numbers staining for S100A4, "a documented EMT epitope".,Slides were double stained for S100A4 and cytokeratin(s).,In the basal epithelium significantly more cells stained for S100A4 compared to infiltrating macrophages, fibroblasts or immune cells: median, 26 (21.3 - 37.3) versus 0 (0 - 9.6) per mm, p < 0.003.,Markedly more S100A4 staining cells were also observed in the Rbm compared to infiltrating macrophages, neutrophils, fibroblasts or immune cells or any sub-type: 58 (37.3 - 92.6) versus 0 (0 - 4.8) cells/mm Rbm, p < 0.003.,Cells in the basal epithelium 26 (21.3 - 37.3) per mm) and Rbm (5.9 (2.3 - 13.8) per mm) frequently double stained for both cytokeratin and S100A4.,These data provide additional support for active EMT in COPD airways. | 1 |
The Global initiative for chronic Obstructive Lung Disease (GOLD) defines COPD as a fixed post-bronchodilator ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) below 0.7.,Age-dependent cut-off values below the lower fifth percentile (LLN) of this ratio derived from the general population have been proposed as an alternative.,We wanted to assess the diagnostic accuracy and prognostic capability of the GOLD and LLN definition when compared to an expert-based diagnosis.,In a prospective cohort study, 405 patients aged ≥ 65 years with a general practitioner's diagnosis of COPD were recruited and followed up for 4.5 (median; quartiles 3.9; 5.1) years.,Prevalence rates of COPD according to GOLD and three LLN definitions and diagnostic performance measurements were calculated.,The reference standard was the diagnosis of COPD of an expert panel that used all available diagnostic information, including spirometry and bodyplethysmography.,Compared to the expert panel diagnosis, 'GOLD-COPD' misclassified 69 (28%) patients, and the three LLNs misclassified 114 (46%), 96 (39%), and 98 (40%) patients, respectively.,The GOLD classification led to more false positives, the LLNs to more false negative diagnoses.,The main predictors beyond the FEV1/FVC ratio for an expert diagnosis of COPD were the FEV1 % predicted, and the residual volume/total lung capacity ratio (RV/TLC).,Adding FEV1 and RV/TLC to GOLD or LLN improved the diagnostic accuracy, resulting in a significant reduction of up to 50% of the number of misdiagnoses.,The expert diagnosis of COPD better predicts exacerbations, hospitalizations and mortality than GOLD or LLN.,GOLD criteria over-diagnose COPD, while LLN definitions under-diagnose COPD in elderly patients as compared to an expert panel diagnosis.,Incorporating FEV1 and RV/TLC into the GOLD-COPD or LLN-based definition brings both definitions closer to expert panel diagnosis of COPD, and to daily clinical practice. | Patients with chronic obstructive pulmonary disease (COPD) are included in several national pneumococcal vaccination recommendations whereas asthma patients are not.,The objective of this study was to evaluate pneumonia-related hospitalization risk in patients with COPD or asthma and vaccination impact.,We identified patients with documented pneumococcal vaccination from a cohort of veterans with either a diagnosis of asthma or COPD and their matched controls.,Patients were identified between October 1, 1997 and September 30, 1998 and followed for 5 years.,For each group we identified pneumococcal pneumonia hospitalizations and all pneumonia-related hospitalizations in the periods before and after vaccination.,We estimated hospitalization rates and compared rates in the asthma and COPD groups to controls using negative binomial regression models.,We identified 16,074 COPD patients (average age 65.8 years), 14,028 controls for the COPD patients (average age 67.5 years), 2,746 asthma patients (average age 53.0 years), and 1,345 controls for the asthma patients (average age 59.2 years).,Compared to controls, the adjusted risk of pneumococcal pneumonia hospitalizations before pneumococcal vaccination was COPD = 8.02 (95% CI, 4.44-14.48) and asthma = 0.76 (0.17-3.53).,For any pneumonia-related hospitalization, the adjusted risk was COPD = 3.91 (3.40-4.50) and asthma = 1.45 (0.85-2.46).,After vaccination, events decreased in all groups.,The adjusted risk for pneumococcal pneumonia hospitalizations postvaccination was COPD = 3.87 (2.55-5.88) and asthma = 0.30 (0.04-1.99).,For any pneumonia-related hospitalization the adjusted risk was COPD = 3.71 (3.33-4.13) and asthma = 0.79 (0.50-1.25).,This study supports the value of vaccinating COPD patients; however, the value of vaccination for asthma patients is less certain. | 1 |
During 2007-2010, the National Health and Nutrition Examination Survey (NHANES) conducted a spirometry component which obtained pre-bronchodilator pulmonary lung function data on a nationally representative sample of US adults aged 6-79 years and post-bronchodilator pulmonary lung function data for the subset of adults with airflow limitation.,The goals of this study were to 1) compute prevalence estimates of chronic obstructive pulmonary disease (COPD) using pre-bronchodilator and post-bronchodilator spirometry measurements and fixed ratio and lower limit of normal (LLN) diagnostic criteria and 2) examine the potential impact of nonresponse on the estimates.,This analysis was limited to those aged 40-79 years who were eligible for NHANES pre-bronchodilator spirometry (n=7,104).,Examinees with likely airflow limitation were further eligible for post-bronchodilator testing (n=1,110).,Persons were classified as having COPD based on FEV1/FVC < 70% (fixed ratio) or FEV1/FVC < lower limit of normal (LLN) based on person’s age, sex, height, and race/ethnicity.,Those without spirometry but self-reporting both daytime supplemental oxygen therapy plus emphysema and/or current chronic bronchitis were also classified as having COPD.,The final analytic samples for pre-bronchodilator and post-bronchodilator analyses were 77.1% (n=5,477) and 50.8% (n=564) of those eligible, respectively.,To account for non-response, NHANES examination weights were adjusted to the eligible pre-bronchodilator and post-bronchodilator subpopulations.,In 2007-2010, using the fixed ratio criterion and pre-bronchodilator test results, COPD prevalence was 20.9% (SE 1.1) among US adults aged 40-79 years.,Applying the same criterion to post-bronchodilator test results, prevalence was 14.0% (SE 1.0).,Using the LLN criterion and pre-bronchodilator test results, the COPD prevalence was 15.4% (SE 0.8), while applying the same criterion to post-bronchodilator test results, prevalence was 10.2% (SE 0.8).,The overall COPD prevalence among US adults aged 40-79 years varied from 10.2% to 20.9% based on whether pre- or post-bronchodilator values were used and which diagnostic criterion (fixed ratio or LLN) was applied.,The overall prevalence decreased by approximately 33% when airflow limitation was based on post-bronchodilator as compared to pre-bronchodilator spirometry, regardless of which diagnostic criterion was used. | This review proposes a critical reassessment (based entirely on published evidence) of the following seven common beliefs about chronic obstructive pulmonary disease (COPD): (1) COPD is one disease.,(2) There is a valid definition for COPD.,(The current definition includes cases of irreversible asthma and bronchiectasis, and occasionally, other obstructive lung conditions).,(3) Irreversible asthma in smokers and COPD cannot be differentiated.,(4) A “chronic bronchitis” form of COPD exists and is characterized by blue bloater status and normal carbon monoxide diffusion studies.,(5) Phenotyping has no bearing on medication choice in COPD.,(6) Computerized scoring of lung attenuation on CT scans can diagnose emphysema.,(Emphysema scores overlap in irreversible asthma and COPD); however, qualitative visual changes may be useful for differentiation.,(7) A definable entity called the overlap (of COPD and asthma) syndrome exists.,Conflict over the abovementioned points denies patients proper phenotype-guided therapy and encourages a multidrug approach to COPD management.,The recently coined term, overlap syndrome, invites a double-barreled therapy aimed at asthma and COPD, despite the absence of any agreement about how to define the syndrome and the lack of any related drug trials (in the area of inhaled corticosteroids).,A diagnosis of COPD is associated with high morbidity and escalating costs, suggesting the need for a thorough new examination of the evidence. | 1 |
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 | Reduced physical activity is an important feature of Chronic Obstructive Pulmonary Disease (COPD).,Various activity monitors are available but their validity is poorly established.,The aim was to evaluate the validity of six monitors in patients with COPD.,We hypothesized triaxial monitors to be more valid compared to uniaxial monitors.,Thirty-nine patients (age 68±7years, FEV1 54±18%predicted) performed a one-hour standardized activity protocol.,Patients wore 6 monitors (Kenz Lifecorder (Kenz), Actiwatch, RT3, Actigraph GT3X (Actigraph), Dynaport MiniMod (MiniMod), and SenseWear Armband (SenseWear)) as well as a portable metabolic system (Oxycon Mobile).,Validity was evaluated by correlation analysis between indirect calorimetry (VO2) and the monitor outputs: Metabolic Equivalent of Task [METs] (SenseWear, MiniMod), activity counts (Actiwatch), vector magnitude units (Actigraph, RT3) and arbitrary units (Kenz) over the whole protocol and slow versus fast walking.,Minute-by-minute correlations were highest for the MiniMod (r = 0.82), Actigraph (r = 0.79), SenseWear (r = 0.73) and RT3 (r = 0.73).,Over the whole protocol, the mean correlations were best for the SenseWear (r = 0.76), Kenz (r = 0.52), Actigraph (r = 0.49) and MiniMod (r = 0.45).,The MiniMod (r = 0.94) and Actigraph (r = 0.88) performed better in detecting different walking speeds.,The Dynaport MiniMod, Actigraph GT3X and SenseWear Armband (all triaxial monitors) are the most valid monitors during standardized physical activities.,The Dynaport MiniMod and Actigraph GT3X discriminate best between different walking speeds. | 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. | Little is known about patients who frequently visit the emergency department (ED) for acute exacerbation of chronic obstructive pulmonary disease (AECOPD).,We aimed to quantify the proportion and characteristics of patients with frequent ED visits for AECOPD and associated healthcare utilization.,We conducted a retrospective cohort study of adults aged ≥40 years with at least one ED visit for AECOPD between 2010 and 2011, derived from population-based all-payer data of State ED and Inpatient Databases for two large and diverse states: California and Florida.,Outcome measures were frequency of ED visits for AECOPD, 30-day ED revisits, subsequent hospitalizations, near-fatal events (AECOPD involving mechanical ventilation), and charges for both ED and inpatient services (available only for Florida) during the year after the first ED visit.,The analytic cohort comprised 98,280 unique patients with 154,736 ED visits for AECOPD.,During the 1-year period, 29.4% (95% CI, 29.1%-29.7%) of the patients had two or more (frequent) visits, accounting for 55.2% (95% CI, 54.9%-55.4%) of all ED visits for AECOPD.,In the multivariable model, significant predictors of frequent ED visits were age 55-74 years (vs. 40-54 years), male sex, non-Hispanic white or black race, Medicaid insurance (vs. private), and lower median household income (all P < 0.001).,At the visit-level, 12.3% of ED visits for AECOPD were 30-day revisit events (95% CI, 12.1%-12.4%).,Additionally, 62.8% of ED visits for AECOPD (95% CI, 62.6%-63.0%) resulted in a hospitalization; patients with frequent ED visits comprised 55.5% (95% CI, 55.2%-55.8%) of all hospitalizations.,Furthermore, 7.3% (95% CI, 7.3%-7.5%) of ED visits for AECOPD led to a near-fatal event; patients with frequent ED visits accounted for 64.4% (95% CI, 63.5%-65.3%) of all near-fatal events.,Total charges for AECOPD were $1.94 billion (95% CI, $1.90-1.97 billion) in Florida; patients with frequent ED visits accounted for $1.07 billion (95% CI, $1.04-1.09 billion).,In this large cohort study, we found that 29% had frequent ED visits for AECOPD and that lower socioeconomic status was significantly associated with a higher frequency of ED visits.,Individuals with frequent ED visits for AECOPD accounted for a substantial amount of healthcare utilization and financial burden. | 1 |
Asthma and chronic obstructive pulmonary disease (COPD) are both highly prevalent conditions that can coexist in the same individual: the so-called ‘asthma -COPD overlap’ (ACO).,Its prevalence and prognosis vary widely depending on how ACO is defined in each publication, the severity of bronchial obstruction of patients included and the treatment they are receiving.,Although there is a lack of evidence about the biology of ACO, the overlap of both diseases should express a mixture of a Th1 inflammatory pattern (characteristic of COPD) and a Th2 signature (characteristic of asthma).,In this review we support a novel algorithm for ACO diagnosis proposed by the Spanish Respiratory Society (SEPAR), based on a sequential evaluation that considers: (a) the presence of chronic airflow limitation in a smoker or ex-smoker patient ⩾35 years old; (b) a current diagnosis of asthma; and (c) the existence of a very positive bronchodilator test (PBT; ⩾15% and ⩾400 ml) or the presence of eosinophilia in blood (⩾300 eosinophils/μl).,This algorithm can identify those patients who may benefit from a treatment with inhaled corticosteroids (ICSs) and maybe from biological drugs in a near future.,In addition, it is easily applicable in clinical practice.,The major disadvantage is that it groups patients with very different characteristics under the ACO’s umbrella.,In view of this heterogeneity, we recommend a strategy of defining specific and measurable therapeutic objectives for every single patient and identifying the traits that can be treated to achieve those objectives. | Influenza is a frequent cause of exacerbations of chronic obstructive pulmonary disease (COPD).,Exacerbations are associated with worsening of the airflow obstruction, hospitalisation, reduced quality of life, disease progression, death, and ultimately, substantial healthcare-related costs.,Despite longstanding recommendations to vaccinate vulnerable high-risk groups against seasonal influenza, including patients with COPD, vaccination rates remain sub-optimal in this population.,We conducted a systematic review to summarise current evidence from randomised controlled trials (RCTs) and observational studies on the immunogenicity, safety, efficacy, and effectiveness of seasonal influenza vaccination in patients with COPD.,The selection of relevant articles was based on a three-step selection procedure according to predefined inclusion and exclusion criteria.,The search yielded 650 unique hits of which 48 eligible articles were screened in full-text.,Seventeen articles describing 13 different studies were found to be pertinent to this review.,Results of four RCTs and one observational study demonstrate that seasonal influenza vaccination is immunogenic in patients with COPD.,Two studies assessed the occurrence of COPD exacerbations 14 days after influenza vaccination and found no evidence of an increased risk of exacerbation.,Three RCTs showed no significant difference in the occurrence of systemic effects between groups receiving influenza vaccine or placebo.,Six out of seven studies on vaccine efficacy or effectiveness indicated long-term benefits of seasonal influenza vaccination, such as reduced number of exacerbations, reduced hospitalisations and outpatient visits, and decreased all-cause and respiratory mortality.,Additional large and well-designed observational studies would contribute to understanding the impact of disease severity and patient characteristics on the response to influenza vaccination.,Overall, the evidence supports a positive benefit-risk ratio for seasonal influenza vaccination in patients with COPD, and supports current vaccination recommendations in this population.,The online version of this article (doi:10.1186/s12890-017-0420-8) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) represents an important public health challenge.,Patients are confronted with limitations during activities of daily living (ADLs).,Resident loved ones of patients with COPD may be uniquely positioned to witness these limitations.,COPD may have an impact on not only the patients’ life, but also on the lives of the resident loved ones.,Furthermore, COPD exacerbation-related hospital admissions often occur in patients with COPD.,However, whether and to what extent these admissions influence resident loved ones’ burden and health status remains currently unknown.,Therefore, the primary objectives of this study are to investigate the differences between patients with COPD and resident loved ones’ perceptions of patients’ health status and problematic ADLs and to study prospectively the effects of a COPD exacerbation on resident loved ones’ perceptions of patients’ health status and problematic ADLs.,An observational, longitudinal study will be performed in 192 patients with COPD and their 192 resident loved ones.,Primary outcomes are daily functioning, ADL, disease-specific health status, generic health status and dyspnoea.,These will be assessed during home visits at baseline and after 12 months.,Additional home visits will be performed when a COPD exacerbation-related hospital admission occurs during the 12-month follow-up period.,This protocol was approved by the Medical Ethics Committee of the Catharina Hospital Eindhoven, the Netherlands (NL42721.060.12/M12-1280) and is registered in the Dutch Trial Register (NTR3941). | It is not known why survival differs between men and women in oxygen-dependent chronic obstructive pulmonary disease (COPD).,The present study evaluates differences in comorbidity between men and women, and tests the hypothesis that comorbidity contributes to sex-related differences in mortality in oxygen-dependent COPD.,National prospective study of patients aged 50 years or older, starting long-term oxygen therapy (LTOT) for COPD in Sweden between 1992 and 2008.,Comorbidities were obtained from the Swedish Hospital Discharge Register.,Sex-related differences in comorbidity were estimated using logistic regression, adjusting for age, smoking status and year of inclusion.,The effect of comorbidity on overall mortality and the interaction between comorbidity and sex were evaluated using Cox regression, adjusting for age, sex, PaO2 breathing air, FEV1, smoking history and year of inclusion.,In total, 8,712 patients (55% women) were included and 6,729 patients died during the study period.,No patient was lost to follow-up.,Compared with women, men had significantly more arrhythmia, cancer, ischemic heart disease and renal failure, and less hypertension, mental disorders, osteoporosis and rheumatoid arthritis (P<0.05 for all odds ratios).,Comorbidity was an independent predictor of mortality, and the effect was similar for the sexes.,Women had lower mortality, which remained unchanged even after adjusting for comorbidity; hazard ratio 0.73 (95% confidence interval, 0.68-0.77; P<0.001).,Comorbidity is different in men and women, but does not explain the sex-related difference in mortality in oxygen-dependent COPD. | 1 |
Long-acting bronchodilators are central in the pharmacological management of patients with chronic obstructive pulmonary disease (COPD).,The aim of this systematic review is to provide an overview of the studies evaluating the safety and clinical efficacy of inhaled glycopyrronium bromide, a novel long-acting muscarinic antagonist, in patients with COPD.,This study was performed as a systematic literature review.,Inhaled glycopyrronium bromide seems to be a safe and well tolerated long-acting muscarinic antagonist with a fast onset of action.,In patients suffering from moderate to severe COPD, glycopyrronium bromide has clinically important effects on level of forced expiratory volume in one second, use of relief medication, percentage of days with no use of rescue medication, daytime dyspnea scores, and probably also on health status.,Furthermore, in this group of patients, glycopyrronium bromide has beneficial effects on dynamic hyperinflation and exercise tolerance.,Glycopyrronium bromide has been shown to reduce the rate of exacerbations in patients with moderate to severe COPD, but long-term controlled trials with exacerbation rate as the primary outcome variable have not been published yet.,Once-daily inhaled glycopyrronium bromide has characteristics important for use in COPD, including a fast onset of action, sustained 24-hour bronchodilatation, and improvement in exercise tolerance, and therefore appears to have the potential for a significant role in the future management of COPD. | Events of the past decade have stimulated development of new drug formulations and delivery devices that have improved the efficiency, ease of use, and environmental impact of inhaled drug therapy.,Respimat® Soft Mist™ Inhaler is a novel, multidose, propellant-free, hand-held, liquid inhaler that represents a new category of inhaler devices.,The aerosol cloud generated by Respimat contains a higher fraction of fine particles than most pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs), and the aerosol spray exits the inhaler more slowly and for a longer duration than with pMDIs.,This translates into higher lung drug deposition and lower oropharyngeal deposition, making it possible to give lower nominal doses of delivered drugs without lowering efficacy.,In clinical trials in patients with COPD, bronchodilator drugs delivered from Respimat were equally effective at half of the dose delivered from a pMDI.,In one study of inhaler preference, Respimat was preferred over the pMDI by patients with COPD and other obstructive lung diseases.,Respimat is a valuable addition to the range of inhaler devices available to the patient with COPD. | 1 |
Key characteristics of chronic obstructive pulmonary disease (COPD) that significantly affect health-related quality of life (HRQoL) include chest symptoms, dyspnea, cough, sputum production, and exacerbations.,Additional areas of impact are sleep, fatigue, emotional well-being, social functioning, and coping.,Patient-reported outcomes (PROs) are essential to evaluate symptoms, impact of symptoms on activities of daily living, and treatment response.,This review summarizes COPD-specific PRO endpoints from randomized controlled trials of approved and commonly used COPD drugs.,A search conducted in “ClinicalTrials.gov” to identify COPD clinical trials (only completed Phase III and IV) incorporating PRO endpoints yielded a total of 104 clinical trials for inclusion in this analysis.,Both symptom-based and HRQoL-specific PRO measures were reported.,Several COPD-specific PRO measures are available; however, the St.,George’s Respiratory Questionnaire (SGRQ) and the Baseline and Transition Dyspnea Indexes (BDI/TDI) were reported in the majority of the studies.,Results reflected a gap in terms of full coverage of key impacted areas from a patient’s perspective.,Methodological issues identified in this review related to scoring of instruments require careful consideration, as these challenges may limit the complete assessment of drug benefits.,Selection of PRO measures aligned with the expected treatment benefit of a drug in a clinical trial should reflect patients’ perspective holistically. | The glucagon-like peptide-1 receptor (GLP-1R) agonist - liraglutide (LIR) - is an insulin secretagogue for the treatment of diabetes and has been proven to have therapeutic potential in the treatment of COPD.,Evidence suggested that activating GLP-1R signaling might have immunomodulating and anti-inflammatory effects.,COPD is characterized by dysregulation of immunity, oxidative stress, and excessive inflammation responses.,The aim of this study was to investigate whether GLP-1R signaling had a regulatory role in COPD immunity.,Fifty-seven COPD patients in a stable condition and 51 age-, sex-, and smoking history-matched non-COPD subjects provided blood samples for isolation of peripheral blood mononuclear cells (PBMCs).,GLP-1R expression was measured, and its association with clinical parameters and plasma cytokines was analyzed.,T cell function was assessed at baseline and after regulating GLP-1R expression.,GLP-1R expression decreased in circulating PBMCs of COPD patients, which was associated with decreased interferon (IFN)-γ expression.,Reduced IFN-γ production stimulated by phytohemagglutinin (PHA) and increased programmed cell death protein 1 (PD-1) expression on T cells were observed in COPD patients compared with non-COPD subjects.,Treatment with LIR could upregulate the GLP-1R expression, and this was observed to restore the antigen-stimulated IFN-γ production and downregulate PD-1 expression in T cells.,PBMCs of COPD patients showed defective GLP-1R signaling and functional T-lymphocyte abnormalities that could be rescued by LIR treatment. | 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. | There is much description in the literature of how patients with chronic obstructive pulmonary disease (COPD) manage their breathlessness and engage in self-care activities; however, little of this is from the perspective of those with less severe disease, who are primarily managed in primary care.,This study aimed to understand the self-care experiences of patients with COPD who are primarily managed in primary care, and to examine the challenges of engaging in such behaviors.,Semistructured interviews were carried out with 15 patients with COPD as part of a larger project evaluating a self-management intervention.,Thematic analysis was supported by NVivo software (version 8, QSR International, Melbourne, Australia).,Three main themes are described, ie, experiencing and understanding symptoms of COPD, current self-care activities, and the importance of family perceptions in managing COPD.,Self-care activities evolved spontaneously as participants experienced symptoms of COPD.,However, there was a lack of awareness about whether these strategies would impact upon symptoms.,Perceptions of COPD by family members posed a challenge to self-care for some participants.,Health care professionals should elicit patients’ prior disease experiences and utilize spontaneous attempts at disease management in future self-management.,These findings have implications for promoting self-management and enhancing quality of life. | 1 |
The 2019 coronavirus disease (COVID-19) pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2).,Clinical outcomes, including mortality, are worse in males, older individuals and patients with comorbidities.,COPD patients are included in shielding strategies due to their susceptibility to virus-induced exacerbations, compromised pulmonary function and high prevalence of associated comorbidities.,Using evidence from basic science and cohort studies, this review addresses key questions concerning COVID-19 and COPD.,First, are there mechanisms by which COPD patients are more susceptible to SARS-CoV-2 infection?,Secondly, do inhaled corticosteroids offer protection against COVID-19?,And, thirdly, what is the evidence regarding clinical outcomes from COVID-19 in COPD patients?,This up-to-date review tackles some of the key issues which have significant impact on the long-term outlook for COPD patients in the context of COVID-19.,This up-to-date review tackles some of the key issues which have significant impact on the long-term outlook for COPD patients in the context of COVID-19https://bit.ly/36PKzEO | 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 |
Cognitive behavioral therapy (CBT) is increasingly recommended in the management of people living with chronic obstructive pulmonary disease (COPD).,This rapid review presents the evidence base for CBT for people with COPD and describes 1) the nature of CBT interventions and comparators in controlled trials (high or low resource intensity); and 2) factors influencing intervention effects on health outcomes (anxiety, depression, breathlessness, quality of life and exercise capacity).,Primary studies reporting CBT interventions in adults with COPD were identified with data extracted by a single reviewer (20% of studies checked for data accuracy).,Studies were synthesized descriptively with meta-analyses (random effects models) of controlled trials undertaken to report mean standardized effect sizes (95% CI) for health outcomes.,Random effects meta-regression models explored whether CBT target, intervention dosage, intensity, facilitator profession, delivery mode, clinically significant anxiety/depression, trial design/quality and sample size predicted effect size.,The search identified 33 primary studies published between 1996 and 2019 (controlled trials n=24, single group cohort n=6, case exemplars n=2, phenomenological n=1).,Controlled trials frequently compared high-intensity CBT interventions against enhanced/usual care (n=12) or high-intensity CBT interventions against high-intensity comparators (n=11).,When all controlled studies were included, small, significant improvements favoring CBT were evident across all health outcomes (SMD ranged from −0.27 to 0.35, p<0.05).,When intensity dyads were considered, significant improvements were evident only when high-intensity CBT interventions were compared to enhanced usual care/usual care (SMDs ranged from −0.45 to 0.54, p <0.05).,No other variable consistently predicted intervention effect sizes across all health outcomes.,Overall, the evidence base supports the use of CBT for a range of health outcomes in people with COPD.,Consistent benefits were evident when high-resource-intensive CBT interventions were compared to usual care.,Low-resource-intensity CBT warrants further investigation in settings where cost of comprehensive care is prohibitive. | Identifying the predictors of noninvasive ventilation (NIV) failure has attracted significant interest because of the strong link between failure and poor outcomes.,However, very little attention has been paid to the timing of the failure.,This narrative review focuses on the causes of NIV failure and risk factors and potential remedies for NIV failure, based on the timing factor.,The possible causes of immediate failure (within minutes to <1 h) are a weak cough reflex, excessive secretions, hypercapnic encephalopathy, intolerance, agitation, and patient-ventilator asynchrony.,The major potential interventions include chest physiotherapeutic techniques, early fiberoptic bronchoscopy, changing ventilator settings, and judicious sedation.,The risk factors for early failure (within 1 to 48 h) may differ for hypercapnic and hypoxemic respiratory failure.,However, most cases of early failure are due to poor arterial blood gas (ABGs) and an inability to promptly correct them, increased severity of illness, and the persistence of a high respiratory rate.,Despite a satisfactory initial response, late failure (48 h after NIV) can occur and may be related to sleep disturbance.,Every clinician dealing with NIV should be aware of these risk factors and the predicted parameters of NIV failure that may change during the application of NIV.,Close monitoring is required to detect early and late signs of deterioration, thereby preventing unavoidable delays in intubation. | 1 |
