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Remodelling in COPD has at least two dimensions: small airway wall thickening and destruction of alveolar walls.,Recent studies indicate that there is some similarity between alveolar and small airway wall matrix remodelling.,The aim of this study was to characterise and assess similarities in alveolar and small airway wall matrix remodelling, and TGF-β signalling in COPD patients of different GOLD stages.,Lung tissue sections of 14 smoking controls, 16 GOLD II and 19 GOLD IV patients were included and stained for elastin and collagens as well as hyaluronan, a glycosaminoglycan matrix component and pSMAD2.,Elastin was significantly decreased in COPD patients not only in alveolar, but also in small airway walls.,Interestingly, both collagen and hyaluronan were increased in alveolar as well as small airway walls.,The matrix changes were highly comparable between GOLD stages, with collagen content in the alveolar wall increasing further in GOLD IV.,A calculated remodelling index, defined as elastin divided over collagen and hyaluronan, was decreased significantly in GOLD II and further lowered in GOLD IV patients, suggesting that matrix component alterations are involved in progressive airflow limitation.,Interestingly, there was a positive correlation present between the alveolar and small airway wall stainings of the matrix components, as well as for pSMAD2.,No differences in pSMAD2 staining between controls and COPD patients were found.,In conclusion, remodelling in the alveolar and small airway wall in COPD is markedly similar and already present in moderate COPD.,Notably, alveolar collagen and a remodelling index relate to lung function. | Chronic obstructive pulmonary disease (COPD) is characterized by abnormal extracellular matrix (ECM) turnover.,Recently, activation of the WNT/β-catenin pathway has been associated with abnormal ECM turnover in various chronic diseases.,We determined WNT-pathway gene expression in pulmonary fibroblasts of individuals with and without COPD and disentangled the role of β-catenin in fibroblast phenotype and function.,We assessed the expression of WNT-pathway genes and the functional role of β-catenin, using MRC-5 human lung fibroblasts and primary pulmonary fibroblasts of individuals with and without COPD.,Pulmonary fibroblasts expressed mRNA of genes required for WNT signaling.,Stimulation of fibroblasts with TGF-β1, a growth factor important in COPD pathogenesis, induced WNT-5B, FZD8, DVL3 and β-catenin mRNA expression.,The induction of WNT-5B, FZD6, FZD8 and DVL3 mRNA by TGF-β1 was higher in fibroblasts of individuals with COPD than without COPD, whilst basal expression was similar.,Accordingly, TGF-β1 activated β-catenin signaling, as shown by an increase in transcriptionally active and total β-catenin protein expression.,Furthermore, TGF-β1 induced the expression of collagen1α1, α-sm-actin and fibronectin, which was attenuated by β-catenin specific siRNA and by pharmacological inhibition of β-catenin, whereas the TGF-β1-induced expression of PAI-1 was not affected.,The induction of transcriptionally active β-catenin and subsequent fibronectin deposition induced by TGF-β1 were enhanced in pulmonary fibroblasts from individuals with COPD.,β-catenin signaling contributes to ECM production by pulmonary fibroblasts and contributes to myofibroblasts differentiation.,WNT/β-catenin pathway expression and activation by TGF-β1 is enhanced in pulmonary fibroblasts from individuals with COPD.,This suggests an important role of the WNT/β-catenin pathway in regulating fibroblast phenotype and function in COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is a diverse respiratory disease characterised by bronchiolitis, small airway obstruction, and emphysema.,Innate immune cells play a pivotal role in the disease's progression, and in particular, lung macrophages exploit their prevalence and strategic localisation to orchestrate immune responses.,To date, alveolar and interstitial resident macrophages as well as blood monocytes have been described in the lungs of patients with COPD contributing to disease pathology by changes in their functional repertoire.,In this review, we summarise recent evidence from human studies and work with animal models of COPD with regard to altered functions of each of these myeloid cell populations.,We primarily focus on the dysregulated capacity of alveolar macrophages to secrete proinflammatory mediators and proteases, induce oxidative stress, engulf microbes and apoptotic cells, and express surface and intracellular markers in patients with COPD.,In addition, we discuss the differences in the responses between alveolar macrophages and interstitial macrophages/monocytes in the disease and propose how the field should advance to better understand the implications of lung macrophage functions in COPD. | Chronic obstructive pulmonary disease (COPD) is characterized by excessive inflammation and disturbed bacterial clearance in the airways.,Although cigarette smoke (CS) exposure poses a major risk, vitamin D deficiency could potentially contribute to COPD progression.,Many in vitro studies demonstrate important anti-inflammatory and antibacterial effects of vitamin D, but a direct contribution of vitamin D deficiency to COPD onset and disease progression has not been explored.,In the current study, we used a murine experimental model to investigate the combined effect of vitamin D deficiency and CS exposure on the development of COPD-like characteristics.,Therefore, vitamin D deficient or control mice were exposed to CS or ambient air for a period of 6 (subacute) or 12 weeks (chronic).,Besides lung function and structure measurements, we performed an in depth analysis of the size and composition of the cellular infiltrate in the airways and lung parenchyma and tested the ex vivo phagocytic and oxidative burst capacity of alveolar macrophages.,Vitamin D deficient mice exhibited an accelerated lung function decline following CS exposure compared to control mice.,Furthermore, early signs of emphysema were only observed in CS-exposed vitamin D deficient mice, which was accompanied by elevated levels of MMP-12 in the lung.,Vitamin D deficient mice showed exacerbated infiltration of inflammatory cells in the airways and lung parenchyma after both subacute and chronic CS exposure compared to control mice.,Furthermore, elevated levels of typical proinflammatory cytokines and chemokines could be detected in the bronchoalveolar lavage fluid (KC and TNF-α) and lung tissue (IP-10, MCP-1, IL-12) of CS-exposed vitamin D deficient mice compared to control mice.,Finally, although CS greatly impaired the ex vivo phagocytic and oxidative burst function of alveolar macrophages, vitamin D deficient mice did not feature an additional defect.,Our data demonstrate that vitamin D deficiency both accelerates and aggravates the development of characteristic disease features of COPD.,As vitamin D deficiency is highly prevalent, large randomized trials exploring effects of vitamin D supplementation on lung function decline and COPD onset are needed.,The online version of this article (doi:10.1186/s12931-015-0271-x) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) affects over 250 million people globally, carrying a notable economic burden.,This systematic literature review aimed to highlight the economic burden associated with moderate-to-very severe COPD and to investigate key drivers of healthcare resource utilization (HRU), direct costs and indirect costs for this patient population.,Relevant publications published between January 1, 2006 and November 14, 2016 were captured from the Embase, MEDLINE and MEDLINE In-Process databases.,Supplemental searches from relevant 2015-2016 conferences were also performed.,Titles and abstracts were reviewed by two independent researchers against pre-defined inclusion and exclusion criteria.,Studies were grouped by the type of economic outcome presented (HRU or costs).,Where possible, data were also grouped according to COPD severity and/or patient exacerbation history.,In total, 73 primary publications were included in this review: 66 reported HRU, 22 reported direct costs and one reported indirect costs.,Most of the studies (94%) reported on data from either Europe or North America.,Trends were noted across multiple studies for higher direct costs (including mean costs per patient per year and mean costs per exacerbation) being associated with increasingly severe COPD and/or a history of more frequent or severe exacerbations.,Similar trends were noted according to COPD severity and/or exacerbation history for rate of hospitalization and primary care visits.,Multivariate analyses were reported by 29 studies and demonstrated the statistical significance of these associations.,Several other drivers of increased costs and HRU were highlighted for patients with moderate-to-very severe COPD, including comorbidities, and treatment history.,Moderate-to-very severe COPD represents a considerable economic burden for healthcare providers despite the availability of efficacious treatments and comprehensive guidelines on their use.,Further research is warranted to ensure cost-efficient COPD management, to improve treatments and ease budgetary pressures. | Alterations in the composition of the lung microbiome associated with adverse clinical outcomes, known as dysbiosis, have been implicated with disease severity and exacerbations in COPD.,To characterise longitudinal changes in the lung microbiome in the AERIS study (Acute Exacerbation and Respiratory InfectionS in COPD) and their relationship with associated COPD outcomes.,We surveyed 584 sputum samples from 101 patients with COPD to analyse the lung microbiome at both stable and exacerbation time points over 1 year using high-throughput sequencing of the 16S ribosomal RNA gene.,We incorporated additional lung microbiology, blood markers and in-depth clinical assessments to classify COPD phenotypes.,The stability of the lung microbiome over time was more likely to be decreased in exacerbations and within individuals with higher exacerbation frequencies.,Analysis of exacerbation phenotypes using a Markov chain model revealed that bacterial and eosinophilic exacerbations were more likely to be repeated in subsequent exacerbations within a subject, whereas viral exacerbations were not more likely to be repeated.,We also confirmed the association of bacterial genera, including Haemophilus and Moraxella, with disease severity, exacerbation events and bronchiectasis.,Subtypes of COPD have distinct bacterial compositions and stabilities over time.,Some exacerbation subtypes have non-random probabilities of repeating those subtypes in the future.,This study provides insights pertaining to the identification of bacterial targets in the lung and biomarkers to classify COPD subtypes and to determine appropriate treatments for the patient.,Results, NCT01360398. | 1 |
Exacerbations of COPD are a major burden to patients, and yet little is understood about heterogeneity.,It contributes to the current persistent one-size-fits-all treatment.,To replace this treatment by more personalized, precision medicine, new insights are required.,We assessed the heterogeneity of exacerbations by functional respiratory imaging (FRI) in 3-dimensional models of airways and lungs.,The trial was designed as a multicenter trial of patients with an acute exacerbation of COPD who were assessed by FRI, pulmonary function tests, and patient-reported outcomes, both in the acute stage and during resolution.,Forty seven patients were assessed.,FRI analyses showed significant improvements in hyperinflation (a decrease in total volume at functional residual capacity of −0.25±0.61 L, p≤0.01), airway volume at total lung capacity (+1.70±4.65 L, p=0.02), and airway resistance.,As expected, these improvements correlated partially with changes in the quality of life and in conventional lung function test parameters.,Patients with the same changes in pulmonary function differ in regional disease activity measured by FRI.,FRI is a useful tool to get a better insight into exacerbations of COPD, and significant improvements in its indices can be demonstrated from the acute phase to resolution even in relatively small groups.,It clearly visualizes the marked variability within and between individuals in ventilation and resistance during exacerbations and is a tool for the assessment of the heterogeneity of COPD exacerbations. | Salbutamol and ipratropium bromide improve lung function in patients with chronic obstructive pulmonary disease (COPD).,However, their bronchodilating effect has not yet been compared in the central and distal airways.,Functional imaging using computational fluid dynamics offers the possibility of making such a comparison.,The objective of this study was to assess the effects of salbutamol and ipratropium bromide on the geometry and computational fluid dynamics-based resistance of the central and distal airways.,Five patients with Global Initiative for Chronic Obstructive Lung Disease Stage III COPD were randomized to a single dose of salbutamol or ipratropium bromide in a crossover manner with a 1-week interval between treatments.,Patients underwent lung function testing and a multislice computed tomography scan of the thorax that was used for functional imaging.,Two hours after dosing, the patients again underwent lung function tests and repeat computed tomography.,Lung function parameters, including forced expiratory volume in 1 second, vital capacity, overall airway resistance, and specific airway resistance, changed significantly after administration of each product.,On functional imaging, the bronchodilating effect was greater in the distal airways, with a corresponding drop in airway resistance, compared with the central airways.,Salbutamol and ipratropium bromide were equally effective at first glance when looking at lung function tests, but when viewed in more detail with functional imaging, hyporesponsiveness could be shown for salbutamol in one patient.,Salbutamol was more effective in the other patients.,This pilot study gives an innovative insight into the modes of action of salbutamol and ipratropium bromide in patients with COPD, using the new techniques of functional imaging and computational fluid dynamics. | 1 |
We recently reported that epithelial-mesenchymal transition (EMT) is active in the airways in chronic obstructive pulmonary disease (COPD), suggesting presence of an active profibrotic and promalignant stroma.,With no data available on potential treatment effects, we undertook a blinded analysis of inhaled corticosteroids (ICS) effects versus placebo on EMT markers in previously obtained endobronchial biopsies in COPD patients, as a “proof of concept” study.,Assessment of the effects of inhaled fluticasone propionate (FP; 500 μg twice daily for 6 months) versus placebo in 34 COPD patients (23 on fluticasone propionate and eleven on placebo).,The end points were epidermal growth factor receptor (EGFR; marker of epithelial activation) and the biomarkers of EMT: reticular basement membrane (Rbm) fragmentation (“hallmark” structural marker), matrix metalloproteinase-9 (MMP-9) cell expression, and S100A4 expression in basal epithelial and Rbm cells (mesenchymal transition markers).,Epithelial activation, “clefts/fragmentation” in the Rbm, and changes in the other biomarkers all regressed on ICS, at or close to conventional levels of statistical significance.,From these data, we have been able to nominate primary and secondary end points and develop power calculations that would be applicable to a definitive prospective study.,Although only a pilot “proof of concept” study, this trial provided strong suggestive support for an anti-EMT effect of ICS in COPD airways.,A larger and fully powered prospective study is now indicated as this issue is likely to be extremely important.,Such studies may clarify the links between ICS use and better clinical outcomes and protection against lung cancer in COPD. | Chronic Obstructive Pulmonary Disease (COPD) is associated with bronchial epithelial changes, including squamous cell metaplasia and goblet cell hyperplasia.,These features are partially attributed to activation of the epidermal growth factor receptor (EGFR).,Whereas smoking cessation reduces respiratory symptoms and lung function decline in COPD, inflammation persists.,We determined epithelial proliferation and composition in bronchial biopsies from current and ex-smokers with COPD, and its relation to duration of smoking cessation.,114 COPD patients were studied cross-sectionally: 99 males/15 females, age 62 ± 8 years, median 42 pack-years, no corticosteroids, current (n = 72) or ex-smokers (n = 42, median cessation duration 3.5 years), postbronchodilator FEV1 63 ± 9% predicted.,Squamous cell metaplasia (%), goblet cell (PAS/Alcian Blue+) area (%), proliferating (Ki-67+) cell numbers (/mm basement membrane), and EGFR expression (%) were measured in intact epithelium of bronchial biopsies.,Ex-smokers with COPD had significantly less epithelial squamous cell metaplasia, proliferating cell numbers, and a trend towards reduced goblet cell area than current smokers with COPD (p = 0.025, p = 0.001, p = 0.081, respectively), but no significant difference in EGFR expression.,Epithelial features were not different between short-term quitters (<3.5 years) and current smokers.,Long-term quitters (≥3.5 years) had less goblet cell area than both current smokers and short-term quitters (medians: 7.9% vs.,14.4%, p = 0.005; 7.9% vs.,13.5%, p = 0.008; respectively), and less proliferating cell numbers than current smokers (2.8% vs.,18.6%, p < 0.001).,Ex-smokers with COPD had less bronchial epithelial remodelling than current smokers, which was only observed after long-term smoking cessation (>3.5 years).,NCT00158847 | 1 |
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. | The 2013 GOLD classification system for COPD distinguishes four stages: A (low symptoms, low exacerbation risk), B (high symptoms, low risk), C (low symptoms, high risk) and D (high symptoms, high risk).,Assessment of risk is based on exacerbation history and airflow obstruction, whatever results in a higher risk grouping.,The previous system was solely based on airflow obstruction.,Earlier studies compared the predictive performance of new and old classification systems with regards to mortality and exacerbations.,The objective of this study was to compare the ability of both classifications to predict the number of future (total and severe) exacerbations and mortality in a different patient population, and to add an outcome measure to the comparison: lung function decline.,Patient-level data from the UPLIFT trial were used to analyze 4-year survival in a Weibull model, with GOLD stages at baseline as covariates.,A generalized linear model was used to compare the numbers of exacerbations (total and severe) per stage.,Analyses were repeated with stages C and D divided into substages depending on lung function and exacerbation history.,Lung function decline was analysed in a repeated measures model.,Mortality increased from A to D, but there was no difference between B and C.,For the previous GOLD stages 2-4, survival curves were clearly separated.,Yearly exacerbation rates were: 0.53, 0.72 and 0.80 for stages 2-4; and 0.35, 0.45, 0.58 and 0.74 for A-D.,Annual rates of lung function decline were: 47, 38 and 26 ml for stages 2-4 and 44, 48, 38 and 39 for stages A-D.,With regards to model fit, the new system performed worse at predicting mortality and lung function decline, and better at predicting exacerbations.,Distinguishing between the sub-stages of high-risk led to substantial improvements.,The new classification system is a modest step towards a phenotype approach.,It is probably an improvement for the prediction of exacerbations, but a deterioration for predicting mortality and lung function decline.,ClinicalTrials.gov NCT00144339 (September 2, 2005).,The online version of this article (doi:10.1186/1471-2466-14-163) contains supplementary material, which is available to authorized users. | 1 |
COPD prevalence is highly variable and geographical altitude has been linked to it, yet with conflicting results.,We aimed to investigate this association, considering well known risk factors.,A pooled analysis of individual data from the PREPOCOL-PLATINO-BOLD-EPI-SCAN studies was used to disentangle the population effect of geographical altitude on COPD prevalence.,Post-bronchodilator FEV1/FVC below the lower limit of normal defined airflow limitation consistent with COPD.,High altitude was defined as >1500 m above sea level.,Undiagnosed COPD was considered when participants had airflow limitation but did not report a prior diagnosis of COPD.,Among 30,874 participants aged 56.1 ± 11.3 years from 44 sites worldwide, 55.8% were women, 49.6% never-smokers, and 12.9% (3978 subjects) were residing above 1500 m.,COPD prevalence was significantly lower in participants living at high altitude with a prevalence of 8.5% compared to 9.9%, respectively (p < 0.005).,However, known risk factors were significantly less frequent at high altitude.,Hence, in the adjusted multivariate analysis, altitude itself had no significant influence on COPD prevalence.,Living at high altitude, however, was associated with a significantly increased risk of undiagnosed COPD.,Furthermore, subjects with airflow limitation living at high altitude reported significantly less respiratory symptoms compared to subjects residing at lower altitude.,Living at high altitude is not associated with a difference in COPD prevalence after accounting for individual risk factors.,However, high altitude itself was associated with an increased risk of undiagnosed COPD. | Studies suggest that COPD prevalence may vary between countries.,We conducted an ecological study of data from COPD prevalence articles to assess the influence of differences in country-level risk factors on COPD prevalence.,Our study covered English language articles published during 2003-2014.,Qualified articles used spirometry to assess COPD prevalence and used representative samples from national or subnational populations.,Stepwise binomial regression was used to analyze associations between study- and country-level factors and COPD prevalence.,Eighty articles provided 1,583 measures of COPD prevalence for subjects in different sex, age, and smoking categories for 112 districts in 41 countries.,Adjusted prevalence rates for COPD were significantly lower for Australia/New Zealand and the Mediterranean and significantly higher for Latin America, compared to North America, Southeast Asia, and Northern Europe.,Country-level socioeconomic development variables had an uneven and mixed association with COPD prevalence.,High elevation above sea level was shown to be a protective factor for COPD.,Study-level variables for the established risk factors of sex, age, and smoking explained 64% of variability in COPD prevalence.,Country-level risk factors raised the explanatory power to 72%.,Approximately 28% of worldwide variability in COPD prevalence remained unexplained.,Our study suggests that COPD prevalence varies across world regions, even after adjustment for established risk factors.,Major country-level risk factors contributing to the worldwide epidemic of COPD remain to be investigated. | 1 |
Physical activity limitation is common in chronic obstructive pulmonary disease (COPD), and is associated with worse health status, and increased hospitalisation and mortality.,Long-acting bronchodilators, either alone or in combination, have been shown to improve exercise intolerance.,However, none of these studies were designed with physical activity as primary outcome.,This study assessed the effect of indacaterol/glycopyrronium fixed dose combination (IND/GLY) 110/50 μg once daily (OD) versus placebo on lung hyperinflation (inspiratory capacity [IC]) and physical activity in patients with moderate-to-severe COPD.,In this multicentre, randomised, double-blind, placebo-controlled crossover study, patients received IND/GLY or placebo OD in two 21-day treatment periods (14-day washout between periods).,Eligible patients were ≥40 years of age, current or ex-smokers (smoking history ≥10 pack-years), with post-salbutamol forced expiratory volume in 1 s (FEV1) 40-80 % predicted, and FEV1:forced vital capacity <0.70.,The co-primary endpoints were peak IC after 21 days and average daily activity-related energy expenditure.,Key secondary endpoints were average number of steps per day and the duration of at least moderate activity per day.,Peak IC and FEV1 on Day 1, and trough IC and FEV1 after 21 days were other secondary endpoints.,A total of 194 patients were randomised (65.5 % male, mean age 62.8 years, mean FEV1 61.6 % predicted), with 183 (94.3 %) completing the study.,Compared with placebo, IND/GLY significantly increased peak IC after 21 days (difference 202 mL, p < 0.0001), activity-related energy expenditure (difference 36.7 kcal/day, p = 0.040), and the average number of steps per day (difference 358, p = 0.029), with a trend towards an improvement in the duration of at least moderate activity (difference 4.4 min, p = 0.264).,IND/GLY was associated with statistically significant improvements versus placebo in peak IC and FEV1 on Day 1, and trough IC and FEV1 after 21 days.,The incidence of treatment-emergent adverse events was 22.8 % with IND/GLY and 22.9 % with placebo.,In this study, compared with placebo, IND/GLY reduced hyperinflation, and, despite no patient education or lifestyle advice, improved daily physical activity levels.,This suggests that IND/GLY has the potential to impact two of the main clinical concerns in the care of patients with COPD.,ClinicalTrials.gov number: NCT01996319.,The online version of this article (doi:10.1186/s12890-016-0256-7) contains supplementary material, which is available to authorized users. | Maintaining and improving physical functioning is key to mitigating the cycle of deconditioning associated with chronic obstructive pulmonary disease (COPD).,We evaluated the impact of free combination of the long-acting anticholinergic tiotropium plus the long-acting β2-agonist olodaterol on physical functioning in a real-world clinical setting.,In this open-label noninterventional study, Global initiative for chronic Obstructive Lung Disease (GOLD) B-D patients with COPD aged ≥40 years were treated for 4-6 weeks with either tiotropium 5 μg + olodaterol 5 μg (both via Respimat® inhaler) or tiotropium 18 μg (HandiHaler®) + olodaterol 5 μg (Respimat®) once daily.,Physical functioning was assessed by the self-reported 10-item Physical Functioning Questionnaire (PF-10).,The primary end point was the percentage of patients achieving therapeutic success, defined as a 10-point increase in the PF-10 between baseline (visit 1) and weeks 4-6 (visit 2).,Secondary end points included absolute PF-10 scores, Physicians’ Global Evaluation, satisfaction with Respimat® and adverse events.,A total of 1,858 patients were treated: 1,298 (69.9%) with tiotropium 5 μg + olodaterol 5 μg and 560 (30.1%) with tiotropium 18 μg + olodaterol 5 μg.,At study end, 1,683 (92.6%) and 1,556 patients (85.6%) continued using tiotropium and olodaterol, respectively; 48.9% (95% confidence interval: 46.5, 51.3) achieved the primary end point.,Therapeutic success rates were significantly higher for maintenance-naïve patients compared to those who had received prior therapy (59.1% vs 44.5%; P<0.0001), largely driven by maintenance-treatment-naïve GOLD B (59.8%) and C (63.0%) patients.,Absolute physical functioning scores increased from an average baseline of 44.0 (standard deviation: 25.2) to 54.2 (standard deviation: 26.9) at visit 2.,Patients’ general condition improved from baseline to visit 2, and patients were largely satisfied with the Respimat® inhaler.,Adverse events were reported by 7.5% of patients; the most common were respiratory in nature.,Tiotropium + olodaterol improved physical functioning within 4-6 weeks in patients with moderate-to-very severe COPD.,GOLD B and C patients with no prior maintenance treatment demonstrated the greatest benefit. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) have a high prevalence of osteoporosis.,The clinical sequel of osteoporosis is fracture.,Patients with COPD who experience a fracture also have increased morbidity and mortality.,Currently, the types of all-cause and site-specific fracture among patients with COPD are unknown.,Thus, we elucidated the all-cause and site-specific fractures among patients with COPD.,A retrospective, population-based, cohort study was conducted utilizing the Taiwan Longitudinal Health Insurance Database.,Patients with COPD were defined as those who were hospitalized with an International Classification of Diseases, Ninth Revision, Clinical Modification code of 490 to 492 or 496 between 2001 and 2011.,The index date was set as the date of discharge.,The study patients were followed from the index date to the date when they sought care for any type of fracture, date of death, date of health insurance policy termination, or the last day of 2013.,The types of fracture analyzed in this study included vertebral, rib, humeral, radial and ulnar/wrist, pelvic, femoral, and tibial and fibular fractures.,The cohort consisted of 11,312 patients with COPD.,Among these patients, 1944 experienced fractures.,The most common site-specific fractures were vertebral, femoral, rib, and forearm fractures (radius, ulna, and wrist) at 32.4%, 31%, 12%, and 11.8%, respectively.,The adjusted hazard ratios of fracture were 1.71 [95% confidence interval (95% CI) = 1.56-1.87] for female patient with COPD and 1.50 (95% CI = 1.39-1.52) for patients with osteoporosis after covariate adjustment.,Vertebral and hip fractures are common among patients with COPD, especially among males with COPD.,Many comorbidities contribute to the high risk of fracture among patients with COPD. | COPD is well known to frequently coexist with osteoporosis.,Bone fractures often occur and may affect mortality in COPD patients.,However, in-hospital mortality related to bone fractures in COPD patients has been poorly studied.,This retrospective study investigated in-hospital mortality of COPD patients with bone fractures using a national inpatient database in Japan.,Data of COPD patients admitted with bone fractures, including hip, vertebra, shoulder, and forearm fractures to 1,165 hospitals in Japan between July 2010 and March 2013, were extracted from the Diagnosis Procedure Combination database.,The clinical characteristics and mortalities of the patients were determined.,Multivariable logistic regression analysis was also performed to determine the factors associated with in-hospital mortality of COPD patients with hip fractures.,Among 5,975 eligible patients, those with hip fractures (n=4,059) were older, had lower body mass index (BMI), and had poorer general condition than those with vertebral (n=1,477), shoulder (n=281), or forearm (n=158) fractures.,In-hospital mortality was 7.4%, 5.2%, 3.9%, and 1.3%, respectively.,Among the hip fracture group, surgical treatment was significantly associated with lower mortality (adjusted odds ratio, 0.43; 95% confidence interval, 0.32-0.56) after adjustment for patient backgrounds.,Higher in-hospital mortality was associated with male sex, lower BMI, lower level of consciousness, and having several comorbidities, including pneumonia, lung cancer, congestive heart failure, chronic liver disease, and chronic renal failure.,COPD patients with hip fractures had higher mortality than COPD patients with other types of fracture.,Surgery for hip fracture was associated with lower mortality than conservative treatment. | 1 |
Chronic infections are associated with exacerbation in patients with chronic obstructive pulmonary disease (COPD).,The major objective of the management of these patients is the prevention and effective treatment of exacerbations.,Patients that have increased sputum production, associated with purulence and worsening shortness of breath, are the ones that will benefit from antibiotic therapy.,It is important to give the appropriate antibiotic therapy to prevent treatment failure, relapse, and the emergence of resistant pathogens.,In some patients, systemic corticosteroids are also indicated to improve symptoms.,In order to identify which patients are more likely to benefit from these therapies, clinical guidelines recommend stratifying patients based on their risk factor associated with poor outcome or recurrence.,It has been identified that patients with more severe disease, recurrent infection and presence of purulent sputum are the ones that will be more likely to benefit from this therapy.,Another approach related to disease prevention could be the use of prophylactic antibiotics during steady state condition.,Some studies have evaluated the continuous or the intermittent use of antibiotics in order to prevent exacerbations.,Due to increased bacterial resistance to antibiotics and the presence of side effects, several antibiotics have been developed to be nebulized for both treatment and prevention of acute exacerbations.,There is a need to design long-term studies to evaluate these interventions in the natural history of the disease.,The purpose of this publication is to review our understanding of the role of bacterial infection in patients with COPD exacerbation, the role of antibiotics, and future interventions. | Computed tomography scan images have been used to identify different radiological COPD phenotypes based on the presence and severity of emphysema, bronchial wall thickening, and bronchiectasis.,Bronchiectasis is defined as an abnormal dilation of the bronchi, usually as a result of chronic airway inflammation and/or infection.,The prevalence of bronchiectasis in patients with COPD is high, especially in advanced stages.,The identification of bronchiectasis in COPD has been defined as a different clinical COPD phenotype with greater symptomatic severity, more frequent chronic bronchial infection and exacerbations, and poor prognosis.,A causal association has not yet been proven, but it is biologically plausible that COPD, and particularly the infective and exacerbator COPD phenotypes, could be the cause of bronchiectasis without any other known etiology, beyond any mere association or comorbidity.,The study of the relationship between COPD and bronchiectasis could have important clinical implications, since both diseases have different and complementary therapeutic approaches.,Longitudinal studies are needed to investigate the development of bronchiectasis in COPD, and clinical trials with treatments aimed at reducing bacterial loads should be conducted to investigate their impact on the reduction of exacerbations and improvements in the long-term evolution of the disease. | 1 |
The Minimal Clinically Important Difference (MCID) assesses what change on a measurement tool can be considered minimal clinically relevant.,Although the recall period can influence questionnaire scores, it is unclear if it influences the MCID.,This study is the first to examine longitudinally the impact of the recall period of an anchor question and its design on the MCID of COPD health status tools using the COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ) and the St.,George’s Respiratory Questionnaire (SGRQ).,Moderate to very severe COPD patients without respiratory co-morbidities were recruited during 3-week Pulmonary Rehabilitation (PR).,CAT, CCQ and SGRQ were completed at baseline, discharge, 3, 6, 9 and 12 months.,A 15-point Global Rating of Change scale (GRC) was completed at each follow-up.,A five-point GRC was used as second anchor at 12 months.,Mean change scores of a subset of patients indicating a minimal improvement on each of the anchor questions were considered the MCID.,The MCID estimates over different time periods were compared with one another by evaluating the degree of overlap of Confidence Intervals (CI) adjusted for dependency.,In total 451 patients were included (57.9 ± 6.6 years, 65% male, 50/39/11% GOLD II/III/IV), of which 309 completed follow-up.,Baseline health status scores were 20.2 ± 7.3 (CAT), 2.9 ± 1.2 (CCQ) and 50.7 ± 17.3 (SGRQ).,MCID estimates for improvement ranged − 3.1 to − 1.4 for CAT, − 0.6 to − 0.3 for CCQ, and − 10.3 to − 7.6 for SGRQ.,Absolute higher - though not significant - MCIDs were observed for CAT and CCQ directly after PR.,Significantly absolute lower MCID estimates were observed for CAT (difference − 1.4: CI -2.3 to − 0.5) and CCQ (difference − 0.2: CI -0.3 to −0.1) using a five-point GRC.,The recall period of a 15-point anchor question seemed to have limited impact on the MCID for improvement of CAT, CCQ and SGRQ during PR; although a 3-week MCID estimate directly after PR might lead to absolute higher values.,However, the design of the anchor question was likely to influence the MCID of CAT and CCQ.,RIMTCORE trial #DRKS00004609 and #12107 (Ethik-Kommission der Bayerischen Landesärztekammer).,The online version of this article (10.1186/s12955-018-0950-7) contains supplementary material, which is available to authorized users. | Patient-reported outcomes (PRO) questionnaires are being increasingly used in COPD clinical studies.,The challenge facing investigators is to determine what change is significant, ie what is the minimal clinically important difference (MCID).,This study aimed to identify the MCID for the clinical COPD questionnaire (CCQ) in terms of patient referencing, criterion referencing, and by the standard error of measurement (SEM).,Patients were ≥40 years of age, diagnosed with COPD, had a smoking history of >10 pack-years, and were participating in a randomized, controlled clinical trial comparing intravenous and oral prednisolone in patients admitted with an acute exacerbation of COPD.,The CCQ was completed on Days 1-7 and 42.,A Global Rating of Change (GRC) assessment was taken to establish the MCID by patient referencing.,For criterion referencing, health events during a period of 1 year after Day 42 were included in this analysis.,210 patients were recruited, 168 completed the CCQ questionnaire on Day42.,The MCID of the CCQ total score, as indicated by patient referencing in terms of the GRC, was 0.44.,The MCID of the CCQ in terms of criterion referencing for the major outcomes was 0.39, and calculation of the SEM resulted in a value of 0.21.,This investigation, which is the first to determine the MCID of a PRO questionnaire via more than one approach, indicates that the MCID of the CCQ total score is 0.4. | 1 |
Epidemiologic studies investigating the differences in respiratory outcomes between asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) and chronic obstructive pulmonary disease (COPD) in an Asian population are lacking.,We conducted a population-based cohort study to compare the incidence of acute respiratory events between ACOS and COPD cohorts in Taiwan.,This study investigated the incidence of acute respiratory events, namely, pneumonia, acute exacerbation, acute respiratory failure, and cardiopulmonary arrest, in 8571 patients with physician-diagnosed ACOS between 2000 and 2007 from the Longitudinal Health Insurance Database.,The comparison cohort comprised 17,088 COPD patients, frequency-matched according to age, sex, and the index-year.,The duration of follow-up was measured for each patient from the index date to 5 years thereafter.,We used univariable and multivariable Poisson regression models to analyze the risk of acute respiratory events by including the variables of sex, age, and comorbidity.,The overall prevalence of ACOS was approximately 17.4% in patients with COPD.,The prevalence of ACOS increased with age.,During the 5-year follow-up, a greater incidence of acute respiratory events was observed in the ACOS cohort than in the COPD cohort (11.5 and 4.62, per 100 person-years, respectively) with an adjusted incidence rate ratio (IRR) of 1.72 (95% confidence interval [CI] = 1.63-1.81).,Compared with the COPD cohort, the ACOS patients had a 1.13-fold adjusted IRR of pneumonia (95% CI = 1.07-1.20) and a 2.58-fold adjusted IRR of acute exacerbation (95% CI = 2.43-2.74).,Clinicians should be aware of frequent exacerbation of ACOS and prescribe appropriate treatment. | 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. | 1 |
