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Fixed dose combination (FDC) dual bronchodilators that co-administer a long acting β2-adrenoceptor agonist (LABA) and a long acting muscarinic antagonist (LAMA) are a new class of inhaled treatment for chronic obstructive pulmonary disease (COPD).,This review focuses on the clinical evidence for the benefit of LABA/LAMA FDCs compared with monocomponent treatments, and also compared with active comparators that are widely used for the treatment of COPD, namely tiotropium and salmeterol-fluticasone.,Novel FDC dual bronchodilators include QVA149 and umeclidinium/vilanterol (UMEC/VI).,Long term clinical trials show that QVA149 and UMEC/VI are superior to monocomponent therapy in terms of trough forced expiratory volume in 1 s (FEV1), although the FEV1 improvement was limited to approximately 80-90% of the added monocomponent values.,This suggests that the effect of combining a LABA and a LAMA is not fully additive.,LABA/LAMA FDC were associated with the largest mean changes in symptoms and health status that were above the minimal clinically important difference, in contrast to the monocomponents.,Furthermore, these LABA/LAMA FDCs demonstrated superiority over the active comparators tiotropium and salmeterol-fluticasone in terms of trough FEV1 and patient-reported outcomes.,LABA/LAMA FDCs offer a simplified means of maximizing bronchodilation for COPD patients, with the improvements in lung function being mirrored by benefits in terms of symptoms and exacerbations.,The use of LABA/LAMA FDCs in clinical practice is set to grow and further studies are needed to define their optimal place in treatment guidelines. | Bronchodilators represent the hallmark of symptomatic treatment of Chronic Obstructive Pulmonary Disease (COPD).,There are four categories of bronchodilators: anticholinergics, methylxanthines, short-acting β2-agonists, and long-acting β2-agonists such as formoterol.,Significant research has been performed to investigate the efficacy, safety and tolerability of formoterol in the therapeutic field of COPD.,Formoterol exhibits a rapid onset of bronchodilation similar to that observed with salbutamol, yet its long bronchodilatory duration is comparable to salmeterol.,In addition, formoterol presents with a clear superiority in lung function improvement compared with either ipratropium bromide or oral theophylline, while its efficacy improves when administered in combination with ipratropium.,Formoterol has been shown to better reduce dynamic hyperinflation, which is responsible for exercise intolerance and dyspnea in COPD patients, compared with other bronchodilators, whereas it exerts synergistic effect with tiotropium.,Moreover, formoterol reduces exacerbations, increases days free of use of rescue medication and improves patients’ quality of life and disease symptoms.,Formoterol has a favorable safety profile and is better tolerated than theophylline.,Collectively, data extracted from multicenter clinical trials support formoterol as a valid therapeutic option in the treatment of COPD. | 1 |
Individuals with COPD may present reduced peripheral muscle strength, leading to impaired mobility.,Comprehensive pulmonary rehabilitation (PR) should include strength training, in particular to lower limbs.,Furthermore, simple tools for the assessment of peripheral muscle performance are required.,To assess the peripheral muscle performance of COPD patients by the sit-to-stand test (STST), as compared to the one-repetition maximum (1-RM), considered as the gold standard for assessing muscle strength in non-laboratory situations, and to evaluate the responsiveness of STST to a PR program.,Sixty moderate-to-severe COPD inpatients were randomly included into either the specific strength training group or into the usual PR program group.,Patients were assessed on a 30-second STST and 1-minute STST, 1-RM, and 6-minute walking test (6MWT), before and after PR.,Bland-Altman plots were used to evaluate the agreement between 1-RM and STST.,The two groups were not different at baseline.,In all patients, 1-RM was significantly related to the 30-second STST (r=0.48, P<0.001) and to 1-minute STST (r=0.36, P=0.005).,The 30-second STST was better tolerated in terms of the perceived fatigue (P=0.002) and less time consuming (P<0.001) test.,In the specific strength training group significant improvements were observed in the 30-second STST (P<0.001), 1-minute STST (P=0.005), 1-RM (P<0.001), and in the 6MWT (P=0.001).,In the usual PR program group, significant improvement was observed in the 30-second STST (P=0.042) and in the 6MWT (P=0.001).,Our study shows that in stable moderate-to-severe inpatients with COPD, STST is a valid and reliable tool to assess peripheral muscle performance of lower limbs, and is sensitive to a specific PR program. | Resistance training (RT) is thought to be effective in preventing muscle depletion, whereas endurance training (ET) is known to improve exercise capacity and health-related quality of life (HRQoL) in chronic obstructive pulmonary disease (COPD).,Our objectives were to assess the efficiency of combining RT with ET compared with ET alone.,We identified eligible studies through a systematic multi-database search.,One author checked titles and abstracts for relevance using broad inclusion criteria, whilst two independent authors checked the full-text copies for eligibility.,Two authors independently extracted data, and we assessed the risk of bias and quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation guidelines.,We included 11 randomized controlled trials (331 participants) and 2 previous systematic reviews.,The meta-analyses showed equal improvements in HRQoL, walking distance and exercise capacity.,However, we found moderate quality evidence of a significant increase in leg muscle strength favouring a combination of RT and ET (standardized mean difference of 0.69 (95% confidence interval: 0.39-0.98).,In conclusion, we found significantly increased leg muscle strength favouring a combination of RT with ET compared with ET alone.,Therefore, we recommend that RT should be incorporated in rehabilitation of COPD together with ET. | 1 |
Inadequacy of antioxidant nuclear factor-E2-related factor 2 (Nrf2) and endoplasmic reticulum stress-mediated unfolded protein response has been implicated in severe chronic obstructive pulmonary disease (COPD) and cigarette smoking-induced emphysema.,As evidence suggests that the ability to upregulate Nrf2 expression may influence the progression of COPD and no data exist up to now in ex-smokers with mild-moderate COPD, this study was first aimed to evaluate Nrf2 and unfolded protein response expression in peripheral blood mononuclear cells (PBMC) of mild-moderate ex-smokers with COPD compared to smoking habit-matched non-COPD subjects.,Then, we tested whether oxidative stress persists after cigarette smoking cessation and whether the concentrations of oxidized phospholipids (oxidation products of the phospholipid 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine [oxPAPC]) in the PBMC of the same subjects may have a causative role in determining the upregulation of Nrf2.,The expression (mRNA and protein) of Nrf2 and of its related gene heme oxygenase-1 was significantly increased in COPD group without differences in the unfolded protein response.,Plasma malondialdehyde, the circulating marker of oxidative stress, and oxPAPC in PBMC were significantly higher in COPD than in non-COPD subjects.,The fact that the expression of p47phox, a subunit of NADPH oxidase, was increased in PBMC of COPD patients and that it was directly correlated with oxPAPC may indicate that oxPAPC may be one of the determinants of oxidative stress-induced Nrf2 upregulation.,Finally, we also demonstrated that lung function inversely correlated with plasma malondialdehyde and with Nrf2 and heme oxygenase-1 mRNA expression in all subjects.,Our results indicate that mild-moderate ex-smokers with COPD may be able to counteract oxidative stress by increasing the expression of Nrf2/antioxidant-response elements.,Because Nrf2 failure significantly contributes to the development of COPD, our findings suggest that the possibility to prevent Nrf2 reduction may open a new scenario in helping to prevent the oxidative stress-associated lung function decline. | The morbidity and mortality associated with COPD exacts a considerable economic burden.,Comorbidities in COPD are associated with poor health outcomes and increased costs.,Our objective was to assess the impact of comorbidities on COPD-associated costs in a large administrative claims dataset.,This was a retrospective observational study of data from the Truven Health MarketScan Commercial Claims and Encounters and the MarketScan Medicare Supplemental Databases from January 1, 2009, to September 30, 2012.,Resource consumption was measured from the index date (date of first occurrence of non-rule-out COPD diagnosis) to 360 days after the index date.,Resource use (all-cause and disease-specific [ie, COPD- or asthma-related] ED visits, hospitalizations, office visits, other outpatient visits, and total length of hospital stay) and health-care costs (all-cause and disease-specific costs for ED visits, hospitalizations, office visits, and other outpatient visits and medical, prescription, and total health-care costs) were assessed.,Generalized linear models were used to evaluate the impact of comorbidities on total health-care costs, adjusting for age, sex, geographic location, baseline health-care use, employment status, and index COPD medication.,Among 183,681 patients with COPD, the most common comorbidities were cardiovascular disease (34.8%), diabetes (22.8%), asthma (14.7%), and anemia (14.2%).,Most patients (52.8%) had one or two comorbidities of interest.,The average all-cause total health-care costs from the index date to 360 days after the index date were highest for patients with chronic kidney disease ($41,288) and anemia ($38,870).,The impact on total health-care costs was greatest for anemia ($10,762 more, on average, than a patient with COPD without anemia).,Our analysis demonstrated that high resource use and costs were associated with COPD and multiple comorbidities. | 1 |
Cigarette smoke (CS) is a major risk factor for the development of lung cancer and chronic obstructive pulmonary disease (COPD).,Epithelial-mesenchymal transition (EMT) commonly coexists in lung cancer and COPD.,CS triggers many factors including matrix metalloproteinases (MMPs) production, contributing to EMT progression in the lungs.,Here, how Shp2 signaling regulates the CS-induced MMP-9 production and EMT progression were investigated in mouse lungs and in pulmonary epithelial cell cultures (NCI-H292) found CS induced MMP-9 production, EMT progression (increased vimentin and α-SMA; decreased E-cadherin) and collagen deposition in lung tissues; cigarette smoke extract (CSE) induced MMP-9 production and EMT-related phenotypes in NCI-H292 cells, which were partially prevented by Shp2 KO/KD or Shp2 inhibition.,The CSE exposure induced EMT phenotypes were suppressed by MMP-9 inhibition.,Recombinant MMP-9 induced EMT, which was prevented by MMP-9 inhibition or Shp2 KD/inhibition.,Mechanistically, CS and CSE exposure resulted in ERK1/2, JNK and Smad2/3 phosphorylation, which were suppressed by Shp2 KO/KD/inhibition.,Consequentially, the CSE exposure-induced MMP-9 production and EMT progression were suppressed by ERK1/2, JNK and Smad2/3 inhibitors.,Thus, CS induced MMP-9 production and EMT resulted from activation of Shp2/ERK1/2/JNK/Smad2/3 signaling pathways.,Our study contributes to the underlying mechanisms of pulmonary epithelial structural changes in response to CS, which may provide novel therapeutic solutions for treating associated diseases, such as COPD and lung cancer. | Cigarette smoke (CS)-induced mitochondrial damage with increased reactive oxygen species (ROS) production has been implicated in COPD pathogenesis by accelerating senescence.,Mitophagy may play a pivotal role for removal of CS-induced damaged mitochondria, and the PINK1 (PTEN-induced putative kinase 1)-PARK2 pathway has been proposed as a crucial mechanism for mitophagic degradation.,Therefore, we sought to investigate to determine if PINK1-PARK2-mediated mitophagy is involved in the regulation of CS extract (CSE)-induced cell senescence and in COPD pathogenesis.,Mitochondrial damage, ROS production, and cell senescence were evaluated in primary human bronchial epithelial cells (HBEC).,Mitophagy was assessed in BEAS-2B cells stably expressing EGFP-LC3B, using confocal microscopy to measure colocalization between TOMM20-stained mitochondria and EGFP-LC3B dots as a representation of autophagosome formation.,To elucidate the involvement of PINK1 and PARK2 in mitophagy, knockdown and overexpression experiments were performed.,PINK1 and PARK2 protein levels in lungs from patients were evaluated by means of lung homogenate and immunohistochemistry.,We demonstrated that CSE-induced mitochondrial damage was accompanied by increased ROS production and HBEC senescence.,CSE-induced mitophagy was inhibited by PINK1 and PARK2 knockdown, resulting in enhanced mitochondrial ROS production and cellular senescence in HBEC.,Evaluation of protein levels demonstrated decreased PARK2 in COPD lungs compared with non-COPD lungs.,These results suggest that PINK1-PARK2 pathway-mediated mitophagy plays a key regulatory role in CSE-induced mitochondrial ROS production and cellular senescence in HBEC.,Reduced PARK2 expression levels in COPD lung suggest that insufficient mitophagy is a part of the pathogenic sequence of COPD. | 1 |
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. | Home telehealth has the potential to benefit heart failure (HF) and chronic obstructive pulmonary disease (COPD) patients, however large-scale deployment is yet to be achieved.,The aim of this review was to assess levels of uptake of home telehealth by patients with HF and COPD and the factors that determine whether patients do or do not accept and continue to use telehealth.,This research performs a narrative synthesis of the results from included studies.,Thirty-seven studies met the inclusion criteria.,Studies that reported rates of refusal and/or withdrawal found that almost one third of patients who were offered telehealth refused and one fifth of participants who did accept later abandoned telehealth.,Seven barriers to, and nine facilitators of, home telehealth use were identified.,Research reports need to provide more details regarding telehealth refusal and abandonment, in order to understand the reasons why patients decide not to use telehealth.,The online version of this article (doi:10.1007/s12160-014-9607-x) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) and lung cancer, closely related to smoking, are major lung diseases affecting millions of individuals worldwide.,The generated gas mixture of smoking is proved to contain about 4,500 components such as carbon monoxide, nicotine, oxidants, fine particulate matter, and aldehydes.,These components were considered to be the principle factor driving the pathogenesis and progression of pulmonary disease.,A large proportion of lung cancer patients showed a history of COPD, which demonstrated that there might be a close relationship between COPD and lung cancer.,In the early stages of smoking, lung barrier provoked protective response and DNA repair are likely to suppress these changes to a certain extent.,In the presence of long-term smoking exposure, these mechanisms seem to be malfunctioned and lead to disease progression.,The infiltration of inflammatory cells to mucosa, submucosa, and glandular tissue caused by inhaled cigarette smoke is responsible for the destruction of matrix, blood supply shortage, and epithelial cell death.,Conversely, cancer cells have the capacity to modulate the proliferation of epithelial cells and produce of new vascular networks.,Comprehension understanding of mechanisms responsible for both pathologies is necessary for the prevention and treatment of COPD and lung cancer.,In this review, we will summarize related articles and give a glance of possible mechanism between cigarette smoking induced COPD and lung cancer. | Oxidative stress and inflammation are hypothesized to contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD).,Resveratrol (trans-3,5,4′-trihydroxystilbene) is known for its antioxidant and anti-inflammatory properties.,The study aimed to investigate the effects of resveratrol in a rat model with COPD on the regulation of oxidative stress and inflammation via the activation of Sirtuin1 (SIRTl) and proliferator-activated receptor-γ coactivator-1α (PGC-1α).,Thirty Wistar rats were randomly divided into three groups: control group, COPD group and resveratrol intervention group.,The COPD model was established by instilling with lipopolysaccharide (LPS) and challenging with cigarette smoke (CS).,The levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) in serum were measured.,The levels of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were measured.,The expression levels of SIRT1 and PGC-1α in the lung tissues were examined by immunohistochemistry as well as real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) and western blotting analysis.,After the treatment with resveratrol (50 mg/kg), compared with the COPD group, alleviation of inflammation and reconstruction in the small airways of the lungs were seen.,Resveratrol might be correlated not only with the lower level of MDA and the higher activity of SOD, but also with the upregulation of SIRT1 and PGC-1α expression.,Resveratrol treatment decreased serum levels of IL-6 and IL-8.,Our findings indicate that resveratrol had a therapeutic effect in our rat COPD model, which is related to the inhibition of oxidative stress and inflammatory response.,The mechanism may be related to the activation and upgrading of the SIRT1/PGC-1α signaling pathways.,Thus resveratrol might be a therapeutic modality in COPD. | 1 |
Airway eosinophilic inflammation is a characteristic of asthmatic patients and of a sub group of COPD subjects.,Blood eosinophils are deemed as a good surrogate marker of sputum eosinophilic inflammation; however, controversial data have been published particularly in COPD.,The aim of our study was to compare blood and sputum eosinophils in COPD and asthmatic patients in “real life”.,Sputum was induced in stable patients with COPD or asthma with hypertonic saline solution and blood eosinophils were evaluated.,Frequency of comorbidities was recorded.,Correlations were performed stratifying patients by disease and comorbidities.,146 patients, 57 with COPD and 89 with asthma were evaluated.,Blood and sputum eosinophils expressed as percentages were correlated in COPD (rho = 0.40; p = 0.004), but the entity of correlation was lower compared with asthmatic subjects (rho = 0.71; p < 0.0001).,When blood eosinophils were expressed as counts the correlation was slightly lower than when expressed as percentages in COPD (rho = 0.35; p = 0.01) and in asthmatic patients (rho = 0.68; p < 0.0001).,In COPD patients older than 73 years or with blood eosinophils higher than the median value (210.6 eos/μl), or co-diagnosed with hypertension, ischemic heart disease or atrial fibrillation no correlation between blood and sputum eosinophils was found.,However, the effect of ischemic heart disease and atrial fibrillation could be driven by hypertension since most of these patients have this comorbidity.,Blood eosinophils correlated with sputum eosinophils to a lesser degree in COPD than in asthmatic patients.,Older age, high blood eosinophils and hypertension affected the correlation between blood and sputum eosinophils, more studies are needed to evaluate the role of other cardiac comobidities. | Small airways disease (SAD) is a cardinal feature of chronic obstructive pulmonary disease (COPD) first recognized in the nineteenth century.,The diverse histopathological features associated with SAD underpin the heterogeneous nature of COPD.,Our understanding of the key molecular mechanisms which drive the pathological changes are not complete.,In this article we will provide a historical overview of key histopathological studies which have helped shape our understanding of SAD and discuss the hallmark features of airway remodelling, mucous plugging and inflammation.,We focus on the relationship between SAD and emphysema, SAD in the early stages of COPD, and the mechanisms which cause SAD progression, including bacterial colonization and exacerbations.,We discuss the need to specifically target SAD to attenuate the progression of COPD. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of acute worsening of respiratory symptoms that require additional therapy.,These events play a pivotal role in the natural course of the disease and are associated with a progressive decline in lung function, reduced health status, a low physical activity level, tremendous health care costs, and increased mortality.,Although most exacerbations have an infectious origin, the underlying mechanisms are heterogeneous and specific predictors of their occurrence in individual patients are currently unknown.,Accurate prediction and early diagnosis of exacerbations is essential to develop novel targets for prevention and personalized treatments to reduce the impact of these events.,Several potential biomarkers have previously been studied, these however lack specificity, accuracy and do not add value to the available clinical predictors.,At present, microbial composition and host-microbiome interactions in the lung are increasingly recognized for their role in affecting the susceptibility to exacerbations, and may steer towards a novel direction in the management of COPD exacerbations.,This narrative review describes the current challenges and unmet needs in the management of acute exacerbations of COPD.,Exacerbation triggers, biological clusters, current treatment strategies, and their limitations, previously studied biomarkers and prediction tools, the lung microbiome and its role in COPD exacerbations as well as future directions are discussed. | 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. | 1 |
An important goal of chronic obstructive pulmonary disease (COPD) treatment is to reduce the frequency of exacerbations.,Some observations suggest a decline in exacerbation rates in clinical trials over time.,A more systematic understanding would help to improve the design and interpretation of COPD trials.,We performed a systematic review and meta-regression of the placebo groups in published randomized controlled trials reporting exacerbations as an outcome.,A Bayesian negative binomial model was developed to accommodate results that are reported in different formats; results are reported with credible intervals (CI) and posterior tail probabilities (pB).,Of 1114 studies identified by our search, 55 were ultimately included.,Exacerbation rates decreased by 6.7% (95% CI (4.4, 9.0); pB < 0.001) per year, or 50% (95% CI (36, 61)) per decade.,Adjusting for available study and baseline characteristics such as forced expiratory volume in 1 s (FEV1) did not alter the observed trend considerably.,Two subsets of studies, one using a true placebo group and the other allowing inhaled corticosteroids in the “placebo” group, also yielded consistent results.,In conclusion, this meta-regression indicates that the rate of COPD exacerbations decreased over the past two decades to a clinically relevant extent independent of important prognostic factors.,This suggests that care is needed in the design of new trials or when comparing results from older trials with more recent ones.,Also a considerable effect of adjunct therapy on COPD exacerbations can be assumed.,PROSPERO 2018 CRD4218118823.,The online version of this article (10.1186/s12931-019-1163-2) contains supplementary material, which is available to authorized users. | Airway inflammation, especially neutrophilic airway inflammation, is a cardinal pathophysiologic feature in chronic obstructive pulmonary disease (COPD) patients.,The ideal biomarkers characterizing the inflammation might have important potential clinical applications in disease assessment and therapeutic intervention.,Sputum myeloperoxidase (MPO) is recognized as a marker of neutrophil activity.,The purpose of this meta-analysis is to determine whether sputum MPO levels could reflect disease status or be regulated by regular medications for COPD.,Studies were identified by searching PubMed, Embase, the Cochrane Database, CINAHL and http://www.controlled-trials.com for relevant reports published before September 2012.,Observational studies comparing sputum MPO in COPD patients and healthy subjects or asthmatics, or within the COPD group, and studies comparing sputum MPO before and after treatment were all included.,Data were independently extracted by two investigators and analyzed using STATA 10.0 software.,A total of 24 studies were included in the meta-analysis.,Sputum MPO levels were increased in stable COPD patients when compared with normal controls, and this increase was especially pronounced during exacerbations as compared with MPO levels during the stable state.,Theophylline treatment was able to reduce MPO levels in COPD patients, while glucocorticoid treatment failed to achieve the same result.,Sputum MPO might be a promising biomarker for guiding COPD management; however, further investigations are needed to confirm this. | 1 |
As part of the Respiratory Disease Specific Program (DSP) conducted to provide observations of clinical practice from a physician and matched patient viewpoint, this study aimed to establish how patients with COPD are treated according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification system and to quantify the symptom burden.,Data were obtained from the Respiratory DSP, a cross-sectional survey of patients with a diagnosis of COPD consulting for routine care in France, Germany, Italy, Spain, the UK, and the USA during the third quarter of 2013.,Patients’ exacerbation risk and symptom data were used for classification into GOLD groups A−D based on GOLD 2014 criteria.,Prescribing practices were stratified by physician type and time since patient diagnosis.,A total of 903 physicians participated in the Respiratory DSP, with data from 1,641 patients included in this analysis.,Most patients were classified into GOLD groups B (n=742; 45.2%) and D (n=704; 42.9%).,Patients in groups A and D were most likely to be treated in line with GOLD recommendations (61.5% and 77.5%, respectively), compared with 40.1% for group B.,Patients with a diagnosis within the past 12 months were more likely to be treated according to recommendations.,Inhaled corticosteroids (ICSs) in combination with one or more long-acting bronchodilator were prescribed across all GOLD groups.,Patterns of treatment were, in general, similar for patients treated by a primary care physician or a pulmonologist.,COPD assessment test scores ≥10 indicating a high symptom burden were reported for >80% of patients.,This analysis confirmed a high symptom burden among patients with COPD and indicates some misalignment of prescribing with GOLD recommendations, particularly regarding the role of ICS/long-acting β2-agonist (LABA) and ICS/LABA + long-acting muscarinic antagonist combinations across the different GOLD groups. | Low adherence to Global initiative for chronic Obstructive Lung Disease (GOLD) guideline recommendations has been reported worldwide.,There has been no study on the adherence to GOLD guidelines for COPD treatment in Turkey.,To investigate the rates of adherence to GOLD 2010 guidelines for COPD treatment among pulmonologists.,A multi-center, cross-sectional, observational study was carried out in eleven pulmonary outpatient clinics across Turkey.,Adherence to GOLD was evaluated through hospital records.,Demographic and clinical data were recorded.,Study included 719 patients (mean age: 62.9±9.7 years; males 85.4%) of whom 16 was classified as GOLD Stage I, 238 as II, 346 as III, and 119 as IV, and only 59.5% received appropriate treatment.,Rates of guideline adherence varied across GOLD stages (I, 6.3%; II, 14.7%; III, 84.4%; and IV, 84%).,Causes of inappropriate therapies were overtreatment (Stage I, 100% and Stage II, 91.1%), undertreatment (Stage III, 3.3% and Stage IV, 10.9%) and lack of treatment (Stage II, 3.8%; Stage III, 2.3%; and Stage IV, 5.9%).,The most preferred regimen (43.4%) was long-acting β2-agonist-inhaled corticosteroid-long-acting muscarinic antagonist.,Overall, 614 patients (89%) received treatment containing inhaled corticosteroid.,Pulmonologists in Turkey have low rates of adherence to GOLD guidelines in COPD treatment.,Inappropriateness of therapies was due to overtreatment in early stages and excessive use of inhaled corticosteroid (ICS) in all disease stages. | 1 |