Since the introduction of the Quality and Outcomes framework, there has been some evidence of improvement in the management of chronic obstructive pulmonary disease (COPD) patients in the United Kingdom through increasing rates of smoking cessation advice and immunisations against influenza.,However, it is unknown whether disease-specific management criteria, disease outcomes and diagnosis have improved.,To describe changes in the management and outcomes of patients with COPD in UK general practice between 2000 and 2009.,The study was done on a retrospective cohort using data from The Health Improvement Network UK primary care database.,We calculated age at diagnosis of COPD and death, total number of short-term oral corticosteroid courses and consultations, and proportion of patients with very severe COPD and on triple inhaled therapy for each year between 2000 and 2009.,We identified 92,576 patients with COPD.,The mean age at COPD diagnosis decreased from 68.1 years in 2000 to 66.7 years in 2009.,The mean age at death increased from 78.2 years in 2000 to 78.8 years in 2009.,The number of prescribed courses of oral corticosteroids increased from 0.6 in 2000 to 0.8 in 2009.,The number of consultations increased from 9.4 in 2004 to 11.3 in 2009.,The risk of having very severe COPD decreased from 9.4% in 2004 to 6.8% in 2009.,The likelihood of patients with very severe COPD receiving triple therapy increased from 25% in 2004 to 59% in 2009.,The trends suggest that management and outcomes observed in patients with COPD may have improved since the year 2000. | Exacerbation-associated health-related quality of life (HRQoL) in patients with severe and very severe chronic obstructive pulmonary disease (COPD) is ill-defined.,This study describes patterns, HRQoL, and the work productivity impact of COPD-related moderate and SEV exacerbations in patients with SEV/VSEV COPD, focusing on the chronic bronchitis subtype.,A US sample of SEV and VSEV COPD patients with recent moderate or SEV exacerbation was recruited.,Along with the demographic and clinical data collected from medical records, patients reported on exacerbation frequency, health-related quality of life (HRQoL) (using the St George’s Respiratory Questionnaire for COPD [SGRQ-C] and the European Quality of Life-5 Dimensions [EQ-5D]™ index), and work productivity and activity impairment (using the Work Productivity and Activity Impairment Questionnaire - Specific Health Problem [WPAI-SHP]).,The HRQoL-related impacts of exacerbation frequency, time since exacerbation, and last exacerbation severity were evaluated via linear regressions.,A total of 314 patients (190 SEV/124 VSEV, mean age =68.0 years, 51% male, 28% current smokers) were included.,In the previous 12 months, patients reported an average of 1.8 moderate exacerbations and 0.9 SEV exacerbations.,Overall, 16% of patients were employed and reported a high percentage of overall work impairment (42.4% ± 31.1%).,Activity impairment was positively associated with recent exacerbation severity (SEV 64.6% ± 26.8% versus moderate 55.6% ± 28.2%) (P=0.006).,The HRQoL was significantly worse for SEV versus VSEV COPD (EQ-5D: 0.62 ± 0.23 versus 0.70 ± 0.17, respectively, and SGRQ-C: 70.1 ± 21.3 versus 61.1 ± 19.0, respectively) (P<0.001).,Worse current HRQoL was reported by patients with a SEV versus moderate recent exacerbation (EQ-5D: 0.63 ± 0.21 versus 0.70 ± 0.20, respectively) (P=0.003); SGRQ-C: 70.3 ± 19.9 versus 61.7 ± 20.1, respectively (P<0.001).,One additional exacerbation in the previous 12 months was associated with a 2.4-point SGRQ-C increase and a 0.02-point EQ-5D index decrease.,The severity and frequency of COPD-related moderate/SEV exacerbations in SEV and VSEV COPD patients were positively associated with poor HRQoL and work productivity and activity impairment. | 1 |
There is a need for biomarkers to better characterise individuals with COPD and to aid with the development of therapeutic interventions.,A panel of putative blood biomarkers was assessed in a subgroup of the Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) cohort.,Thirty-four blood biomarkers were assessed in 201 subjects with COPD, 37 ex-smoker controls with normal lung function and 37 healthy non-smokers selected from the ECLIPSE cohort.,Biomarker repeatability was assessed using baseline and 3-month samples.,Intergroup comparisons were made using analysis of variance, repeatability was assessed through Bland-Altman plots, and correlations between biomarkers and clinical characteristics were assessed using Spearman correlation coefficients.,Fifteen biomarkers were significantly different in individuals with COPD when compared to former or non-smoker controls.,Some biomarkers, including tumor necrosis factor-α and interferon-γ, were measurable in only a minority of subjects whilst others such as C-reactive protein showed wide variability over the 3-month replication period.,Fibrinogen was the most repeatable biomarker and exhibited a weak correlation with 6-minute walk distance, exacerbation rate, BODE index and MRC dyspnoea score in COPD subjects. 33% (66/201) of the COPD subjects reported at least 1 exacerbation over the 3 month study with 18% (36/201) reporting the exacerbation within 30 days of the 3-month visit.,CRP, fibrinogen interleukin-6 and surfactant protein-D were significantly elevated in those COPD subjects with exacerbations within 30 days of the 3-month visit compared with those individuals that did not exacerbate or whose exacerbations had resolved.,Only a few of the biomarkers assessed may be useful in diagnosis or management of COPD where the diagnosis is based on airflow obstruction (GOLD).,Further analysis of more promising biomarkers may reveal utility in subsets of patients.,Fibrinogen in particular has emerged as a potentially useful biomarker from this cohort and requires further investigation.,SCO104960, clinicaltrials.gov identifier NCT00292552 | There is a paucity of surrogate lung-specific biological markers that can be used to track disease progression and predict clinical outcomes in chronic obstructive pulmonary disease (COPD).,The principal aim of this pilot study was to determine whether circulating surfactant protein D (SPD) or Clara Cell protein-16 (CC16) levels are associated with lung function or health status in patients with severe COPD.,We studied 23 patients with advanced COPD.,Lung function measurements, Chronic Respiratory Disease Questionnaire (CRQ) scores, and serum levels of SPD, CC16, and C-reactive protein (CRP) were determined at baseline and at 3 months.,At baseline, FEV1 was inversely associated with serum SPD levels (P = 0.045) but not with CC16 (P = 0.675) or CRP levels (P = 0.549).,Over a 3 month period, changes in SPD levels correlated significantly with changes in CRQ scores (adjusted P = 0.008) such that patients who had the largest declines in serum SPD levels experienced the largest gains in health status.,The association was particularly notable between circulating SPD level and the dyspnea domain of the CRQ score (P = 0.018).,Changes in CC16 or CRP levels did not correlate with changes in CRQ scores.,Changes in serum SPD levels tracked well with changes in health status over a 3 month period in patients with severe COPD.,These data suggest that circulating SPD levels may be useful biomarkers to track health outcomes of COPD patients. | 1 |
Background: Evidence-based guidelines are needed for effective delivery of home oxygen therapy to appropriate patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD).,Methods: The multidisciplinary panel created six research questions using a modified Delphi approach.,A systematic review of the literature was completed, and the Grading of Recommendations Assessment, Development and Evaluation approach was used to formulate clinical recommendations.,Recommendations: The panel found varying quality and availability of evidence and made the following judgments: 1) strong recommendations for long-term oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe chronic resting hypoxemia, 2) a conditional recommendation against long-term oxygen use in patients with COPD with moderate chronic resting hypoxemia, 3) conditional recommendations for ambulatory oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe exertional hypoxemia, 4) a conditional recommendation for ambulatory liquid-oxygen use in patients who are mobile outside the home and require >3 L/min of continuous-flow oxygen during exertion (very-low-quality evidence), and 5) a recommendation that patients and their caregivers receive education on oxygen equipment and safety (best-practice statement).,Conclusions: These guidelines provide the basis for evidence-based use of home oxygen therapy in adults with COPD or ILD but also highlight the need for additional research to guide clinical practice. | Chronic obstructive pulmonary disease (COPD) is a common disease that severely threatens human health.,Acute exacerbation of COPD (AECOPD) is a major cause of disease progression and death, and causes huge medical expenditures.,This consensus statement represents a description of clinical features of AECOPD in the People’s Republic of China and a set of recommendations.,It is intended to provide clinical guidelines for community physicians, pulmonologists and other health care providers for the prevention, diagnosis, and treatment of AECOPD. | 1 |
Self-management of exacerbations in COPD patients is important to reduce exacerbation impact.,There is a need for more comprehensive and individualized interventions to improve exacerbation-related self-management behavior.,The use of mobile health (mHealth) could help to achieve a wide variety of behavioral goals.,Understanding of patients and health care providers perspectives towards using mHealth in promoting self-management will greatly enhance the development of solutions with optimal usability and feasibility.,Therefore, the aim of this study was to explore perceptions of COPD patients and their health care providers towards using mHealth for self-management of exacerbations.,A qualitative study using focus group interviews with COPD patients (n = 13) and health care providers (HCPs) (n = 6) was performed to explore perceptions towards using mHealth to support exacerbation-related self-management.,Data were analyzed by a thematic analysis.,COPD patients and HCPs perceived mostly similar benefits and barriers of using mHealth for exacerbation-related self-management.,These perceived benefits and barriers seem to be important drivers in the willingness to use mHealth.,Both patients and HCPs strengthen the need for a multi-component and tailored mHealth intervention that improves patients’ exacerbation-related self-management by determining their health status and providing adequate information, decision support and feedback on self-management behavior.,Most importantly, patients and HCPs considered an mHealth intervention as support to improve self-management and emphasized that it should never replace patients’ own feelings nor undermine their own decisions.,In addition, the intervention should be complementary to regular contact with HCPs, as personal contact with a HCP was considered to be very important.,To optimize engagement with mHealth, patients should have a positive attitude toward using mHealth and an mHealth intervention should be attractive, rewarding and safe.,This study provided insight into perceptions of COPD patients and their HCPs towards using mHealth for self-management of exacerbations.,This study points out that future mHealth interventions should focus on developing self-management skills over time by providing adequate information, decision support and feedback on self-management behavior and that mHealth should complement regular care.,To optimize engagement, mHealth interventions should be attractive, rewarding, safe and tailored to the patient needs.,The online version of this article (10.1186/s12913-018-3545-4) contains supplementary material, which is available to authorized users. | Within telehealth there are a number of domains relevant to pulmonary care: telemonitoring, teleassistance, telerehabilitation, teleconsultation and second opinion calls.,In the last decade, several studies focusing on the effects of various telemanagement programs for patients with chronic obstructive pulmonary disease (COPD) have been published but with contradictory findings.,From the literature, the best telemonitoring outcomes come from programs dedicated to aged and very sick patients, frequent exacerbators with multimorbidity and limited community support; programs using third-generation telemonitoring systems providing constant analytical and decisionmaking support (24 h/day, 7 days/week); countries where strong community links are not available; and zones where telemonitoring and rehabilitation can be delivered directly to the patient’s location.,In the near future, it is expected that telemedicine will produce changes in work practices, cultural attitudes and organization, which will affect all professional figures involved in the provision of care.,The key to optimizing the use of telemonitoring is to correctly identify who the ideal candidates are, at what time they need it, and for how long.,The time course of disease progression varies from patient to patient; hence identifying for each patient a ‘correct window’ for initiating telemonitoring could be the correct solution.,In conclusion, as clinicians, we need to identify the specific challenges we face in delivering care, and implement flexible systems that can be customized to individual patients’ requirements and adapted to our diverse healthcare contexts. | 1 |
Thoracic computed tomography (CT) scans are widely performed in clinical practice, often leading to detection of airway or parenchymal abnormalities in asymptomatic or minimally symptomatic individuals.,However, clinical relevance of CT abnormalities is uncertain in the general population.,We evaluated data from 1361 participants aged ≥40 years from a Canadian prospective cohort comprising 408 healthy never-smokers, 502 healthy ever-smokers, and 451 individuals with spirometric evidence of chronic obstructive pulmonary disease (COPD) who had thoracic CT scans.,CT images of subjects were visually scored for respiratory bronchiolitis(RB), emphysema(E), bronchial-wall thickening(BWT), expiratory air-trapping(AT), and bronchiectasis(B).,Multivariable logistic regression models were used to assess associations of CT features with respiratory symptoms, dyspnea, health status as determined by COPD assessment test, and risk of clinically significant exacerbations during 12 months follow-up.,About 11% of life-time never-smokers demonstrated emphysema on CT scans.,Prevalence increased to 30% among smokers with normal lung function and 36%, 50%, and 57% among individuals with mild, moderate or severe/very severe COPD, respectively.,Presence of emphysema on CT was associated with chronic cough (OR,2.11; 95%CI,1.4-3.18); chronic phlegm production (OR,1.87; 95% CI,1.27-2.76); wheeze (OR,1.61; 95% CI,1.05-2.48); dyspnoea (OR,2.90; 95% CI,1.41-5.98); CAT score≥10(OR,2.17; 95%CI,1.42-3.30) and risk of ≥2 exacerbations over 12 months (OR,2.17; 95% CI, 1.42-3.0).,Burden of thoracic CT abnormalities is high among Canadians ≥40 years of age, including never-smokers and smokers with normal lung function.,Detection of emphysema on CT scans is associated with pulmonary symptoms and increased risk of exacerbations, independent of smoking or lung function. | Gastroesophageal reflux disease (GERD) is one of the most common causes of chronic cough and a potential risk factor for exacerbation of chronic obstructive pulmonary disease (COPD).,The aim of this study was to investigate the prevalence and risk factors of GERD in patients with COPD and association between GERD and COPD exacerbation.,Data were collected from the National Health Insurance Database of Korea.,The subjects were 40 years old and older, who had COPD as primary or secondary diagnosis codes and utilized health care resource to receive prescriptions of COPD medication at least twice in 2009.,Univariate logistic regression was performed to understand the relationship between COPD and GERD, and multiple logistic regression analysis was performed with adjustment for several confounding factors.,The prevalence of GERD in COPD patients was 28% (39,987/141,057).,Old age, female gender, medical aid insurance type, hospitalization, and emergency room (ER) visit were associated with GERD.,Most of COPD medications except inhaled muscarinic antagonists were associated with GERD.,The logistic regression analysis showed that the presence of GERD was associated with increased risk of hospitalization (OR 1.54, CI 1.50 to 1.58, p<0.001) and frequent ER visits (OR 1.55, CI 1.48 to 1.62, p<0.001).,The prevalence of GERD in patients with COPD was high.,Old age, female gender, medical aid insurance type, and many COPD medications except inhaled muscarinic antagonists were associated with GERD.,The presence of GERD was associated with COPD exacerbation. | 1 |
The quest for the right combination of bronchodilators with different mechanisms of action such as long-acting muscarinic antagonists and long-acting β-agonists in the management of stable moderate-to-severe chronic obstructive pulmonary disease (COPD) is a topic of intense research activity currently, given the rising morbidity and mortality due to this disease.,The fixed-dose combination of aclidinium bromide and formoterol fumarate in a single inhaler seems to offer superior advantages over either drugs given alone or as separate inhalers concurrently.,Since the fixed-dose combination needs to be given twice daily, it is likely to achieve control of symptoms most crucial to the quality of life in COPD, namely, the morning hours.,This is reflected in significant trough FEV1 (forced expiratory volume in 1 second) improvements after the dose.,This paper reviews the various studies related to this combination put in the perspective of its safety and efficacy and potential benefits over other therapeutic options.,However, there is a dearth of data on the long-term safety and efficacy in terms of improvement in lung function.,This combination could emerge as an excellent option in the management of stable COPD if data on exacerbation rates and patient-reported outcomes become available from longer-term studies.,Moreover, we need some more studies to define the ideal phenotype of COPD best suited for the use of this combination. | Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.,Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks.,Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.,In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment.,Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies.,Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg.,Incidence of adverse events was comparable between the FDCs and the mono-components.,These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.,Lung function and symptomatic benefits of daily tiotropium+olodaterol fixed-dose combination in moderate to very severe COPDhttp://ow.ly/DIKiY | 1 |
We aimed to evaluate correlations between computed tomography (CT) parameters and pulmonary function test (PFT) parameters according to disease severity in patients with chronic obstructive pulmonary disease (COPD), and to determine whether CT parameters can be used to predict PFT indices.,A total of 370 patients with COPD were grouped based on disease severity according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) I-IV criteria.,Emphysema index (EI), air-trapping index, and airway parameters such as the square root of wall area of a hypothetical airway with an internal perimeter of 10 mm (Pi10) were measured using automatic segmentation software.,Clinical characteristics including PFT results and quantitative CT parameters according to GOLD criteria were compared using ANOVA.,The correlations between CT parameters and PFT indices, including the ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) and FEV1, were assessed.,To evaluate whether CT parameters can be used to predict PFT indices, multiple linear regression analyses were performed for all patients, Group 1 (GOLD I and II), and Group 2 (GOLD III and IV).,Pulmonary function deteriorated with increase in disease severity according to the GOLD criteria (p < 0.001).,Parenchymal attenuation parameters were significantly worse in patients with higher GOLD stages (p < 0.001), and Pi10 was highest for patients with GOLD III (4.41 ± 0.94 mm).,Airway parameters were nonlinearly correlated with PFT results, and Pi10 demonstrated mild correlation with FEV1/FVC in patients with GOLD II and III (r = 0.16, p = 0.06 and r = 0.21, p = 0.04, respectively).,Parenchymal attenuation parameters, airway parameters, EI, and Pi10 were identified as predictors of FEV1/FVC for the entire study sample and for Group 1 (R2 = 0.38 and 0.22, respectively; p < 0.001).,However, only parenchymal attenuation parameter, EI, was identified as a predictor of FEV1/FVC for Group 2 (R2 = 0.37, p < 0.001).,Similar results were obtained for FEV1.,Airway and parenchymal attenuation parameters are independent predictors of pulmonary function in patients with mild COPD, whereas parenchymal attenuation parameters are dominant independent predictors of pulmonary function in patients with severe COPD. | Preserved Ratio Impaired Spirometry (PRISm), defined as a reduced FEV1 in the setting of a preserved FEV1/FVC ratio, is highly prevalent and is associated with increased respiratory symptoms, systemic inflammation, and mortality.,Studies investigating quantitative chest tomographic features, genetic associations, and subtypes in PRISm subjects have not been reported.,Data from current and former smokers enrolled in COPDGene (n = 10,192), an observational, cross-sectional study which recruited subjects aged 45-80 with ≥10 pack years of smoking, were analyzed.,To identify epidemiological and radiographic predictors of PRISm, we performed univariate and multivariate analyses comparing PRISm subjects both to control subjects with normal spirometry and to subjects with COPD.,To investigate common genetic predictors of PRISm, we performed a genome-wide association study (GWAS).,To explore potential subgroups within PRISm, we performed unsupervised k-means clustering.,The prevalence of PRISm in COPDGene is 12.3%.,Increased dyspnea, reduced 6-minute walk distance, increased percent emphysema and decreased total lung capacity, as well as increased segmental bronchial wall area percentage were significant predictors (p-value <0.05) of PRISm status when compared to control subjects in multivariate models.,Although no common genetic variants were identified on GWAS testing, a significant association with Klinefelter’s syndrome (47XXY) was observed (p-value < 0.001).,Subgroups identified through k-means clustering include a putative “COPD-subtype”, “Restrictive-subtype”, and a highly symptomatic “Metabolic-subtype”.,PRISm subjects are clinically and genetically heterogeneous.,Future investigations into the pathophysiological mechanisms behind and potential treatment options for subgroups within PRISm are warranted.,Clinicaltrials.gov Identifier: NCT000608764.,The online version of this article (doi:10.1186/s12931-014-0089-y) contains supplementary material, which is available to authorized users. | 1 |
Background: To validate the ‘Test of Adherence to Inhalers’ (TAI), a 12-item questionnaire designed to assess the adherence to inhalers in patients with COPD or asthma.,Methods: A total of 1009 patients with asthma or COPD participated in a cross-sectional multicenter study.,Patients with electronic adherence ≥80% were defined as adherents.,Construct validity, internal validity, and criterion validity were evaluated.,Self-reported adherence was compared with the Morisky-Green questionnaire.,Results: Factor analysis study demonstrated two factors, factor 1 was coincident with TAI patient domain (items 1 to 10) and factor 2 with TAI health-care professional domain (items 11 and 12).,The Cronbach's alpha was 0.860 and the test-retest reliability 0.883.,TAI scores correlated with electronic adherence (ρ=0.293, p=0.01).,According to the best cut-off for 10 items (score 50, area under the ROC curve 0.7), 569 (62.5%) patients were classified as non-adherents.,The non-adherence behavior pattern was: erratic 527 (57.9%), deliberate 375 (41.2%), and unwitting 242 (26.6%) patients.,As compared to Morisky-Green test, TAI showed better psychometric properties.,Conclusions: The TAI is a reliable and homogeneous questionnaire to identify easily non-adherence and to classify from a clinical perspective the barriers related to the use of inhalers in asthma and COPD. | Chronic obstructive pulmonary disease (COPD) is a major public health problem, associated with considerable morbidity and health care costs.,The global burden of COPD morbidity is predicted to rise substantially in the coming decade, but could be moderated by better use of existing management strategies.,Smoking cessation, medication therapy, and pulmonary rehabilitation have all been shown to diminish morbidity and improve patient outcomes.,But each of these strategies requires adherence.,Adherence is crucial for optimizing clinical outcomes in COPD, with nonadherence resulting in a significant health and economic burden.,Suboptimal medication adherence is common among COPD patients, due to a number of factors that involve the medication, the delivery device, the patient, and the health professionals caring for the patient.,Lack of medication adherence needs to be identified and addressed by using simplified treatment regimens, increasing patient knowledge about self-management, and enhancing provider skills in patient education, communication, and adherence counseling.,This article reports some of the challenges of medication nonadherence faced by the clinician in the management of COPD, and suggests ways to evaluate and improve adherence effectively in primary care. | 1 |
Rationale: In the phase III, 52-week ETHOS (Efficacy and Safety of Triple Therapy in Obstructive Lung Disease) trial in chronic obstructive pulmonary disease (COPD) (NCT02465567), triple therapy with budesonide/glycopyrrolate/formoterol fumarate (BGF) significantly reduced all-cause mortality compared with glycopyrrolate/formoterol fumarate (GFF).,However, 384 of 8,509 patients were missing vital status at Week 52 in the original analyses.,Objectives: To assess the robustness of the ETHOS mortality findings after additional data retrieval for patients missing Week 52 vital status in the original analyses.,Methods: Patients with moderate to very severe COPD and prior history of exacerbation received twice-daily dosing with 320/18/9.6 μg of BGF (BGF 320), 160/18/9.6 μg of BGF (BGF 160), 18/9.6 μg of GFF, or 320/9.6 μg of budesonide/formoterol fumarate (BFF) (all delivered via a single metered-dose Aerosphere inhaler).,Time to death (all-cause) was a prespecified secondary endpoint.,Measurements and Main Results: In the final retrieved dataset, which included Week 52 vital status for 99.6% of the intent-to-treat population, risk of death with BGF 320 was significantly lower than GFF (hazard ratio, 0.51; 95% confidence interval, 0.33-0.80; unadjusted P = 0.0035).,There were no significant differences in mortality when comparing BGF 320 with BFF (hazard ratio, 0.72; 95% confidence interval, 0.44-1.16; P = 0.1721), nor were significant differences observed when comparing BGF 160 against either dual comparator.,Results were similar when the first 30, 60, or 90 days of treatment were excluded from the analysis.,Deaths from cardiovascular causes occurred in 0.5%, 0.8%, 1.4%, and 0.5% of patients in the BGF 320, BGF 160, GFF, and BFF groups, respectively.,Conclusions: Using final retrieved vital status data, triple therapy with BGF 320 reduced the risk of death compared with GFF, but was not shown to significantly reduce the risk of death compared with BFF, in patients with COPD.,Triple therapy containing a lower dose of inhaled corticosteroid (BGF 160) was not shown to significantly reduce the risk of death compared with the dual therapy comparators. | Chronic obstructive pulmonary disease (COPD) is characterized by incompletely reversible airflow obstruction.,Direct measurement of airways resistance using invasive techniques has revealed that the site of obstruction is located in the small conducting airways, ie, bronchioles with a diameter < 2 mm.,Anatomical changes in these airways include structural abnormalities of the conducting airways (eg, peribronchiolar fibrosis, mucus plugging) and loss of alveolar attachments due to emphysema, which result in destabilization of these airways related to reduced elastic recoil.,The relative contribution of structural abnormalities in small conducting airways and emphysema has been a matter of much debate.,The present article reviews anatomical changes and inflammatory mechanisms in small conducting airways and in the adjacent lung parenchyma, with a special focus on recent anatomical and imaging data suggesting that the initial event takes place in the small conducting airways and results in a dramatic reduction in the number of airways, together with a reduction in the cross-sectional area of remaining airways.,Implications of these findings for the development of novel therapies are briefly discussed. | 1 |
Chronic obstructive pulmonary disease (COPD) is one of the top five major causes of morbidity and mortality worldwide.,Despite worldwide health care efforts, costs, and medical research, COPD figures demonstrate a continuously increasing tendency in mortality.,This is contrary to other top causes of death, such as neoplasm, accidents, and cardiovascular disease.,A major factor affecting COPD-related mortality is the acute exacerbation of COPD (AECOPD).,Exacerbations and comorbidities contribute to the overall severity in individual patients.,Despite the underestimation by the physicians and the patients themselves, AECOPD is a really devastating event during the course of the disease, similar to acute myocardial infarction in patients suffering from coronary heart disease.,In this review, we focus on the evidence that supports the claim that AECOPD is the “stroke of the lungs”.,AECOPD can be viewed as: a Semicolon or disease’s full-stop period, Triggering a catastrophic cascade, usually a Relapsing and Overwhelming event, acting as a Killer, needing Emergent treatment. | Natural history of chronic obstructive pulmonary disease (COPD) is punctuated by exacerbations; however, little is known about prognosis of the first-ever COPD exacerbation and variables predicting its outcomes.,A population-based cohort study among COPD patients with their first-ever exacerbations requiring hospitalizations was conducted.,Main outcomes were in-hospital mortality and one-year mortality after discharge.,Demographics, comorbidities, medications and in-hospital events were obtained to explore outcome predictors.,The cohort comprised 4204 hospitalized COPD patients, of whom 175 (4%) died during the hospitalization.,In-hospital mortality was related to higher age (odds ratio [OR]: 1.05 per year; 95% confidence interval [CI]: 1.03-1.06) and Charlson comorbidity index score (OR: 1.08 per point; 95% CI: 1.01-1.15); angiotensin II receptor blockers (OR: 0.61; 95% CI: 0.38-0.98) and β blockers (OR: 0.63; 95% CI: 0.41-0.95) conferred a survival benefit.,At one year after discharge, 22% (871/4029) of hospital survivors were dead.,On multivariate Cox regression analysis, age and Charlson comorbidity index remained independent predictors of one-year mortality.,Longer hospital stay (hazard ratio [HR] 1.01 per day; 95% CI: 1.01-1.01) and ICU admission (HR: 1.33; 95% CI: 1.03-1.73) during the hospitalization were associated with higher mortality risks.,Prescription of β blockers (HR: 0.79; 95% CI: 0.67-0.93) and statins (HR: 0.66; 95% CI: 0.47-0.91) on hospital discharge were protective against one-year mortality.,Even the first-ever severe COPD exacerbation signifies poor prognosis in COPD patients.,Comorbidities play a crucial role in determining outcomes and should be carefully assessed.,Angiotensin II receptor blockers, β blockers and statins may, in theory, have dual cardiopulmonary protective properties and probably alter prognosis of COPD patients.,Nevertheless, the limitations inherent to a claims database study, such as the diagnostic accuracy of COPD and its exacerbation, should be born in mind. | 1 |