Chronic obstructive pulmonary disease (COPD) was the fourth leading cause of death worldwide in 2015.,Current treatments for patients ease discomfort and help decrease disease progression; however, none improve lung function or change mortality.,COPD is heterogeneous in its molecular and clinical presentation, making it difficult to understand disease aetiology and define robust therapeutic strategies.,Given the complexity of the disease we propose a precision medicine approach to understanding and better treating COPD.,It is possible that multiOMICs can be used as a tool to integrate data from multiple fields.,Moreover, analysis of electronic medical records could aid in the treatment of patients and in the predictions of outcomes.,The Precision Medicine Initiative created in 2015 has made precision medicine approaches to treat disease a reality; one of these diseases being COPD. | Smoking and subsequent development of COPD is an ever-increasing epidemic in Arabian Gulf and Middle East countries, with no signs of decline.,The important fact to be highlighted is that this COPD epidemic of increasing incidence and prevalence is mostly unrecognized by patients, due to the common attribution of symptoms to “smoker’s cough”, and the underdiagnosis and undertreatment by physicians because the common signs and symptoms masquerade as asthma.,Consequently, there are long-term adverse effects of missing the diagnosis.,The purpose of this review article is to focus upon the status of COPD in Arabian Gulf and Middle East countries, stressing the increasing burden of smoking and COPD, to emphasize the specific factors leading to rise in prevalence of COPD, to bring to light the underdiagnosis and undermanagement of COPD, and to treat COPD in conformity with standard guidelines with local and regional modifications.,This review ends with suggestions and recommendations to the health department to formulate policies and to generate awareness among the general public about the side effects of smoking and consequences of COPD. | 1 |
COPD is a progressive condition involving chronic inflammation and parenchymal destruction with resulting airflow limitation.,COPD is associated with worsening airflow limitation over time and increased frequency of COPD exacerbations, leading to increased mortality and morbidity.,The effects of COPD extend beyond the lungs, as multiple comorbidities may occur with COPD, including cardiovascular disease, diabetes mellitus, osteoporosis, depression, and pneumonia.,COPD exacerbations are associated with a rapid worsening of baseline symptoms that requires prompt management and may necessitate hospitalization in the case of a severe episode.,Patients with COPD exacerbations require urgent management of symptoms to prevent further worsening, and preventative steps may be taken to help reduce the number and frequency of future exacerbations.,Roflumilast is a potent and selective inhibitor of the enzyme phosphodiesterase-4 that targets the systemic inflammation associated with COPD.,Roflumilast has a variety of anti-inflammatory effects including decreasing inflammatory mediators and the expression of cell surface markers and inhibition of apoptosis.,Several clinical trials evaluating roflumilast in the treatment of COPD have demonstrated significant improvements from baseline versus placebo in lung function, including increases in mean pre- and postbronchodilator forced expiratory volume in 1 second and forced vital capacity.,Data suggest that roflumilast reduces moderate to severe exacerbations with the benefit most well established in patients with severe disease.,Given this evidence, roflumilast, as part of a combination regimen with long-acting bronchodilators, appears to be a reasonable treatment option for patients with severe to very severe COPD associated with chronic bronchitis and a history of exacerbations. | 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 |
Current treatment strategies to stratify exacerbation risk rely on history of ≥2 events in the previous year.,To understand year-to-year variability and factors associated with consistent exacerbations over time, we present a prospective analysis of the SPIROMICS cohort.,We analyzed SPIROMICS participants with COPD and three years of prospective data (n=1,105).,We classified participants according to yearly exacerbation frequency.,Stepwise logistic regression compared factors associated with individuals experiencing ≥1 AECOPD in every year for three years versus none.,During three years follow-up, 48·7% of participants experienced at least one AECOPD, while the majority (51·3%) experienced none.,Only 2·1% had ≥2 AECOPD in each year.,An inconsistent pattern (both years with and years without AECOPD) was common (41·3% of the group), particularly among GOLD stages 3 and 4 subjects (56·1%).,In logistic regression, consistent AECOPD (≥1 event per year for three years) as compared to no AECOPD were associated with higher baseline symptom burden assessed with the COPD Assessment Test, previous exacerbations, greater evidence of small airway abnormality by computed tomography, lower Interleukin-15 (IL-15) and elevated Interleukin-8 (IL-8).,Although AECOPD are common, the exacerbation status of most individuals varies markedly from year to year.,Among participants who experienced any AECOPD over three years, very few repeatedly experienced ≥2 events/year.,In addition to symptoms and history of exacerbations in the prior year, we identified several novel biomarkers associated with consistent exacerbations, including CT-defined small airway abnormality, IL-15 and IL-8. | Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) was proposed by the science committees of both Global Initiative for Asthma (GINA) and Global Initiative for Chronic Obstructive Lung Disease (GOLD).,However, the definition of ACOS has remained unclear all over the world, and the prevalence rate of ACOS is basically dependent on the patient’s symptoms or the physician’s opinion, based on questionnaire testing.,In the current case report, we investigated the prevalence rate of COPD patients with high levels of fractional exhaled nitric oxide (FENO) or immunoglobulin E (IgE) as candidate markers of ACOS in COPD, as a multicenter, cross-sectional study.,Outpatients with COPD were enrolled from Tohoku University Hospital, Sendai, Japan, and five hospitals (Tohoku University Hospital, Sendai, Japan; NTT East Tohoku Hospital, Sendai, Japan; Wakayama Medical University Hospital, Kimiidera, Japan; Hiraka General Hospital, Yokote, Japan; Iwate Prefectural Isawa Hospital, Oshu, Japan) with pulmonary physicians from March 1, 2013 to February 28, 2014.,When they were estimated using 35 ppb as the cutoff value of FENO, the prevalence rate of ACOS was 16.3% in COPD.,When estimated by both FENO and IgE, the high-FENO/high-IgE group was 7.8% in COPD.,To the best of our knowledge, this study is the first to detect the prevalence rate of ACOS in COPD populations by using objective biomarkers.,The results from the current study should be useful to identify the subgroup requiring early intervention by inhaled corticosteroids/long-acting beta agonist combination in COPD in order to improve the long-term management for ACOS. | 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. | The diagnosis of COPD is dependent upon clinical judgment and confirmation of the presence of airflow obstruction using spirometry.,Spirometry is now routinely available; however, spirometry incorrectly performed or interpreted can lead to misdiagnosis.,We aimed to determine whether spirometry undertaken in primary care for patients suspected to have COPD was of sufficient quality and whether their spirometry was correctly interpreted.,Two chest physicians re-read all spirometric readings for both quality of the procedure and interpretation, received as a part of COPD validation studies using data from the Clinical Practice Research Datalink (CPRD).,We then used logistic regression to investigate predictors of correct interpretation.,Spirometry traces were obtained for 306 patients, of which 221 (72.2%) were conducted in primary care.,Of those conducted in primary care, 98.6% (n=218) of spirometry traces were of adequate quality.,Of those traces that were of adequate quality and conducted in primary care, and in whom a general practitioner (GP) diagnosis of COPD had been made, 72.5% (n=218) were consistent with obstruction.,Historical records for asthma diagnosis significantly decreased odds of correct interpretation.,The quality of the spirometry procedure undertaken in primary care is high.,However, this was not reflected in the quality of interpretation, suggesting an unmet training in primary care.,The quality of the spirometry procedure as demonstrated by spirometric tracings provides a re-assurance for the use of spirometric values available in the electronic health care record databases for research purposes. | 1 |
A gap exists between guidelines and real-world clinical practice for the management and treatment of chronic obstructive pulmonary disease (COPD).,Although this has narrowed in the last decade, there is room for improvement in detection rates, treatment choices and disease monitoring.,In practical terms, primary care practitioners need to become aware of the huge impact of COPD on patients, have non-judgemental views of smoking and of COPD as a chronic disease, use a holistic consultation approach and actively motivate patients to adhere to treatment.,This article is based on discussions at a virtual meeting of leading Nordic experts in COPD (the authors) who were developing an educational programme for COPD primary care in the Nordic region.,The article aims to describe the diagnosis and lifelong management cycle of COPD, with a strong focus on providing a hands-on, practical approach for medical professionals to optimise patient outcomes in COPD primary care. | Wnt signaling pathways are tightly controlled under a physiological condition, under which they play key roles in many biological functions, including cell fate specification and tissue regeneration.,Increasing lines of evidence recently demonstrated that a dysregulated activation of Wnt signaling, particularly the Wnt/β-catenin signaling, was involved in the pathogenesis of chronic pulmonary diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).,In this respect, Wnt signaling interacts with other cellular signaling pathways to regulate the initiation and pathogenic procedures of airway inflammation and remodeling, pulmonary myofibroblast proliferation, epithelial-to-mesenchymal transition (EMT), and development of emphysema.,Intriguingly, Wnt/β-catenin signaling is activated in IPF; an inhibition of this signaling leads to an alleviation of pulmonary inflammation and fibrosis in experimental models.,Conversely, Wnt/β-catenin signaling is inactivated in COPD tissues, and its reactivation results in an amelioration of airspace enlargement with a restored alveolar epithelial structure and function in emphysema models.,These studies thus imply distinct mechanisms of Wnt/β-catenin signaling in the pathogenesis of these two chronic pulmonary diseases, indicating potential targets for COPD and IPF treatments.,This review article aims to summarize the involvement and pathogenic roles of Wnt signaling pathways in the COPD and IPF, with a focus on the implication of Wnt/β-catenin signaling as underlying mechanisms and therapeutic targets in these two incurable diseases. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities.,The main cause is smoking tobacco, but other factors have been identified.,Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli.,The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both.,Comorbidities include ischaemic heart disease, diabetes, and lung cancer.,Bronchodilators constitute the mainstay of treatment: β2 agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids).,Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification.,Future research should be directed towards the development of agents that notably affect the course of disease. | This study aimed to determine whether periodontal status is related to a decline in lung function in a general Japanese population.,We followed a total of 1,650 community-dwelling individuals (≥40 years) without chronic obstructive pulmonary disease, with at least one teeth, for 3 years.,Periodontal status was assessed at baseline by clinical attachment loss (CAL) and probing pocket depth (PPD) at two sites for each tooth, and the mean values were calculated for each subject.,Lung function was measured at baseline and follow-up using spirometry, and longitudinal decline in forced expiratory volume in one second (FEV1) was calculated.,Multivariate Poisson regression with robust error variance was used to estimate risk ratio (RR).,After adjusting for potential confounders including smoking status, there was a tendency for the adjusted RR of developing rapid lung function decline (≥160 mL/3years, the highest quartile of the distribution of FEV1 declines) to increase as mean CAL levels increased (P trend = 0.039).,Likewise, a positive association was observed between mean PPD levels and RR of developing rapid lung function decline (P trend = 0.047).,Our findings suggest deterioration of periodontal status could be a risk factor for rapid lung function decline in the general Japanese population. | 1 |
The global increase in the prevalence and incidence of obesity has called serious attention to this issue as a major public health concern.,Obesity is associated with many chronic diseases, including cardiovascular disease and diabetes, and recently the role of overweight and obesity in lung disease has received new interest.,Independently of obesity, diet also plays a role as a risk factor for many chronic diseases, and evidence is accumulating to support a role for diet in the prevention and management of several lung diseases.,Chronic obstructive lung disease is the third-leading cause of death globally, and both obesity and diet appear to play roles in its pathophysiology.,Obesity has been associated with decreased lung-function measures in population-based studies, with increased prevalence of several lung diseases and with compromised pulmonary function.,In contrast, obesity has a protective effect against mortality in severe chronic obstructive pulmonary disease (COPD).,Nutrient intake and dietary patterns have also been associated with lung-function measures and the development and progression of COPD.,Taken together, this suggests that a focus on obesity and diet should be part of public health campaigns to reduce the burden of lung disease, and could have important implications for clinicians in the management of their patients.,Future research should also focus on elucidating these relationships in diverse populations and age-groups, and on understanding the complex interaction between behavior, environment, and genetics in the development and progression of COPD.,The goal of this article is to review current evidence regarding the role that obesity and diet play in the development of COPD, and in COPD-related outcomes. | The landmark study of Fletcher and Peto on the natural history of tobacco smoke-related chronic airflow obstruction suggested that decline in the forced expiratory volume in the first second (FEV1) in chronic obstructive pulmonary disease (COPD) is slow at the beginning, becoming faster with more advanced disease.,The present authors reviewed spirometric data of COPD patients included in the placebo arms of recent clinical trials to assess the lung function decline of each stage, defined according to the severity of airflow obstruction as proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.,In large COPD populations the mean rate of FEV1 decline in GOLD stages II and III is between 47 and 79 mL/year and 56 and 59 mL/year, respectively, and lower than 35 mL/year in GOLD stage IV.,Few data on FEV1 decline are available for GOLD stage I.,Hence, the loss of lung function, assessed as expiratory airflow reduction, seems more accelerated and therefore more relevant in the initial phases of COPD.,To have an impact on the natural history of COPD, it is logical to look at the effects of treatment in the earlier stages. | 1 |
Substantial evidence suggests that there is genetic susceptibility to chronic obstructive pulmonary disease (COPD).,To identify common genetic risk variants, we performed a genome-wide association study in 2940 cases and 1380 smoking controls with normal lung function.,We demonstrate a novel susceptibility locus at 4q22.1 in FAM13A (rs7671167, OR=0.76, P=8.6×10−8) and provide evidence of replication in one case-control and two family-based cohorts (for all studies, combined P=1.2×10−11). | There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD).,The only known genetic risk factor is severe deficiency of α1-antitrypsin, which is present in 1-2% of individuals with COPD.,We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study.,The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population.,Logistic regression models with adjustments of covariates were used to analyze the case-control populations.,Family-based association analyses were conducted for a diagnosis of COPD and lung function in the family populations.,Two SNPs at the α-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study.,They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48×10−10, (rs8034191) and 5.74×10−10 (rs1051730).,Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations.,The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%.,The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels.,Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; doi:10.1371/journal.pgen.1000429).,The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD.,CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer. | 1 |
Chronic obstructive pulmonary disease (COPD) symptoms in the morning, including dyspnea and sputum production, affect patients’ quality of life and limit their ability to carry out even simple morning activities.,It is now emerging that these symptoms are associated with increased risk of exacerbations and work absenteeism, suggesting that they have a more profound impact on patients than previously thought.,The development of validated patient-reported outcome (PRO) questionnaires to capture patients’ experience of COPD symptoms in the morning is, therefore, vital for establishing effective and comprehensive management strategies.,Although it is well established that long-acting bronchodilators are effective in improving COPD symptoms, the limited available data on their impact on morning symptoms and activities have been obtained with non-validated PRO questionnaires.,In this review, we discuss the impact of COPD symptoms in the morning and available tools used to evaluate them, and highlight specific gaps that need to be addressed to develop standardized instruments able to meet regulatory requirement.,We also present available evidence on the effect of pharmacological therapies on morning symptoms. | Chronic obstructive pulmonary disease (COPD) is a common disease in the general population and it places a considerable burden on patients, with the disease negatively affecting quality of life.,In practice, patients with COPD generally seek medical attention because of symptoms, particularly breathlessness, and the resulting physical limitations, which affect the health-related quality of life (HR-QOL) in patients.,The defining feature of COPD is airflow limitation that causes air trapping and increased hyperinflation as the ventilation rate increases during physical effort.,Hyperinflation causes or worsens breathlessness as breathing becomes inefficient, with the end result being an avoidance of physical exertion and a cycle of increasing dyspnea caused by inactivity and deconditioning, with deleterious effects on HR-QOL.,Current published guidelines for COPD state that the goals of pharmacologic therapy should be to control symptoms, improve health status and exercise tolerance, and reduce the frequency of COPD exacerbations.,Effective and sustained bronchodilation has emerged as a key strategy for improving dyspnea and ability to exercise.,As there is no cure for COPD, a major goal of treatment and of research into new therapies is to improve HR-QOL in COPD patients.,More recently, indacaterol, an inhaled ultra-long-acting β2-agonist (24-hour action), has been approved in many countries at different doses (between 75 and 300 μg once daily) for treatment of patients with stable but symptomatic COPD.,The aim of this review was to explore once-daily indacaterol clinical data as related to improvement in HR-QOL in COPD.,Indacaterol studies have shown significant improvements in lung function of COPD patients, and these improvements have also translated into clinically meaningful improvements in patient symptoms and HR-QOL. | 1 |
MicroRNAs (miRNAs) play essential roles in the development of COPD.,In this study, we aimed to identify and validate potential miRNA biomarkers in frequent and non-frequent exacerbators of COPD patients using bioinformatic analysis.,The candidate miRNA biomarkers in COPD were screened from Gene Expression Omnibus (GEO) dataset and identified using GEO2R online tool.,Then, we performed bioinformatic analyses including target prediction, gene ontology (GO), pathway enrichment analysis and construction of protein-protein interaction (PPI) network.,Furthermore, the expression of the identified miRNAs in peripheral blood monocular cells (PBMCs) of COPD patients was validated using quantitative real-time polymerase chain reaction (qRT-PCR).,MiR-23a, miR-25, miR-145 and miR-224 were identified to be significantly downregulated in COPD patients compared with healthy controls.,GO analysis showed the four miRNAs involved in apoptotic, cell differentiation, cell proliferation and innate immune response.,Pathway analysis showed that the targets of these miRNAs were associated with p53, TGF-β, Wnt, VEGF and MAPK signal pathway.,In healthy controls, the miR-25 and miR-224 levels were significantly decreased in smokers compared with nonsmokers (P<0.001 and P<0.05, respectively).,In COPD patients, the levels of miR-23a, miR-25, miR-145 and miR-224 were associated with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages.,Notably, miR-23a and miR-145 were significantly elevated in non-frequent exacerbators compared with frequent exacerbators (P<0.05), and miR-23a showed higher area under the receiver-operator characteristic curve (AUROC) than miR-145 (0.707 vs 0.665, P<0.05).,MiR-23a, miR-25, miR-145 and miR-224 were associated with the development of COPD, and miR-23a might be a potential biomarker for discriminating the frequent exacerbators from non-frequent exacerbators. | Chronic obstructive pulmonary disease (COPD) is a common, highly debilitating disease of the airways, primarily caused by smoking.,Chronic inflammation and structural remodelling are key pathological features of this disease, in part caused by the aberrant function of airway smooth muscle (ASM) cells under the regulation of transforming growth factor (TGF)‐β. miRNA are short, noncoding gene transcripts involved in the negative regulation of specific target genes, through their interactions with mRNA.,Previous studies have proposed that mRNA‐145 (miR‐145) may interact with SMAD3, an important downstream signalling molecule of the TGF‐β pathway.,TGF‐β was used to stimulate primary human ASM cells isolated from healthy nonsmokers, healthy smokers and COPD patients.,This resulted in a TGF‐β‐dependent increase in CXCL8 and IL‐6 release, most notably in the cells from COPD patients.,TGF‐β stimulation increased SMAD3 expression, only in cells from COPD patients, with a concurrent increased miR‐145 expression.,Regulation of miR‐145 was found to be negatively controlled by pathways involving the MAP kinases, MEK‐1/2 and p38 MAPK.,Subsequent, overexpression of miR‐145 (using synthetic mimics) in ASM cells from patients with COPD suppressed IL‐6 and CXCL8 release, to levels comparable to the nonsmoker controls.,Therefore, this study suggests that miR‐145 negatively regulates pro‐inflammatory cytokine release from ASM cells in COPD by targeting SMAD3. | 1 |
It has recently been proposed that the concept of clinical control in COPD may be useful for deciding treatment in COPD, but the original control criteria (OCC) were considered too restrictive.,Define and subsequently validate “modified” control criteria (MCC) of COPD.,Prospective observational study in COPD patients with a 1-year follow-up.,Control was defined as the presence of low clinical impact and clinical stability.,To evaluate clinical impact, the following clinical parameters were assessed: the degree of dyspnea, use of rescue medication, physical activity, and sputum color.,Stability was assessed by clinical changes and exacerbations in the last 3 months.,The COPD assessment test score and their changes were also evaluated as alternative control criteria.,To define the MCC, adjustment for disease severity using BODEx index (MCC-B) or FEV1 (MCC-F) was evaluated, and the best cutoff point was established.,Time to first combined event (emergency visit, hospitalization, or death) was analyzed to evaluate the predictive capacity of risk of the OCC, MCC-B, and MCC-F.,We included 265 patients, 224 (83.9%) men, with a mean age (±SD) of 68±9 years and FEV1 of 58%±17%.,The proportion of controlled patients was higher using clinical MCC-B or MCC-F (61.5% and 59.6%) than OCC (27.5%).,Similar percentages were found using COPD assessment test scores.,The time to the first combined event was significantly greater in controlled patients using MCC criteria (P<0.001, all cases).,The predictive capacity of risk was similar in MCC-B (c-statistic [C]=0.639) and MCC-F (C=0.637) and higher than OCC (C=0.589).,The new MCC identified a higher number of controlled COPD patients.,These patients have a better quality of life and lower risk of poor outcomes.,The concept of control and the new MCC could be a useful tool to optimize therapy. | Several fixed-dose combinations (FDCs) of long-acting bronchodilators (a long-acting muscarinic antagonist [LAMA] plus a long-acting β2-agonist [LABA]) are available for the treatment of COPD.,Studies of these FDCs have demonstrated substantial improvements in lung function (forced expiratory volume in 1 second) in comparison with their respective constituent monocomponents.,Improvements in patient-reported outcomes (PROs), such as symptoms and health status, as well as exacerbation rates, have been reported compared with a LABA or LAMA alone, but results are less consistent.,The inconsistencies may in part be owing to differences in study design, methods used to assess study end points, and patient populations.,Nevertheless, these observations tend to support an association between improvements in forced expiratory volume in 1 second and improvements in symptom-based outcomes.,In order to assess the effects of FDCs on PROs and evaluate relationships between PROs and changes in lung function, we performed a systematic literature search of publications reporting randomized controlled trials of FDCs.,Results of this literature search were independently assessed by two reviewers, with a third reviewer resolving any conflicting results.,In total, 22 Phase III randomized controlled trials of FDC bronchodilators in COPD were identified, with an additional study including a post-literature search (ten for indacaterol-glycopyrronium once daily, eight for umeclidinium-vilanterol once daily, three for tiotropium-olodaterol once daily, and two for aclidinium-formoterol twice daily).,Results from these studies demonstrated that the LAMA-LABA FDCs significantly improved lung function compared with their component monotherapies or other single-agent treatments.,Furthermore, LABA-LAMA combinations also generally improved symptoms and health status versus monotherapies, although some discrepancies between lung function and PROs were observed.,Overall, the safety profiles of the FDCs were similar to placebo.,Further research is required to examine more closely any relationship between lung function and PROs in patients receiving LABA-LAMA combinations. | 1 |
To estimate excess health care expenditures associated with gastroesophageal reflux disease (GERD) among elderly individuals with chronic obstructive pulmonary disease (COPD) and examine the contribution of predisposing characteristics, enabling resources, need variables, personal health care practices, and external environment factors to the excess expenditures, using the Blinder-Oaxaca linear decomposition technique.,This study utilized a cross-sectional, retrospective study design, using data from multiple years (2006-2009) of the Medicare Current Beneficiary Survey linked with fee-for-service Medicare claims.,Presence of COPD and GERD was identified using diagnoses codes.,Health care expenditures consisted of inpatient, outpatient, prescription drugs, dental, medical provider, and other services.,For the analysis, t-tests were used to examine unadjusted subgroup differences in average health care expenditures by the presence of GERD.,Ordinary least squares regressions on log-transformed health care expenditures were conducted to estimate the excess health care expenditures associated with GERD.,The Blinder-Oaxaca linear decomposition technique was used to determine the contribution of predisposing characteristics, enabling resources, need variables, personal health care practices, and external environment factors, to excess health care expenditures associated with GERD.,Among elderly Medicare beneficiaries with COPD, 29.3% had co-occurring GERD.,Elderly Medicare beneficiaries with COPD/GERD had 1.5 times higher ($36,793 vs $24,722 [P<0.001]) expenditures than did those with COPD/no GERD.,Ordinary least squares regression revealed that individuals with COPD/GERD had 36.3% (P<0.001) higher expenditures than did those with COPD/no GERD.,Overall, 30.9% to 43.6% of the differences in average health care expenditures were explained by differences in predisposing characteristics, enabling resources, need variables, personal health care practices, and external environment factors between the two groups.,Need factors explained up to 41% of the differences in average health care expenditures between the two groups.,Among elderly Medicare beneficiaries with COPD, the presence of GERD was associated with higher expenditures.,Need factors primarily contributed to the differences in average health care expenditures, suggesting that the comanagement of chronic conditions may reduce excess health care expenditures associated with GERD. | The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) is a concise health status measure for COPD.,COPD patients have a variety of comorbidities, but little is known about their impact on quality of life.,This study was designed to investigate comorbid factors that may contribute to high CAT scores.,An observational study at Keio University and affiliated hospitals enrolled 336 COPD patients and 67 non-COPD subjects.,Health status was assessed by the CAT, the St.,Georges Respiratory Questionnaire (SGRQ), and all components of the Medical Outcomes Study Short-Form 36-Item (SF-36) version 2, which is a generic measure of health.,Comorbidities were identified based on patients’ reports, physicians’ records, and questionnaires, including the Frequency Scale for the Symptoms of Gastro-esophageal reflux disease (GERD) and the Hospital Anxiety and Depression Scale.,Dual X-ray absorptiometry measurements of bone mineral density were performed.,The CAT showed moderate-good correlations with the SGRQ and all components of the SF-36.,The presence of GERD, depression, arrhythmia, and anxiety was significantly associated with a high CAT score in the COPD patients.,Symptomatic COPD patients have a high prevalence of comorbidities.,A high CAT score should alert the clinician to a higher likelihood of certain comorbidities such as GERD and depression, because these diseases may co-exist unrecognized.,Clinical trial registered with UMIN (UMIN000003470). | 1 |
The purpose of the current study was to determine the association between sedentary time and physical activity with clinically relevant health outcomes among adults with impaired spirometry and those with or without self-reported obstructive lung disease (asthma or COPD).,Data from participants of the Canadian Longitudinal Study on Aging were used for analysis (n = 4156).,Lung function was assessed using spirometry.,Adults were said to have impaired spirometry if their Forced Expiratory Volume in 1 s was <5th percentile lower limit of normal (LLN).,A modified version of the Physical Activity Scale for the Elderly was used to assess sitting time and physical activity levels.,Healthcare use and quality of life outcomes were assessed using self report.,Among those with asthma, participating in strengthening activities was associated with lower odds of reporting poor perceived health (OR = 0.65, CI: 0.53, 0.79), poor perceived mental-health (OR = 0.73, CI: 0.60, 0.88), unhealthy aging (OR = 0.68, CI: 0.56, 0.83), and reporting an emergency department visit in the past 12 months (OR = 0.76, CI: 0.60, 0.95).,Among those with COPD, those who reported highest weekly sedentary time had higher odds of reporting poor perceived health (OR = 2.70, CI: 1.72, 4.24), poor perceived mental-health (OR = 1.99, CI: 1.29, 3.06), and unhealthy aging (OR = 3.04, CI: 1.96, 4.72).,Among those below the LLN, sitting time (OR = 2.57, CI: 1.40, 4.72) and moderate intensity physical activity (OR = 0.23, CI: 0.09, 0.63) were associated with overnight hospital stays.,Higher physical activity levels and lower sedentary time may be associated with lower healthcare use and better quality of life.,This research may have implications related to the use of physical activity for improving health outcomes and quality of life among adults with obstructive lung disease or impaired spirometry.,The online version of this article (10.1186/s12890-018-0659-8) contains supplementary material, which is available to authorized users. | Persons with Chronic Obstructive Pulmonary Disease (COPD), performing some level of regular physical activity, have a lower risk of both COPD-related hospital admissions and mortality.,COPD patients of all stages seem to benefit from exercise training programs, thereby improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue.,Physical inactivity, which becomes more severe with increasing age, is a point of concern in healthy older adults.,COPD might worsen this scenario, but it is unclear to what degree.,This literature review aims to present the extent of the impact of COPD on objectively-measured daily physical activity (DPA).,The focus is on the extent of the impact that COPD has on duration, intensity, and counts of DPA, as well as whether the severity of the disease has an additional influence on DPA.,A literature review was performed in the databases PubMed [MEDLINE], Picarta, PEDRO, ISI Web of Knowledge and Google scholar.,After screening, 11 studies were identified as being relevant for comparison between COPD patients and healthy controls with respect to duration, intensity, and counts of DPA.,Four more studies were found to be relevant to address the subject of the influence the severity of the disease may have on DPA.,The average percentage of DPA of COPD patients vs. healthy control subjects for duration was 57%, for intensity 75%, and for activity counts 56%.,Correlations of DPA and severity of the disease were low and/or not significant.,From the results of this review, it appears that patients with COPD have a significantly reduced duration, intensity, and counts of DPA when compared to healthy control subjects.,The intensity of DPA seems to be less affected by COPD than duration and counts.,Judging from the results, it seems that severity of COPD is not strongly correlated with level of DPA.,Future research should focus in more detail on the relation between COPD and duration, intensity, and counts of DPA, as well as the effect of disease severity on DPA, so that these relations become more understandable. | 1 |
Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies.,To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552).,Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years.,We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation.,Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p<0.001) and exacerbation frequency (1.5 (1.5) vs.,0.9 (1.1) per year, p<0.001) compared to non-inflamed ones.,As a descriptive study our results show associations but do not prove causality.,Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice.,Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment. | Fibrinogen is a marker of systemic inflammation and may be important in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD).,We used baseline data from Atherosclerosis Risk in Communities and Cardiovascular Health Studies to determine the relation between fibrinogen levels and COPD and to examine how fibrinogen levels at baseline affected outcomes of death, development of COPD, lung function decline, and COPD-hospitalizations.,Our study sample included 20,192 subjects, of whom 2995 died during the follow-up period.,The mean fibrinogen level was 307.6 mg/dL and 10% of the sample had levels >393.0 mg/dL.,Subjects with Stage 3 or 4 COPD were more likely to have a fibrinogen level >393.0 mg/dL (odds ratio 2.28, 95% confidence interval [CI]: 1.79-2.95).,In the longitudinal adjusted models, fibrinogen levels >393 mg/dL predicted mortality (hazards ratio 1.54, 95% CI: 1.39-1.70), COPD-related hospitalization (hazards ratio 1.45, 95% CI: 1.27-1.67), and incident Stage 2 COPD (odds ratio 1.36, 95% CI: 1.07-1.74).,Similar findings were seen with continuous fibrinogen levels.,In the Atherosclerosis Risk in Communities/Cardiovascular Health Studies cohort data, higher fibrinogen levels are predictors of mortality, COPD-related hospitalizations, and incident Stage 2 COPD. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is often caused by smoking and other stressors.,This causes oxidative stress, which induces numerous changes on both the transcriptome and proteome of the cell.,We aimed to examine if the endomembrane pathway, including the endoplasmic reticulum (ER), Golgi, and lysosomes, was disrupted in fibroblasts from COPD patients as opposed to healthy ever‐smokers or never‐smokers, and if the response to stress differed.,Different cellular compartments involved in the endomembrane pathway, as well as mRNA expression and apoptosis, were examined before and after the addition of stress in lung fibroblasts from never‐smokers, ever‐smokers, and patients with COPD.,We found that the ER, Golgi, and lysosomes were disorganized in fibroblasts from COPD patients under baseline conditions.,After a time course with ER stress inducing chemicals, changes to the phenotypes of cellular compartments in COPD patient fibroblasts were observed, and the expression of the ER stress‐induced gene ERP72 was upregulated more in the COPD patient's cells compared to ever‐smokers or never‐smokers.,Lastly, a tendency of increased active Caspase‐3 was observed in COPD fibroblasts.,Our results show that COPD patients have phenotypic changes in the lung fibroblasts endomembrane pathway, and respond differently to stress.,Furthermore, these fibroblasts were cultured for several weeks outside the body, but they were not able to regain proper ER structure, indicating that the internal changes to the endomembrane system are permanent in smokers.,This vulnerability to cellular stress might be a cause as to why some smokers develop COPD. | Chronic obstructive pulmonary disease (COPD) is characterized by loss of elastic fibres from small airways and alveolar walls, with the decrease in elastin increasing with disease severity.,It is unclear why there is a lack of repair of elastic fibres.,We have examined fibroblasts cultured from lung tissue from subjects with or without COPD to determine if the secretory profile explains lack of tissue repair.,In this study, fibroblasts were cultured from lung parenchyma of patients with mild COPD [Global initiative for chronic Obstructive Lung Disease (GOLD) 1, n= 5], moderate to severe COPD (GOLD 2-3, n= 12) and controls (non-COPD, n= 5).,Measurements were made of proliferation, senescence-associated β-galactosidase-1, mRNA expression of IL-6, IL-8, MMP-1, tropoelastin and versican, and protein levels for IL-6, IL-8, PGE2, tropoelastin, insoluble elastin, and versican.,GOLD 2-3 fibroblasts proliferated more slowly (P < 0.01), had higher levels of senescence-associated β-galactosidase-1 (P < 0.001) than controls and showed significant increases in mRNA and/or protein for IL-6 (P < 0.05), IL-8 (P < 0.01), MMP-1 (P < 0.05), PGE2 (P < 0.05), versican (P < 0.05) and tropoelastin (P < 0.05). mRNA expression and/or protein levels of tropoelastin (P < 0.01), versican (P < 0.05), IL-6 (P < 0.05) and IL-8 (P < 0.05) were negatively correlated with FEV1% of predicted.,Insoluble elastin was not increased.,In summary, fibroblasts from moderate to severe COPD subjects display a secretory phenotype with up-regulation of inflammatory molecules including the matrix proteoglycan versican, and increased soluble, but not insoluble, elastin.,Versican inhibits assembly of tropoelastin into insoluble elastin and we conclude that the pro-inflammatory phenotype of COPD fibroblasts is not compatible with repair of elastic fibres. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by varying trajectories of decline.,Information regarding the prognostic value of preventing short-term clinically important deterioration (CID) in lung function, health status, or first moderate/severe exacerbation as a composite endpoint of worsening is needed.,We evaluated post hoc the link between early CID and long-term adverse outcomes.,CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV1), ≥4-unit increase in St George’s Respiratory Questionnaire (SGRQ) score from baseline, and/or a moderate/severe exacerbation during enrollment in two 3-year studies.,Presence of CID was assessed at 6 months for the principal analysis (TORCH) and 12 months for the confirmatory analysis (ECLIPSE).,Association between presence (+) or absence (-) of CID and long-term deterioration in FEV1, SGRQ, future risk of exacerbations, and all-cause mortality was assessed.,In total, 2870 (54%; TORCH) and 1442 (73%; ECLIPSE) patients were CID+.,At 36 months, in TORCH, CID+ patients (vs CID-) had sustained clinically significant worsening of FEV1 (- 117 mL; 95% confidence interval [CI]: - 134, - 100 mL; P < 0.001) and SGRQ score (+ 6.42 units; 95% CI: 5.40, 7.45; P < 0.001), and had higher risk of exacerbations (hazard ratio [HR]: 1.61 [95% CI: 1.50, 1.72]; P < 0.001) and all-cause mortality (HR: 1.41 [95% CI: 1.15, 1.72]; P < 0.001).,Similar risks post-CID were observed in ECLIPSE.,A CID within 6-12 months of follow-up was consistently associated with increased long-term risk of exacerbations and all-cause mortality, and predicted sustained meaningful loss in FEV1 and health status amongst survivors.,NCT00268216; NCT00292552.,The online version of this article (10.1186/s12931-018-0928-3) contains supplementary material, which is available to authorized users. | Chronic Obstructive Pulmonary Disease (COPD) is a common disease with significant health and economic consequences.,This study assesses the burden of COPD in the general population, and the influence of exacerbations (E-COPD) on disease progression and costs.,This is a secondary data analysis of healthcare administrative databases of the region of Lombardy, in northern Italy.,The study included ≥ 40 year-old patients hospitalized for a severe E-COPD (index event) during 2006.,Patients were classified in relation to the number and type of E-COPD experienced in a three-year pre-index period.,Subjects were followed up until December 31st, 2009, collecting data on healthcare resource use and vital status.,15857 patients were enrolled -9911 males, mean age: 76 years (SD 10).,Over a mean follow-up time of 2.4 years (1.36), 81% of patients had at least one E-COPD with an annual rate of 3.2 exacerbations per person-year and an all-cause mortality of 47%.,A history of exacerbation influenced the occurrence of new E-COPD and mortality after discharge for an E-COPD.,On average, the healthcare system spent 6725€ per year per person (95%CI 6590-6863).,Occurrence and type of exacerbations drove the direct healthcare cost.,Less than one quarter of patients presented claims for pulmonary function tests.,COPD imposes a substantial burden on healthcare systems, mainly attributable to the type and occurrence of E-COPD, or in other words, to the exacerbator phenotypes.,A more tailored approach to the management of COPD patients is required. | 1 |
Background: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD).,It represents a collaborative effort on the part of a panel of expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thoracic Society.,Methods: Comprehensive evidence syntheses were performed on all relevant studies that addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts.,The evidence was appraised, rated, and graded, and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.,Results: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations: 1) a strong recommendation for the use of long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance; 2) a conditional recommendation for the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year; 3) a conditional recommendation for ICS withdrawal for patients with COPD receiving triple therapy (ICS/LABA/LAMA) if the patient has had no exacerbations in the past year; 4) no recommendation for or against ICS as an additive therapy to long-acting bronchodilators in patients with COPD and blood eosinophilia, except for those patients with a history of one or more exacerbations in the past year requiring antibiotics or oral steroids or hospitalization, for whom ICS is conditionally recommended as an additive therapy; 5) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and 6) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy.,Conclusions: The task force made recommendations regarding the pharmacologic treatment of COPD based on currently available evidence.,Additional research in populations that are underrepresented in clinical trials is needed, including studies in patients with COPD 80 years of age and older, those with multiple chronic health conditions, and those with a codiagnosis of COPD and asthma. | Tiotropium-olodaterol, formulated in the Respimat soft-mist inhaler, is an inhaled fixed-dose combination (FDC) of a long-acting muscarinic antagonist (LAMA) and a long-acting β2-agonist (LABA), commercialized under the name of Spiolto or Stiolto.,The efficacy of tiotropium-olodaterol 5-5 μg once daily in adult patients with COPD was documented in eleven large, multicenter trials of up to 52 weeks duration.,Tiotropium-olodaterol 5-5 μg not only improved spirometric values to a significantly greater extent than placebo but also resulted in statistically significant beneficial effects on dyspnea, markers of hyperinflation, use of rescue medication, health-related quality of life, and exercise endurance.,Improvements exceeded the minimal clinically important difference (MCID) for forced expiratory volume in 1 second (FEV1), dyspnea, and quality of life.,Differences between tiotropium-olodaterol 5-5 μg and the respective monocomponents were statistically significant for FEV1, dyspnea, markers of hyperinflation, use of rescue medication, and health-related quality of life, but did not reach the MCID.,However, dual bronchodilatation significantly increased the number of patients who exceeded the MCID for dyspnea and quality of life.,Moreover, tiotropium-olodaterol 5-5 μg was significantly more effective than salmeterol-fluticasone (FDC) twice daily at improving pulmonary function.,Differences between tiotropium-olodaterol and other LAMA/LABA FDCs were not observed for FEV1 or other efficacy markers.,Therefore, tiotropium-olodaterol is a valuable option in the treatment of COPD patients who remain symptomatic under monotherapy. | 1 |
Chronic obstructive pulmonary disease, COPD, is an increasing cause of morbidity and mortality worldwide, and an imbalance between proteases and antiproteases has been implicated to play a role in COPD pathogenesis.,Matrix metalloproteinases (MMP) are important proteases that along with their inhibitors, tissue inhibitors of metalloproteinases (TIMP), affect homeostasis of elastin and collagen, of importance for the structural integrity of human airways.,Small observational studies indicate that these biomarkers are involved in the pathogenesis of COPD.,The aim of this study was to investigate serum levels of MMP-9 and TIMP-1 in a large Swedish population-based cohort, and their association with disease severity and important clinical symptoms of COPD such as productive cough.,Spirometry was performed and peripheral blood samples were collected in a populations-based cohort (median age 67 years) comprising subjects with COPD (n = 594) and without COPD (n = 948), in total 1542 individuals.,Serum MMP-9 and TIMP-1 concentrations were measured with enzyme linked immunosorbant assay (ELISA) and related to lung function data and symptoms.,Median serum MMP-9 values were significantly higher in COPD compared with non-COPD 535 vs. 505 ng/ml (P = 0.017), without any significant differences in serum TIMP-1-levels or MMP-9/TIMP-1-ratio.,In univariate analysis, productive cough and decreasing FEV1% predicted correlated significantly with increased MMP-9 among subjects with COPD (P = 0.004 and P = 0.001 respectively), and FEV1% predicted remained significantly associated to MMP-9 in a multivariate model adjusting for age, sex, pack years and productive cough (P = 0.033).,Productive cough and decreasing FEV1 were each associated with MMP-9 in COPD, and decreasing FEV1 remained significantly associated with MMP-9 also after adjustment for common confounders in this population-based COPD cohort.,The increased serum MMP-9 concentrations in COPD indicate an enhanced proteolytic activity that is related to disease severity, and further longitudinal studies are important for the understanding of MMP-9 in relation to the disease process and the pathogenesis of different COPD phenotypes. | Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation.,Autophagy is a degradative process involving lysosomal turnover of cellular components, though its role in human diseases remains unclear.,Increased autophagy was observed in lung tissue from COPD patients, as indicated by electron microscopic analysis, as well as by increased activation of autophagic proteins (microtubule-associated protein-1 light chain-3B, LC3B, Atg4, Atg5/12, Atg7).,Cigarette smoke extract (CSE) is an established model for studying the effects of cigarette smoke exposure in vitro.,In human pulmonary epithelial cells, exposure to CSE or histone deacetylase (HDAC) inhibitor rapidly induced autophagy.,CSE decreased HDAC activity, resulting in increased binding of early growth response-1 (Egr-1) and E2F factors to the autophagy gene LC3B promoter, and increased LC3B expression.,Knockdown of E2F-4 or Egr-1 inhibited CSE-induced LC3B expression.,Knockdown of Egr-1 also inhibited the expression of Atg4B, a critical factor for LC3B conversion.,Inhibition of autophagy by LC3B-knockdown protected epithelial cells from CSE-induced apoptosis.,Egr-1 −/− mice, which displayed basal airspace enlargement, resisted cigarette-smoke induced autophagy, apoptosis, and emphysema.,We demonstrate a critical role for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke exposure in vitro and in vivo.,The induction of autophagy at early stages of COPD progression suggests novel therapeutic targets for the treatment of cigarette smoke induced lung injury. | 1 |
To estimate excess health care expenditures associated with gastroesophageal reflux disease (GERD) among elderly individuals with chronic obstructive pulmonary disease (COPD) and examine the contribution of predisposing characteristics, enabling resources, need variables, personal health care practices, and external environment factors to the excess expenditures, using the Blinder-Oaxaca linear decomposition technique.,This study utilized a cross-sectional, retrospective study design, using data from multiple years (2006-2009) of the Medicare Current Beneficiary Survey linked with fee-for-service Medicare claims.,Presence of COPD and GERD was identified using diagnoses codes.,Health care expenditures consisted of inpatient, outpatient, prescription drugs, dental, medical provider, and other services.,For the analysis, t-tests were used to examine unadjusted subgroup differences in average health care expenditures by the presence of GERD.,Ordinary least squares regressions on log-transformed health care expenditures were conducted to estimate the excess health care expenditures associated with GERD.,The Blinder-Oaxaca linear decomposition technique was used to determine the contribution of predisposing characteristics, enabling resources, need variables, personal health care practices, and external environment factors, to excess health care expenditures associated with GERD.,Among elderly Medicare beneficiaries with COPD, 29.3% had co-occurring GERD.,Elderly Medicare beneficiaries with COPD/GERD had 1.5 times higher ($36,793 vs $24,722 [P<0.001]) expenditures than did those with COPD/no GERD.,Ordinary least squares regression revealed that individuals with COPD/GERD had 36.3% (P<0.001) higher expenditures than did those with COPD/no GERD.,Overall, 30.9% to 43.6% of the differences in average health care expenditures were explained by differences in predisposing characteristics, enabling resources, need variables, personal health care practices, and external environment factors between the two groups.,Need factors explained up to 41% of the differences in average health care expenditures between the two groups.,Among elderly Medicare beneficiaries with COPD, the presence of GERD was associated with higher expenditures.,Need factors primarily contributed to the differences in average health care expenditures, suggesting that the comanagement of chronic conditions may reduce excess health care expenditures associated with GERD. | Never smokers comprise a substantial proportion of patients with COPD.,Their characteristics and possible risk factors in this population are not yet well defined.,We analyzed data from 14 countries that participated in the international, population-based Burden of Obstructive Lung Disease (BOLD) study.,Participants were aged ≥ 40 years and completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors.,A diagnosis of COPD was based on the postbronchodilator FEV1/FVC ratio, according to current GOLD (Global Initiative for Obstructive Lung Disease) guidelines.,In addition to this, the lower limit of normal (LLN) was evaluated as an alternative threshold for the FEV1/FVC ratio.,Among 4,291 never smokers, 6.6% met criteria for mild (GOLD stage I) COPD, and 5.6% met criteria for moderate to very severe (GOLD stage II+) COPD.,Although never smokers were less likely to have COPD and had less severe COPD than ever smokers, never smokers nonetheless comprised 23.3% (240/1,031) of those classified with GOLD stage II+ COPD.,This proportion was similar, 20.5% (171/832), even when the LLN was used as a threshold for the FEV1/FVC ratio.,Predictors of COPD in never smokers include age, education, occupational exposure, childhood respiratory diseases, and BMI alterations.,This multicenter international study confirms previous evidence that never smokers comprise a substantial proportion of individuals with COPD.,Our data suggest that, in addition to increased age, a prior diagnosis of asthma and, among women, lower education levels are associated with an increased risk for COPD among never smokers. | 1 |
Cough and sputum production are frequent in chronic obstructive pulmonary disease (COPD).,The objective of this study was to examine the relationship between cough and sputum production and health-related quality of life in COPD.,A cross-sectional study was conducted in the French Initiatives COPD cohort and assessed cough and sputum production within the past 7 days using the cough and sputum assessment questionnaire (CASA-Q), health-related quality of life, spirometry, smoking status, dyspnea, exacerbations, anxiety and depression, and comorbidities.,One hundred and seventy-eight stable COPD patients were included (age, 62 [56-69] years, 128 male, forced expiratory volume in 1 second [FEV1]: 57 [37-72] % predicted) (median [Q1-Q3]).,In univariate analyses, health-related quality of life (Saint George’s respiratory questionnaire total score) was associated with each CASA-Q domain and with chronic bronchitis, exacerbations, dyspnea, FEV1, depression, and anxiety.,All four domains introduced separately were independently associated with health-related quality of life.,When introduced together in multivariate analyses, only the cough impact domain remained independently associated with health-related quality of life (R2=0.60).,With chronic bronchitis (standard definition) instead of the CASA-Q, the R2 was lower (R2=0.54).,This study provides evidence that current cough in the previous 7 days is an important determinant of health-related quality of life impairment in stable COPD patients. | Exacerbations of chronic obstructive pulmonary disease (COPD) are defined as sustained worsening of a patient’s condition beyond normal day-to-day variations that is acute in onset, and that may also require a change in medication and/or hospitalization.,Exacerbations have a significant and prolonged impact on health status and outcomes, and negative effects on pulmonary function.,A significant proportion of exacerbations are unreported and therefore left untreated, leading to a poorer prognosis than those treated.,COPD exacerbations are heterogeneous, and various phenotypes have been proposed which differ in biologic basis, prognosis, and response to therapy.,Identification of biomarkers could enable phenotype-driven approaches for the management and prevention of exacerbations.,For example, several biomarkers of inflammation can help to identify exacerbations most likely to respond to oral corticosteroids and antibiotics, and patients with a frequent exacerbator phenotype, for whom preventative treatment is appropriate.,Reducing the frequency of exacerbations would have a beneficial impact on patient outcomes and prognosis.,Preventative strategies include modification of risk factors, treatment of comorbid conditions, the use of bronchodilator therapy with long-acting β2-agonists or long-acting muscarinic antagonists, and inhaled corticosteroids.,A better understanding of the mechanisms underlying COPD exacerbations will help to optimize use of the currently available and new interventions for preventing and treating exacerbations. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of worsening of symptoms, leading to substantial morbidity and mortality.,COPD exacerbations are associated with increased airway and systemic inflammation and physiological changes, especially the development of hyperinflation.,They are triggered mainly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation.,Some patients are particularly susceptible to exacerbations, and show worse health status and faster disease progression than those who have infrequent exacerbations.,Several pharmacological interventions are effective for the reduction of exacerbation frequency and severity in COPD such as inhaled steroids, long-acting bronchodilators, and their combinations.,Non-pharmacological therapies such as pulmonary rehabilitation, self-management, and home ventilatory support are becoming increasingly important, but still need to be studied in controlled trials.,The future of exacerbation prevention is in assessment of optimum combinations of pharmacological and non-pharmacological therapies that will result in improvement of health status, and reduction of hospital admission and mortality associated with COPD. | The possible relationship between chronic inflammatory diseases and their co-morbidities has become an increasing focus of research.,Both chronic periodontitis and chronic obstructive pulmonary disease are neutrophilic, inflammatory conditions characterized by the loss of local connective tissue.,Evidence suggests an association and perhaps a causal link between the two diseases.,However, the nature of any relationship between them is unclear, but if pathophysiologically established may have wide-reaching implications for targeted treatments to improve outcomes and prognosis.,There have been a number of epidemiological studies undertaken demonstrating an independent association between chronic periodontitis and chronic obstructive pulmonary disease.,However, many of them have significant limitations, and drawing firm conclusions regarding causality may be premature.,Although the pathology of both these diseases is complex and involves many cell types, such as CD8 positive cells and macrophages, both conditions are predominantly characterized by neutrophilic inflammation.,Increasingly, there is evidence that the two conditions are underpinned by similar pathophysiological processes, especially centered on the functions of the neutrophil.,These include a disturbance in protease/anti-protease and redox state balance.,The association demonstrated by epidemiological studies, as well as emerging similarities in pathogenesis at the level of the neutrophil, suggest a basis for testing the effects of treatment for one condition upon the severity of the other.,Although the evidence of an independent association between chronic periodontitis and chronic obstructive pulmonary disease grows stronger, there remains a lack of definitive studies designed to establish causality and treatment effects.,There is a need for future research to be focused on answering these questions. | 1 |
A device called FeelBreathe (FB)® was designed, developed, and patented for inspiratory muscle training.,The main aim was to determine the acute responses on lung ventilation, gas exchange, and heart rate during exercise in patients with chronic obstructive pulmonary disease (COPD) with and without the use of FB.,In this study, a randomized cross-over trial was performed with 18 men diagnosed with COPD (FEV1 between 30% and 70% of its predicted value).,Each participant randomly conducted two trials with 30 min of rest between them with the same protocol on a treadmill for 10 min at a constant rate of 50% of VO2peak.,Each test was performed randomly and in a crossover randomized design in two different conditions: (1) oronasal breathing; and (2) nasal breathing with FB (nasal ventilatory flow restriction device).,It was observed that FB had positive effects on dynamic hyperinflation, breathing pattern, and breathing efficiency, with higher expiratory and inspiratory time.,Despite these differences, blood oxygen saturation percentage, oxygen uptake, and heart rate showed a similar response for both conditions during exercise.,The results suggest that exercise performed with FB improved ventilatory responses compared to the oronasal mode in COPD patients.,This new tool could be used during most daily tasks and exercise programs. | Objective: The objective was to assess the effects of a nasal restriction device for inspiratory muscle training, called Feelbreathe®, added to a rehabilitation program (RP) on exercise capacity, quality of life, dyspnea and inspiratory muscle strength in patients with stable COPD.,Methods: Patients were randomized into three groups, one performed a supervised RP using the Feelbreathe® device (FB group), the second group developed the same RP with oronasal breathing without FB (ONB group) and the third was the control group (CG).,We evaluated inspiratory muscle strength (PImax), dyspnea (mMRC), quality of life (CAT) and exercise capacity (6MWT) before and after 8-week of RP.,Results: A total of 16 patients completed the study, seven in FB group, five in ONB group and four in the CG.,After the RP, the FB group showed a significant increase in PImax (93.3 ± 19.1 vs.,123.0 ± 15.8 mmHg) and in the 6MWT distance (462.9 ± 71.8 m vs.,529.1 ± 50.1 m) and a decrease in the CAT score (9.7 ± 6.5 vs.,5.9 ± 6.0) and in the mMRC dyspnea score.,FB provides greater improvement in PImax, dyspnea, quality of life and 6MWT than ONB.,Conclusions: The Feelbreathe® device provides greater improvements in quality of life, dyspnea, exercise capacity and inspiratory muscle strength compared to patients that did not use it. | 1 |
Regular use of inhaled corticosteroids (ICS) in patients with obstructive lung diseases has been associated with a higher risk of pneumonia, particularly in COPD.,The risk of pneumonia has not been previously evaluated in relation to ICS particle size and dose used.,Historical cohort, UK database study of 23,013 patients with obstructive lung disease aged 12-80 years prescribed extra-fine or fine-particle ICS.,The endpoints assessed during the outcome year were diagnosis of pneumonia, acute exacerbations and acute respiratory events in relation to ICS dose.,To determine the association between ICS particle size, dose and risk of pneumonia in unmatched and matched treatment groups, logistic and conditional logistic regression models were used.,14788 patients were stepped-up to fine-particle ICS and 8225 to extra-fine ICS.,On unmatched analysis, patients stepping-up to extra-fine ICS were significantly less likely to be coded for pneumonia (adjusted odds ratio [aOR] 0.60; 95% CI 0.37, 0.97]); experience acute exacerbations (adjusted risk ratio [aRR] 0.91; 95%CI 0.85, 0.97); and acute respiratory events (aRR 0.90; 95%CI 0.86, 0.94) compared with patients stepping-up to fine-particle ICS.,Patients prescribed daily ICS doses in excess of 700 mcg (fluticasone propionate equivalent) had a significantly higher risk of pneumonia (OR [95%CI] 2.38 [1.17, 4.83]) compared with patients prescribed lower doses, irrespective of particle size.,These findings suggest that patients with obstructive lung disease on extra-fine particle ICS have a lower risk of pneumonia than those on fine-particle ICS, with those receiving higher ICS doses being at a greater risk. | This randomized, double-blind, Phase IIIb study evaluated the 24-hour bronchodilatory efficacy of aclidinium bromide versus placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).,Methods: Patients received aclidinium 400 μg twice daily (morning and evening), tiotropium 18 μg once daily (morning), or placebo for 6 weeks.,The primary endpoint was change from baseline in forced expiratory volume in 1 second area under the curve for the 24-hour period post-morning dose (FEV1 AUC0-24) at week 6.,Secondary and additional endpoints included FEV1 AUC12-24, COPD symptoms (EXAcerbations of chronic pulmonary disease Tool-Respiratory Symptoms [E-RS] total score and additional symptoms questionnaire), and safety.,Results: Overall, 414 patients were randomized and treated (FEV1 1.63 L [55.8% predicted]).,Compared with placebo, FEV1 AUC0-24 and FEV1 AUC12-24 were significantly increased from baseline with aclidinium (Δ = 150 mL and 160 mL, respectively; p < 0.0001) and tiotropium (Δ = 140 mL and 123 mL, respectively; p < 0.0001) at week 6.,Significant improvements in E-RS total scores over 6 weeks were numerically greater with aclidinium (p < 0.0001) than tiotropium (p < 0.05) versus placebo.,Only aclidinium significantly reduced the severity of early-morning cough, wheeze, shortness of breath, and phlegm, and of nighttime symptoms versus placebo (p < 0.05).,Adverse-event (AE) incidence (28%) was similar between treatments.,Few anticholinergic AEs (<1.5%) or serious AEs (<3%) occurred in any group.,Conclusions: Aclidinium provided significant 24-hour bronchodilation versus placebo from day 1 with comparable efficacy to tiotropium after 6 weeks.,Improvements in COPD symptoms were consistently numerically greater with aclidinium versus tiotropium.,Aclidinium was generally well tolerated. | 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. | The objective of this pilot study was to investigate the use of and satisfaction with a chronic obstructive pulmonary disease (COPD) telehealth program applied in both primary and secondary care.,The program consisted of four modules: 1) activity coach for ambulant activity monitoring and real-time coaching of daily activity behavior, 2) web-based exercise program for home exercising, 3) self-management of COPD exacerbations via a triage diary on the web portal, including self-treatment of exacerbations, and 4) teleconsultation.,Twenty-nine COPD patients were randomly assigned to either the intervention group (telehealth program for 9 months) or the control group (usual care).,Page hits on the web portal showed the use of the program, and the Client Satisfaction Questionnaire showed satisfaction with received care.,The telehealth program with decision support showed good satisfaction (mean 26.4, maximum score 32).,The program was accessed on 86% of the treatment days, especially the diary.,Patient adherence with the exercise scheme was low (21%).,Health care providers seem to play an important role in patients’ adherence to telehealth in usual care.,Future research should focus on full-scale implementation in daily care and investigating technological advances, like gaming, to increase adherence. | 1 |
The effect of smoking cessation on the oxidative stress in patients with chronic obstructive pulmonary disease (COPD) was assessed.,We recruited 73 smokers with COPD (study group), whose blood was analysed before smoking cessation, after the 1st, 2nd, and 3rd months of abstinence, 35 healthy nonsmokers (Control I), and 35 smokers with COPD (Control II).,Blood was taken once in Control I and 4 times (every month) in Control II.,In the study group conjugated dienes (CDs) level in plasma and erythrocytes before smoking cessation was 3 and 6.5 times higher than in Control I, respectively (P < 0.001), while thiobarbituric acid-reactive substances (TBARS) level was 89% (P < 0.001) and 51% higher (P < 0.01), respectively.,Superoxide dismutase (SOD) activity was 40% higher (P < 0.05) while glutathione peroxidase (GPx) was 41% lower (P < 0.001) than in Control I.,In Control II, the similar differences as compared to Control I were observed throughout the study.,Smoking cessation resulted in decrease of CDs, TBARS, and SOD and GPx increase, with no changes in catalase and vitamins A and E.,COPD is accompanied by oxidative stress.,A three-month tobacco abstinence facilitated restoring the oxidant-antioxidant balance systemically, but it did not affect spirometric parameters. | Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide.,Low-grade systemic inflammation is considered a hallmark of COPD that potentially links COPD to increased rate of systemic manifestations of the disease.,Obesity with/without the metabolic syndrome and cachexia represent two poles of metabolic abnormalities that may relate to systemic inflammation.,On one hand systemic inflammatory syndrome likely reflects inflammation in the lungs, i.e. results from lung-to plasma spillover of inflammatory mediators.,On the other hand, obesity-related hypoxia results in local inflammatory response within adipose tissue per se, and may contribute to elevations in circulatory mediators by spillover from the adipose tissue to the systemic compartment.,The extent to which systemic hypoxia contributes to the adipose tissue inflammation remains unknown.,We assume that in patients with COPD and concurrent obesity at least three factors play a role in the systemic inflammatory syndrome: the severity of pulmonary impairment, the degree of obesity-related adipose tissue hypoxia, and the severity of systemic hypoxia due to reduced pulmonary functions.,The present review summarizes the epidemiological and clinical evidence linking COPD to obesity, the role of adipose tissue as an endocrine organ, and the role of hypoxia in adipose tissue inflammation. | 1 |
Beta (β)-blockers are under-prescribed in patients with heart failure (HF) and concurrent chronic obstructive pulmonary disease (COPD) due to concerns about adverse pulmonary effects and a poor understanding of the effects of these drugs.,We aimed to evaluate the survival effects of β-blockers in patients with coexistent HF and COPD.,Using the Taiwan National Health Insurance Research Database, we conducted a nationwide population-based study.,Patients with coexistent HF and COPD diagnosed between 2000 and 2009 were enrolled.,Doses of the 3 β-blockers proven to be beneficial to HF (carvedilol, bisoprolol, and metoprolol) during the study period were extracted.,The primary endpoint was cumulative survival.,Patients were followed until December 31, 2009.,The study included 11,558 subjects, with a mean follow-up period of 4.07 years.,After adjustment for age, sex, comorbidities, and severity of HF and COPD, bisoprolol use showed a dose-response survival benefit [low dose: adjusted hazard ratio (HR) = 0.76, 95% confidence interval (CI) = 0.59-0.97, P = 0.030; high dose: adjusted HR = 0.40, 95% CI = 0.26-0.63, P < 0.001] compared with nonusers, whereas no survival difference was observed for carvedilol or metoprolol.,Compared with patients with HF alone, this special HF + COPD cohort received significantly fewer targeted β-blockers (108.8 vs 137.3 defined daily doses (DDDs)/person-year, P < 0.001) and bisoprolol (57.9 vs 70.8 DDDs/person-year, P < 0.001).,In patients with coexisting HF and COPD, this study demonstrated a dose-response survival benefit of bisoprolol use, but not of carvedilol or metoprolol use. | Chronic obstructive pulmonary disease (COPD) is present in approximately one-third of all congestive heart failure (CHF) patients, and is a key cause of underprescription and underdosing of β-blockers, largely owing to concerns about precipitating respiratory deterioration.,For these reasons, the aim of this study was to evaluate the impact of β-blockers on the long-term outcomes in CHF patients with COPD.,In addition, we compared the effects of two different β-blockers, carvedilol and bisoprolol.,The study was a retrospective, non-randomized, single center trial.,Acute decompensated HF patients with COPD were classified according to the oral drug used at discharge into β-blocker (n=86; carvedilol [n=52] or bisoprolol [n=34]) and non-β-blocker groups (n=46).,The primary endpoint was all-cause mortality between the β-blocker and non-β-blocker groups during a mean clinical follow-up of 33.9 months.,The secondary endpoints were the differences in all-cause mortality and the hospitalization rates for CHF and/or COPD exacerbation between patients receiving carvedilol and bisoprolol.,The mortality rate was higher in patients without β-blockers compared with those taking β-blockers (log-rank P=0.039), and univariate analyses revealed that the use of β-blockers was the only factor significantly correlated with the mortality rate (hazard ratio: 0.41; 95% confidence interval: 0.17-0.99; P=0.047).,Moreover, the rate of CHF and/or COPD exacerbation was higher in patients treated with carvedilol compared with bisoprolol (log-rank P=0.033).,In the multivariate analysis, only a past history of COPD exacerbation significantly increased the risk of re-hospitalization due to CHF and/or COPD exacerbation (adjusted hazard ratio: 3.11; 95% confidence interval: 1.47-6.61; P=0.003).,These findings support the recommendations to use β-blockers in HF patients with COPD.,Importantly, bisoprolol reduced the incidence of CHF and/or COPD exacerbation compared with carvedilol. | 1 |
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. | Combination of the inhaled long-acting muscarinic antagonist umeclidinium (UMEC; GSK573719) with the long-acting β2-agonist vilanterol (VI) is an approved maintenance treatment for COPD in the US and EU.,We compared the efficacy and safety of UMEC/VI with placebo in patients with COPD of Asian ancestry.,In this 24-week, Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, patients were randomized 1:1:1 to UMEC/VI 125/25 μg, UMEC/VI 62.5/25 μg, or placebo.,The primary efficacy end point was trough forced expiratory volume in 1 second (FEV1) on day 169; secondary end points were Transition Dyspnea Index (TDI) focal score at week 24 and weighted mean (WM) FEV1 over 0-6 hours postdose on day 1.,Additional end points and safety were also assessed.,Both UMEC/VI 125/25 μg and UMEC/VI 62.5/25 μg statistically significantly improved trough FEV1 at day 169 versus placebo (UMEC/VI 125/25 μg, 0.216 L, [95% confidence interval [CI] 0.175-0.257]; UMEC/VI 62.5/25 μg, 0.151 L, 95% CI 0.110-0.191; both P<0.001).,Statistically significant improvements in TDI score were observed for both UMEC/VI groups versus placebo (UMEC/VI 125/25 μg, 0.9, 95% CI 0.3-1.4, P=0.002; UMEC/VI 62.5/25 μg, 0.7, 95% CI 0.1-1.2, P=0.016).,On day 1, both UMEC/VI groups improved 0-6-hour WM FEV1 versus placebo (UMEC/VI 125/25 μg, 0.182 L 95% CI 0.161-0.203; UMEC/VI 62.5/25 μg, 0.160 L, 95% CI 0.139-0.181; both P<0.001).,Statistically significant improvements for UMEC/VI groups versus placebo were observed for rescue albuterol use at weeks 1-24 (puffs/day, both P<0.001).,The incidence of adverse events was similar across groups.,In Asian patients with COPD, once-daily UMEC/VI 125/25 μg and UMEC 62.5/25 μg resulted in clinically meaningful and statistically significant improvements in lung-function end points versus placebo.,Symptomatic and quality of life measures also improved.,The safety profile of UMEC/VI was consistent with previous studies. | 1 |
Smoke exposure is known to decrease total pulmonary surfactant and alter its composition, but the role of surfactant in chronic obstructive pulmonary disease (COPD) remains unknown.,We aimed to analyze the compositional changes in the surfactant lipidome in COPD and identify specific lipids associated with pulmonary function decline.,Bronchoalveolar lavage (BAL) fluid was obtained from 12 former smokers with COPD and 5 non-smoking, non-asthmatic healthy control volunteers.,Lipids were extracted and analyzed by liquid chromatography and mass spectrometry.,Pulmonary function data were obtained by spirometry, and correlations of lung function with lipid species were determined.,Wild-type C57BL/6 mice were exposed to 6 months of second-hand smoke in a full-body chamber.,Surfactant lipids were decreased by 60% in subjects with COPD.,All phospholipid classes were dramatically decreased, including ether phospholipids, which have not been studied in pulmonary surfactant.,Availability of phospholipid, cholesterol, and sphingomyelin in BAL strongly correlated with pulmonary function and this was attributable to specific lipid species of phosphatidylcholine with surface tension reducing properties, and of phosphatidylglycerol with antimicrobial roles, as well as to other less studied lipid species.,Mice exposed to smoke for six months recapitulated surfactant lipidomic changes observed in human subjects with COPD.,In summary, we show that the surfactant lipidome is substantially altered in subjects with COPD, and decreased availability of phospholipids correlated with decreased pulmonary function.,Further investigation of surfactant alterations in COPD would improve our understanding of its physiopathology and reveal new potential therapeutic targets. | COPD is underdiagnosed and its early assessment is problematic.,It has been suggested that symptomatic smokers with normal FEV1/FVC (Stage 0 COPD, GOLD criteria) can develop COPD in the future.,Potential early biomarkers in COPD include the matrix metallo-proteinases (MMPs).,It is not yet known, whether alterations in MMP expression are associated with smoking alone or with the risk of developing COPD.,In this cross-sectional study MMP-8, MMP-9 and MMP-12 were determined from induced sputum and plasma by ELISA, immunocytochemistry, zymography, and/or Western blot in non-smokers (n = 32), smokers with symptoms (Stage 0, GOLD criteria) (n = 23) or without symptoms (n = 23).,Only MMP-8 differentiated Stage 0 COPD from non-symptomatic smokers (p = 0.02).,MMP-9 levels were significantly elevated in the induced sputum of non-symptomatic smokers and Stage 0 COPD (p = 0.01, p < 0.001) compared to non-smokers, but did not differ between the two subgroups of smokers.,MMP-12 was higher only at Stage 0 compared to non-smokers (p = 0.04).,MMP-8, MMP-9 and MMP-12 immunoreactivity was localized in macrophages and neutrophils, especially in smokers.,MMP-8 levels correlated significantly with the small airway flow parameters (MEF50, MEF25) (p = 0.005 and p = 0.0004) and markers of neutrophil activation (myeloperoxidase, lactoferrin).,In conclusion MMP-8 may differentiate Stage 0 from healthy smokers. | 1 |