Exacerbations of COPD are managed differently, but whether treatment of one exacerbation predicts the likelihood of subsequent events is unknown.,We examined whether the treatment given for exacerbations predicted subsequent outcomes.,This was a post-hoc analysis of 17,135 patients with COPD from TIOtropium Safety and Performance In Respimat® (TIOSPIR®).,Patients treated with tiotropium with one or more moderate to severe exacerbations on study were analyzed using descriptive statistics, logistic and Cox regression analysis, and Kaplan-Meier plots.,Of 8,061 patients with moderate to severe exacerbation(s), demographics were similar across patients with exacerbations treated with antibiotics and/or steroids or hospitalization.,Exacerbations treated with systemic corticosteroids alone or in combination with antibiotics had the highest risk of subsequent exacerbation (HR: 1.21, P=0.0004 and HR: 1.33, P<0.0001, respectively), and a greater risk of having a hospitalized (severe) exacerbation (HR: 1.59 and 1.63, P<0.0001, respectively) or death (HR: 1.50, P=0.0059 and HR: 1.47, P=0.0002, respectively) compared with exacerbations treated with antibiotics alone.,Initial hospitalization led to the highest risk of subsequent hospitalization (all-cause or COPD related [severe exacerbation], HR: 3.35 and 4.31, P<0.0001, respectively) or death (all-cause or COPD related, HR: 3.53 and 5.54, P<0.0001, respectively) versus antibiotics alone.,These data indicate that the way exacerbations are treated initially is a useful guide to the patient’s subsequent clinical course.,Factors that clinicians consider when making treatment choices require further clarification. | The efficacy and safety of once-daily tiotropium + olodaterol (T+O) maintenance treatment was demonstrated in the large, multinational, replicate, randomized, Phase III, Tonado® 1 (NCT01431274) and 2 (NCT01431287) studies in patients with moderate to very severe COPD.,However, there may be racial differences in the effects of T+O on lung function in patients with COPD.,In this Tonado® subgroup analysis, we assessed efficacy and safety of T+O in Japanese participants.,Versus the overall population, the 413 Japanese patients randomized and treated were slightly older, with more men, lower body mass index, lower baseline St George’s Respiratory Questionnaire (SGRQ) scores, fewer current smokers, but with higher pack-year smoking history.,A lower proportion of Japanese patients used inhaled corticosteroids, short-acting muscarinic antagonists, or short- or long-acting β-adrenergic agonists at baseline, but use of long-acting muscarinic antagonists was higher.,At Week 24, mean improvements with T+O 5/5 μg in forced expiratory volume in 1 second area under the curve from 0-3 hours response were 151 mL versus olodaterol and 134 mL versus tiotropium 5 μg; mean improvements with T+O 2.5/5 μg were 87 mL versus olodaterol and 70 mL versus tiotropium 2.5 μg.,Mean improvements with T+O 5/5 μg in trough forced expiratory volume in 1 second were 131 mL versus olodaterol and 108 mL versus tiotropium 5 μg; mean improvements with T+O 2.5/5 μg were 60 mL versus olodaterol and 47 mL versus tiotropium 2.5 μg.,SGRQ scores improved from baseline to a greater extent with both doses of T+O versus monotherapies.,Responses were similar in the overall population.,Adverse-event incidence was generally balanced across treatment groups.,Consistent with results from the overall population, T+O 5/5 μg was superior to each monotherapy for lung function and SGRQ in the Japanese sub-population of patients with COPD in Tonado®. | 1 |
Rationale: Pulmonary rehabilitation (PR) after hospitalizations for exacerbations of chronic obstructive pulmonary disease (COPD) improves exercise capacity and health-related quality of life and reduces readmissions.,However, posthospitalization PR uptake is low.,To date, no trials of interventions to increase uptake have been conducted.,Objectives: To study the effect of a codesigned education video as an adjunct to usual care on posthospitalization PR uptake.,Methods: The present study was an assessor- and statistician-blinded randomized controlled trial with nested, qualitative interviews of participants in the intervention group.,Participants hospitalized with COPD exacerbations were assigned 1:1 to receive either usual care (COPD discharge bundle including PR information leaflet) or usual care plus the codesigned education video delivered via a handheld tablet device at discharge.,Randomization used minimization to balance age, sex, FEV1 % predicted, frailty, transport availability, and previous PR experience.,Measurements and Main Results: The primary outcome was PR uptake within 28 days of hospital discharge.,A total of 200 patients were recruited, and 196 were randomized (51% female, median FEV1% predicted, 36 [interquartile range, 27-48]).,PR uptake was 41% and 34% in the usual care and intervention groups, respectively (P = 0.37), with no differences in secondary (PR referral and completion) or safety (readmissions and death) endpoints.,A total of 6 of the 15 participants interviewed could not recall receiving the video.,Conclusions: A codesigned education video delivered at hospital discharge did not improve posthospitalization PR uptake, referral, or completion. | This study aimed to document the perspective of patients with chronic obstructive pulmonary disease (COPD) who underwent home-based pulmonary rehabilitation (HBPR) in a clinical trial.,In this qualitative study, open-ended questions explored participants’ views regarding HBPR.,Thirteen semi-structured interviews were analysed using a thematic analysis approach.,Major themes from interviews included the positive impact of HBPR on physical fitness, breathing and mood.,Participants valued the flexibility and convenience of the programme.,Participants also highlighted the importance of social support received, both from the physiotherapist over the phone and from family and friends who encouraged their participation.,Reported challenges were difficulties in initiating exercise, lack of variety in training and physical incapability.,While most participants supported the home setting, one participant would have preferred receiving supervised exercise training at the hospital.,Participants also reported that HBPR had helped establish an exercise routine and improved their disease management.,This study suggests that people with COPD valued the convenience of HBPR, experienced positive impacts on physical fitness and symptoms and felt supported by their community and programme staff.,This highly structured HBPR model may be acceptable to some people with COPD as an alternative to centre-based pulmonary rehabilitation. | 1 |
The purpose of this study was to quantitatively assess the effects of water-based Liuzijue exercise on patients with COPD and compare it with land-based Liuzijue exercise.,Participants were randomly allocated to one of three groups: the water-based Liuzijue exercise group (WG), the land-based Liuzijue exercise group (LG), and the control group (CG).,CG participants accepted no exercise intervention, while training groups performed Liuzijue exercise according to Health Qigong Liuzijue (People’s Republic of China) in different environments for 60-min sessions twice a week for 3 months.,Of the 50 patients enrolled, 45 (90%) completed the 3-month intervention.,The CG showed decreased expiratory muscle strength, extensor and flexor endurance ratio (ER) of the elbow joints and flexor peak torque (PT), total work (TW), and ER of the knee joints (p<0.05).,Both training groups showed improved respiratory muscle strength, which differed from the CG (p<0.001).,In addition, extensor and flexor TW of the elbow joints in the training groups were increased (p<0.01), and the WG differed from the CG in extensor TW and ER and flexor TW (p<0.01), while the LG differed from the CG in flexor TW and extensor ER (p<0.05).,PT, PT/body weight (BW), and TW in the knee joint extensor in the training groups were increased as well (PT and PT/BW: p<0.05, TW: p<0.01), and the WG differed from the CG in terms of knee joints outcomes, while the LG differed from the CG in flexor TW only (p<0.05).,Water-based Liuzijue exercise has beneficial effects on COPD patients’ respiratory muscle strength and peripheral skeletal muscle function, and additional benefits may exist in endurance of upper limbs and strength and endurance of lower limbs when compared with land-based Liuzijue exercise. | Chronic obstructive pulmonary disease (COPD) is a major public health problem worldwide.,However, several studies that have assessed the role of traditional Chinese exercise in the management of this disease include broad variations in sample sizes and results.,Therefore, this meta-analysis was conducted to assess the effects of traditional Chinese exercise on patients with COPD.,Two investigators independently identified and extracted data from selected articles.,A computerized search of electronic databases through August 2015 was conducted.,Mean differences (MDs) and 95% confidence intervals (CIs) were calculated to analyze the combined data.,The methodological quality was evaluated using the Cochrane risk-of-bias tool.,Heterogeneity was assessed with the I2 test.,Ten randomized, controlled trials (RCTs) involving 622 patients met the inclusion criteria.,There were significant improvements in the 6-minute walking distance test (6 MWD;MWD = 12.10 m; 95% CI, 7.56-16.65 m; p<0.001); forced expiratory volume in one second (FEV1% predicted; WMD = 9.02; 95% CI, 6.80-11.23; p<0.00001); forced expiratory volume in 1 second/forced vital capacity (FEV(1)/FVC) ratio (Tiffenau Index; WMD = 6.67; 95% CI, 5.09-8.24; p<0.00001); and quality of life, as evaluated by the Chronic Respiratory Disease Questionnaire (CRDQ; WMD = 0.85 score; 95% CI, 0.52-1.18; p<0.00001).,Traditional Chinese exercise could provide an effective alternative method for managing COPD.,Larger and higher-quality trials are required. | 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. | Recent investigations showed single associations between uric acid levels, functional parameters, exacerbations and mortality in COPD patients.,The aim of this study was to describe the role of uric acid within the network of multiple relationships between function, exacerbation and comorbidities.,We used baseline data from the German COPD cohort COSYCONET which were evaluated by standard multiple regression analyses as well as path analysis to quantify the network of relations between parameters, particularly uric acid.,Data from 1966 patients were analyzed.,Uric acid was significantly associated with reduced FEV1, reduced 6-MWD, higher burden of exacerbations (GOLD criteria) and cardiovascular comorbidities, in addition to risk factors such as BMI and packyears.,These associations remained significant after taking into account their multiple interdependences.,Compared to uric acid levels the diagnosis of hyperuricemia and its medication played a minor role.,Within the limits of a cross-sectional approach, our results strongly suggest that uric acid is a biomarker of high impact in COPD and plays a genuine role for relevant outcomes such as physical capacity and exacerbations.,These findings suggest that more attention should be paid to uric acid in the evaluation of COPD disease status. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory disease, primarily affecting the airways.,Stable biomarkers characterizing the inflammatory phenotype of the disease, relevant for disease activity and suited to predict disease progression are needed to monitor the efficacy and safety of drug interventions.,We therefore analyzed a large panel of markers in bronchoalveolar lavage, bronchial biopsies, serum and induced sputum of 23 healthy smokers and 24 smoking COPD patients (GOLD II) matched for age and gender.,Sample collection was performed twice within a period of 6 weeks.,Assays for over 100 different markers were validated for the respective matrices prior to analysis.,In our study, we found 51 markers with a sufficient repeatability (intraclass correlation coefficient >0.6), most of these in serum.,Differences between groups were observed for markers from all compartments, which extends (von-Willebrand-factor) and confirms (e.g.,C-reactive-protein, interleukin-6) previous findings.,No correlations between lung and serum markers were observed, including A1AT.,Airway inflammation defined by sputum neutrophils showed only a moderate repeatability.,This could be improved, when a combination of neutrophils and four sputum fluid phase markers was used to define the inflammatory phenotype.In summary, our study provides comprehensive information on the repeatability and interrelationship of pulmonary and systemic COPD-related markers.,These results are relevant for ongoing large clinical trials and future COPD research.,While serum markers can discriminate between smokers with and without COPD, they do not seem to sufficiently reflect the disease-associated inflammatory processes within the airways. | Tobacco-related lung diseases, including chronic obstructive pulmonary disease (COPD), are major causes of lung-related disability and death worldwide.,Acute exacerbation of COPD (AE-COPD) is commonly associated with upper and lower respiratory tract viral infections and can result in respiratory failure in those with advanced lung disease.,We sought to determine the mechanism underlying COPD exacerbation and host response to pathogen-derived factors.,Over a 24-month period, we assessed the viral causes for upper and lower respiratory tract infections in patients with COPD (n = 155) and control subjects (n = 103).,We collected nasal and bronchoalveolar lavage fluid and peripheral blood under baseline and exacerbated conditions.,We determined the effect of human rhinovirus (HRV) proteinases on T-cell activation in human subjects and mice.,HRVs are isolated from nasal and lung fluid from subjects with AE-COPD.,Bronchoalveolar lavage fluid and CD4 T cells from patients with COPD exhibited a TH1 and TH2 cell cytokine phenotype during acute infection.,HRV-encoded proteinase 2A activated monocyte-derived dendritic cells in vitro and induced strong TH1 and TH2 immune responses from CD4 T cells.,Intranasal administration of recombinant rhinovirus proteinase 2A in mice resulted in an increase in airway hyperreactivity, lung inflammation, and IL-4 and IFN-γ production from CD4 T cells.,Our findings suggest that patients with severe COPD show TH1- and TH2-biased responses during AE-COPD.,HRV-encoded proteinase 2A, like other microbial proteinases, could provide a TH1- and TH2-biasing adjuvant factor during upper and lower respiratory tract infection in patients with severe COPD.,Alteration of the immune response to secreted viral proteinases might contribute to worsening of dyspnea and respiratory failure in patients with COPD. | 1 |
Early treatment of COPD exacerbations has shown to be important.,Despite a non-negligible negative impact on health related quality of life, a large proportion of these episodes is not reported (no change in treatment).,Little is known whether (low burden) strategies are able to capture these unreported exacerbations.,The Clinical COPD Questionnaire (CCQ) is a short questionnaire with great evaluative properties in measuring health status.,The current explorative study evaluates the discriminative properties of weekly CCQ assessment in detecting exacerbations.,In a multicentre prospective cohort study, 121 patients, age 67.4 ± 10.5 years, FEV1 47.7 ± 18.5% pred were followed for 6 weeks by daily diary card recording and weekly CCQ assessment.,Weeks were retrospectively labeled as stable or exacerbation (onset) weeks using the Anthonisen symptom diary-card algorithm.,Change in CCQ total scores are significantly higher in exacerbation-onset weeks, 0.35 ± 0.69 compared to -0.04 ± 0.37 in stable weeks (p < 0.001).,Performance of the Δ CCQ total score discriminating between stable and exacerbation onset weeks was sufficient (area under the ROC curve 0.75).,At a cut off point of 0.2, sensitivity was 62.5 (50.3-73.4), specificity 82.0 (79.3-84.4), and a positive and negative predictive value of 43.5 (35.0-51.0) and 90.8 (87.8-93.5), respectively.,Using this cut off point, 22 (out of 38) unreported exacerbations were detected while 39 stable patients would have been false positively 'contacted'.,Weekly CCQ assessment is a promising, low burden method to detect unreported exacerbations.,Further research is needed to validate discriminative performance and practical implications of the CCQ in detecting exacerbations in daily care. | 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 |
Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous.,We sought to investigate the sputum cellular, mediator, and microbiome profiles of both asthma and COPD exacerbations.,Patients with severe asthma or moderate-to-severe COPD were recruited prospectively to a single center.,Sputum mediators were available in 32 asthmatic patients and 73 patients with COPD assessed at exacerbation.,Biologic clusters were determined by using factor and cluster analyses on a panel of sputum mediators.,Patterns of clinical parameters, sputum mediators, and microbiome communities were assessed across the identified clusters.,The asthmatic patients and patients with COPD had different clinical characteristics and inflammatory profiles but similar microbial ecology.,Three exacerbation biologic clusters were identified.,Cluster 1 was COPD predominant, with 27 patients with COPD and 7 asthmatic patients exhibiting increased blood and sputum neutrophil counts, proinflammatory mediators (IL-1β, IL-6, IL-6 receptor, TNF-α, TNF receptors 1 and 2, and vascular endothelial growth factor), and proportions of the bacterial phylum Proteobacteria.,Cluster 2 had 10 asthmatic patients and 17 patients with COPD with increased blood and sputum eosinophil counts, type 2 mediators (IL-5, IL-13, CCL13, CCL17, and CCL26), and proportions of the bacterial phylum Bacteroidetes.,Cluster 3 had 15 asthmatic patients and 29 patients with COPD with increased type 1 mediators (CXCL10, CXCL11, and IFN-γ) and proportions of the phyla Actinobacteria and Firmicutes.,A biologic clustering approach revealed 3 subgroups of asthma and COPD exacerbations, each with different percentages of patients with overlapping asthma and COPD.,The sputum mediator and microbiome profiles were distinct between clusters. | Oral taxa are often found in the chronic obstructive pulmonary disease (COPD) lung microbiota, but it is not clear if this is due to a physiologic process such as aspiration or experimental contamination at the time of specimen collection.,Microbiota samples were obtained from nine subjects with mild or moderate COPD by swabbing lung tissue and upper airway sites during lung lobectomy.,Lung specimens were not contaminated with upper airway taxa since they were obtained surgically.,The microbiota were analyzed with 16S rRNA gene qPCR and 16S rRNA gene hypervariable region 3 (V3) sequencing.,Data analyses were performed using QIIME, SourceTracker, and R.,Streptococcus was the most common genus in the oral, bronchial, and lung tissue samples, and multiple other taxa were present in both the upper and lower airways.,Each subject’s own bronchial and lung tissue microbiota were more similar to each other than were the bronchial and lung tissue microbiota of two different subjects (permutation test, p = 0.0139), indicating more within-subject similarity than between-subject similarity at these two lung sites.,Principal coordinate analysis of all subject samples revealed clustering by anatomic sampling site (PERMANOVA, p = 0.001), but not by subject.,SourceTracker analysis found that the sources of the lung tissue microbiota were 21.1% (mean) oral microbiota, 8.7% nasal microbiota, and 70.1% unknown.,An analysis using the neutral theory of community ecology revealed that the lung tissue microbiota closely reflects the bronchial, oral, and nasal microbiota (immigration parameter estimates 0.69, 0.62, and 0.74, respectively), with some evidence of ecologic drift occurring in the lung tissue.,This is the first study to evaluate the mild-moderate COPD lung tissue microbiota without potential for upper airway contamination of the lung samples.,In our small study of subjects with COPD, we found oral and nasal bacteria in the lung tissue microbiota, confirming that aspiration is a source of the COPD lung microbiota. | 1 |
Viral-bacterial co-infections are associated with severe exacerbations of COPD.,Epithelial antimicrobial peptides, including human β-defensin-2 (HBD-2), are integral to innate host defenses.,In this study, we examined how co-infection of airway epithelial cells with rhinovirus and Pseudomonas aeruginosa modulates HBD-2 expression, and whether these responses are attenuated by cigarette smoke and in epithelial cells obtained by bronchial brushings from smokers with normal lung function or from COPD patients.,When human airway epithelial cells from normal lungs were infected with rhinovirus, Pseudomonas aeruginosa, or the combination, co-infection with rhinovirus and bacteria resulted in synergistic induction of HBD-2 (p<0.05).,The combination of virus and flagellin replicated this synergistic increase (p<0.05), and synergy was not seen using a flagella-deficient mutant Pseudomonas (p<0.05).,The effects of Pseudomonas aeruginosa were mediated via interactions of flagellin with TLR5.,The effects of HRV-16 depended upon viral replication but did not appear to be mediated via the intracellular RNA helicases, retinoic acid-inducible gene-I or melanoma differentiation-associated gene-5.,Cigarette smoke extract significantly decreased HBD-2 production in response to co-infection.,Attenuated production was also observed following co-infection of cells obtained from healthy smokers or COPD patients compared to healthy controls (p<0.05).,We conclude that co-exposure to HRV-16 and Pseudomonas aeruginosa induces synergistic production of HBD-2 from epithelial cells and that this synergistic induction of HBD-2 is reduced in COPD patients.,This may contribute to the more severe exacerbations these patients experience in response to viral-bacterial co-infections. | Several regions of the genome have shown to be associated with COPD in genome-wide association studies of common variants.,To determine rare and potentially functional single nucleotide polymorphisms (SNPs) associated with the risk of COPD and severity of airflow limitation.,3226 current or former smokers of European ancestry with lung function measures indicative of Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 COPD or worse were genotyped using an exome array.,An analysis of risk of COPD was carried out using ever smoking controls (n=4784).,Associations with %predicted FEV1 were tested in cases.,We followed-up signals of interest (p<10−5) in independent samples from a subset of the UK Biobank population and also undertook a more powerful discovery study by meta-analysing the exome array data and UK Biobank data for variants represented on both arrays.,Among the associated variants were two in regions previously unreported for COPD; a low frequency non-synonymous SNP in MOCS3 (rs7269297, pdiscovery=3.08×10−6, preplication=0.019) and a rare SNP in IFIT3, which emerged in the meta-analysis (rs140549288, pmeta=8.56×10−6).,In the meta-analysis of % predicted FEV1 in cases, the strongest association was shown for a splice variant in a previously unreported region, SERPINA12 (rs140198372, pmeta=5.72×10−6).,We also confirmed previously reported associations with COPD risk at MMP12, HHIP, GPR126 and CHRNA5.,No associations in novel regions reached a stringent exome-wide significance threshold (p<3.7×10−7).,This study identified several associations with the risk of COPD and severity of airflow limitation, including novel regions MOCS3, IFIT3 and SERPINA12, which warrant further study. | 1 |
This study was undertaken to determine the association between cardiac function and therapy with beta2-adrenoceptor agonists (β2-agonists), β-blockers, or β-blocker-β-agonist combination therapy in elderly male patients with chronic obstructive pulmonary disease (COPD).,This was a retrospective cohort study of 220 elderly male COPD patients (mean age 84.1 ± 6.9 years).,The patients were divided into four groups on the basis of the use of β-blockers and β2-agonists.,N-terminal fragment pro-B-type natriuretic peptide (NT pro-BNP), left ventricular ejection fraction (LVEF), and other relevant parameters were measured and recorded.,At follow-up, the primary end point was all-cause mortality.,Multiple linear regression analysis revealed no significant associations between NT pro-BNP and the use of β2-agonists (β = 35.502, P = 0.905), β-blockers (β = 3.533, P = 0.989), or combination therapy (β = 298.635, P = 0.325).,LVEF was not significantly associated with the use of β2-agonists (β = −0.360, P = 0.475), β-blockers (β = −0.411, P = 0.284), or combination therapy (β = −0.397, P = 0.435).,Over the follow-up period, 52 patients died, but there was no significant difference in mortality among the four groups (P = 0.357).,Kaplan-Meier analysis showed no significant difference among the study groups (log-rank test, P = 0.362).,After further multivariate adjustment, use of β2-agonists (hazard ratio [HR] 0.711, 95% confidence interval [CI] 0.287-1.759; P = 0.460), β-blockers (HR 0.962, 95% CI 0.405-2.285; P = 0.930), or combination therapy (HR 0.638, 95% CI 0.241-1.689; P < 0.366) were likewise not correlated with mortality.,There was no association between the use of β2-agonists, β-blockers, or β-blocker-β2-agonist combination therapy with cardiac function and all-cause mortality in elderly male COPD patients, which indicated that they may be used safely in this population. | The mortality and incidence of chronic obstructive pulmonary disease (COPD) and coronary heart disease increase with age.,Despite the clear evidence of beta blockers (BBs) effectiveness, there is a general reluctance to use them in patients with COPD due to a perceived contraindication and fear of inducing adverse reactions and bronchspasm.,BBs are well tolerated in patients with cardiac disease and concomitant COPD with no evidence of worsening of respiratory symptoms or FEV1, and the safety of BBs in patients with COPD has been demonstrated, but their use in this group of patients remains low.,The cumulative evidence from trials and meta-analysis indicates that cardioselective BBs should not be withheld in patients with reactive airway disease or COPD.,Patients with COPD have a high incidence of cardiac events necessitating careful consideration of prophylactic treatment.,The benefits of beta blockade in this group appear to outweigh any potential risk of side effects according to the available evidence.,In this article, we will discuss the use of BBs in patients with COPD and review the evidence for their use and safety in this group of patients. | 1 |
The pathogenesis of chronic obstructive pulmonary disease (COPD) is characterized by an interaction of environmental influences, particularly cigarette smoking, and genetic determinants.,Given the global increase in COPD, research on the genomic variants that affect susceptibility to this complex disorder is reviving.,In the present study, we investigated whether single nucleotide polymorphisms in 'a disinter-grin and metalloprotease' 33 (ADAM33) are associated with the development and course of COPD.,We genotyped 150 German COPD patients and 152 healthy controls for the presence of the F+1 and S_2 SNPs in ADAM 33 that lead to the base pair exchange G to A and C to G, respectively.,To assess whether these genetic variants are influential in the course of COPD, we subdivided the cohort into two subgroups comprising 60 patients with a stable and 90 patients with an unstable course of disease.,In ADAM33, the frequency of the F+1 A allele was 35.0% among stable and 43.9% among unstable COPD subjects, which was not significantly different from the 35.5% found in the controls (P = 0.92 and P = 0.07, respectively).,The frequency of the S_2 mutant allele in subjects with a stable COPD was 23.3% (P = 0.32), in subjects with an unstable course 30.6% (P = 0.47).,The study shows that there is no significant difference in the distribution of the tested SNPs between subjects with and without COPD.,Furthermore, these polymorphisms appear to have no consequences for the stability of the disease course. | We have previously identified Urokinase Plasminogen Activator Receptor (PLAUR) as an asthma susceptibility gene.,In the current study we tested the hypothesis that PLAUR single nucleotide polymorphisms (SNPs) determine baseline lung function and contribute to the development of Chronic Obstructive Pulmonary Disease (COPD) in smokers.,25 PLAUR SNPs were genotyped in COPD subjects and individuals with smoking history (n = 992).,Linear regression was used to determine the effects of polymorphism on baseline lung function (FEV1, FEV1/FVC) in all smokers.,Genotype frequencies were compared in spirometry defined smoking controls (n = 176) versus COPD cases (n = 599) and COPD severity (GOLD stratification) using logistic regression.,Five SNPs showed a significant association (p < 0.01) with baseline lung function; rs2302524(Lys220Arg) and rs2283628(intron 3) were associated with lower and higher FEV1 respectively. rs740587(-22346), rs11668247(-20040) and rs344779(-3666) in the 5'region were associated with increased FEV1/FVC ratio. rs740587 was also protective for COPD susceptibility and rs11668247 was protective for COPD severity although no allele dose relationship was apparent.,Interestingly, several of these associations were driven by male smokers not females.,This study provides tentative evidence that the asthma associated gene PLAUR also influences baseline lung function in smokers.,However the case-control analyses do not support the conclusion that PLAUR is a major COPD susceptibility gene in smokers.,PLAUR is a key serine protease receptor involved in the generation of plasmin and has been implicated in airway remodelling. | 1 |