The term multimorbidity is usually defined as the coexistence of two or more chronic conditions within an individual, whereas the term comorbidity traditionally describes patients with an index condition and one or more additional conditions.,Multimorbidity of chronic conditions markedly worsens outcomes in patients, increases treatment burden and increases health service costs.,Although patients with chronic respiratory disease often have physical comorbidities, they also commonly experience psychological problems such as depression and anxiety.,Multimorbidity is associated with increased health-care utilisation and specifically with an increased number of prescription drugs in individuals with multiple chronic conditions such as chronic obstructive pulmonary disease.,This npj Primary Care Respiratory Medicine Education Section case study involves a patient in a primary care consultation presenting several common diseases prevalent in people of this age.,The patient takes nine different drugs at this moment, one or more pills for each condition, which amounts to polypharmacy.,The problems related with polypharmacy recommend that a routine medication review by primary care physicians be performed to reduce the risk of adverse effects of polypharmacy among those with multiple chronic conditions.,The primary care physician has the challenging role of integrating all of the clinical problems affecting the patient and reviewing all medicaments (including over-the-counter medications) taken by the patient at any point in time, and has the has the key to prevent the unwanted consequences of polypharmacy.,Multimorbid chronic disease management can be achieved with the use of care planning, unified disease templates, use of information technology with appointment reminders and with the help of the wider primary care and community teams. | Low health literacy is associated with low adherence to self-management in many chronic diseases.,Additionally, health beliefs are thought to be determinants of self-management behaviors.,In this study we sought to determine the association, if any, of health literacy and health beliefs among elderly individuals with COPD.,We enrolled a cohort of patients with COPD from two academic urban settings in New York, NY and Chicago, IL.,Health literacy was measured using the Short Test of Functional Health Literacy in Adults.,Using the framework of the Self-Regulation Model, illness and medication beliefs were measured with the Brief Illness Perception Questionnaire (B-IPQ) and Beliefs about Medications Questionnaire (BMQ).,Unadjusted analyses, with corresponding Cohen’s d effect sizes, and multiple logistic regression were used to assess the relationships between HL and illness and medication beliefs.,We enrolled 235 participants, 29% of whom had low health literacy.,Patients with low health literacy were more likely to belong to a racial minority group (p<0.001), not be married (p = 0.006), and to have lower income (p<0.001) or education (p<0.001).,In unadjusted analyses, patients with low health literacy were less likely to believe they will always have COPD (p = 0.003, Cohen’s d = 0.42), and were more likely to be concerned about their illness ((p = 0.04, Cohen’s d = 0.17).,In analyses adjusted for sociodemographic factors and other health beliefs, patients with low health literacy were less likely to believe that they will always have COPD (odds ratio [OR]: 0.78, 95% confidence interval [CI]: 0.65-0.94).,In addition, the association of low health literacy with expressed concern about medications remained significant (OR: 1.20, 95% CI: 1.05-1.37) though the association of low health literacy with belief in the necessity of medications was no longer significant (OR: 0.92, 95% CI: 0.82-1.04).,In this cohort of urban individuals with COPD, low health literacy was prevalent, and associated with illness beliefs that predict decreased adherence.,Our results suggest that targeted strategies to address low health literacy and related illness and medications beliefs might improve COPD medication adherence and other self-management behaviors. | 1 |
COPD patients with increased airway eosinophilic inflammation show a favorable response to inhaled corticosteroids (ICS) in combination with a long-acting bronchodilator.,Recent studies have demonstrated a significant correlation of sputum eosinophilia with blood eosinophils and periostin.,We investigated whether high blood eosinophils and plasma periostin were associated with an improvement in forced expiratory volume in 1 second (FEV1) after 3-month treatment with ICS/long-acting beta2-agonist (LABA) in stable COPD patients.,Blood eosinophils and plasma periostin levels were measured in 130 stable COPD subjects selected from the Korean Obstructive Lung Disease cohort.,Subjects began a 3-month ICS/LABA treatment after washout period.,High blood eosinophils (>260/µL, adjusted odds ratio =3.52, P=0.009) and high plasma periostin (>23 ng/mL, adjusted odds ratio =3.52, P=0.013) were significantly associated with FEV1 responders (>12% and 200 mL increase in FEV1 from baseline after treatment).,Moreover, the addition of high blood eosinophils to age, baseline positive bronchodilator response, and FEV1 <50% of the predicted value significantly increased the area under the curve for prediction of FEV1 responders (from 0.700 to 0.771; P=0.045).,High blood eosinophils and high plasma periostin were associated with improved lung function after 3-month ICS/LABA treatment.,In particular, high blood eosinophils, in combination with age and baseline lung function parameters, might be a possible biomarker for identification of COPD patients with favorable FEV1 improvement in response to ICS/LABA treatment. | Chronic obstructive pulmonary disease (COPD) and asthma may overlap and converge in older people (overlap syndrome).,It was hypothesized that patients with overlap syndrome may have different clinical characteristics such as sputum eosinophilia, and better responsiveness to treatment with inhaled corticosteroid (ICS).,Sixty-three patients with stable COPD (forced expiratory volume in 1 second [FEV1] ≤80%) underwent pulmonary function tests, including reversibility of airflow limitation, arterial blood gas analysis, analysis of inflammatory cells in induced sputum, and chest high-resolution computed tomography.,The inclusion criteria for COPD patients with asthmatic symptoms included having asthmatic symptoms such as episodic breathlessness, wheezing, cough, and chest tightness worsening at night or in the early morning (COPD with asthma group).,The clinical features of COPD patients with asthmatic symptoms were compared with those of COPD patients without asthmatic symptoms (COPD without asthma group).,The increases in FEV1 in response to treatment with ICS were significantly higher in the COPD with asthma group.,The peripheral eosinophil counts and sputum eosinophil counts were significantly higher.,The prevalence of patients with bronchial wall thickening on chest high-resolution computed tomography was significantly higher.,A significant correlation was observed between the increases in FEV1 in response to treatment with ICS and sputum eosinophil counts, and between the increases in FEV1 in response to treatment with ICS and the grade of bronchial wall thickening.,Receiver operating characteristic curve analysis revealed 82.4% sensitivity and 84.8% specificity of sputum eosinophil count for detecting COPD with asthma, using 2.5% as the cutoff value.,COPD patients with asthmatic symptoms had some clinical features.,ICS should be considered earlier as a potential treatment in such patients.,High sputum eosinophil counts and bronchial wall thickening on chest high-resolution computed tomography might therefore be a good predictor of response to ICS. | 1 |
Randomized controlled trials (RCTs) indicate that long-acting bronchodilator combinations, such as β2-agonist (LABA)/muscarinic antagonist (LAMA), have favorable efficacy compared with commonly used COPD treatments.,The objective of this analysis was to compare the efficacy and safety of LABA/LAMA with LAMA or LABA/inhaled corticosteroid (ICS) in adults with stable moderate-to-very-severe COPD.,This systematic review and meta-analysis (PubMed/MEDLINE, Embase, Cochrane Library and clinical trial/manufacturer databases) included RCTs comparing ≥12 weeks’ LABA/LAMA treatment with LAMA and/or LABA/ICS (approved doses only).,Eligible studies were independently selected by two authors using predefined data fields; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.,Eighteen studies (23 trials) were eligible (N=20,185).,LABA/LAMA significantly improved trough forced expiratory volume in 1 second (FEV1) from baseline to week 12 versus both LAMA and LABA/ICS (0.07 L and 0.08 L, P<0.0001), with patients more likely to achieve clinically important improvements in FEV1 of >100 mL (risk ratio [RR]: 1.33, 95% confidence interval [CI]: [1.20, 1.46] and RR: 1.44, 95% CI: [1.33, 1.56], respectively, the number needed to treat being eight and six, respectively).,LABA/LAMA improved transitional dyspnea index and St George’s Respiratory Questionnaire scores at week 12 versus LAMA (both P<0.0001), but not versus LABA/ICS, and reduced rescue medication use versus both (P<0.0001 and P=0.001, respectively).,LABA/LAMA significantly reduced moderate/severe exacerbation rate compared with LABA/ICS (RR 0.82, 95% CI: [0.75, 0.91]).,Adverse event (AE) incidence was no different for LABA/LAMA versus LAMA treatment, but it was lower versus LABA/ICS (RR 0.94, 95% CI: [0.89, 0.99]), including a lower pneumonia risk (RR 0.59, 95% CI: [0.43, 0.81]).,LABA/LAMA presented a lower risk for withdrawals due to lack of efficacy versus LAMA (RR: 0.66, 95% CI: [0.51, 0.87]) and due to AEs versus LABA/ICS (RR: 0.83, 95% CI: [0.69, 0.99]).,The greater efficacy and comparable safety profiles observed with LABA/LAMA combinations versus LAMA or LABA/ICS support their potential role as first-line treatment options in COPD.,These findings are of direct relevance to clinical practice because we included all currently available LABA/LAMAs and comparators, only at doses approved for clinical use. | A combination therapy with inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA) is recommended in severe chronic obstructive pulmonary disease (COPD) patients experiencing frequent exacerbations.,Currently, there are five ICS/LABA combination products available on the market.,The purpose of this study was to systematically review the efficacy of various ICS/LABA combinations with a network meta-analysis.,Several databases and manufacturer’s websites were searched for relevant clinical trials.,Randomized control trials, at least 12 weeks duration, comparing an ICS/LABA combination with active control or placebo were included.,Moderate and severe exacerbations were chosen as the outcome assessment criteria.,The primary analyses were conducted with a Bayesian Markov chain Monte Carlo method.,Most of the ICS/LABA combinations reduced moderate-to-severe exacerbations as compared with placebo and LABA, but none of them reduced severe exacerbations.,However, many studies excluded patients receiving long-term oxygen therapy.,Moderate-dose ICS was as effective as high-dose ICS in reducing exacerbations when combined with LABA.,ICS/LABA combinations had a class effect with regard to the prevention of COPD exacerbations.,Moderate-dose ICS/LABA combination therapy would be sufficient for COPD patients when indicated.,The efficacy of ICS/LABA combination therapy appeared modest and had no impact in reducing severe exacerbations.,Further studies are needed to evaluate the efficacy of ICS/LABA combination therapy in severely affected COPD patients requiring long-term oxygen therapy. | 1 |
Low mitochondrial content and oxidative capacity are well-established features of locomotor muscle dysfunction, a prevalent and debilitating systemic occurrence in patients with chronic obstructive pulmonary disease (COPD).,Although the exact cause is not firmly established, physical inactivity and oxidative stress are among the proposed underlying mechanisms.,Here, we assess the impact of COPD pathophysiology on mitochondrial DNA (mtDNA) integrity, biogenesis, and cellular oxidative capacity in locomotor muscle of COPD patients and healthy controls.,We hypothesized that the high oxidative stress environment of COPD muscle would yield a higher presence of deletion-containing mtDNA and oxidative-deficient fibers and impaired capacity for mitochondrial biogenesis.,Vastus lateralis biopsies were analyzed from 29 COPD patients and 19 healthy age-matched controls for the presence of mtDNA deletions, levels of oxidatively damaged DNA, mtDNA copy number, and regulators of mitochondrial biogenesis as well the proportion of oxidative-deficient fibers (detected histologically as cytochrome c oxidase-deficient, succinate dehydrogenase positive (COX−/SDH+ )).,Additionally, mtDNA copy number and mitochondrial transcription factor A (TFAM) content were measured in laser captured COX−SDH+ and normal single fibers of both COPD and controls.,Compared to controls, COPD muscle exhibited significantly higher levels of oxidatively damaged DNA (8-hydroxy-2-deoxyguanosine (8-OHdG) levels = 387 ± 41 vs. 258 ± 21 pg/mL) and higher prevalence of mtDNA deletions (74 vs. 15 % of subjects in each group), which was accompanied by a higher abundance of oxidative-deficient fibers (8.0 ± 2.1 vs.,1.5 ± 0.4 %).,Interestingly, COPD patients with mtDNA deletions had higher levels of 8-OHdG (457 ± 46 pg/mL) and longer smoking history (66.3 ± 7.5 years) than patients without deletions (197 ± 29 pg/mL; 38.0 ± 7.3 years).,Transcript levels of regulators of mitochondrial biogenesis and oxidative metabolism were upregulated in COPD compared to controls.,However, single fiber analyses of COX−/SDH+ and normal fibers exposed an impairment in mitochondrial biogenesis in COPD; in healthy controls, we detected a marked upregulation of mtDNA copy number and TFAM protein in COX−/SDH+ compared to normal fibers, reflecting the expected compensatory attempt by the oxidative-deficient cells to increase energy levels; in contrast, they were similar between COX−/SDH+ and normal fibers in COPD patients.,Taken together, these findings suggest that although the signaling factors regulating mitochondrial biogenesis are increased in COPD muscle, impairment in the translation of these signals prevents the restoration of normal oxidative capacity.,Single fiber analyses provide the first substantive evidence that low muscle oxidative capacity in COPD cannot be explained by physical inactivity alone and is likely driven by the disease pathophysiology. | Sarcopenia is characterized by a progressive and generalized decrease of strength and muscle mass.,Muscle mass loss is prevalent in patients with chronic obstructive pulmonary disease (COPD) as a result of both the disease and aging.,Some methods have been proposed to assess body composition (and therefore identify muscle mass loss) in this population.,Despite the high accuracy of some methods, they require sophisticated and costly equipment.,The purpose of this study was to infer the occurrence of muscle mass loss measured by a sophisticated method (dual energy X-ray absorptiometry [DEXA]) using a more simple and affordable equipment (dynamometer).,Fifty-seven stable subjects with COPD were evaluated for anthropometric characteristics, lung function, functional exercise capacity, body composition, and peripheral muscle strength.,A binary logistic regression model verified whether knee-extension strength (measured by dynamometry) could infer muscle mass loss (from DEXA).,Patients with decreased knee-extension strength were 5.93 times more likely to have muscle mass loss, regardless of sex, disease stage, and functional exercise capacity (P=0.045).,Knee-extension dynamometry was able to infer muscle mass loss in patients with COPD. | 1 |
We sought to assess whether the effects of mesenchymal stromal cells (MSC) on lung inflammation and remodeling in experimental emphysema would differ according to MSC source and administration route.,Emphysema was induced in C57BL/6 mice by intratracheal (IT) administration of porcine pancreatic elastase (0.1 UI) weekly for 1 month.,After the last elastase instillation, saline or MSCs (1×105), isolated from either mouse bone marrow (BM), adipose tissue (AD) or lung tissue (L), were administered intravenously (IV) or IT.,After 1 week, mice were euthanized.,Regardless of administration route, MSCs from each source yielded: 1) decreased mean linear intercept, neutrophil infiltration, and cell apoptosis; 2) increased elastic fiber content; 3) reduced alveolar epithelial and endothelial cell damage; and 4) decreased keratinocyte-derived chemokine (KC, a mouse analog of interleukin-8) and transforming growth factor-β levels in lung tissue.,In contrast with IV, IT MSC administration further reduced alveolar hyperinflation (BM-MSC) and collagen fiber content (BM-MSC and L-MSC).,Intravenous administration of BM- and AD-MSCs reduced the number of M1 macrophages and pulmonary hypertension on echocardiography, while increasing vascular endothelial growth factor.,Only BM-MSCs (IV > IT) increased the number of M2 macrophages.,In conclusion, different MSC sources and administration routes variably reduced elastase-induced lung damage, but IV administration of BM-MSCs resulted in better cardiovascular function and change of the macrophage phenotype from M1 to M2. | 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 |
Patients with chronic obstructive pulmonary disease (COPD) repeat acute exacerbations (AE).,Global Initiative for Chronic Obstructive Lung Disease (GOLD) is only available for patients in stable phase.,Currently, there is a lack of assessment and prediction methods for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients during hospitalization.,To enhance the monitoring and treatment of AECOPD patients, we develop a novel C5.0 decision tree classifier to predict the prognosis of AECOPD hospitalized patients with objective clinical indicators.,The medical records of 410 hospitalized AECOPD patients are collected and 28 features including vital signs, medical history, comorbidities and various inflammatory indicators are selected.,The overall accuracy of the proposed C5.0 decision tree classifier is 80.3% (65 out of 81 participants) with 95% Confidence Interval (CI):(0.6991, 0.8827) and Kappa 0.6054.,In addition, the performance of the model constructed by C5.0 exceeds the C4.5, classification and regression tree (CART) model and the iterative dichotomiser 3 (ID3) model.,The C5.0 decision tree classifier helps respiratory physicians to assess the severity of the patient early, thereby guiding the treatment strategy and improving the prognosis of patients. | Chronic obstructive pulmonary disease (COPD) is combination of progressive lung diseases.,The diagnosis of COPD is generally based on the pulmonary function testing, however, difficulties underlie in prognosis of smokers or early stage of COPD patients due to the complexity and heterogeneity of the pathogenesis.,Computational analyses of omics technologies are expected as one of the solutions to resolve such complexities.,We obtained transcriptomic data by in vitro testing with exposures of human bronchial epithelial cells to the inducers for early events of COPD to identify the potential descriptive marker genes.,With the identified genes, the machine learning technique was employed with the publicly available transcriptome data obtained from the lung specimens of COPD and non-COPD patients to develop the model that can reflect the risk continuum across smoking and COPD.,The expression levels of 15 genes were commonly altered among in vitro tissues exposed to known inducible factors for earlier events of COPD (exposure to cigarette smoke, DNA damage, oxidative stress, and inflammation), and 10 of these genes and their corresponding proteins have not previously reported as COPD biomarkers.,Although these genes were able to predict each group with 65% accuracy, the accuracy with which they were able to discriminate COPD subjects from smokers was only 29%.,Furthermore, logistic regression enabled the conversion of gene expression levels to a numerical index, which we named the “potential risk factor (PRF)” index.,The highest significant index value was recorded in COPD subjects (0.56 at the median), followed by smokers (0.30) and non-smokers (0.02).,In vitro tissues exposed to cigarette smoke displayed dose-dependent increases of PRF, suggesting its utility for prospective risk estimation of tobacco products.,Our experimental-based transcriptomic analysis identified novel genes associated with COPD, and the 15 genes could distinguish smokers and COPD subjects from non-smokers via machine-learning classification with remarkable accuracy.,We also suggested a PRF index that can quantitatively reflect the risk continuum across smoking and COPD pathogenesis, and we believe it will provide an improved understanding of smoking effects and new insights into COPD. | 1 |
Lung hyperinflation and exercise intolerance are hallmarks of chronic obstructive pulmonary disease (COPD).,However, their relationship remains uncertain.,A combined analysis of two placebo-controlled, randomized studies examined the effects of the long-acting muscarinic antagonist umeclidinium (UMEC) and long-acting β2-agonist vilanterol (VI) separately and in combination on static hyperinflation, exercise endurance time (EET), and their relationship in patients with COPD.,Patients with moderate-to-severe stable COPD and resting functional residual capacity >120% predicted were randomized to UMEC/VI 62.5/25 μg, UMEC 62.5 μg, VI 25 μg, or placebo for 12 weeks.,Inspiratory capacity (IC), residual volume (RV), total lung capacity (TLC), and EET in an endurance shuttle-walk test were measured.,In this post hoc analysis, IC/TLC, RV/TLC, and IC were used as hyperinflation markers.,After 12 weeks, UMEC/VI and UMEC and VI showed significant improvements in hyperinflation versus placebo when measured by absolute change from baseline in IC/TLC (trough and 3 hours postdose [P≤0.011]).,UMEC/VI showed significant improvements versus UMEC and VI in absolute changes in IC/TLC (trough and 3 hours postdose [P≤0.001]).,Statistical significance for comparisons with placebo and between treatments for absolute changes in IC and percentage changes in RV/TLC followed similar patterns to those for absolute changes in IC/TLC.,UMEC/VI showed significant improvements in EET versus placebo at day 2 and week 12, measured as change from baseline in seconds (P≤0.002) and as a percentage from baseline (P≤0.005).,There was a lack of evidence to suggest a correlation between improvements in static hyperinflation and EET at any time point.,Although the dual bronchodilator UMEC/VI demonstrated greater improvements in static hyperinflation markers than UMEC or VI and significant improvements in exercise endurance, no direct relationship was observed between static hyperinflation and exercise endurance. | 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 |
Despite the severe symptoms experienced by dying COPD patients, specialized palliative care (SPC) services focus mainly on cancer patients.,We aimed to study the access to SPC that COPD and lung cancer (LC) patients receive and how that access affects the need for acute hospital care.,A descriptive regional registry study using data acquired through VAL, the Stockholm Regional Council’s central data warehouse, which covers nearly all healthcare use in the county of Stockholm.,All the patients who died of COPD or LC from 2015 to 2019 were included.,T-tests, chi-2 tests, and univariable and multivariable logistic regression analyses were performed on the accumulated data.,In total, 6479 patients, (2917 with COPD and 3562 with LC) were studied.,The patients with LC had more access to SPC during the last three months of life than did those with COPD (77% vs. 18%, respectively; p < .0001), whereas patients with COPD were more likely to be residents of nursing homes than those with LC (32% vs. 9%, respectively; p < .0001).,Higher socioeconomic status (SES) (p < .01) and patient age < 80 years (p < .001) were associated with increased access to SPC for LC patients.,Access to SPC correlated with fewer emergency room visits (p < .0001 for both COPD and LC patients) and fewer admissions to acute hospitals during the last month of life (p < .0001 for both groups).,More COPD patients died in acute hospitals than lung cancer patients, (39% vs. 20%; χ2 = 287, p < .0001), with significantly lower figures for those who had access to SPC (p < .0001).,Compared to dying COPD patients, LC patients have more access to SPC.,Access to SPC reduces the need for emergency room visits and admissions to acute hospitals. | Information about daily physical activity levels (PAL) in subjects with undiagnosed chronic obstructive pulmonary disease (COPD) is scarce.,This study aims to assess PA and to investigate the associations between PA and clinical characteristics in subjects with newly diagnosed COPD.,Fifty-nine subjects with a new spirometry-based diagnosis of mild (n=38) and moderate (n=21) COPD (63±6 years, 68% male) were matched with 65 smoking controls (62±7 years, 75% male).,PA (daily steps, time spent in moderate-to-vigorous intense physical activities (MVPA) and PAL) was measured by accelerometry.,Dyspnoea, complete pulmonary function tests, peripheral muscle strength and exercise capacity served as clinical characteristics.,PA was significantly lower in COPD versus smoking controls (7986±2648 vs 9765±3078 steps, 64 (27-120) vs 110 (55-164) min of MVPA, 1.49±0.21 vs 1.62±0.24 PAL respectively, all p<0.05).,Subjects with COPD with either mild symptoms of dyspnoea (mMRC 1), those with lower diffusion capacity (TL,co), low 6 min walking distance (6MWD) or low maximal oxygen uptake (VO2 peak) had significantly lower PA.,Multiple regression analysis identified 6 MWD and TL,co as independent predictors of PA in COPD.,The reduction in PA starts early in the disease, even when subjects are not yet diagnosed with COPD.,Inactivity is more pronounced in subjects with mild symptoms of dyspnoea, lower levels of diffusion capacity and exercise capacity. | 1 |
We have previously reported that the lungs of patients with very severe chronic obstructive pulmonary disease (COPD) contain significantly higher numbers of alveolar macrophages than those of non-smokers or smokers.,M1 and M2 macrophages represent pro- and anti-inflammatory populations, respectively.,However, the roles of M1 and M2 alveolar macrophages in COPD remain unclear.,Immunohistochemical techniques were used to examine CD163, CD204 and CD206, as M2 markers, expressed on alveolar macrophages in the lungs of patients with mild to very severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I (mild) n = 11, II (moderate) n = 9, III (severe) n = 2, and IV (very severe) n = 16).,Fifteen smokers and 10 non-smokers were also examined for comparison.,There were significantly higher numbers of alveolar macrophages in COPD patients than in smokers and non-smokers.,The numbers and percentages of CD163+, CD204+ or CD206+ alveolar macrophages in patients with COPD at GOLD stages III and IV were significantly higher than in those at GOLD stages I and II, and those in smokers and non-smokers.,In patients with COPD, there was a significant negative correlation between the number of CD163+, CD204+ or CD206+ alveolar macrophages and the predicted forced expiratory volume in one second.,Overexpression of CD163, CD204 and CD206 on lung alveolar macrophages may be involved in the pathogenesis of COPD. | Chronic obstructive pulmonary disease (COPD) is influenced by environmental and genetic factors.,An important fraction of COPD cases harbor a major genetic determinant, inherited ZZ (Glu342Lys) α1-antitrypsin deficiency (AATD).,A study was undertaken to investigate gene expression patterns in end-stage COPD lungs from patients with and without AATD.,Explanted lungs of end-stage ZZ AATD-related (treated and non-treated with AAT augmentation therapy) and “normal” MM COPD, and liver biopsies from patients suffering from liver cirrhosis with and without ZZ AATD were used for gene expression analysis by Affymetrix microarrays or RT-PCR.,A total of 162 genes were found to be differentially expressed (p-value ≤ 0.05 and |FC| ≥ 2) between MM and ZZ COPD patients.,Of those, 134 gene sets were up-regulated and 28 were down-regulated in ZZ relative to MM lung tissue.,A subgroup of genes, zinc finger protein 165, snail homolog 1 (Drosophila) (SNAI1), and Krüppel-like transcription factors (KLFs) 4 (gut), 9 and 10, perfectly segregated ZZ and MM COPD patients.,The higher expression of KLF 9 and KLF10 has been verified in the replication cohort with AATD-related end-stage lung emphysema and liver cirrhosis.,Furthermore, higher expression of KLF9, SNAI1 and DEFA1 was found in ZZ COPD lungs without augmentation therapy relative to MM COPD or ZZ COPD with augmentation therapy.,These results reveal the involvement of transcriptional regulators of the zinc-finger family in COPD pathogenesis and provide deeper insight into the pathophysiological mechanisms of COPD with and without AATD. | 1 |