The burden of chronic obstructive lung disease (COPD) is increasing in women, with recent evidence suggesting gender differences in disease characteristics and potentially in treatment outcomes.,FLAME was a 52-week randomized controlled trial in patients with severe-to-very-severe COPD and a history of exacerbations.,In this post-hoc analysis, gender-based baseline differences and treatment outcomes between indacaterol/glycopyrronium 110/50 μg once daily (IND/GLY) and salmeterol/fluticasone 50/500 twice daily (SFC) were assessed in terms of rate of exacerbations, time-to-first exacerbation, lung function, health status, and rescue medication use.,This post-hoc analysis included 2557 men and 805 women.,Baseline characteristics differed between genders, with women being younger, having better lung function and more often experiencing ≥2 exacerbations in the previous year.,Compared with SFC, IND/GLY treatment was associated with reductions in the annualized rates of moderate/severe exacerbations (rate ratio [95% CI]: 0.81 [0.73-0.91], 0.89 [0.74-1.07] in men and women, respectively).,Similarly, time-to-first moderate/severe exacerbation was also delayed (hazard ratio [95% CI]: 0.79 [0.70-0.89] and 0.76 [0.63-0.91] in men and women, respectively).,Results were similar for all (mild/moderate/severe) exacerbations.,Improvements in lung function, health status and rescue medication use with IND/GLY vs SFC were comparable between men and women.,The smaller sample size for women may account for some observed discrepancies in treatment responses.,Although there were gender differences in baseline characteristics, IND/GLY demonstrated similar trends for exacerbation prevention and lung function improvement in men and women with moderate-to-very-severe COPD and a history of exacerbations compared with SFC.,Small differences in the effects seen between genders may be attributed to the different sizes of the two groups and need to be further evaluated in randomized trials that are appropriately powered for gender analysis.,Post hoc analysis of the FLAME study.,ClinicalTrials.gov number: NCT01782326.,Registered 1 February 2013. | T lymphocytes are believed to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD).,How T cells are recruited to the lungs and contribute to the inflammatory process is largely unknown.,COPD is a heterogeneous disease, and discriminating disease phenotypes based on distinct molecular and cellular pathways may provide new approaches for individualized diagnosis and therapies.,Bronchoalveolar lavage (BAL) and blood samples were obtained from 40 never-smokers, 40 smokers with normal lung function, and 38 COPD patients.,T-cell chemokine receptor expression was analyzed with flow cytometry, and soluble BAL cytokines and chemokines were measured using a cytokine multiplex assay.,Correlations with gender and clinical characteristics including lung imaging were investigated using multivariate modeling.,Th1/Tc1- and Th2/Tc2-associated soluble analytes and T-cell chemokine receptors were analyzed as cumulative Th1/Tc1 and Th2/Tc2 immune responses.,A higher expression of chemokine receptor CCR5 on CD8+ T cells in BAL and higher percentage of CXCR3+CD8+ T cells in blood was found in female smokers with COPD compared to those without COPD.,CCR5 expression on CD4+ and CD8+ T cells was lower in BAL from male smokers with COPD compared to those without COPD.,Among female smokers with COPD, Th1/Tc1 immune response was linked to BAL macrophage numbers and goblet cell density, and Th2/Tc2 response was associated with the measures of emphysema on high-resolution computed tomography.,The highly gender-dependent T-cell profile in COPD indicates different links between cellular events and clinical manifestations in females compared to males.,Our findings may reveal mechanisms of importance for the difference in clinical course in female COPD patients compared to males. | 1 |
The aetiology of acute exacerbations of COPD (AECOPD) is incompletely understood.,Understanding the relationship between chronic bacterial airway infection and viral exposure may explain the incidence and seasonality of these events.,In this prospective, observational cohort study (NCT01360398), patients with COPD aged 40-85 years underwent sputum sampling monthly and at exacerbation for detection of bacteria and viruses.,Results are presented for subjects in the full cohort, followed for 1 year.,Interactions between exacerbation occurrence and pathogens were investigated by generalised estimating equation and stratified conditional logistic regression analyses.,The mean exacerbation rate per patient-year was 3.04 (95% CI 2.63 to 3.50).,At AECOPD, the most common bacterial species were non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis, and the most common virus was rhinovirus.,Logistic regression analyses (culture bacterial detection) showed significant OR for AECOPD occurrence when M. catarrhalis was detected regardless of season (5.09 (95% CI 2.76 to 9.41)).,When NTHi was detected, the increased risk of exacerbation was greater in high season (October-March, OR 3.04 (1.80 to 5.13)) than low season (OR 1.22 (0.68 to 2.22)).,Bacterial and viral coinfection was more frequent at exacerbation (24.9%) than stable state (8.6%).,A significant interaction was detected between NTHi and rhinovirus presence and AECOPD risk (OR 5.18 (1.92 to 13.99); p=0.031).,AECOPD aetiology varies with season.,Rises in incidence in winter may be driven by increased pathogen presence as well as an interaction between NTHi airway infection and effects of viral infection.,Results, NCT01360398. | Potentially pathogenic microorganisms can be detected by quantitative real-time polymerase chain reaction (qPCR) in sputum from patients with COPD, although how this technique relates to culture and clinical measures of disease is unclear.,We used cross-sectional and longitudinal data to test the hypotheses that qPCR is a more sensitive measure of bacterial presence and is associated with neutrophilic airway inflammation and adverse clinical outcomes.,Sputum was collected from 174 stable COPD subjects longitudinally over 12 months.,Microbial sampling using culture and qPCR was performed.,Spirometry and sputum measures of airway inflammation were assessed.,Sputum was qPCR-positive (>106 copies/mL) in 77/152 samples (Haemophilus influenzae [n=52], Moraxella catarrhalis [n=24], Streptococcus pneumoniae [n=19], and Staphylococcus aureus [n=7]).,Sputum was culture-positive in 50/174 samples, with 49 out of 50 culture-positive samples having pathogen-specific qPCR bacterial loads >106 copies/mL.,Samples that had qPCR copy numbers >106/mL, whether culture-positive or not, had increased sputum neutrophil counts.,H. influenzae qPCR copy numbers correlated with sputum neutrophil counts (r=0.37, P<0.001), were repeatable within subjects, and were >106/mL three or more times in 19 patients, eight of whom were repeatedly sputum culture-positive.,Persistence, whether defined by culture, qPCR, or both, was associated with a higher sputum neutrophil count, lower forced expiratory volume in 1 second (FEV1), and worsened quality of life.,qPCR identifies a significant number of patients with potentially bacteria-associated neutrophilic airway inflammation and disease that are not identified by traditional culture-based methods. | 1 |
Data have highlighted the potential bias introduced by withdrawal of inhaled corticosteroids at randomization in chronic obstructive pulmonary disease trials examining inhaled corticosteroids.,Analyses were conducted to determine whether this was true of inhaled anticholinergic withdrawal in tiotropium trials.,A pooled analysis of randomized, double-blind, placebo-controlled, parallel-group tiotropium trials of at least six months’ duration was performed.,Trials had similar inclusion and exclusion criteria.,Exacerbation definition was standardized.,Patients were divided into two groups, ie, D (anticholinergics discontinued at randomization, previously prescribed) and ND (anticholinergics not discontinued, not previously prescribed).,Demographics were balanced between the D (n = 5846) and ND (n = 6317) groups, except for higher cumulative smoking (56 pack-years versus 48 pack-years), lower forced expiratory volume in one second (FEV1)/forced vital capacity (43% versus 48%), and lower baseline FEV1 (35.8% predicted versus 42.4% predicted) in the D group.,In both groups, tiotropium reduced the risk for an exacerbation (hazard ratio [HR] = 0.83, P < 0.0001 [D] versus 0.79, P < 0.0001 [ND]) and a hospitalized exacerbation (HR = 0.85, P = 0.0467 versus 0.79, P = 0.0094).,Tiotropium reduced the number of exacerbations per patient-year (rate ratio [RR] = 0.82, P < 0.0001 [D] versus RR = 0.80, P < 0.0001 [ND]) and associated hospitalizations per patient-year (RR = 0.88, P = 0.015 [D] versus RR = 0.74, P < 0.0001 [ND]).,Tiotropium reduced exacerbations in patients who did and did not have anticholinergics discontinued upon randomization in clinical trials. | Objective To systematically review the risk of mortality associated with long term use of tiotropium delivered using a mist inhaler for symptomatic improvement in chronic obstructive pulmonary disease.,Data sources Medline, Embase, the pharmaceutical company clinical trials register, the US Food and Drug Administration website, and ClinicalTrials.gov for randomised controlled trials from inception to July 2010.,Study selection Trials were selected for inclusion if they were parallel group randomised controlled trials of tiotropium solution using a mist inhaler (Respimat Soft Mist Inhaler, Boehringer Ingelheim) versus placebo for chronic obstructive pulmonary disease; the treatment duration was more than 30 days, and they reported data on mortality.,Relative risks of all cause mortality were estimated using a fixed effect meta-analysis, and heterogeneity was assessed with the I2 statistic.,Results Five randomised controlled trials were eligible for inclusion.,Tiotropium mist inhaler was associated with a significantly increased risk of mortality (90/3686 v 47/2836; relative risk 1.52, 95% confidence interval, 1.06 to 2.16; P=0.02; I2=0%).,Both 10 µg (2.15, 1.03 to 4.51; P=0.04; I2=9%) and 5 µg (1.46, 1.01 to 2.10; P=0.04; I2=0%) doses of tiotropium mist inhaler were associated with an increased risk of mortality.,The overall estimates were not substantially changed by sensitivity analysis of the fixed effect analysis of the five trials combined using the random effects model (1.45, 1.02 to 2.07; P=0.04), limiting the analysis to three trials of one year’s duration each (1.50, 1.05 to 2.15), or the inclusion of additional data on tiotropium mist inhaler from another investigational drug programme (1.42, 1.01 to 2.00).,The number needed to treat for a year with the 5 µg dose to see one additional death was estimated to be 124 (95% confidence interval 52 to 5682) based on the average control event rate from the long term trials.,Conclusions This meta-analysis explains safety concerns by regulatory agencies and indicates a 52% increased risk of mortality associated with tiotropium mist inhaler in patients with chronic obstructive pulmonary disease. | 1 |
Comorbidities are frequent in chronic obstructive pulmonary disease (COPD) and significantly impact on patients’ quality of life, exacerbation frequency, and survival.,There is increasing evidence that certain diseases occur in greater frequency amongst patients with COPD than in the general population, and that these comorbidities significantly impact on patient outcomes.,Although the mechanisms are yet to be defined, many comorbidities likely result from the chronic inflammatory state that is present in COPD.,Common problems in the clinical management of COPD include recognizing new comorbidities, determining the impact of comorbidities on patient symptoms, the concurrent treatment of COPD and comorbidities, and accurate prognostication.,The majority of comorbidities in COPD should be treated according to usual practice, and specific COPD management is infrequently altered by the presence of comorbidities.,Unfortunately, comorbidities are often under-recognized and under-treated.,This review focuses on the epidemiology of ten major comorbidities in patients with COPD.,Further, we emphasize the clinical impact upon prognosis and management considerations.,This review will highlight the importance of comorbidity identification and management in the practice of caring for patients with COPD. | Little is known about iron deficiency (ID) and anemia in Chronic Obstructive Pulmonary Disease (COPD).,The purposes of this study were: (i) To study the prevalence and treatment of anemia and ID in patients hospitalized with an exacerbation of COPD. (ii) to study the hematological responses and degree of dyspnea before and after correction of anemia with subcutaneous Erythropoiesis Stimulating Agents (ESAs) and intravenous (IV) iron therapy, in ambulatory anemic patients with both COPD and chronic kidney disease.,(i) We examined the hospital records of all patients with an acute exacerbation of COPD (AECOPD) to assess the investigation, prevalence, and treatment of anemia and ID. (ii) We treated 12 anemic COPD outpatients with the combination of ESAs and IV-iron, given once weekly for 5 weeks.,One week later we measured the hematological response and the severity of dyspnea by Visual Analogue Scale (VAS).,(i) Anemia and iron deficiency in hospitalized COPD patients: Of 107 consecutive patients hospitalized with an AECOPD, 47 (43.9%) were found to be anemic on admission.,Two (3.3%) of the 60 non-anemic patients and 18 (38.3%) of the 47 anemic patients had serum iron, percent transferrin saturation (%Tsat) and serum ferritin measured.,All 18 (100%) anemic patients had ID, yet none had oral or IV iron subscribed before or during hospitalization, or at discharge. (ii) Intervention outpatient study: ID was found in 11 (91.7%) of the 12 anemic ambulatory patients.,Hemoglobin (Hb), Hematocrit (Hct) and the VAS scale scores increased significantly with the ESAs and IV-iron treatment.,There was a highly significant correlation between the ∆Hb and ∆VAS; rs = 0.71 p = 0.009 and between the ∆Hct and ∆VAS; rs = 0.8 p = 0.0014.,ID is common in COPD patients but is rarely looked for or treated.,Yet correction of the ID in COPD patients with ESAs and IV iron can improve the anemia, the ID, and may improve the dyspnea. | 1 |
Chronic obstructive pulmonary disease (COPD) exacerbations are accompanied with increased systemic inflammation, which accelerate the pulmonary function injury and impair the quality of life.,Prompt and effective treatments for COPD exacerbations slow down the disease progression, but an objective instrument to assess the efficacy of the treatments following COPD exacerbations is lacking nowadays.,The COPD Assessment Test (CAT) is an 8-item questionnaire designed to assess and quantify health status and symptom burden in COPD patients.,We hypothesize that the change in CAT score is related to the treatment response following COPD exacerbations.,78 inpatients with clinician-diagnosed acute exacerbation of COPD (AECOPD) completed the CAT, St George’s Respiratory Questionnaire (SGRQ) and modified Medical Research Council (mMRC) Dyspnea Scale both at exacerbation and the 7th day of therapy, and a subgroup of 39 patients performed the pulmonary function test.,Concentrations of serum C-reactive protein (CRP) and plasma fibrinogen were assayed at the same time.,Correlations between the CAT and other measurements were examined.,After 7 days’ therapy, the CAT and SGRQ scores, mMRC grades, as well as the concentrations of CRP and fibrinogen all decreased significantly (P < 0.001).,Meanwhile, the FEV1% predicted had a significant improvement (P < 0.001).,The CAT scores were significantly correlated with concurrent concentrations of CRP and fibrinogen, SGRQ scores, FEV1% predicted and mMRC grades (P < 0.05).,The change in CAT score was positively correlated with the change of CRP (r = 0.286, P < 0.05), SGRQ score (r = 0.725, P < 0.001) and mMRC grades (r = 0.593, P < 0.001), but not with fibrinogen (r = 0.137, P > 0.05) or FEV1% predicted (r = -0.101, P > 0.05).,No relationship was found between the changes of SGRQ score and CRP and fibrinogen (P>0.05).,The CAT is associate with the changes of systemic inflammation following COPD exacerbations.,Moreover, the CAT is responsive to the treatments, similar to other measures such as SGRQ, mMRC dyspnea scale and pulmonary function.,Therefore, the CAT is a potentially useful instrument to assess the efficacy of treatments following COPD exacerbations. | COPD is prevalent in Western society and its incidence is rising in the developing world.,Acute exacerbations of COPD, about 50% of which are unreported, lead to deterioration in quality of life and contribute significantly to disease burden.,Quality of life deteriorates with time; thus, most of the health burden occurs in more severe disease.,COPD severity and frequent and more severe exacerbations are all related to an increased risk of mortality.,Inhaled corticosteroids (ICS) have similar effects on quality of life but ICS/long-acting bronchodilator combinations and the long-acting antimuscarinic tiotropium all improve health status and exacerbation rates and are likely to have an effect on mortality but perhaps only with prolonged use.,Erythromycin has been shown to decrease the rate of COPD exacerbations.,Pulmonary rehabilitation and regular physical activity are indicated in all severities of COPD and improve quality of life.,Noninvasive ventilation is associated with improved quality of life.,Long-term oxygen therapy improves mortality but only in hypoxic COPD patients.,The choice of an inhaler device is a key component of COPD therapy and this requires more attention from physicians than perhaps we are aware of.,Disease management programs, characterized as they are by patient centeredness, improve quality of life and decrease hospitalization rates.,Most outcomes in COPD can be modified by interventions and these are well tolerated and have acceptable safety profiles. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation, mucus hypersecretion, and emphysema, which lead to reduced lung function and breathlessness.,The pathologies of COPD are due to an abnormal immune response.,Invariant natural killer T (iNKT) cells are an important population of innate lymphocytes and have been implicated in the regulation of immune responses associated with a broad range of diseases including COPD.,We have here analyzed the role of iNKT cells in a model of COPD induced by repeated intranasal administration of iNKT cell agonist α-galactosylceramide (α-GalCer).,Our results demonstrated that mice that received repeated intranasal administration of α-GalCer had molecular and inflammatory features of COPD including airway inflammation with significant increases in infiltration of macrophages and lymphocytes, CD8+ T cells, as well as proinflammatory cytokines IL-6 and TNF-α.,In particular, these mice also showed the presence of pulmonary emphysema, mucus production, and pulmonary fibrosis.,Furthermore, neutralization of IL-4 reduced α-GalCer induced emphysema.,This study indicates the importance of iNKT cells in the pathogenesis of COPD by an IL-4 dependent mechanism. | Regulatory T cells have been implicated in the pathogenesis of COPD by the increased expression of CD25 on helper T cells along with enhanced intracellular expression of FoxP3 and low/absent CD127 expression on the cell surface.,Regulatory T cells were investigated in BALF from nine COPD subjects and compared to fourteen smokers with normal lung function and nine never-smokers.,In smokers with normal lung function, the expression of CD25+CD4+ was increased, whereas the proportions of FoxP3+ and CD127+ were unchanged compared to never-smokers.,Among CD4+ cells expressing high levels of CD25, the proportion of FoxP3+ cells was decreased and the percentage of CD127+ was increased in smokers with normal lung function.,CD4+CD25+ cells with low/absent CD127 expression were increased in smokers with normal lung function, but not in COPD, when compared to never smokers.,The reduction of FoxP3 expression in BALF from smokers with normal lung function indicates that the increase in CD25 expression is not associated with the expansion of regulatory T cells.,Instead, the high CD127 and low FoxP3 expressions implicate a predominantly non-regulatory CD25+ helper T-cell population in smokers and stable COPD.,Therefore, we suggest a smoking-induced expansion of predominantly activated airway helper T cells that seem to persist after COPD development. | 1 |
Neutrophils play a central role in innate immunity, inflammation, and resolution.,Unresolving neutrophilia features as a disrupted inflammatory process in the airways of patients with chronic obstructive pulmonary disease (COPD) and severe asthma.,The extent to which this may be linked to disease pathobiology remains obscure and could be further confounded by indication of glucocorticoids or concomitant respiratory infections.,The formation of neutrophil extracellular traps (NETs) represents a specialized host defense mechanism that entrap and eliminate invading microbes.,NETs are web-like scaffolds of extracellular DNA in complex with histones and neutrophil granular proteins, such as myeloperoxidase and neutrophil elastase.,Distinct from apoptosis, NET formation is an active form of cell death that could be triggered by various microbial, inflammatory, and endogenous or exogenous stimuli.,NETs are reportedly enriched in neutrophil-dominant refractory lung diseases, such as COPD and severe asthma.,Evidence for a pathogenic role for respiratory viruses (e.g., Rhinovirus), bacteria (e.g., Staphylococcus aureus) and fungi (e.g., Aspergillus fumigatus) in NET induction is emerging.,Dysregulation of this process may exert localized NET burden and contribute to NETopathic lung inflammation.,Disentangling the role of NETs in human health and disease offer unique opportunities for therapeutic modulation.,The chemokine CXCR2 receptor regulates neutrophil activation and migration, and small molecule CXCR2 antagonists (e.g., AZD5069, danirixin) have been developed to selectively block neutrophilic inflammatory pathways.,NET-stabilizing agents using CXCR2 antagonists are being investigated in proof-of-concept studies in patients with COPD to provide mechanistic insights.,Clinical validation of this type could lead to novel therapeutics for multiple CXCR2-related NETopathologies.,In this Review, we discuss the emerging role of NETs in the clinicopathobiology of COPD and severe asthma and provide an outlook on how novel NET-stabilizing therapies via CXCR2 blockade could be leveraged to disrupt NETopathic inflammation in disease-specific phenotypes. | We have previously shown that NK (CD56+CD3-) and NKT-like (CD56+CD3+) cells are reduced in both numbers and cytotoxicity in peripheral blood.,The aim of the present study was to investigate their numbers and function within induced sputum.,Induced sputum cell numbers and intracellular granzyme B and perforin were analysed by flow cytometry.,Immunomagnetically selected CD56+ cells (NK and NKT-like cells) were used in an LDH release assay to determine cytotoxicity.,The proportion of NK cells and NKT-like cells in smokers with COPD (COPD subjects) was significantly higher (12.7% and 3%, respectively) than in healthy smokers (smokers) (5.7%, p < 0.01; 1%, p < 0.001) and non-smoking healthy subjects (HNS) (4.2%, p < 0.001; 0.8%, p < 0.01).,The proportions of NK cells and NKT-like cells expressing both perforin and granzyme B were also significantly higher in COPD subjects compared to smokers and HNS.,CD56+ cells from COPD subjects were significantly more cytotoxic (1414 biological lytic activity) than those from smokers (142.5; p < 0.01) and HNS (3.8; p < 0.001) and were inversely correlated to FEV1. (r = -0.75; p = 0.0098).,We have shown an increased proportion of NK and NKT-like cells in the induced sputum of COPD subjects and have demonstrated that these cells are significantly more cytotoxic in COPD subjects than smokers and HNS. | 1 |
There is no clinically useful score to predict chronic obstructive pulmonary disease (COPD) exacerbations.,We aimed to derive this by analyzing data from three existing COPD clinical trials of budesonide/formoterol, formoterol, or placebo in patients with moderate-to-very-severe COPD and a history of exacerbations in the previous year.,Predictive variables were selected using Cox regression for time to first severe COPD exacerbation.,We determined absolute risk estimates for an exacerbation by identifying variables in a binomial model, adjusting for observation time, study, and treatment.,The model was further reduced to clinically useful variables and the final regression coefficients scaled to obtain risk scores of 0-100 to predict an exacerbation within 6 months.,Receiver operating characteristic (ROC) curves and the corresponding C-index were used to investigate the discriminatory properties of predictive variables.,The best predictors of an exacerbation in the next 6 months were more COPD maintenance medications prior to the trial, higher mean daily reliever use, more exacerbations during the previous year, lower forced expiratory volume in 1 second/forced vital capacity ratio, and female sex.,Using these risk variables, we developed a score to predict short-term (6-month) risk of COPD exacerbations (SCOPEX).,Budesonide/formoterol reduced future exacerbation risk more than formoterol or as-needed short-acting β2-agonist (salbutamol).,SCOPEX incorporates easily identifiable patient characteristics and can be readily applied in clinical practice to target therapy to reduce COPD exacerbations in patients at the highest risk. | To quantify the relationship between severity of chronic obstructive pulmonary disease (COPD) as expressed by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and the annual exacerbation frequency in patients with COPD.,We performed a systematic literature review to identify randomized controlled trials and cohort studies reporting the exacerbation frequency in COPD patients receiving usual care or placebo.,Annual frequencies were determined for total exacerbations defined by an increased use of health care (event-based), total exacerbations defined by an increase of symptoms, and severe exacerbations defined by a hospitalization.,The association between the mean forced expiratory volume in one second (FEV1)% predicted of study populations and the exacerbation frequencies was estimated using weighted log linear regression with random effects.,The regression equations were applied to the mean FEV1% predicted for each GOLD stage to estimate the frequency per stage.,Thirty-seven relevant studies were found, with 43 reports of total exacerbation frequency (event-based, n = 19; symptom-based, n = 24) and 14 reports of frequency of severe exacerbations.,Annual event-based exacerbation frequencies per GOLD stage were estimated at 0.82 (95% confidence interval 0.46-1.49) for mild, 1.17 (0.93-1.50) for moderate, 1.61 (1.51-1.74) for severe, and 2.10 (1.51-2.94) for very severe COPD.,Annual symptom-based frequencies were 1.15 (95% confidence interval 0.67-2.07), 1.44 (1.14-1.87), 1.76 (1.70-1.88), and 2.09 (1.57-2.82), respectively.,For severe exacerbations, annual frequencies were 0.11 (95% confidence interval 0.02-0.56), 0.16 (0.07-0.33), 0.22 (0.20-0.23), and 0.28 (0.14-0.63), respectively.,Study duration or type of study (cohort versus trial) did not significantly affect the outcomes.,This study provides an estimate of the exacerbation frequency per GOLD stage, which can be used for health economic and modeling purposes. | 1 |
Inhaled drug delivery is the cornerstone treatment for asthma and chronic obstructive pulmonary disease (COPD).,However, use of inhaler devices can be challenging, potentially leading to critical errors in handling that can significantly reduce drug delivery to the lungs and effectiveness of treatment.,A systematic review was conducted to define ‘critical’ errors and their impact on health outcomes and resource use between 2004 and 2016, using key search terms for inhaler errors in asthma and COPD (Search-1) and associated health-economic and patient burden (Search-2).,Search-1 identified 62 manuscripts, 47 abstracts, and 5 conference proceedings (n = 114 total).,Search-2 identified 9 studies.,We observed 299 descriptions of critical error.,Age, education status, previous inhaler instruction, comorbidities and socioeconomic status were associated with worse handling error frequency.,A significant association was found between inhaler errors and poor disease outcomes (exacerbations), and greater health-economic burden.,We have shown wide variations in how critical errors are defined, and the evidence shows an important association between inhaler errors and worsened health outcomes.,Given the negative impact diminished disease outcomes impose on resource use, our findings highlight the importance of achieving optimal inhaler technique, and a need for a consensus on defining critical and non-critical errors.,The online version of this article (10.1186/s12931-017-0710-y) contains supplementary material, which is available to authorized users. | For optimal efficacy, an inhaler should deliver doses consistently and be easy for patients to use with minimal instruction.,The delivery characteristics, patients’ correct use, and preference of two single-dose dry powder inhalers (Breezhaler and HandiHaler) were evaluated in two complementary studies.,The first study examined aerodynamic particle size distribution, using inhalation profiles of seven patients with moderate to very severe chronic obstructive pulmonary disease (COPD).,The second was an open-label, two-period, 7-day crossover study, evaluating use of the inhalers with placebo capsules by 82 patients with mild to severe COPD.,Patients’ correct use of the inhalers was assessed after reading written instructions on Day 1, and after training and 7 days of daily use.,Patients’ preference was assessed after completion of both study periods.,Patient inhalation profiles showed average peak inspiratory flows of 72 L/minute through Breezhaler and 36 L/minute through HandiHaler.,For Breezhaler and HandiHaler, fine particle fractions were 27% and 10%, respectively.,In the second study, correct use of Breezhaler and HandiHaler was achieved by >77% of patients for any step after 7 days; 61% of patients showed an overall preference for Breezhaler and 31% for HandiHaler (P = 0.01).,Breezhaler is a low-resistance inhaler suitable for use by patients with a range of disease severities.,Most patients used both inhalers correctly after 7 days, but more patients showed an overall preference for the Breezhaler compared with the HandiHaler.,These are important factors for optimum dose delivery and successful COPD management. | 1 |
To estimate patient- and episode-level direct costs of chronic obstructive pulmonary disease (COPD) among commercially insured patients in the US.,In this retrospective claims-based analysis, commercial enrollees with evidence of COPD were grouped into five mutually exclusive cohorts based on the most intensive level of COPD-related care they received in 2006, ie, outpatient, urgent outpatient (outpatient care in addition to a claim for an oral corticosteroid or antibiotic within seven days), emergency department (ED), standard inpatient admission, and intensive care unit (ICU) cohorts.,Patient- level COPD-related annual health care costs, including patient- and payer-paid costs, were compared among the cohorts.,Adjusted episode-level costs were calculated.,Of the 37,089 COPD patients included in the study, 53% were in the outpatient cohort, 37% were in the urgent outpatient cohort, 3% were in the ED cohort, and the standard admission and ICU cohorts together comprised 6%.,Mean (standard deviation, SD) annual COPD-related health care costs (2008 US$) increased across the cohorts (P < 0.001), ranging from $2003 ($3238) to $43,461 ($76,159) per patient.,Medical costs comprised 96% of health care costs for the ICU cohort.,Adjusted mean (SD) episode-level costs were $305 ($310) for an outpatient visit, $274 ($336) for an urgent outpatient visit, $327 ($65) for an ED visit, $9745 ($2968) for a standard admission, and $33,440 for an ICU stay.,Direct costs of COPD-related care for commercially insured patients are driven by hospital stays with or without ICU care.,Exacerbation prevention resulting in reduced need for inpatient care could lower costs. | An exacerbation of chronic obstructive pulmonary disease (COPD) is the most common respiratory condition necessitating admission to hospital.,Many of these are relatively mild in nature and as a consequence, there is increasing interest in immediate and early discharge of patients with nonsevere exacerbations.,Following initial assessment, “hospital at home” or “assisted discharge” schemes enable suitable patients with COPD to be discharged into the community earlier than normally anticipated.,The putative implication is that substantial financial savings can be made in addition to increasing the availability of in-patient beds, without compromising patient care or satisfaction.,We highlight the current literature which has evaluated the role of hospital at home and assisted discharge schemes and discuss our own “real life” service operating in a large teaching hospital in Scotland. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) have increased susceptibility to respiratory tract infection, which contributes to disease progression and mortality, but mechanisms of increased susceptibility to infection remain unclear.,The aim of this study was to determine whether glucose concentrations were increased in airway samples (nasal lavage fluid, sputum, and bronchoalveolar lavage fluid) from patients with stable COPD and to determine the effects of viral infection on sputum glucose concentrations and how airway glucose concentrations relate to bacterial infection.,We measured glucose concentrations in airway samples collected from patients with stable COPD and smokers and nonsmokers with normal lung function.,Glucose concentrations were measured in patients with experimentally induced COPD exacerbations, and these results were validated in patients with naturally acquired COPD exacerbations.,Relationships between sputum glucose concentrations, inflammatory markers, and bacterial load were examined.,Sputum glucose concentrations were significantly higher in patients with stable COPD compared with those in control subjects without COPD.,In both experimental virus-induced and naturally acquired COPD exacerbations, sputum and nasal lavage fluid glucose concentrations were increased over baseline values.,There were significant correlations between sputum glucose concentrations and sputum inflammatory markers, viral load, and bacterial load.,Airway samples with higher glucose concentrations supported more Pseudomonas aeruginosa growth in vitro.,Airway glucose concentrations are increased in patients with stable COPD and further increased during COPD exacerbations.,Increased airway glucose concentrations might contribute to bacterial infections in both patients with stable and those with exacerbated COPD.,This has important implications for the development of nonantibiotic therapeutic strategies for the prevention or treatment of bacterial infection in patients with COPD. | Oxidative stress is associated with the pathogenesis of cigarette smoke related lung diseases, but longitudinal effects of smoking cessation on oxidant markers in the airways are unknown.,This study included 61 smokers; 21 with chronic bronchitis or COPD, 15 asthmatics and 25 asymptomatic smokers followed up for 3 months after smoking cessation.,Fractional exhaled nitric oxide (FeNO), sputum neutrophil counts, sputum 8-isoprostane, nitrotyrosine and matrix metalloproteinase-8 (MMP-8) were investigated at baseline and 1 and 3 months after smoking cessation.,After 3 months 15 subjects had succeeded in quitting of smoking and in these subjects symptoms improved significantly.,Unexpectedly, however, sputum neutrophils increased (p = 0.046) after smoking cessation in patients with chronic bronchitis/COPD.,At baseline, the other markers did not differ between the three groups so these results were combined for further analysis.,Sputum 8-isoprostane declined significantly during the follow-up at 3 months (p = 0.035), but levels still remained significantly higher than in non-smokers.,The levels of FeNO, nitrotyrosine and MMP-8 did not change significantly during the 3 months after smoking cessation.,Whilst symptoms improve after smoking cessation, the oxidant and protease burden in the airways continues for months. | 1 |