Although COPD among non-smokers (NS-COPD) is common, little is known about this phenotype.,We compared NS-COPD subjects with smoking COPD (S-COPD) patients in a rural Indian population using a variety of clinical, physiological, radiological, sputum cellular and blood biomarkers.,Two hundred ninety subjects (118 healthy, 79 S-COPD, 93 NS-COPD) performed pre- and post-bronchodilator spirometry and were followed for 2 years to study the annual rate of decline in lung function.,Body plethysmography, impulse oscillometry, inspiratory-expiratory HRCT, induced sputum cellular profile and blood biomarkers were compared between 49 healthy, 45 S-COPD and 55 NS-COPD subjects using standardized methods.,Spirometric response to oral corticosteroids was measured in 30 female NS-COPD patients.,Compared to all male S-COPD subjects, 47% of NS-COPD subjects were female, were younger by 3.2 years, had greater body mass index, a slower rate of decline in lung function (80 vs 130 mL/year), more small airways obstruction measured by impulse oscillometry (p < 0.001), significantly less emphysema (29% vs 11%) on CT scans, lower values in lung diffusion parameters, significantly less neutrophils in induced sputum (p < 0.05) and tended to have more sputum eosinophils.,Hemoglobin and red cell volume were higher and serum insulin lower in S-COPD compared to NS-COPD.,Spirometric indices, symptoms and quality of life were similar between S-COPD and NS-COPD.,There was no improvement in spirometry in NS-COPD patients after 2 weeks of an oral corticosteroid.,Compared to S-COPD, NS-COPD is seen in younger subjects with equal male-female predominance, is predominantly a small-airway disease phenotype with less emphysema, preserved lung diffusion and a slower rate of decline in lung function. | We aimed to compare impulse oscillation system (IOS) and traditional pulmonary function tests (PFTs) for the assessment of the severity of chronic obstructive pulmonary disease (COPD), and to assess the use of IOS parameters to identify patients who were forced expiratory volume in 1 second (FEV1)%pred < 50%.,Patients with COPD (n = 215) were enrolled at the Ninth Hospital of Xi’an Affiliated Hospital of Xi’an Jiaotong University between October 2014 and September 2016.,All patients were assessed by traditional PFT and IOS.,Diagnostic performance of IOS parameters to determine indication for patients of FEV1%pred < 50% was assessed on receiver-operating characteristics (ROC) curve analysis.,Out of 215 patients, 18, 83, 78, and 36 patients were classified as grade 1, 2, 3, and 4, respectively, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity grading.,On Spearman correlation analysis, FEV1%pred, MMEF 75%-25%, and residual volume/total lung capacity (RV/TLC) correlated with total respiratory impedance (Z5)%pred, resistance at 5 Hz (R5)-resistance at 20 Hz (R20), R5-R20% R5, R5, R5%pred, frequency response (Fres), reactance area (Ax), and reactance at 5 Hz (X5).,On ROC curve analysis, the area under the curve (AUC) of X5 absolute value, Fres, Ax, Z5%pred, R5-R20, and R5-R20% R5 were 0.748, 0.755, 0.760, 0.705, 0.715, and 0.735, respectively, for COPD patients who required inhalational glucocorticoid therapy.,IOS parameters showed a good correlation with traditional pulmonary function parameters; reactance parameters showed a stronger correlation than that of the resistance parameters.,IOS can be used as an alternative method for pulmonary function assessment in patients with COPD with FEV1%pred < 50% who need inhalational glucocorticoid therapy.,Clinical trial registration number: ChiCTR-OCH-14004904. | 1 |
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. | Nontypeable Haemophilus influenzae (NTHI) may play a role as an infectious trigger in the pathogenesis of chronic obstructive pulmonary disease (COPD).,Few data are available regarding the influence of acute and persistent infection on tissue remodelling and repair factors such as transforming growth factor (TGF)-β.,NTHI infection in lung tissues obtained from COPD patients and controls was studied in vivo and using an in vitro model.,Infection experiments were performed with two different clinical isolates.,Detection of NTHI was done using in situ hybridization (ISH) in unstimulated and in in vitro infected lung tissue.,For characterization of TGF-β signaling molecules a transcriptome array was performed.,Expression of the TGF-pseudoreceptor BMP and Activin Membrane-bound Inhibitor (BAMBI) was analyzed using immunohistochemistry (IHC), ISH and PCR.,CXC chemokine ligand (CXCL)-8, tumor necrosis factor (TNF)-α and TGF-β expression were evaluated in lung tissue and cell culture using ELISA.,In 38% of COPD patients infection with NTHI was detected in vivo in contrast to 0% of controls (p < 0.05).,Transcriptome arrays showed no significant changes of TGF-β receptors 1 and 2 and Smad-3 expression, whereas a strong expression of BAMBI with upregulation after in vitro infection of COPD lung tissue was demonstrated.,BAMBI was expressed ubiquitously on alveolar macrophages (AM) and to a lesser degree on alveolar epithelial cells (AEC).,Measurement of cytokine concentrations in lung tissue supernatants revealed a decreased expression of TGF-β (p < 0.05) in combination with a strong proinflammatory response (p < 0.01).,We show for the first time the expression of the TGF pseudoreceptor BAMBI in the human lung, which is upregulated in response to NTHI infection in COPD lung tissue in vivo and in vitro.,The combination of NTHI-mediated induction of proinflammatory cytokines and inhibition of TGF-β expression may influence inflammation induced tissue remodeling. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is one of the top leading causes of death and disability, and its management is focused on reducing risk factors, relieving symptoms, and preventing exacerbations.,The study aim was to describe COPD prescribing patterns in Greece by using existing health administrative data for outpatients.,This is a retrospective cross-sectional study based on prescriptions collected by the largest social insurance fund, during the first and last trimester of 2012.,Selection criteria were the prescription of specific active substances and a COPD diagnosis.,Extracted information included active substance, strength, pharmaceutical form and number of packages prescribed, diagnosis, time of dispensing, as well as insurees’ age, gender, percentage of co-payment and social security unique number.,Statistical analysis included descriptive statistics and logistic regression.,174,357 patients received medicines for COPD during the study period.,Patients were almost equally distributed between male and female, and age above 55 years was strongly correlated with COPD.,Most patients received a long-acting beta agonist plus inhaled corticosteroid combination (LABA +ICS), followed by long-acting muscarinic agonist (LAMA). 63% patients belonging in the 35-54 age received LABA+ICS.,LAMA was prescribed more frequently among males and was strongly correlated with COPD.,The study provides big data analysis of Greek COPD prescribing patterns.,It highlights the need for appropriate COPD classification in primary care illustrating the role of electronic prescribing in ensuring appropriate prescribing.,Moreover, it indicates possible gender differences in treatment response or disease severity, and the impact of statutory co-payments on prescribing. | Greece has one of the highest rates of smoking and chronic obstructive pulmonary disease (COPD) in Europe.,The study aimed to record both the disease characteristics among a sample of Greek COPD patients and the nationwide rates of newly diagnosed COPD cases.,In this noninterventional, epidemiological cross-sectional study, a representative nationwide sample of 45 respiratory centers provided data on the following: 1) the demographic and clinical characteristics of COPD patients and 2) newly diagnosed COPD cases monitored over a period of 6 months by each physician.,Data from 6,125 COPD patients were collected.,Advanced age (median age: 68 years), male predominance (71.3%), largely overweight status with median body mass index (BMI) =27.5 kg/m2, high percentage of current and ex-smokers (89.8%), and presence of comorbidities (81.9%) were evident in the sample.,According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 criteria, majority of the COPD patients had moderate or severe airflow limitation (61%).,Severity of airflow limitation was significantly associated with older age, male sex, obesity, ex-smoking status, and presence of comorbidity (all P-values <0.001).,A total of 61.3% of the patients received medication, mostly bronchodilators (64.4%) and fixed-dose combinations of long-acting β2-agonists and inhaled corticosteroids (39.9%), while 35.9% reported taking medication on demand.,The majority (81.1%) of patients reported a preference for fewer inhalations of their bronchodilator therapy.,Based on the mixed-effect Poisson model, the rate of newly diagnosed COPD cases was estimated to be 18.2% (95% confidence interval: 14.9-22.3) per pulmonologist/3 months.,Of those newly diagnosed, the majority of patients had mild or moderate airflow limitation (78.2%).,The Greek Obstructive Lung Disease Epidemiology and health ecoNomics study reflected the real-life profile of COPD patients and provided evidence on the profile of new COPD cases in Greece.,Various demographic factors were delineated, which can assist in designing more effective diagnostic and management strategies for COPD in Greece. | 1 |
There is growing evidence that many diseases develop, progress, and respond to therapy differently in men and women.,This variability may manifest as a result of sex-specific structures in gene regulatory networks that influence how those networks operate.,However, there are few methods to identify and characterize differences in network structure, slowing progress in understanding mechanisms driving sexual dimorphism.,Here we apply an integrative network inference method, PANDA (Passing Attributes between Networks for Data Assimilation), to model sex-specific networks in blood and sputum samples from subjects with Chronic Obstructive Pulmonary Disease (COPD).,We used a jack-knifing approach to build an ensemble of likely networks for each sex.,By adapting statistical methods to compare these network ensembles, we were able to identify strong differential-targeting patterns associated with functionally-related sets of genes, including those involved in mitochondrial function and energy metabolism.,Network analysis also identified several potential sex- and disease-specific transcriptional regulators of these pathways.,Network analysis yielded insight into potential mechanisms driving sexual dimorphism in COPD that were not evident from gene expression analysis alone.,We believe our ensemble approach to network analysis provides a principled way to capture sex-specific regulatory relationships and could be applied to identify differences in gene regulatory patterns in a wide variety of diseases and contexts.,The online version of this article (doi:10.1186/s12918-014-0118-y) contains supplementary material, which is available to authorized users. | Tobacco smoking is the main risk factor of chronic obstructive pulmonary disease (COPD) but not all smokers develop the disease.,An abnormal pulmonary and systemic inflammatory response to smoking is thought to play a major pathogenic role in COPD, but this has never been tested directly.,We studied the systemic biomarker and leukocyte transcriptomic response (Affymetrix microarrays) to smoking exposure in 10 smokers with COPD and 10 smokers with normal spirometry.,We also studied 10 healthy never smokers (not exposed to smoking) as controls.,Because some aspects of COPD may differ in males and females, and the inflammatory response to other stressors (infection) might be different in man and women, we stratified participant recruitment by sex.,Differentially expressed genes were validated by q-PCR.,Ontology enrichment was evaluated and interaction networks inferred.,Principal component analysis identified sex differences in the leukocyte transcriptomic response to acute smoking.,In both genders, we identified genes that were differentially expressed in response to smoking exclusively in COPD patients (COPD related signature) or smokers with normal spirometry (Smoking related signature), their ontologies and interaction networks.,The use of an experimental intervention (smoking exposure) to investigate the transcriptomic response of peripheral leukocytes in COPD is a step beyond the standard case-control transcriptomic profiling carried out so far, and has facilitated the identification of novel COPD and Smoking expression related signatures which differ in males and females. | 1 |
The aim of this study was to assess the current evidence for long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combinations (FDCs) in the treatment of COPD.,A systematic literature search of randomized controlled trials published in English up to September 2017 of LABA/LAMA FDCs vs LABA or LAMA or LABA/inhaled corticosteroid (ICS) FDCs in COPD patients was performed using PubMed, Embase, Scopus, and Google Scholar.,Outcomes including forced expiratory volume in 1 second (FEV1), Transition Dyspnea Index (TDI) scores, St George’s Respiratory Questionnaire (SGRQ) scores, exacerbations, exercise tolerance (endurance time [ET]), inspiratory capacity (IC), and rescue medication use were evaluated.,In total, 27 studies were included in the review.,LABA/LAMA FDCs significantly improved lung function (FEV1) at 12 weeks compared with LABA or LAMA or LABA/ICS.,These effects were maintained over time.,Significant improvements with LABA/LAMA FDCs vs each evaluated comparator were also observed in TDI and SGRQ scores, even if significant differences between different LABA/LAMA FDCs were detected.,Only the LABA/LAMA FDC indacaterol/glycopyrronium has shown superiority vs LAMA and LABA/ICS for reducing exacerbation rates, while olodaterol/tiotropium and indacaterol/glycopyrronium have been shown to improve ET and IC vs the active comparators.,Rescue medication use was significantly reduced by LABA/LAMA FDCs vs the evaluated comparators.,LABA/LAMA FDCs were safe, with no increase in the risk of adverse events with LABA/LAMA FDCs vs the monocomponents.,Evidence supporting the efficacy of LABA/LAMA FDCs for COPD is heterogeneous, particularly for TDI and SGRQ scores, exacerbation rates, ET, and IC.,So far, indacaterol/glycopyrronium is the LABA/LAMA FDC that has the strongest evidence for superiority vs LABA, LAMA, and LABA/ICS FDCs across the evaluated outcomes.,LABA/LAMA FDCs were safe; however, more data should be collected in a real-world setting to confirm their safety. | Improvements in ventilatory mechanics with tiotropium increases exercise tolerance during pulmonary rehabilitation.,We wondered whether tiotropium also increased physical activities outside of pulmonary rehabilitation.,COPD patients participating in 8 weeks of pulmonary rehabilitation were studied in a randomized, double-blind, placebo-controlled trial of tiotropium 18 μg daily (tiotropium = 47, placebo = 44).,Study drug was administered for 5 weeks prior to, 8 weeks during, and 12 weeks following pulmonary rehabilitation.,Patients completed a questionnaire documenting participation in pre-defined activities outside of pulmonary rehabilitation during the 2 weeks prior to each visit.,Patients who submitted an activity questionnaire at week 4 and on at least one subsequent visit were included in the analysis.,For each patient, the number of sessions was multiplied with the duration of each activity and then summed to give overall activity duration.,Patients (n = 46) had mean age of 67 years, mean baseline FEV1 of 0.84 L (33% predicted).,Mean (SE) increase in duration of activities (minutes during 2 weeks prior to each visit) from week 4 (prior to PR) to week 13 (end of PR) was 145 (84) minutes with tiotropium and 66 (96) minutes with placebo.,The increase from week 4 to week 25 (end of follow-up) was 262 (96) and 60 (93) minutes for the respective groups.,Increases in activity duration from week 4 to weeks 17, 21, and 25 were statistically significant with tiotropium.,No statistical differences over time were observed within the placebo-treated group and differences between groups were not significant.,Tiotropium appears to amplify the effectiveness of pulmonary rehabilitation as seen by increases in patient self-reported participation in physical activities. | 1 |
To determine the impact of adherence to long-term oxygen therapy (LTOT) on quality of life, dyspnea, and exercise capacity in patients with COPD and exertional hypoxemia followed for one year.,Patients experiencing severe hypoxemia during a six-minute walk test (6MWT) performed while breathing room air but not at rest were included in the study.,At baseline and after one year of follow-up, all patients were assessed for comorbidities, body composition, SpO2, and dyspnea, as well as for anxiety and depression, having also undergone spirometry, arterial blood gas analysis, and the 6MWT with supplemental oxygen.,The Saint George’s Respiratory Questionnaire (SGRQ) was used in order to assess quality of life, and the Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity (BODE) index was calculated.,The frequency of exacerbations and the mortality rate were noted.,Treatment nonadherence was defined as LTOT use for < 12 h per day or no LTOT use during exercise.,A total of 60 patients with COPD and exertional hypoxemia were included in the study.,Of those, 10 died and 11 experienced severe hypoxemia during follow-up, 39 patients therefore being included in the final analysis.,Of those, only 18 (46.1%) were adherent to LTOT, showing better SGRQ scores, higher SpO2 values, and lower PaCO2 values than did nonadherent patients.,In all patients, SaO2, the six-minute walk distance, and the BODE index worsened after one year.,There were no differences between the proportions of adherence to LTOT at 3 and 12 months of follow-up.,Quality of life appears to be lower in patients with COPD and exertional hypoxemia who do not adhere to LTOT than in those who do.,In addition, LTOT appears to have a beneficial effect on COPD symptoms (as assessed by SGRQ scores).,(Brazilian Registry of Clinical Trials - ReBEC; identification number RBR-9b4v63 [http://www.ensaiosclinicos.gov.br]) | People with chronic obstructive pulmonary disease (COPD) continue to experience dyspnea with activities of daily living (ADL) despite optimal medical management.,Information and communication technologies may facilitate collaborative symptom management and could potentially increase the reach of such interventions to those who are unable to attend face-to-face pulmonary rehabilitation or self-management programs.,The purpose of this randomized study was to test the efficacy of two 6-month dyspnea self-management programs, Internet-based (eDSMP) and face-to-face (fDSMP), on dyspnea with ADL in people living with COPD.,We randomly assigned 50 participants with moderate to severe COPD who were current Internet users to either the eDSMP (n = 26) or fDSMP (n = 24) group.,The content of the two programs was similar, focusing on education, skills training, and ongoing support for dyspnea self-management, including independent exercise.,The only difference was the mode (Internet/personal digital assistant [PDA] or face-to-face) in which the education sessions, reinforcement contacts, and peer interactions took place.,Participants returned to one of two academic clinical sites for evaluation at 3 and 6 months.,The primary outcome of dyspnea with ADL was measured with the Chronic Respiratory Questionnaire.,Secondary outcomes of exercise behavior, exercise performance, COPD exacerbations, and mediators, such as self-efficacy and social support, were also measured.,A satisfaction survey was administered and a semistructured exit interview was conducted at the final visit.,The study was stopped early due to multiple technical challenges with the eDSMP, but follow-up was completed on all enrolled participants.,Data were available for 39 participants who completed the study (female: 44%; age: 69.5 ± 8.5 years; percent predicted forced expiratory volume in 1 s: 49.6 ± 17.0%).,The fDSMP and eDSMP showed similar clinically meaningful changes in dyspnea with ADL from baseline to 3 months (fDSMP: + 3.3 points; eDSMP: + 3.5 points) and sustained these improvements at 6 months (fDSMP: + 4.0 points; eDSMP: + 2.5 points; time effects P < .001; group by time P = .51).,Self-reported endurance exercise time (P = .001), physical functioning (P = .04), and self-efficacy for managing dyspnea (P = .02) also showed positive improvements over time in both groups with no significant differences with respect to program modality.,Participants who completed the study reported favorable satisfaction with the programs.,Although there were numerous technical challenges with the eDSMP, both dyspnea self-management programs were effective in reducing dyspnea with ADL in the short term.,Our findings will need to be confirmed in a larger randomized trial with more mature Web and personal digital assistant tools, use of a control group, and longer follow-up.,clinicaltrials.gov NCT00102401, http://www.webcitation.org/5X8CX4gLC | 1 |
No previous study has investigated the adherence rate of North-African pulmonologists to the 2017-GOLD PTGs.,To investigate the adherence rate of Tunisian pulmonologists to the 2017-GOLD PTGs and to identify the barriers to their adherence.,This was a cohort study involving clinically stable COPD patients who presented to a pulmonology outpatient consultation.,The patients were classified as having been appropriately and inappropriately (over- or undertreatment) treated for the GOLD group.,Logistic regression was performed to determine the adherence barriers to the 2017-GOLD PTGs.,A total of 296 patients were included (88.1% males, mean age: 68 ± 10 years; GOLD A (7.1%), B (36.1%), C (4.1%), and D (52.7%)).,The pulmonologists' adherence rate to the 2017-GOLD PTGs was 29.7%.,There was a significant statistical difference between the adherence rates among the four GOLD groups (A: 19.0%, B: 20.6%, C: 8.3%, and D: 39.1%; p = 0.001).,Differences were statistically significant between the GOLD group D and groups B (p = 0.001).,Differences were statistically significant between the GOLD group D and groups B (p = 0.001).,Differences were statistically significant between the GOLD group D and groups B (,The adherence rate of Tunisian pulmonologists to the 2017-GOLD PTGs is low.,It seems that the patients' age, socioeconomic level, national health insurance coverage, and GOLD groups influenced their adherence. | Socioeconomic status (SES) is a strong social determinant of health.,There remains a limited understanding of the association between SES and COPD prevalence among low- and middle-income countries where the majority of COPD-related morbidity and mortality occurs.,We examined the association between SES and COPD prevalence using data collected in Argentina, Bangladesh, Chile, Peru, and Uruguay.,We compiled lung function, demographic, and SES data from three population-based studies for 11,042 participants aged 35-95 years.,We used multivariable alternating logistic regressions to study the association between COPD prevalence and SES indicators adjusted for age, sex, self-reported daily smoking, and biomass fuel smoke exposure.,Principal component analysis was performed on monthly household income, household size, and education to create a composite SES index.,Overall COPD prevalence was 9.2%, ranging from 1.7% to 15.4% across sites.,The adjusted odds ratio of having COPD was lower for people who completed secondary school (odds ratio [OR] =0.73, 95% CI 0.55-0.98) and lower with higher monthly household income (OR =0.96 per category, 95% CI 0.93-0.99).,When combining SES factors into a composite index, we found that the odds of having COPD was greater with lower SES (interquartile OR =1.23, 95% CI 1.05-1.43) even after controlling for subject-specific factors and environmental exposures.,In this analysis of multiple population-based studies, lower education, lower household income, and lower composite SES index were associated with COPD.,Since household income may be underestimated in population studies, adding household size and education into a composite index may provide a better surrogate for SES. | 1 |
Chronic obstructive pulmonary disease (COPD) is emphysema and/or chronic bronchitis characterised by long-term breathing problems and poor airflow.,The prevalence of COPD has increased over the last decade and the drugs most commonly used to treat it, such as glucocorticoids and bronchodilators, have significant therapeutic effects; however, they also cause side effects, including infection and immunosuppression.,Here we reviewed the pathogenesis and progression of COPD and elaborated on the effects and mechanisms of newly developed molecular targeted COPD therapeutic drugs.,Among these new drugs, we focussed on thioredoxin (Trx).,Trx effectively prevents the progression of COPD by regulating redox status and protease/anti-protease balance, blocking the NF-κB and MAPK signalling pathways, suppressing the activation and migration of inflammatory cells and the production of cytokines, inhibiting the synthesis and the activation of adhesion factors and growth factors, and controlling the cAMP-PKA and PI3K/Akt signalling pathways.,The mechanism by which Trx affects COPD is different from glucocorticoid-based mechanisms which regulate the inflammatory reaction in association with suppressing immune responses.,In addition, Trx also improves the insensitivity of COPD to steroids by inhibiting the production and internalisation of macrophage migration inhibitory factor (MIF).,Taken together, these findings suggest that Trx may be the ideal drug for treating COPD. | Asthma and chronic obstructive pulmonary disease (COPD) are obstructive airway disorders which differ in their underlying causes and phenotypes but overlap in patterns of pharmacological treatments.,In both asthma and COPD, oxidative stress contributes to airway inflammation by inducing inflammatory gene expression.,The redox-sensitive transcription factor, nuclear factor (NF)-kappaB (NF-κB), is an important participant in a broad spectrum of inflammatory networks that regulate cytokine activity in airway pathology.,The anti-inflammatory actions of glucocorticoids (GCs), a mainstay treatment for asthma, involve inhibition of NF-κB induced gene transcription.,Ligand bound GC receptors (GRs) bind NF-κB to suppress the transcription of NF-κB responsive genes (i.e., transrepression).,However, in severe asthma and COPD, the transrepression of NF-κB by GCs is negated as a consequence of post-translational changes to GR and histones involved in chromatin remodeling.,Therapeutics which target NF-κB activation, including inhibitors of IκB kinases (IKKs) are potential treatments for asthma and COPD.,Furthermore, reversing GR/histone acetylation shows promise as a strategy to treat steroid refractory airway disease by augmenting NF-κB transrepression.,This review examines NF-κB signaling in airway inflammation and its potential as target for treatment of asthma and COPD. | 1 |
Tobacco use and other cardiovascular risk factors often accompany chronic obstructive pulmonary disease (COPD).,This study derived and validated the Summit Score to predict mortality in people with COPD and cardiovascular risks.,SUMMIT trial subjects (N=16,485) ages 40-80 years with COPD were randomly assigned 50%/50% to derivation (N=8181) and internal validation (N=8304).,Three external COPD validations from Intermountain Healthcare included outpatients with cardiovascular risks (N=9251), outpatients without cardiovascular risks (N=8551), and inpatients (N=26,170).,Cox regression evaluated 40 predictors of all-cause mortality.,SUMMIT treatments including combined fluticasone furoate (FF) 100μg/vilanterol 25μg (VI) were not included in the score.,Mortality predictors were FEV1, heart rate, systolic blood pressure, body mass index, age, smoking pack-years, prior COPD hospitalizations, myocardial infarction, heart failure, diabetes, anti-thrombotics, anti-arrhythmics, and xanthines.,Combined in the Summit Score (derivation: c=0.668), quartile 4 vs 1 had HR=4.43 in SUMMIT validation (p<0.001, 95% CI=3.27, 6.01, c=0.662) and HR=8.15 in Intermountain cardiovascular risk COPD outpatients (p<0.001, 95% CI=5.86, 11.34, c=0.736), and strongly predicted mortality in the other Intermountain COPD populations.,Among all SUMMIT subjects with scores 14-19, FF 100μg/VI 25μg vs placebo had HR=0.76 (p=0.0158, 95% CI=0.61, 0.95), but FF 100μg/VI 25μg was not different from placebo for scores <14 or >19.,In this post hoc analysis of SUMMIT trial data, the Summit Score was derived and validated in multiple Intermountain COPD populations.,The score was used to identify a subpopulation in which mortality risk was lower for FF 100μg/VI 25μg treatment.,The SUMMIT trial is registered at ClinicalTrials.gov as number NCT01313676. | A multidimensional assessment of COPD was recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) in 2013 and revised in 2017.,We examined the ability of the GOLD 2017 and the new 16 subgroup (1A-4D) classifications to predict clinical outcomes, including exacerbation and mortality, and compared them with the GOLD 2013 classifications.,Patients with COPD were recruited from January 2006 to December 2017.,The predictive abilities of grades 1-4 and groups A-D were examined through a logistic regression analysis with receiver operating curve estimations and area under the curve (AUC).,A total of 553 subjects with COPD were analyzed.,The mortality rate was 48.6% during a median follow-up period of 5.2 years.,Both the GOLD 2017 and the 2013 group A-D classifications had good predictive ability for total and severe exacerbations, for which the AUCs were 0.79 vs 0.77 and 0.79 vs 0.78, respectively.,The AUCs for the GOLD 2017 groups A-D, grades 1-4, and the GOLD 2013 group A-D classifications were 0.70, 0.66, and 0.70 for all-cause mortality and 0.73, 0.71, and 0.74 for respiratory cause mortality, respectively.,Combining the spirometric staging with the grouping for the GOLD 2017 subgroups (1A-4D), the all-cause mortality rate for group B and D patients was significantly increased from subgroups 1B-4B (27.7%, 50.6%, 53.3%, and 69.2%, respectively) and groups 1D-4D (55.0%, 68.8%, 82.1%, and 90.5%, respectively).,The AUCs of subgroups (1A-4D) were 0.73 and 0.77 for all-cause and respiratory mortality, respectively; the new classification was determined more accurate than the GOLD 2017 for predicting mortality (P<0.0001).,The GOLD 2017 classification performed well by identifying individuals at risk of exacerbation, but its predictive ability for mortality was poor among COPD patients.,Combining the spirometric staging with the grouping increased the predictive ability for all-cause and respiratory mortality.,We validate the ability of the GOLD 2017 and 16 subgroup (1A-4D) classifications to predict clinical outcome for COPD patients.,The GOLD 2017 classification performed well by identifying individuals at risk of exacerbation, but its predictive ability for mortality was poor.,The new 16 subgroup (1A-4D) classification combining the spirometric 1-4 staging and the A-D grouping increased the predictive ability for mortality and was better than the GOLD 2017 for predicting all-cause and respiratory mortality among COPD patients. | 1 |