Patients with COPD have an increased risk for community-acquired pneumonia, which is further increased by inhaled corticosteroids.,To assess effects of the corticosteroids, budesonide and fluticasone propionate, on macrophage bacterial responses in COPD.,Monocyte-derived macrophages (MDMs) generated from blood monocytes from 10 non-smoker controls (NoS), 20 smokers without COPD (Sm), and 40 subjects with moderate to severe COPD (21 ex-smokers (COPD-ES) and 19 current smokers (COPD-S)) were pre-treated with budesonide or fluticasone (10 nM-1 μM) and challenged with live non-typeable Haemophilus influenzae (NTHI) or Streptococcus pneumoniae (SP).,Cell surface bacterial recognition receptor expression (flow cytometry) and cytokine release (bead array) were analyzed.,NTHI and SP reduced bacterial recognition receptor expression on MDMs from COPD and Sm, but not NoS (except TLR4).,SR-AI and MARCO were reduced by both NTHI and SP, whereas other receptors by either NTHI or SP.,Among COPD subjects, COPD-ES demonstrated a greater number of reductions as compared to COPD-S.,NTHI reduced SR-AI, MARCO, CD11b, CD35 and CD206 in COPD-ES while only SR-AI and CD11b in COPD-S.,SP reduced SRA-1, CD1d, TLR2 and TLR4 in both COPD-ES and COPD-S, and reduced MARCO and CD93 only in COPD-ES.,All receptors reduced in COPD by NTHI and most by SP, were also reduced in Sm.,Budesonide counteracted the receptor reductions induced by both NTHI (CD206 p = 0.03, MARCO p = 0.08) and SP (SR-AI p = 0.02) in COPD-ES.,Fluticasone counteracted only SP-induced reductions in TLR2 (p = 0.008 COPD-ES and p = 0.04 COPD-S) and TLR4 (p = 0.02 COPD-ES).,Cytokine release was equivalently reduced by both corticosteroids.,Reduction in macrophage bacterial recognition receptors during bacterial exposure could provide a mechanism for the increased pneumonia risk in COPD.,Differential effects of budesonide and fluticasone propionate on macrophage bacterial recognition receptor expression may contribute to the higher pneumonia incidence reported with fluticasone propionate. | This study aimed to measure the serum levels of interleukin (IL)-17, IL-10, and IL-35 in patients with stable chronic obstructive pulmonary disease (COPD) and disclose the correlations between their expression levels and clinical factors of patients.,A total of 75 patients with stable COPD (47 males and 28 females) and 30 healthy controls (15 males and 15 females) were included in this study.,The serum levels of IL-17, IL-10, and IL-35 were determined by enzyme-linked immunosorbent assay.,The correlations between their expression levels and clinical factors of patients were determined using linear regression methods.,The serum level of IL-17 was upregulated in stable COPD, and increased IL-17 expression was positively correlated with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading, modified Medical Research Council (mMRC) score, and long clinical history (P<0.05), but negatively correlated with the pulmonary function (P<0.05) of patients.,The serum levels of IL-10 and IL-35 were downregulated in stable COPD, and decreased IL-10 and IL-35 levels negatively correlated with the smoking status, GOLD grading, mMRC score, and long clinical history (P<0.05), but positively correlated with the pulmonary function (P<0.05) of patients.,Moreover, the level of IL-17 negatively correlated with IL-10 and IL-35, but IL-10 positively correlated with IL-35.,The serum levels of IL-17, IL-10, and IL-35 correlated with the clinical factors of COPD, indicating that they can serve as indicators to estimate the progression of COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is a devastating lung disease, mainly due to cigarette smoking, which represents the third cause of mortality worldwide.,The mechanisms driving its epithelial salient features remain largely elusive.,We aimed to evaluate the activation and the role of the canonical, β-catenin-dependant WNT pathway in the airway epithelium from COPD patients.,The WNT/β-catenin pathway was first assessed by WNT-targeted RNA sequencing of the air/liquid interface-reconstituted bronchial epithelium from COPD and control patients.,Airway expression of total and active β-catenin was assessed in lung sections, as well as WNT components in laser-microdissected airway epithelium.,Finally, we evaluated the role of WNT at the bronchial epithelial level by modulating the pathway in the reconstituted COPD epithelium.,We show that the WNT/β-catenin pathway is upregulated in the COPD airway epithelium as compared with that of non-smokers and control smokers, in targeted RNA-sequencing of in vitro reconstituted airway epithelium, and in situ in lung tissue and laser-microdissected epithelium.,Extrinsic activation of this pathway in COPD-derived airway epithelium inhibited epithelial differentiation, polarity and barrier function, and induced TGF-β-related epithelial-to-mesenchymal transition (EMT).,Conversely, canonical WNT inhibition increased ciliated cell numbers, epithelial polarity and barrier function, whilst inhibiting EMT, thus reversing COPD features.,In conclusion, the aberrant reactivation of the canonical WNT pathway in the adult airway epithelium recapitulates the diseased phenotype observed in COPD patients, suggesting that this pathway or its downstream effectors could represent a future therapeutic target.,This study was supported by the Fondation Mont-Godinne, the FNRS and the WELBIO. | Emphysema is mainly caused by cigarette smoking and is characterized by the loss of alveolar integrity and an enlargement of the alveolar space.,However, mechanisms involved in its development are not fully understood.,Alveolar cell apoptosis has been previously investigated in the lung of emphysematous subjects as a potential contributor to the loss of alveolar cell and has been found abnormally elevated.,Though, mechanisms involved in the increased alveolar apoptosis that occurs in emphysema have now become a prolific field of research.,Those mechanisms are reviewed here with special focus on how they affect cell viability and how they may be implicated in emphysema.,Moreover, we suggest a model that integrates all those mechanisms to explain the increased alveolar apoptosis observed in emphysema.,This review also includes some reflections and suggestions on the research to come. | 1 |
Improving patients’ information needs (IN) may contribute to better control in COPD.,This study analyses IN using Lung Information Needs Questionnaire (LINQ) following an educational intervention, evaluates how clinical characteristics modify IN, and studies high IN as a prognostic factor for COPD exacerbations and hospital admissions.,Cohort of 143 patients with initial diagnosis of COPD included in a structured educational program.,Two months after completing the program, IN was assessed using LINQ.,Correlations between IN and clinical variables of COPD and distribution of IN in different clinical groups were analyzed.,Univariate and multivariate analysis was performed to determine influence of IN on exacerbations and COPD admissions over the following year.,LINQ scored 6.3±2.9.,There were no differences in LINQ scoring between different clinical groups, but LINQ score positively correlated with age (r=0.184, p=0.029).,High IN was a predictor of COPD hospitalizations (HR 2.3 [95% CI 1.1-5.1] (p=0.029)) but not of less severe exacerbations (p=0.334).,IN was not associated with any clinical variables, but it correlated with age.,High IN proved to be an independent predictor of admissions. | Chronic obstructive pulmonary disease (COPD) is one of the most prevalent diseases in the World, and one of the most important causes of mortality and morbidity.,In adults 40 years and older, it affects more than 10% of the population and has enormous personal, family and social burden.,Tobacco smoking is its main cause, but not the only one, and there is probably a genetic predisposition that increases the risk in some patients.,The paradigm of this disease is changing in Spain, with an increase of women that has occurred in recent years.,Many of the physiopathological mechanisms of this condition are well known, but the psychological alterations to,which it leads, the impact of COPD on relatives and caregivers, the limitation of daily life observed in these patients, and the economic and societal burden that they represent for the health system, are not so well-known.,A major problem is the high under-diagnosis, mainly due to difficulties for obtaining, in a systematic way, spirometries in hospitals and health-care centers.,For this reason, the Fundación de Ciencias de la Salud and the Spanish National Network Center for Research in Respiratory Diseases (CIBERES) have brought together experts in COPD, patients and their organizations, clinical psychologists, experts in health economics, nurses and journalists to obtain their opinion about COPD in Spain.,They also discussed the scientific bibliometrics on COPD that is being carried out from the CIBERES and speculated on the future of this condition.,The format of the meeting consisted in the discussion of a series of questions that were addressed by different speakers and discussed until a consensus conclusion was reached. | 1 |
Culture-independent microbial sequencing techniques have revealed that the respiratory tract harbours a complex microbiome not detectable by conventional culturing methods.,The contribution of the microbiome to chronic obstructive pulmonary disease (COPD) pathobiology and the potential for microbiome-based clinical biomarkers in COPD are still in the early phases of investigation.,Sputum is an easily obtainable sample and has provided a wealth of information on COPD pathobiology, and thus has been a preferred sample type for microbiome studies.,Although the sputum microbiome likely reflects the respiratory microbiome only in part, there is increasing evidence that microbial community structure and diversity are associated with disease severity and clinical outcomes, both in stable COPD and during the exacerbations.,Current evidence has been limited to mainly cross-sectional studies using 16S rRNA gene sequencing, attempting to answer the question ‘who is there?’,Longitudinal studies using standardised protocols are needed to answer outstanding questions including differences between sputum sampling techniques.,Further, with advancing technologies, microbiome studies are shifting beyond the examination of the 16S rRNA gene, to include whole metagenome and metatranscriptome sequencing, as well as metabolome characterisation.,Despite being technically more challenging, whole-genome profiling and metabolomics can address the questions ‘what can they do?’,and ‘what are they doing?’,This review provides an overview of the basic principles of high-throughput microbiome sequencing techniques, current literature on sputum microbiome profiling in COPD, and a discussion of the associated limitations and future perspectives. | A sputum eosinophilia is observed in 10-40% of COPD subjects.,The blood eosinophil count is a biomarker of sputum eosinophilia, but whether it is associated with bronchial submucosal eosinophils is unclear.,In 20 COPD subjects and 21 controls we assessed the number of bronchial submucosal eosinophils and reticular basement membrane thickening and found these were positively correlated with the blood eosinophil percentage.,In COPD, blood eosinophils are a good biomarker of bronchial eosinophilia and remodelling. | 1 |
Dual bronchodilator therapy is recommended for symptomatic patients with chronic obstructive pulmonary disease (COPD).,There are limited data on effects of a combination of two long-acting bronchodilators on lung function including body plethysmography.,This multicentre, randomised, double-blind, single-dose, cross-over, placebo-controlled study evaluated efficacy and safety of the free combination of indacaterol maleate (IND) and glycopyrronium bromide (GLY) versus IND alone on spirometric and body plethysmography parameters, including inspiratory capacity (IC), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), total lung capacity (TLC) and airway resistance (Raw) in moderate-to-severe COPD patients.,Seventy-eight patients with FEV1 % pred. (mean ± SD) 56 ± 13% were randomised.,The combination of IND + GLY versus IND presented a numerically higher peak-IC (Δ = 0.076 L, 95% confidence interval [CI]: −0.010 - 0.161 L; p = 0.083), with a statistically significant difference in mean IC over 4 h (Δ = 0.054 L, 95%CI 0.022 - 0.086 L; p = 0.001).,FEV1, FVC and Raw, but not TLC, were consistently significantly improved by IND + GLY compared to IND alone.,Safety profiles of both treatments were comparable.,The free combination of IND + GLY improved lung function parameters as evaluated by spirometry and body plethysmography, with a similar safety profile compared to IND alone.,NCT01699685,The online version of this article (doi:10.1186/s12931-016-0498-1) contains supplementary material, which is available to authorized users. | The aims of the study were: (1) to compare numerical parameters of specific airway resistance (total, sRawtot, effective, sRaweff and at 0.5 L · s−1, sRaw0.5) and indices obtained from the forced oscillation technique (FOT: resistance extrapolated at 0 Hz [Rrs0 Hz], mean resistance [Rrsmean], and resistance/frequency slope [Rrsslope]) and (2) to assess their relationships with dyspnea in chronic obstructive pulmonary disease (COPD).,A specific statistical approach, principal component analysis that also allows graphic representation of all correlations between functional parameters was used.,A total of 108 patients (mean ± SD age: 65 ± 9 years, 31 women; GOLD stages: I, 14; II, 47; III, 39 and IV, 8) underwent spirometry, body plethysmography, FOT, and Medical Research Council (MRC) scale assessments.,Principal component analysis determined that the functional parameters were described by three independent dimensions (airway caliber, lung volumes and their combination, specific resistance) and that resistance parameters of the two techniques were not equivalent, obviously.,Correlative analyses further showed that Rawtot and Raweff (and their specific resistances) can be considered as equivalent and correlated with indices that are considered to explore peripheral airways (residual volume (RV), RV/ total lung capacity (TLC), Rrsslope), while Rrsmean and Raw0.5 explored more central airways.,Only specific resistances taking into account the specific resistance loop area (sRawtot and sRaweff) and Rrsslope were statistically linked to dyspnea.,Parameters obtained from both body plethysmography and FOT can explore peripheral airways, and some of these parameters (sRawtot, sRaweff, and Rrsslope) are linked to activity-related dyspnea in moderate to severe COPD patients. | 1 |
A loss of physical functioning (i.e., a low physical capacity and/or a low physical activity) is a common feature in patients with chronic obstructive pulmonary disease (COPD).,To date, the primary care physiotherapy and specialized pulmonary rehabilitation are clearly underused, and limited to patients with a moderate to very severe degree of airflow limitation (GOLD stage 2 or higher).,However, improved referral rates are a necessity to lower the burden for patients with COPD and for society.,Therefore, a multidisciplinary group of healthcare professionals and scientists proposes a new model for referral of patients with COPD to the right type of exercise-based care, irrespective of the degree of airflow limitation.,Indeed, disease instability (recent hospitalization, yes/no), the burden of disease (no/low, mild/moderate or high), physical capacity (low or preserved) and physical activity (low or preserved) need to be used to allocate patients to one of the six distinct patient profiles.,Patients with profile 1 or 2 will not be referred for physiotherapy; patients with profiles 3-5 will be referred for primary care physiotherapy; and patients with profile 6 will be referred for screening for specialized pulmonary rehabilitation.,The proposed Dutch model has the intention to get the right patient with COPD allocated to the right type of exercise-based care and at the right moment. | Dyspnea is a distressing, debilitating, and near-ubiquitous symptom affecting patients with COPD.,In addition to the functional consequences of dyspnea, which include activity limitation and reduced exercise tolerance, it is important to consider its psychological impact on patients with COPD, such as onset of depression or anxiety.,Moreover, the anticipation of dyspnea itself can have a significant effect on patients’ emotions and behavior, with patients frequently self-limiting physical activity to avoid what has become the hallmark symptom of COPD.,Dyspnea is, therefore, a key target for COPD treatments.,Pharmacologic treatments can optimize respiratory mechanics, provide symptom relief, and reduce patients’ increased inspiratory neural drive to breathe.,However, it is important to acknowledge the value of non-pharmacologic interventions, such as pulmonary rehabilitation and patient self-management education, which have proven to be invaluable tools for targeting the affective components of dyspnea.,Furthermore, it is important to encourage maintenance of physical activity to optimize long-term patient outcomes.,Here, we review the physiological and psychological consequences of activity-related dyspnea in COPD, assess the efficacy of modern management strategies in improving this common respiratory symptom, and discuss key unmet clinical and research needs that warrant further immediate attention. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) are at higher risk of stroke than those without COPD.,This study aims to explore the impact of inhaled pharmacotherapy on stroke risk in COPD patients during a three-year follow-up, using a nationwide, population-based study and a matched cohort design.,The study cohort comprised 10,413 patients who had received COPD treatment between 2004 and 2006; 41,652 randomly selected subjects comprised the comparison cohort.,Cox proportional hazard regressions and two-stage propensity score calibration were performed to determine the impact of various inhaled therapies including short-acting muscarinic antagonists, long-acting muscarinic antagonists, short-acting β-agonists (SABAs), long-acting β-agonists (LABAs), and LABA plus inhaled corticosteroid (ICS), on the risk after adjustment for patient demographic characteristics and comorbid disorders.,Of the 52,065 sampled patients, 2,689 (5.2%) developed stroke during follow-up, including 727 (7.0%) from the COPD cohort and 1,962 (4.7%) from the comparison cohort (p < 0.001).,Treatment with SABA was associated with 1.67-fold (95% CI 1.45-1.91; p < 0.001) increased risk of stroke in COPD patients.,By contrast, the cumulative incidence of stroke was significantly lower in those treated with LABA plus ICS than those treated without (adjusted hazard ratio 0.75, 95% CI 0.60-0.94, p = 0.014).,Among COPD patients, the use of inhaled SABA is associated with an increased risk of stroke, and combination treatment with inhaled LABA and ICS relates to a risk reduction.,Further prospective research is needed to verify whether LABA plus ICS confers protection against stroke in patients with COPD. | 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 |
The purpose of this study was to evaluate the association of serum lymphocyte level with several clinical parameters in COPD.,The study population included 451 COPD patients from the Korean Obstructive Lung Disease cohort study.,Serum lymphocyte level was measured every year along with various clinical parameters, such as lung function, 6-min walking (6 MW) distance, quality of life using COPD assessment test (CAT) and St.,George's Respiratory Questionnaire (SGRQ) scores, exacerbations, and survival.,Serum lymphocyte level less than 20% was considered as a low lymphocyte level.,Normal lymphocyte and low lymphocyte groups comprised of 409 (90.7%) and 42 (9.3%) patients, respectively.,Clustered analysis showed that patients in low lymphocyte group had a lower post-bronchodilator forced expiratory volume in 1 s % predicted (estimated mean = − 5.70%; P = 0.001), a lower forced vital capacity % predicted (estimated mean = − 5.63%; P = 0.005), a shorter 6 MW distance (estimated mean = − 41.31 m; P < 0.001), a higher CAT score (estimated mean = 2.62; P = 0.013), and a higher SGRQ score (estimated mean = 10.10; P < 0.001).,Serum lymphocyte level was not associated with frequent acute exacerbations nor mortality.,Low serum lymphocyte group showed poorer pulmonary function, lower 6 MW distance, and worse quality of life.,Serum lymphocyte levels could be a simple and widely available predictive marker for variable clinical outcomes in COPD patients. | Neutrophil to lymphocyte ratio (NLR) in peripheral blood is a useful systemic inflammatory response biomarker.,However, NLR has not been studied in patients with chronic obstructive pulmonary disease (COPD).,This study was aimed to evaluate the usefulness of NLR in patients with COPD.,NLR was prospectively measured and compared in patients with COPD exacerbation (n = 59), patients with stable COPD (n = 61), and healthy controls (n = 28).,NLR in patients with COPD exacerbation was repeatedly measured in the convalescent period.,The correlation between NLR and clinical parameters was evaluated, and the predictors for respiratory hospitalization were analyzed by multivariate logistic regression.,NLR values were significantly higher in patients with COPD exacerbation compared with stable COPD patients and controls (12.4 ± 10.6, 2.4 ± 0.7, 1.4 ± 0.5, respectively; p < 0.001).,NLR was significantly decreased during the convalescent period in patients with COPD exacerbation (4.5 ± 4.6 vs.,11.5 ± 8.8, p < 0.001).,NLR exhibited a significant correlation with the body mass index, degree of airway obstruction, dyspnea, and exercise capacity (BODE) index, the 6-minute walk test, and the modified Medical Research Council scale.,NLR ≥ 2.8 was an independent predictor with a borderline significance for respiratory hospitalization (odds ratio, 2.083; p = 0.079).,Body mass index and forced expiratory volume in 1 second were independent predictors for respiratory hospitalization.,NLR is a straightforward and effective biomarker of COPD exacerbation that may serve as a predictor for respiratory hospitalization in patients with COPD. | 1 |
The present work adopted a systems pharmacology-based approach to provide new insights into the active compounds and therapeutic targets of Bufei Yishen formula (BYF) for the treatment of chronic obstructive pulmonary disease (COPD).,In addition, we established a rat model of cigarette smoke- and bacterial infection-induced COPD to validate the mechanisms of BYF action that were predicted in systems pharmacology study.,The systems pharmacology model derived 216 active compounds from BYF and 195 potential targets related to various diseases.,The compound-target network showed that each herbal drug in the BYF formula acted on similar targets, suggesting potential synergistic effects among these herbal drugs.,The ClueGo assay, a Cytoscape plugin, revealed that most targets were related to activation of MAP kinase and matrix metalloproteinases.,By using target-diseases network analysis, we found that BYF had great potential to treatment of multiple diseases, such as respiratory tract diseases, immune system, and cardiovascular diseases.,Furthermore, we found that BYF had the ability to prevent COPD and its comorbidities, such as ventricular hypertrophy, in vivo.,Moreover, BYF inhibited the inflammatory cytokine, and hypertrophic factors expression, protease-antiprotease imbalance and the collagen deposition, which may be the underlying mechanisms of action of BYF. | Traditional Chinese medicine (TCM) has been used to treat chronic obstructive pulmonary disease (COPD) for many years.,This study aimed to evaluate the efficacy and safety of the comprehensive therapy based on the three common TCM patterns in stable COPD patients.,A four-center, open-label randomized controlled method was conducted.,A total of 352 patients were divided into the trial group (n = 176, treated with conventional Western medicine and Bu-Fei Jian-Pi granules, Bu-Fei Yi-Shen granules, and Yi-Qi Zi-Shen granules based on the TCM patterns respectively) and the control group (n = 176, treated with conventional Western medicine).,The frequency and duration of acute exacerbation, lung function, clinical symptoms, 6-minute walking distance (6MWD), dyspnea scale and quality of life were observed during a 6-month treatment period and at a further 12-month follow-up.,A total of 306 patients completed the study fully.,The full analysis set (FAS) population was 350 and the per-protocol analysis set (PPS) population was 306.,After the 6-month treatment and 12-month follow-up, there were significant differences between the trial and control group in the following: frequency of acute exacerbation (FAS: P = 0.000; PPS: P = 0.000); duration of acute exacerbation (FAS: P = 0.000; PPS: P = 0.001); FEV1 (FAS: P = 0.007; PPS: P = 0.008); symptoms (FAS: P = 0.001; PPS: P = 0.001); 6MWD (FAS: P = 0.045; PPS: P = 0.042); dyspnea scale (FAS: P = 0.002; PPS: P = 0.004); and physical domain (FAS: P = 0.000; PPS: P = 0.000), psychological domain (FAS: P = 0.008; PPS: P = 0.011), social domain (FAS: P = 0.001; PPS: P = 0.000) and environment domain (FAS: P = 0.015; PPS: P = 0.009) of the WHOQOL-BREF questionnaire.,There were no differences between the trial and control group in FVC, FEV1% and adverse events.,Based on the TCM patterns, Bu-Fei Jian-Pi granules, Bu-Fei Yi-Shen granules and Yi-Qi Zi-Shen granules have beneficial effects on measured outcomes in stable COPD patients over the 6-month treatment and 12-month follow-up, with no relevant between-group differences in adverse events.,This trial was registered at Chinese Clinical Trial Register Center, ChiCTR-TRC-11001406. | 1 |
The rising disease burden from chronic obstructive pulmonary disease (COPD) requires new approaches.,We suggest an approach based around three elements: inflammometry and multidimensional assessment to identify therapeutic targets and case management to design and implement an individualised treatment programme based on these assessments.,This tailored approach to treatment would maximise efficacy, limit cost and permit a better risk-benefit ratio of treatment.,The advantages include the ability to add up the benefits of individual therapies leading to a cumulative therapeutic benefit that is greater than each individual therapy alone.,We can now design a multifaceted inflammometry intervention for airway diseases based on targeting eosinophilic inflammation, non-eosinophilic pathways and systemic inflammation.,COPD is a complex and challenging disease.,The use of inflammometry and multidimensional assessment is necessary to identify relevant treatment targets and maximise the scope of therapy while limiting unnecessary use of drugs.,An individualised programme of management can be designed and coordinated by using a case manager.,This new approach may provide tangible benefits to people with COPD. | Chronic obstructive pulmonary disease (COPD) and asthma may overlap and converge in older people (overlap syndrome).,It was hypothesized that patients with overlap syndrome may have different clinical characteristics such as sputum eosinophilia, and better responsiveness to treatment with inhaled corticosteroid (ICS).,Sixty-three patients with stable COPD (forced expiratory volume in 1 second [FEV1] ≤80%) underwent pulmonary function tests, including reversibility of airflow limitation, arterial blood gas analysis, analysis of inflammatory cells in induced sputum, and chest high-resolution computed tomography.,The inclusion criteria for COPD patients with asthmatic symptoms included having asthmatic symptoms such as episodic breathlessness, wheezing, cough, and chest tightness worsening at night or in the early morning (COPD with asthma group).,The clinical features of COPD patients with asthmatic symptoms were compared with those of COPD patients without asthmatic symptoms (COPD without asthma group).,The increases in FEV1 in response to treatment with ICS were significantly higher in the COPD with asthma group.,The peripheral eosinophil counts and sputum eosinophil counts were significantly higher.,The prevalence of patients with bronchial wall thickening on chest high-resolution computed tomography was significantly higher.,A significant correlation was observed between the increases in FEV1 in response to treatment with ICS and sputum eosinophil counts, and between the increases in FEV1 in response to treatment with ICS and the grade of bronchial wall thickening.,Receiver operating characteristic curve analysis revealed 82.4% sensitivity and 84.8% specificity of sputum eosinophil count for detecting COPD with asthma, using 2.5% as the cutoff value.,COPD patients with asthmatic symptoms had some clinical features.,ICS should be considered earlier as a potential treatment in such patients.,High sputum eosinophil counts and bronchial wall thickening on chest high-resolution computed tomography might therefore be a good predictor of response to ICS. | 1 |
Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous.,We sought to investigate the sputum cellular, mediator, and microbiome profiles of both asthma and COPD exacerbations.,Patients with severe asthma or moderate-to-severe COPD were recruited prospectively to a single center.,Sputum mediators were available in 32 asthmatic patients and 73 patients with COPD assessed at exacerbation.,Biologic clusters were determined by using factor and cluster analyses on a panel of sputum mediators.,Patterns of clinical parameters, sputum mediators, and microbiome communities were assessed across the identified clusters.,The asthmatic patients and patients with COPD had different clinical characteristics and inflammatory profiles but similar microbial ecology.,Three exacerbation biologic clusters were identified.,Cluster 1 was COPD predominant, with 27 patients with COPD and 7 asthmatic patients exhibiting increased blood and sputum neutrophil counts, proinflammatory mediators (IL-1β, IL-6, IL-6 receptor, TNF-α, TNF receptors 1 and 2, and vascular endothelial growth factor), and proportions of the bacterial phylum Proteobacteria.,Cluster 2 had 10 asthmatic patients and 17 patients with COPD with increased blood and sputum eosinophil counts, type 2 mediators (IL-5, IL-13, CCL13, CCL17, and CCL26), and proportions of the bacterial phylum Bacteroidetes.,Cluster 3 had 15 asthmatic patients and 29 patients with COPD with increased type 1 mediators (CXCL10, CXCL11, and IFN-γ) and proportions of the phyla Actinobacteria and Firmicutes.,A biologic clustering approach revealed 3 subgroups of asthma and COPD exacerbations, each with different percentages of patients with overlapping asthma and COPD.,The sputum mediator and microbiome profiles were distinct between clusters. | The toll-like receptors (TLRs) are a key component of host defense in the respiratory epithelium.,Cigarette smoking is associated with increased susceptibility to infection, while COPD is characterised by bacterial colonisation and infective exacerbations.,We found reduced TLR4 gene expression in the nasal epithelium of smokers compared with non-smoking controls, while TLR2 expression was unchanged.,Severe COPD was associated with reduced TLR4 expression compared to less severe disease, with good correlation between nasal and tracheal expression.,We went on to examine the effect of potential modulators of TLR4 expression in respiratory epithelium pertinent to airways disease.,Using an airway epithelial cell line, we found a dose-dependent downregulation in TLR4 mRNA and protein expression by stimulation with cigarette smoke extracts.,Treatment with the corticosteroids fluticasone and dexamethasone resulted in a dose-dependent reduction in TLR4 mRNA and protein.,The functional significance of this effect was demonstrated by impaired IL-8 and HBD2 induction in response to LPS.,Stimulation with salmeterol (10-6 M) caused upregulation of TLR4 membrane protein presentation with no upregulation of mRNA, suggesting a post-translational effect.,The effect of dexamethasone and salmeterol in combination was additive, with downregulation of TLR4 gene expression, and no change in membrane receptor expression.,Modulation of TLR4 in respiratory epithelium may have important implications for airway inflammation and infection in response to inhaled pathogens. | 1 |