31-77% of patients with COPD have vitamin D deficiency and insufficiency, with results being highly variable between studies.,Vitamin D may also correlate with disease characteristics.,To find out the prevalence of vitamin D deficiency and insufficiency in patients with COPD admitted for exacerbation and a risk factors for lower vitamin D levels among comorbidities and COPD characteristics.,152 patients were studied for vitamin D serum levels (25(OH)D).,All of them were also assessed for diabetes mellitus (DM) and metabolic syndrome (MS).,Data were gathered also for smoking status and exacerbations in last year.,All patients completed CAT and mMRC questionnaires and underwent spirometry.,A total of 83,6% of patients have reduced levels of vitamin D. 42,8% (65/152) have vitamin D insufficiency (defined as 25-50 nmol/L) and 40,8% (62/152) have vitamin D deficiency (<25 nmol/L).,The mean level of 25(OH)D for all patients is 31,97 nmol/L (95%CI 29,12-34,68).,Vitamin D deficiency and insufficiency are more prevalent in females vs. males (97,7 vs 77,8%; p = 0.003).,The prevalence and severity of vitamin D deficiency and insufficiency in this study is significantly higher when compared to an unselected Bulgarian population (prevalence 75,8%; mean level 38,75 nmol/L).,Vitamin D levels correlate with quality of life (measured by the mMRC scale) and lung function (FVC, FEV1, FEV6, FEF2575, FEV3, but not with FEV1/FVC ratio and PEF), it does not correlate with the presence of arterial hypertension, DM, MS and number of moderate, severe and total exacerbations.,Vitamin D deficiency is a risk factor for longer hospital stay.,The patients with COPD admitted for exacerbation are a risk group for vitamin D deficiency and insufficiency, which is associated with worse disease characteristics. | COPD patients may be at increased risk for vitamin D (25(OH)D) deficiency, but risk factors for deficiency among COPD patients have not been extensively reported.,Serum 25(OH)D levels were measured by liquid chromatography double mass spectrometry in subjects aged 40-76 years from Western Norway, including 433 COPD patients (GOLD stage II-IV) and 325 controls.,Levels <20 ng/mL defined deficiency.,Season, sex, age, body mass index (BMI), smoking, GOLD stage, exacerbation frequency, arterial oxygen tension (PaO2), respiratory symptoms, depression (CES-D score≥16), comorbidities (Charlson score), treatment for osteoporosis, use of inhaled steroids, and total white blood count were examined for associations with 25(OH)D in both linear and logistic regression models.,COPD patients had an increased risk for vitamin D deficiency compared to controls after adjustment for seasonality, age, smoking and BMI.,Variables associated with lower 25(OH)D levels in COPD patients were obesity ( = −6.63), current smoking ( = −4.02), GOLD stage III- IV ( = −4.71, = −5.64), and depression ( = −3.29).,Summertime decreased the risk of vitamin D deficiency (OR = 0.22).,COPD was associated with an increased risk of vitamin D deficiency, and important disease characteristics were significantly related to 25(OH)D levels. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) are progressively limited in their ability to undertake normal everyday activities by a combination of exertional dyspnoea and peripheral muscle weakness.,COPD is characterised by expiratory flow limitation, resulting in air trapping and lung hyperinflation.,Hyperinflation increases acutely under conditions such as exercise or exacerbations, with an accompanying sharp increase in the intensity of dyspnoea to distressing and intolerable levels.,Air trapping, causing increased lung hyperinflation, can be present even in milder COPD during everyday activities.,The resulting activity-related dyspnoea leads to a vicious spiral of activity avoidance, physical deconditioning, and reduced quality of life, and has implications for the early development of comorbidities such as cardiovascular disease.,Various strategies exist to reduce hyperinflation, notably long-acting bronchodilator treatment (via reduction in flow limitation and improved lung emptying) and an exercise programme (via decreased respiratory rate, reducing ventilatory demand), or their combination.,Optimal bronchodilation can reduce exertional dyspnoea and increase a patient's ability to exercise, and improves the chance of successful outcome of a pulmonary rehabilitation programme.,There should be a lower threshold for initiating treatments appropriate to the stage of the disease, such as long-acting bronchodilators and an exercise programme for patients with mild-to-moderate disease who experience persistent dyspnoea. | Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms and pathological consequences.,Although primarily viewed as a respiratory disease, COPD has both pulmonary and extrapulmonary effects, which have an impact on many aspects of physical, emotional, and mental well-being.,Traditional assessment of COPD relies heavily on measuring lung function, specifically forced expiratory volume in 1 second (FEV1).,However, the evidence suggests that FEV1 is a relatively poor correlate of symptoms such as breathlessness and the impact of COPD on daily life.,Furthermore, many consequences of the disease, including anxiety and depression and the ability to perform daily activities, can only be described and reported reliably by the patient.,Thus, in order to provide a comprehensive view of the effects of interventions in clinical trials, it is essential that spirometry is accompanied by assessments using patient-reported outcome (PRO) instruments.,We provide an overview of patient-reported outcome concepts in COPD, such as breathlessness, physical functioning, and health status, and evaluate the tools used for measuring these concepts.,Particular attention is given to the newly developed instruments emerging in response to recent regulatory guidelines for the development and use of PROs in clinical trials.,We conclude that although data from the development and validation of these new PRO instruments are emerging, to build the body of evidence that supports the use of a new instrument takes many years.,Furthermore, new instruments do not necessarily have better discriminative or evaluative properties than older instruments.,The development of new PRO tools, however, is crucial, not only to ensure that key COPD concepts are being reliably measured but also that the relevant treatment effects are being captured in clinical trials.,In turn, this will help us to understand better the patient’s experience of the disease. | 1 |
Inhaled corticosteroids (ICS) reduce exacerbation rates and improve health status but can increase the risk of pneumonia in COPD.,The GLUCOLD study, investigating patients with mild-to-moderate COPD, has shown that long-term (2.5-year) ICS therapy induces anti-inflammatory effects.,The literature suggests that cigarette smoking causes ICS insensitivity.,The aim of this study is to compare anti-inflammatory effects of ICS in persistent smokers and persistent ex-smokers in a post-hoc analysis of the GLUCOLD study.,Persistent smokers (n = 41) and persistent ex-smokers (n = 31) from the GLUCOLD cohort were investigated.,Effects of ICS treatment compared with placebo were estimated by analysing changes in lung function, hyperresponsiveness, and inflammatory cells in sputum and bronchial biopsies during short-term (0-6 months) and long-term (6-30 months) treatment using multiple regression analyses.,Bronchial mast cells were reduced by short-term and long-term ICS treatment in both smokers and ex-smokers.,In contrast, CD3+, CD4+, and CD8+ cells were reduced by short-term ICS treatment in smokers only.,In addition, sputum neutrophils and lymphocytes, and bronchial CD8+ cells were reduced after long-term treatment in ex-smokers only.,No significant interactions existed between smoking and ICS treatment.,Even in the presence of smoking, long-term ICS treatment may lead to anti-inflammatory effects in the lung.,Some anti-inflammatory ICS effects are comparable in smokers and ex-smokers with COPD, other effects are cell-specific.,The clinical relevance of these findings, however, are uncertain. | Combined inhaled long-acting beta-agonists and corticosteroids (LABA+ICS) are costly.,They are recommended in severe or very severe chronic obstructive pulmonary disease (COPD).,They should not be prescribed in mild or moderate disease.,In COPD ICS are associated with side-effects including risk of pneumonia.,We quantified appropriateness of prescribing and examined the risks and costs associated with overuse.,Data were extracted from the electronic and paper records of 41 London general practices (population 310,775) including spirometry, medications and exacerbations.,We classified severity, assessed appropriateness of prescribing using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for 2009, and performed a sensitivity analysis using the broader recommendations of the 2011 revision.,3537 patients had a diagnosis of COPD.,Spirometry was recorded for 2458(69%). 709(29%) did not meet GOLD criteria. 1749(49%) with confirmed COPD were analysed: 8.6% under-treated, 38% over-treated.,Over-prescription of ICS in GOLD stage I or II (n=403, 38%) and in GOLD III or IV without exacerbations (n=231, 33.6%) was common.,An estimated 12 cases (95%CI 7-19) annually of serious pneumonia were likely among 897 inappropriately treated. 535 cases of overtreatment involved LABA+ICS with a mean per patient cost of £553.56/year (€650.03).,Using the broader indications for ICS in the 2011 revised GOLD guideline 25% were still classified as over-treated.,The estimated risk of 15 cases of pneumonia (95%CI 8-22) in 1074 patients currently receiving ICS would rise by 20% to 18 (95%CI 9.8-26.7) in 1305 patients prescribed ICS if all with GOLD grade 3 and 4 received LABA+ICS.,Over-prescription of ICS in confirmed COPD was widespread with considerable potential for harm.,In COPD where treatment is often escalated in the hope of easing the burden of disease clinicians should consider both the risks and benefits of treatment and the costs where the benefits are unproven. | 1 |
Chinese medicine is commonly used to combine with pharmacotherapy for the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD).,Six Chinese herb formulas involving Weijing decoction, Maxingshigan decoction, Yuebijiabanxia decoction, Qingqihuatan decoction, Dingchuan decoction and Sangbaipi decoction are recommended in Chinese medicine clinical guideline or textbook, to relieve patients with phlegm-heat according to Chinese syndrome differentiation.,However, the comparative effectiveness among these six formulas has not been investigated in published randomised controlled trials.,We plan to summarise the direct and indirect evidence for these six formulas combined with pharmacotherapy to determine the relative merits options for the management of AECOPD.,We will perform the comprehensive search for the randomised controlled trials to evaluate the effectiveness of six Chinese herb formulas recommended in Chinese medicine clinical guideline or textbook.,The combination of pharmacotherapy includes bronchodilators, antibiotics and corticosteroids that are routinely prescribed for AECOPD.,The primary outcome will be lung function, arterial blood gases and length of hospital stay.,The data screening and extraction will be conducted by two different reviewers.,The quality of RCT will be assessed according to the Cochrane handbook risk of bias tool.,The Bayes of network meta-analysis (NMA) will be conducted with WinBUGS to compare the effectiveness of six formulas.,We will also use the surface under the cumulative ranking curve (SUCRA) to obtain the comprehensive rank for these treatments.,This review does not require ethics approval and the results of NMA will be submitted to a peer-review journal.,PROSPERO (CRD42016052699). | 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 |
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 | 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 |
COPD is a highly heterogeneous disease composed of different phenotypes with different aetiological and prognostic profiles and current classification systems do not fully capture this heterogeneity.,In this study we sought to discover, describe and validate COPD subtypes using cluster analysis on data derived from electronic health records.,We applied two unsupervised learning algorithms (k-means and hierarchical clustering) in 30,961 current and former smokers diagnosed with COPD, using linked national structured electronic health records in England available through the CALIBER resource.,We used 15 clinical features, including risk factors and comorbidities and performed dimensionality reduction using multiple correspondence analysis.,We compared the association between cluster membership and COPD exacerbations and respiratory and cardiovascular death with 10,736 deaths recorded over 146,466 person-years of follow-up.,We also implemented and tested a process to assign unseen patients into clusters using a decision tree classifier.,We identified and characterized five COPD patient clusters with distinct patient characteristics with respect to demographics, comorbidities, risk of death and exacerbations.,The four subgroups were associated with 1) anxiety/depression; 2) severe airflow obstruction and frailty; 3) cardiovascular disease and diabetes and 4) obesity/atopy.,A fifth cluster was associated with low prevalence of most comorbid conditions.,COPD patients can be sub-classified into groups with differing risk factors, comorbidities, and prognosis, based on data included in their primary care records.,The identified clusters confirm findings of previous clustering studies and draw attention to anxiety and depression as important drivers of the disease in young, female patients.,The online version of this article (10.1186/s12911-019-0805-0) contains supplementary material, which is available to authorized users. | Antimicrobial treatment for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) remains controversial.,In some cases AECOPD are caused by microorganisms that are resistant to treatments recommended by guidelines.,Our aims were: 1) identify the risk factors associated with infection by microorganisms resistant to conventional treatment (MRCT), 2) Compare the clinical characteristics and outcomes of patients with AECOPD resulting from MRCT against those with AECOPD from other causes.,We prospective analysed a cohort of patients admitted with severe AECOPD (2009 to 2015) who were assigned to three groups: patients with MRCT (those patients with germs resistant to antibiotics recommended in guidelines), patients with microorganisms sensitive to conventional antimicrobial treatment (MSCT), and patients with negative microbiology results who had not previously received antibiotics.,Multinomial logistic regression analyses were used to examine the associations between microbial aetiology groups and risk factors.,The association between LOS and risk factors was also tested in simple and multiple analyses, and similar inclusion criteria were applied for the linear regression analysis.,Of the 451 patients admitted, 195 patients (43%) were included.,Respiratory cultures were positive in 86(44%) and negative in 109(56%).,MRCT were isolated in 34 cases (40%) and MSCT in 52 (60%).,Patients with MRCT had more AECOPD in the previous year, received more antibiotic treatment in the previous three months, had more severe disease, higher dyspnoea and a positive respiratory culture in the previous year (mainly for Pseudomonas aeruginosa).,The following conditions were independent factors for MRCT isolation: non-current smoker (odds ratio [OR] 4.19 [95% confidence interval [CI] 1.29-13.67], p = 0.017), ≥ 2 AECOPD or ≥ 1 admission for AECOPD in the previous year (OR 4.13 [95% CI 1.52-11.17], p = 0.005), C-reactive protein < 5 mg/dL; (OR 3.58 [95% CI 1.41-9.07], p = 0.007).,Mortality rates were comparable at 30-days, one year and 3 years; however, patients in the MRCT group had longer hospital stays.,In conclusion, there are risk factors for resistant germs in AECOPD; however, the presence of these germs does not increase mortality.,Patients with isolation of MRCT had longer length of stay.,The online version of this article (10.1186/s12931-018-0820-1) contains supplementary material, which is available to authorized users. | 1 |
Inhaled medications are the cornerstone of treatment and management of asthma and COPD.,However, inhaler device errors are common among patients and have been linked with reduced symptom control, an increased risk of exacerbations, and increased healthcare utilisation.,These observations have prompted GINA (Global INitiative for Asthma) and GOLD (Global initiative for chronic Obstructive Lung Disease) to recommend regular assessment of inhaler technique in a bid to improve therapeutic outcomes.,To better define the relationship between device errors and health outcomes (clinical outcomes, quality of life, and healthcare utilisation) in asthma and COPD, we conducted a systematic review of the literature, with a particular focus on the methods used to assess the relationship between device errors and outcomes.,Sixteen studies were identified (12 in patients with asthma, one in patients with COPD, and three in both asthma and COPD) with varying study designs, endpoints, and patient populations.,Most of the studies reported that inhalation errors were associated with worse disease outcomes in patients with asthma or COPD.,Patients who had a reduction in errors over time had improved outcomes.,These findings suggest that time invested by healthcare professionals is vital to improving inhalation technique in asthma and COPD patients to improve health outcomes. | The combination of aclidinium bromide, a long-acting anticholinergic, and formoterol fumarate, a long-acting beta2-agonist (400/12 μg twice daily) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease (COPD), and is approved in the European Union as a maintenance treatment.,The effect of this combination on symptoms of COPD and exacerbations is less well established.,We examined these outcomes in a pre-specified analysis of pooled data from two 24-week, double-blind, parallel-group, active- and placebo-controlled, multicentre, randomised Phase III studies (ACLIFORM and AUGMENT).,Patients ≥40 years with moderate to severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <70 % and FEV1 ≥30 % but <80 % predicted normal) were randomised (ACLIFORM: 2:2:2:2:1; AUGMENT: 1:1:1:1:1) to twice-daily aclidinium/formoterol 400/12 μg or 400/6 μg, aclidinium 400 μg, formoterol 12 μg or placebo via Genuair™/Pressair®.,Dyspnoea (Transition Dyspnoea Index; TDI), daily symptoms (EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [E-RS] questionnaire), night-time and early-morning symptoms, exacerbations (Healthcare Resource Utilisation [HCRU] and EXACT definitions) and relief-medication use were assessed.,The pooled intent-to-treat population included 3394 patients.,Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 (all p < 0.05).,Over 24 weeks, significant improvements in E-RS total score, overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with aclidinium/formoterol 400/12 μg versus placebo and both monotherapies (all p < 0.05).,The rate of moderate or severe HCRU exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg compared with placebo (p < 0.05) but not monotherapies; the rate of EXACT-defined exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg versus placebo (p < 0.01) and aclidinium (p < 0.05).,Time to first HCRU or EXACT exacerbation was longer with aclidinium/formoterol 400/12 μg compared with placebo (all p < 0.05) but not the monotherapies.,Relief-medication use was reduced with aclidinium/formoterol 400/12 μg versus placebo and aclidinium (p < 0.01).,Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo, aclidinium and formoterol in patients with moderate to severe COPD.,Furthermore, aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo.,NCT01462942 and NCT01437397 (ClinicalTrials.gov),The online version of this article (doi:10.1186/s12931-015-0250-2) contains supplementary material, which is available to authorized users. | 1 |
Acute COPD exacerbations account for much of the rising disability and costs associated with COPD, but data on predictive risk factors are limited.,The goal of the current study was to develop a robust, clinically based model to predict frequent exacerbation risk.,Patients identified from the Optimum Patient Care Research Database (OPCRD) with a diagnostic code for COPD and a forced expiratory volume in 1 second/forced vital capacity ratio <0.7 were included in this historical follow-up study if they were ≥40 years old and had data encompassing the year before (predictor year) and year after (outcome year) study index date.,The data set contained potential risk factors including demographic, clinical, and comorbid variables.,Following univariable analysis, predictors of two or more exacerbations were fed into a stepwise multivariable logistic regression.,Sensitivity analyses were conducted for subpopulations of patients without any asthma diagnosis ever and those with questionnaire data on symptoms and smoking pack-years.,The full predictive model was validated against 1 year of prospective OPCRD data.,The full data set contained 16,565 patients (53% male, median age 70 years), including 9,393 patients without any recorded asthma and 3,713 patients with questionnaire data.,The full model retained eleven variables that significantly predicted two or more exacerbations, of which the number of exacerbations in the preceding year had the strongest association; others included height, age, forced expiratory volume in 1 second, and several comorbid conditions.,Significant predictors not previously identified included eosinophilia and COPD Assessment Test score.,The predictive ability of the full model (C statistic 0.751) changed little when applied to the validation data set (n=2,713; C statistic 0.735).,Results of the sensitivity analyses supported the main findings.,Patients at risk of exacerbation can be identified from routinely available, computerized primary care data.,Further study is needed to validate the model in other patient populations. | The time of year when patients experience exacerbations of chronic obstructive pulmonary disease is a much-overlooked feature of the disease.,The higher incidence of exacerbations in winter has important consequences for patients in terms of increased morbidity and mortality.,The seasonality also imposes a considerable burden on already-overloaded health care services, with both primary care consultations and hospital admissions increasing in number.,The seasonality of exacerbations varies with latitude, and is greater in more temperate climates, where there may be less protection from outdoor and indoor cold exposure.,The precise causes of the seasonality are unknown, but thought to be partly due to the increased prevalence of respiratory viral infections circulating in cold, damp conditions.,Increased susceptibility to viral infection may also be a mechanism mediated through increased airway inflammation or possibly reduced vitamin D levels.,The seasonality of exacerbations informs us about the triggers of exacerbations and suggests possible strategies to reduce their number. | 1 |
Blood eosinophil count has been proposed as a predictor of response to inhaled corticosteroid (ICS) in the prevention of acute exacerbations of COPD.,An optimal threshold of blood eosinophil count for prescribing ICS has not been agreed.,Doubt has been cast on the role by observational studies.,The role of inhaled corticosteroids in this relationship, independent of long-acting bronchodilators, has not been examined.,We conducted a systematic review of post-hoc analyses of randomised controlled trials (RCTs) and observational studies examining three blood eosinophil thresholds and the independent role of ICS.,Included studies were categorised by the form (relative or absolute count) and cut point of eosinophil threshold used.,Thresholds assessed were relative eosinophil count of 2%, and absolute counts of 150 cells/μL and 300 cells/μL.,Three meta-analyses of the effect of ICS use in post-hoc analyses of RCTs based on these counts were carried out.,Initial analysis included all studies of ICS vs. any non-ICS regimen.,Further analysis examined the effect of ICS, independent of the effect of long-acting bronchodilators.,Sixteen studies examined the association between blood eosinophil count and response of exacerbation risk to ICS, in COPD patients.,Eleven studies (25,881 patients) were post-hoc analyses of RCTs.,Five studies (109,704 patients) were retrospective observational studies.,The independent effect of ICS on the reduction of exacerbation risk was 20% at ≥2% blood eosinophil threshold (RR, 0.80; 95% CI, 0.74-0.85), 35% at ≥150 cells/μL blood eosinophil threshold (RR, 0.65; 0.52-0.79), and 39% at ≥300 cells/μL blood eosinophil threshold (RR, 0.61; 0.44-0.78).,No association was found in four out of five observational studies.,This is the first systematic review to assess, in post-hoc analyses of RCTs, the independent effect of ICS in reducing the risk of COPD exacerbation across a range of blood eosinophil thresholds.,Association between ICS prescription and reduced exacerbation risk at these thresholds was confirmed.,The lack of association found in the observational studies questions the relevance of these observations to a “real world” COPD population.,To clarify the clinical utility of this biomarker, the association should be tested in prospective effectiveness studies. | Factors predicting prescriptions of triple therapy were investigated in a large group of general practitioners in Italy.,In the population treated by identified general practitioners, a cohort of newly diagnosed chronic obstructive pulmonary disease patients was extracted from IMS Health Longitudinal Database during the period 2010-2013.,From the diagnosis, 1-year follow-up was evaluated.,Thirty-two thousand forty-six newly diagnosed chronic obstructive pulmonary disease patients were evaluated (57.7% male, mean age 67 years).,During 2 years prior to diagnosis less than 13% of patients were requested with a pulmonology evaluation and less than 5% with a spirometry; 65.1% cases were prescribed with a respiratory drug, which in 9.6% of cases was inhaled corticosteroid/long-acting β2-agonist fixed-dose combination.,Two thousand and twenty eight patients (6.3% of the newly diagnosed chronic obstructive pulmonary disease patients) were treated with triple therapy during the first year of follow-up, whose 858 (42.3%) starting immediately, and 762 (37.6%) following an initial treatment with inhaled corticosteroid/long-acting β2-agonist fixed-dose combination.,Being older, being requested with pulmonologist evaluation or spirometry, being prescribed with a inhaled corticosteroid/long-acting β2-agonist fixed-dose combination at diagnosis resulted independent predictors of triple therapy use.,An improved education program for doctors promoting correct use of medication for chronic lung disease is needed in Italy.,Current guidelines state that inhaled corticosteroids (ICSs) should be reserved for patients with severe chronic obstructive pulmonary disease (COPD), but it appears that doctors do not always follow this advice.,Fabiano Di Marco, at San Paolo Hospital-Università degli Studi di Milano, and co-workers analyzed data from 32,046 COPD patients newly-diagnosed by family doctors in Italy between 2010 and 2013.,When the researchers followed up on patients after 1 year, 2028 (6.3%) of newly-diagnosed patients were being treated with triple inhaled therapy incorporating ICSs-42% of these patients had started triple therapy immediately upon diagnosis.,Being an older male and having been prescribed with a ICS/LABA FDC at diagnosis were strong predictors of triple therapy use within 1 year from the diagnosis. | 1 |
COPD often coexists with chronic conditions that may influence disease prognosis.,We investigated associations between chronic (co)morbidities and exacerbations in primary care COPD patients.,Retrospective cohort study based on 2012-2013 electronic health records from 179 Dutch general practices.,Comorbidities from patients with physician-diagnosed COPD were categorized according to International Classification of Primary Care (ICPC) codes.,Chi-squared tests, uni- and multivariable logistic, and Cox regression analyses were used to study associations with exacerbations, defined as oral corticosteroid prescriptions.,Fourteen thousand six hundred three patients with COPD could be studied (mean age 67 (SD 12) years, 53% male) for two years.,At baseline 12,826 (88%) suffered from ≥1 comorbidities, 3263 (22%) from ≥5.,The most prevalent comorbidities were hypertension (35%), coronary heart disease (19%), and osteoarthritis (18%).,Several comorbidities showed statistically significant associations with frequent (i.e., ≥2/year) exacerbations: heart failure (odds ratio [OR], 95% confidence interval: 1.72; 1.38-2.14), blindness & low vision (OR 1.46; 1.21-1.75), pulmonary cancer (OR 1.85; 1.28-2.67), depression 1.48; 1.14-1.91), prostate disorders (OR 1.50; 1.13-1.98), asthma (OR 1.36; 1.11-1.70), osteoporosis (OR 1.41; 1.11-1.80), diabetes (OR 0.80; 0.66-0.97), dyspepsia (OR 1.25; 1.03-1.50), and peripheral vascular disease (OR 1.20; 1.00-1.45).,From all comorbidity categories, having another chronic respiratory disease beside COPD showed the highest risk for developing a new exacerbation (Cox hazard ratio 1.26; 1.17-1.36).,Chronic comorbidities are highly prevalent in primary care COPD patients.,Several chronic comorbidities were associated with having frequent exacerbations and increased exacerbation risk. | Treatment of chronic diseases such as chronic obstructive pulmonary disease (COPD) is complicated by the presence of comorbidities.,The objective of this analysis was to estimate the prevalence of comorbidity in COPD using nationally-representative data.,This study draws from a multi-year analytic sample of 14,828 subjects aged 45+, including 995 with COPD, from the National Health and Nutrition Examination Survey (NHANES), 1999-2008.,COPD was defined by self-reported physician diagnosis of chronic bronchitis or emphysema; patients who reported a diagnosis of asthma were excluded.,Using population weights, we estimated the age-and-gender-stratified prevalence of 22 comorbid conditions that may influence COPD and its treatment.,Subjects 45+ with physician-diagnosed COPD were more likely than subjects without physician-diagnosed COPD to have coexisting arthritis (54.6% vs.,36.9%), depression (20.6% vs.,12.5%), osteoporosis (16.9% vs.,8.5%), cancer (16.5% vs.,9.9%), coronary heart disease (12.7% vs.,6.1%), congestive heart failure (12.1% vs.,3.9%), and stroke (8.9% vs.,4.6%).,Subjects with COPD were also more likely to report mobility difficulty (55.6% vs.,32.5%), use of >4 prescription medications (51.8% vs.,32.1), dizziness/balance problems (41.1% vs.,23.8%), urinary incontinence (34.9% vs.,27.3%), memory problems (18.5% vs.,8.8%), low glomerular filtration rate (16.2% vs.,10.5%), and visual impairment (14.0% vs.,9.6%).,All reported comparisons have p < 0.05.,Our study indicates that COPD management may need to take into account a complex spectrum of comorbidities.,This work identifies which conditions are most common in a nationally-representative set of COPD patients (physician-diagnosed), a necessary step for setting research priorities and developing clinical practice guidelines that address COPD within the context of comorbidity. | 1 |
Recent telehealth studies have demonstrated minor impact on patients affected by long-term conditions.,The use of technology does not guarantee the compliance required for sustained collection of high-quality symptom and physiological data.,Remote monitoring alone is not sufficient for successful disease management.,A patient-centred design approach is needed in order to allow the personalisation of interventions and encourage the completion of daily self-management tasks.,A digital health system was designed to support patients suffering from chronic obstructive pulmonary disease in self-managing their condition.,The system includes a mobile application running on a consumer tablet personal computer and a secure backend server accessible to the health professionals in charge of patient management.,The patient daily routine included the completion of an adaptive, electronic symptom diary on the tablet, and the measurement of oxygen saturation via a wireless pulse oximeter.,The design of the system was based on a patient-centred design approach, informed by patient workshops.,One hundred and ten patients in the intervention arm of a randomised controlled trial were subsequently given the tablet computer and pulse oximeter for a 12-month period.,Patients were encouraged, but not mandated, to use the digital health system daily.,The average used was 6.0 times a week by all those who participated in the full trial.,Three months after enrolment, patients were able to complete their symptom diary and oxygen saturation measurement in less than 1 m 40s (96% of symptom diaries).,Custom algorithms, based on the self-monitoring data collected during the first 50 days of use, were developed to personalise alert thresholds.,Strategies and tools aimed at refining a digital health intervention require iterative use to enable convergence on an optimal, usable design.,‘Continuous improvement’ allowed feedback from users to have an immediate impact on the design of the system (e.g., collection of quality data), resulting in high compliance with self-monitoring over a prolonged period of time (12-month).,Health professionals were prompted by prioritisation algorithms to review patient data, which led to their regular use of the remote monitoring website throughout the trial.,Trial registration: ISRCTN40367841.,Registered 17/10/2012. | Chronic obstructive pulmonary disease (COPD) is a highly prevalent condition associated with a high health care resource consumption and health care expenditures, driven mainly by exacerbations-related hospitalizations.,Telemedicine has been proposed as a mean for timely detection of exacerbation, but the available evidence is inadequate to provide conclusive information on its efficacy.,The aim of this study is to evaluate the efficacy of a telemonitoring system in reducing COPD-related hospitalizations in an elderly population with COPD.,This is a parallel arms, randomized trial including patients aged 65 or older with COPD in GOLD stages II and III enrolled in a Pulmonary Medicine outpatient facility.,Patients were randomly assigned to receive a non-invasive system able to telemonitor vital signs (oxygen saturation, heart rate, near-body temperature, overall physical activity) or standard care, and were followed up for 9 months.,The outcome measures were the number of exacerbations and exacerbation-related hospitalization.,Fifty patients were included in the telemonitoring group and 49 in the control group.,The incidence rate of respiratory events was 28/100 person/years in the telemonitoring group vs. 42/100 person/years in the control group (incidence rate ratio: 0.67, 95% CI: 0.32 - 1.36).,The corresponding figures for hospital admissions where 13/100 person/years and 20/100 person/years, respectively (IRR: 0.66, 95% CI: 0.21 - 1.86).,In our study, COPD patients followed up with the aid of a multiparametric remote monitoring system experienced a lower rate of exacerbations and COPD-related hospitalizations compared to patients followed up using the standard model of care.,These results need to be replicated in larger studies before they can be applied to the general COPD population.,Trial registration number: NCT01481506 (clinicaltrials.gov).,Funding: co-financed by Lazio Region and Intersistemi Inc. | 1 |
The objective of this study was to compare the cost-effectiveness of the fixed-dose combination (FDC) of tiotropium + olodaterol Respimat® FDC with tiotropium alone for patients with chronic obstructive pulmonary disease (COPD) in the Italian health care setting using a newly developed patient-level Markov model that reflects the current understanding of the disease.,While previously published models have largely been based around a cohort approach using a Markov structure and GOLD stage stratification, an individual-level Markov approach was selected for the new model.,Using patient-level data from the twin TOnado trials assessing Tiotropium + olodaterol Respimat® FDC versus tiotropium, outcomes were modelled based on the trough forced expiratory volume (tFEV1) of over 1000 patients in each treatment arm, tracked individually at trial visits through the 52-week trial period, and after the trial period it was assumed to decline at a constant rate based on disease stage.,Exacerbation risk was estimated based on a random-effects logistic regression analysis of exacerbations in UPLIFT.,Mortality by age and disease stage was estimated from an analysis of TIOSPIR trial data.,Cost of bronchodilators and other medications, routine management, and costs of treatment for moderate and severe exacerbations for the Italian setting were included.,A cost-effectiveness analysis was conducted over a 15-year time horizon from the perspective of the Italian National Health Service.,Aggregating total costs and quality-adjusted life years (QALYs) for each treatment cohort over 15 years and comparing tiotropium + olodaterol Respimat® FDC with tiotropium alone, resulted in mean incremental costs per patient of €1167 and an incremental cost-effectiveness ratio (ICER) of €7518 per additional QALY with tiotropium + olodaterol Respimat® FDC.,The lung function outcomes observed for tiotropium + olodaterol Respimat® FDC in TOnado drove the results in terms of slightly higher mean life-years (12.24 versus 12.07) exacerbation-free months (11.36 versus 11.32) per patient and slightly fewer moderate and severe exacerbations per patient-year (0.411 versus 0.415; 0.21 versus 0.24) versus tiotropium.,Probabilistic sensitivity analyses showed tiotropium + olodaterol Respimat® FDC to be the more cost-effective treatment in 95.2% and 98.4% of 500 simulations at thresholds of €20,000 and €30,000 per QALY respectively.,Tiotropium + olodaterol Respimat® FDC is a cost-effective bronchodilator in the maintenance treatment of COPD for the Italian health care system. | 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. | 1 |
It is desirable to facilitate the use of an affordable, reliable, and portable spirometer, for earlier diagnosis of COPD in China, particularly in rural areas.,The aim of this study was to assess the agreement of a handheld “disposable pneumotachograph” (D-PNEU) spirometer with the gold standard spirometer and to evaluate its diagnostic accuracy of spirometric classification of airflow obstruction.,A total of 241 adult Chinese subjects ranging from healthy to those with mixed levels of pulmonary disease performed spirometry in a conventional body plethysmograph, and using a D-PNEU device in randomized order.,The three best spirometric tests were recorded for comparative analysis.,A Bland-Altman graph was created to assess the agreement between devices.,Using FEV1/FVC <70% as the “gold standard” for obstruction, the accuracy of classifying the severity of airway obstruction for all subjects was assessed.,For the specific individuals (n=159) able to exhale for at least 6 seconds, the accuracy of classifying airway obstruction was further assessed.,For this purpose, a receiver operating characteristic curve was used to determine an optimal cutoff point of FEV1/FEV6 ratio obtained by the D-PNEU device, which matched the global definition of FEV1/FVC <70% by the traditional spirometer.,The Bland-Altman analysis showed that the between-device agreement for key airflow metrics was within clinically acceptable limits.,The D-PNEU device had 87.1% accuracy in the classification of severity of obstruction in all 241 subjects, when using FEV1/FVC<70% as the “gold standard” for both devices.,The D-PNEU device had 93.7% accuracy in the 159 individuals able to exhale for at least 6 seconds, when a cutoff point of FEV1/FEV6 was 74%.,A disposable handheld spirometry device is capable of accurately identifying and quantifying airway obstruction in patients deemed to be at risk, however, caution should be exercised and all available brands should be tested. | To evaluate the effectiveness of an early detection program for chronic obstructive pulmonary disease (COPD) in a primary care setting in Japan.,Participants of ≥40 years of age who regularly visited a general practitioner's clinic due to chronic disease were asked to complete a COPD screening questionnaire (COPD Population Screener; COPD-PS) and undergo simplified spirometry using a handheld spirometric device.,Patients who showed possible COPD were referred to a respiratory specialist and underwent a detailed examination that included spirometry and chest radiography.,A total of 111 patients with possible COPD were referred for close examination.,Among these patients, 27 patients were newly diagnosed with COPD.,The patients with COPD were older, had lower BMI values, and had a longer smoking history in comparison to non-COPD patients.,COPD patients also had more comorbid conditions.,A diagnosis of COPD was significantly associated with a high COPD-PS score (p<0.001) and the detection of possible airflow limitation evaluated by the handheld spirometric device (p<0.01).,An ROC curve analysis demonstrated that 5 points was the best COPD-PS cut-off value for the diagnosis of COPD.,The combination of both tools showed 40.7% of sensitivity and 96.4% of specificity.,The use of the COPD-PS plus a handheld spirometric device could facilitate the early detection of undiagnosed COPD in primary care. | 1 |