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 | Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary disease (COPD) exacerbations and increase pneumonia risk, through unknown mechanisms.,Rhinoviruses precipitate most exacerbations and increase susceptibility to secondary bacterial infections.,Here, we show that the ICS fluticasone propionate (FP) impairs innate and acquired antiviral immune responses leading to delayed virus clearance and previously unrecognised adverse effects of enhanced mucus, impaired antimicrobial peptide secretion and increased pulmonary bacterial load during virus-induced exacerbations.,Exogenous interferon-β reverses these effects.,FP suppression of interferon may occur through inhibition of TLR3- and RIG-I virus-sensing pathways.,Mice deficient in the type I interferon-α/β receptor (IFNAR1−/−) have suppressed antimicrobial peptide and enhanced mucin responses to rhinovirus infection.,This study identifies type I interferon as a central regulator of antibacterial immunity and mucus production.,Suppression of interferon by ICS during virus-induced COPD exacerbations likely mediates pneumonia risk and raises suggestion that inhaled interferon-β therapy may protect.,Corticosteroid therapy is frequently used for chronic obstructive pulmonary disease (COPD) but its use is associated with increased risk of pneumonia.,Here the authors show that corticosteroid use impairs innate and adaptive immunity to rhinovirus infection, which is restored by exogenous IFNβ. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is characterised by reduced lung function and is the third leading cause of death globally.,Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97.,A genetic risk score was associated with COPD susceptibility (odds ratios per standard deviation of the risk score (~6 alleles) (95% confidence interval) 1.24 (1.20-1.27), P=5.05x10-49) and we observed a 3.7 fold difference in COPD risk between highest and lowest genetic risk score deciles in UK Biobank.,The 97 signals show enrichment in development, elastic fibres and epigenetic regulation pathways.,We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications. | Promotion of a healthy lifestyle and non-pharmacological interventions in the treatment of chronic obstructive pulmonary disease (COPD) has received great attention in recent decades.,The aim of this study was to investigate trends in leisure time physical activity (PA), smoking, alcohol consumption and body mass index (BMI) from 2000 to 2010 in Danish individuals with and without COPD.,Analyses were based on data provided by The Danish Health and Morbidity’s three cross-sectional surveys from 2000, 2005 and 2010.,Data compromised level of leisure time PA, smoking, alcohol consumption, BMI and sociodemographic characteristics.,Participants aged 25 years or older with and without COPD were included in the analyses.,In multiple logistic regression analyses, odds ratio (OR) of being physically active in the leisure time in 2010 compared to 2000 was 1.70 (95 % CI: 1.28-2.26), p < 0.001, and 1.32 (1.22-1.43), p < 0.001, in participants with and without COPD, respectively.,Being a non-smoker in 2010 compared to 2000 was associated with an OR of 1.41 (1.07-1.85), p = 0.015, and 1.73 (1.63-1.85), p < 0.001, in participants with and without COPD.,The OR of not exceeding national recommended alcohol limits was 0.64 (0.45-0.93), p = 0.020, and 1.19 (1.09-1.29), p < 0.001, in participants with and without COPD.,In a multiple linear regression analysis, the time frame from 2000 to 2010 was associated with an increased BMI of 1.18 kg · m−2 (0.52-1.84), p < 0.001, and 0.74 kg · m−2 (0.63-0.86), p < 0.001, in participants with and without COPD.,The COPD participants with higher levels of education and/or living in a marriage or a relationship were more likely to be physically active, non-smoking and not exceeding the recommended alcohol limits.,From the 2000 to 2010, Danish individuals aged 25 years with and without COPD, increased their leisure time PA level and reduced smoking.,Lower socioeconomic status was associated with a reduced level of PA, smoking and an increased alcohol intake.,Future national health campaigns and treatment strategies need to target this socioeconomic impact.,The reported increased PA level and reduced smoking may have important implications in relation to a reduced morbidity and mortality risk in Danish patients with COPD. | 1 |
Reactive oxygen species (ROS) form as a natural by-product of the normal metabolism of oxygen and play important roles within the cell.,Under normal circumstances the cell is able to maintain an adequate homeostasis between the formation of ROS and its removal through particular enzymatic pathways or via antioxidants.,If however, this balance is disturbed a situation called oxidative stress occurs.,Critically, oxidative stress plays important roles in the pathogenesis of many diseases, including cancer.,Epigenetics is a process where gene expression is regulated by heritable mechanisms that do not cause any direct changes to the DNA sequence itself, and disruption of epigenetic mechanisms has important implications in disease.,Evidence is emerging that histone deacetylases (HDACs) play decisive roles in regulating important cellular oxidative stress pathways including those involved with sensing oxidative stress and those involved with regulating the cellular response to oxidative stress.,In particular aberrant regulation of these pathways by HDACs may play critical roles in cancer progression.,In this review we discuss the current evidence linking epigenetics and oxidative stress and cancer, using chronic obstructive pulmonary disease and non-small cell lung cancer to illustrate the importance of epigenetics on these pathways within these disease settings. | Despite the status of chronic obstructive pulmonary disease (COPD) as a major global health problem, no currently available therapies can limit COPD progression.,Therefore, an urgent need exists for the development of new and effective treatments for COPD.,An improved understanding in the molecular pathogenesis of COPD can potentially identify molecular targets to facilitate the development of new therapeutic modalities.,Among the best approaches for understanding the molecular basis of COPD include gene expression profiling techniques, such as serial analysis of gene expression or microarrays.,Using these methods, recent studies have mapped comparative gene expression profiles of lung tissues from patients with different stages of COPD relative to healthy smokers or non-smokers.,Such studies have revealed a number of differentially-regulated genes associated with COPD progression, which include genes involved in the regulation of inflammation, extracellular matrix, cytokines, chemokines, apoptosis, and stress responses.,These studies have shed new light on the molecular mechanisms of COPD, and suggest novel targets for clinical treatments. | 1 |
Chronic obstructive pulmonary disease (COPD) is a common chronic disease, and its morbidity and mortality are increasing.,There are many studies that have tried to explain the pathogenesis of COPD from genetic susceptibility, to identify the susceptibility of COPD factors, which play a role in early prevention, early detection and the early treatment.,However, it is well known that COPD is an inflammatory disease characterized by incomplete reversible airflow limitation in which genes interact with the environment.,In recent years, many studies have proved gene polymorphisms and COPD correlation.,However, there is less research on the relationship between COPD and genome-wide association study (GWAS), epigenetics and apoptosis.,In this paper, we summarized the correlation between gene level and COPD from the following four aspects: the GWAS, the gene polymorphism, the epigenetics and the apoptosis, and the relationship between COPD and gene is summarized comprehensively. | The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally. | 1 |
Introduction: The use of antibiotics is based on the clinician’s experience and judgment, and antibiotics may often be overused in the treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,Eosinophils have been studied as biomarkers of bacterial infection and prognostic factors in chronic obstructive pulmonary disease and AECOPD.,Thus, the purpose of this study was to determine whether eosinophils could be used to determine bacterial infection in AECOPD events.,Methods: We retrospectively analyzed the medical records of patients admitted to Korea University Guro Hospital for AECOPD between January 2011 and May 2017.,Data pertaining to baseline characteristics, results of previous pulmonary function tests, treatment information during the admission period, and history of pulmonary treatment were collected before admission.,Results: A total of 736 AECOPD events were eligible for inclusion and were divided into two groups based on the eosinophil count: those involving eosinophil counts of less than 2% (546 events) and those involving counts of 2% or more (190 events).,In univariate analysis, the only bacterial pathogen identification events and bacterial-viral pathogen co-identification events were significantly more frequent in the group with eosinophil counts of less than 2% (P=0.010 and P=0.001, respectively).,In logistic regression analysis, the rates of only bacterial pathogen identification [odds ratios =1.744; 95% confidence interval, 1.107-2.749; P=0.017] and bacterial-viral pathogen co-identification [odds ratios=2.075; 95% confidence interval, 1.081-3.984; P=0.028] were higher in the group with eosinophil count less than 2%.,Conclusion: In conclusion, eosinophil counts of less than 2% are potential indicators of a bacterial infection in AECOPD events.,Eosinophils could thus serve as a reference for the use of antibiotics in AECOPD treatment. | COPD patients with increased airway eosinophilic inflammation show a favorable response to inhaled corticosteroids (ICS) in combination with a long-acting bronchodilator.,Recent studies have demonstrated a significant correlation of sputum eosinophilia with blood eosinophils and periostin.,We investigated whether high blood eosinophils and plasma periostin were associated with an improvement in forced expiratory volume in 1 second (FEV1) after 3-month treatment with ICS/long-acting beta2-agonist (LABA) in stable COPD patients.,Blood eosinophils and plasma periostin levels were measured in 130 stable COPD subjects selected from the Korean Obstructive Lung Disease cohort.,Subjects began a 3-month ICS/LABA treatment after washout period.,High blood eosinophils (>260/µL, adjusted odds ratio =3.52, P=0.009) and high plasma periostin (>23 ng/mL, adjusted odds ratio =3.52, P=0.013) were significantly associated with FEV1 responders (>12% and 200 mL increase in FEV1 from baseline after treatment).,Moreover, the addition of high blood eosinophils to age, baseline positive bronchodilator response, and FEV1 <50% of the predicted value significantly increased the area under the curve for prediction of FEV1 responders (from 0.700 to 0.771; P=0.045).,High blood eosinophils and high plasma periostin were associated with improved lung function after 3-month ICS/LABA treatment.,In particular, high blood eosinophils, in combination with age and baseline lung function parameters, might be a possible biomarker for identification of COPD patients with favorable FEV1 improvement in response to ICS/LABA treatment. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients.,Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype.,This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes.,These patients are therefore a priority for research and treatment.,The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection.,Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment.,Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype.,This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.,The online version of this article (doi:10.1186/1741-7015-11-181) contains supplementary material, which is available to authorized users. | As chronic obstructive pulmonary disease (COPD) is a heterogeneous disease it is unlikely that all patients will benefit equally from a given therapy.,Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, has been shown to improve lung function in moderate and severe COPD but its effect on exacerbations in unselected populations was inconclusive.,This led to the question of whether a responsive subset existed that could be investigated further.,The datasets of two previous replicate, randomized, double-blind, placebo-controlled, parallel-group studies (oral roflumilast 500 μg or placebo once daily for 52 weeks) that were inconclusive regarding exacerbations were combined in a post-hoc, pooled analysis to determine whether roflumilast reduced exacerbations in a more precisely defined patient subset.,The pooled analysis included 2686 randomized patients.,Roflumilast significantly decreased exacerbations by 14.3% compared with placebo (p = 0.026).,Features associated with this reduction were: presence of chronic bronchitis with or without emphysema (26.2% decrease, p = 0.001), presence of cough (20.9% decrease, p = 0.006), presence of sputum (17.8% decrease, p = 0.03), and concurrent use of inhaled corticosteroids (ICS; 18.8% decrease, p = 0.014).,The incidence of adverse events was similar with roflumilast and placebo (81.5% vs 80.1%), but more patients in the roflumilast group had events assessed as likely or definitely related to the study drug (21.5% vs 8.3%).,This post-hoc, pooled analysis showed that roflumilast reduced exacerbation frequency in a subset of COPD patients whose characteristics included chronic bronchitis with/without concurrent ICS.,These observations aided the design of subsequent phase 3 studies that prospectively confirmed the reduction in exacerbations with roflumilast treatment.,ClinicalTrials.gov identifiers: NCT00076089 and NCT00430729. | 1 |
Asthma and chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) is an increasingly recognized phenotype.,Few randomized clinical trials have been conducted in patients with ACOS; therefore, scientific evidence concerning ACOS is scarce and a therapeutic approach remains unclear.,The aim of this study was to evaluate current treatment trends for patients with ACOS, identified as those with a dual definition of asthma and COPD, in a real-world COPD cohort.,Data were analyzed from patients with asthma and COPD in the USA, France, Germany, Italy, Spain, and the UK who participated in the 2012 and 2013 Adelphi Respiratory Disease Specific Programmes (DSPs).,Patients with ACOS were identified in the COPD population; these patients had a physician-confirmed, concomitant asthma diagnosis.,Physicians completed a patient record form providing information on patient and disease characteristics including prescribed respiratory treatment.,Pairwise comparisons were made between the ACOS, asthma, and COPD populations using χ2 tests.,In total, 9,042 patients with asthma-only, 7,119 patients with COPD-only, and 523 patients with ACOS (a dual diagnosis of asthma and COPD) participated in the study.,The most commonly prescribed regimens were inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) + long-acting muscarinic antagonist (LAMA); (ACOS 30%, asthma 1.4%, and COPD 32%), ICS/LABA (19%, 41.5%, and 17%, respectively), and LAMA (6%, 0.4%, and 19%, respectively); 18% of patients with ACOS were not prescribed an ICS.,Patients with ACOS had a significantly higher incidence of gastroesophageal reflux disease, diabetes, and obesity and experienced more exacerbations in the past year than those with COPD or asthma.,The majority of patients with ACOS, as defined in this research, were prescribed similar treatment to those with COPD.,There is a need, however, for better treatment for patients with ACOS, as indicated by symptoms and exacerbation levels.,A clearer therapeutic approach for patients with ACOS is required. | The BEACON study evaluated the efficacy and safety of QVA149, a once-daily dual bronchodilator containing a fixed-dose combination of the long-acting β2-agonist (LABA) indacaterol and long-acting muscarinic antagonist (LAMA) glycopyrronium (NVA237), in development for the treatment of patients with chronic obstructive pulmonary disease (COPD), compared with the free-dose concurrent administration of indacaterol plus glycopyrronium (IND+GLY).,In this multicenter, double-blind, parallel group study, patients with stage II or stage III COPD (Global initiative for chronic Obstructive Lung Disease [GOLD] 2010) were randomized (1:1) to once-daily QVA149 (110 μg indacaterol/50 μg glycopyrronium) or concurrent administration of indacaterol (150 μg) and glycopyrronium (50 μg) via the Breezhaler® device (Novartis AG, Basel, Switzerland) for 4 weeks.,The primary endpoint was to evaluate the noninferiority of QVA149 as compared with concurrent administration of IND+GLY, for trough forced expiratory volume in 1 second (FEV1) after 4 weeks of treatment.,The other assessments included FEV1 area under the curve from 0 to 4 hours (AUC0-4 hours) at day 1 and week 4, symptom scores, rescue medication use, safety, and tolerability over the 4-week study period.,Of 193 patients randomized, 187 (96.9%) completed the study.,Trough FEV1 at week 4 for QVA149 and IND+GLY was 1.46 L ± 0.02 and 1.46 L ± 0.18, respectively.,The FEV1 AUC0-4 hours at day 1 and week 4 were similar between the two treatment groups.,Both treatment groups had a similar reduction in symptom scores and rescue medication use for the 4-week treatment period.,Overall, 25.6% of patients in QVA149 group and 25.2% in the IND+GLY group experienced an adverse event, with the majority being mild-to-moderate in severity.,No deaths were reported during the study or during the 30 days follow-up period.,The BEACON study demonstrated that once-daily QVA149 provides an efficacy and safety profile similar to the concurrent administration of its monocomponents indacaterol and glycopyrronium. | 1 |
The use of adequate self-management strategies for people with chronic obstructive pulmonary disease (COPD) reduces healthcare use, improves health-related quality of life (HRQoL) and recovery after acute exacerbations.,However, not many people with COPD receive support that promotes the use of such strategies and therefore new methods to facilitate and promote the use of self-management strategies are highly warranted.,This pilot trial aims to evaluate the feasibility of the study design and study procedures considering effectiveness of the novel intervention, the COPD-web.,The overall design is a pragmatic controlled pilot trial with preassessments and postassessments and a parallel process evaluation.,Patients with the diagnosis of COPD will be eligible for the study.,The intervention group will be recruited when visiting one of the six participating primary care units in Sweden.,The control group will be identified from the unit's computerised registers.,The intervention, the COPD-web, is an interactive web page with two sections; one directed at people with COPD and one at healthcare professionals.,The sections aim to support patients’ self-management skills-and to facilitate the provision of support for self-management strategies, respectively.,Effectiveness with regard to patients’ symptoms, HRQoL, knowledge of and readiness for COPD-related self-management, health literacy, self-efficacy for physical activity and time spent in physical activity and time being sedentary, and further, healthcare professionals’ knowledge of and readiness to support COPD-related self-management strategies will be assessed using questionnaires at 3 and 12 months.,The process evaluation will include observations and interviews.,Ethical approval has been obtained.,Findings will be presented at conferences, submitted for publication in peer-reviewed publications and presented to the involved healthcare professionals, patients and to patient organisations.,ClinicalTrials.gov: NCT02696187 | Chronic obstructive pulmonary disease (COPD), a major cause of morbidity and mortality worldwide, often occurs in the presence of comorbidities, which may influence experience and management of the disease.,No prior research seems to have gained perspectives of newly diagnosed primary care COPD patients in the context of multimorbidity.,This qualitative study aimed to explore the impact of a new diagnosis of COPD in the context of multimorbidity and also sought to gain a better understanding of how patients react to the diagnosis and incorporate it into their lives.,Participants were identified from a cohort of primary care patients with multimorbidity recently diagnosed with COPD.,Data was collected via semi-structured interviews from nine male and eight female participants.,Thematic analysis was performed and the data interpreted from a constructivist perspective.,Five core themes regarding COPD were induced: (i) reaction to diagnosis, (ii) impact on function and health behaviour, (iii) factors influencing self-management capacity, (iv) healthcare utilisation and (v) interplay of comorbidities.,Most participants had difficulty recognising the importance of COPD and its long-term implications.,For many, the salience of another chronic condition outweighed COPD.,Self-management capacity and utilisation of healthcare services were challenged by low prioritisation of COPD among other comorbidities.,This study provides an insight into how primary care patients feel about being diagnosed with COPD, as well as their prioritisation of the disease in the context of multimorbidity.,It highlights the need for tailored education and personalised management incorporating patients’ perspectives in primary care. | 1 |
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 | To assess the importance of inflammation in chronic obstructive pulmonary disease (COPD) by measuring airway and systemic inflammatory biomarkers in Japanese patients with the disease and relevant control groups.,This was the first study of its type in Japanese COPD patients.,It was a non-treatment study in which 100 participants were enrolled into one of three groups: nonsmoking controls, current or ex-smoking controls, and COPD patients.,All participants underwent standard lung function assessments and provided sputum and blood samples from which the numbers of inflammatory cells and concentrations of biomarkers were measured, using standard procedures.,The overall trends observed in levels of inflammatory cells and biomarkers in sputum and blood in COPD were consistent with previous reports in Western studies.,Increasing levels of neutrophils, interleukin 8 (IL-8), surfactant protein D (SP-D), and Krebs von den Lungen 6 (KL-6) in sputum and clara cell 16 (CC-16), high-sensitivity C-reactive protein (hs-CRP), and KL-6 in serum and plasma fibrinogen were seen in the Japanese COPD patients compared with the non-COPD control participants.,In sputum, significant correlations were seen between total cell count and matrix metalloproteinase 9 (MMP-9; P<0.001), neutrophils and MMP-9 (P<0.001), macrophages and KL-6 (P<0.01), total cell count and IL-8 (P<0.05), neutrophils and IL-8 (P<0.05), and macrophages and MMP-9 (P<0.05).,Significant correlations were also observed between some inflammatory cells in sputum and biomarkers in serum, with the most significant between serum CC-16 and both total cell count (P<0.005) and neutrophils (P<0.005) in sputum.,These results provide evidence for the first time that COPD in Japanese patients is a multicomponent disease, involving both airway and systemic inflammation, in addition to airway obstruction.,Therefore, intervention with anti-inflammatory therapy may provide additional benefit in disease management of COPD in Japan. | 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. | Chronic obstructive pulmonary disease (COPD) is a commonly reported cause of death and associated with smoking.,However, COPD mortality is high in poor countries with low smoking rates.,Spirometric restriction predicts mortality better than airflow obstruction, suggesting that the prevalence of restriction could explain mortality rates attributed to COPD.,We have studied associations between mortality from COPD and low lung function, and between both lung function and death rates and cigarette consumption and gross national income per capita (GNI).,National COPD mortality rates were regressed against the prevalence of airflow obstruction and spirometric restriction in 22 Burden of Obstructive Lung Disease (BOLD) study sites and against GNI, and national smoking prevalence.,The prevalence of airflow obstruction and spirometric restriction in the BOLD sites were regressed against GNI and mean pack years smoked.,National COPD mortality rates were more strongly associated with spirometric restriction in the BOLD sites (<60 years: men rs=0.73, p=0.0001; women rs=0.90, p<0.0001; 60+ years: men rs=0.63, p=0.0022; women rs=0.37, p=0.1) than obstruction (<60 years: men rs=0.28, p=0.20; women rs=0.17, p<0.46; 60+ years: men rs=0.28, p=0.23; women rs=0.22, p=0.33).,Obstruction increased with mean pack years smoked, but COPD mortality fell with increased cigarette consumption and rose rapidly as GNI fell below US$15 000.,Prevalence of restriction was not associated with smoking but also increased rapidly as GNI fell below US$15 000.,Smoking remains the single most important cause of obstruction but a high prevalence of restriction associated with poverty could explain the high ‘COPD’ mortality in poor countries. | 1 |
Two 1-year studies evaluated the long-term efficacy and safety of tiotropium 5 or 10 μg versus placebo, inhaled via the Respimat® Soft Mist™ Inhaler (SMI).,The two studies were combined and had 4 co-primary endpoints (trough FEV1 response, Mahler Transition Dyspnea Index [TDI] and St George’s Respiratory Questionnaire scores all at week 48, and COPD exacerbations per patient-year).,A total of 1990 patients with COPD participated (mean FEV1: 1.09 L).,The mean trough FEV1 response of tiotropium 5 or 10 μg relative to placebo was 127 or 150 mL, respectively (both P < 0.0001).,The COPD exacerbation rate was significantly lower with tiotropium 5 μg (RR = 0.78; P = 0.002) and tiotropium 10 μg (RR = 0.73; P = 0.0008); the health-related quality of life and Mahler TDI co-primary endpoints were significantly improved with both doses (both P < 0.0001).,Adverse events were generally balanced except anticholinergic class effects, which were more frequent with active treatment.,Fatal events occurred in 2.4% (5 μg), 2.7% (10 μg), and 1.6% (placebo) of patients; these differences were not significant.,Tiotropium Respimat® SMI 5 μg demonstrated sustained improvements in patients with COPD relative to placebo and similar to the 10 μg dose but with a lower frequency of anticholinergic adverse events. | Clinical manifestations of chronic obstructive pulmonary disease (COPD), including airflow limitation, dyspnea, and activity limitation, ultimately lead to impaired health-related quality of life (HRQoL).,This 9-month, randomized, double-blind, multicenter study compared the effect of once-daily tiotropium 18 μg and placebo on HRQoL, spirometric parameters, and exacerbations in 554 patients with moderate-to-severe COPD.,HRQoL was assessed using the St.,George’s Respiratory Questionnaire (SGRQ) and the new 8-item Visual Simplified Respiratory Questionnaire (VSRQ), which is currently being validated.,The primary efficacy endpoint was the proportion of patients achieving a reduction of at least 4 units in the SGRQ total score at study end (Month 9).,Mean ± SD baseline SGRQ total score was 47.4 ± 18.1.,Significantly more tiotropium-treated patients achieved a reduction of at least 4 units in the SGRQ score vs placebo at study end (59.1% vs 48.2%, respectively; p = 0.029).,Tiotropium significantly improved spirometric parameters (forced expiratory volume in 1 second [FEV1]: 0.11 ± 0.02 L vs 0.01 ± 0.02 L; between-group difference: 0.10 ± 0.03 L, p = 0.0001) and reduced exacerbations vs placebo.,Maintenance treatment with tiotropium provided significant and clinically relevant improvements in HRQoL, as measured by the SGRQ. | 1 |