Chronic obstructive pulmonary disease (COPD) is combination of progressive lung diseases.,The diagnosis of COPD is generally based on the pulmonary function testing, however, difficulties underlie in prognosis of smokers or early stage of COPD patients due to the complexity and heterogeneity of the pathogenesis.,Computational analyses of omics technologies are expected as one of the solutions to resolve such complexities.,We obtained transcriptomic data by in vitro testing with exposures of human bronchial epithelial cells to the inducers for early events of COPD to identify the potential descriptive marker genes.,With the identified genes, the machine learning technique was employed with the publicly available transcriptome data obtained from the lung specimens of COPD and non-COPD patients to develop the model that can reflect the risk continuum across smoking and COPD.,The expression levels of 15 genes were commonly altered among in vitro tissues exposed to known inducible factors for earlier events of COPD (exposure to cigarette smoke, DNA damage, oxidative stress, and inflammation), and 10 of these genes and their corresponding proteins have not previously reported as COPD biomarkers.,Although these genes were able to predict each group with 65% accuracy, the accuracy with which they were able to discriminate COPD subjects from smokers was only 29%.,Furthermore, logistic regression enabled the conversion of gene expression levels to a numerical index, which we named the “potential risk factor (PRF)” index.,The highest significant index value was recorded in COPD subjects (0.56 at the median), followed by smokers (0.30) and non-smokers (0.02).,In vitro tissues exposed to cigarette smoke displayed dose-dependent increases of PRF, suggesting its utility for prospective risk estimation of tobacco products.,Our experimental-based transcriptomic analysis identified novel genes associated with COPD, and the 15 genes could distinguish smokers and COPD subjects from non-smokers via machine-learning classification with remarkable accuracy.,We also suggested a PRF index that can quantitatively reflect the risk continuum across smoking and COPD pathogenesis, and we believe it will provide an improved understanding of smoking effects and new insights into COPD. | This study assessed the effects of inhaled corticosteroid (ICS) on airway vascular remodeling in chronic obstructive pulmonary disease (COPD).,Thirty-four subjects with mild-to-moderate COPD were randomly allocated 2:1 to ICS or placebo treatment in a double-blinded clinical trial over 6 months.,Available tissue was compared before and after treatment for vessel density, and expression of VEGF, TGF-β1, and TGF-β1-related phosphorylated transcription factors p-SMAD 2/3.,This clinical trial has been registered and allocated with the Australian New Zealand Clinical Trials Registry (ANZCTR) on 17/10/2012 with reference number ACTRN12612001111864.,There were no significant baseline differences between treatment groups.,With ICS, vessels and angiogenic factors did not change in hypervascular reticular basement membrane, but in the hypovascular lamina propria (LP), vessels increased and this had a proportionate effect on lung air trapping.,There was modest evidence for a reduction in LP vessels staining for VEGF with ICS treatment, but a marked and significant reduction in p-SMAD 2/3 expression.,Six-month high-dose ICS treatment had little effect on hypervascularity or angiogenic growth factors in the reticular basement membrane in COPD, but normalized hypovascularity in the LP, and this was physiologically relevant, though accompanied by a paradoxical reduction in growth factor expression. | 1 |
Dual bronchodilator therapy is reserved as a second-line treatment in patients with chronic obstructive pulmonary disease (COPD) and provides benefits in lung function and health status versus monotherapy.,The aim of this study was to determine whether early initiation of a dual bronchodilator versus monotherapy reduced the risk of deterioration in COPD.,This post hoc pooled analysis investigated the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 mcg/day compared with tiotropium (TIO) 18 mcg/day in a maintenance-naïve (MN) subgroup of patients relative to the intent-to-treat (ITT) population from three 6-month active comparator studies (n = 1747).,Other treatment arms (UMEC/VI 125/25, VI 25 and UMEC 125) comprised 850 patients in total but were not included in this analysis.,The primary endpoint was trough forced expiratory volume in 1 s (FEV1).,St George’s Respiratory Questionnaire (SGRQ) score, rescue medication use, and a novel composite endpoint of short-term clinically important deterioration (CID; ≥100 ml decrease in trough FEV1, ≥4-unit increase in SGRQ score, or a COPD exacerbation) were also assessed.,UMEC/VI improved trough FEV1 versus TIO at day 169 [least squares mean (95% confidence interval): MN: 146 ml (102-189) and ITT: 95 ml (71-118); both P < 0.001].,Both UMEC/VI and TIO improved SGRQ and rescue use in the two populations, with greater improvements in rescue use with UMEC/VI versus TIO.,UMEC/VI reduced the risk of short-term clinically important deterioration versus TIO [hazard ratio; 95% confidence interval: MN: 0.66 (0.51-0.85); ITT: 0.62 (0.54-0.71), both P ≤ 0.001].,Adverse events were similar across both populations and treatments.,Early use of dual-bronchodilator therapy has superior efficacy on lung function and may reduce the risk of short-term deterioration compared to monotherapy in symptomatic patients with COPD.,Clinical trial registration: GSK analysis 202066 (NCT01316900/DB2113360, NCT01316913/DB2113374, NCT01777334/ZEP117115).,Funding: This study was funded by GSK.,The online version of this article (doi:10.1007/s12325-016-0430-6) 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 |
Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD).,In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new.,In combination, these variants strongly predict COPD in independent patient populations.,Furthermore, the combined effect of these variants showed generalizability across smokers and never-smokers, and across ancestral groups.,We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function associated variants.,This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD. | Cigarette smoking causes Chronic Obstructive Pulmonary Disease (COPD), the 3rd leading cause of death in the U.S.,CFTR ion transport dysfunction has been implicated in COPD pathogenesis, and is associated with chronic bronchitis.,However, susceptibility to smoke induced lung injury is variable and the underlying genetic contributors remain unclear.,We hypothesized that presence of CFTR mutation heterozygosity may alter susceptibility to cigarette smoke induced CFTR dysfunction.,Consequently, COPD patients with chronic bronchitis may have a higher rate of CFTR mutations compared to the general population.,Primary human bronchial epithelial cells derived from F508del CFTR heterozygotes and mice with (CFTR+/-) and without (CFTR+/+) CFTR heterozygosity were exposed to whole cigarette smoke (WCS); CFTR-dependent ion transport was assessed by Ussing chamber electrophysiology and nasal potential difference measurements, respectively.,Caucasians with COPD and chronic bronchitis, age 40 to 80 with FEV1/FVC < 0.70 and FEV1 < 60% predicted, were selected for genetic analysis from participants in the NIH COPD Clinical Research Network’s Azithromycin for Prevention of Exacerbations of COPD in comparison to 32,900 Caucasian women who underwent prenatal genetic testing.,Genetic analysis involved an allele-specific genotyping of 89 CFTR mutations.,Exposure to WCS caused a pronounced reduction in CFTR activity in both CFTR (+/+) cells and F508del CFTR (+/-) cells; however, neither the degree of decrement (44.7% wild-type vs.,53.5% F508del heterozygous, P = NS) nor the residual CFTR activity were altered by CFTR heterozygosity.,Similarly, WCS caused a marked reduction in CFTR activity measured by NPD in both wild type and CFTR heterozygous mice, but the severity of decrement (91.1% wild type vs.,47.7% CF heterozygous, P = NS) and the residual activity were not significantly affected by CFTR genetic status.,Five of 127 (3.9%) COPD patients with chronic bronchitis were heterozygous for CFTR mutations which was not significantly different from controls (4.5%) (P = NS).,The magnitude of WCS induced reductions in CFTR activity was not affected by the presence of CFTR mutation heterozygosity.,CFTR mutations do not increase the risk of COPD with chronic bronchitis.,CFTR dysfunction due to smoking is primarily an acquired phenomenon and is not affected by the presence of congenital CFTR mutations. | 1 |
Chronic obstructive pulmonary disease (COPD) is one of the main contributors to the global burden of disease.,The aim of this systematic review was to quantify the disease burden of COPD in China and to determine the risk factors of the disease.,The number of studies included in the review was 47 with an average quality assessment score of 7.70 out of 10.,Reported COPD prevalence varied between 1.20% and 8.87% in different provinces/cities across China.,The prevalence rate of COPD was higher among men (7.76%) than women (4.07%).,The disease was more prevalent in rural areas (7.62%) than in urban areas (6.09%).,The diagnostic rate of COPD patients in China varied from 23.61% to 30.00%.,The percentage of COPD patients receiving outpatient treatment was around 50%, while the admission rate ranged between 8.78% and 35.60%.,Tobacco exposure and biomass fuel/solid fuel usage were documented as two important risk factors of COPD.,COPD ranked among the top three leading causes of death in China.,The direct medical cost of COPD ranged from 72 to 3,565 USD per capita per year, accounting for 33.33% to 118.09% of local average annual income.,The most commonly used scales for the assessment of quality of life (QoL) included Saint George Respiratory Questionnaire, Airways Questionnaire 20, SF-36, and their revised versions.,The status of QoL was worse among COPD patients than in non-COPD patients, and COPD patients were at higher risks of depression.,The COPD burden in China was high in terms of economic burden and QoL.,In view of the high smoking rate and considerable concerns related to air pollution and smog in China, countermeasures need to be taken to improve disease prevention and management to reduce disease burdens raised by COPD. | 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. | 1 |
There is a substantial and continually growing literature on the effectiveness and implementation of discrete telehealth interventions for health condition management.,However, it is difficult to predict which technologies are likely to work and be used in practice.,In this context, identifying the core mechanisms associated with successful telehealth implementation is relevant to consolidating the likely elements for ensuring a priori optimal design and deployment of telehealth interventions for supporting patients with long-term conditions (LTCs).,We adopted a two-stage realist synthesis approach to identify the core mechanisms underpinning telehealth interventions.,In the second stage of the review, we tested inductively and refined our understanding of the mechanisms.,We reviewed qualitative papers focused on COPD, heart failure, diabetes, and behaviours and complications associated with these conditions.,The review included 15 papers published 2009 to 2014.,Three concepts were identified, which suggested how telehealth worked to engage and support health-related work.,Whether or not and how a telehealth intervention enables or limits the possibility for relationships with professionals and/or peers.,Telehealth has the potential to reshape and extend existing relationships, acting as a partial substitute for the role of health professionals.,The second concept is fit: successful telehealth interventions are those that can be well integrated into everyday life and health care routines and the need to be easy to use, compatible with patients’ existing environment, skills, and capacity, and that do not significantly disrupt patients’ lives and routines.,The third concept is visibility: visualisation of symptoms and feedback has the capacity to improve knowledge, motivation, and a sense of empowerment; engage network members; and reinforce positive behaviour change, prompts for action and surveillance.,Upfront consideration should be given to the mechanisms that are most likely to ensure the successful development and implementation of telehealth interventions.,These include considerations about whether and how the telehealth intervention enables or limits the possibility for relationships with professionals and peers, how it fits with existing environment and capacities to self-manage, and visibility-enabling-enhanced awareness to self and others. | Objective To determine whether supported self management in chronic obstructive pulmonary disease (COPD) can reduce hospital readmissions in the United Kingdom.,Design Randomised controlled trial.,Setting Community based intervention in the west of Scotland.,Participants Patients admitted to hospital with acute exacerbation of COPD.,Intervention Participants in the intervention group were trained to detect and treat exacerbations promptly, with ongoing support for 12 months.,Main outcome measures The primary outcome was hospital readmissions and deaths due to COPD assessed by record linkage of Scottish Morbidity Records; health related quality of life measures were secondary outcomes.,Results 464 patients were randomised, stratified by age, sex, per cent predicted forced expiratory volume in 1 second, recent pulmonary rehabilitation attendance, smoking status, deprivation category of area of residence, and previous COPD admissions.,No difference was found in COPD admissions or death (111/232 (48%) v 108/232 (47%); hazard ratio 1.05, 95% confidence interval 0.80 to 1.38).,Return of health related quality of life questionnaires was poor (n=265; 57%), so that no useful conclusions could be made from these data.,Pre-planned subgroup analysis showed no differential benefit in the primary outcome relating to disease severity or demographic variables.,In an exploratory analysis, 42% (75/150) of patients in the intervention group were classified as successful self managers at study exit, from review of appropriateness of use of self management therapy.,Predictors of successful self management on stepwise regression were younger age (P=0.012) and living with others (P=0.010).,COPD readmissions/deaths were reduced in successful self managers compared with unsuccessful self managers (20/75 (27%) v 51/105 (49%); hazard ratio 0.44, 0.25 to 0.76; P=0.003).,Conclusion Supported self management had no effect on time to first readmission or death with COPD.,Exploratory subgroup analysis identified a minority of participants who learnt to self manage; this group had a significantly reduced risk of COPD readmission, were younger, and were more likely to be living with others.,Trial registration Clinical trials NCT 00706303. | 1 |
Dendritic cells (DCs) control immunity and play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD).,However, the expression of function-associated surface molecules on circulating DCs in COPD is unknown.,Four-colour flow cytometry was used to compare blood DC surface molecules of 54 patients with COPD (median age: 59 years; median FEV1: 38% predicted, median CAT score: 24) with two age-matched control groups with normal lung function: 21 current smokers and 21 never-smokers.,Concentrations of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) and the mDC/pDC ratio did not differ between the groups.,The increased expression of BDCA-1, BDCA-3, CD86 and CCR5 on mDCs in patients with COPD did not significantly differ from smokers with normal lung function.,In contrast, COPD was specifically characterised by a decreased expression of the anti-inflammatory co-stimulatory molecule PD-L1 on pDCs and an increased expression of the pro-inflammatory co-stimulatory molecule OX40 ligand (OX40L) on mDCs.,These changes were not confined to patients with elevated systemic inflammation markers (leukocytes, c-reactive protein, interleukin-6, fibrinogen).,The ratio of OX40L to PD-L1 expression (OX40L/PD-L1 ratio), a quantitative measure of imbalanced DC co-stimulation, correlated with the severity of pulmonary emphysema in patients with COPD.,An imbalance of DC co-stimulation might contribute to the pathogenesis of COPD.,The online version of this article (doi:10.1186/s12931-015-0174-x) contains supplementary material, which is available to authorized users. | Smoking is a known cause of the outcomes COPD, chronic bronchitis (CB) and emphysema, but no previous systematic review exists.,We summarize evidence for various smoking indices.,Based on MEDLINE searches and other sources we obtained papers published to 2006 describing epidemiological studies relating incidence or prevalence of these outcomes to smoking.,Studies in children or adolescents, or in populations at high respiratory disease risk or with co-existing diseases were excluded.,Study-specific data were extracted on design, exposures and outcomes considered, and confounder adjustment.,For each outcome RRs/ORs and 95% CIs were extracted for ever, current and ex smoking and various dose response indices, and meta-analyses and meta-regressions conducted to determine how relationships were modified by various study and RR characteristics.,Of 218 studies identified, 133 provide data for COPD, 101 for CB and 28 for emphysema.,RR estimates are markedly heterogeneous.,Based on random-effects meta-analyses of most-adjusted RR/ORs, estimates are elevated for ever smoking (COPD 2.89, CI 2.63-3.17, n = 129 RRs; CB 2.69, 2.50-2.90, n = 114; emphysema 4.51, 3.38-6.02, n = 28), current smoking (COPD 3.51, 3.08-3.99; CB 3.41, 3.13-3.72; emphysema 4.87, 2.83-8.41) and ex smoking (COPD 2.35, 2.11-2.63; CB 1.63, 1.50-1.78; emphysema 3.52, 2.51-4.94).,For COPD, RRs are higher for males, for studies conducted in North America, for cigarette smoking rather than any product smoking, and where the unexposed base is never smoking any product, and are markedly lower when asthma is included in the COPD definition.,Variations by sex, continent, smoking product and unexposed group are in the same direction for CB, but less clearly demonstrated.,For all outcomes RRs are higher when based on mortality, and for COPD are markedly lower when based on lung function.,For all outcomes, risk increases with amount smoked and pack-years.,Limited data show risk decreases with increasing starting age for COPD and CB and with increasing quitting duration for COPD.,No clear relationship is seen with duration of smoking.,The results confirm and quantify the causal relationships with smoking. | 1 |
The aim of this pooled analysis was to assess the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 µg dual bronchodilation versus placebo in elderly symptomatic patients with chronic obstructive pulmonary disease (COPD).,We conducted a post hoc pooled analysis of data from 10 randomized controlled trials (RCTs).,Change from baseline (CFB) in trough forced expiratory volume in 1 s (FEV1), proportion of FEV1 responders (≥ 100-mL increase from baseline), and safety were analyzed in patients aged < 65, ≥ 65, and ≥ 75 years on Days 28, 56, and 84 (12-week analysis of parallel-group design studies), Days 28, 56, 84, 112, 140, 168, and 169 (24-week analysis of parallel-group design studies), and Days 2, 42, and 84 (12-week analysis of crossover design studies).,The UMEC/VI intent-to-treat (ITT) populations comprised 2246, 1296, and 472 patients in the 12-week parallel-group, 24-week parallel-group, and 12-week crossover analysis, respectively (≥ 65 years: 36-44%; ≥ 75 years: 7-11%).,The placebo ITT populations comprised 528, 280, and 505 patients, respectively (≥ 65 years: 37-41%; ≥ 75 years: 5-11%).,Significant improvements in trough FEV1 and significantly greater proportions of FEV1 responders were seen with UMEC/VI compared with placebo in all analyses regardless of patient age or timepoint considered (p ≤ 0.023), except Day 84 trough FEV1 CFB in the 12-week crossover analysis in patients aged ≥ 75 years (p = 0.064).,UMEC/VI safety profile was similar to placebo in all age groups.,In this pooled analysis of RCT data, once-daily UMEC/VI was well tolerated and provided clinically significant lung function benefits compared with placebo in younger and older patients with COPD.,GlaxoSmithKline (study 208125).,The online version of this article (10.1007/s40266-018-0558-y) contains supplementary material, which is available to authorized users. | Inhaled umeclidinium (UMEC) and the combination of inhaled UMEC with vilanterol (UMEC/VI) are approved maintenance treatments for chronic obstructive pulmonary disease in the US and EU.,This was a randomized, open-label, three-period crossover, single- and repeat-dose study to assess the pharmacokinetics (PK), safety, and tolerability of inhaled UMEC/VI 62.5/25 μg (delivering 55/22 μg) and UMEC/VI 125/25 μg (delivering 113/22 μg) compared with their monotherapy components (UMEC 62.5 μg, UMEC 125 μg and, VI 25 μg [delivering 55, 113, and 22 μg, respectively]) in healthy Chinese subjects (n=20).,UMEC and VI were rapidly absorbed following single and repeat dosing (time to maximum plasma concentration [tmax]: UMEC = 5 min; VI = 5 min).,The median tlast was 2-4 h for UMEC and 1-2 h for VI following single doses of UMEC/VI and UMEC monotherapy (both doses).,UMEC reached steady-state prior to Day 10; steady-state for VI could not be assessed.,UMEC accumulation following repeat dosing was 11-34% based on Cmax and 19-59% based on area under the concentration-time curve from time zero to 2 h (AUC(0-2)).,VI accumulation following repeat dosing was 25-66% based on Cmax and 17-43% based on AUC(0-2).,The evidence was not sufficient to suggest that systemic exposure was substantially different between UMEC/VI combination therapy and the constituent monotherapies following single or repeat dosing.,Following both single- and repeat-dose administration, the inter-subject coefficient of variation for all UMEC PK parameter estimates ranged from 12% to 165% for all treatments, indicating a wide range of variability in inhaled PK parameters.,Twelve subjects experienced ≥1 adverse event (AE).,Six subjects experienced ≥1 treatment-related AE; the most commonly reported treatment-related AE was chest discomfort (n=3 [15%]).,No clinically important changes in vital signs or electrocardiogram parameters were reported.,These data suggest that single- and repeat-dose administration of UMEC/VI combination therapy in healthy Chinese subjects did not result in substantial differences in systemic exposure compared with UMEC and VI as monotherapies.,Clinicaltrials.gov NCT01899638 NCT01899638 | 1 |
Asthma and chronic obstructive pulmonary disease (COPD) are chronic airway inflammatory diseases that share some common features, although these diseases are somewhat different in etiologies, clinical features, and treatment policies.,The aim of this study is to investigate the common microRNA-mediated changes in bronchial epithelial cells of asthma and COPD.,The microRNA profiles in primary bronchial epithelial cells from asthma (AHBE) and COPD (CHBE) patients and healthy subjects (NHBE) were analyzed with next-generation sequencing (NGS) and the significant microRNA changes common in AHBE and CHBE were extracted.,The upregulation of hsa-miR-10a-5p and hsa-miR-146a-5p in both AHBE and CHBE was confirmed with quantitative polymerase chain reaction (qPCR).,Using bioinformatic methods, we further identified putative targets of these microRNAs, which were downregulated in both AHBE and CHBE: miR-10a-5p might suppress BCL2, FGFR3, FOXO3, PDE4A, PDE4C, and PDE7A; miR-146a-5p might suppress BCL2, INSR, PDE4D, PDE7A, PDE7B, and PDE11A.,We further validated significantly decreased expression levels of FOXO3 and PDE7A in AHBE and CHBE than in NHBE with qPCR.,Increased serum miR-146a-5p level was also noted in patients with asthma and COPD as compared with normal control subjects.,In summary, our study revealed possible mechanisms mediated by miR-10a-5p and miR-146a-5p in the pathogenesis of both asthma and COPD.,The findings might provide a scientific basis for developing novel diagnostic and therapeutic strategies. | Cytotoxic lymphocytes are increased in the airways of COPD patients.,Whether this increase is driven primarily by the disease or by smoking is not clear, nor whether it correlates with the rate of decline in lung function.,Bronchoscopy with BAL was performed in 52 subjects recruited from the longitudinal OLIN COPD study according to pre-determined criteria; 12 with COPD and a rapid decline in lung function (loss of FEV1 ≥ 60 ml/year), 10 with COPD and a non-rapid decline in lung function (loss of FEV1 ≤ 30 ml/year), 15 current and ex-smokers and 15 non-smokers with normal lung function.,BAL lymphocyte subsets were determined using flow cytometry.,In BAL fluid, the proportions of NK, iNKT and NKT-like cells all increased with pack-years.,Within the COPD group, NK cells - but not iNKT or NKT-like cells - were significantly elevated also in subjects that had quit smoking.,In contrast, current smoking was associated with a marked increase in iNKT and NKT-like cells but not in NK cells.,Rate of lung function decline did not significantly affect any of the results.,In summary, increased proportions of NK cells in BAL fluid were associated with COPD; iNKT and NKT-like cells with current smoking but not with COPD.,Interestingly, NK cell percentages did not normalize in COPD subjects that had quit smoking, indicating that these cells might play a role in the continued disease progression seen in COPD even after smoking cessation.,Clinicaltrials.gov identifier NCT02729220.,The online version of this article (10.1186/s12931-018-0940-7) contains supplementary material, which is available to authorized users. | 1 |
The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.,The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada.,Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified.,The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.,The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively.,The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th.,The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first.,Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.,The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation.,Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality. | Antibiotics are recommended for severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) admitted to intensive care units (ICU).,Serum procalcitonin (PCT) could be a useful tool for selecting patients with a lower probability of developing bacterial infection, but its measurement has not been investigated in this population.,We conducted a single center prospective cohort study in consecutive COPD patients admitted to the ICU for AECOPD between September 2005 and September 2006.,Sputum samples or tracheal aspirates were tested for the presence of bacteria and viruses.,PCT levels were measured at the time of admittance, six hours, and 24 hours using a sensitive immunoassay.,Thirty nine AECOPD patients were included, 31 of which (79%) required a ventilator support at admission.,The median [25%-75% interquartile range] PCT level, assessed in 35/39 patients, was: 0.096 μg/L [IQR, 0.065 to 0.178] at the time of admission, 0.113 μg/L [IQR, 0.074 to 0.548] at six hours, and 0.137 μg/L [IQR, 0.088 to 0.252] at 24 hours.,The highest PCT (PCTmax) levels were less than 0.1 μg/L in 14/35 (40%) patients and more than 0.25 μg/L in 10/35 (29%) patients, suggesting low and high probability of bacterial infection, respectively.,Five species of bacteria and nine species of viruses were detected in 12/39 (31%) patients.,Among the four patients positive for Pseudomonas aeruginosa, one had a PCTmax less than 0.25 μg/L and three had a PCTmax less than 0.1 μg/L.,The one patient positive for Haemophilus influenzae had a PCTmax more than 0.25 μg/L.,The presence or absence of viruses did not influence PCT at time of admission (0.068 vs 0.098 μg/L respectively, P = 0.80).,The likelihood of bacterial infection is low among COPD patients admitted to ICU for AECOPD (40% with PCT < 0.1 μg/L) suggesting a possible inappropriate use of antibiotics.,Further studies are necessary to assess the impact of a procalcitonin-based therapeutic strategy in critically ill COPD patients.,The online version of this article (doi:10.1186/1471-2334-8-145) contains supplementary material, which is available to authorized users. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) impairs the function of the diaphragm by placing it at a mechanical disadvantage, shortening its operating length and changing the mechanical linkage between its various parts.,This makes the diaphragm's contraction less effective in raising and expanding the lower rib cage, thereby increasing the work of breathing and reducing the functional capacity.,To compare the effects of diaphragmatic stretch and manual diaphragm release technique on diaphragmatic excursion in patients with COPD.,This randomised crossover trial included 20 clinically stable patients with mild and moderate COPD classified according to the GOLD criteria.,The patients were allocated to group A or group B by block randomization done by primary investigator.,The information about the technique was concealed in a sealed opaque envelope and revealed to the patients only after allocation of groups.,After taking the demographic data and baseline values of the outcome measures (diaphragm mobility by ultrasonography performed by an experienced radiologist and chest expansion by inch tape performed by the therapist), group A subjects underwent the diaphragmatic stretch technique and the group B subjects underwent the manual diaphragm release technique.,Both the interventions were performed in 2 sets of 10 deep breaths with 1-minute interval between the sets.,The two outcome variables were recorded immediately after the intervention.,A wash-out period of 3 hours was maintained to neutralize the effect of given intervention.,Later the patients of group A and group B were crossed over to the other group.,In the diaphragmatic stretch technique, there was a statistically significant improvement in the diaphragmatic excursion before and after the treatment.,On the right side, p=0.00 and p=0.003 in the midclavicular line and midaxillary line.,On the left side, p=0.004 and p=0.312 in the midclavicular and midaxillary line.,In manual diaphragm release technique, there was a statistically significant improvement before and after the treatment.,On the right side, p=0.000 and p=0.000 in the midclavicular line and midaxillary line.,On the left side, p=0.002 and p=0.000 in the midclavicular line and midaxillary line.,There was no statistically significant difference in diaphragmatic excursion in the comparison of the postintervention values of both techniques.,The diaphragmatic stretch technique and manual diaphragm release technique can be safely recommended for patients with clinically stable COPD to improve diaphragmatic excursion. | Patients with chronic obstructive pulmonary disease (COPD) fall frequently, although the risk of falls may seem less important than the respiratory consequences of the disease.,Nevertheless, falls are associated to increased mortality, decreased independence and physical activity levels, and worsening of quality of life.,The aims of this systematic review was to evaluate information in the literature with regard to whether impaired postural control is more prevalent in COPD patients than in healthy age-matched subjects, and to assess the main characteristics these patients present that contribute to impaired postural control.,Five databases were searched with no dates or language limits.,The MEDLINE, PubMed, EMBASE, Web of Science, and PEDro databases were searched using “balance”, “postural control”, and “COPD” as keywords.,The search strategies were oriented and guided by a health science librarian and were performed on March 27, 2014.,The studies included were those that evaluated postural control in COPD patients as their main outcome and scored more than five points on the PEDro scale.,Studies supplied by the database search strategy were assessed independently by two blinded researchers.,A total of 484 manuscripts were found using the “balance in COPD or postural control in COPD” keywords.,Forty-three manuscripts appeared more than once, and 397 did not evaluate postural control in COPD patients as the primary outcome.,Thus, only 14 studies had postural control as their primary outcome.,Our study examiners found only seven studies that had a PEDro score higher than five points.,The examiners’ interrater agreement was 76.4%.,Six of those studies were accomplished with a control group and one study used their patients as their own controls.,The studies were published between 2004 and 2013.,Patients with COPD present postural control impairment when compared with age-matched healthy controls.,Associated factors contributing to impaired postural control were muscle weakness, physical inactivity, elderly age, need for supplemental oxygen, and limited mobility. | 1 |