Chronic obstructive pulmonary disease (COPD) is a major cause of mortality.,Patients with advanced disease often have a poor quality of life, such that guidelines recommend providing palliative care in their last year of life.,Uptake and use of palliative care in advanced COPD is low; difficulty in predicting 1-year mortality is thought to be a major contributing factor.,We identified two primary care COPD cohorts using UK electronic healthcare records (Clinical Practice Research Datalink).,The first cohort was randomised equally into training and test sets.,An external dataset was drawn from a second cohort.,A risk model to predict mortality within 12 months was derived from the training set using backwards elimination Cox regression.,The model was given the acronym BARC based on putative prognostic factors including body mass index and blood results (B), age (A), respiratory variables (airflow obstruction, exacerbations, smoking) (R) and comorbidities (C).,The BARC index predictive performance was validated in the test set and external dataset by assessing calibration and discrimination.,The observed and expected probabilities of death were assessed for increasing quartiles of mortality risk (very low risk, low risk, moderate risk, high risk).,The BARC index was compared to the established index scores body mass index, obstructive, dyspnoea and exacerbations (BODEx), dyspnoea, obstruction, smoking and exacerbations (DOSE) and age, dyspnoea and obstruction (ADO).,Fifty-four thousand nine hundred ninety patients were eligible from the first cohort and 4931 from the second cohort.,Eighteen variables were included in the BARC, including age, airflow obstruction, body mass index, smoking, exacerbations and comorbidities.,The risk model had acceptable predictive performance (test set: C-index = 0.79, 95% CI 0.78-0.81, D-statistic = 1.87, 95% CI 1.77-1.96, calibration slope = 0.95, 95% CI 0.9-0.99; external dataset: C-index = 0.67, 95% CI 0.65-0.7, D-statistic = 0.98, 95% CI 0.8-1.2, calibration slope = 0.54, 95% CI 0.45-0.64) and acceptable accuracy predicting the probability of death (probability of death in 1 year, n high-risk group, test set: expected = 0.31, observed = 0.30; external dataset: expected = 0.22, observed = 0.27).,The BARC compared favourably to existing index scores that can also be applied without specialist respiratory variables (area under the curve: BARC = 0.78, 95% CI 0.76-0.79; BODEx = 0.48, 95% CI 0.45-0.51; DOSE = 0.60, 95% CI 0.57-0.61; ADO = 0.68, 95% CI 0.66-0.69, external dataset: BARC = 0.70, 95% CI 0.67-0.72; BODEx = 0.41, 95% CI 0.38-0.45; DOSE = 0.52, 95% CI 0.49-0.55; ADO = 0.57, 95% CI 0.54-0.60).,The BARC index performed better than existing tools in predicting 1-year mortality.,Critically, the risk score only requires routinely collected non-specialist information which, therefore, could help identify patients seen in primary care that may benefit from palliative care.,The online version of this article (10.1186/s12916-019-1310-0) contains supplementary material, which is available to authorized users. | Prediction models for exacerbations in patients with chronic obstructive pulmonary disease (COPD) are scarce.,Our aim was to develop and validate a new model to predict exacerbations in patients with COPD.,The derivation cohort consisted of patients aged 65 years or over, with a COPD diagnosis, who were followed up over 24 months.,The external validation cohort consisted of another cohort of COPD patients, aged 50 years or over.,Exacerbations of COPD were defined as symptomatic deterioration requiring pulsed oral steroid use or hospitalization.,Logistic regression analysis including backward selection and shrinkage were used to develop the final model and to adjust for overfitting.,The adjusted regression coefficients were applied in the validation cohort to assess calibration of the predictions and calculate changes in discrimination applying C-statistics.,The derivation and validation cohort consisted of 240 and 793 patients with COPD, of whom 29% and 28%, respectively, experienced an exacerbation during follow-up.,The final model included four easily assessable variables: exacerbations in the previous year, pack years of smoking, level of obstruction, and history of vascular disease, with a C-statistic of 0.75 (95% confidence interval [CI]: 0.69-0.82).,Predictions were well calibrated in the validation cohort, with a small loss in discrimination potential (C-statistic 0.66 [95% CI 0.61-0.71]).,Our newly developed prediction model can help clinicians to predict the risk of future exacerbations in individual patients with COPD, including those with mild disease. | 1 |
The use of a severity score to help orientation decisions could improve the efficiency of care for acute exacerbations of COPD (AECOPD).,We previously developed a score (‘2008 score’, based on age, dyspnea grade at steady state and number of clinical signs of severity) predicting in-hospital mortality in patients with AECOPD visiting emergency departments (EDs).,External validity of this score remained to be assessed.,To test the predictive properties of the ‘2008 score’ in a population of patients hospitalized in medical respiratory wards for AECOPD, and determine whether a new score specifically derived from this population would differ from the previous score in terms of components or predictive performance.,Data from a cohort study in 1824 patients hospitalized in a medical ward for an AECOPD were analyzed.,Patients were categorized using the 2008 score and its predictive characteristics for in-hospital mortality rates were assessed.,A new score was developed using multivariate logistic regression modeling in a randomly selected derivation population sample followed by testing in the remaining population (validation sample).,Robustness of results was assessed by case-by-case validation.,The 2008 score was characterized by a c-statistic at 0.77, a sensitivity of 69% and a specificity of 76% for prediction of in-hospital mortality.,The new score comprised the same variables plus major cardiac comorbidities and was characterized by a c-statistic of 0.78, a sensitivity of 77% and specificity of 66%.,A score using simple clinical variables has robust properties for predicting the risk of in-hospital death in patients hospitalized for AECOPD.,Adding cardiac comorbidities to the original score increased its sensitivity while decreasing its specificity.,The online version of this article (doi:10.1186/s12931-014-0099-9) contains supplementary material, which is available to authorized users. | Patients with chronic obstructive pulmonary disease (COPD) commonly suffer from acute exacerbations (AECOPD) and display varying disease severity.,However, there is no available biomarker for the classification of AECOPD.,This study is aimed at investigating the sputum cellular profiles to classify patients with AECOPD.,A total of 83 patients with AECOPD and 26 healthy controls were recruited.,Their demographic and clinical characteristics were recorded, and their lung function was examined.,The phenotypes of sputum inflammatory cells were characterised, and the concentrations of sputum and serum amyloid-A (SAA), C-reactive protein (CRP), interleukin-6 (IL-6), and matrix metalloproteinase-9 (MMP-9) were measured.,Based on the sputum inflammatory cell profiles, individual patients were categorized into one of the four subgroups with inflammatory eosinophilic, neutrophilic, paucigranulocytic, and mixed granulocytic AECOPD.,Most AECOPD patients were reevaluated within 12-14 months after discharge.,There were 10 (12%) eosinophilic, 36 (43%) neutrophilic, 5 (6%) mixed granulocytic, and 32 (39%) paucigranulocytic AECOPD patients.,The patients with mixed granulocytic or neutrophilic AECOPD had a higher BODE score, more sputum inflammatory cells, lower lung function, and longer hospital stay, accompanied by higher concentrations of sputum MMP-9, IL-6 and CRP, and serum SAA, IL-6 and CRP.,Notably, 83% of patients with neutrophilic AECOPD displayed evidence of bacterial infection and many of them responded poorly to standard therapies.,In addition, patients with mixed granulocytic or neutrophilic stable COPD remained at lower lung functions and higher levels of inflammation.,Patients with AECOPD display heterogeneous inflammation, and the profiles of sputum inflammatory cells may be used as valuable biomarkers for the classification of AECOPD patients. | 1 |
Self-management interventions are considered effective in patients with COPD, but trials have shown inconsistent results and it is unknown which patients benefit most.,This study aimed to summarize the evidence on effectiveness of self-management interventions and identify subgroups of COPD patients who benefit most.,Randomized trials of self-management interventions between 1985 and 2013 were identified through a systematic literature search.,Individual patient data of selected studies were requested from principal investigators and analyzed in an individual patient data meta-analysis using generalized mixed effects models.,Fourteen trials representing 3,282 patients were included.,Self-management interventions improved health-related quality of life at 12 months (standardized mean difference 0.08, 95% confidence interval [CI] 0.00-0.16) and time to first respiratory-related hospitalization (hazard ratio 0.79, 95% CI 0.66-0.94) and all-cause hospitalization (hazard ratio 0.80, 95% CI 0.69-0.90), but had no effect on mortality.,Prespecified subgroup analyses showed that interventions were more effective in males (6-month COPD-related hospitalization: interaction P=0.006), patients with severe lung function (6-month all-cause hospitalization: interaction P=0.016), moderate self-efficacy (12-month COPD-related hospitalization: interaction P=0.036), and high body mass index (6-month COPD-related hospitalization: interaction P=0.028 and 6-month mortality: interaction P=0.026).,In none of these subgroups, a consistent effect was shown on all relevant outcomes.,Self-management interventions exert positive effects in patients with COPD on respiratory-related and all-cause hospitalizations and modest effects on 12-month health-related quality of life, supporting the implementation of self-management strategies in clinical practice.,Benefits seem similar across the subgroups studied and limiting self-management interventions to specific patient subgroups cannot be recommended. | Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD).,We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.,This retrospective analysis of data from the 4-year UPLIFT® (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo.,Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0, >0-1, >1-2, and >2).,Spirometry and the St George’s Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry).,In total, 5992 patients (mean age 65 years, 75% male) were randomized.,Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV1) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units).,Corresponding rates of decline in postbronchodilator FEV1 (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium).,Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium).,The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium).,The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations.,Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD.,Increasing rates of hospitalized exacerbations are associated with increasing risk of death. | 1 |
In addition to their respiratory symptoms, patients with COPD experience multiple, co-occurring symptoms.,The aims of this study were to identify subgroups of COPD patients based on their distinct experiences with 14 symptoms and to determine how these subgroups differed in demographic and clinical characteristics and disease-specific quality of life.,Patients with moderate, severe, and very severe COPD (n=267) completed a number of self-report questionnaires.,Latent class analysis was used to identify subgroups of patients with distinct symptom experiences based on the occurrence of self-reported symptoms using the Memorial Symptom Assessment Scale.,Based on the probability of occurrence of a number of physical and psychological symptoms, three subgroups of patients (ie, latent classes) were identified and named “high”, “intermediate”, and “low”.,Across the three latent classes, the pairwise comparisons for the classification of airflow limitation in COPD were not significantly different, which suggests that measurements of respiratory function are not associated with COPD patients’ symptom burden and their specific needs for symptom management.,While patients in both the “high” and “intermediate” classes had high occurrence rates for respiratory symptoms, patients in the “high” class had the highest occurrence rates for psychological symptoms.,Compared with the “intermediate” class, patients in the “high” class were younger, more likely to be women, had significantly more acute exacerbations in the past year, and reported significantly worse disease-specific quality of life scores.,These findings suggest that subgroups of COPD patients with distinct symptom experiences can be identified.,Patients with a higher symptom burden warrant more detailed assessments and may have therapeutic needs that would not be identified using current classifications based only on respiratory function. | 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 mechanisms underlying altered susceptibility and propensity to severe Coronavirus disease 2019 (COVID-19) disease in at-risk groups such as patients with chronic obstructive pulmonary disease (COPD) are poorly understood.,Inhaled corticosteroids (ICSs) are widely used in COPD, but the extent to which these therapies protect or expose patients to risk of severe COVID-19 is unknown.,The aim of this study was to evaluate the effect of ICSs following pulmonary expression of the SARS-CoV-2 viral entry receptor angiotensin-converting enzyme-2 (ACE2).,We evaluated the effect of ICS administration on pulmonary ACE2 expression in vitro in human airway epithelial cell cultures and in vivo in mouse models of ICS administration.,Mice deficient in the type I IFN-α/β receptor (Ifnar1−/−) and administration of exogenous IFN-β were used to study the functional role of type-I interferon signaling in ACE2 expression.,We compared sputum ACE2 expression in patients with COPD stratified according to use or nonuse of ICS.,ICS administration attenuated ACE2 expression in mice, an effect that was reversed by exogenous IFN-β administration, and Ifnar1−/− mice had reduced ACE2 expression, indicating that type I interferon contributes mechanistically to this effect.,ICS administration attenuated expression of ACE2 in airway epithelial cell cultures from patients with COPD and in mice with elastase-induced COPD-like changes.,Compared with ICS nonusers, patients with COPD who were taking ICSs also had reduced sputum expression of ACE2.,ICS therapies in COPD reduce expression of the SARS-CoV-2 entry receptor ACE2.,This effect may thus contribute to altered susceptibility to COVID-19 in patients with COPD. | The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) a pandemic [1].,COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,COVID-19 displays symptoms ranging from mild to severe (pneumonia) that can lead to death in some individuals [2-4].,As of 18 April 2020, there have been 2 280 945 cases of COVID-19 worldwide and 156 354 deaths [5].,SARS-CoV-2 uses the angiotensin-converting enzyme II (ACE-2) as the cellular entry receptor [6].,While the virus can infect individuals of any age, to date, most of the severe cases have been described in those >55 years of age and with significant comorbidities, such as COPD [7].,Here, we determined whether patients with COPD have increased expression of ACE-2 in bronchial epithelial cells in the lower respiratory tract.,Smokers and those with COPD have increased airway expression of ACE-2, which is the entry receptor for the COVID-19 virus.,This may explain the increased risk of severe COVID-19 in these subpopulations and highlight the importance of smoking cessation.https://bit.ly/3bC29es | 1 |
The aim of this study is to identify genetic loci associated with post-bronchodilator FEV1/FVC and FEV1, and develop a multi-gene predictive model for lung function in COPD.,Genome-wide association study (GWAS) of post-bronchodilator FEV1/FVC and FEV1 was performed in 1645 non-Hispanic White European descent smokers.,A functional rare variant in SERPINA1 (rs28929474: Glu342Lys) was significantly associated with post-bronchodilator FEV1/FVC (p = 1.2 × 10− 8) and FEV1 (p = 2.1 × 10− 9).,In addition, this variant was associated with COPD (OR = 2.3; p = 7.8 × 10− 4) and severity (OR = 4.1; p = 0.0036).,Heterozygous subjects (CT genotype) had significantly lower lung function and higher percentage of COPD and more severe COPD than subjects with the CC genotype.,8.6% of the variance of post-bronchodilator FEV1/FVC can be explained by SNPs in 10 genes with age, sex, and pack-years of cigarette smoking (P < 2.2 × 10− 16).,This study is the first to show genome-wide significant association of rs28929474 in SERPINA1 with lung function.,Of clinical importance, heterozygotes of rs28929474 (4.7% of subjects) have significantly reduced pulmonary function, demonstrating a major impact in smokers.,The multi-gene model is significantly associated with CT-based emphysema and clinical outcome measures of severity.,Combining genetic information with demographic and environmental factors will further increase the predictive power for assessing reduced lung function and COPD severity.,The online version of this article (10.1186/s12881-018-0656-z) contains supplementary material, which is available to authorized users. | Club cell protein (CC16) is expressed primarily by club cells possesses anti-inflammatory properties and is located in the bronchiolar epithelium.,Previous studies have demonstrated that CC16 deficiency is associated with the progression of chronic obstructive pulmonary disease (COPD).,In the present study, the therapeutic effects of recombinant rat CC16 protein in mice with COPD were examined and the underlying mechanisms investigated.,A total of 30 adult male C57/BL6 mice were randomly divided into three groups (10 mice/group).,A mouse COPD model was generated by exposing 20 mice to cigarette smoke (CS) for 24 weeks.,A total of 10 mice were treated intranasally with rCC16 (2.5 µg/g body weight) and control mice were exposed to normal room air.,Results indicated that rCC16 treatment ameliorated pathological damage in the lungs and reduced the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8, which were induced by CS exposure.,After rCC16 administration, endogenous CC16 was upregulated and the body weight of COPD mice was increased, whereas the opposite was observed in CS-exposed mice.,Additionally, rCC16 treatment inhibited the DNA binding of NF-κB/p65 in lung tissues and reduced nuclear translocation of NF-κB/p65 in BALF and epithelial cells.,Moreover, rCC16 treatment lead to a decrease in the total number of BALF cells, including macrophages, which was elevated in COPD mice.,In conclusion, the present results demonstrate that rCC16 has therapeutic effects on COPD by downregulating pro-inflammatory factors via the NF-κB pathway. | 1 |
The long-acting muscarinic antagonists umeclidinium (UMEC) and tiotropium (TIO) are approved once-daily maintenance therapies for COPD.,This study investigated the efficacy and safety of UMEC versus TIO in COPD.,This was a 12-week, multicenter, randomized, blinded, double-dummy, parallel-group, non-inferiority study.,Patients were randomized 1:1 to UMEC 62.5 μg plus placebo or TIO 18 μg plus placebo.,The primary end point was trough forced expiratory volume in 1 second (FEV1) at day 85 (non-inferiority margin −50 mL; per-protocol [PP] population).,Other end points included weighted mean FEV1 over 0-24 and 12-24 hours post-dose.,Patient-reported outcomes comprised Transition Dyspnea Index score, St George’s Respiratory Questionnaire total score, and COPD Assessment Test score.,Adverse events were also assessed.,In total, 1,017 patients were randomized to treatment.,In the PP population, 489 and 487 patients received UMEC and TIO, respectively.,In the PP population, change from baseline in trough FEV1 was greater with UMEC versus TIO at day 85, meeting non-inferiority and superiority margins (difference: 59 mL; 95% confidence interval [CI]: 29-88; P<0.001).,Similar results were observed in the intent-to-treat analysis of trough FEV1 at day 85 (53 mL, 95% CI: 25-81; P<0.001).,Improvements in weighted mean FEV1 over 0-24 hours post-dose at day 84 were similar with UMEC and TIO but significantly greater with UMEC versus TIO over 12-24 hours post-dose (70 mL; P=0.015).,Clinically meaningful improvements in Transition Dyspnea Index and St George’s Respiratory Questionnaire were observed with both treatments at all time points.,No differences were observed between UMEC and TIO in patient-reported outcomes.,Overall incidences of adverse events were similar for UMEC and TIO.,UMEC 62.5 μg demonstrated superior efficacy to TIO 18 μg on the primary end point of trough FEV1 at day 85.,Safety profiles were similar for both treatments. | NVA237 is a once-daily dry-powder formulation of the long-acting muscarinic antagonist glycopyrronium bromide in development for the treatment of chronic obstructive pulmonary disease (COPD).,The glycopyrronium bromide in COPD airways clinical study 1 (GLOW1) evaluated the efficacy, safety and tolerability of NVA237 in patients with moderate-to-severe COPD.,Patients with COPD with a smoking history of ≥ 10 pack-years, post-bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and ≥ 30% predicted normal and FEV1/forced vital capacity < 0.70 were enrolled.,Patients were randomized to double-blind treatment with NVA237 50 μg once daily or placebo for 26 weeks with inhaled/intranasal corticosteroids or H1 antagonists permitted in patients stabilized on them prior to study entry.,The primary outcome measure was trough FEV1 at Week 12.,A total of 822 patients were randomized to NVA237 (n = 552) or placebo (n = 270).,Least squares mean (± standard error) trough FEV1 at Week 12 was significantly higher in patients receiving NVA237 (1.408 ± 0.0105 L), versus placebo (1.301 ± 0.0137 L; treatment difference 108 ± 14.8 mL, p < 0.001).,Significant improvements in trough FEV1 were apparent at the end of Day 1 and sustained through Week 26.,FEV1 was significantly improved in the NVA237 group versus placebo throughout the 24-hour periods on Day 1 and at Weeks 12 and 26, and at all other visits and timepoints.,Transition dyspnoea index focal scores and St.,George's Respiratory Questionnaire scores were significantly improved with NVA237 versus placebo at Week 26, with treatment differences of 1.04 (p < 0.001) and-2.81 (p = 0.004), respectively.,NVA237 significantly reduced the risk of first moderate/severe COPD exacerbation by 31% (p = 0.023) and use of rescue medication by 0.46 puffs per day (p = 0.005), versus placebo.,NVA237 was well tolerated and had an acceptable safety profile, with a low frequency of cardiac and typical antimuscarinic adverse effects.,Once-daily NVA237 was safe and well tolerated and provided rapid, sustained improvements in lung function, improvements in dyspnoea, and health-related quality of life, and reduced the risk of exacerbations and the use of rescue medication.,ClinicalTrials.gov: NCT01005901 | 1 |
Chronic obstructive pulmonary disease (COPD) is a leading cause of death, morbidity, and health-care spending.,The Halifax, Nova Scotia-based INSPIRED COPD Outreach Program™ has proved highly beneficial for patients and the health-care system.,With direct investment of <$1-million CAD, a pan-Canadian quality improvement collaborative (QIC) supported the spread of INSPIRED to 19 teams in the 10 Canadian provinces contingent upon participation in evaluation.,The collaborative evaluation followed a mixed-methods summative approach relying on collated quantitative data, team documents, and surveys sent to core members of the 19 teams.,Survey questions included a series of multiple-choice responses, Likert scale ratings, and open-ended questions.,The qualitative evaluation entailed key informant interviews and focus groups undertaken between February and April 2016 post-collaborative.,Teams reported that the year-long QIC helped bring focus to a needed, though often overlooked area of improvement, facilitating innovation spread.,They report examples of new work practices as well as unanticipated cultural change (given the short QIC time frame).,Most teams gained new skills in quality improvement (QI) and evidence-based medicine, showing progress in their ability to measure and implement COPD care improvements.,Teams felt networking with other teams across the country toward a common solution as well as learning from a team of clinical innovators and evidence-based innovation were critical to their success.,Factors affecting sustainability included local leadership support, involvement of frontline clinicians, and sharing milestones to motivate continued QI.,The INSPIRED QIC enabled teams across Canada to adapt and implement a new COPD care model for high users of health-care with rapid improvements to work practices, cultural change, and skill sets, and at relatively low cost. | Chronic obstructive pulmonary disease (COPD) is common but largely underdiagnosed.,Case-finding initiatives have been evaluated in primary care, but few studies have explored the views of service providers on implementing them in practice.,To explore the views of primary health care providers on case finding for COPD.,A total of 20 semi-structured interviews were conducted from March 2014 to September 2014 among general practitioners, nurses, and managers from practices participating in a large COPD case-finding trial based in primary care in the West Midlands, UK.,Participants’ views were sought to explore perceived benefits, harms, barriers, and facilitators to implementing COPD case finding in practice.,Interviews were transcribed and analyzed using the framework method.,Participants felt that case finding improves patient care but also acknowledged potential harms to providers (increase in workload) and to patients (overdiagnosis).,Insufficient resources, poor knowledge of COPD, and limited access to diagnostic services were viewed as barriers to diagnosis, while provision of community respiratory services, including COPD specialist nurses, and support from secondary care were thought to be facilitators.,Participants also expressed a need for more education on COPD for both patients and clinicians.,Care providers believe that early detection of COPD improves patient care but also has accompanying harms.,Barriers to diagnosing COPD, such as insufficient expertise in primary care and limited access to diagnostic services in the community, should be explored and addressed.,The knowledge and attitudes of the public about COPD and its symptoms should also be investigated to inform future education and awareness-raising strategies. | 1 |
Sputum and blood eosinophil counts predict corticosteroid effects in COPD patients.,Bacterial infection causes increased airway neutrophilic inflammation.,The relationship of eosinophil counts with airway bacterial load in COPD patients is uncertain.,We tested the hypothesis that bacterial load and eosinophil counts are inversely related.,COPD patients were seen at stable state and exacerbation onset.,Sputum was processed for quantitative polymerase chain reaction detection of the potentially pathogenic microorganisms (PPM) H. influenzae, M. catarrhalis and S. pneumoniae.,PPM positive was defined as total load ≥1 × 104copies/ml.,Sputum and whole blood were analysed for differential cell counts.,At baseline, bacterial counts were not related to blood eosinophils, but sputum eosinophil % was significantly lower in patients with PPM positive compared to PPM negative samples (medians: 0.5% vs.,1.25% respectively, p = 0.01).,Patients with PPM positive samples during an exacerbation had significantly lower blood eosinophil counts at exacerbation compared to baseline (medians: 0.17 × 109/L vs.,0.23 × 109/L respectively, p = 0.008), while no blood eosinophil change was observed with PPM negative samples.,These findings indicate an inverse relationship between bacterial infection and eosinophil counts.,Bacterial infection may influence corticosteroid responsiveness by altering the profile of neutrophilic and eosinophilic inflammation.,The online version of this article (doi:10.1186/s12931-017-0570-5) contains supplementary material, which is available to authorized users. | Patients with chronic obstructive pulmonary disease (COPD) commonly suffer from acute exacerbations (AECOPD) and display varying disease severity.,However, there is no available biomarker for the classification of AECOPD.,This study is aimed at investigating the sputum cellular profiles to classify patients with AECOPD.,A total of 83 patients with AECOPD and 26 healthy controls were recruited.,Their demographic and clinical characteristics were recorded, and their lung function was examined.,The phenotypes of sputum inflammatory cells were characterised, and the concentrations of sputum and serum amyloid-A (SAA), C-reactive protein (CRP), interleukin-6 (IL-6), and matrix metalloproteinase-9 (MMP-9) were measured.,Based on the sputum inflammatory cell profiles, individual patients were categorized into one of the four subgroups with inflammatory eosinophilic, neutrophilic, paucigranulocytic, and mixed granulocytic AECOPD.,Most AECOPD patients were reevaluated within 12-14 months after discharge.,There were 10 (12%) eosinophilic, 36 (43%) neutrophilic, 5 (6%) mixed granulocytic, and 32 (39%) paucigranulocytic AECOPD patients.,The patients with mixed granulocytic or neutrophilic AECOPD had a higher BODE score, more sputum inflammatory cells, lower lung function, and longer hospital stay, accompanied by higher concentrations of sputum MMP-9, IL-6 and CRP, and serum SAA, IL-6 and CRP.,Notably, 83% of patients with neutrophilic AECOPD displayed evidence of bacterial infection and many of them responded poorly to standard therapies.,In addition, patients with mixed granulocytic or neutrophilic stable COPD remained at lower lung functions and higher levels of inflammation.,Patients with AECOPD display heterogeneous inflammation, and the profiles of sputum inflammatory cells may be used as valuable biomarkers for the classification of AECOPD patients. | 1 |
Despite the benefits of beta-blockers in patients with established or sub-clinical coronary artery disease, their use in patients with chronic obstructive pulmonary disease (COPD) has been controversial.,Currently, no systematic review has examined the impact of beta-blockers on mortality in COPD.,We systematically searched electronic bibliographic databases including MEDLINE, EMBASE and Cochrane Library for clinical studies that examine the association between beta-blocker use and all cause mortality in patients with COPD.,Risk ratios across studies were pooled using random effects models to estimate a pooled relative risk across studies.,Publication bias was assessed using a funnel plot.,Our search identified nine retrospective cohort studies that met the study inclusion criteria.,The pooled relative risk of COPD related mortality secondary to beta-blocker use was 0.69 (95% CI: 0.62-0.78; I2=82%).,The results of this review are consistent with a protective effect of beta-blockers with respect to all cause mortality.,Due to the observational nature of the included studies, the possibility of confounding that may have affected these results cannot be excluded.,The hypothesis that beta blocker therapy might be of benefit in COPD needs to be evaluated in randomised controlled trials. | Being overweight or obese is associated with a higher rate of survival in patients with advanced chronic obstructive pulmonary disease (COPD).,This paradoxical relationship indicates that the influence of nutritional status on functional parameters should be further investigated.,To investigate the impact of nutritional status on body composition, exercise capacity and respiratory muscle strength in severe chronic obstructive pulmonary disease patients.,Thirty-two patients (nine women) were divided into three groups according to their body mass indices (BMI): overweight/obese (25 ≤ BMI ≤ 34.9 kg/m2, n=8), normal weight (18.5 ≤ BMI ≤ 24.9 kg/m2, n=17) and underweight (BMI <18.5 kg/m2, n=7).,Spirometry, bioelectrical impedance, a six-minute walking distance test and maximal inspiratory and expiratory pressures were assessed.,Airway obstruction was similar among the groups (p=0.30); however, overweight/obese patients had a higher fat-free mass (FFM) index [FFMI=FFM/body weight2 (mean±SEM: 17±0.3 vs.,15±0.3 vs.,14±0.5 m/kg2, p<0.01)], exercise capacity (90±8 vs. 79±6 vs. 57±8 m, p=0.02) and maximal inspiratory pressure (63±7 vs. 57±5 vs. 35±8 % predicted, p=0.03) in comparison to normal weight and underweight patients, respectively.,In addition, on backward multiple regression analysis, FFMI was the unique independent predictor of exercise capacity (partial r=0.52, p<0.01).,Severe chronic obstructive pulmonary disease (COPD) patients who were overweight or obese had a greater FFM, exercise capacity and inspiratory muscle strength than patients with the same degree of airflow obstruction who were of normal weight or underweight, and higher FFM was independently associated with higher exercise capacity.,These characteristics of overweight or obese patients might counteract the drawbacks of excess weight and lead to an improved prognosis in COPD. | 1 |
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. | Chronic obstructive pulmonary disease (COPD) is a major public health problem.,The aim of this study was to identify genes involved in emphysema severity in COPD patients.,Gene expression profiling was performed on total RNA extracted from non-tumor lung tissue from 30 smokers with emphysema.,Class comparison analysis based on gas transfer measurement was performed to identify differentially expressed genes.,Genes were then selected for technical validation by quantitative reverse transcriptase-PCR (qRT-PCR) if also represented on microarray platforms used in previously published emphysema studies.,Genes technically validated advanced to tests of biological replication by qRT-PCR using an independent test set of 62 lung samples.,Class comparison identified 98 differentially expressed genes (p < 0.01).,Fifty-one of those genes had been previously evaluated in differentiation between normal and severe emphysema lung. qRT-PCR confirmed the direction of change in expression in 29 of the 51 genes and 11 of those validated, remaining significant at p < 0.05.,Biological replication in an independent cohort confirmed the altered expression of eight genes, with seven genes differentially expressed by greater than 1.3 fold, identifying these as candidate determinants of emphysema severity.,Gene expression profiling of lung from emphysema patients identified seven candidate genes associated with emphysema severity including COL6A3, SERPINF1, ZNHIT6, NEDD4, CDKN2A, NRN1 and GSTM3. | 1 |
The quality of care can be improved by the development and implementation of evidence-based treatment guidelines.,Different national guidelines for chronic obstructive pulmonary disease (COPD) exist in Europe and relevant differences may exist among them.,This was an evaluation of COPD treatment guidelines published in Europe and Russia in the past 7 years.,Each guideline was reviewed in detail and information about the most important aspects of patient diagnosis, risk stratification and pharmacotherapy was extracted following a standardised process.,Guidelines were available from the Czech Republic, England and Wales, Finland, France, Germany, Italy, Poland, Portugal, Russia, Spain and Sweden.,The treatment goals, criteria for COPD diagnosis, consideration of comorbidities in treatment selection and support for use of long-acting bronchodilators, were similar across treatment guidelines.,There were differences in measures used for stratification of disease severity, consideration of patient phenotypes, criteria for the use of inhaled corticosteroids and recommendations for other medications (e.g. theophylline and mucolytics) in addition to bronchodilators.,There is generally good agreement on treatment goals, criteria for diagnosis of COPD and use of long-acting bronchodilators as the cornerstone of treatment among guidelines for COPD management in Europe and Russia.,However, there are differences in the definitions of patient subgroups and other recommended treatments.,There are important differences between European national COPD guidelineshttp://ow.ly/U2P4y | Despite the availability of national and international guidelines, evidence suggests that chronic obstructive pulmonary disease (COPD) treatment is not always prescribed according to recommendations.,This study evaluated the current management of patients with COPD using a large UK primary-care database.,This analysis used electronic patient records and patient-completed questionnaires from the Optimum Patient Care Research Database.,Data on current management were analyzed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group and presence or absence of a concomitant asthma diagnosis, in patients with a COPD diagnosis at ≥35 years of age and with spirometry results supportive of the COPD diagnosis.,A total of 24,957 patients were analyzed, of whom 13,557 (54.3%) had moderate airflow limitation (GOLD Stage 2 COPD).,The proportion of patients not receiving pharmacologic treatment for COPD was 17.0% in the total COPD population and 17.7% in the GOLD Stage 2 subset.,Approximately 50% of patients in both cohorts were receiving inhaled corticosteroids (ICS), either in combination with a long-acting β2-agonist (LABA; 26.7% for both cohorts) or a LABA and a long-acting muscarinic antagonist (LAMA; 23.2% and 19.9%, respectively).,ICS + LABA and ICS + LABA + LAMA were the most frequently used treatments in GOLD Groups A and B.,Of patients without concomitant asthma, 53.7% of the total COPD population and 50.2% of the GOLD Stage 2 subset were receiving ICS.,Of patients with GOLD Stage 2 COPD and no exacerbations in the previous year, 49% were prescribed ICS.,A high proportion of GOLD Stage 2 COPD patients were symptomatic on their current management (36.6% with modified Medical Research Council score ≥2; 76.4% with COPD Assessment Test score ≥10).,COPD is not treated according to GOLD and National Institute for Health and Care Excellence recommendations in the UK primary-care setting.,Some patients receive no treatment despite experiencing symptoms.,Among those on treatment, most receive ICS irrespective of severity of airflow limitation, asthma diagnosis, and exacerbation history.,Many patients on treatment continue to have symptoms. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) carry significant consequences for patients and are responsible for considerable health-care costs-particularly if hospitalization is required.,Despite the importance of hospitalized exacerbations, relatively little is known about their determinants.,This study aimed to analyze predictors of hospitalized exacerbations and mortality in COPD patients.,This was a retrospective population-based cohort study.,We selected 900 patients with confirmed COPD aged ≥35 years by simple random sampling among all COPD patients in Cantabria (northern Spain) on December 31, 2011.,We defined moderate exacerbations as events that led a care provider to prescribe antibiotics or corticosteroids and severe exacerbations as exacerbations requiring hospital admission.,We observed exacerbation frequency over the previous year (2011) and following year (2012).,We categorized patients according to COPD severity based on forced expiratory volume in 1 second (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grades 1-4).,We estimated the odds ratios (ORs) by logistic regression, adjusting for age, sex, smoking status, COPD severity, and frequent exacerbator phenotype the previous year.,Of the patients, 16.4% had ≥1 severe exacerbations, varying from 9.3% in mild GOLD grade 1 to 44% in very severe COPD patients.,A history of at least two prior severe exacerbations was positively associated with new severe exacerbations (adjusted OR, 6.73; 95% confidence interval [CI], 3.53-12.83) and mortality (adjusted OR, 7.63; 95%CI, 3.41-17.05).,Older age and several comorbidities, such as heart failure and diabetes, were similarly associated.,Hospitalized exacerbations occurred with all grades of airflow limitation.,A history of severe exacerbations was associated with new hospitalized exacerbations and mortality. | The Continuing to Confront COPD International Patient Survey estimated the prevalence and burden of COPD across 12 countries.,Using data from this survey we evaluated the economic impact of COPD.,This cross-sectional, population-based survey questioned 4,343 subjects aged 40 years and older, fulfilling a case definition of COPD based on self-reported physician diagnosis or symptomatology.,Direct cost measures were based on exacerbations of COPD (treated and those requiring emergency department visits and/or hospitalisation), contacts with healthcare professionals, and COPD medications.,Indirect costs were calculated from work loss values using the Work Productivity and Activity Impairment scale.,Combined direct and indirect costs estimated the total societal costs per patient.,The annual direct costs of COPD ranged from $504 (South Korea) to $9,981 (USA), with inpatient hospitalisations (5 countries) and home oxygen therapy (3 countries) being the key drivers of direct costs.,The proportion of patients completely prevented from working due to their COPD ranged from 6% (Italy) to 52% (USA and UK) with 8 countries reporting this to be ≥20%.,Total societal costs per patient varied widely from $1,721 (Russia) to $30,826 (USA) but a consistent pattern across countries showed greater costs among those with increased burden of COPD (symptoms, health status and more severe disease) and a greater number of comorbidities.,The economic burden of COPD is considerable across countries, and requires targeted resources to optimise COPD management encompassing the control of symptoms, prevention of exacerbations and effective treatment of comorbidities.,Strategies to allow COPD patients to remain in work are important for addressing the substantial wider societal costs. | 1 |