As chronic obstructive pulmonary disease (COPD) is known for poor glucocorticoid (GC) response, we hypothesized that polymorphic variants of the glucocorticoid receptor (GR) gene might predispose for COPD and/or disease severity.,Three out of about 50 of the most abundant receptor GR gene polymorphisms were investigated in a case-control study which included 207 patients with chronic bronchitis or COPD (mean FEV1 50.5% predicted, GOLD I-IV) and 106 age matched healthy subjects (mean FEV1 101.8% predicted).,These were genotyped: a) for the N363S (Exon 2; 1220 A > G (I)); b) the BCLI restriction fragment length polymorphism (Intron 2; 647 C > G (II)); and c) the ER2223EK (Exon 2; 198, 200 G > A (III)), using RT-PCR and PCR-RFLP method on genomic DNA isolated from EDTA blood.,Genotype distribution between COPD and healthy subjects were alike in all of these three polymorphisms.,N363S was found in 0.94% of the healthy and 0% of the COPD subjects.,BCLI was detected in 11.3% of the controls and 15.5% of the COPD patients whereas heterozygote frequency was less in the COPD (44.4%) group (controls 60.4%).,ER2223EK lacks in any of the study subjects.,Further, SNPs did not correlate with COPD severity stage (GOLD), exacerbation rates, and clinical course.,COPD is not linked to gene polymorphisms N363S, BCLI-RFLP, and ER2223EK.,Since we analyzed only these 3 receptor gene polymorphisms, this study cannot rule out that other GR gene variants and linkages may be of influence. | Tobacco smoking has been considered the most important risk factor for chronic obstructive pulmonary disease (COPD) development.,However, not all smokers develop COPD and other environmental and genetic susceptibility factors underlie disease pathogenesis.,Recent studies have indicated that the impairment of TLR signaling might play a crucial role in the development of emphysema.,For this purpose we investigated the prevalence and any possible associations of common TLR polymorphisms (T L R2-R753Q, T L R4-D299G, and T L R4-T399I) in a group of 240 heavy smokers (>20 pack years), without overt atherosclerosis disease, of whom 136 had developed COPD and 104 had not.,The presence of T L R4-T399I polymorphism was associated with a 2.4-fold increased risk for COPD development (P = .044), but not with disease stage or frequency of exacerbations.,Considering that infections contribute to COPD and emphysema pathogenesis, our findings possibly indicate that dysfunctional polymorphisms of innate immune genes can affect the development of COPD in smokers.,Although this finding warrants further investigation, it highlights the importance of impaired innate immunity towards COPD development. | 1 |
Multimorbidity has already become common in primary care and will be a challenge in the future.,Primary care in Sweden participates to a great extent in the care of patients with two severe, chronic conditions: chronic obstructive pulmonary disease (COPD) and heart failure.,Both conditions are characterized by high mortality and often coexist.,Age, sex, heart failure and other comorbidities are considered to be the major predictors of mortality in patients with COPD.,We aimed to study the impact of heart failure, other comorbidities, age and sex on mortality in patients with COPD.,A register-based, prospective cohort study conducted in Blekinge County in Sweden with about 150,000 inhabitants.,The study population was comprised of people aged ≥35 years.,The data about diagnoses of COPD and heart failure came from the 2007 health care register, in which we found 984 individuals with a diagnosis of COPD.,Date of death was collected from January 1st, 2008 -August 31st, 2015.,The diagnosis-based Adjusted Clinical Groups (ACG) Case-Mix System 7.1 was used to describe comorbidity.,Each individual was assigned one of six comorbidity levels called resource utilization bands (RUB) graded from 0 to 5.,Estimated eight year mortality in patients with COPD and coexisting heart failure was seven times higher than in patients with COPD alone - odds ratio 7.06 (95% CI 3.88-12.84).,Adjusting for age and male sex resulted in odds ratio 3.75 (95% CI 1.97-7.15).,Further adjusting for other comorbidities resulted in odds ratio 3.26 (95% CI 1.70-6.25).,The mortality was strongly associated with the highest comorbidity level - RUB 5 where the odds ratio was 5.19 (95% CI 2.59-10.38).,Heart failure has an important impact on mortality in patients with COPD.,The mortality in patients with COPD and coexisting heart failure was strongly associated with age, male sex and other comorbidities.,Of those three predictors, only other comorbidities can be influenced.,Heart failure and other comorbidities should be recognized early and properly treated in order to improve survival in patients with coexisting COPD and heart failure. | Multimorbidity, the presence of 2 or more chronic conditions, frequently affects people with chronic obstructive pulmonary disease (COPD).,Many have high-cost, highly complex conditions that have a substantial impact on state Medicaid programs.,We quantified the cost of Medicaid-insured patients with COPD co-diagnosed with other chronic disorders.,We used nationally representative Medicaid claims data to analyze the impact of comorbidities (other chronic conditions) on the disease burden, emergency department (ED) use, hospitalizations, and total health care costs among 291,978 adult COPD patients.,We measured the prevalence of common conditions and their influence on COPD-related and non-COPD-related resource use by using the Elixhauser Comorbidity Index.,Elixhauser comorbidity counts were clustered from 0 to 7 or more.,We performed multivariable logistic regression to determine the odds of ED visits by Elixhauser scores adjusting for age, sex, race/ethnicity, and residence.,Acute care, hospital bed days, and total Medicaid-reimbursed costs increased as the number of comorbidities increased.,ED visits unrelated to COPD were more common than visits for COPD, especially in patients self-identified as black or African American (designated black).,Hypertension, diabetes, affective disorders, hyperlipidemia, and asthma were the most prevalent comorbid disorders.,Substance abuse, congestive heart failure, and asthma were commonly associated with ED visits for COPD.,Female sex was associated with COPD-related and non-COPD-related ED visits.,Comorbidities markedly increased health services use among people with COPD insured with Medicaid, although ED visits in this study were predominantly unrelated to COPD.,Achieving excellence in clinical practice with optimal clinical and economic outcomes requires a whole-person approach to the patient and a multidisciplinary health care team. | 1 |
COPD patients have increased risk of developing pneumonia, which is associated with poor outcomes.,It can be symptomatically indistinguishable from exacerbations, making diagnosis challenging.,Studies of pneumonia in COPD have focused on hospitalised patients and are not representative of the ambulant COPD population.,Therefore, we sought to determine the incidence and aetiology of acute exacerbation events with evidence of pneumonic radiographic infiltrates in an outpatient COPD cohort.,One hundred twenty-seven patients with moderate to very severe COPD aged 42-85 years underwent blood and sputum sampling over one year, at monthly stable visits and within 72 h of exacerbation symptom onset. 343 exacerbations with chest radiographs were included.,20.1% of exacerbations had pneumonic infiltrates.,Presence of infiltrate was highly seasonal (Winter vs summer OR 3.056, p = 0.027).,In paired analyses these exacerbation events had greater increases in systemic inflammation.,Bacterial detection rate was higher in the pneumonic group, with Haemophilus influenzae the most common bacteria in both radiological groups.,Viral detection and sputum microbiota did not differ with chest radiograph appearance.,In an outpatient COPD cohort, pneumonic infiltrates at exacerbation were common, and associated with more intense inflammation.,Bacterial pathogen detection and lung microbiota were not distinct, suggesting that exacerbations and pneumonia in COPD share common infectious triggers and represent a continuum of severity rather than distinct aetiological events.,Trial registration Number: NCT01360398.,The online version of this article (10.1186/s12931-018-0842-8) 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 |
‘Clinically important deterioration’ (CID) is a composite endpoint measuring worsening of the key clinical features of chronic obstructive pulmonary disease (COPD), namely lung function, patient-reported outcomes, and exacerbations.,ACLIFORM and AUGMENT were two 24-week, randomized, double-blind, phase III studies assessing twice-daily (BID) aclidinium bromide (AB) 400 μg/formoterol fumarate (FF) 12 μg.,This pooled post-hoc analysis assessed the effects of AB/FF 400/12 μg on both first and sustained CID events versus placebo and monotherapies in patients with moderate to severe COPD.,A first CID event was defined as the occurrence of a moderate/severe exacerbation or the worsening from baseline in ≥1 of the following: trough forced expiratory volume in 1 second (FEV1; ≥100 mL), Transition Dyspnea Index (TDI) focal score (≥1 unit), or St George’s Respiratory Questionnaire (SGRQ) total score (≥4 units).,A ‘sustained’ CID was defined as a worsening maintained at all subsequent visits from appearance to week 24 or a moderate/severe exacerbation at any time.,CID events were assessed at three visits (weeks 4, 12, and 24); trough FEV1 was also measured at weeks 1 and 18.,AB/FF 400/12 μg reduced the risk of a first CID event by 45% versus placebo (hazard ratio [HR] 0.55, p < 0.001), 18% versus FF 12 μg (HR 0.82, p < 0.01), and 15% versus AB 400 μg (HR 0.85, p < 0.05).,Similarly, AB/FF 400/12 μg reduced the risk of a sustained CID event by 48% versus placebo (HR 0.52, p < 0.001) and 22% versus FF 12 μg (HR 0.78, p < 0.01).,AB/FF 400/12 μg reduced the risk of a first or sustained CID event for all four components versus placebo (trough FEV1 and TDI, first and sustained CID, all p < 0.001; SGRQ first CID p < 0.001; SGRQ sustained CID, p < 0.01; exacerbations first and sustained CID, both p < 0.05) and TDI and SGRQ versus FF 12 μg (TDI, first and sustained CID both p < 0.05; SGRQ first CID p < 0.01), and SGRQ versus AB 400 μg (first CID, p < 0.05).,AB/FF 400/12 μg BID may provide greater airway stability and fewer exacerbations or deteriorations in lung function, health status, or dyspnea compared with placebo or monotherapies.,Clinicaltrials.gov NCT01462942 (ACLIFORM); registered 26 October 2011.,Clinicaltrials.gov NCT01437397 (AUGMENT); registered 19 September 2011.,The online version of this article (doi:10.1186/s12931-017-0583-0) contains supplementary material, which is available to authorized users. | Bronchodilator therapy is the backbone of the management of chronic obstructive pulmonary disease.,In some patients, inhaled corticosteroids can be prescribed in combination with bronchodilators.,Through a subgroup analysis of pooled data from two large phase III clinical trials of bronchodilator therapy according to concomitant inhaled corticosteroid use (user vs. non-user), we sought to evaluate the clinical benefit of adding inhaled corticosteroids to dual bronchodilator therapy in chronic obstructive pulmonary disease.,The primary focus of this analysis of pooled data from the phase III ACLIFORM and AUGMENT studies was to evaluate the efficacy of aclidinium/formoterol on lung function stratified by inhaled corticosteroid use.,We found that lung-function end points were significantly improved regardless of concomitant inhaled corticosteroid use among patients treated with the dual bronchodilator aclidinium/formoterol 400/12 µg twice daily compared with placebo and both monotherapies.,Together with the previously reported observations that aclidinium/formoterol 400/12 µg reduces exacerbations vs. placebo in inhaled corticosteroid users and improves dyspnoea compared to monotherapy in inhaled corticosteroid non-users, these data suggest that both groups achieve lung function improvements, which translates to different clinical benefits depending on whether or not a patient is receiving concomitant inhaled corticosteroids.,A dual bronchodilator therapy taken together with corticosteroid inhalers may benefit patients with severe chronic lung disease.,Bronchodilator drugs relax the lungs and widen airways in patients with chronic obstructive pulmonary disease (COPD).,While recent studies have shown that a dual bronchodilator therapy containing aclidinium and formoterol significantly improves lung function in COPD, little is known about combining the dual therapy with inhaled corticosteroids (ICSs).,Anthony D’Urzo at the University of Toronto, Canada, and co-workers analysed data from 3394 patients with COPD undergoing dual therapy trials.,Of these, 1180 were already taking ICSs.,The team compared symptoms in the ICS group with those not taking ICSs.,The dual therapy improved lung function across both groups regardless of ICS use, though patients gained different clinical benefits depending on ICS use and disease severity. | 1 |
Natriuretic peptides (NPs) are a family of prognostic biomarkers in patients with heart failure (HF).,HF is one of the most frequent comorbidities in patients with chronic obstructive pulmonary disease (COPD).,However, the prognostic role of NP in COPD patients remains unclear.,The aim of this meta-analysis was to evaluate the relation between NP and all-cause mortality in COPD patients.,We performed a systematic review and meta-analysis of observational studies assessing prognostic implications of elevated NP levels on all-cause mortality in COPD patients.,Nine studies were considered for qualitative analysis for a total of 2788 patients.,Only two studies focused on Mid Regional-pro Atrial Natriuretic Peptide (MR-proANP) and brain natriuretic peptide (BNP), respectively, but seven studies focused on pro-BNP (NT-proBNP) and were included in the quantitative analysis.,Elevated NT-proBNP values were related to increased risk of all-cause mortality in COPD patients both with and without exacerbation (hazard ratio (HR): 2.87, p < 0.0001 and HR: 3.34, p = 0.04, respectively).,The results were confirmed also after meta-regression analysis for confounding factors (previous cardiovascular history, hypertension, HF, forced expiratory volume at 1 second and mean age).,NT-proBNP may be considered a reliable predictive biomarker of poor prognosis in patients with COPD. | Background: COPD pathology involves not only the lungs but also extrapulmonary abnormalities.,Osteoporosis is one of the most important abnormalities because it may cause vertebral compression fractures and deteriorate pulmonary function.,COPD patients have many risk factors for osteoporosis, such as low BMI, decreased activity, systemic inflammation, and use of corticosteroids.,Some of these factors have been shown to deteriorate with COPD exacerbations.,We previously demonstrated the correlation between emphysema and osteoporosis and between emphysema progression and COPD exacerbations.,Thus, the hypothesis that exacerbation causes osteoporosis progression in COPD patients was investigated.,Methods: Forty-two COPD patients not on osteoporosis treatment for over 2 years were recruited.,During follow-up, exacerbations had been prospectively recorded.,Thoracic vertebral bone mineral density (BMD) was measured using chest CT, and the annual change in BMD was calculated.,The change was compared between patients with and without a history of exacerbations.,Results: The decrease in thoracic vertebral BMD was greater in patients with than in those without a history of exacerbations (median ABMD mg/ml year: −3.78 versus −0.30, p = 0.02).,Moreover, multivariate regression analysis showed that exacerbations and baseline Pa02 were independent predictors of the BMD decrease (R2 = 0.20, p = 0.007, and R2 = 0.09, p = 0.03, respectively) after adjustment for baseline age, smoking status, and airflow limitation.,Conclusions: This is the first longitudinal study to demonstrate that COPD exacerbations are independently associated with osteoporosis progression.,Osteoporosis progression should be evaluated in COPD patients, especially in those with a history of frequent exacerbations. | 1 |
To identify clusters of patients who may benefit from treatment with an inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) versus LABA alone, in terms of exacerbation reduction, and to validate previously identified clusters of patients with chronic obstructive pulmonary disease (COPD) (based on diuretic use and reversibility).,Post hoc supervised cluster analysis using a modified recursive partitioning algorithm of two 1-year randomised, controlled trials of fluticasone furoate (FF)/vilanterol (VI) versus VI alone, with the primary end points of the annual rate of moderate-to-severe exacerbations.,Global.,3255 patients with COPD (intent-to-treat populations) with a history of exacerbations in the past year.,FF/VI 50/25 µg, 100/25 µg or 200/25 µg, or VI 25 µg; all one time per day.,Mean annual COPD exacerbation rate to identify clusters of patients who benefit from adding an ICS (FF) to VI bronchodilator therapy.,Three clusters were identified, including two groups that benefit from FF/VI versus VI: patients with blood eosinophils >2.4% (RR=0.68, 95% CI 0.58 to 0.79), or blood eosinophils ≤2.4% and smoking history ≤46 pack-years, experienced a reduced rate of exacerbations with FF/VI versus VI (RR=0.78, 95% CI 0.63 to 0.96), whereas those with blood eosinophils ≤2.4% and smoking history >46 pack-years were identified as non-responders (RR=1.22, 95% CI 0.94 to 1.58).,Clusters of patients previously identified in the fluticasone propionate/salmeterol (SAL) versus SAL trials of similar design were not validated; all clusters of patients tended to benefit from FF/VI versus VI alone irrespective of diuretic use and reversibility.,In patients with COPD with a history of exacerbations, those with greater blood eosinophils or a lower smoking history may benefit more from ICS/LABA versus LABA alone as measured by a reduced rate of exacerbations.,In terms of eosinophils, this finding is consistent with findings from other studies; however, the validity of the 2.4% cut-off and the impact of smoking history require further investigation.,NCT01009463; NCT01017952; Post-results. | COPD exacerbations requiring hospitalization increase morbidity and mortality.,Although most COPD exacerbations are neutrophilic, approximately 10%-25% of exacerbations are eosinophilic.,We aimed to evaluate mortality and outcomes of eosinophilic and non-eosinophilic COPD exacerbations and identify new biomarkers that predict survival.,A retrospective observational cohort study was carried out in a tertiary teaching hospital from January 1, 2014 to November 1, 2014.,All COPD patients hospitalized with exacerbations were enrolled in the study at their initial hospitalization and followed-up for 6 months after discharge.,Electronic data were collected from the hospital database.,Subjects’ characteristics, hemogram parameters, CRP levels, neutrophil-to-lymphocyte ratio (NLR), platelet-to-mean platelet volume ratio on admission and discharge, length of hospital stay (days), readmissions, and mortality were recorded.,Patients were grouped according to peripheral blood eosinophil (PBE) levels: Group 1, >2% PBE, eosinophilic; Group 2, non-eosinophilic ≤2%.,Patient survival after hospital discharge was evaluated by Kaplan-Meier survival analysis.,A total of 1,704 patients hospitalized with COPD exacerbation were included.,Approximately 20% were classified as eosinophilic.,Six-month mortality was similar in eosinophilic and non-eosinophilic groups (14.2% and 15.2%, respectively); however, the hospital stay length and readmission rate were longer and higher in the non-eosinophilic group (P<0.001 and P<0.01, respectively).,CRP and NLR were significantly higher in the non-eosinophilic group (both P<0.01).,The platelet-to-mean platelet volume ratio was not different between the two groups.,Cox regression analysis showed that survival was negatively influenced by elevated CRP (P<0.035) and NLR (P<0.001) in the non-eosinophilic group.,Non-eosinophilic patients with COPD exacerbations with high CRP and NLR values had worse outcomes than eosinophilic patients.,PBE and NLR can be helpful markers to guide treatment decisions. | 1 |
Cardiovascular disease is an important comorbidity in patients with chronic obstructive pulmonary disease (COPD).,We aimed to systematically review the evidence for: (1) risk of myocardial infarction (MI) in people with COPD; (2) risk of MI associated with acute exacerbation of COPD (AECOPD); (3) risk of death after MI in people with COPD.,Systematic review and meta-analysis.,MEDLINE, EMBASE and SCI were searched up to January 2015.,Two reviewers screened abstracts and full text records, extracted data and assessed studies for risk of bias.,We used the generic inverse variance method to pool effect estimates, where possible.,Evidence was synthesised in a narrative review where meta-analysis was not possible.,Searches yielded 8362 records, and 24 observational studies were included.,Meta-analysis showed increased risk of MI associated with COPD (HR 1.72, 95% CI 1.22 to 2.42) for cohort analyses, but not in case-control studies: OR 1.18 (0.80 to 1.76).,Both included studies that investigated the risk of MI associated with AECOPD found an increased risk of MI after AECOPD (incidence rate ratios, IRR 2.27, 1.10 to 4.70, and IRR 13.04, 1.71 to 99.7).,Meta-analysis showed weak evidence for increased risk of death for patients with COPD in hospital after MI (OR 1.13, 0.97 to 1.31).,However, meta-analysis showed an increased risk of death after MI for patients with COPD during follow-up (HR 1.26, 1.13 to 1.40).,There is good evidence that COPD is associated with increased risk of MI; however, it is unclear to what extent this association is due to smoking status.,There is some evidence that the risk of MI is higher during AECOPD than stable periods.,There is poor evidence that COPD is associated with increased in hospital mortality after an MI, and good evidence that longer term mortality is higher for patients with COPD after an MI. | Patients with chronic obstructive pulmonary disease (COPD) have increased mortality following myocardial infarction (MI) compared with patients without COPD.,We investigated the extent to which differences in recognition and management after MI could explain the mortality difference.,300 161 patients with a first MI between 2003 and 2013 were identified in the UK Myocardial Ischaemia National Audit Project database.,Logistic regression was used to compare mortality in hospital and at 180 days postdischarge between patients with and without COPD.,Variables relating to inhospital factors (delay in diagnosis, use of reperfusion and time to reperfusion/use of angiography) and use of secondary prevention were sequentially added to models.,Mortality was higher for patients with COPD both inhospital (4.6% vs 3.2%) and at 180 days (12.8% vs 7.7%).,After adjusting for inhospital factors, the effect of COPD on inhospital mortality after MI was reduced for both ST-elevation myocardial infarctions (STEMIs) and non-STEMIs (STEMIs OR 1.24 (95% CI 1.10 to 1.41) to 1.13 (95% CI 0.99 to 1.29); non-STEMIs OR 1.34 (95% CI 1.24 to 1.45) to 1.16 (95% CI 1.07 to 1.26)).,Adjusting for inhospital factors reduced the effect of COPD on mortality after non-STEMI at 180 days (OR 1.56 (95% CI 1.47 to 1.65) to 1.37 (95% CI 1.31 to 1.44)).,Adjusting for use of secondary prevention also reduced the effect of COPD on mortality at 180 days for STEMIs and non-STEMIs (STEMIs OR 1.45 (95% CI 1.31 to 1.61) to 1.25 (95% CI 1.11 to 1.41); non-STEMIs OR 1.37 (95% CI 1.31 to 1.44) to 1.26 (95% CI 1.17 to 1.35).,Delayed diagnosis, timing and use of reperfusion of a STEMI, use of angiography after a non-STEMI and use of secondary prevention medicines are all potential explanations for the mortality gap after MI in people with COPD. | 1 |
The minimal clinically important difference (MCID) defines to what extent change on a health status instrument is clinically relevant, which aids scientists and physicians in measuring therapy effects.,This is the first study that aimed to establish the MCID of the Clinical chronic obstructive pulmonary disease (COPD) Questionnaire (CCQ), the COPD Assessment Test (CAT) and the St George’s Respiratory Questionnaire (SGRQ) in the same pulmonary rehabilitation population using multiple approaches.,In total, 451 COPD patients participated in a 3-week Pulmonary Rehabilitation (PR) programme (58 years, 65% male, 43 pack-years, GOLD stage II/III/IV 50/39/11%).,Techniques used to assess the MCID were anchor-based approaches, including patient-referencing, criterion-referencing and questionnaire-referencing, and the distribution-based methods standard error of measurement (SEM), 1.96SEM and half standard deviation (0.5s.d.).,Patient- and criterion-referencing led to MCID estimates of 0.56 and 0.62 (CCQ); 3.12 and 2.96 (CAT); and 8.40 and 9.28 (SGRQ).,Questionnaire-referencing suggested MCID ranges of 0.28-0.61 (CCQ), 1.46-3.08 (CAT) and 6.86-9.47 (SGRQ).,The SEM, 1.96SEM and 0.5s.d. were 0.29, 0.56 and 0.46 (CCQ); 3.28, 6.43 and 2.80 (CAT); 5.20, 10.19 and 6.06 (SGRQ).,Pooled estimates were 0.52 (CCQ), 3.29 (CAT) and 7.91 (SGRQ) for improvement.,MCID estimates differed depending on the method used.,Pooled estimates suggest clinically relevant improvements needing to exceed 0.40 on the CCQ, 3.00 on the CAT and 7.00 on the SGRQ for moderate to very severe COPD patients.,The MCIDs of the CAT and SGRQ in the literature might be too low, leading to overestimation of treatment effects for patients with COPD. | In 2007, an Asthma/chronic obstructive pulmonary disease (COPD) (AC) service was implemented in the North of the Netherlands to support General Practitioners (GPs) by providing advice from pulmonologists on a systematic basis.,To evaluate the feasibility and effectiveness of this service on patient-related outcomes.,We report baseline data on 11,401 patients and follow-up data from 2,556 patients.,GPs can refer all patients with possible obstructive airway disease (OAD) to the service, which is conducted by the local laboratory.,Patients are assessed in the laboratory using questionnaires and spirometry.,Pulmonologists inspect the data through the internet and send the GP diagnosis and management advice.,A total of 11,401 patients were assessed by the service, covering almost 60% of all adult patients with projected asthma or COPD in the area.,In all, 46% (n=5,268) of the patients were diagnosed with asthma, 18% (n=2,019) with COPD and 7% (n=788) with the overlap syndrome.,A total of 740 (7%) patients were followed up after 3 months because the GP advised them to change medication.,In this group, the proportion of unstable COPD patients (Clinical COPD Questionnaire (CCQ)⩾1) decreased from 63% (n=92) at baseline to 49% (n=72).,The proportion of patients with uncontrolled asthma (Asthma Control Questionnaire (ACQ)⩾1.5) decreased from 41% (n=204) to 23% (n=115).,In all, 938 (8%) patients were followed up after 12 months.,From these patients, the proportion of unstable COPD patients (CCQ⩾1) decreased from 47% (n=115) to 44% (n=107).,The proportion of patients with uncontrolled asthma (ACQ⩾1.5) decreased from 16% (n=95) to 14% (n=85).,The AC service assessed a considerable proportion of patients with OAD in the area, improved patients’ outcomes, and is considered to be feasible and effective. | 1 |
We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy.,Three studies of ≥1-year duration met the inclusion criteria.,Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%).,At baseline, 57-75% of patients had ≥2% blood eosinophils.,Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level.,For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001).,No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively).,In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo).,No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ.,Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations. | 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. | 1 |