Lung volume reduction (LVR) techniques improve lung function in selected patients with emphysema, but the impact of LVR procedures on the asynchronous movement of different chest wall compartments, which is a feature of emphysema, is not known.,We used optoelectronic plethysmography to assess the effect of surgical and bronchoscopic LVR on chest wall asynchrony.,Twenty-six patients were assessed before and 3 months after LVR (surgical [n = 9] or bronchoscopic [n = 7]) or a sham/unsuccessful bronchoscopic treatment (control subjects, n = 10).,Chest wall volumes were divided into six compartments (left and right of each of pulmonary ribcage [Vrc,p], abdominal ribcage [Vrc,a], and abdomen [Vab]) and phase shift angles (θ) calculated for the asynchrony between Vrc,p and Vrc,a (θRC), and between Vrc,a and Vab (θDIA).,Participants had an FEV1 of 34.6 ± 18% predicted and a residual volume of 217.8 ± 46.0% predicted with significant chest wall asynchrony during quiet breathing at baseline (θRC, 31.3° ± 38.4°; and θDIA, −38.7° ± 36.3°).,Between-group difference in the change in θRC and θDIA during quiet breathing following treatment was 44.3° (95% CI, −78 to −10.6; P = .003) and 34.5° (95% CI, 1.4 to 67.5; P = .007) toward 0° (representing perfect synchrony), respectively, favoring the LVR group.,Changes in θRC and θDIA were statistically significant on the treated but not the untreated sides.,Successful LVR significantly reduces chest wall asynchrony in patients with emphysema. | Endoscopic lung volume reduction (ELVR) provides a minimally invasive therapy for patients with severe lung emphysema.,As its impact on right ventricular (RtV) function is undefined, we examined the extent of RtV functional changes following ELVR, as assessed by use of speckle tracking-based RtV deformation analysis.,We enrolled 32 patients with severe emphysematous COPD scheduled for bronchoscopic LVR using endobronchial valves (Zephyr, PulmonX, Inc.), comprising 16 matched clinical responders and 16 non-responders.,Echocardiography was conducted one day prior to ELVR and at an eight-week postprocedural interval.,Patients were predominantly of late middle-age (65.8±8.7yrs), male (62.5%) and presented advanced COPD emphysema (means FEV1 and RV: 32.6% and 239.1% of predicted, respectively).,After ELVR, RtV apical longitudinal strain improved significantly in the total study cohort (-7.96±7.02% vs. -13.35±11.48%, p=0.04), whereas there were no significant changes in other parameters of RtV function such as RtV global longitudinal strain, TAPSE or pulmonary arterial systolic pressure.,In responding patients, 6MWT-improvement correlated with a decrease in NT-proBNP (Pearson´s r: -0.53, p=0.03).,However, clinical non-responders did not exhibit any RtV functional improvement.,ELVR beneficially impacts RtV functional parameters.,Speckle tracking-based RtV apical longitudinal strain analysis allows early determination of RtV contractile gain and identification of clinical responsiveness. | 1 |
There is increasing focus on understanding the nature of chronic obstructive pulmonary disease (COPD) during the earlier stages.,Mild COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1 or the now-withdrawn GOLD stage 0) represents an early stage of COPD that may progress to more severe disease.,This review summarises the disease burden of patients with mild COPD and discusses the evidence for treatment intervention in this subgroup.,Overall, patients with mild COPD suffer a substantial disease burden that includes persistent or potentially debilitating symptoms, increased risk of exacerbations, increased healthcare utilisation, reduced exercise tolerance and physical activity, and a higher rate of lung function decline versus controls.,However, the evidence for treatment efficacy in these patients is limited due to their frequent exclusion from clinical trials.,Careful assessment of disease burden and the rate of disease progression in individual patients, rather than a reliance on spirometry data, may identify patients who could benefit from earlier treatment intervention.,The online version of this article (10.1186/s12931-019-1108-9) contains supplementary material, which is available to authorized users. | Purpose: Assess the clinical and economic consequences associated with an early versus late diagnosis in patients with COPD.,Patients and methods: In a retrospective, observational cohort study, electronic medical record data (2000-2014) were collected from Swedish primary care patients with COPD.,COPD indicators (pneumonia, other respiratory diseases, oral corticosteroids, antibiotics for respiratory infections, prescribed drugs for respiratory symptoms, lung function measurement) registered prior to diagnosis were applied to categorize patients into those receiving early (2 or less indicators) or late diagnosis (3 or more indicators registered >90 days preceding a COPD diagnosis).,Outcome measures included annual rate of and time to first exacerbation, mortality risk, prevalence of comorbidities and health care utilization.,Results: More patients with late diagnosis (n=8827) than with early diagnosis (n=3870) had a recent comorbid diagnosis of asthma (22.0% vs 3.9%; P<0.0001).,Compared with early diagnosis, patients with late diagnosis had a higher exacerbation rate (hazard ratio [HR] 1.89, 95% confidence interval [CI]: 1.83-1.96; P<0.0001) and shorter time to first exacerbation (HR 1.61, 95% CI: 1.54-1.69; P<0.0001).,Mortality was not different between groups overall but higher for late versus early diagnosis, after excluding patients with past asthma diagnosis (HR 1.10, 95% CI: 1.02-1.18; P=0.0095).,Late diagnosis was also associated with higher direct costs than early diagnosis.,Conclusion: Late COPD diagnosis is associated with higher exacerbation rate and increased comorbidities and costs compared with early diagnosis.,The study highlights the need for accurate diagnosis of COPD in primary care in order to reduce exacerbations and the economic burden of COPD. | 1 |
The aim of this study was to explore to what extent a combined counselling and pulmonary rehabilitation program (PR) influences the perception of physical activity (PA) and motivation for behavioral change in PA in individuals with COPD.,The results of previous quantitative trial that investigated the effect of this combined treatment on daily PA were inconclusive.,It is conjectured that a more targeted tailoring of the counselling and PR intervention could improve its effectiveness.,Eighteen individuals with COPD (median age 69, 8 females) who had participated in the PneumoReha program were interviewed twice (following PR and at three-month follow-up).,These interviews were transcribed and analyzed thematically.,Based on the codes thus identified, three categories ‘perception of PA intensity’, ‘quality of motivation to perform PA’, and ‘strategies to cope with barriers’ were used to differentiate ‘types’ of participants.,Four different types of COPD individuals were distinguished.,Study findings indicate that those individuals who participated in the PR program combined with embedded counselling tended to be more active and intrinsically motivated.,A typology of four types of people with COPD was developed, characterized by their perception of activity, individual motivation and strategies for managing barriers.,The patients’ physical activity level might be influenced by their concept of physical activity and the quality of motivation.,Recognizing patients’ different activity behaviors is important for improving the quality of outpatient PR programs and developing tailored (according to each type) counselling interventions embedded in outpatient PR programs.,The study was registered on the website of https://www.clinicaltrials.gov/ with the identifier NCT02455206 (27/05/2015), as well as on the Swiss National Trails Portal SNCTP000001426 (05/21/2015). | There is a need to increase and maintain physical activity in patients with chronic obstructive pulmonary disease (COPD).,We assessed 12-month efficacy and effectiveness of the Urban Training intervention on physical activity in COPD patients.,This randomised controlled trial (NCT01897298) allocated 407 COPD patients from primary and hospital settings 1:1 to usual care (n=205) or Urban Training (n=202).,Urban Training consisted of a baseline motivational interview, advice to walk on urban trails designed for COPD patients in outdoor public spaces and other optional components for feedback, motivation, information and support (pedometer, calendar, physical activity brochure, website, phone text messages, walking groups and a phone number).,The primary outcome was 12-month change in steps·day−1 measured by accelerometer.,Efficacy analysis (with per-protocol analysis set, n=233 classified as adherent to the assigned intervention) showed adjusted (95% CI) 12-month difference +957 (184-1731) steps·day−1 between Urban Training and usual care.,Effectiveness analysis (with intention-to-treat analysis set, n=280 patients completing the study at 12 months including unwilling and self-reported non-adherent patients) showed no differences between groups.,Leg muscle pain during walks was more frequently reported in Urban Training than usual care, without differences in any of the other adverse events.,Urban Training, combining behavioural strategies with unsupervised outdoor walking, was efficacious in increasing physical activity after 12 months in COPD patients, with few safety concerns.,However, it was ineffective in the full population including unwilling and self-reported non-adherent patients.,Urban Training in COPD increased physical activity after 12 months but not in self-reported non-adherent patientshttp://ow.ly/dc2C30lnAEs | 1 |
The combination of asthma and chronic obstructive pulmonary disease (COPD), or ACOS is a recently defined syndrome.,The epidemiology of the condition is poorly described and previous research has suggested ACOS is associated with worse outcomes than either condition alone.,We therefore decided to complete a systematic review of the published literature.,This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta- Analyses guidelines.,A structured search was performed in the PubMed, Embase, and Medline databases up to Feb 2015 to identify studies reporting incidence, prevalence, health care utilization, morbidity, or mortality in COPD and asthma.,A total of 19 studies were included in the present study.,The pooled prevalence of overlap among COPD was 27% (95% CI: 0.16-0.38, p<0.0001) and 28% (95% CI: 0.09-0.47, p = 0.0032) in the population and hospital-based studies, respectively.,We found no significant difference between ACOS and COPD in terms of gender, smoking status, lung function and 6mWD.,However, in comparison to subject with only COPD, ACOS subjects were significantly younger, had higher BMI, healthcare utilization, and lower HRQoL.,ACOS is a common condition that exists in a substantial proportion of subjects with COPD.,ACOS represents a distinct clinical phenotype with more frequent exacerbations, hospitalization, worse health-related quality of life, and higher healthcare costs than either disease alone.,There is a critical need to better define the management and treatment of this syndrome. | Many patients with asthma or chronic obstructive pulmonary disease (COPD) have overlapping characteristics of both diseases.,By spirometric definition, patients with both fixed airflow obstruction (AO) and bronchodilator reversibility or fixed AO and bronchial hyperresponsiveness can be considered to have asthma-COPD overlap syndrome (ACOS).,However, patients regarded to have ACOS by spirometric criteria alone are heterogeneous and can be classified by phenotype.,Eosinophilic inflammation, a history of allergic disease, and smoke exposure are important components in the classification of ACOS.,Each phenotype has a different underlying pathophysiology, set of characteristics, and prognosis.,Medical treatment for ACOS should be tailored according to phenotype.,A narrower definition of ACOS that includes both spirometric and clinical criteria is needed. | 1 |
This study aimed to inform understanding of how to optimise patient-perceived benefits from a breathlessness service designed for patients with moderate to very severe chronic obstructive pulmonary disease (COPD).,The Westmead Breathlessness Service (WBS) trains patients to self-manage over an 8-week programme, with multidisciplinary input and home visits.,A qualitative approach was taken, using semi-structured telephone interviews.,Each transcript was globally rated as suggesting ‘significant’, ‘some’ or ‘no’ impact from WBS, and thematic analysis used an integrative approach.,Forty-one consecutive participants were interviewed to reach ‘information power’.,Eighteen (44%) participants reported ‘significant’ impact, 17 (41%) ‘some’ impact, and two (5%) ‘no’ impact.,Improvements to breathlessness were usually in the affective and impact dimensions but, more uncommonly, also sensory-perceptual.,Participants who benefited in self-esteem, confidence and motivation attributed this to one-to-one multidisciplinary coaching and home visits.,Further research should test whether including/excluding more intensive programme elements based on individual need might improve cost-effectiveness. | Self-management interventions for chronic obstructive pulmonary disease (COPD) can improve quality of life, reduce hospital admissions, and improve symptoms.,However, many factors impede engagement for patients and practitioners.,Qualitative research, with its focus on subjective experience, can provide invaluable insights into such factors.,Therefore, a systematic review and synthesis of qualitative evidence on COPD self-management from the perspective of patients, carers, and practitioners was conducted.,Following a systematic search and screening, 31 studies were appraised and data extracted for analysis.,This review found that patients can adapt to COPD; however, learning to self-manage is often a protracted process.,Emotional needs are considerable; frustration, depression, and anxiety are common.,In addition, patients can face an assortment of losses and limitations on their lifestyle and social interaction.,Over time, COPD can consume their existence, reducing motivation.,Support from family can prove vital, yet tinged with ambivalence and burden.,Practitioners may not have sufficient time, resources, or appropriate skills or confidence to provide effective self-management support, particularly in regard to patients’ psychosocial needs.,This can compound patients’ capability to engage in self-management.,For COPD self-management to be effective, patients’ psychosocial needs must be prioritised alongside medication and exacerbation management.,In addition, patients’ personal beliefs regarding COPD and its management should be reviewed periodically to avoid problematic behaviours and enhance positive adaptions to the disease.,Patients with COPD are not a homogenous group and no one intervention will prove effective for all.,Finally, practitioners require greater education, training, and support to successfully assist patients. | 1 |
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide.,COPD results from chronic inflammation of the lungs.,Current treatments, including physical and chemical therapies, provide limited results.,Stem cells, particularly mesenchymal stem cells (MSCs), are used to treat COPD.,Here, we evaluated the safety and efficacy of umbilical cord-derived (UC)-MSCs for treating COPD.,Twenty patients were enrolled, 9 at stage C and 11 at stage D per the Global Initiative for Obstructive Lung Disease (GOLD) classification.,Patients were infused with 106 cells/kg of expanded allogeneic UC-MSCs.,All patients were followed for 6 months after the first infusion.,The treatment end-point included a comprehensive safety evaluation, pulmonary function testing (PFT), and quality-of-life indicators including questionnaires, the 6-min walk test (6MWT), and systemic inflammation assessments.,All patients completed the full infusion and 6-month follow-up.,No infusion-related toxicities, deaths, or severe adverse events occurred that were deemed related to UC-MSC administration.,The UC-MSC-transplanted patients showed a significantly reduced Modified Medical Research Council score, COPD assessment test, and number of exacerbations.,However, the forced expiratory volume in 1 s, C-reactive protein, and 6MWT values were nonsignificantly reduced after treatment (1, 3, and 6 months) compared with those before the treatment.,Systemic UC-MSC administration appears to be safe in patients with moderate-to-severe COPD, can significantly improve their quality of life, and provides a basis for subsequent cell therapy investigations.,ISRCTN, ISRCTN70443938.,Registered 06 July 2019 | COPD is characterised by tissue destruction and inflammation.,Given the lack of curative treatments and the progressive nature of the disease, new treatments for COPD are highly relevant.,In vitro cell culture and animal studies have demonstrated that mesenchymal stromal cells (MSCs) have the capacity to modify immune responses and to enhance tissue repair.,These properties of MSCs provided a rationale to investigate their potential for treatment of a variety of diseases, including COPD.,Preclinical models support the hypothesis that MSCs may have clinical efficacy in COPD.,However, although clinical trials have demonstrated the safety of MSC treatment, thus far they have not provided evidence for MSC efficacy in the treatment of COPD.,In this review, we discuss the rationale for MSC-based cell therapy in COPD, the main findings from in vitro and in vivo preclinical COPD model studies, clinical trials in patients with COPD and directions for further research. | 1 |
The aim of this study was to assess the current evidence for long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combinations (FDCs) in the treatment of COPD.,A systematic literature search of randomized controlled trials published in English up to September 2017 of LABA/LAMA FDCs vs LABA or LAMA or LABA/inhaled corticosteroid (ICS) FDCs in COPD patients was performed using PubMed, Embase, Scopus, and Google Scholar.,Outcomes including forced expiratory volume in 1 second (FEV1), Transition Dyspnea Index (TDI) scores, St George’s Respiratory Questionnaire (SGRQ) scores, exacerbations, exercise tolerance (endurance time [ET]), inspiratory capacity (IC), and rescue medication use were evaluated.,In total, 27 studies were included in the review.,LABA/LAMA FDCs significantly improved lung function (FEV1) at 12 weeks compared with LABA or LAMA or LABA/ICS.,These effects were maintained over time.,Significant improvements with LABA/LAMA FDCs vs each evaluated comparator were also observed in TDI and SGRQ scores, even if significant differences between different LABA/LAMA FDCs were detected.,Only the LABA/LAMA FDC indacaterol/glycopyrronium has shown superiority vs LAMA and LABA/ICS for reducing exacerbation rates, while olodaterol/tiotropium and indacaterol/glycopyrronium have been shown to improve ET and IC vs the active comparators.,Rescue medication use was significantly reduced by LABA/LAMA FDCs vs the evaluated comparators.,LABA/LAMA FDCs were safe, with no increase in the risk of adverse events with LABA/LAMA FDCs vs the monocomponents.,Evidence supporting the efficacy of LABA/LAMA FDCs for COPD is heterogeneous, particularly for TDI and SGRQ scores, exacerbation rates, ET, and IC.,So far, indacaterol/glycopyrronium is the LABA/LAMA FDC that has the strongest evidence for superiority vs LABA, LAMA, and LABA/ICS FDCs across the evaluated outcomes.,LABA/LAMA FDCs were safe; however, more data should be collected in a real-world setting to confirm their safety. | Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease.,For each patient, four of five treatments were administered once daily for 6 weeks, with a 21-day washout between treatments: tiotropium/olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg, olodaterol 5 µg or placebo, all via the Respimat inhaler.,Primary outcomes were inspiratory capacity prior to exercise and exercise endurance time during constant work-rate cycle ergometry to symptom limitation at 75% of peak incremental work rate after 6 weeks (2 h post-dose).,295 and 291 patients were treated in MORACTO 1 and 2, respectively.,Tiotropium/olodaterol 2.5/5 and 5/5 µg provided significant improvements in inspiratory capacity versus placebo and monotherapies (p<0.0001), and significant improvements in exercise endurance time versus placebo (p<0.0001).,Intensity of breathing discomfort was reduced following both doses of tiotropium/olodaterol versus placebo (p<0.0001).,Once-daily tiotropium/olodaterol yielded improvements in lung hyperinflation versus placebo and statistically significant improvements versus monotherapies.,Tiotropium/olodaterol also showed improvements in dyspnoea and exercise tolerance versus placebo but not consistently versus monotherapies.,T/O reduces lung hyperinflation in COPD versus T, O or placebo and increases exercise endurance versus placebohttp://ow.ly/ml3G307XW6a | 1 |
: To verify the accordance of functional and morphometric parameters during the development of emphysema.,: BALB/c mice received a nasal drop of either papain or saline solution and were studied after 1, 3, 15, 28, and 40 days.,Functional parameters, such as airway resistance, tissue damping, and tissue elastance, were analyzed.,To evaluate the structural changes and possible mechanisms involved in this disease, we measured the mean linear intercept, the volume proportions of elastic and collagen fibers, the number of macrophages, the numbers of cells expressing metalloprotease 12 and 8-isoprostane in lung parenchyma.,: We only observed decreases in tissue elastance and tissue damping on the 28th day, with a concomitant increase in the mean linear intercept, indicating the presence of emphysema.,However, only the mean linear intercept values remained increased until the 40th day.,The volume proportion of collagen fibers was increased from the 15th day to the 40th day, whereas the volume proportion of elastic fibers was only increased on the 40th day.,The number of macrophages increased beginning on the 1st day.,The expression of metalloproteinase 12 was increased from the 3rd day until the 40th day.,However, 8-isoprostane expression was only increased on the 1st and 3rd days.,: In this study, morphometric parameters were found to be more reliable for detecting the presence of emphysema than the functional parameters measured by respiratory mechanics.,Further investigations are necessary to understand how the extracellular matrix remodeling observed in the lung parenchyma could be involved in this process. | Chronic obstructive pulmonary disease (COPD) is a common and deadly disease.,One of the hallmarks of COPD is an accelerated decline in lung function, as measured by spirometry.,Inflammation, oxidative stress and other pathways are hypothesized to be important in this deterioration.,Because progressive airflow obstruction is associated with considerable morbidity and mortality, a major goal of COPD treatment has been to slow or prevent the accelerated decline in lung function.,Until recently, the only known effective intervention was smoking cessation.,However, newly reported large clinical trials have shown that commonly used medications may help slow the rate of lung function decline.,The effect of these medications is modest (and thus required such large, expensive trials) and to be of clinical benefit, therapy would likely need to start early in the course of disease and be prolonged.,Such a treatment strategy aimed at preservation of lung function would need to be balanced against the side effects and costs of prolonged therapy.,A variety of newer classes of medications may help target other pathophysiologically important pathways, and could be used in the future to prevent lung function decline in COPD. | 1 |
Extracellular matrix (ECM) creates the tissue microenvironment and serves a role in airway wall remodeling in chronic obstructive pulmonary disease (COPD).,However, the biological function of ECM in COPD remains to be elucidated.,In the present study, 24 healthy Sprague Dawley rats were randomized to normal and COPD groups.,COPD was established by intratracheal injection with lipopolysaccharide over 30 days.,Subsequently, airway smooth muscle cells (ASMCs) were isolated from rats and served as a model to assess the effects of three ECM components, including collagen type I, laminin and collagen type III (COL-3).,Functional analysis in vitro, using cell counting kit-8, flow cytometry, wound healing and cell adhesion assays indicated that the ECM components could promote cell proliferation, cell cycle progression, migration and adhesion ability, respectively.,Furthermore, as demonstrated by ELISA, treatment with ECM components increased levels of C-X-C motif chemokine ligand 1 (CXCL1), CXCL8 and interleukin-6 in ASMCs.,Expression of transforming growth factor β1 (TGFβ1), fibroblast growth factor-1 (FGF-1) and tissue inhibitor of metalloproteinase 1 (TIMP1) was increased, and expression of matrix metalloproteinase-9 (MMP-9) was decreased following treatment with ECM components, as demonstrated by reverse transcription-quantitative polymerase chain reaction and western blot analysis.,Additionally, specific activation of phosphoinositide 3-kinase (PI3K) signaling, using insulin-like growth factor-1 (IGF-1), promoted cell proliferation and cell cycle progression, increased expression of TGFβ1, FGF-1, PI3K, AKT, phospho-AKT, serine/threonine-protein kinase mTOR (mTOR), phospho-mTOR and TIMP1, promoted cell migration capacity and reduced the expression level of MMP-9 in cells from COPD rats.,Consistently, PI3K inhibitor LY294002 exerted the opposite effect to IGF-1.,In conclusion, ECM proteins promoted proliferation, migration and adhesion of ASMCs form rat models of COPD through activation of the PI3K/AKT signaling pathway. | : To verify the accordance of functional and morphometric parameters during the development of emphysema.,: BALB/c mice received a nasal drop of either papain or saline solution and were studied after 1, 3, 15, 28, and 40 days.,Functional parameters, such as airway resistance, tissue damping, and tissue elastance, were analyzed.,To evaluate the structural changes and possible mechanisms involved in this disease, we measured the mean linear intercept, the volume proportions of elastic and collagen fibers, the number of macrophages, the numbers of cells expressing metalloprotease 12 and 8-isoprostane in lung parenchyma.,: We only observed decreases in tissue elastance and tissue damping on the 28th day, with a concomitant increase in the mean linear intercept, indicating the presence of emphysema.,However, only the mean linear intercept values remained increased until the 40th day.,The volume proportion of collagen fibers was increased from the 15th day to the 40th day, whereas the volume proportion of elastic fibers was only increased on the 40th day.,The number of macrophages increased beginning on the 1st day.,The expression of metalloproteinase 12 was increased from the 3rd day until the 40th day.,However, 8-isoprostane expression was only increased on the 1st and 3rd days.,: In this study, morphometric parameters were found to be more reliable for detecting the presence of emphysema than the functional parameters measured by respiratory mechanics.,Further investigations are necessary to understand how the extracellular matrix remodeling observed in the lung parenchyma could be involved in this process. | 1 |