Readmission rates following hospitalisation for COPD exacerbations are unacceptably high, and the contributing factors are poorly understood.,Our objective was to summarise and evaluate the factors associated with 30- and 90-day all-cause readmission following hospitalisation for an exacerbation of COPD.,We systematically searched electronic databases from inception to 5 November 2019.,Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.,Study quality was assessed using a modified version of the Newcastle-Ottawa Scale.,We synthesised a narrative from eligible studies and conducted a meta-analysis where this was possible using a random-effects model.,In total, 3533 abstracts were screened and 208 full-text manuscripts were reviewed.,A total of 32 papers met the inclusion criteria, and 14 studies were included in the meta-analysis.,The readmission rate ranged from 8.8-26.0% at 30 days and from 17.5-39.0% at 90 days.,Our narrative synthesis showed that comorbidities, previous exacerbations and hospitalisations, and increased length of initial hospital stay were the major risk factors for readmission at 30 and 90 days.,Pooled adjusted odds ratios (95% confidence intervals) revealed that heart failure (1.29 (1.22-1.37)), renal failure (1.26 (1.19-1.33)), depression (1.19 (1.05-1.34)) and alcohol use (1.11 (1.07-1.16)) were all associated with an increased risk of 30-day all-cause readmission, whereas being female was a protective factor (0.91 (0.88-0.94)).,Comorbidities, previous exacerbations and hospitalisation, and increased length of stay were significant risk factors for 30- and 90-day all-cause readmission after an index hospitalisation with an exacerbation of COPD.,Clinicians need to take a holistic approach including attention to comorbidities in the pre-discharge care of patients with COPD exacerbations to reduce the potential risk of readmission.http://bit.ly/2sucXKV | Chronic Obstructive Pulmonary Disease (COPD) represents the 3rd leading cause of death in the world.,The underlying pathophysiological mechanisms have been the focus of extensive research in the past.,The lung has a complex architecture, where structural cells interact continuously with immune cells that infiltrate into the pulmonary tissue.,Both types of cells express chemokines and chemokine receptors, making them sensitive to modifications of concentration gradients.,Cigarette smoke exposure and recurrent exacerbations, directly and indirectly, impact the expression of chemokines and chemokine receptors.,Here, we provide an overview of the evidence regarding chemokines involvement in COPD, and we hypothesize that a dysregulation of this tightly regulated system is critical in COPD evolution, both at a stable state and during exacerbations.,Targeting chemokines and chemokine receptors could be highly attractive as a mean to control both chronic inflammation and bronchial remodeling.,We present a special focus on the CXCL8-CXCR1/2, CXCL9/10/11-CXCR3, CCL2-CCR2, and CXCL12-CXCR4 axes that seem particularly involved in the disease pathophysiology. | 1 |
The aim of this study was to describe the impact of chronic obstructive pulmonary disease (COPD) on health status in the Burden of Obstructive Lung Disease (BOLD) populations.,We conducted a cross-sectional, general population-based survey in 11 985 subjects from 17 countries.,We measured spirometric lung function and assessed health status using the Short Form 12 questionnaire.,The physical and mental health component scores were calculated.,Subjects with COPD (post-bronchodilator forced expiratory volume in 1 s/forced vital capacity <0.70, n = 2269) had lower physical component scores (44±10 versus 48±10 units, p<0.0001) and mental health component scores (51±10 versus 52±10 units, p = 0.005) than subjects without COPD.,The effect of reported heart disease, hypertension and diabetes on physical health component scores (-3 to -4 units) was considerably less than the effect of COPD Global Initiative for Chronic Obstructive Lung Disease grade 3 (-8 units) or 4 (-11 units).,Dyspnoea was the most important determinant of a low physical and mental health component scores.,In addition, lower forced expiratory volume in 1 s, chronic cough, chronic phlegm and the presence of comorbidities were all associated with a lower physical health component score.,COPD is associated with poorer health status but the effect is stronger on the physical than the mental aspects of health status.,Severe COPD has a greater negative impact on health status than self-reported cardiovascular disease and diabetes.,COPD is related to worse health status: impairment is greater than in self-reported cardiovascular diseases or diabeteshttp://ow.ly/p1cIx | Pulmonary rehabilitation is an important treatment for patients with Chronic Obstructive Pulmonary Disease, who are often vitamin D deficient.,As vitamin D status is linked to skeletal muscle function, we aimed to explore if high dose vitamin D supplementation can improve the outcomes of rehabilitation in Chronic Obstructive Pulmonary Disease.,This study is a post-hoc subgroup analysis of a larger randomized trial comparing a monthly dose of 100.000 IU of vitamin D with placebo to reduce exacerbations.,50 Subjects who followed a rehabilitation program during the trial are included in this analysis.,We report changes from baseline in muscle strength and exercise performance between both study arms after 3 months of rehabilitation.,Vitamin D intervention resulted in significantly higher median vitamin D levels compared to placebo (51 [44-62] ng/ml vs 15 [13-30] ng/ml; p < 0.001).,Patients receiving vitamin D had significantly larger improvements in inspiratory muscle strength (-11±12 cmH2O vs 0±14 cmH2O; p = 0.004) and maximal oxygen uptake (110±211 ml/min vs -20±187 ml/min; p = 0.029).,Improvements in quadriceps strength (15±16 Nm) or six minutes walking distance (40±55 meter) were not significantly different from the effects in the placebo group (7±19 Nm and 11±74 meter; p>0.050).,High dose vitamin D supplementation during rehabilitation may have mild additional benefits to training. | 1 |
Physical activity (PA) is impaired from the early stages of COPD, is associated with a worsening of disease prognosis, and causes COPD patients to restrict their daily activities in order to avoid breathlessness.,The development of a simple tool to estimate physical activity level (PAL) could be useful for the management of COPD.,We investigated the differences in PA according to the modified Medical Research Council (mMRC) grade in patients with COPD.,A cross-sectional study was performed on stable outpatients with COPD.,PA was measured for 2 weeks using a triaxial accelerometer, and dyspnea grade was evaluated in all patients using the mMRC scale.,Ninety-eight patients were recruited.,Significant differences in PA duration were observed at all intensities according to the mMRC grade.,Despite treatment with controller medications, 59.2% of COPD patients had low PAL, which was <1.5 metabolic equivalents multiplied by hour per day.,COPD patients with an mMRC grade ≥2, which was the most balanced cutoff point in the receiver operating characteristic curve, showed a higher reduction rate of PAL (80.0% at mMRC grade 2, 71.4% at mMRC grade 3, and 100% at mMRC grade 4).,PA differed according to the mMRC grade, and mMRC grade ≥2 could predict a low PAL.,Therefore, assessment of breathlessness by the mMRC questionnaire would be useful to stratify the risks of reduced PA in COPD. | Breathlessness is a primary clinical feature of chronic obstructive pulmonary disease (COPD).,We aimed to describe the frequency of and factors associated with breathlessness in a cohort of COPD patients identified from the Clinical Practice Research Datalink (CPRD), a general practice electronic medical records database.,Patients with a record of COPD diagnosis after January 1 2008 were identified in the CPRD.,Breathlessness was assessed using the Medical Research Council (MRC) dyspnoea scale, with scoring ranging from 1-5, which has been routinely administered as a part of the regular assessment of patients with COPD in the general practice since April 2009.,Stepwise multivariate logistic regression estimated independent associations with dyspnoea.,Negative binomial regression evaluated a relationship between breathlessness and exacerbation rate during follow-up.,The total cohort comprised 49,438 patients diagnosed with COPD; 40,425 (82%) had any MRC dyspnoea grade recorded.,Of those, 22,770 (46%) had moderate-to-severe dyspnoea (MRC≥3).,Breathlessness increased with increasing airflow limitation; however, moderate-to-severe dyspnoea was also observed in 32% of patients with mild airflow obstruction.,Other factors associated with increased dyspnoea grade included female gender, older age (≥70 years), obesity (BMI ≥30), history of moderate-to-severe COPD exacerbations, and frequent visits to the general practitioner.,Patients with worse breathlessness were at higher risk of COPD exacerbations during follow-up.,Moderate-to-severe dyspnoea was reported by >40% of patients diagnosed with COPD in primary care.,Presence of dyspnoea, including even a perception of mild dyspnoea (MRC = 2), was associated with increased disease severity and a higher risk of COPD exacerbations during follow-up. | 1 |
Cigarette smoking is the most common risk factor for chronic obstructive pulmonary disease (COPD).,However, few studies of the attitudes toward COPD of smokers, the group at risk of developing this condition, have been conducted.,The purpose of this study was to explore the awareness of and attitudes toward COPD of current smokers.,The sample consisted of 502 individuals aged 45 and older from throughout Korea who smoked at least 10 packs of cigarettes per year.,Telephone interviews using a structured questionnaire were conducted with respondents.,First, we evaluated the health status of subjects, finding that 45.4% considered themselves to be in good health.,We also asked about COPD-related symptoms, and 60.6% of subjects reported such symptoms.,However, only 1.2% of subjects had been diagnosed with or treated for COPD, only 0.4% spontaneously mentioned COPD as a respiratory disease, and only 26.5% recognized COPD as a respiratory disease after seeing a list of such diseases.,Television ranked as the top source of information about COPD.,The willingness of 45.0% of subjects to stop smoking increased after being informed about COPD.,Despite having COPD-related symptoms, most smokers did not know that COPD is a respiratory disease.,The attitudes of smokers toward COPD and smoking cessation varied according to socioeconomic status.,In summary, a continuous effort to increase the awareness of COPD among smokers is needed.,Additionally, strategies tailored according to different socioeconomic groups will also be necessary. | Guideline recommendations for chronic obstructive pulmonary disease (COPD) are based on the results of large pharmaceutically-sponsored COPD studies (LPCS).,There is a paucity of data on disease characteristics at the primary care level, while the majority of COPD patients are treated in primary care.,We aimed to evaluate the external validity of six LPCS (ISOLDE, TRISTAN, TORCH, UPLIFT, ECLIPSE, POET-COPD) on which current guidelines are based, in relation to primary care COPD patients, in order to inform future clinical practice guidelines and trials.,Baseline data of seven primary care databases (n = 3508) from Europe were compared to baseline data of the LPCS.,In addition, we examined the proportion of primary care patients eligible to participate in the LPCS, based on inclusion criteria.,Overall, patients included in the LPCS were younger (mean difference (MD)-2.4; p = 0.03), predominantly male (MD 12.4; p = 0.1) with worse lung function (FEV1% MD -16.4; p<0.01) and worse quality of life scores (SGRQ MD 15.8; p = 0.01).,There were large differences in GOLD stage distribution compared to primary care patients.,Mean exacerbation rates were higher in LPCS, with an overrepresentation of patients with ≥1 and ≥2 exacerbations, although results were not statistically significant.,Our findings add to the literature, as we revealed hitherto unknown GOLD I exacerbation characteristics, showing 34% of mild patients had ≥1 exacerbations per year and 12% had ≥2 exacerbations per year.,The proportion of primary care patients eligible for inclusion in LPCS ranged from 17% (TRISTAN) to 42% (ECLIPSE, UPLIFT).,Primary care COPD patients stand out from patients enrolled in LPCS in terms of gender, lung function, quality of life and exacerbations.,More research is needed to determine the effect of pharmacological treatment in mild to moderate patients.,We encourage future guideline makers to involve primary care populations in their recommendations. | 1 |
Chronic obstructive pulmonary disease (COPD) affects over 250 million people globally, carrying a notable economic burden.,This systematic literature review aimed to highlight the economic burden associated with moderate-to-very severe COPD and to investigate key drivers of healthcare resource utilization (HRU), direct costs and indirect costs for this patient population.,Relevant publications published between January 1, 2006 and November 14, 2016 were captured from the Embase, MEDLINE and MEDLINE In-Process databases.,Supplemental searches from relevant 2015-2016 conferences were also performed.,Titles and abstracts were reviewed by two independent researchers against pre-defined inclusion and exclusion criteria.,Studies were grouped by the type of economic outcome presented (HRU or costs).,Where possible, data were also grouped according to COPD severity and/or patient exacerbation history.,In total, 73 primary publications were included in this review: 66 reported HRU, 22 reported direct costs and one reported indirect costs.,Most of the studies (94%) reported on data from either Europe or North America.,Trends were noted across multiple studies for higher direct costs (including mean costs per patient per year and mean costs per exacerbation) being associated with increasingly severe COPD and/or a history of more frequent or severe exacerbations.,Similar trends were noted according to COPD severity and/or exacerbation history for rate of hospitalization and primary care visits.,Multivariate analyses were reported by 29 studies and demonstrated the statistical significance of these associations.,Several other drivers of increased costs and HRU were highlighted for patients with moderate-to-very severe COPD, including comorbidities, and treatment history.,Moderate-to-very severe COPD represents a considerable economic burden for healthcare providers despite the availability of efficacious treatments and comprehensive guidelines on their use.,Further research is warranted to ensure cost-efficient COPD management, to improve treatments and ease budgetary pressures. | Quality of life (QoL) has a weak relationship with lung function (LF) impairment in COPD; some cope well despite poor LF, whereas others suffer disproportionate QoL impairment despite well-preserved LF.,Adjuvant non-pharmacological interventions such as rehabilitation and psychological/behavioural support may help if acceptable and targeted appropriately, but they are under-used and sometimes declined by patients.,This study aimed to explore and understand variations in experiences and coping strategies in patients with different severities of disease and disease-specific QoL.,Thirty-four participants were purposively sampled across a spectrum of LF and QoL impairment, to cover a grid of sub-groups (‘very severe LF, good QoL’, moderate LF, poor QoL’ and so on).,Semi-structured interviews, digitally recorded, were analysed by thematic analysis.,Data saturation was achieved.,Four themes emerged: symptom impact, coping strategies, coping challenges and support needs.,Most of them described using multiple coping strategies, yet over half reported significant challenges coping with COPD, including psychological impact, non-acceptance of diagnosis and/or disease progression, effects of co-morbidities and inadequate self-management skills.,Approximately half of the participants wanted further help, ideally non-pharmacological, across all LF impairment groups but mainly with lower QoL.,Those with lower QoL additionally reported greater psychological distress and greater use of non-pharmacological support strategies where accessible.,Patients who develop effective coping strategies have a better QoL independent of objective LF, whereas others cope poorly, are aware of this and report more use of non-pharmacological approaches.,This study suggests that severely impaired QoL, irrelevant of lung function, is a powerful patient-centred indication to explore the positive benefits of psychological and behavioural support for distressed COPD patients. | 1 |
Chronic obstructive pulmonary disease (COPD) is one of the most common causes of mortality and a major contributor to morbidity.,Longitudinal clinical practice data yielding information on the characteristics of the disease, its natural course, and management are limited.,To investigate and describe the COPD population from a nationwide perspective during an 11-year period (1999-2009) with a focus on management, co-morbidity, and mortality.,This observational retrospective epidemiological study linked electronic medical records data from patients with COPD in primary care to mandatory Swedish hospital, drug and Cause of Death registry data from 1999 to 2009 (PATHOS).,A total of 21,361 patients with a COPD diagnosis were included (mean age 68.0 years, 53% females).,The proportion of patients diagnosed in primary care increased from 59% in 1999 to 81% in 2009 and the mean age at diagnosis decreased from 73 to 66 years.,The number of exacerbations decreased from 3.0 to 1.3 and COPD-related hospitalisations decreased from 1.02 to 0.20 per patient per year.,Prescriptions of long-acting muscarinic antagonists and fixed combinations of inhaled corticosteroid/long-acting β2-agonist inhalers increased from 0% to 36% and 37%, respectively.,The most common co-morbidities were hypertension, heart failure, ischaemic heart disease, and diabetes.,Overall life expectancy was 8.3±6.8 years shorter in patients with COPD than in the general population, and all-cause mortality was 3.5 times higher.,Management of COPD in Sweden has improved during the 11-year study period.,Despite this, patients with COPD have a substantially reduced life expectancy than the general population. | Chronic obstructive pulmonary disease (COPD) is considered to be a respiratory disease with systemic manifestations.,Some multidimensional staging systems, not based solely on the level of airflow limitation, have been developed; however, these systems have rarely been compared.,We previously recruited 150 male outpatients with COPD for an analysis of factors related to mortality.,For this report, we examined the discriminative and prognostic predictive properties of three COPD multidimensional measurements.,These indices were the modified BODE (mBODE), which includes body mass index, airflow obstruction, dyspnea, and exercise capacity; the ADO, composed of age, dyspnea, and airflow obstruction; and the modified DOSE (mDOSE), comprising dyspnea, airflow obstruction, smoking status, and exacerbation frequency.,Among these indices, the frequency distribution of the mBODE index was the most widely and normally distributed.,Univariate Cox proportional hazards analyses revealed that the scores on three indices were significantly predictive of 5-year mortality of COPD (P < 0.001).,The scores on the mBODE and ADO indices were more significantly predictive of mortality than forced expiratory volume in 1 second, the Medical Research Council dyspnea score, and the St.,George’s Respiratory Questionnaire total score.,However, peak oxygen uptake on progressive cycle ergometry was more significantly related to mortality than the scores on the three indices (P < 0.0001).,The multidimensional staging systems using the mBODE, ADO, and mDOSE indices were significant predictors of mortality in COPD patients, although exercise capacity had a more significant relationship with mortality than those indices.,The mBODE index was superior to the others for its discriminative property.,Further discussion of the definition of disease severity is necessary to promote concrete multidimensional staging systems as a new disease severity index in guidelines for the management of COPD. | 1 |
Chronic airflow obstruction affects a wide range of airway diseases, the most frequent of which are asthma, COPD, and bronchiectasis; they are clearly identifiable in their extremes, but quite frequently overlap in some of their pathophysiological and clinical characteristics.,This has generated the description of new mixed or overlapping disease phenotypes with no clear biological grounds.,In this special article, a group of experts provides their perspective and proposes approaching the treatment of chronic airway disease (CAD) through the identification of a series of therapeutic goals (TG) linked to treatable traits (TT) - understood as clinical, physiological, or biological characteristics that are quantifiable using biomarkers.,This therapeutic approach needs validating in a clinical trial with the strategy of identification of TG and treatment according to TT for each patient independently of their prior diagnosis. | Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder characterized by incompletely reversible airflow obstruction.,Bacterial infection of the lower respiratory tract contributes to approximately 50% of COPD exacerbations.,Even during periods of stable lung function, the lung harbors a community of bacteria, termed the microbiome.,The role of the lung microbiome in the pathogenesis of COPD remains unknown.,The COPD lung microbiome, like the healthy lung microbiome, appears to reflect microaspiration of oral microflora.,Here we describe the COPD lung microbiome of 22 patients with Moderate or Severe COPD compared to 10 healthy control patients.,The composition of the lung microbiomes was determined using 454 pyrosequencing of 16S rDNA found in bronchoalveolar lavage fluid.,Sequences were analyzed using mothur, Ribosomal Database Project, Fast UniFrac, and Metastats.,Our results showed a significant increase in microbial diversity with the development of COPD.,The main phyla in all samples were Actinobacteria, Firmicutes, and Proteobacteria.,Principal coordinate analyses demonstrated separation of control and COPD samples, but samples did not cluster based on disease severity.,However, samples did cluster based on the use of inhaled corticosteroids and inhaled bronchodilators.,Metastats analyses demonstrated an increased abundance of several oral bacteria in COPD samples. | 1 |
To determine if there is a relationship between the levels of serum uric acid and the different Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages (1-4) classified by the severity of the airflow limitation in patients with stable chronic obstructive pulmonary disease (COPD).,Electronic databases, including PubMed®, Embase®, Web of Science™ and China National Knowledge Infrastructure (CNKI), were searched from inception to December 2018.,Observational studies that reported serum uric acid levels in stable COPD patients were included.,Two investigators independently extracted data and RevMan version 5.3 was used to carry out the statistical analyses.,Seven studies with 932 stable COPD patients and 401 healthy control subjects were included in this meta-analysis.,Serum uric acid levels were significantly higher in stable COPD patients compared with healthy control subjects (mean difference [MD] 1.91, 95% confidence interval [CI] 1.55, 2.28).,Serum uric acid levels were significantly lower in the GOLD 1+2 subgroup compared with the GOLD 3+4 subgroup (MD −1.39, 95% CI −1.63, −1.15).,Serum uric acid might be a useful biomarker for identifying disease severity in stable COPD patients, but further studies are needed to confirm this finding. | Hypoxemia is a major complication of COPD and is a strong predictor of mortality.,We previously identified independent risk factors for the presence of resting hypoxemia in the COPDGene cohort.,However, little is known about characteristics that predict onset of resting hypoxemia in patients who are normoxic at baseline.,We hypothesized that a combination of clinical, physiologic, and radiographic characteristics would predict development of resting hypoxemia after 5-years of follow-up in participants with moderate to severe COPD,We analyzed 678 participants with moderate-to-severe COPD recruited into the COPDGene cohort who completed baseline and 5-year follow-up visits and who were normoxic by pulse oximetry at baseline.,Development of resting hypoxemia was defined as an oxygen saturation ≤88% on ambient air at rest during follow-up.,Demographic and clinical characteristics, lung function, and radiographic indices were analyzed with logistic regression models to identify predictors of the development of hypoxemia.,Forty-six participants (7%) developed resting hypoxemia at follow-up.,Enrollment at Denver (OR 8.30, 95%CI 3.05-22.6), lower baseline oxygen saturation (OR 0.70, 95%CI 0.58-0.85), self-reported heart failure (OR 6.92, 95%CI 1.56-30.6), pulmonary artery (PA) enlargement on computed tomography (OR 2.81, 95%CI 1.17-6.74), and prior severe COPD exacerbation (OR 3.31, 95%CI 1.38-7.90) were independently associated with development of resting hypoxemia.,Participants who developed hypoxemia had greater decline in 6-min walk distance and greater 5-year decline in quality of life compared to those who remained normoxic at follow-up.,Development of clinically significant hypoxemia over a 5-year span is associated with comorbid heart failure, PA enlargement and severe COPD exacerbation.,Further studies are needed to determine if treatments targeting these factors can prevent new onset hypoxemia.,COPDGene is registered at ClinicalTrials.gov: NCT00608764 (Registration Date: January 28, 2008),The online version of this article (doi:10.1186/s12890-016-0331-0) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) is a highly prevalent condition associated with a high health care resource consumption and health care expenditures, driven mainly by exacerbations-related hospitalizations.,Telemedicine has been proposed as a mean for timely detection of exacerbation, but the available evidence is inadequate to provide conclusive information on its efficacy.,The aim of this study is to evaluate the efficacy of a telemonitoring system in reducing COPD-related hospitalizations in an elderly population with COPD.,This is a parallel arms, randomized trial including patients aged 65 or older with COPD in GOLD stages II and III enrolled in a Pulmonary Medicine outpatient facility.,Patients were randomly assigned to receive a non-invasive system able to telemonitor vital signs (oxygen saturation, heart rate, near-body temperature, overall physical activity) or standard care, and were followed up for 9 months.,The outcome measures were the number of exacerbations and exacerbation-related hospitalization.,Fifty patients were included in the telemonitoring group and 49 in the control group.,The incidence rate of respiratory events was 28/100 person/years in the telemonitoring group vs. 42/100 person/years in the control group (incidence rate ratio: 0.67, 95% CI: 0.32 - 1.36).,The corresponding figures for hospital admissions where 13/100 person/years and 20/100 person/years, respectively (IRR: 0.66, 95% CI: 0.21 - 1.86).,In our study, COPD patients followed up with the aid of a multiparametric remote monitoring system experienced a lower rate of exacerbations and COPD-related hospitalizations compared to patients followed up using the standard model of care.,These results need to be replicated in larger studies before they can be applied to the general COPD population.,Trial registration number: NCT01481506 (clinicaltrials.gov).,Funding: co-financed by Lazio Region and Intersistemi Inc. | The prevalence of major chronic illnesses, such as chronic obstructive pulmonary disease (COPD) and diabetes, is increasing.,Pulmonary rehabilitation and diabetes self-management education are important in the management of COPD and diabetes respectively.,However, not everyone can participate in the programmes offered at a hospital or other central locations, for reasons such as travel and transport.,Internet-enabled home-based programmes have the potential to overcome these barriers.,This study aims to assess patient acceptability of the delivery form and components of Internet-enabled programmes based on home groups for comprehensive pulmonary rehabilitation and for diabetes self-management education.,We have developed Internet-enabled home programmes for comprehensive pulmonary rehabilitation and for diabetes self-management education that include group education, group exercising (COPD only), individual consultations, educational videos and a digital health diary.,Our prototype technology platform makes use of each user’s own TV at home, connected to a computer, and a remote control.,We conducted a six-week home trial with 10 participants: one group with COPD and one with diabetes.,The participants were interviewed using semi-structured interviews.,Both home-based programmes were well accepted by the participants.,The group setting at home made it possible to share experiences and to learn from questions raised by others, as in conventional group education.,In the sessions, interaction and discussion worked well, despite the structure needed for turn taking.,The thematic educational videos were well accepted although they were up to 40 minutes long and their quality was below TV broadcasting standards.,Taking part in group exercising at home under the guidance of a physiotherapist was also well accepted by the participants.,Participants in the COPD group appreciated the social aspect of group education sessions and of exercising together, each in their own home.,The digital health diary was used as background information in the individual consultations and by some participants as a self-management tool.,Participant retention was high, with no dropouts.,None of the participants reported that the six-week duration of the home programmes was too long.,The Internet-enabled programmes for home-based groups in pulmonary rehabilitation and diabetes education were generally well accepted by the participants.,Our findings indicate that conventional programmes have the potential to be delivered in socially supportive group settings at home. | 1 |
Exacerbations, a leading cause of hospitalization in patients with chronic obstructive pulmonary disease (COPD), affect the quality of life and prognosis.,Treatment recommendations as provided in the evidence-based guidelines are not consistently followed, partly due to absence of simplified task-oriented approach to care.,In this study, we describe the development and implementation of a clinical pathway (CP) and evaluate its effectiveness in the management of COPD exacerbation.,We developed a CP and evaluated its effectiveness in a non-randomized prospective study with historical controls on patients admitted for exacerbation of COPD to Universiti Kebangsaan Malaysia Medical Centre (UKMMC).,Consecutive patients who were admitted between June 2009 and December 2010 were prospectively recruited into the CP group.,Non-CP historical controls were obtained from case records of patients admitted between January 2008 and January 2009.,Clinical outcomes were evaluated by comparing the length of stay (LOS), complication rates, readmissions, and mortality rates.,Ninety-five patients were recruited in the CP group and 98 patients were included in the non-CP historical group.,Both groups were comparable with no significant differences in age, sex and severity of COPD (p = 0.641).,For clinical outcome measures, patients in the CP group had shorter length of stay than the non-CP group (median (IQR): 5 (4-7) days versus 7 (7-9) days, p < 0.001) and 24.1% less complications (14.7% versus 38.8%, p < 0.001).,We did not find any significant differences in readmission and mortality rates.,The implementation of CP -reduced the length of stay and complication rates of patients hospitalized for acute exacerbation of COPD. | Randomized controlled trials, evidence-based medicine, clinical guidelines, and total quality management are some of the approaches used to render science-based health care services.,The clinical pathway for hospitalized patients suffering from acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is poorly established, although a clinical pathway is an integral part of total quality management.,To evaluate the outcomes of patients hospitalized with AECOPD in Japan, treated with a clinical pathway following published guidelines.,Prospective data were collected for patients with AECOPD admitted to a general hospital over a 5-year period since 2003.,The clinical pathway was designed to establish general rules for the entire treatment protocol.,The clinical pathway indicates which treatments and interventions should be performed, and when.,In this study, health care providers were required to check the clinical pathway sheets to determine the next step of treatment.,This study analyzed 276 hospitalizations in 165 patients.,The clinical pathway was interrupted and defined as a dropout in 45 cases (16.3%).,Nine patients died during hospitalization (3.3%).,Oxygen was administered in 232 hospitalizations (84.1%).,Noninvasive positive pressure ventilation (NPPV) treatment was administered in 110 hospitalizations (39.9%).,The rate of intubation in those cases where NPPV treatment had been administered was 8.2% (9 cases out of 110).,The average length of stay (LOS) was 20.3 days, and the median value was 15 days.,The LOS was longer than 30 days in 34 admissions (12.3%), mainly due to complications.,AECOPD can be managed using a clinical pathway.,This clinical pathway could fill the gap between guidelines and clinical practice. | 1 |
The respiratory microbiome is altered in COPD patients but its relationship with core components of the disease, such as the severity of airflow limitation, the frequency of exacerbations or the circulating levels of eosinophils, is unclear.,Cross-sectional study comprising 72 clinically stable COPD patients (mean age 68 [SD 7.9] years; FEV1 48.7 [SD 20.1]% of reference) who provided spontaneous sputum samples for 16S rRNA gene amplification and sequencing.,The microbiome composition was analysed with QIIME.,We observed that: (1) more severe airflow limitation was associated with reduced relative abundance (RA) of Treponema and an increase in Pseudomonas; (2) patients with ≥2 exacerbations the previous year showed a significantly different bacterial community with respect to non-exacerbators (p = 0.014), with changes in 13 genera, including an increase of Pseudomonas, and finally, (3) peripheral eosinophils levels ≥2% were associated with more diverse microbiome [Chao1 224.51 (74.88) vs 277.39 (78.92) p = 0.006; Shannon 3.94 (1.05) vs 4.54 (1.06) p = 0.020], and a significant increase in the RAs of 20 genera.,The respiratory microbiome in clinically stable COPD patients varies significantly according to the severity of airflow limitation, previous history of exacerbations and circulating eosinophils levels.,The online version of this article (10.1186/s12890-019-0867-x) contains supplementary material, which is available to authorized users. | While a subgroup of patients with exacerbations of chronic obstructive pulmonary disease (COPD) clearly benefit from antibiotics, their identification remains challenging.,We hypothesised that selective assessment of the balance between the two dominant bacterial groups (Gammaproteobacteria (G) and Firmicutes (F)) in COPD sputum samples might reveal a subgroup with a bacterial community structure change at exacerbation that was restored to baseline on recovery and potentially reflects effective antibiotic treatment.,Phylogenetically specific 16S rRNA genes were determined by quantitative real time PCR to derive a G:F ratio in serial sputum samples from 66 extensively-phenotyped COPD exacerbation episodes.,Cluster analysis based on Euclidean distance measures, generated across the 4 visit times (stable and exacerbation day: 0,14 and 42) for the 66 exacerbation episodes, revealed three subgroups designated HG, HF, and GF reflecting predominance or equivalence of the two target bacterial groups.,While the other subgroups showed no change at exacerbation, the HG cluster (n = 20) was characterized by G:F ratios that increased significantly at exacerbation and returned to baseline on recovery (p<0.00001); ratios in the HG group also correlated positively with inflammatory markers and negatively with FEV1.,At exacerbation G:F showed a significant receiver-operator-characteristic curve to identify the HG subgroup (AUC 0.90, p<0.0001).,The G:F ratio at exacerbation can be determined on a timescale compatible with decisions regarding clinical management.,We propose that the G:F ratio has potential for use as a biomarker enabling selective use of antibiotics in COPD exacerbations and hence warrants further clinical evaluation. | 1 |