Immunoglobulin G subclass deficiency (IgGSCD) is a relatively common primary immunodeficiency disease (PI) in adults.,The biological significance of IgGSCD in patients with chronic airway diseases is controversial.,We conducted a retrospective study to characterize the clinical features of IgGSCD in this population.,This study examined the medical charts from 59 adult patients with IgGSCD who had bronchial asthma or chronic obstructive pulmonary disease (COPD) from January 2007 to December 2012.,Subjects were classified according to the 10 warning signs developed by the Jeffrey Modell Foundation (JMF) and divided into two patient groups: group I (n = 17) met ≥ two JMF criteria, whereas group II (n = 42) met none.,IgG3 deficiency was the most common subclass deficiency (88.1%), followed by IgG4 (15.3%).,The most common infectious complication was pneumonia, followed by recurrent bronchitis, and rhinosinusitis.,The numbers of infections, hospitalizations, and exacerbations of asthma or COPD per year were significantly higher in group I than in group II (P < 0.001, P = 0.012, and P < 0.001, respectively).,The follow-up mean forced expiratory volume (FEV1) level in group I was significantly lower than it was at baseline despite treatment of asthma or COPD (P = 0.036).,In conclusion, IgGSCD is an important PI in the subset of patients with chronic airway diseases who had recurrent upper and lower respiratory infections as they presented with exacerbation-prone phenotypes, decline in lung function, and subsequently poor prognosis. | Recurrent acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are common, debilitating, costly and often difficult to prevent.,We reviewed records of patients who had COPD and immunoglobulin (Ig) treatment as adjunctive preventative treatment for AECOPD, and documented all AECOPD episodes for one year before and after initiation of Ig treatment.,We graded AECOPD episodes as moderate for prescription of antibiotics and/or corticosteroids or for visit to the Emergency Department, and as severe for hospital admission.,We conducted a retrospective within-subject self-controlled risk interval analysis to compare the outcome of annual AECOPD rate before and after treatment.,We identified 22 cases of certain COPD, of which three had early discontinuation of Ig treatment due to rash and local swelling to subcutaneous Ig, and five had incomplete records leaving 14 cases for analyses.,The median baseline IgG level was 5.9 g/L (interquartile range 4.1-7.4).,Eight had CT radiographic bronchiectasis.,Overall, the incidence of AECOPD was consistently and significantly reduced in frequency from mean 4.7 (± 3.1) per patient-year before, to 0.6 (± 1.0) after the Ig treatment (p = 0.0001).,There were twelve episodes of severe AECOPD (in seven cases) in the year prior, and one in the year after Ig treatment initiation (p = 0.016).,Ig treatment appears to decrease the frequency of moderate and severe recurrent AECOPD.,A prospective, controlled evaluation of adjunctive Ig treatment to standard therapy of recurrent AECOPD is warranted. | 1 |
Latest evidence suggests that periodontitis is prevalent among patients with chronic obstructive pulmonary disease (COPD), while recent studies have also reported a potential benefit of periodontal treatment on several COPD outcomes.,This systematic review aims to determine the impact of periodontal treatment on exacerbation rate, lung function and quality of life of COPD patients.,A systematic search of electronic databases of PubMed, Scopus, Virtual Health Library, ScienceDirect, Wiley Online Library, Web of Science, ProQuest Dissertation and Theses Global and Google Scholar was conducted.,Search restricted to studies involving human subjects which were published from January 2000 to March 2020 in English language.,Distiller Systematic Review software was used for data management.,Risk of bias was assessed using Risk of Bias 2 (RoB2) and Risk of Bias for non-randomized studies of intervention (ROBINS-I) tools.,Overall quality of evidence was judged based on Grading of Recommendations Assessment, Development and Evaluation working group methodology.,Out of 1442 articles retrieved, 7 full text articles were included in the review.,Limited evidence suggests that periodontal treatment in patients with COPD and periodontitis is associated with reduced exacerbation frequency and a slower lung function decline rate, while its effects on quality of life remain unclear.,In addition, periodontal treatment in COPD is associated with lower hospitalization rates and reduced all-cause mortality.,Significant methodological differences were noted amongst included studies, while very low-to-moderate overall quality of evidence was demonstrated.,Although it is reasonable to advise COPD patients not to neglect their dental health, further studies are warranted to determine the role of periodontal therapy on COPD clinical outcomes.,Trial Registration: PROSPERO 2020 (CRD42020158481). https://www.crd.york.ac.uk/prospero/display_record.php?,ID=CRD42020158481,The online version contains supplementary material available at 10.1186/s12890-021-01429-2. | Azithromycin (AZM) reduces pulmonary inflammation and exacerbations in patients with COPD having emphysema.,The antimicrobial effects of AZM on the lower airway microbiome are not known and may contribute to its beneficial effects.,Here we tested whether AZM treatment affects the lung microbiome and bacterial metabolites that might contribute to changes in levels of inflammatory cytokines in the airways.,20 smokers (current or ex-smokers) with emphysema were randomised to receive AZM 250 mg or placebo daily for 8 weeks.,Bronchoalveolar lavage (BAL) was performed at baseline and after treatment.,Measurements performed in acellular BAL fluid included 16S rRNA gene sequences and quantity; 39 cytokines, chemokines and growth factors and 119 identified metabolites.,The response to lipopolysaccharide (LPS) by alveolar macrophages after ex-vivo treatment with AZM or bacterial metabolites was assessed.,Compared with placebo, AZM did not alter bacterial burden but reduced α-diversity, decreasing 11 low abundance taxa, none of which are classical pulmonary pathogens.,Compared with placebo, AZM treatment led to reduced in-vivo levels of chemokine (C-X-C) ligand 1 (CXCL1), tumour necrosis factor (TNF)-α, interleukin (IL)-13 and IL-12p40 in BAL, but increased bacterial metabolites including glycolic acid, indol-3-acetate and linoleic acid.,Glycolic acid and indol-3-acetate, but not AZM, blunted ex-vivo LPS-induced alveolar macrophage generation of CXCL1, TNF-α, IL-13 and IL-12p40.,AZM treatment altered both lung microbiota and metabolome, affecting anti-inflammatory bacterial metabolites that may contribute to its therapeutic effects.,NCT02557958. | 1 |
Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression.,A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs).,PQTLs consistently replicated between the two cohorts.,Features of pQTLs were compared to previously reported expression QTLs (eQTLs).,Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests.,We identified 527 highly significant (p < 8 X 10−10) pQTLs in 38 (43%) of blood proteins tested.,Most pQTL SNPs were novel with low overlap to eQTL SNPs.,The pQTL SNPs explained >10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC).,Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes.,Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins.,The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates.,Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema.,In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms.,Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group. | The identification and validation of biomarkers to support the assessment of novel therapeutics for COPD continues to be an important area of research.,The aim of the current study was to identify systemic protein biomarkers correlated with measures of COPD severity, as well as specific protein signatures associated with comorbidities such as metabolic syndrome. 142 protein analytes were measured in serum of 140 patients with stable COPD, 15 smokers without COPD and 30 non-smoking controls.,Seven analytes (sRAGE, EN-RAGE, NGAL, Fibrinogen, MPO, TGF-α and HB-EGF) showed significant differences between severe/very severe COPD, mild/moderate COPD, smoking and non-smoking control groups.,Within the COPD subjects, univariate and multivariate analyses identified analytes significantly associated with FEV1, FEV1/FVC and DLCO.,Most notably, a set of 5 analytes (HB-EGF, Fibrinogen, MCP-4, sRAGE and Sortilin) predicted 21% of the variability in DLCO values.,To determine common functions/pathways, analytes were clustered in a correlation network by similarity of expression profile.,While analytes related to neutrophil function (EN-RAGE, NGAL, MPO) grouped together to form a cluster associated with FEV1 related parameters, analytes related to the EGFR pathway (HB-EGF, TGF-α) formed another cluster associated with both DLCO and FEV1 related parameters.,Associations of Fibrinogen with DLCO and MPO with FEV1/FVC were stronger in patients without metabolic syndrome (r = −0.52, p = 0.005 and r = −0.61, p = 0.023, respectively) compared to patients with coexisting metabolic syndrome (r = −0.25, p = 0.47 and r = −0.15, p = 0.96, respectively), and may be driving overall associations in the general cohort.,In summary, our study has identified known and novel serum protein biomarkers and has demonstrated specific associations with COPD disease severity, FEV1, FEV1/FVC and DLCO.,These data highlight systemic inflammatory pathways, neutrophil activation and epithelial tissue injury/repair processes as key pathways associated with COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is set to become the third most frequent cause of death and also the third largest cause of global morbidity by 2020.,In China, where the population is aging rapidly, COPD has become one of the leading causes of disability and a large economic burden.,An epidemiological assessment of the COPD in China is required, with a focus on the number of cases living with disease, main determinants of the disease and time trends.,We systematically searched large Chinese bibliographic databases and English databases to identify spirometry-based epidemiological studies of the prevalence of COPD in China diagnosed according to GOLD criteria.,We estimated age- and gender-specific prevalence of COPD using a multilevel mixed-effect logistic regression.,We also presented the time trends of COPD between 1990 and 2010 by age, gender and setting (urban vs rural).,In 1990, the prevalence of COPD ranged from 0.49% (95% CI = 0.29-0.85) in <20 years group to 20.95% (95% CI = 14.04-27.04) in> = 80 years group, and the crude prevalence for China was 2.70% (95% CI = 1.86-3.51).,In 2010, the prevalence in <20 years was 0.55% (95% CI = 0.37-1.04) and in> = 80 years was 22.89% (95% CI = 18.13-28.96), with the crude prevalence for China of 3.84% (95% CI = 3.30-4.77).,The COPD prevalence in males was about two-fold higher than in females, and it increased with increasing age.,Between 1990-2010, the total number of Chinese people living with COPD increased by 66.73%, from 30.90 million (95% CI = 21.28-40.02) in 1990 to 51.52 million (95% CI = 44.26-63.93) in 2010.,This increase was most striking in middle age, and greater in females than in males from 30 years up to 64 years.,Our estimates, which used an independent approach to acquiring data and development of analytical methods, and were based on a more complete data set, are remarkably similar to those produced recently by the GBD 2013 collaboration, differing by only about 5% in the estimated number of COPD cases in 1990 and by 1% in 2010.,COPD is a highly prevalent disease in China and its importance is growing steadily.,The number of people living with COPD has increased substantially between 1990 and 2010.,COPD is more frequent in males and in rural areas.,Optimised primary and secondary prevention and treatment is urgently needed to counter this growing trend.,Improved epidemiological studies will be required to assist development of more effective strategies of prevention and treatment of COPD in China in the next decade and beyond. | Multidrug resistance-associated protein-1 (MRP1) protects against oxidative stress and toxic compounds generated by cigarette smoking, which is the main risk factor for chronic obstructive pulmonary disease (COPD).,We have previously shown that single nucleotide polymorphisms (SNPs) in MRP1 significantly associate with level of FEV1 in two independent population based cohorts.,The aim of our study was to assess the associations of MRP1 SNPs with FEV1 level, MRP1 protein levels and inflammatory markers in bronchial biopsies and sputum of COPD patients.,Five SNPs (rs212093, rs4148382, rs504348, rs4781699, rs35621) in MRP1 were genotyped in 110 COPD patients.,The effects of MRP1 SNPs were analyzed using linear regression models.,One SNP, rs212093 was significantly associated with a higher FEV1 level and less airway wall inflammation.,Another SNP, rs4148382 was significantly associated with a lower FEV1 level, higher number of inflammatory cells in induced sputum and with a higher MRP1 protein level in bronchial biopsies.,This is the first study linking MRP1 SNPs with lung function and inflammatory markers in COPD patients, suggesting a role of MRP1 SNPs in the severity of COPD in addition to their association with MRP1 protein level in bronchial biopsies. | 1 |
Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation. | Asthma and chronic obstructive pulmonary disease (COPD) are obstructive airway disorders which differ in their underlying causes and phenotypes but overlap in patterns of pharmacological treatments.,In both asthma and COPD, oxidative stress contributes to airway inflammation by inducing inflammatory gene expression.,The redox-sensitive transcription factor, nuclear factor (NF)-kappaB (NF-κB), is an important participant in a broad spectrum of inflammatory networks that regulate cytokine activity in airway pathology.,The anti-inflammatory actions of glucocorticoids (GCs), a mainstay treatment for asthma, involve inhibition of NF-κB induced gene transcription.,Ligand bound GC receptors (GRs) bind NF-κB to suppress the transcription of NF-κB responsive genes (i.e., transrepression).,However, in severe asthma and COPD, the transrepression of NF-κB by GCs is negated as a consequence of post-translational changes to GR and histones involved in chromatin remodeling.,Therapeutics which target NF-κB activation, including inhibitors of IκB kinases (IKKs) are potential treatments for asthma and COPD.,Furthermore, reversing GR/histone acetylation shows promise as a strategy to treat steroid refractory airway disease by augmenting NF-κB transrepression.,This review examines NF-κB signaling in airway inflammation and its potential as target for treatment of asthma and COPD. | 1 |
Oral taxa are often found in the chronic obstructive pulmonary disease (COPD) lung microbiota, but it is not clear if this is due to a physiologic process such as aspiration or experimental contamination at the time of specimen collection.,Microbiota samples were obtained from nine subjects with mild or moderate COPD by swabbing lung tissue and upper airway sites during lung lobectomy.,Lung specimens were not contaminated with upper airway taxa since they were obtained surgically.,The microbiota were analyzed with 16S rRNA gene qPCR and 16S rRNA gene hypervariable region 3 (V3) sequencing.,Data analyses were performed using QIIME, SourceTracker, and R.,Streptococcus was the most common genus in the oral, bronchial, and lung tissue samples, and multiple other taxa were present in both the upper and lower airways.,Each subject’s own bronchial and lung tissue microbiota were more similar to each other than were the bronchial and lung tissue microbiota of two different subjects (permutation test, p = 0.0139), indicating more within-subject similarity than between-subject similarity at these two lung sites.,Principal coordinate analysis of all subject samples revealed clustering by anatomic sampling site (PERMANOVA, p = 0.001), but not by subject.,SourceTracker analysis found that the sources of the lung tissue microbiota were 21.1% (mean) oral microbiota, 8.7% nasal microbiota, and 70.1% unknown.,An analysis using the neutral theory of community ecology revealed that the lung tissue microbiota closely reflects the bronchial, oral, and nasal microbiota (immigration parameter estimates 0.69, 0.62, and 0.74, respectively), with some evidence of ecologic drift occurring in the lung tissue.,This is the first study to evaluate the mild-moderate COPD lung tissue microbiota without potential for upper airway contamination of the lung samples.,In our small study of subjects with COPD, we found oral and nasal bacteria in the lung tissue microbiota, confirming that aspiration is a source of the COPD lung microbiota. | 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. | 1 |
The development of culture-independent techniques for microbiological analysis shows that bronchial tree is not sterile in either healthy or chronic obstructive pulmonary disease (COPD) individuals.,With the advance of sequencing technologies, lung microbiome has become a new frontier for pulmonary disease research, and such advance has led to better understanding of the lung microbiome in COPD.,This review aimed to summarize the recent advances in lung microbiome, its relationships with COPD, and the possible mechanisms that microbiome contributed to COPD pathogenesis.,Literature search was conducted using PubMed to collect all available studies concerning lung microbiome in COPD.,The search terms were “microbiome” and “chronic obstructive pulmonary disease”, or “microbiome” and “lung/pulmonary”.,The papers in English about lung microbiome or lung microbiome in COPD were selected, and the type of articles was not limited.,The lung is a complex microbial ecosystem; the microbiome in lung is a collection of viable and nonviable microbiota (bacteria, viruses, and fungi) residing in the bronchial tree and parenchymal tissues, which is important for health.,The following types of respiratory samples are often used to detect the lung microbiome: sputum, bronchial aspirate, bronchoalveolar lavage, and bronchial mucosa.,Disordered bacterial microbiome is participated in pathogenesis of COPD; there are also dynamic changes in microbiota during COPD exacerbations.,Lung microbiome may contribute to the pathogenesis of COPD by manipulating inflammatory and/or immune process.,Normal lung microbiome could be useful for prophylactic or therapeutic management in COPD, and the changes of lung microbiome could also serve as biomarkers for the evaluation of COPD. | Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory condition in adults and is characterized by progressive airflow limitation that is not fully reversible.,The main etiological agents linked with COPD are cigarette smoking and biomass exposure but respiratory infection is believed to play a major role in the pathogenesis of both stable COPD and in acute exacerbations.,Acute exacerbations are associated with more rapid decline in lung function and impaired quality of life and are the major causes of morbidity and mortality in COPD.,Preventing exacerbations is a major therapeutic goal but currently available treatments for exacerbations are not very effective.,Historically, bacteria were considered the main infective cause of exacerbations but with the development of new diagnostic techniques, respiratory viruses are also frequently detected in COPD exacerbations.,This article aims to provide a state-of-the art review of current knowledge regarding the role of infection in COPD, highlight the areas of ongoing debate and controversy, and outline emerging technologies and therapies that will influence future diagnostic and therapeutic pathways in COPD. | 1 |
Smoking and smoke from biomass burning (BB) are the main environmental risk factors for COPD.,Clinical differences have been described between COPD related to smoking and related to wood smoke, but no studies have shown genetic differences between patients exposed to these two risk factors.,To investigate a possible association of tumor necrosis factor (TNF) promoter polymorphisms, we conducted a case-control study.,A total of 1,322 subjects were included in four groups: patients with a diagnosis of COPD secondary to smoking (COPD-S, n=384), patients with COPD secondary to biomass burning (COPD-BB, n=168), smokers without COPD (SWOC, n=674), and biomass burning-exposed subjects (BBES n=96).,Additionally, a group of 950 Mexican mestizos (MMs) was included as a population control.,Three single nucleotide polymorphisms (SNPs) were selected in the TNF gene (rs1800629, rs361525, and rs1800750) and one SNP in the lymphotoxin alpha gene (rs909253).,Statistically significant differences were found with genotype GA of the rs1800629: COPD-S vs SWOC, (p<0.001, odds ratio [OR] =2.55, 95% CI=1.53-4.27); COPD-S vs COPD-BB (p,0.01).,When performing the comparison of the less severe (G1: I + II) and the more severe (G2: III + IV) levels, differences were identified in G1 (p<0.05, OR=1.94, 95% CI=1.04-3.63) and G2 (p<0.001, OR=3.68, 95% CI=1.94-3.07) compared with SWOC.,Regarding genotype GA of rs361525, it has been associated when comparing COPD-BB vs BBES (p=0.0079, OR=5.99, 95% CI=1.38-53.98).,The heterozygous genotype GA of polymorphisms rs1800629 and rs361525 in the TNF promoter are associated with the risk of COPD. | 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) patients include those who have never smoked.,However, risk factors other than smoking in never-smokers have not been elucidated sufficiently.,This study investigated the risk factors for COPD among never-smokers in Korea using population-based data.,The data were retrieved from the Korean National Health and Nutrition Survey IV conducted from 2007 to 2009.,Among subjects aged 40 years or older who underwent appropriate pulmonary function tests, never-smokers not diagnosed with asthma and not showing a restrictive pattern on pulmonary function tests were enrolled.,Risk factors of COPD in never-smokers were analyzed using logistic regression models.,Among 24,871 participants in the representative Korean cohort, 3,473 never-smokers were enrolled.,COPD patients accounted for 7.6% of the never-smokers.,In the logistic regression analysis, low education status (odds ratio [OR]: 2.0; 95% confidence interval [CI]: 1.2-3.2), occupational exposure (OR: 2.6; 95% CI: 1.3-5.3), a history of tuberculosis (OR: 4.5; 95% CI: 2.3-8.7), bronchiectasis (OR: 6.0; 95% CI: 1.4-25.4), male sex (OR: 4.2; 95% CI: 2.6-6.7), advanced age (60-69 years vs 40-49 years; OR: 3.8; 95% CI: 2.0-7.0), and being underweight (body mass index <18.5 vs 18.0-24.9 kg/m2; OR: 3.1; 95% CI: 1.0-9.4) were associated with the development of COPD.,Low education status, manual labor, a history of tuberculosis and bronchiectasis, as well as male sex, advanced age and being underweight were risk factors for COPD in Korean never-smokers. | Exposure to air pollution due to combustion of biomass fuels remains one of the significant risk factors for chronic respiratory diseases such as chronic bronchitis.,There is a need to identify the minimum threshold level of biomass index that is significantly associated with chronic bronchitis.,This study was undertaken to identify a threshold for biomass exposure index in a rural women population in Mysore district, south India.,A cross-sectional survey was conducted in a representative population of Mysore and Nanjangud taluks.,Eight villages each from Mysore and Nanjangud were randomly selected based on the list of villages from census 2001.,A house-to-house survey was carried out by trained field workers using the Burden of Obstructive Diseases questionnaire, which evaluated the biomass smoke exposure and chronic bronchitis.,All the women aged above 30 yr were included in the study.,A total of 2011 women from Mysore and 1942 women from Nanjangud participated in the study.,All women were non-smoking and used biomass fuels as the primary fuel for cooking.,A threshold of biomass fuel exposure of 60 was identified on multivariate analysis in Mysore district after adjusting for age, passive smoking and working in a occupational exposure to dust, as the minimum required for a significant association with chronic bronchitis.,One in every 20 women in Mysore district exposed to biomass fuel exposure index of 110 or more developed chronic bronchitis.,The minimum threshold of biomass exposure index of 60 is necessary to have a significant risk of developing chronic bronchitis in women.,The number needed to harm to develop chronic bronchitis reduces with increasing biomass exposure index and women residing in rural Nanjangud have a higher risk for developing chronic bronchitis as compared to women in Mysore. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by the progression of irreversible airflow limitation and is a leading cause of morbidity and mortality worldwide.,Although several crucial mechanisms of COPD pathogenesis have been studied, the precise mechanism remains unknown.,Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are released from almost all cell types and are recognized as novel cell-cell communication tools.,They have been shown to carry and transfer a wide variety of molecules, such as microRNAs, messenger RNAs, and proteins, which are involved in physiological functions and the pathology of various diseases.,Recently, EVs have attracted considerable attention in pulmonary research.,In this review, we summarize the recent findings of EV-mediated COPD pathogenesis.,We also discuss the potential clinical usefulness of EVs as biomarkers and therapeutic agents for the treatment of COPD. | Microparticles (MPs) are small membrane vesicles of 0.1-1 µm which are released by cells following chemical, physical, and apoptotic stimuli.,MPs represent more than a miniature version of the cell.,Their composition and function depend not only on cellular origin, but also on stimuli.,Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by nearly irreversible lung destruction which results in airway limitation.,We investigated the presence and source of MPs in sputum of COPD patients to evaluate if changes in MP number and origin may reflect the pathophysiological conditions of disease and may serve as potential biomarkers for diagnostic and prognostic use.,Induced sputum samples were collected from 18 male subjects and liquefied with Sputasol.,MPs obtained were immunolabeled for leukocyte (CD11a), granulocyte (CD66b), monocyte-macrophage (CD11b), platelets and megakaryocytic cells (CD41), endothelial cells (CD31), and red blood cells (CD235ab) and analyzed by cytofluorimetry.,There was a negative correlation between CD31-MPs and forced expiratory volume in 1 second (R=−53, P<0.05) and CD66b-MP level was correlated with worse performance index of COPD such as the Body mass index airflow Obstruction, Dyspnea, and Exercise capacity (BODE); they were negatively correlated with 6-minute walking test: 0.65 and −0.64, respectively (P<0.05).,CD235ab-MPs showed a negative correlation with body mass index (R=−0.86, P<0.05), while there was a positive correlation with dyspnea index (R=0.91, P<0.05).,The main finding of this study was that MPs were detected in the sputum of patients affected by COPD.,The phenotype of some of them was related to the main COPD parameters.,These results suggest that MPs could be implicated in the pathogenesis of COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by a decline of lung function and symptoms such as chronic bronchitis and emphysema leading from lung tissue destruction.,Increased activity of matrix metalloproteinases (MMPs) and an imbalance between MMPs and their tissue inhibitors (TIMPs) are considered as factors influencing the pathogenesis of COPD.,We investigated the role of genetic polymorphism and expression level of MMP-9 and concentration of its complexes with TIMPs in the development of COPD among Polish patients.,We analyzed SNP in the promoter region of MMP-9 gene (rs3918242) using PCR-RFLP method among 335 COPD patients and 309 healthy individuals.,Additionally, 60 COPD patients and 61 controls were tested for copy number variants (CNV) of MMP-9 (by quantitative real-time PCR) and serum levels of MMP-9 and its complexes with TIMP1 and TIMP2 (using ELISA).,All subjects were analyzed for lung function using spirometry (FEV1% and FEV1/FVC parameters).,We observed that allele and genotype frequencies of the SNP rs3918242, as well as the number of gene copies, were similar in COPD patient and controls groups.,Serum levels of MMP-9 and MMP-9/TIMP1 complex were significantly higher in COPD patients in comparison to controls groups, although independently of analyzed gene polymorphisms.,Additionally, the significant inverse relationships between parameters of lung function (FEV1% and FEV1/FVC) and proteins level were found in ridge regression models, especially we found that FEV1% decreased when MMP-9 level increased in controls and patients with COPD group.,In conclusion, we found that COPD patients were predisposed to produce more MMP-9 and MMP-9/TIMP1 complex than healthy individuals.,This phenomenon is probably associated with the disease-related lung environment but not with genetic features of the MMP-9. | Matrix metalloproteinases (MMPs) and C-reactive protein (CRP) are involved in chronic obstructive pulmonary disease (COPD) pathogenesis.,The aim of the present work was to determine plasma concentrations of MMPs and CRP in COPD associated to biomass combustion exposure (BE) and tobacco smoking (TS).,Pulmonary function tests, plasma levels of MMP-1, MMP-7, MMP-9, MMP-9/TIMP-1 and CRP were measured in COPD associated to BE (n = 40) and TS (n =40) patients, and healthy non-smoking (NS) healthy women (controls, n = 40).,Plasma levels of MMP-1, MMP-7, MMP-9, and MMP-9/TIMP-1 and CRP were higher in BE and TS than in the NS healthy women (p <0.01).,An inverse correlation between MMP-1, MMP-7, MMP-9, MMP-9/TIMP-1 and CRP plasma concentrations and FEV1 was observed.,Increase of MMPs and CRP plasma concentrations in BE suggests a systemic inflammatory phenomenon similar to that observed in COPD associated to tobacco smoking, which may also play a role in COPD pathogenesis. | 1 |
Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases of the airway, although the drivers and site of the inflammation differ between diseases.,Asthmatics with a neutrophilic airway inflammation are associated with a poor response to corticosteroids, whereas asthmatics with eosinophilic inflammation respond better to corticosteroids.,Biologicals targeting the Th2-eosinophil nexus such as anti-interleukin (IL)-4, anti-IL-5, and anti-IL-13 are ineffective in asthma as a whole but are more effective if patients are selected using cellular (eg, eosinophils) or molecular (eg, periostin) biomarkers.,This highlights the key role of individual inflammatory mediators in driving the inflammatory response and for accurate disease phenotyping to allow greater understanding of disease and development of patient-oriented antiasthma therapies.,In contrast to asthmatic patients, corticosteroids are relatively ineffective in COPD patients.,Despite stratification of COPD patients, the results of targeted therapy have proved disappointing with the exception of recent studies using CXC chemokine receptor (CXCR)2 antagonists.,Currently, several other novel mediator-targeted drugs are undergoing clinical trials.,As with asthma specifically targeted treatments may be of most benefit in specific COPD patient endotypes.,The use of novel inflammatory mediator-targeted therapeutic agents in selected patients with asthma or COPD and the detection of markers of responsiveness or nonresponsiveness will allow a link between clinical phenotypes and pathophysiological mechanisms to be delineated reaching the goal of endotyping patients. | Evidence suggests that suppressor of cytokine signaling 1 (SOCS1) is crucial for the negative regulation of inflammation.,We investigated the relationship between smoking, SOCS1, and leukotriene B4 (LTB4) in vitro and in clinical samples of COPD; besides which we detected the impact of LTB4 receptor 1 (BLT1) antagonist on inflammation.,SOCS1 expression in bronchial mucosa was determined by immunohistochemistry and real-time polymerase chain reaction.,We also detect SOCS1 and BLT1 expression in alveolar macrophages from bronchoalveolar lavage fluid (BALF) by real time-PCR, in addition to measuring the level of cytokines in BALF using enzyme-linked immunosorbent assay.,In vitro, we investigated the expression of SOCS1 in cigarette smoke extract-induced mouse macrophage cell line RAW264.7 by real-time polymerase chain reaction and Western blot, and detected the level of cytokines in the supernatant by enzyme-linked immunosorbent assay.,Then, we investigated the effects of BLT1 antagonist U-75302 on SOCS1 expression in these cells.,We obtained endobronchial biopsies (15 COPD patients and 12 non-COPD control subjects) and BALF (20 COPD patients and 20 non-COPD control subjects), and our results showed that SOCS1 expression significantly decreased in lung tissues from COPD patients.,Inflammatory cytokines in BALF were higher in COPD and these inflammatory cytokines negatively correlate with SOCS1 levels.,Further, the BLT1 antagonist restored SOCS1 expression and in turn inhibited inflammatory cytokine secretion in vitro.,Long-term cigarette smoke exposure induced SOCS1 degradation and LTB4 accumulation, which was associated with emphysema and inflammation.,A BLT1 antagonist might be a potential therapeutic candidate for the treatment of COPD. | 1 |
The understanding of whether and to what extent employment status affects readmission and mortality is limited in patients with COPD.,To explore how employment status affects readmission and mortality after first admission to the hospital with acute exacerbation of COPD (AECOPD).,This study used Danish national registry-based data.,All patients admitted for the first time to the hospital between 1999 and 2014 with a diagnosis of AECOPD, age 35-59, without a previous asthma diagnosis were included in the study.,Employment status effect on 30-, 90-, and 365-day readmission and mortality was examined using logistic regression, adjusting for relevant confounders.,A total of 11,850 COPD patients were included in the study of which 3563 (30%) were working, 1368 (12%) unemployed, 840 (7%) on sick leave, and 6079 (51%) receiving early retirement.,Patients receiving early retirement had, compared to patients working, an adjusted increased likelihood of readmission at 30, 90, and 365 days (odds ratio (OR) 1.26 (CI95% (1.06-1.49)), 1.33 (CI95% (1.16-1.53)), and 1.48 (CI95% (1.33-1.66)), respectively).,An increased likelihood was also seen in unemployed at 365 days follow-up (OR 1.44 (CI95% (1.22-1.68))).,Early retirement was associated with an increased mortality at 30, 90, and 365 days (OR 1.39 (CI95% (1.07-1.80)) 1.37 (CI95% (1.09-1.79)) and 1.48 (CI95% (1.25-1.75)), respectively).,An increased likelihood was also seen in patients receiving sick leave (OR 1.57 (CI95% (1.21-2.04))).,Patients with COPD who are not working at the time of first admission have a higher likelihood of readmission and mortality. | For the high prevalence of frail in patients with chronic obstructive pulmonary disease (COPD), further study should explore an in-depth understanding of the relationship between frailty and prognosis of COPD.,To determine the correlation between frailty and risk of acute exacerbation, hospitalizations, and mortality in older patients with stable COPD.,Consecutive older adults (≥65) diagnosed with stable COPD from January 2018 to July 2019, with an average follow-up of 546 days (N = 309).,Frailty was defined by the Fried frailty phenotype.,Poisson regression was performed to assess the influence of frailty on the incidence of acute exacerbations of COPD (AECOPD) and all-cause hospitalizations in a year.,Cox regression was performed to evaluate the effect of frailty on all-cause mortality in patients with stable COPD.,The prevalence of frailty was 49.8%.,The most common phenotypic characteristics were weakness (99.4%) followed by slowness (92.9%).,After adjustment, frailty increased the incidence of AECOPD (IRR = 1.75, 95% CI: 1.09-2.82) and all-cause hospitalizations (IRR = 1.39, 95% CI 1.04-1.87) within a year.,Slowness was associated with AECOPD (IRR = 1.77, 95% CI: 1.03-3.03), and weakness was associated with increased all-cause hospitalizations (IRR = 1.53, 95% CI: 1.04-2.25).,The all-cause mortality risk was more than twofold higher in frail patients (HR = 2.54, 95% CI: 1.01-6.36) than non-frail patients.,Low physical activity (HR = 2.66, 95% CI: 1.17-6.05) and weight loss (HR = 2.15, 95% CI: 1.02-4.51) were significantly associated with increased all-cause mortality in patients with COPD.,Frailty increased the incidence of acute exacerbation and hospitalization, as well as increased mortality in older patients with stable COPD.,This knowledge will help physicians identify high-risk groups with COPD and frailty who may benefit from targeted interventions to prevent disease progression. | 1 |
The association between body mass index (BMI) and mortality in patients suffering from chronic obstructive pulmonary disease (COPD) has been a subject of interest for decades.,However, the evidence is inadequate to draw robust conclusions because some studies were generally small or with a short follow-up.,We carried out a search in MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE database for relevant studies.,Relative risks (RRs) with 95% confidence interval (CI) were calculated to assess the association between BMI and mortality in patients with COPD.,In addition, a baseline risk-adjusted analysis was performed to investigate the strength of this association.,22 studies comprising 21,150 participants were included in this analysis.,Compared with patients having a normal BMI, underweight individuals were associated with higher mortality (RR = 1.34, 95% CI = 1.01-1.78), whereas overweight (RR = 0.47, 95% CI = 0.33-0.68) and obese (RR = 0.59, 95% CI = 0.38-0.91) patients were associated with lower mortality.,We further performed a baseline risk-adjusted analysis and obtained statistically similar results.,Our study showed that for patients with COPD being overweight or obese had a protective effect against mortality.,However, the relationship between BMI and mortality in different classes of obesity needed further clarification in well-designed clinical studies. | 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. | 1 |
Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease characterized by nonreversible airway obstruction.,Well-characterized symptoms such as exertional dyspnea and fatigue have a negative impact on patients’ quality of life (QoL) and restrict physical activity in daily life.,The impact of COPD symptoms on QoL is often underestimated; for example, 36% of patients who describe their symptoms as being mild-to-moderate also admit to being too breathless to leave the house.,Additionally, early morning and nighttime symptoms are a particular problem.,Methods are available to allow clinicians to accurately assess COPD symptoms, including patient questionnaires.,Integrated approaches to COPD management, particularly pulmonary rehabilitation, are effective strategies for addressing symptoms, improving exercise capacity and, potentially, also increasing physical activity.,Inhaled bronchodilators continue to be the mainstay of drug therapy in COPD, where options can be tailored to meet patients’ needs with careful selection of the inhaled medication and the device used for its delivery.,Overall, an integrated approach to disease management should be considered for improving QoL and subsequent patient outcomes in COPD. | 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 |
Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants.,We have previously identified iron-responsive element binding protein 2 (IRP2) as an important COPD susceptibility gene, with IRP2 protein increased in the lungs of individuals with COPD.,Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD.,By integrating RIP-Seq, RNA-Seq, gene expression and functional enrichment clustering analysis, we identified IRP2 as a regulator of mitochondrial function in the lung.,IRP2 increased mitochondrial iron loading and cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD.,Frataxin-deficient mice with higher mitochondrial iron loading had impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas synthesis of cytochrome c oxidase (Sco2)-deficient mice with reduced COX were protected from CS-induced pulmonary inflammation and impairment of MCC.,Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD.,Mitochondrial iron chelation also alleviated CS-impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD. | Chronic Obstructive Pulmonary Disease (COPD) has significant systemic effects beyond the lungs amongst which muscle wasting is a prominent contributor to exercise limitation and an independent predictor of morbidity and mortality.,The molecular mechanisms leading to skeletal muscle dysfunction/wasting are not fully understood and are likely to be multi-factorial.,The need to develop therapeutic strategies aimed at improving skeletal muscle dysfunction/wasting requires a better understanding of the molecular mechanisms responsible for these abnormalities.,Microarrays are powerful tools that allow the investigation of the expression of thousands of genes, virtually the whole genome, simultaneously.,We aim at identifying genes and molecular pathways involved in skeletal muscle wasting in COPD.,We assessed and compared the vastus lateralis transcriptome of COPD patients with low fat free mass index (FFMI) as a surrogate of muscle mass (COPDL) (FEV1 30 ± 3.6%pred, FFMI 15 ± 0.2 Kg.m−2) with patients with COPD and normal FFMI (COPDN) (FEV1 44 ± 5.8%pred, FFMI 19 ± 0.5 Kg.m−2) and a group of age and sex matched healthy controls (C) (FEV1 95 ± 3.9%pred, FFMI 20 ± 0.8 Kg.m−2) using Agilent Human Whole Genome 4x44K microarrays.,The altered expression of several of these genes was confirmed by real time TaqMan PCR.,Protein levels of P21 were assessed by immunoblotting.,A subset of 42 genes was differentially expressed in COPDL in comparison to both COPDN and C (PFP < 0.05; −1.5 ≥ FC ≥ 1.5).,The altered expression of several of these genes was confirmed by real time TaqMan PCR and correlated with different functional and structural muscle parameters.,Five of these genes (CDKN1A, GADD45A, PMP22, BEX2, CGREF1, CYR61), were associated with cell cycle arrest and growth regulation and had been previously identified in studies relating muscle wasting and ageing.,Protein levels of CDKN1A, a recognized marker of premature ageing/cell cycle arrest, were also found to be increased in COPDL.,This study provides evidence of differentially expressed genes in peripheral muscle in COPD patients corresponding to relevant biological processes associated with skeletal muscle wasting and provides potential targets for future therapeutic interventions to prevent loss of muscle function and mass in COPD.,The online version of this article (doi:10.1186/s12931-014-0139-5) contains supplementary material, which is available to authorized users. | 1 |
Pulmonary rehabilitation is effective in all stages of COPD.,The availability and utilization of pulmonary rehabilitation resources, and the characteristics of COPD patients receiving rehabilitation, were investigated in primary and secondary care in central Sweden.,Data on available pulmonary rehabilitation resources were collected using questionnaires, to 14 hospitals and 54 primary health care centers, and information on utilization of different rehabilitation professionals was obtained from questionnaires completed by 1,329 COPD patients from the same centers.,Multivariable logistic regression examined associations with having received rehabilitation in the previous year.,In primary care, nurse-based asthma/COPD clinics were common (87%), with additional separate access to other rehabilitation professionals.,In secondary care, rehabilitation was more often offered as part of a multidisciplinary teamwork (71%).,In total, 36% of the patients met an asthma/COPD nurse in the previous year.,Utilization was lower in primary than in secondary care for physiotherapists (7% vs 16%), occupational therapists (3% vs 10%), nutritionists (5% vs 13%), and counselors (1% vs 4%).,A higher COPD Assessment Test score and frequent exacerbations were associated with higher utilization of all rehabilitation professionals.,Pulmonary rehabilitation resources are available but underutilized, and receiving rehabilitation is more common in severe COPD.,Treatment recommendations need to be better implemented, especially in mild and moderate COPD. | Patients with COPD experience exacerbations that may require hospitalization.,Patients do not always feel supported upon discharge and frequently get readmitted.,A Self-management Program of Activity, Coping, and Education for COPD (SPACE for COPD), a brief self-management program, may help address this issue.,To investigate if SPACE for COPD employed upon hospital discharge would reduce readmission rates at 3 months, compared with usual care.,This is a prospective, single-blinded, two-center trial (ISRCTN84599369) with participants admitted for an exacerbation, randomized to usual care or SPACE for COPD.,Measures, including health-related quality of life and exercise capacity, were taken at baseline (hospital discharge) and at 3 months.,The primary outcome measure was respiratory readmission at 3 months.,Seventy-eight patients were recruited (n=39 to both groups).,No differences were found in readmission rates or mortality at 3 months between the groups.,Ten control patients were readmitted within 30 days compared to five patients in the intervention group (P>0.05).,Both groups significantly improved their exercise tolerance and Chronic Respiratory Questionnaire (CRQ-SR) results, with between-group differences approaching statistical significance for CRQ-dyspnea and CRQ-emotion, in favor of the intervention.,The “Ready for Home” survey revealed that patients receiving the intervention reported feeling better able to arrange their life to cope with COPD, knew when to seek help about feeling unwell, and more often took their medications as prescribed, compared to usual care (P<0.05).,SPACE for COPD did not reduce readmission rates at 3 months above that of usual care.,However, encouraging results were seen in secondary outcomes for those receiving the intervention.,Importantly, SPACE for COPD appears to be safe and may help prevent readmission with 30 days. | 1 |
Background: It is the first study in Poland and one of the first in the world to assess the nutrition of patients with chronic obstructive pulmonary disease (COPD) treated with long-term oxygen therapy (LTOT).,Methods: The study group consisted of 110 COPD patients treated with LTOT.,Anthropometric measurements and spirometry were performed.,The diet of patients was assessed using a 3-day nutrition diary.,Results: When assessing the degree of airflow obstruction (FEV1% N) depending on the BMI in patients treated with LTOT, a statistically significant correlation was demonstrated between the BMI and the value of the FEV% N parameter (p = 0.0093).,Patients with COPD with a BMI >30 had statistically significantly higher values of FEV1% N than patients with a BMI in the range of 20-24.9 (p = 0.0278).,Intake of calcium, vitamins A, C, D, E and folates was lower than the recommended daily intake in more than 95% of COPD patients.,Conclusions: The diet of COPD patients treated with long-term oxygen therapy was improperly balanced, with deficiencies of important nutrients.,Airflow obstruction in the respiratory tract was significantly smaller in obese patients, and greater in patients with diagnosed malnutrition. | The aim of this study was to examine the effects of exposure to air pollution and cigarette smoke on respiratory function, respiratory symptoms, and the prevalence of COPD in individuals aged ≥50 years.,We used spirometry and medical questionnaires to screen 433 individuals from Omuta City, Japan, an area with high levels of air pollution.,Non smokers had a high estimated COPD prevalence rate of 16%.,Among smokers, the estimated prevalence of COPD was 29% in seniors (50- to 74-years group) and 37% in the elderly (>75 years group).,We also found a correlation between levels of suspended particulate matter and COPD.,Both smoking and chronic exposure to air pollution (>5 years) decreased respiratory function, exacerbated respiratory symptoms, and increased the prevalence of COPD.,We strongly recommend periodic screening for the elderly patients to facilitate early detection of respiratory disease. | 1 |
This study aims to investigate the disease knowledge and self-management behavior of patients with chronic obstructive pulmonary disease (COPD) in the respiratory ward of a tertiary hospital in China, and analyze the relationship between these.,A total of 360 COPD patients were surveyed using the internationally validated COPD Questionnaire (COPD-Q), the COPD Patients’ Self-Management Behavior Scale and a general sociodemographic questionnaire, and 346 valid responses were obtained.,The results revealed that the surveyed COPD patients scored an average of 4.90 ± 2.50 points (maximal of 13 points) on the COPD-Q and 117.23 ± 20.56 points on the COPD Self-Management Behavior Scale, in which 86.1% of COPD patients were classified as having low to medium levels of self-management behavior.,Pearson correlation analysis revealed that the total points on the COPD Self-Management Behavior Scale, symptom management, daily life management, emotional management and information management were all positively correlated to the disease knowledge of COPD (P < .01).,In addition to COPD knowledge, the multiple regression analysis revealed that age, marital status and place of residence could also affect self-management behavior.,The level of disease knowledge and self-management behaviors of patients with COPD is rather low in China.,COPD knowledge level was found to correlate with the level of self-management behavior.,Health education that enhances the disease knowledge of COPD patients might thereby be necessary to help improve self-management behavior. | Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are common in patients with underlying moderate to severe COPD and are associated with increased health and economic burden.,International and Chinese guidelines recommend using glucocorticoids for the management of AECOPD because glucocorticoid therapy has been shown to benefit clinical outcomes.,However, only scant data are available for current status of glucocorticoid therapy in hospitalized AECOPD patients in China.,The aim of the study was to identify current use of glucocorticoids for the treatment of AECOPD in China.,This retrospective, multicenter, noninterventional study evaluated the treatment pattern of AECOPD in patients hospitalized from January 2014 to September 2014 at 43 sites (41 tertiary hospitals and two secondary hospitals) in China.,The endpoints of the study were the percentage of patients receiving glucocorticoids by different routes of administration, doses and duration, mortality, and the mean length of hospitalization.,A total of 4569 patients (90.17%) received glucocorticoids for AECOPD treatment.,A combination of nebulized and systemic route was most frequently used (40.51%), followed by using nebulized route alone (38.00%), systemic route alone (15.45%), and inhaled route other than nebulization (6.04%).,Furthermore, the most commonly prescribed glucocorticoids of the nebulized, intravenous, inhaled (other than nebulized) and oral route was budesonide (69.4%), methylprednisolone sodium succinate (45.31%), fluticasone propionate (19.54%), and prednisone acetate (11.90%), respectively.,The in-hospital mortality rate was 1.24% and the mean length of hospitalization was 12.22 ± 6.20 days (± SD).,Our study was the first study of the treatment pattern of glucocorticoids in the management of hospitalized AECOPD patients in China.,Data indicates that there is a gap in the implementation of international guidelines for the treatment of AECOPD in China.,Further studies are warranted to clarify the appropriate glucocorticoids strategy for the management of AECOPD to determine the optimal route of administration, dose and duration, and resulting clinical outcomes. | 1 |
We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy.,Three studies of ≥1-year duration met the inclusion criteria.,Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%).,At baseline, 57-75% of patients had ≥2% blood eosinophils.,Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level.,For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001).,No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively).,In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo).,No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ.,Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations. | Chronic obstructive pulmonary disease (COPD) and asthma may overlap and converge in older people (overlap syndrome).,It was hypothesized that patients with overlap syndrome may have different clinical characteristics such as sputum eosinophilia, and better responsiveness to treatment with inhaled corticosteroid (ICS).,Sixty-three patients with stable COPD (forced expiratory volume in 1 second [FEV1] ≤80%) underwent pulmonary function tests, including reversibility of airflow limitation, arterial blood gas analysis, analysis of inflammatory cells in induced sputum, and chest high-resolution computed tomography.,The inclusion criteria for COPD patients with asthmatic symptoms included having asthmatic symptoms such as episodic breathlessness, wheezing, cough, and chest tightness worsening at night or in the early morning (COPD with asthma group).,The clinical features of COPD patients with asthmatic symptoms were compared with those of COPD patients without asthmatic symptoms (COPD without asthma group).,The increases in FEV1 in response to treatment with ICS were significantly higher in the COPD with asthma group.,The peripheral eosinophil counts and sputum eosinophil counts were significantly higher.,The prevalence of patients with bronchial wall thickening on chest high-resolution computed tomography was significantly higher.,A significant correlation was observed between the increases in FEV1 in response to treatment with ICS and sputum eosinophil counts, and between the increases in FEV1 in response to treatment with ICS and the grade of bronchial wall thickening.,Receiver operating characteristic curve analysis revealed 82.4% sensitivity and 84.8% specificity of sputum eosinophil count for detecting COPD with asthma, using 2.5% as the cutoff value.,COPD patients with asthmatic symptoms had some clinical features.,ICS should be considered earlier as a potential treatment in such patients.,High sputum eosinophil counts and bronchial wall thickening on chest high-resolution computed tomography might therefore be a good predictor of response to ICS. | 1 |
Neutrophil extracellular traps (NETs) have been observed in the airway in patients with chronic obstructive pulmonary disease (COPD), but their clinical and pathophysiologic implications have not been defined.,We sought to determine whether NETs are associated with disease severity in patients with COPD and how they are associated with microbiota composition and airway neutrophil function.,NET protein complexes (DNA-elastase and histone-elastase complexes), cell-free DNA, and neutrophil biomarkers were quantified in soluble sputum and serum from patients with COPD during periods of disease stability and during exacerbations and compared with clinical measures of disease severity and the sputum microbiome.,Peripheral blood and airway neutrophil function were evaluated by means of flow cytometry ex vivo and experimentally after stimulation of NET formation.,Sputum NET complexes were associated with the severity of COPD evaluated by using the composite Global Initiative for Obstructive Lung Disease scale (P < .0001).,This relationship was due to modest correlations between NET complexes and FEV1, symptoms evaluated by using the COPD assessment test, and higher levels of NET complexes in patients with frequent exacerbations (P = .002).,Microbiota composition was heterogeneous, but there was a correlation between NET complexes and both microbiota diversity (P = .009) and dominance of Haemophilus species operational taxonomic units (P = .01).,Ex vivo airway neutrophil phagocytosis of bacteria was reduced in patients with increased sputum NET complexes.,Consistent results were observed regardless of the method of quantifying sputum NETs.,Failure of phagocytosis could be induced experimentally by incubating healthy control neutrophils with soluble sputum from patients with COPD.,NET formation is increased in patients with severe COPD and associated with more frequent exacerbations and a loss of microbiota diversity. | 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. | 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. | Nonadherence to medication and incorrect use of inhalers represent significant barriers to optimal disease management of patients with chronic obstructive pulmonary disease (COPD).,Thus, health care professionals (HCPs) play a critical role in educating their patients on appropriate inhaler use and in ensuring medication adherence.,However, many patients do not receive appropriate inhaler training or have not had their inhaler technique checked.,The Real-life Experience and Accuracy of inhaLer use (REAL) survey was a computer-assisted, telephonic survey consisting of 23 questions gathering real-world information on correct inhaler use, inhalation technique, device attributes, adherence, dosing accuracy, training, correct device use, ease of use, and factors that influence patient adherence in commercially available inhalers delivering COPD maintenance therapy.,All results are based on patient-reported data.,The survey was conducted between January 4, 2016 and February 2, 2016.,A total of 764 patients using various inhalers (Breezhaler® =186; Ellipta® =191; Genuair® =194; Respimat® =201) with mild to very severe COPD, with a mean ± SD age 56±9.8 years, completed the survey.,Patient self-reported adherence was significantly lower in younger patients compared to older patients (p=0.020).,Eighty-three percent of patients indicated that a demonstration (in-person) was “very helpful” versus 58% for video.,Patient preferences for training methods were as follows: demonstration of inhaler use (83%), video (58%), instructions for use (51%), and leaflet (34%).,Twenty-nine percent of patients had not been checked to see if they were using their device correctly by a HCP within the last two years.,Patients who were checked were significantly more adherent than unchecked patients (p=0.020).,The majority of the patients using Breezhaler reported either being very confident or confident of having taken a full dose, which was higher than those using Genuair, Ellipta (α=0.05), and Respimat (α=0.05).,Treatment adherence in the last 30 days was highest with Breezhaler followed by Respimat, Ellipta, and Genuair.,The REAL survey identified attributes that influenced patient adherence and optimal inhaler use.,Predictive attributes that influence patient adherence which HCPs should be aware of include age and disease severity.,Modifiable attributes which the HCP can influence include correct inhaler use training, choice of training methods, checking patient inhaler technique at subsequent visits, and device selection.,Inhalers are integral in the effective management of patients with COPD; it is therefore important that patients use the inhaler correctly and have full confidence in the dosage. | 1 |