Evidence from several studies show poor guideline adherence to COPD treatment, but no such study has been undertaken in Norway.,The objectives of this study, was to estimate and compare the guideline adherence to COPD treatment in general population-based and hospital-recruited COPD patients, and find possible predictors of guideline adherence.,From the prospective, observational EconCOPD-study, we analysed guideline adherence for 90 population-based COPD cases compared to 245 hospital-recruited COPD patients.,Overall guideline adherence was defined as correct pharmacological treatment, and influenza vaccination the preceding year, and having received smoking cessation advice.,Multivariate logistic regression analysis was performed with the dichotomous outcome overall guideline adherence adjusting for relevant variables.,The overall guideline adherence for population-based COPD cases was 6.7%, significantly lower than the 29.8% overall guideline-adherence amongst hospital-recruited COPD patients.,Adherence to pharmacological treatment guidelines was 10.0 and 35.5%, for the two recruitment sources, respectively.,GOLD-stage 3 to 4 was associated with significantly better guideline adherence compared to GOLD-stage 2 (OR (95% CI) 18.9 (8.37,42.7)).,The unadjusted difference between the two recruitment sources was completely explained by degree of airflow obstruction.,Overall guideline adherence was very low for both recruitment sources.,We call for increased attention from authorities and healthcare personnel to improve the quality of care given to this patient group.,The online version of this article (10.1186/s12890-018-0756-8) contains supplementary material, which is available to authorized users. | Pulmonary rehabilitation (PR) improves exercise capacity and health status in patients with COPD, but many patients assessed for PR do not complete therapy.,It is unknown whether socioeconomic deprivation associates with rates of completion of PR or the magnitude of clinical benefits bequeathed by PR.,PR services across England and Wales enrolled patients to the National PR audit in 2015.,Deprivation was assessed using Index of Multiple Deprivation (IMD) derived from postcodes.,Study outcomes were completion of therapy and change in measures of exercise performance and health status.,Univariate and multivariate analyses investigated associations between IMD and these outcomes.,210 PR programmes enrolled 7413 patients.,Compared with the general population, the PR sample lived in relatively deprived neighbourhoods.,There was a statistically significant association between rates of completion of PR and quintile of deprivation (70% in the least and 50% in the most deprived quintiles).,After baseline adjustments, the risk ratio (95% CI) for patients in the most deprived relative to the least deprived quintile was 0.79 (0.73 to 0.85), p<0.001.,After baseline adjustments, IMD was not significantly associated with improvements in exercise performance and health status.,In a large national dataset, we have shown that patients living in more deprived areas are less likely to complete PR.,However, deprivation was not associated with clinical outcomes in patients who complete therapy.,Interventions targeted at enhancing referral, uptake and completion of PR among patients living in deprived areas could reduce morbidity and healthcare costs in such hard-to-reach populations. | 1 |
Statins have anti-inflammatory and immunomodulating properties which could possibly influence inflammatory airways disease.,We assessed evidence for disease modifying effects of statin treatment in patients with chronic obstructive pulmonary disease (COPD).,A systematic review was conducted of studies which reported effects of statin treatment in COPD.,Data sources searched included MEDLINE, EMBASE and reference lists.,Eight papers reporting nine original studies met the selection criteria.,One was a randomized controlled trial (RCT), one a retrospective nested case-control study, five were retrospective cohort studies of which one was linked with a case-control study, and one was a retrospective population-based analysis.,Outcomes associated with treatment with statins included decreased all-cause mortality in three out of four studies (OR/HR 0.48-0.67 in three studies, OR 0.99 in one study), decreased COPD-related mortality (OR 0.19-0.29), reduction in incidence of respiratory-related urgent care (OR 0.74), fewer COPD exacerbations (OR 0.43), fewer intubations for COPD exacerbations (OR 0.1) and attenuated decline in pulmonary function.,The RCT reported improvement in exercise capacity and dyspnea after exercise associated with decreased levels of C-reactive protein and Interleukin-6 in statin users, but no improvement of lung function.,There is evidence from observational studies and one RCT that statins may reduce morbidity and/or mortality in COPD patients.,Further interventional studies are required to confirm these findings. | The purpose of our study was to examine the association of prior outpatient use of statins and angiotensin converting enzyme (ACE) inhibitors on mortality for subjects ≥ 65 years of age hospitalized with acute COPD exacerbations.,We conducted a retrospective national cohort study using Veterans Affairs administrative data including subjects ≥65 years of age hospitalized with a COPD exacerbation.,Our primary analysis was a multilevel model with the dependent variable of 90-day mortality and hospital as a random effect, controlling for preexisting comorbid conditions, demographics, and other medications prescribed.,We identified 11,212 subjects with a mean age of 74.0 years, 98% were male, and 12.4% of subjects died within 90-days of hospital presentation.,In this cohort, 20.3% of subjects were using statins, 32.0% were using ACE inhibitors or angiotensin II receptor blockers (ARB).,After adjusting for potential confounders, current statin use (odds ratio 0.51, 95% confidence interval 0.40-0.64) and ACE inhibitor/ARB use (0.55, 0.46-0.66) were significantly associated with decreased 90-day mortality.,Use of statins and ACE inhibitors prior to admission is associated with decreased mortality in subjects hospitalized with a COPD exacerbation.,Randomized controlled trials are needed to examine whether the use of these medications are protective for those patients with COPD exacerbations. | 1 |
Many patients with COPD are underdiagnosed, including patients with coexisting lung cancer.,We conducted a retrospective study of COPD prevalence and outcomes among all patients diagnosed with lung cancer at our institution during a 2-year period.,Patients with known COPD (group A) were compared with those who received a diagnosis of COPD at the time of their oncologic workup (group B).,A total of 306 patients were diagnosed with lung cancer during the study period, including 87 with COPD (28.6%).,Sixty percent of patients with coexisting lung cancer and COPD were unaware of their obstructive airways disease prior to the lung cancer diagnosis.,Patients in group A were older (74+9 vs 69+9 years; P=0.03), had more severe obstruction (% of predicted forced expiratory volume in one second [FEV1%] 55+17 vs 71+13; P=0.04), more emphysema (91% vs 65%; P=0.02), and worse diffusing capacity of the lungs for carbon monoxide 59+19% vs 72+22%; P=0.01) than patients in group B, but the latter had more advanced lung cancer (27.3% vs 13.8% stage IV disease; P=0.01) and consumed more outpatient resources (P=0.03).,Overall mortality was similar (56% vs 58%).,However, stage-adjusted mortality showed a trend toward greater mortality in group B patients (1.87 [0.91-3.85]; P=0.087).,COPD infradiagnosis is common in patients with coexisting lung cancer and is associated with more advanced cancer stage, greater outpatient resource consumption, and may be associated with greater stage-adjusted mortality. | Chronic obstructive pulmonary disease (COPD) has been consistently associated with increased risk of lung cancer.,However, previous studies have had limited ability to determine whether the association is due to smoking.,The Environment And Genetics in Lung cancer Etiology (EAGLE) population-based case-control study recruited 2100 cases and 2120 controls, of whom 1934 cases and 2108 controls reported about diagnosis of chronic bronchitis, emphysema, COPD (chronic bronchitis and/or emphysema), or asthma more than 1 year before enrollment.,We estimated odds ratios (OR) and 95% confidence intervals (CI) using logistic regression.,After adjustment for smoking, other previous lung diseases, and study design variables, lung cancer risk was elevated among individuals with a history of chronic bronchitis (OR = 2.0, 95% CI = 1.5-2.5), emphysema (OR = 1.9, 95% CI = 1.4-2.8), or COPD (OR = 2.5, 95% CI = 2.0-3.1).,Among current smokers, association between chronic bronchitis and lung cancer was strongest among lighter smokers.,Asthma was associated with a decreased risk of lung cancer in males (OR = 0.48, 95% CI = 0.30-0.78).,These results suggest that the associations of personal history of chronic bronchitis, emphysema, and COPD with increased risk of lung cancer are not entirely due to smoking.,Inflammatory processes may both contribute to COPD and be important for lung carcinogenesis. | 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. | Interactions between spirometry and patient-reported outcomes in COPD are not well understood.,This systematic review and study-level analysis investigated the relationship between changes in FEV1 and changes in health status with bronchodilator therapy.,Six databases (to October 2009) were searched to identify studies with long-acting bronchodilator therapy reporting FEV1 and health status, dyspnoea or exacerbations.,Mean and standard deviations of treatment effects were extracted for each arm of each study.,Relationships between changes in trough FEV1 and outcomes were assessed using correlations and random-effects regression modelling.,The primary outcome was St George's Respiratory Questionnaire (SGRQ) total score.,Thirty-six studies (≥3 months) were included.,Twenty-two studies (23,654 patients) with 49 treatment arms each contributing one data point provided SGRQ data.,Change in trough FEV1 and change in SGRQ total score were negatively correlated (r = -0.46, p < 0.001); greater increases in FEV1 were associated with greater reductions (improvements) in SGRQ.,The correlation strengthened with increasing study duration from 3 to 12 months.,Regression modelling indicated that 100 mL increase in FEV1 (change at which patients are more likely to report improvement) was associated with a statistically significant reduction in SGRQ of 2.5 (95% CI 1.9, 3.1), while a clinically relevant SGRQ change (4.0) was associated with 160.6 (95% CI 129.0, 211.6) mL increase in FEV1.,The association between change in FEV1 and other patient-reported outcomes was generally weak.,Our analyses indicate, at a study level, that improvement in mean trough FEV1 is associated with proportional improvements in health status. | 1 |
Socioeconomic status (SES) is a strong social determinant of health.,There remains a limited understanding of the association between SES and COPD prevalence among low- and middle-income countries where the majority of COPD-related morbidity and mortality occurs.,We examined the association between SES and COPD prevalence using data collected in Argentina, Bangladesh, Chile, Peru, and Uruguay.,We compiled lung function, demographic, and SES data from three population-based studies for 11,042 participants aged 35-95 years.,We used multivariable alternating logistic regressions to study the association between COPD prevalence and SES indicators adjusted for age, sex, self-reported daily smoking, and biomass fuel smoke exposure.,Principal component analysis was performed on monthly household income, household size, and education to create a composite SES index.,Overall COPD prevalence was 9.2%, ranging from 1.7% to 15.4% across sites.,The adjusted odds ratio of having COPD was lower for people who completed secondary school (odds ratio [OR] =0.73, 95% CI 0.55-0.98) and lower with higher monthly household income (OR =0.96 per category, 95% CI 0.93-0.99).,When combining SES factors into a composite index, we found that the odds of having COPD was greater with lower SES (interquartile OR =1.23, 95% CI 1.05-1.43) even after controlling for subject-specific factors and environmental exposures.,In this analysis of multiple population-based studies, lower education, lower household income, and lower composite SES index were associated with COPD.,Since household income may be underestimated in population studies, adding household size and education into a composite index may provide a better surrogate for SES. | 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. | 1 |
In the Phase III, 24-week KRONOS study (NCT02497001), triple therapy with budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) reduced exacerbation rates versus glycopyrrolate/formoterol fumarate (GFF) MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD) and no requirement for a history of exacerbations.,We report a post hoc analysis investigating whether the benefits observed were driven by patients with ≥1 exacerbation in the 12 months prior to the study.,Patients received BGF MDI 320/18/9.6 µg, GFF MDI 18/9.6 µg, budesonide/formoterol fumarate (BFF) MDI 320/9.6 µg, or budesonide/formoterol fumarate dry powder inhaler (BUD/FORM DPI) 400/12 µg twice-daily.,Post hoc analyses were conducted on exacerbation and lung function results from patients with and without a documented exacerbation in the 12 months prior to the study.,Overall, 74% (1411/1896) of the modified-intent-to-treat (mITT) population had no moderate/severe exacerbations in the 12 months prior to the study.,BGF MDI reduced exacerbation rates versus GFF MDI in the prior (58%; unadjusted p=0.0003) and no prior (48%; unadjusted p=0.0001) exacerbations subgroups.,The magnitude of reduction in exacerbation rates was generally similar within subgroups for BGF MDI versus BFF MDI and BUD/FORM DPI.,In the prior exacerbations subgroup, risk during treatment for time to first exacerbation was lower with BGF MDI versus GFF MDI (p=0.0022) and BFF MDI (p=0.0110); excluding the first 30 days of data yielded similar results.,The magnitude of reduction in exacerbation rates for BGF MDI compared with GFF MDI increased with eosinophil count.,In patients with or without a history of exacerbations in the 12 months prior to the study, BGF MDI reduced exacerbation rates versus GFF MDI, suggesting results observed in the overall population were not driven by the small subgroup with a prior history of exacerbations. | Chronic obstructive pulmonary disease (COPD) is one of the top five major causes of morbidity and mortality worldwide.,Despite worldwide health care efforts, costs, and medical research, COPD figures demonstrate a continuously increasing tendency in mortality.,This is contrary to other top causes of death, such as neoplasm, accidents, and cardiovascular disease.,A major factor affecting COPD-related mortality is the acute exacerbation of COPD (AECOPD).,Exacerbations and comorbidities contribute to the overall severity in individual patients.,Despite the underestimation by the physicians and the patients themselves, AECOPD is a really devastating event during the course of the disease, similar to acute myocardial infarction in patients suffering from coronary heart disease.,In this review, we focus on the evidence that supports the claim that AECOPD is the “stroke of the lungs”.,AECOPD can be viewed as: a Semicolon or disease’s full-stop period, Triggering a catastrophic cascade, usually a Relapsing and Overwhelming event, acting as a Killer, needing Emergent treatment. | 1 |
Our aim was to assess the impact of comorbidities on existing COPD prognosis scores.,A total of 543 patients with COPD (FEV1 <80% and FEV1/FVC <70%) were included between January 2003 and January 2004.,Patients were stable for at least 6 weeks before inclusion and were followed for 5 years without any intervention by the research team.,Comorbidities and causes of death were established from medical reports or information from primary care medical records.,The GOLD system and the body mass index, obstruction, dyspnea and exercise (BODE) index were used for COPD classification.,Patients were also classified into four clusters depending on the respiratory disease and comorbidities.,Cluster analysis was performed by combining multiple correspondence analyses and automatic classification.,Receiver operating characteristic curves and the area under the curve (AUC) were calculated for each model, and the DeLong test was used to evaluate differences between AUCs.,Improvement in prediction ability was analyzed by the DeLong test, category-free net reclassification improvement and the integrated discrimination index.,Among the 543 patients enrolled, 521 (96%) were male, with a mean age of 68 years, mean body mass index 28.3 and mean FEV1% 55%.,A total of 167 patients died during the study follow-up.,Comorbidities were prevalent in our cohort, with a mean Charlson index of 2.4.,The most prevalent comorbidities were hypertension, diabetes mellitus and cardiovascular diseases.,On comparing the BODE index, GOLDABCD, GOLD2017 and cluster analysis for predicting mortality, cluster system was found to be superior compared with GOLD2017 (0.654 vs 0.722, P=0.006), without significant differences between other classification models.,When cardiovascular comorbidities and chronic renal failure were added to the existing scores, their prognostic capacity was statistically superior (P<0.001).,Comorbidities should be taken into account in COPD management scores due to their prevalence and impact on mortality. | Chronic obstructive pulmonary disease (COPD) is associated with substantial health impact that may already become apparent in early disease.,This study aims to examine the features of subjects with COPD in a Dutch population-based sample and compare their physical status, mental status, and social status to non-COPD subjects.,This study made use of Longitudinal Aging Study Amsterdam (LASA) data.,Demographics, clinical characteristics, self-reported diseases, post-bronchodilator spirometry, physical, mental, and social status were assessed.,A number of 810 subjects (50.5% male, mean age 60.5 ± 2.9 years) were included.,Subjects with COPD (n = 68, mean FEV1 67.6 [IQR 60.4-80.4] %.) had a slower walking speed than non-COPD subjects, p = 0.033.,When compared to non-COPD subjects, COPD subjects gave a lower rating on their health (physical subscale of SF-12: 15 [IQR 16.0-19.0] vs.,18 [IQR 11.0-17.0] points) and life (EQ5D VAS: 75 [IQR 70.0-90.0] vs. 80 points [IQR 65.0-85.5]) surveys.,COPD subjects also had a more impaired disease-specific health status (CAT: 9.5 ± 5.9 vs.,6.7 ± 5.2, respectively), were less likely to have a partner (69% vs. 84%, respectively) and received emotional support less often (24% vs. 36%, respectively) compared to non-COPD subjects (All comparisons p < 0.001).,In a population-based sample, subjects with COPD had a reduced physical performance, a more impaired disease-specific health status and were more socially deprived compared to non-COPD subjects.,These impairments need to be taken into consideration when setting up a management program for patients with mild COPD.,Patients with early-stage chronic lung disease need holistic support to limit the physical, mental and social impacts of the condition.,There is more to chronic obstructive pulmonary disease (COPD) than persistent airflow limitation; systemic effects, including loss of muscle strength and higher risk of heart conditions, mental health and social problems can manifest from the early stages.,Frits Franssen at CIRO, the Netherlands, and co-workers interviewed 810 participants aged 55-65 from the Longitudinal Aging Study Amsterdam to investigate the physical, mental and social status of COPD sufferers and compare them with healthy controls.,Those with COPD were more likely to walk slower, tire easily and perceive themselves as having poor overall health.,Socially, COPD patients were less likely to have long-term partners and felt the need for more emotional support than their healthy peers. | 1 |
Self-management interventions for chronic obstructive pulmonary disease (COPD) can improve quality of life, reduce hospital admissions, and improve symptoms.,However, many factors impede engagement for patients and practitioners.,Qualitative research, with its focus on subjective experience, can provide invaluable insights into such factors.,Therefore, a systematic review and synthesis of qualitative evidence on COPD self-management from the perspective of patients, carers, and practitioners was conducted.,Following a systematic search and screening, 31 studies were appraised and data extracted for analysis.,This review found that patients can adapt to COPD; however, learning to self-manage is often a protracted process.,Emotional needs are considerable; frustration, depression, and anxiety are common.,In addition, patients can face an assortment of losses and limitations on their lifestyle and social interaction.,Over time, COPD can consume their existence, reducing motivation.,Support from family can prove vital, yet tinged with ambivalence and burden.,Practitioners may not have sufficient time, resources, or appropriate skills or confidence to provide effective self-management support, particularly in regard to patients’ psychosocial needs.,This can compound patients’ capability to engage in self-management.,For COPD self-management to be effective, patients’ psychosocial needs must be prioritised alongside medication and exacerbation management.,In addition, patients’ personal beliefs regarding COPD and its management should be reviewed periodically to avoid problematic behaviours and enhance positive adaptions to the disease.,Patients with COPD are not a homogenous group and no one intervention will prove effective for all.,Finally, practitioners require greater education, training, and support to successfully assist patients. | Self-management is recognised as an essential criteria for the provision of high quality care for chronic obstructive pulmonary disease (COPD).,The management of COPD is usually delivered by a wide range of healthcare practitioners.,This study aimed to understand the factors affecting self-management of COPD from the perspectives of the different multidisciplinary healthcare teams involved in COPD care.,Semi-structured interviews were conducted with participants from primary care, specialist respiratory and pulmonary rehabilitation (PR) teams.,Purposive sampling and snowballing were employed in participant recruitment.,All interviews were audio-recorded and transcribed verbatim and data were analysed thematically.,A total of 20 participants (eight primary care practitioners, seven respiratory specialists and five PR practitioners) were interviewed until data saturation was reached.,Participants identified a range of complex and interrelated factors affecting COPD self-management that were grouped into three broad categories-patient, practitioner and organisational/system-level factors.,Patient-level factors were predominantly considered as barriers, with COPD knowledge and understanding, and the individual patients’ life circumstances/context being the most prominent issues.,Practitioner-level factors identified were practitioners’ speciality, interest and experience in respiratory conditions as the overarching factor that influenced how self-management was understood and practiced.,A number of organisational/system-level factors were identified by all practitioners, including inconsistency of referral pathways and the wide variations of different self-management planning tools.,Factors affecting self-management of COPD across these three levels need to be tackled equally in order to improve the effectiveness of interventions and to embed and integrate self-management support approaches into routine practice.,Better co-ordination between healthcare services, practitioners and patients may help improve self-management for chronic lung disease.,Self-management is crucial for patients with chronic obstructive pulmonary disease (COPD), but it can be difficult for healthcare workers to monitor and support patient progress.,Oladapo Ogunbayo at Newcastle University, UK, and co-workers conducted interviews with healthcare practitioners to explore perceived barriers to successful self-management of COPD.,Three distinct categories emerged; those at patient level, practitioner level and organisational level, the needs of which should be carefully balanced to improved self-management.,Patient knowledge and understanding of COPD, alongside individual life circumstances, were often barriers to effective self-care.,Those practitioners with specialist respiratory knowledge took a more holistic approach to self-management than their primary care counterparts.,A lack of continuity between services and across self-management planning tools presented further barriers. | 1 |
With increasing availability of different treatments for chronic obstructive pulmonary disease (COPD), we sought to understand patient preferences for COPD treatment in the UK, USA, and Germany using a discrete choice experiment (DCE).,Qualitative research identified six attributes associated with COPD maintenance treatments: ease of inhaler use, exacerbation frequency, frequency of inhaler use, number of different inhalers used, side effect frequency, and out-of-pocket costs.,A DCE using these attributes, with three levels each, was designed and tested through cognitive interviews and piloting.,It comprised 18 choice sets, selected using a D-efficient experimental design.,Demographics and disease history were collected and the final DCE survey was completed online by participants recruited from panels in the UK, USA and Germany.,Responses were analyzed using mixed logit models, with results expressed as odds ratios (ORs).,Overall, 450 participants (150 per country) completed the DCE; most (UK and Germany, 97.3%; USA, 98.0%) were included in the final analysis.,Based on relative attribute importance, avoidance of side effects was found to be most important (UK: OR 11.65; USA: OR 7.17; Germany: OR 11.45; all p<0.0001), followed by the likelihood of fewer exacerbations (UK: OR 2.22; USA: OR 1.63; Germany: OR 2.54; all p<0.0001) and increased ease of use (UK: OR 1.84; USA: OR 1.84; Germany: OR 1.60; all p<0.0001).,Number of inhalers, out-of-pocket costs, and frequency of inhaler use were found to be less important.,Preferences were relatively consistent across the three countries.,All participants required a reduction in exacerbations to accept more frequent inhaler use or use of more inhalers.,When selecting COPD treatment, individuals assigned the highest value to the avoidance of side effects, experiencing fewer exacerbations, and ease of inhaler use.,Ensuring that patients’ preferences are considered may encourage treatment compliance. | COPD is a treatable disease with increasing prevalence worldwide.,Treatment aims to stop disease progression, to improve quality of life, and to reduce exacerbations.,We aimed to evaluate the association of the stage of COPD on adherence to inhaled therapy and the relationship between adherence and COPD exacerbations.,A retrospective analysis of patients hospitalized for acute exacerbation of COPD in a tertiary care hospital in Upper Austria and discharged with a guideline conform inhaled therapy was performed.,Follow-up data on medical utilization was recorded for the subsequent 24 months.,Adherence to inhaled therapy was defined according to the percentage of prescribed inhalers dispensed to the patient and classified as complete (> 80%), partial (50-80%) or low (< 50%).,Out of 357 patients, 65.8% were male with a mean age of 66.5 years and a mean FEV1 of 55.0%pred.,Overall, 35.3% were current smokers, and only 3.9% were never-smokers.,In 77.0% inhaled triple therapy (LAMA + LABA + ICS) was prescribed.,33.6% showed complete adherence to their therapy (33.2% in men, 34.4% in women), with a mean age of 67.0 years.,Mean medication possession ratio by GOLD spirometry class I - IV were 0.486, 0.534, 0.609 and 0.755, respectively (p = 0.002).,Hence, subjects with complete adherence to therapy had a significantly lower FEV1 compared to those with low adherence (49.2%pred. vs 59.2%pred., respectively; p < 0.001).,The risk of exacerbations leading to hospitalization was 10-fold higher in GOLD spirometry class IV compared to GOLD spirometry class I, which was even more evident in multivariate analysis (OR 13.62).,Complete adherence to inhaled therapy was only seen in 33.6% and was higher among those with more severe COPD.,Not applicable. | 1 |
Little is known about the interactions between the lung microbiome and host response in chronic obstructive pulmonary disease (COPD).,We performed a longitudinal 16S ribosomal RNA gene-based microbiome survey on 101 sputum samples from 16 healthy subjects and 43 COPD patients, along with characterization of host sputum transcriptome and proteome in COPD patients.,Dysbiosis of sputum microbiome was observed with significantly increased relative abundance of Moraxella in COPD versus healthy subjects and during COPD exacerbations, and Haemophilus in COPD ex-smokers versus current smokers.,Multivariate modeling on sputum microbiome, host transcriptome and proteome profiles revealed that significant associations between Moraxella and Haemophilus, host interferon and pro-inflammatory signaling pathways and neutrophilic inflammation predominated among airway host-microbiome interactions in COPD.,While neutrophilia was positively correlated with Haemophilus, interferon signaling was more strongly linked to Moraxella.,Moreover, while Haemophilus was significantly associated with host factors both in stable state and during exacerbations, Moraxella-associated host responses were primarily related to exacerbations.,Our study highlights a significant airway host-microbiome interplay associated with COPD inflammation and exacerbations.,These findings indicate that Haemophilus and Moraxella influence different components of host immune response in COPD, and that novel therapeutic strategies should consider targeting these bacteria and their associated host pathways in COPD.,The online version of this article (10.1186/s12931-019-1085-z) contains supplementary material, which is available to authorized users. | Some patients with chronic obstructive pulmonary disease (COPD) show increased airway inflammation and bacterial colonization during stable phase.,The aim of this study was to follow COPD patients and investigate chronic colonization with pathogenic bacteria during stable disease phase, and relate these findings to clinical parameters, inflammatory pattern, lung function, and exacerbations.,Forty-three patients with COPD were included while in a stable state and followed up monthly until exacerbation or for a maximum of 6 months.,The patients completed the Clinical COPD Questionnaire and Medical Research Council dyspnea scale questionnaires, and exhaled breath condensate was collected, followed by spirometry, impulse oscillometry, and sputum induction.,Ten patients were chronically colonized (ie, colonized at all visits) with Haemophilus influenzae during stable phase.,These patients had higher sputum levels of leukotriene B4 (P<0.001), 8-isoprostane (P=0.002), myeloperoxidase activity (P=0.028), and interleukin-8 (P=0.02) during stable phase when compared with other patients.,In addition, they had lower forced vital capacity (P=0.035) and reactance at 5 Hz (P=0.034), but there was no difference in forced expiratory volume in 1 second (FEV1), FEV1 % predicted, forced vital capacity % predicted, exhaled breath condensate biomarkers, C-reactive protein, or Clinical COPD Questionnaire and Medical Research Council dyspnea scale results.,Three patients had intermittent colonization (colonized at only some visits) of H. influenzae during stable phase, and had lower levels of inflammatory biomarkers in sputum when compared with the chronically colonized patients.,The difference in airway inflammation seen during stable phase in patients chronically colonized with H. influenzae was not observed during exacerbations.,Some COPD patients who were chronically colonized with H. influenzae during stable phase showed increased airway inflammation and reduced lung volumes when compared with non-chronically colonized patients. | 1 |