It has been suggested that withdrawal of inhaled corticosteroids (ICS) in COPD patients on maintenance treatment results in deterioration of symptoms, lung function and exacerbations.,The aim of this real-life, prospective, multicentric study was to investigate whether withdrawal of ICS in COPD patients at low risk of exacerbation is linked to a deterioration in lung function and symptoms and to a higher frequency of exacerbations.,914 COPD patients, on maintenance therapy with bronchodilators and ICS, FEV1>50% predicted, and <2 exacerbations/year were recruited.,Upon decision of the primary physicians, 59% of patients continued their ICS treatment whereas in 41% of patients ICS were withdrawn and regular therapy was continued with long-acting bronchodilators mostly (91% of patients).,FEV1, CAT (COPD Assessment Test), and occurrence of exacerbations were measured at the beginning (T0) and at the end (T6) of the 6 months observational period.,816 patients (89.3%) concluded the study.,FEV1, CAT and exacerbations history were similar in the two groups (ICS and no ICS) at T0 and at T6.,We did not observe any deterioration of lung function symptoms, and exacerbation rate between the two groups at T0 and T6.,We conclude that the withdrawal of ICS, in COPD patients at low risk of exacerbation, can be safe provided that patients are left on maintenance treatment with long-acting bronchodilators. | Background: Combination therapy with a long-acting bronchodilator and an inhaled corticosteroid (ICS) is recommended in patients with chronic obstructive pulmonary disease (COPD) who have frequent exacerbations.,The efficacy and tolerability of the combination of budesonide/formoterol have been demonstrated in patients with COPD when administered via the dry powder inhaler (DPI) in a 1-year study and when administered via the hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) in a 6-month study.,Objective: This study assessed the long-term efficacy and tolerability of budesonide/formoterol HFA pMDI in patients with moderate to very severe COPD.,Methods: This was a 12-month, randomized, double-blind, double-dummy, parallel-group, active- and placebo-controlled, multicentre study (NCT00206167) of 1964 patients aged ≥40 years with moderate to very severe COPD conducted from 2005 to 2007 at 237 sites in the US, Europe and Mexico.,After 2 weeks of treatment based on previous therapy (ICSs, short-acting bronchodilators allowed), patients received one of the following treatments twice daily: budesonide/formoterol pMDI 160/4.5 μg × two inhalations (320/9 μg); budesonide/formoterol pMDI 80/4.5 μg × two inhalations (160/9 μg); formoterol DPI 4.5 μg × two inhalations (9 μg); or placebo.,Main outcome measures: The co-primary efficacy variables were pre-dose forced expiratory volume in 1 second (FEV1) and 1-hour post-dose FEV1.,Results: Budesonide/formoterol 320/9 μg demonstrated greater improvements in pre-dose FEV1 versus formoterol (p = 0.008), and both budesonide/formoterol doses demonstrated greater improvements in 1-hour post-dose FEV1 versus placebo (p < 0.001).,The rate of COPD exacerbations was lower in both budesonide/formoterol groups compared with formoterol and placebo (p ≤ 0.004).,Both budesonide/formoterol doses were more effective than placebo (p ≤ 0.006) for controlling dyspnoea and improving health status (St George’s Respiratory Questionnaire).,All treatments were generally well tolerated.,The incidence of pneumonia was not different for active (3.4-4.0%) and placebo (5.0%) groups.,Conclusions: Budesonide/formoterol pMDI (320/9 μg and 160/9 μg) improved pulmonary function and reduced symptoms and exacerbations over 1 year in patients with moderate to very severe COPD.,Only budesonide/formoterol pMDI 320/9 μg demonstrated greater efficacy for both co-primary variables compared with formoterol DPI 9 μg.,Both budesonide/formoterol pMDI dosages were well tolerated relative to formoterol and placebo.,Supplementary material is available for this article at 10.2165/00003495-200969050-00004 and is accessible for authorized users. | 1 |
Pulmonary rehabilitation (PR) reduces the number and duration of hospital admissions and readmissions, and improves health-related quality of life in patients with COPD.,Despite clinical guideline recommendations, under-referral and limited uptake to PR contribute to poor treatment access.,We reviewed published literature on the effectiveness of interventions to improve referral to and uptake of PR in patients with COPD when compared to standard care, alternative interventions, or no intervention.,The review followed recognized methods.,Search terms included “pulmonary rehabilitation” AND “referral” OR “uptake” applied to MEDLINE, EMBASE, CINAHL, PsycINFO, ASSIA, BNI, Web of Science, and Cochrane Library up to January 2018.,Titles, abstracts, and full papers were reviewed independently and quality appraised.,The protocol was registered (PROSPERO # 2016:CRD42016043762).,We screened 5,328 references.,Fourteen papers met the inclusion criteria.,Ten assessed referral and five assessed uptake (46,146 patients, 409 clinicians, 82 hospital departments, 122 general practices).,One was a systematic review which assessed uptake.,Designs, interventions, and scope of studies were diverse, often part of multifaceted evidence-based management of COPD.,Examples included computer-based prompts at practice nurse review, patient information, clinician education, and financial incentives.,Four studies reported statistically significant improvements in referral (range 3.5%-36%).,Two studies reported statistically significant increases in uptake (range 18%-21.5%).,Most studies had methodological and reporting limitations.,Meta-analysis was not conducted due to heterogeneity of study designs.,This review demonstrates the range of approaches aimed at increasing referral and uptake to PR but identifies limited evidence of effectiveness due to the heterogeneity and limitations of study designs.,Research using robust methods with clear descriptions of intervention, setting, and target population is required to optimize access to PR across a range of settings. | 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 |
Patients with chronic obstructive pulmonary disease (COPD) often have poor health-related quality of life (HRQoL) that is disproportionate to their degree of airflow limitation.,This study evaluated the association between St George’s Respiratory Questionnaire for COPD (SGRQ-C) score and forced expiratory volume in one second and investigated the factors responsible for high SGRQ-C score according to severity of airflow limitation.,Data from 1,264 COPD patients were obtained from the Korean COPD Subgroup Study (KOCOSS) cohort.,Patients were categorized into two groups according to severity of airflow limitation: mild-to-moderate and severe-to-very severe COPD groups.,We evaluated the clinical factors associated with high SGRQ-C score (≥25) in each COPD patient group.,Of the 1,264 COPD patients, 902 (71.4%) had mild-to-moderate airflow limitation and 362 (28.6%) had severe-to-very severe airflow limitation.,Of the mild-to-moderate COPD patients, 59.2% (534/902) had high SGRQ-C score, while 80.4% (291/362) of the severe-to-very severe COPD patients had high SGRQ-C score.,The association between SGRQ-C score and post-bronchodilator forced expiratory volume in one second (% predicted) was very weak in the mild-to-moderate COPD patients (r=−0.103, p=0.002) and weak in the severe-to-very severe COPD patients (r=−0.219, p<0.001).,Multiple logistic regression analysis revealed that age, being an ex- or current smoker, lower level of education, cough, dyspnea, and number of comorbidities with congestive heart failure, hyperlipidemia, and depression were significantly associated with high SGRQ-C score in mild-to-moderate COPD patients.,In comparison, being an ex-smoker and having respiratory symptoms including sputum and dyspnea were significant factors associated with high SGRQ-C score in severe-to-very severe COPD patients.,In addition to the respiratory symptoms of dyspnea and cough, high SGRQ-C score was associated with extra-pulmonary comorbidities in mild-to-moderate COPD patients.,However, only respiratory symptoms such as sputum and dyspnea were significantly associated with high SGRQ-C score in severe-to-very severe COPD patients.,This indicates the need for an improved management strategy for relieving respiratory symptoms in COPD patients with poor HRQoL.,In addition, attention should be paid to extra-pulmonary comorbidities, especially in mild-to-moderate COPD patients with poor HRQoL. | Oxidative stress occurs when free radicals and other reactive species overwhelm the availability of antioxidants.,Reactive oxygen species (ROS), reactive nitrogen species, and their counterpart antioxidant agents are essential for physiological signaling and host defense, as well as for the evolution and persistence of inflammation.,When their normal steady state is disturbed, imbalances between oxidants and antioxidants may provoke pathological reactions causing a range of nonrespiratory and respiratory diseases, particularly chronic obstructive pulmonary disease (COPD).,In the respiratory system, ROS may be either exogenous from more or less inhalative gaseous or particulate agents such as air pollutants, cigarette smoke, ambient high-altitude hypoxia, and some occupational dusts, or endogenously generated in the context of defense mechanisms against such infectious pathogens as bacteria, viruses, or fungi.,ROS may also damage body tissues depending on the amount and duration of exposure and may further act as triggers for enzymatically generated ROS released from respiratory, immune, and inflammatory cells.,This paper focuses on the general relevance of free radicals for the development and progression of both COPD and pulmonary emphysema as well as novel perspectives on therapeutic options.,Unfortunately, current treatment options do not suffice to prevent chronic airway inflammation and are not yet able to substantially alter the course of COPD.,Effective therapeutic antioxidant measures are urgently needed to control and mitigate local as well as systemic oxygen bursts in COPD and other respiratory diseases.,In addition to current therapeutic prospects and aspects of genomic medicine, trending research topics in COPD are presented. | 1 |
Estimation suggests that at least 4 million people die, annually, as a result of chronic respiratory disease (CRD).,The Global Alliance against Chronic Respiratory Diseases (GARD) was formed following a mandate from the World Health Assembly to address this serious and growing health problem.,To investigate the prevalence of CRD in Russian symptomatic patients and to evaluate the frequency of major risk factors for CRD in Russia.,A cross-sectional, population-based epidemiological study using the GARD questionnaire on adults from 12 regions of the Russian Federation.,Common respiratory symptoms and risk factors were recorded.,Spirometry was performed in respondents with suspected CRD.,Allergic rhinitis (AR) and chronic bronchitis (CB) were defined by the presence of related symptoms according to the Allergic Rhinitis and its Impact on Asthma and the Global Initiative for Obstructive Lung Disease guidelines; asthma was defined based on disease symptoms; chronic obstructive pulmonary disease (COPD) was defined as a post-bronchodilator forced expiratory volume per 1 second/forced vital capacity ratio <0.7 in symptomatic patients, following the Global Initiative for Obstructive Lung Disease guidelines.,The number of questionnaires completed was 7,164 (mean age 43.4 years; 57.2% female).,The prevalence of asthma symptoms was 25.7%, AR 18.2%, and CB 8.6%.,Based on patient self-reported diagnosis, 6.9% had asthma, 6.5% AR, and 22.2% CB.,The prevalence of COPD based on spirometry in patients with respiratory symptoms was estimated as 21.8%.,The prevalence of respiratory diseases and risk factors was high in Russia when compared to available data.,For bronchial asthma and AR, the prevalence for related symptoms was higher than self-reported previous diagnosis. | Chronic Obstructive Pulmonary Disease (COPD) is a chronic disease with repeated exacerbations resulting in gradual debilitation.,The quality of life has been shown to be poor in patients with COPD despite efforts to improve self-management.,However, the evidence on the benefit of self-management in COPD is conflicting.,Whether this could be due to other unmet needs of patients have not been investigated.,Therefore, we aimed to explore unmet needs of patients from both patients and doctors managing COPD.,We conducted a qualitative study with doctors and patients in Malaysia.,We used convenience sampling to recruit patients until data saturation.,Eighteen patients and eighteen doctors consented and were interviewed using a semi-structured interview guide.,The interviews were audio-recorded, transcribed verbatim and checked by the interviewers.,Data were analysed using a thematic approach.,The themes were similar for both the patients and doctors.,Three main themes emerged: knowledge and awareness of COPD, psychosocial and physical impact of COPD and the utility of self-management.,Knowledge about COPD was generally poor.,Patients were not familiar with the term chronic obstructive pulmonary disease or COPD.,The word ‘asthma’ was used synonymously with COPD by both patients and doctors.,Most patients experienced difficulties in their psychosocial and physical functions such as breathlessness, fear and helplessness.,Most patients were not confident in self-managing their illness and prefer a more passive role with doctors directing their care.,In conclusion, our study showed that knowledge of COPD is generally poor.,There was mislabelling of COPD as asthma by both patients and physicians.,This could have resulted in the lack of understanding of treatment options, outcomes, and prognosis of COPD.,The misconception that cough due to COPD was contagious, and breathlessness that resulted from COPD, had important physical and psychosocial impact, and could lead to social isolation.,Most patients and physicians did not favour self-management approaches, suggesting innovations based on self-management may be of limited benefit. | 1 |
Critically ill patients with chronic obstructive respiratory diseases (CORD) who require intensive care unit (ICU) admission are at particular risk for invasive bronchial-pulmonary aspergillosis (IBPA).,The purpose of this study is to investigate clinical features for rapid recognition of IBPA in critically ill patients with CORD.,We included 55 consecutive CORD patients in a respiratory ICU in a prospective, single-center, cohort study.,In this study, IBPA combined two entities: ATB and IPA.,Thirteen of 55 patients were diagnosed with IBPA.,Before ICU admission, three variables were independent predictors of IBPA with statistical significance: more than three kinds of antibiotics used before the ICU admission, accumulated doses of corticosteroids (>350 mg) received before the ICU admission, and APACHE II scores >18 (OR, 1.208; P = 0.022; OR, 8.661; P = 0.038; and OR, 19.488; P = 0.008, respectively).,After ICU admission, more IBPA patients had a high fever (>38.5°C) (46.2% versus 11.9%; P = 0.021), wheeze without exertion (84.6% versus 50.0%; P = 0.027), dry rales (84.6% versus 40.4%; P = 0.005), higher white blood cell counts (21 × 109/L versus 9.4 × 109/L; P = 0.012), lower mean arterial pressures (77.9 mm Hg versus 90.5 mm Hg; P = 0.019), and serum creatinine clearances (36.2 ml/min versus 68.8 ml/min; P < 0.001), and liver-function and coagulation abnormalities.,Bronchospasm, sputum ropiness, and plaque formation were more common for IBPA patients during bronchoscopy (66.7% versus 14.3%; P = 0.082; 18% versus 0; P = 0.169; and 73% versus 13%; P = 0.003, respectively).,More IBPA patients had nodules and patchiness on chest radiograph on day 1 of admission, which rapidly progressed to consolidation on day 7.,IBPA mortality was higher than that of non-IBPA patients (69.2% versus 16.7%; P = 0.001).,IBPA may be suspected in critically ill CORD patients with respiratory failure and clinical and bronchoscopic manifestations of severe infection, bronchospasm, and rapid progression of radiologic lesions that are irresponsive to steroids and antibiotics.,To avoid misdiagnosis and establish the microbiologic etiology, early bronchoscopy and tight radiologic follow-up should be performed. | 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 |
Bone marrow-derived mesenchymal stem cells (MSCs) have been identified as one possible strategy for the treatment of chronic obstructive pulmonary disease (COPD).,Our previous studies have demonstrated that MSC administration has therapeutic potential in airway inflammation and emphysema via a paracrine mechanism.,We proposed that MSCs reverse the inflammatory process and restore impaired lung function through their interaction with macrophages.,In our study, the rats were exposed to cigarette smoke (CS), followed by the administration of MSCs into the lungs for 5 weeks.,Here we show that MSC administration alleviated airway inflammation and emphysema through the down-regulation of cyclooxygenase-2 (COX-2) and COX-2-mediated prostaglandin E2 (PGE2) production, possibly through the effect on alveolar macrophages.,In vitro co-culture experiments provided evidence that MSCs down-regulated COX-2/PGE2 in macrophages through inhibition of the activation-associated phosphorylation of p38 MAPK and ERK.,Our data suggest that MSCs may relieve airway inflammation and emphysema in CS-exposed rat models, through the inhibition of COX-2/PGE2 in alveolar macrophages, mediated in part by the p38 MAPK and ERK pathways.,This study provides a compelling mechanism for MSC treatment in COPD, in addition to its paracrine mechanism. | Regenerative or stem cell therapy is an emerging field of treatment based on stimulation of endogenous resident stem cells or administration of exogenous stem cells to treat diseases or injury and to replace malfunctioning or damaged tissues.,Current evidence suggests that in the lung, these cells may participate in tissue homeostasis and regeneration after injury.,Animal and human studies have demonstrated that tissue-specific stem cells and bone marrow-derived cells contribute to lung tissue regeneration and protection, and thus administration of exogenous stem/progenitor cells or humoral factors responsible for the activation of endogenous stem/progenitor cells may be a potent next-generation therapy for chronic obstructive pulmonary disease.,The use of bone marrow-derived stem cells could allow repairing and regenerate the damaged tissue present in chronic obstructive pulmonary disease by means of their engraftment into the lung.,Another approach could be the stimulation of resident stem cells by means of humoral factors or photobiostimulation. | 1 |
Once-daily long-acting β2-agonists (LABAs) are an important treatment option, either alone or in combination with other inhaled long-acting bronchodilators in the management of chronic obstructive pulmonary disease (COPD).,To audit the effectiveness of indacaterol as maintenance therapy in patients with moderate-to-severe COPD (Global initiative for chronic Obstructive Lung Disease [GOLD] stage II/III).,This was a single-center audit of a primary care COPD cohort comprising all patients treated with indacaterol following treatment escalation (as per National Institute for Health and Care Excellence guidelines) or failure with other therapies.,The sample was restricted to patients treated for a minimum of 12 months with indacaterol, for whom preswitching and follow-up spirometry as well as exacerbation frequency data were available (GOLD spirometry guidelines).,Pulmonary function was assessed by spirometry (recorded as forced expiratory volume in 1 second [FEV1] expressed as percentage predicted).,Relevant self-reported qualitative information was recorded in descriptive terms for quality of life (QoL) assessment.,A total of 15 patients met the audit inclusion criteria (66.6% male, mean age 64.9±7.7 years).,COPD disease duration ranged from 1 to 22 years; 93% had GOLD stage II or III COPD.,Follow-up ranged in duration from 12 to 27 months.,Indacaterol was associated with a significant reduction in exacerbation frequency compared with the 12 months prior to initiation (P=0.02).,In those patients who experienced three or more exacerbations/year, mean exacerbation rate fell from 5.43±1.07 to 2.43±0.2 after 12 months treatment with indacaterol (P=0.02).,A reduction in dyspnea was noted in 53% of patients.,Similarly, improvements in exercise tolerance and well-being were self-reported in 67% and 93%, respectively.,Indacaterol was found to be an effective LABA as an escalation or switch medication in patients with moderate-to-severe COPD.,Indacaterol was effective both as monotherapy and in combination with a long-acting muscarinic antagonist.,Switching to indacaterol from a LABA/inhaled corticosteroid fixed-combination inhaler significantly reduced the number of acute exacerbations and also improved self-reported QoL. | Exacerbations of chronic obstructive pulmonary disease (COPD) are a major burden to patients and to society.,Little is known about the possible role of day-to-day patient-reported outcomes during an exacerbation.,This study aims to describe the day-to-day course of patient-reported health status during exacerbations of COPD and to assess its value in predicting clinical outcomes.,Data from two randomized controlled COPD exacerbation trials (n = 210 and n = 45 patients) were used to describe both the feasibility of daily collection of and the day-to-day course of patient-reported outcomes during outpatient treatment or admission to hospital.,In addition to clinical parameters, the BORG dyspnea score, the Clinical COPD Questionnaire (CCQ), and the St George’s Respiratory Questionnaire were used in Cox regression models to predict treatment failure, time to next exacerbation, and mortality in the hospital study.,All patient-reported outcomes showed a distinct pattern of improvement.,In the multivariate models, absence of improvement in CCQ symptom score and impaired lung function were independent predictors of treatment failure.,Health status and gender predicted time to next exacerbation.,Five-year mortality was predicted by age, forced expiratory flow in one second % predicted, smoking status, and CCQ score.,In outpatient management of exacerbations, health status was found to be less impaired than in hospitalized patients, while the rate and pattern of recovery was remarkably similar.,Daily health status measurements were found to predict treatment failure, which could help decision-making for patients hospitalized due to an exacerbation of COPD. | 1 |
Apoptosis plays a central role in the pathogenesis of chronic obstructive pulmonary disease (COPD), and this process can be regulated by mitochondrial transcription factor A (mtTFA).,Epigenetics is involved in the regulation and modification of the genes involved in lung cancer and COPD.,In this study, we determined the expression of mtTFA and its methylation levels in the COPD patients with lung cancer.,Twenty-one squamous cell lung cancer patients, 11 with COPD and 10 without COPD, undergoing pneumonectomy were enrolled.,The apoptotic index (AI) of pulmonary vascular endothelial cells was analyzed by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay.,The expression of mtTFA mRNA and protein was measured using PCR, immunohistochemistry and Western-blot.,Methylation of the mtTFA promoter was detected using bisulfite sequencing PCR.,Compared to the non-COPD group, the AI was higher, and expression of mtTFA mRNA and protein was lower in the COPD group (P<0.001).,Expression of the mtTFA protein was positively correlated with FEV1/Pre (r = 0.892, P<0.001), and negatively correlated with AI (r = −0.749, P<0.001) and smoke index (r = −0.763, P<0.001).,Percentage of mtTFA promoter methylation in the COPD patients was significantly higher compared to the non-COPD patients (P<0.05).,These results suggest that the expression of mtTFA mRNA and protein is down-regulated in the lung tissue from the COPD patients with squamous cell lung cancer, and the level of mtTFA protein is related to apoptosis of pulmonary vascular endothelial cells.,Aberrant mtTFA methylation may also play an important role in the pathogenesis of COPD. | 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 |
Debate exists regarding which endpoints most sensitively reflect day-to-day variation in chronic obstructive pulmonary disease (COPD) symptoms and are most useful in clinical practice to predict COPD exacerbations.,We hypothesized that short-acting β2-agonist (SABA) reliever use would predict short- and long-term exacerbation risk in COPD patients.,We performed a retrospective analysis of data from a study (ClinicalTrials.gov registration: NCT00419744) comparing budesonide/formoterol 320/9 μg with formoterol 9 μg (both twice daily) in patients with moderate-to-very-severe COPD; reliever salbutamol 90 μg was provided.,First occurrence of reliever use >4 (low), >10 (medium), and >20 (high) inhalations/day was assessed as a predictor of short-term (3-week) exacerbation risk.,Mean daily reliever use in the week preceding the 2-month visit was investigated as a predictor of the long-term (10-month) exacerbation risk, using intervals of 2-5, 6-9, and ≥10 inhalations/day.,Overall, 810 patients were included (61 % male; mean age 63.2 years; post-bronchodilator forced expiratory volume in 1 s 37.7 % of predicted).,First occurrence of low, medium, or high reliever use was predictive of an exacerbation within the following 3 weeks; exacerbation risk increased significantly with increasing reliever use.,Mean reliever use over 1 week was predictive of long-term exacerbation risk.,Patients with mean use of 2-5, 6-9, and ≥10 inhalations/day exhibited 21 %, 67 %, and 135 % higher exacerbation rates, respectively, in the following 10 months, compared with <2 inhalations/day.,Budesonide/formoterol was associated with lower short- and long-term exacerbation risk than formoterol in all reliever-use groups.,SABA reliever use is a predictor of short- and long-term exacerbation risk in moderate-to-very-severe COPD patients with a history of exacerbations receiving budesonide/formoterol or formoterol. | Exercise limitation, dynamic hyperinflation, and exertional dyspnea are key features of symptomatic chronic obstructive pulmonary disease (COPD).,We assessed the effects of glycopyrronium bromide (NVA237), a once-daily, long-acting muscarinic antagonist, on exercise tolerance in patients with moderate to severe COPD.,Patients were randomized to a cross-over design of once-daily NVA237 50 μg or placebo for 3 weeks, with a 14-day washout.,Exercise endurance, inspiratory capacity (IC) during exercise, IC and expiratory volumes from spirometry, plethysmographic lung volumes, leg discomfort and dyspnea under exercise (Borg scales), and transition dyspnea index were measured on Days 1 and 21 of treatment.,The primary endpoint was endurance time during a submaximal constant-load cycle ergometry test on Day 21.,A total of 108 patients were randomized to different treatment groups (mean age, 60.5 years; mean post-bronchodilator, forced expiratory volume in 1 second [FEV1] 57.1% predicted).,Ninety-five patients completed the study.,On Day 21, a 21% difference in endurance time was observed between patients treated with NVA237 and those treated with placebo (P < 0.001); the effect was also significant from Day 1, with an increase of 10%.,Dynamic IC at exercise isotime and trough FEV1 showed significant and clinically relevant improvements from Day 1 of treatment that were maintained throughout the study.,This was accompanied by inverse decreases in residual volume and functional residual capacity.,NVA237 was superior to placebo (P < 0.05) in decreasing leg discomfort (Borg CR10 scale) on Day 21 and exertional dyspnea on Days 1 and 21 (transition dyspnea index and Borg CR10 scale at isotime).,The safety profile of NVA237 was similar to that of the placebo.,NVA237 50 μg once daily produced immediate and significant improvement in exercise tolerance from Day 1.,This was accompanied by sustained reductions in lung hyperinflation (indicated by sustained and significant improvements in IC at isotime), and meaningful improvements in trough FEV1 and dyspnea.,Improvements in exercise endurance increased over time, suggesting that mechanisms beyond improved lung function may be involved in enhanced exercise tolerance.,(ClinicalTrials.gov Identifier: NCT01154127). | 1 |
Concerns have been raised that treatment of COPD with inhaled corticosteroids may increase pneumonia risk.,Responding to a request from the European Medicines Agency Pharmacovigilance Risk Assessment Committee, a pooled analysis of interventional studies compared pneumonia risk with inhaled budesonide-containing versus non-budesonide-containing treatments and the impact of other clinically relevant factors.,AstraZeneca-sponsored, parallel-group, double-blind, randomized controlled trials meeting the following criteria were included: >8 weeks’ duration; ≥60 patients with COPD; inhaled budesonide treatment arm (budesonide/formoterol or budesonide); and non-budesonide-containing comparator arm (formoterol or placebo).,Primary and secondary outcomes were time to first pneumonia treatment-emergent serious adverse event (TESAE) and treatment-emergent adverse event (TEAEs), respectively, analyzed using Cox regression models stratified by study.,Eleven studies were identified; 10,570 out of 10,574 randomized patients receiving ≥1 dose of study treatment were included for safety analysis (budesonide-containing, n=5,750; non-budesonide-containing, n=4,820).,Maximum exposure to treatment was 48 months.,The overall pooled hazard ratio (HR), comparing budesonide versus non-budesonide-containing treatments, was 1.15 for pneumonia TESAEs (95% confidence interval [CI]: 0.83, 1.57) and 1.13 for pneumonia TEAEs (95% CI: 0.94, 1.36).,The annual incidence of pneumonia TESAEs was 1.9% and 1.5% for budesonide-containing and non-budesonide-containing treatments, respectively.,Comparing budesonide/formoterol with non-budesonide-containing treatment, the HRs for pneumonia TESAEs and TEAEs were 1.00 (95% CI: 0.69, 1.44) and 1.21 (95% CI: 0.93, 1.57), respectively.,For budesonide versus placebo, HRs were 1.57 for pneumonia TESAEs (95% CI: 0.90, 2.74) and 1.07 for pneumonia TEAEs (95% CI: 0.83, 1.38).,This pooled analysis found no statistically significant increase in overall risk for pneumonia TESAEs or TEAEs with budesonide-containing versus non-budesonide-containing treatments.,However, a small increase in risk with budesonide-containing treatment cannot be ruled out; there is considerable heterogeneity in study designs and patient characteristics, particularly in the early budesonide studies, and each study contributes <40 pneumonia TESAEs. | The clinical efficacy and safety of a mometasone furoate/formoterol fumarate (MF/F) fixed-dose combination formulation administered via a metered-dose inhaler was investigated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).,Two 52-week, multicenter, double-blind, placebo-controlled trials with identical study designs were conducted in current or ex-smokers (aged ≥40 years), and pooled study results are presented herein.,Subjects (n = 2251) were randomized to 26 weeks of twice-daily treatment with MF/F 400/10 μg, MF/F 200/10 μg, MF 400 μg, F 10 μg, or placebo.,After the 26-week treatment period, placebo subjects completed the trial and 75% of subjects on active treatment entered a 26-week safety extension.,Coprimary efficacy variables were mean changes in forced expiratory volume in one second (FEV1), area under the curve from 0 to 12 hours postdose (AUC0-12 h), and morning predose/trough FEV1 from baseline to the week 13 endpoint.,Key secondary efficacy variables were St George’s Respiratory Questionnaire scores, symptom-free nights, time-to-first exacerbation, and partly stable COPD at the week 26 endpoint.,In the 26-week treatment period, significantly greater increases in FEV1 AUC0-12 h occurred with MF/F 400/10 versus MF 400 and placebo at the week 13 and week 26 endpoints (P ≤ 0.032).,These increases were over three-fold greater with MF/F 400/10 than with MF 400.,Also, significantly greater increases in morning predose/trough FEV1 occurred with MF/F 400/10 versus F 10 and placebo at the week 13 endpoint (P < 0.05).,The increase was four-fold greater with MF/F 400/10 than with F 10.,All active treatment groups achieved minimum clinically important differences from baseline (>4 units) in St George’s Respiratory Questionnaire scores at week 26.,Symptom-free nights increased by ≥14% in the MF/F 400/10, MF 400, and F 10 groups (P ≤ 0.033 versus placebo).,The incidence of exacerbations was lower in the MF/F groups (≤33.3%) than it was in the MF, formoterol, and placebo groups (≥33.8%) over the 26-week treatment period.,The incidence of adverse events was similar in the active-treated and placebo-treated subjects across 26 weeks of treatment.,Over the 1-year study period, there were no notable differences in the incidence or types of adverse events between the MF/F 400/10 and MF/F 200/10 groups compared with the MF or formoterol groups.,Differences in rates of individual treatment-emergent adverse events were <3% between treatment groups.,Rates of pneumonia were low (≤2%) across all treatment groups.,Patients treated with MF/F demonstrated significant improvements in lung function, health status, and exacerbation rates.,Although significant improvements were seen with both doses, a trend showing a dose-response effect was observed in the lung function measurements. | 1 |
The quality of care can be improved by the development and implementation of evidence-based treatment guidelines.,Different national guidelines for chronic obstructive pulmonary disease (COPD) exist in Europe and relevant differences may exist among them.,This was an evaluation of COPD treatment guidelines published in Europe and Russia in the past 7 years.,Each guideline was reviewed in detail and information about the most important aspects of patient diagnosis, risk stratification and pharmacotherapy was extracted following a standardised process.,Guidelines were available from the Czech Republic, England and Wales, Finland, France, Germany, Italy, Poland, Portugal, Russia, Spain and Sweden.,The treatment goals, criteria for COPD diagnosis, consideration of comorbidities in treatment selection and support for use of long-acting bronchodilators, were similar across treatment guidelines.,There were differences in measures used for stratification of disease severity, consideration of patient phenotypes, criteria for the use of inhaled corticosteroids and recommendations for other medications (e.g. theophylline and mucolytics) in addition to bronchodilators.,There is generally good agreement on treatment goals, criteria for diagnosis of COPD and use of long-acting bronchodilators as the cornerstone of treatment among guidelines for COPD management in Europe and Russia.,However, there are differences in the definitions of patient subgroups and other recommended treatments.,There are important differences between European national COPD guidelineshttp://ow.ly/U2P4y | Treatment of stable chronic obstructive pulmonary disease (COPD) with long-acting bronchodilator (LABD) medications is recommended by the 2014 Global initiative for chronic Obstructive Lung Disease (GOLD) guidelines.,The primary objective of this study was to examine LABD prescription fills after a COPD-related hospitalization.,This retrospective observational study used claims from Truven Health MarketScan® Commercial and Medicare Supplemental databases.,Patients (age ≥40, commercial; age ≥65, Medicare supplemental) had a first hospitalization with a primary COPD diagnosis between April 1, 2009 and June 30, 2011 (index hospitalization) and were continuously enrolled for 1 year before and 9 months after hospitalization.,Patients were categorized according to pre-index and/or post-index pharmacy claims.,A total of 27,738 patients had an index hospitalization and met inclusion/exclusion criteria.,Of those, 19,783 patients had COPD as a primary or secondary diagnosis during the year before index hospitalization and were included in the analysis.,Approximately one quarter of the patients (26.32%) did not fill a prescription for an LABD or short-acting bronchodilator both 90 days before and 90 days after hospitalization.,During the 90-day pre-index period, 40.57% of patients filled an LABD (with or without a short-acting bronchodilator) prescription.,Over half of the patients (56.88%) filled an LABD prescription at some point during the 180-day post-index period, but, of those, a significantly greater proportion of patients filled an LABD prescription in the 1- to 90-day post-index period than in the 91- to 180-day post-index period (51.27% versus 43.66%; P<0.0001).,A significant proportion of COPD patients in this study did not fill an LABD prescription before hospitalization for COPD.,Moreover, hospitalization did not appear to greatly impact LABD initiation.,Lastly, patients who did not fill an LABD prescription within the first 90 days posthospitalization were not likely to fill an LABD prescription later.,Taken together, the results of this study suggest that many patients with COPD are undertreated. | 1 |
Cholesterol-ester transfer protein (CETP) plays a role in atherosclerosis, the inflammatory response to endotoxemia and in experimental and human sepsis.,Functional alterations in lipoprotein (LP) metabolism and immune cell populations, including macrophages, occur during sepsis and may be related to comorbidities such as chronic obstructive pulmonary disease (COPD).,Macrophages are significantly associated with pulmonary emphysema, and depending on the microenvironment, might exhibit an M1 or M2 phenotype.,Macrophages derived from the peritoneum and bone marrow reveal CETP that contributes to its plasma concentration.,Here, we evaluated the role of CETP in macrophage polarization and elastase-induced pulmonary emphysema (ELA) in human CETP-expressing transgenic (huCETP) (line 5203, C57BL6/J background) male mice and compared it to their wild type littermates.,We showed that bone marrow-derived macrophages from huCETP mice reduce polarization toward the M1 phenotype, but with increased IL-10.,Compared to WT, huCETP mice exposed to elastase showed worsened lung function with an increased mean linear intercept (Lm), reflecting airspace enlargement resulting from parenchymal destruction with increased expression of arginase-1 and IL-10, which are M2 markers.,The cytokine profile revealed increased IL-6 in plasma and TNF, and IL-10 in bronchoalveolar lavage (BAL), corroborating with the lung immunohistochemistry in the huCETP-ELA group compared to WT-ELA.,Elastase treatment in the huCETP group increased VLDL-C and reduced HDL-C.,Elastase-induced pulmonary emphysema in huCETP mice promotes lung M2-like phenotype with a deleterious effect in experimental COPD, corroborating the in vitro result in which CETP promoted M2 macrophage polarization.,Our results suggest that CETP is associated with inflammatory response and influences the role of macrophages in COPD. | The prevalence of physical frailty and its clinical characteristics in advanced chronic obstructive pulmonary disease (COPD) is unknown, as well as the usefulness of functional capacity tests to screen for physical frailty.,The aim of the study was to evaluate the proportion and clinical portrait of COPD patients with chronic respiratory failure exhibiting physical frailty at the time of referral to home-based pulmonary rehabilitation.,We also evaluate the usefulness of the short physical performance battery (SPPB) and timed-up and go (TUG) as potential screening tools for physical frailty.,Finally, we evaluated the specific contribution of gait speed to the frailty Fried total score.,This was a prospective observational study in which physical frailty was defined using Fried criteria (body mass loss, exhaustion, low physical activity, slower walking and weakness).,Clinical portrait was documented from daily physical activity, exercise tolerance, functional capacity, anxiety and depressive symptoms, health-related quality of life, and fatigue scores.,The ability of the SPPB and TUG to predict physical frailty was investigated using receiver operating characteristic curves.,Contribution of each Fried criteria was evaluated with a principal component analysis (PCA).,Amongst the 44 included participants (FEV1, 33 ± 13% of predicted), 19 were physically frail.,Frail individuals had lower daily steps number, exercise tolerance and functional capacity, and higher fatigue, anxiety, and depressive symptom scores (p<0.05) compared to non-frail individuals.,SPPB and TUG did not have an acceptable detection accuracy for screening physical frailty.,PCA indicated that gait speed was the main contributor to the Fried total score of physical frailty.,Physical frailty affects a large proportion of COPD patients with chronic respiratory failure starting a home-based intervention and was associated with worse clinical status.,Although the present results need to be confirmed by adequately powered studies, gait speed seems to have the potential to become a simple screening tool for physical frailty in this population. | 1 |
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