The goals of COPD therapy are to prevent and control symptoms, reduce the frequency and severity of exacerbations, and improve exercise tolerance.,The triple combination therapy of inhaled corticosteroids (ICSs), long-acting beta2 agonists (LABAs), and long-acting muscarinic antagonists (LAMAs) has become an option for maintenance treatment of COPD and as a “step-up” therapy from single or double combination treatments.,There is evidence that triple combination ICS/LABA/LAMA with different inhalers improves lung function, symptoms, and health status and reduces exacerbations.,A new triple fixed-dose combination of extrafine beclomethasone dipropionate (100 µg/puff)/formoterol fumarate (6 µg/puff)/glycopyrronium bromide (12.5 µg/puff) has been developed as a hydrofluoroalkane pressurized metered dose inhaler.,Two large pivotal studies showed that this extrafine fixed ICS/LABA/LAMA triple combination is superior to fixed ICS/LABA combined therapy and also superior to the LAMA tiotropium in terms of lung function and exacerbation prevention in COPD patients at risk of exacerbation.,This review considers the new information provided by these clinical trials of extrafine triple therapy and the implications for the clinical management of COPD patients. | To establish the dose−response for pharmacodynamics (bronchodilatation), safety and pharmacokinetics for a nebulized formulation of the long acting muscarinic antagonist glycopyrrolate (EP-101) with a high efficiency nebulizer in patients with chronic obstructive pulmonary disease (COPD).,Patients with moderate to severe COPD (GOLD II/III), with reversible lung function, were enrolled into this randomized, double-blind, placebo-controlled, six period crossover study (n = 42).,Patients received single doses of EP-101 (12.5-400 μg) and placebo via a high efficiency nebulizer (eFlow® PARI nebulizer), with washout between treatments.,Plasma pharmacokinetics were assessed in a subset of patients (n = 11).,All treatments were well tolerated with similar adverse event rates reported with placebo and at all doses.,There were no clinically relevant changes in heart rate, systolic and diastolic blood pressure or in ECG parameters including QTc interval.,Following treatment with EP-101 at all doses there was a rapid bronchodilator response within 5 min.,Significant improvements in mean change from baseline FEV1 at 24 h were reported at doses ≥50 μg compared with placebo, with a clear dose−response relationship.,Mean changes in FEV1 were 0.10 l (95% CI 0.06, 0.14) and 0.12 l (95% CI 0.08, 0.16) for 100 μg and 200 μg, respectively.,Single doses of EP-101 ranging from 12.5 μg to 400 μg were well tolerated.,EP-101 delivered by high efficiency nebulizer device produced a rapid onset of bronchodilatation with clinically meaningful improvements in lung function maintained over a 24 h period at all doses >50 μg. | 1 |
The aim of the study was to characterize pharmacokinetics of tiotropium solution 5 µg compared to powder 18 µg and assess dose-dependency of tiotropium solution pharmacodynamics in comparison to placebo.,In total 154 patients with chronic obstructive pulmonary disease (COPD) were included in this multicenter, randomized, double-blind within-solution (1.25, 2.5, 5 µg, and placebo), and open-label powder 18 µg, crossover study, including 4-week treatment periods.,Primary end points were peak plasma concentration (Cmax,ss), and area under the plasma concentration-time profile (AUC0-6h,ss), both at steady state.,The pharmacodynamic response was assessed by serial spirometry (forced expiratory volume in 1 second/forced vital capacity).,Safety was evaluated as adverse events and by electrocardiogram/Holter.,Tiotropium was rapidly absorbed with a median tmax,ss of 5-7 minutes postdosing for both devices.,The gMean ratio of solution 5 µg over powder 18 µg was 81% (90% confidence interval, 73-89%) for Cmax,ss and 76% (70-82%) for AUC0-6h,ss, indicating that bioequivalence was not established.,Dose ordering for bronchodilation was observed.,Powder 18 µg and solution 5 µg were most effective, providing comparable bronchodilation.,All treatments were well tolerated with no apparent relation to dose or device.,Comparable bronchodilator efficacy to powder18 µg at lower systemic exposure supports tiotropium solution 5 µg for maintenance treatment of COPD. | Two replicate, multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase III studies investigated the long-term efficacy and safety of once-daily olodaterol via Respimat® versus placebo and formoterol over 48 weeks in patients with moderate to very severe chronic obstructive pulmonary disease receiving usual-care background therapy.,Patients received once-daily olodaterol 5 or 10 μg, twice-daily formoterol 12 μg, or placebo.,Co-primary end points were forced expiratory volume in 1 second (FEV1) area under the curve from 0-3 hours response, FEV1 trough response, and Mahler transition dyspnea index total score after 24 weeks; secondary end points included St George’s Respiratory Questionnaire.,Overall, 904 (Study 1222.13) and 934 (Study 1222.14) patients received treatment.,Olodaterol significantly improved FEV1 area under the curve from 0-3 hours versus placebo in both studies (with olodaterol 5 μg, 0.151 L and 0.129 L; with olodaterol 10 μg, 0.165 L and 0.154 L; for all comparisons P<0.0001) and FEV1 trough responses versus placebo (0.053-0.085 L; P<0.01), as did formoterol.,Primary analysis revealed no significant difference in transition dyspnea index focal score for any active treatment versus placebo.,Post hoc analysis using pattern mixture modeling (accounting for discontinuations) demonstrated statistical significance for olodaterol versus placebo.,St George’s Respiratory Questionnaire total score was significantly improved with olodaterol, but not formoterol, versus placebo.,No safety signals were identified from adverse-event or other safety data.,Once-daily olodaterol 5 μg and 10 μg is efficacious in patients with moderate to very severe chronic obstructive pulmonary disease on usual-care maintenance therapy, with a satisfactory safety profile. | 1 |
The general practitioner (GP) is the first contact with the health care system for most patients with COPD in Denmark.,We studied, if participating in an educational program could improve adherence to guidelines, not least for diagnosis, staging, and treatment of the disease.,Two cross-sectional surveys were performed precisely one year apart before and after an educational program for the participating GPs.,A total of 124 GPs completed the study; 1716 and 1342 patients with GP-diagnosed COPD and no concomitant asthma, respectively, were included in the two surveys.,The proportion of patients having FEV1 registered in the GPs files increased from 45% to 69% (P < 0.001); and, furthermore, FEV1 % of predicted was recorded in 30% and 56%, respectively, of the cases (P < 0.001).,In line with this, significant improvements were also observed for registration of smoking status (69% to 85%), BMI (8% to 40%), severity of dyspnea (Medical Research Council) (7% to 38%), and FEV1/FVC ratio (28% to 58%) (P < 0.001).,Concerning the management options, improvements were also observed with regard to antismoking counseling, inhalator technique, physical activity, and referral for rehabilitation; use of inhaled corticosteroids in patients with mild COPD (FEV1 > 80%pred) declined from 76% to 45%.,Diagnosis and management of COPD in general practice in Denmark is not according to guidelines, but substantial improvements can be achieved by focused education of GPs and their staff. | The objective of this study was to analyze the clinical and management characteristics of chronic obstructive pulmonary disease (COPD) in men and women, to determine possible gender-associated differences between the two groups of patients.,An observational and descriptive epidemiological study (EPIDEPOC study).,The study included patients with stable COPD and aged ≥ 40 years, evaluated in primary care.,Data were collected relating to sociodemographic variables, clinical characteristics, quality of life (SF-12), severity of disease and treatment.,The results obtained in men and women were compared.,A total of 10,711 patients (75.6% males and 24.4% females) were evaluated.,Significant differences were found between males and females in relation to the following parameters: age (67.4 ± 9.2 years in men vs 66.1 ± 10.8 in women, p < 0.05), smoking (91.9% of the men were smokers or ex-smokers vs 30% of the women), comorbidity (the frequency of hypertension, diabetes, anxiety and depression was greater in women, while ischemic heart disease was more common in men), mental component of quality of life (49.4 ± 10.3 in men vs 44.6 ± 11.9 in women, p < 0.05) and severity of disease (56.5 ± 13.3% in men vs 60.7 ± 3.2 in women, p < 0.05).,As regards treatment, the percentage use of long-acting b2-adrenergic agonists, anticholinergic agents, theophyllines and mucolytic agents was significant greater in men.,The total annual cost of COPD was greater in males than in females (1989.20 ± 2364.47 € vs 1724.53 ± 2106.90, p < 0.05).,The women with COPD evaluated in this study were younger, smoked less and have more comorbidity, a poorer quality of life, and lesser disease severity than men with COPD.,However, they generated a lesser total annual cost of COPD than men. | 1 |
Cardiovascular diseases (CVDs) are arguably the most important comorbidities in chronic obstructive pulmonary disease (COPD).,CVDs are common in people with COPD, and their presence is associated with increased risk for hospitalization, longer length of stay and all-cause and CVD-related mortality.,The economic burden associated with CVD in this population is considerable and the cumulative cost of treating comorbidities may even exceed that of treating COPD itself.,Our understanding of the biological mechanisms that link COPD and various forms of CVD has improved significantly over the past decade.,But despite broad acceptance of the prognostic significance of CVDs in COPD, there remains widespread under-recognition and undertreatment of comorbid CVD in this population.,The reasons for this are unclear; however institutional barriers and a lack of evidence-based guidelines for the management of CVD in people with COPD may be contributory factors.,In this review, we summarize current knowledge relating to the prevalence and incidence of CVD in people with COPD and the mechanisms that underlie their coexistence.,We discuss the implications for clinical practice and highlight opportunities for improved prevention and treatment of CVD in people with COPD.,While we advocate more active assessment for signs of cardiovascular conditions across all age groups and all stages of COPD severity, we suggest targeting those aged under 65 years.,Evidence indicates that the increased risks for CVD are particularly pronounced in COPD patients in mid-to-late-middle-age and thus it is in this age group that the benefits of early intervention may prove to be the most effective. | Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and loss of lung function, and is currently the third largest cause of death in the world.,It is now well established that cardiovascular-related comorbidities such as stroke contribute to morbidity and mortality in COPD.,The mechanisms linking COPD and stroke remain to be fully defined but are likely to be interconnected.,The association between COPD and stroke may be largely dependent on shared risk factors such as aging and smoking, or the association of COPD with traditional stroke risk factors.,In addition, we propose that COPD-related systemic inflammation and oxidative stress may play important roles by promoting cerebral vascular dysfunction and platelet hyperactivity.,In this review, we briefly discuss the pathogenesis of COPD, acute exacerbations of COPD (AECOPD) and cardiovascular comorbidities associated with COPD, in particular stroke.,We also highlight and discuss the potential mechanisms underpinning the link between COPD and stroke, with a particular focus on the roles of systemic inflammation and oxidative stress. | 1 |
Parametric response mapping (PRM) of paired CT lung images has been shown to improve the phenotyping of COPD by allowing for the visualization and quantification of non-emphysematous air trapping component, referred to as functional small airways disease (fSAD).,Although promising, large variability in the standard method for analyzing PRMfSAD has been observed.,We postulate that representing the 3D PRMfSAD data as a single scalar quantity (relative volume of PRMfSAD) oversimplifies the original 3D data, limiting its potential to detect the subtle progression of COPD as well as varying subtypes.,In this study, we propose a new approach to analyze PRM.,Based on topological techniques, we generate 3D maps of local topological features from 3D PRMfSAD classification maps.,We found that the surface area of fSAD (SfSAD) was the most robust and significant independent indicator of clinically meaningful measures of COPD.,We also confirmed by micro-CT of human lung specimens that structural differences are associated with unique SfSAD patterns, and demonstrated longitudinal feature alterations occurred with worsening pulmonary function independent of an increase in disease extent.,These findings suggest that our technique captures additional COPD characteristics, which may provide important opportunities for improved diagnosis of COPD patients. | Bronchodilator responsiveness (BDR) is a common but variable phenomenon in COPD.,The CT characteristics of airway dimensions that differentiate COPD subjects with BDR from those without BDR have not been well described.,We aimed to assess airway dimensions in COPD subjects with and without BDR.,We analyzed subjects with GOLD 1-4 disease in the COPDGene® study who had CT airway analysis.,We divided patients into two groups: BDR + (post bronchodilator ΔFEV1 ≥ 10%) and BDR-(post bronchodilator ΔFEV1 < 10%).,The mean wall area percent (WA%) of six segmental bronchi in each subject was quantified using VIDA.,Using 3D SLICER, airway wall thickness was also expressed as the square root wall area of an airway of 10 mm (Pi10) and 15 mm (Pi15) diameter.,%Emphysema and %gas trapping were also calculated.,2355 subjects in the BDR-group and 1306 in the BDR + group formed our analysis.,The BDR + group had a greater Pi10, Pi15, and mean segmental WA% compared to the BDR-group.,In multivariate logistic regression using gender, race, current smoking, history of asthma, %emphysema, %gas trapping, %predicted FEV1, and %predicted FVC, airway wall measures remained independent predictors of BDR.,Using a threshold change in FEV1 ≥ 15% and FEV1 ≥ 12% and 200 mL to divide patients into groups, the results were similar.,BDR in COPD is independently associated with CT evidence of airway pathology.,This study provides us with greater evidence of changes in lung structure that correlate with physiologic manifestations of airflow obstruction in COPD. | 1 |
Lung hyperinflation and exercise intolerance are hallmarks of chronic obstructive pulmonary disease (COPD).,However, their relationship remains uncertain.,A combined analysis of two placebo-controlled, randomized studies examined the effects of the long-acting muscarinic antagonist umeclidinium (UMEC) and long-acting β2-agonist vilanterol (VI) separately and in combination on static hyperinflation, exercise endurance time (EET), and their relationship in patients with COPD.,Patients with moderate-to-severe stable COPD and resting functional residual capacity >120% predicted were randomized to UMEC/VI 62.5/25 μg, UMEC 62.5 μg, VI 25 μg, or placebo for 12 weeks.,Inspiratory capacity (IC), residual volume (RV), total lung capacity (TLC), and EET in an endurance shuttle-walk test were measured.,In this post hoc analysis, IC/TLC, RV/TLC, and IC were used as hyperinflation markers.,After 12 weeks, UMEC/VI and UMEC and VI showed significant improvements in hyperinflation versus placebo when measured by absolute change from baseline in IC/TLC (trough and 3 hours postdose [P≤0.011]).,UMEC/VI showed significant improvements versus UMEC and VI in absolute changes in IC/TLC (trough and 3 hours postdose [P≤0.001]).,Statistical significance for comparisons with placebo and between treatments for absolute changes in IC and percentage changes in RV/TLC followed similar patterns to those for absolute changes in IC/TLC.,UMEC/VI showed significant improvements in EET versus placebo at day 2 and week 12, measured as change from baseline in seconds (P≤0.002) and as a percentage from baseline (P≤0.005).,There was a lack of evidence to suggest a correlation between improvements in static hyperinflation and EET at any time point.,Although the dual bronchodilator UMEC/VI demonstrated greater improvements in static hyperinflation markers than UMEC or VI and significant improvements in exercise endurance, no direct relationship was observed between static hyperinflation and exercise endurance. | Tiotropium is prescribed for the treatment of chronic obstructive pulmonary disease (COPD) and delivered via HandiHaler® (18 μg once daily) or Respimat® Soft Mist™ inhaler (5 μg once daily).,The recent TIOtropium Safety and Performance In Respimat® (TIOSPIR™) study demonstrated that both exhibit similar safety profiles.,This analysis provides an updated comprehensive safety evaluation of tiotropium® using data from placebo-controlled HandiHaler® and Respimat® trials.,Pooled analysis of adverse event (AE) data from tiotropium HandiHaler® 18 μg and Respimat® 5 μg randomized, double-blind, parallel-group, placebo-controlled, clinical trials in patients with COPD (treatment duration ≥4 weeks).,Incidence rates, rate ratios (RRs), and 95% confidence intervals (CIs) were determined for HandiHaler® and Respimat® trials, both together and separately.,In the 28 HandiHaler® and 7 Respimat® trials included in this analysis, 11,626 patients were treated with placebo and 12,929 with tiotropium, totaling 14,909 (12,469 with HandiHaler®; 2,440 with Respimat®) patient-years of tiotropium exposure.,Mean age was 65 years, and mean prebronchodilator forced expiratory volume in 1 second (FEV1) was 1.16 L (41% predicted).,The risk (RR [95% CI]) of AEs (0.90 [0.87, 0.93]) and of serious AEs (SAEs) (0.94 [0.89, 0.99]) was significantly lower in the tiotropium than in the placebo group (HandiHaler® and Respimat® pooled results), and there was a numerically lower risk of fatal AEs (FAEs) (0.90 [0.79, 1.01]).,The risk of cardiac AEs (0.93 [0.85, 1.02]) was numerically lower in the tiotropium group.,Incidences of typical anticholinergic AEs, but not SAEs, were higher with tiotropium.,Analyzed separately by inhaler, the risks of AE and SAE in the tiotropium groups remained lower than in placebo and similarly for FAEs.,This analysis indicates that tiotropium is associated with lower rates of AEs, SAEs, and similar rates of FAEs than placebo when delivered via HandiHaler® or Respimat® (overall and separately) in patients with COPD. | 1 |
A large proportion of COPD patients do not achieve the recommended level of physical activity.,It is suggested that feedback on the level of activity by using an activity monitoring device (PAM) increases awareness and may stimulate patients to increase their physical activity in daily life.,Our objective was to assess the validity and usability of a simple and low-cost physical activity monitor (Polar A300™) when compared with the validated and established Bodymedia-SenseWear™ (SWA) device.,To assess the diagnostic equivalent, two different PAM devices were used in parallel in 20 COPD patients GOLD I to IV during 3 consecutive days of daily life.,Both systems were compared in terms of steps, calories burned, daily activity time and metabolic equivalents using linear regression analysis and Bland-Altman plots.,Practical usability was examined by a 16-item-questionnaire.,High correlations of both devices were observed with regard to the sensed step count (r = 0.96; p < 0.01) and calories burned (r = 0.74; p < 0.01), and a lower correlation of daily activity (r = 0.25; p < 0.01) was found.,Data analysis over 3 days showed that 90% of the steps (95% CI -4223 to 1887), 100% of the calories (95% CI -2798 to 1887), 90% of the daily activity data (95% CI -12.32, 4065) and 95% of the MET (95% CI -3.11 to 2.75) were within the limits of agreement.,A favorable usability (system-, information- and interface quality) of the A300™ device was shown (p < 0.01).,The A300™ device with easy practical usability was shown not to be inferior for assessment of physical activity time, step count and calorie consumption in COPD patients when compared with the SWA.,It is suggested to consider widespread available devices as commonly used for monitoring recreational sporting activities also in patients for assessment of physical activity in daily life. | Fatigue is a distressing, complex, multidimensional sensation common in individuals with chronic obstructive pulmonary disease (COPD).,While fatigue negatively impacts functional performance and quality of life, there has been little study of the fatigue that affects participants in pulmonary rehabilitation programs.,The purpose of this study was to examine the emotional, behavioral, cognitive, and physical dimensions of fatigue and their relationships to dyspnea, mental health, sleep, and physiologic factors.,A convenience sample of 42 pulmonary rehabilitation participants with COPD completed self-report questionnaires which measured dimensions of fatigue using the Multidimensional Fatigue Inventory, anxiety and depression using the Hospital Anxiety and Depression Scale, and sleep quality using the Pittsburgh Sleep Quality Index.,Data on other clinical variables were abstracted from pulmonary rehabilitation program health records.,Almost all (95.3%) participants experienced high levels of physical fatigue.,High levels of fatigue were also reported for the dimensions of reduced activity (88.1%), reduced motivation (83.3%), mental fatigue (69.9%), and general fatigue (54.5%).,Close to half (42.9%) of participants reported symptoms of anxiety, while almost one quarter (21.4%) reported depressive symptoms.,Age was related to the fatigue dimensions of reduced activity (ρ = 0.43, P < 0.01) and reduced motivation (ρ = 0.31, P < 0.05).,Anxiety was related to reduced motivation (ρ = −0.47, P < 0.01).,Fatigue was not associated with symptoms of depression, sleep quality, gender, supplemental oxygen use, smoking status, or Medical Research Council dyspnea scores.,Fatigue (particularly the physical and reduced motivation dimensions of fatigue) was experienced by almost all participants with COPD attending this pulmonary rehabilitation program.,Fatigue affected greater proportions of participants than either anxiety or depression.,The high prevalence of fatigue may impact on enrolment, participation, and attrition in pulmonary rehabilitation programs.,Further investigation of the nature, correlates, and impact of fatigue in this population is required. | 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. | Information about daily physical activity levels (PAL) in subjects with undiagnosed chronic obstructive pulmonary disease (COPD) is scarce.,This study aims to assess PA and to investigate the associations between PA and clinical characteristics in subjects with newly diagnosed COPD.,Fifty-nine subjects with a new spirometry-based diagnosis of mild (n=38) and moderate (n=21) COPD (63±6 years, 68% male) were matched with 65 smoking controls (62±7 years, 75% male).,PA (daily steps, time spent in moderate-to-vigorous intense physical activities (MVPA) and PAL) was measured by accelerometry.,Dyspnoea, complete pulmonary function tests, peripheral muscle strength and exercise capacity served as clinical characteristics.,PA was significantly lower in COPD versus smoking controls (7986±2648 vs 9765±3078 steps, 64 (27-120) vs 110 (55-164) min of MVPA, 1.49±0.21 vs 1.62±0.24 PAL respectively, all p<0.05).,Subjects with COPD with either mild symptoms of dyspnoea (mMRC 1), those with lower diffusion capacity (TL,co), low 6 min walking distance (6MWD) or low maximal oxygen uptake (VO2 peak) had significantly lower PA.,Multiple regression analysis identified 6 MWD and TL,co as independent predictors of PA in COPD.,The reduction in PA starts early in the disease, even when subjects are not yet diagnosed with COPD.,Inactivity is more pronounced in subjects with mild symptoms of dyspnoea, lower levels of diffusion capacity and exercise capacity. | 1 |
Neutrophil to lymphocyte ratio (NLR) in peripheral blood is a useful systemic inflammatory response biomarker.,However, NLR has not been studied in patients with chronic obstructive pulmonary disease (COPD).,This study was aimed to evaluate the usefulness of NLR in patients with COPD.,NLR was prospectively measured and compared in patients with COPD exacerbation (n = 59), patients with stable COPD (n = 61), and healthy controls (n = 28).,NLR in patients with COPD exacerbation was repeatedly measured in the convalescent period.,The correlation between NLR and clinical parameters was evaluated, and the predictors for respiratory hospitalization were analyzed by multivariate logistic regression.,NLR values were significantly higher in patients with COPD exacerbation compared with stable COPD patients and controls (12.4 ± 10.6, 2.4 ± 0.7, 1.4 ± 0.5, respectively; p < 0.001).,NLR was significantly decreased during the convalescent period in patients with COPD exacerbation (4.5 ± 4.6 vs.,11.5 ± 8.8, p < 0.001).,NLR exhibited a significant correlation with the body mass index, degree of airway obstruction, dyspnea, and exercise capacity (BODE) index, the 6-minute walk test, and the modified Medical Research Council scale.,NLR ≥ 2.8 was an independent predictor with a borderline significance for respiratory hospitalization (odds ratio, 2.083; p = 0.079).,Body mass index and forced expiratory volume in 1 second were independent predictors for respiratory hospitalization.,NLR is a straightforward and effective biomarker of COPD exacerbation that may serve as a predictor for respiratory hospitalization in patients with COPD. | There is a need for biomarkers to better characterise individuals with COPD and to aid with the development of therapeutic interventions.,A panel of putative blood biomarkers was assessed in a subgroup of the Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) cohort.,Thirty-four blood biomarkers were assessed in 201 subjects with COPD, 37 ex-smoker controls with normal lung function and 37 healthy non-smokers selected from the ECLIPSE cohort.,Biomarker repeatability was assessed using baseline and 3-month samples.,Intergroup comparisons were made using analysis of variance, repeatability was assessed through Bland-Altman plots, and correlations between biomarkers and clinical characteristics were assessed using Spearman correlation coefficients.,Fifteen biomarkers were significantly different in individuals with COPD when compared to former or non-smoker controls.,Some biomarkers, including tumor necrosis factor-α and interferon-γ, were measurable in only a minority of subjects whilst others such as C-reactive protein showed wide variability over the 3-month replication period.,Fibrinogen was the most repeatable biomarker and exhibited a weak correlation with 6-minute walk distance, exacerbation rate, BODE index and MRC dyspnoea score in COPD subjects. 33% (66/201) of the COPD subjects reported at least 1 exacerbation over the 3 month study with 18% (36/201) reporting the exacerbation within 30 days of the 3-month visit.,CRP, fibrinogen interleukin-6 and surfactant protein-D were significantly elevated in those COPD subjects with exacerbations within 30 days of the 3-month visit compared with those individuals that did not exacerbate or whose exacerbations had resolved.,Only a few of the biomarkers assessed may be useful in diagnosis or management of COPD where the diagnosis is based on airflow obstruction (GOLD).,Further analysis of more promising biomarkers may reveal utility in subsets of patients.,Fibrinogen in particular has emerged as a potentially useful biomarker from this cohort and requires further investigation.,SCO104960, clinicaltrials.gov identifier NCT00292552 | 1 |
COPD is a significant cause of morbidity and mortality.,In some patients with COPD, eosinophils contribute to inflammation that promotes airway obstruction; approximately a third of stable COPD patients have evidence of eosinophilic inflammation.,Although the eosinophil threshold associated with clinical relevance in patients with COPD is currently subject to debate, eosinophil counts hold potential as biomarkers to guide therapy.,In particular, eosinophil counts may be useful in assessing which patients may benefit from inhaled corticosteroid therapy, particularly regarding exacerbation prevention.,In addition, several therapies targeting eosinophilic inflammation are available or in development, including monoclonal antibodies targeting the IL5 ligand, the IL5 receptor, IL4, and IL13.,The goal of this review was to describe the biologic characteristics of eosinophils, their role in COPD during exacerbations and stable disease, and their use as biomarkers to aid treatment decisions.,We also propose an algorithm for inhaled corticosteroid use, taking into consideration eosinophil counts and pneumonia history, and emerging eosinophil-targeted therapies in COPD. | As a part of the longitudinal Chronic Obstructive Pulmonary Disease (COPD) study, Subpopulations and Intermediate Outcome Measures in COPD study (SPIROMICS), blood samples are being collected from 3200 subjects with the goal of identifying blood biomarkers for sub-phenotyping patients and predicting disease progression.,To determine the most reliable sample type for measuring specific blood analytes in the cohort, a pilot study was performed from a subset of 24 subjects comparing serum, Ethylenediaminetetraacetic acid (EDTA) plasma, and EDTA plasma with proteinase inhibitors (P100™).,105 analytes, chosen for potential relevance to COPD, arranged in 12 multiplex and one simplex platform (Myriad-RBM) were evaluated in duplicate from the three sample types from 24 subjects.,The reliability coefficient and the coefficient of variation (CV) were calculated.,The performance of each analyte and mean analyte levels were evaluated across sample types.,20% of analytes were not consistently detectable in any sample type.,Higher reliability and/or smaller CV were determined for 12 analytes in EDTA plasma compared to serum, and for 11 analytes in serum compared to EDTA plasma.,While reliability measures were similar for EDTA plasma and P100 plasma for a majority of analytes, CV was modestly increased in P100 plasma for eight analytes.,Each analyte within a multiplex produced independent measurement characteristics, complicating selection of sample type for individual multiplexes.,There were notable detectability and measurability differences between serum and plasma.,Multiplexing may not be ideal if large reliability differences exist across analytes measured within the multiplex, especially if values differ based on sample type.,For some analytes, the large CV should be considered during experimental design, and the use of duplicate and/or triplicate samples may be necessary.,These results should prove useful for studies evaluating selection of samples for evaluation of potential blood biomarkers. | 1 |
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