Although many studies on people with Chronic Obstructive Pulmonary Disease (COPD) have examined the mutual impact of physical status and emotional experience, there is limited knowledge about the way COPD people first-hand perceive their condition.,This study was designed to investigate the illness perceptions of the patients and, secondarily, to explore their beliefs about the mind-body relationship.,This qualitative study has exploited an ad-hoc semi-structured interview to collect personal perspectives of participants on their illness.,Twenty-seven patients (15 males and 12 females), with a mild to severe COPD, were recruited within the Respiratory Rehabilitation Unit of Don Carlo Gnocchi Foundation, in Milan.,The thematic analysis of the interviews’ content was facilitated by NVivo (12th version, QSR International®).,The thematic analysis of the corpus resulted in four master themes.,Illness experience has been considered the primary one.,Indeed, dealing with COPD every day allows these people to portray a specific representation of the mind-body relationship, to gain a certain degree of expertise and to develop a perspective on the future.,Individual perceptions of the illness vary among people with COPD, but some common experiences characterize them.,Many patients share a profound belief that their mental state and their physical symptoms are highly interrelated. | COPD is a civilization disease.,It affects up to 8%-10% of population >30 years of age.,Coexistence of depression occurs in 20%-40% of patients with COPD.,Depression and anxiety reduce compliance and worsen prognosis.,The aims of this study were to determine the degree of illness acceptance among patients with COPD, to examine the relation between disease acceptance and perceived anxiety and depression, and to verify which of the sociodemographic and clinical factors are associated with illness acceptance, anxiety, and depression.,The study included 102 patients with COPD (mean age 65.8 years), hospitalized due to exacerbations.,Acceptance of Illness Scale and Hospital Anxiety and Depression Scale were used.,For statistical analysis, Student’s t-test and Pearson’s r correlation coefficient were carried out.,The overall illness acceptance level was moderate with a tendency toward lack of acceptance (mean 20.6, standard deviation [SD] 7.62).,The overall scores were 10.2 (SD 3.32) for anxiety and 10.8 (SD 4.14) for depression, which indicate borderline or high intensity of these symptoms.,Acceptance of illness was negatively correlated with the intensity of depression symptoms (r=−0.46, P<0.05).,Intensity of depression was significantly associated with intensity of smoking, duration of the disease, severity of dyspnea, and living in a rural area.,Early identification and assessment of depression and anxiety symptoms allow health care providers to offer patients at risk of depression a special medical supervision.,Rapid start of antidepressant therapy may increase illness acceptance and improve prognosis among patients with COPD. | 1 |
To investigate the respiratory infectious phenotypes and their impact on length of stay (LOS) and the COPD Assessment Test (CAT) Scale in acute exacerbation of COPD (AECOPD).,We categorized 81 eligible patients into bacterial infection, viral infection, coinfection, and non-infectious groups.,The respiratory virus examination was determined by a liquid bead array xTAG Respiratory Virus Panel in pharyngeal swabs, while bacterial infection was studied by conventional sputum culture.,LOS and CAT as well as demographic information were recorded.,Viruses were detected in 38 subjects, bacteria in 17, and of these, seven had both.,Influenza virus was the most frequently isolated virus, followed by enterovirus/rhinovirus, coronavirus, bocavirus, metapneumovirus, parainfluenza virus types 1, 2, 3, and 4, and respiratory syncytial virus.,Bacteriologic analyses of sputum showed that Pseudomonas aeruginosa was the most common bacteria, followed by Acinetobacter baumannii, Klebsiella, Escherichia coli, and Streptococcus pneumoniae.,The longest LOS and the highest CAT score were detected in coinfection group.,CAT score was positively correlated with LOS.,Respiratory infection is a common causative agent of exacerbations in COPD.,Respiratory coinfection is likely to be a determinant of more severe acute exacerbations with longer LOS.,CAT score may be a predictor of longer LOS in AECOPD. | Early identification of patients with a prolonged stay due to acute exacerbation of chronic obstructive pulmonary disease (COPD) may reduce risk of adverse event and treatment costs.,This study aimed to identify predictors of prolonged stay after acute exacerbation of COPD based on variables on admission; the study also looked to establish a prediction model for length of stay (LOS).,We extracted demographic and clinical data from the medical records of 599 patients discharged after an acute exacerbation of COPD between March 2006 and December 2008 at Oslo University Hospital, Aker.,We used logistic regression analyses to assess predictors of a length of stay above the 75th percentile and assessed the area under the receiving operating characteristic curve to evaluate the model’s performance.,We included 590 patients (54% women) aged 73.2±10.8 years (mean ± standard deviation) in the analyses.,Median LOS was 6.0 days (interquartile range [IQR] 3.5-11.0).,In multivariate analysis, admission between Thursday and Saturday (odds ratio [OR] 2.24 [95% CI 1.60-3.51], P<0.001), heart failure (OR 2.26, 95% CI 1.34-3.80), diabetes (OR 1.90, 95% CI 1.07-3.37), stroke (OR 1.83, 95% CI 1.04-3.21), high arterial PCO2 (OR 1.26 [95% CI 1.13-1.41], P<0.001), and low serum albumin level (OR 0.92 [95% CI 0.87-0.97], P=0.001) were associated with a LOS >11 days.,The statistical model had an area under the receiver operating characteristic curve of 0.73.,Admission between Thursday and Saturday, heart failure, diabetes, stroke, high arterial PCO2, and low serum albumin level were associated with a prolonged LOS.,These findings may help physicians to identify patients that will need a prolonged LOS in the early stages of admission.,However, the predictive model exhibited suboptimal performance and hence is not ready for clinical use. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by progressive worsening of airflow limitation associated with abnormally inflamed airways in older smokers.,Despite correlative evidence for a role for tumor necrosis factor-alpha in the pathogenesis of COPD, the anti-tumor necrosis factor-alpha, infliximab did not show clinical efficacy in a double-blind, placebo-controlled, phase II clinical trial.,This study sought to evaluate the systemic inflammatory profile associated with COPD and to assess the impact of tumor necrosis factor neutralization on systemic inflammation.,Serum samples (n = 234) from the phase II trial were collected at baseline and after 24 weeks of placebo or infliximab.,Additionally, baseline serum samples were obtained from an independent COPD cohort (n = 160) and 2 healthy control cohorts (n = 50; n = 109).,Serum concentrations of a broad panel of inflammation-associated analytes were measured using a 92-analyte multiplex assay.,Twenty-five proteins were significantly elevated and 2 were decreased in COPD, including highly elevated CD40 ligand, brain-derived neurotrophic factor, epidermal growth factor, acute-phase proteins, and neutrophil-associated proteins.,This profile was largely independent of smoking status, age, and clinical phenotype.,The majority of these associations of serum analytes with COPD are novel findings.,Increased serum creatine kinase-muscle/brain and myoglobin correlated modestly with decreased forced expiratory volume at 1 second, suggesting cardiac involvement.,Infliximab did not affect this systemic inflammatory profile.,A robust systemic inflammatory profile was associated with COPD.,This profile was generally independent of disease severity.,Because anti-tumor necrosis factor-alpha did not influence systemic inflammation, how to control the underlying pathology beyond symptom suppression remains unclear.,ClinicalTrials.gov, No.: NCT00056264. | There is mounting evidence that pulmonary arterial hypertension (PAH), asthma and chronic obstructive pulmonary disease (COPD) share important pathological features, including inflammation, smooth muscle contraction and remodeling.,No existing drug provides the combined potential advantages of reducing vascular- and bronchial-constriction, and anti-inflammation.,Vasoactive intestinal peptide (VIP) is widely expressed throughout the cardiopulmonary system and exerts a variety of biological actions, including potent vascular and airway dilatory actions, potent anti-inflammatory actions, improving blood circulation to the heart and lung, and modulation of airway secretions.,VIP has emerged as a promising drug candidate for the treatment of cardiopulmonary disorders such as PAH, asthma, and COPD.,Clinical application of VIP has been limited in the past for a number of reasons, including its short plasma half-life and difficulty in administration routes.,The development of long-acting VIP analogues, in combination with appropriate drug delivery systems, may provide clinically useful agents for the treatment of PAH, asthma, and COPD.,This article reviews the physiological significance of VIP in cardiopulmonary system and the therapeutic potential of VIP-based agents in the treatment of pulmonary diseases. | 1 |
COPDPredict™ is a novel digital application dedicated to providing early warning of imminent COPD (chronic obstructive pulmonary disease) exacerbations for prompt intervention.,Exacerbation prediction algorithms are based on a decision tree model constructed from percentage thresholds for disease state changes in patient-reported wellbeing, forced expiratory volume in one second (FEV1) and C-reactive protein (CRP) levels.,Our study determined the validity of COPDPredict™ to identify exacerbations and provide timely notifications to patients and clinicians compared to clinician-defined episodes.,In a 6-month prospective observational study, 90 patients with COPD and frequent exacerbations registered wellbeing self-assessments daily using COPDPredict™ App and measured FEV1 using connected spirometers.,CRP was measured using finger-prick testing.,Wellbeing self-assessment submissions showed 98% compliance.,Ten patients did not experience exacerbations and treatment was unchanged.,A total of 112 clinician-defined exacerbations were identified in the remaining 80 patients: 52 experienced 1 exacerbation; 28 had 2.2±0.4 episodes.,Sixty-two patients self-managed using prescribed rescue medication.,In 14 patients, exacerbations were more severe but responded to timely escalated treatment at home.,Four patients attended the emergency room; with 2 hospitalised for <72 hours.,Compared to the 6 months pre-COPDPredict™, hospitalisations were reduced by 98% (90 vs 2, p<0.001).,COPDPredict™ identified COPD-related exacerbations at 7, 3 days (median, IQR) prior to clinician-defined episodes, sending appropriate alerts to patients and clinicians.,Cross-tabulation demonstrated sensitivity of 97.9% (95% CI 95.7-99.2), specificity of 84.0% (95% CI 82.6-85.3), positive and negative predictive value of 38.4% (95% CI 36.4-40.4) and 99.8% (95% CI 99.5-99.9), respectively.,High sensitivity indicates that if there is an exacerbation, COPDPredict™ informs patients and clinicians accurately.,The high negative predictive value implies that when an exacerbation is not indicated by COPDPredict™, risk of an exacerbation is low.,Thus, COPDPredict™ provides safe, personalised, preventative care for patients with COPD. | COPD exacerbations have negative impact on patients’ survival.,Several risk factors for grave outcomes of such exacerbations have been descried.,Muscle dysfunction and mass loss were shown to impact negatively on prognosis and survival.,Low activity of the enzyme ALT (Alanine amino-transferase) in the blood is a known indicator for sarcopenia and frailty, however, no previous studies addressed the association of low ALT amongst patients hospitalized due to COPD exacerbation and long-term survival.,This is a historic prospective cohort study of patients hospitalized due to acute COPD exacerbation.,Included were 232 consecutive COPD exacerbation patients.,The median time of follow-up was 34.9 months (IQR 23.13-41.73 months).,During this period 104 (44.8%) patients died.,All patients were grouped to quartiles according to blood ALT levels (after exclusion of cases considered to have hepatic tissue damage (ALT > 40 IU)).,The risk of long-term mortality increased, in a statistically significant manner, amongst patients with low ALT values: the median survival of patients with ALT < 11 IU was 18.5 months only while the median survival for the rest of the study group was not reached.,For ALT < 11 IU; 12-16 IU; 17-20 IU and > 21 IU the mortality rates were 69%; 40.9%; 36.3 and 25% respectively (p < 0.001 for comparison of lower quartile with upper three quartiles).,The crude hazard ratio for mortality amongst patients with ALT levels lower than 11 IU was 2.37 (95% CI; 1.6-3.5).,This increased risk of mortality remained significant after adjustment for age, weight, creatinine, albumin concentration and cardiovascular diseases (HR = 1.83; 95% CI 1.08-3.1, p < 0.05).,Low ALT values, a biomarker of sarcopenia and frailty, are associated with poor long-term survival amongst patients hospitalized due to COPD exacerbation. | 1 |
Combining bronchodilators with different mechanisms of action may improve efficacy and reduce risk of side effects compared to increasing the dose of a single agent in chronic obstructive pulmonary disease (COPD).,We investigated this by combining two long-acting bronchodilators: once-daily muscarinic antagonist tiotropium and once-daily β2-agonist olodaterol.,Two replicate, double-blind, randomized, 12-week studies (ANHELTO 1 [NCT01694771] and ANHELTO 2 [NCT01696058]) evaluated the efficacy and safety of olodaterol 5 μg once daily (via Respimat®) combined with tiotropium 18 μg once daily (via HandiHaler®) versus tiotropium 18 μg once daily (via HandiHaler®) combined with placebo (via Respimat®) in patients with moderate to severe COPD.,Primary efficacy end points were area under the curve from 0-3 hours of forced expiratory volume in 1 second (FEV1 AUC0-3) and trough FEV1 after 12 weeks (for the individual trials).,A key secondary end point was health status by St George’s Respiratory Questionnaire (SGRQ) total score (combined data set).,Olodaterol + tiotropium resulted in significant improvements over tiotropium + placebo in FEV1 AUC0-3 (treatment differences: 0.117 L [P<0.001], ANHELTO 1; 0.106 L [P<0.001], ANHELTO 2) and trough FEV1 (treatment differences: 0.062 L [P<0.001], ANHELTO 1; 0.040 L [P=0.0029], ANHELTO 2); these were supported by secondary end points.,These effects translated to improvements in SGRQ total scores (treatment difference −1.85; P<0.0001).,The tolerability profile of olodaterol + tiotropium was similar to tiotropium monotherapy.,These studies demonstrated that olodaterol (Respimat®) and tiotropium (HandiHaler®) provided bronchodilatory effects above tiotropium alone in patients with COPD.,In general, both treatments were well tolerated. | This retrospective cohort study compared the risks of exacerbations and COPD-related healthcare costs between patients with chronic obstructive pulmonary disease (COPD) initiating tiotropium (TIO) alone and patients initiating triple therapy with fluticasone-salmeterol combination (FSC) added to TIO.,Managed-care enrollees who had an index event of ≥ 1 pharmacy claim for TIO during the study period (January 1, 2003-April 30, 2008) and met other eligibility criteria were categorized into one of two cohorts depending on their medication use.,Patients in the TIO+FSC cohort had combination therapy with TIO and FSC, defined as having an FSC claim on the same date as the TIO claim.,Patients in the TIO cohort had no such FSC use.,The risks of COPD exacerbations and healthcare costs were compared between cohorts during 1 year of follow-up.,The sample comprised 3333 patients (n = 852 TIO+FSC cohort, n = 2481 TIO cohort).,Triple therapy with FSC added to TIO compared with TIO monotherapy was associated with significant reductions in the adjusted risks of moderate exacerbation (hazard ratio 0.772; 95% confidence interval [CI] 0.641, 0.930) and any exacerbation (hazard ratio 0.763; 95% CI 0.646, 0.949) and a nonsignificant reduction in COPD-related adjusted monthly medical costs.,Triple therapy with FSC added to TIO compared with TIO monotherapy was associated with significant reductions in the adjusted risks of moderate exacerbation and any exacerbation over a follow-up period of up to 1 year.,These improvements were gained with triple therapy at roughly equal cost of that of TIO alone. | 1 |
Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous.,We sought to investigate the sputum cellular, mediator, and microbiome profiles of both asthma and COPD exacerbations.,Patients with severe asthma or moderate-to-severe COPD were recruited prospectively to a single center.,Sputum mediators were available in 32 asthmatic patients and 73 patients with COPD assessed at exacerbation.,Biologic clusters were determined by using factor and cluster analyses on a panel of sputum mediators.,Patterns of clinical parameters, sputum mediators, and microbiome communities were assessed across the identified clusters.,The asthmatic patients and patients with COPD had different clinical characteristics and inflammatory profiles but similar microbial ecology.,Three exacerbation biologic clusters were identified.,Cluster 1 was COPD predominant, with 27 patients with COPD and 7 asthmatic patients exhibiting increased blood and sputum neutrophil counts, proinflammatory mediators (IL-1β, IL-6, IL-6 receptor, TNF-α, TNF receptors 1 and 2, and vascular endothelial growth factor), and proportions of the bacterial phylum Proteobacteria.,Cluster 2 had 10 asthmatic patients and 17 patients with COPD with increased blood and sputum eosinophil counts, type 2 mediators (IL-5, IL-13, CCL13, CCL17, and CCL26), and proportions of the bacterial phylum Bacteroidetes.,Cluster 3 had 15 asthmatic patients and 29 patients with COPD with increased type 1 mediators (CXCL10, CXCL11, and IFN-γ) and proportions of the phyla Actinobacteria and Firmicutes.,A biologic clustering approach revealed 3 subgroups of asthma and COPD exacerbations, each with different percentages of patients with overlapping asthma and COPD.,The sputum mediator and microbiome profiles were distinct between clusters. | The 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. | 1 |
Objective To investigate the occurrence of pneumonia and pneumonia related events in patients with chronic obstructive pulmonary disease (COPD) treated with two different fixed combinations of inhaled corticosteroid/long acting β2 agonist.,Design Observational retrospective pairwise cohort study matched (1:1) for propensity score.,Setting Primary care medical records data linked to Swedish hospital, drug, and cause of death registry data for years 1999-2009.,Participants Patients with COPD diagnosed by a physician and prescriptions of either budesonide/formoterol or fluticasone/salmeterol.,Main outcome measures Yearly pneumonia event rates, admission to hospital related to pneumonia, and mortality.,Results 9893 patients were eligible for matching (2738 in the fluticasone/salmeterol group; 7155 in the budesonide/formoterol group), yielding two matched cohorts of 2734 patients each.,In these patients, 2115 (39%) had at least one recorded episode of pneumonia during the study period, with 2746 episodes recorded during 19 170 patient years of follow up.,Compared with budesonide/formoterol, rate of pneumonia and admission to hospital were higher in patients treated with fluticasone/salmeterol: rate ratio 1.73 (95% confidence interval 1.57 to 1.90; P<0.001) and 1.74 (1.56 to 1.94; P<0.001), respectively.,The pneumonia event rate per 100 patient years for fluticasone/salmeterol versus budesonide/formoterol was 11.0 (10.4 to 11.8) versus 6.4 (6.0 to 6.9) and the rate of admission to hospital was 7.4 (6.9 to 8.0) versus 4.3 (3.9 to 4.6).,The mean duration of admissions related to pneumonia was similar for both groups, but mortality related to pneumonia was higher in the fluticasone/salmeterol group (97 deaths) than in the budesonide/formoterol group (52 deaths) (hazard ratio 1.76, 1.22 to 2.53; P=0.003).,All cause mortality did not differ between the treatments (1.08, 0.93 to 1.14; P=0.59).,Conclusions There is an intra-class difference between fixed combinations of inhaled corticosteroid/long acting β2 agonist with regard to the risk of pneumonia and pneumonia related events in the treatment of patients with COPD.,Trial registration Clinical Trials.gov NCT01146392. | The toll-like receptors (TLRs) are a key component of host defense in the respiratory epithelium.,Cigarette smoking is associated with increased susceptibility to infection, while COPD is characterised by bacterial colonisation and infective exacerbations.,We found reduced TLR4 gene expression in the nasal epithelium of smokers compared with non-smoking controls, while TLR2 expression was unchanged.,Severe COPD was associated with reduced TLR4 expression compared to less severe disease, with good correlation between nasal and tracheal expression.,We went on to examine the effect of potential modulators of TLR4 expression in respiratory epithelium pertinent to airways disease.,Using an airway epithelial cell line, we found a dose-dependent downregulation in TLR4 mRNA and protein expression by stimulation with cigarette smoke extracts.,Treatment with the corticosteroids fluticasone and dexamethasone resulted in a dose-dependent reduction in TLR4 mRNA and protein.,The functional significance of this effect was demonstrated by impaired IL-8 and HBD2 induction in response to LPS.,Stimulation with salmeterol (10-6 M) caused upregulation of TLR4 membrane protein presentation with no upregulation of mRNA, suggesting a post-translational effect.,The effect of dexamethasone and salmeterol in combination was additive, with downregulation of TLR4 gene expression, and no change in membrane receptor expression.,Modulation of TLR4 in respiratory epithelium may have important implications for airway inflammation and infection in response to inhaled pathogens. | 1 |
Malnutrition is common in patients with COPD; however, little is known about its impacts on health-related quality of life (QoL) among patients with COPD.,This study aimed to explore the nutritional status and dietary intake among outpatients with COPD in Vietnam and its possible associations with QoL.,A cross-sectional study was carried out in COPD outpatients visiting the COPD management unit at the National Lung Hospital, Hanoi, Vietnam between May 2017 and July 2017.,Consecutive outpatients with a confirmed diagnosis of COPD were recruited with written inform consent.,The nutritional status of participants was assessed using Subjective Global Assessment (SGA), and dietary intake via a 24-hour recall interview.,The St George Respiratory Questionnaire (SGRQ) for COPD was used to investigate the participants’ QoL.,Sociodemographic and clinical data were extracted from hospital records.,Of 168 COPD outpatients involved in the study, three-quarters (74.4%) were diagnosed as malnourished (SGA B/C) and 81.5% reported unintentional weight loss.,Most of the patients did not meet their estimated energy and protein requirements (85.7% and 89.9%, respectively).,Malnutrition was significantly associated with disease severity (P=0.039) and ratio of protein intake to estimated requirement (P=0.005).,QoL was low for all levels of malnutrition or disease severity, with well-nourished participants and those with less disease severity having better QoL (P=0.006 and P<0.001, respectively).,With an extra meal per day, the odds of having malnutrition decreased 5.6 times (P<0.05) and the total SGRQ reduced 3.61 scores (P<0.05) indicating a better QoL.,Malnutrition and weight loss are prevalent among COPD outpatients.,Most of the patients had inadequate dietary intake and low QoL.,Nutrition counselling including increasing the number of meals per day with a focus on energy- and protein-rich foods may help improving nutritional status and QoL of patients with COPD in Vietnam. | Muscle wasting and chronic inflammation are predominant features of patients with COPD.,Systemic inflammation is associated with an accelerated decline in lung function.,In this study, the prevalence of sarcopenia and the relationships between sarcopenia and systemic inflammations in patients with stable COPD were investigated.,In a cross-sectional design, muscle strength and muscle mass were measured by handgrip strength (HGS) and bioelectrical impedance analysis in 80 patients with stable COPD.,Patients (≥40 years old) diagnosed with COPD were recruited from outpatient clinics, and then COPD stages were classified.,Sarcopenia was defined as the presence of both low muscle strength (by HGS) and low muscle mass (skeletal muscle mass index [SMMI]).,Levels of circulating inflammatory biomarkers (IL-6 and high-sensitivity TNFα [hsTNFα]) were measured.,Sarcopenia was prevalent in 20 (25%) patients.,Patients with sarcopenia were older, had lower body mass index, and a higher percentage of cardiovascular diseases.,In addition, they had significantly higher modified Medical Research Council scores and lower 6-minute walk distance than those without sarcopenia.,HGS was significantly correlated with age, modified Medical Research Council score, and COPD Assessment Test scores.,Both HGS and SMMI had associations with IL-6 and hsTNFα (HGS, r=−0.35, P=0.002; SMMI, r=−0.246, P=0.044) level.,In multivariate analysis, old age, lower body mass index, presence of cardiovascular comorbidities, and higher hsTNFα levels were significant determinants for sarcopenia in patients with stable COPD.,Sarcopenia is very common in patients with stable COPD, and is associated with more severe dyspnea-scale scores and lower exercise tolerance.,Systemic inflammation could be an important contributor to sarcopenia in the stable COPD population. | 1 |
Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by airflow limitation associated with an abnormal inflammatory response of the lungs to noxious particles and gases, caused primarily by cigarette smoking.,Increased oxidative burden plays an important role in the pathogenesis of COPD.,There is a delicate balance between the toxicity of oxidants and the protective function of the intracellular and extracellular antioxidant defense systems, which is critically important for the maintenance of normal pulmonary functions.,Several biomarkers of oxidative stress are available and have been evaluated in COPD.,In this review, we summarize the main literature findings about circulating oxidative stress biomarkers, grouped according to their method of detection, measured in COPD subjects. | This study assessed the effects of inhaled corticosteroid (ICS) on airway vascular remodeling in chronic obstructive pulmonary disease (COPD).,Thirty-four subjects with mild-to-moderate COPD were randomly allocated 2:1 to ICS or placebo treatment in a double-blinded clinical trial over 6 months.,Available tissue was compared before and after treatment for vessel density, and expression of VEGF, TGF-β1, and TGF-β1-related phosphorylated transcription factors p-SMAD 2/3.,This clinical trial has been registered and allocated with the Australian New Zealand Clinical Trials Registry (ANZCTR) on 17/10/2012 with reference number ACTRN12612001111864.,There were no significant baseline differences between treatment groups.,With ICS, vessels and angiogenic factors did not change in hypervascular reticular basement membrane, but in the hypovascular lamina propria (LP), vessels increased and this had a proportionate effect on lung air trapping.,There was modest evidence for a reduction in LP vessels staining for VEGF with ICS treatment, but a marked and significant reduction in p-SMAD 2/3 expression.,Six-month high-dose ICS treatment had little effect on hypervascularity or angiogenic growth factors in the reticular basement membrane in COPD, but normalized hypovascularity in the LP, and this was physiologically relevant, though accompanied by a paradoxical reduction in growth factor expression. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are an important measure of disease severity in terms of impaired disease progression, increased recovery time, healthcare resource utilization, overall morbidity and mortality.,We aimed to quantify exacerbation and healthcare resource utilization rates among COPD patients in Sweden with respect to baseline treatments, exacerbation history, and comorbidities.,Patients with a COPD or chronic bronchitis (CB) diagnosis in secondary care at age of ≥40 years on 1.7.2009 were identified and followed until 1.7.2010 or death.,Severe exacerbations were defined as hospitalizations due to respiratory disease, and healthcare resource utilization was measured by all-cause hospitalizations and secondary care visits.,Poisson regression was used adjusting for age, gender, time since COPD/CB diagnosis, and Charlson comorbidity index.,In 88,548 patients (54% females, mean age 72 years), previous respiratory hospitalizations and current high use of COPD medication (double or triple therapy) predicted an 8.3-fold increase in severe exacerbation rates and 1.8-fold increase in healthcare resource utilization rates in the following year, compared to patients without combination treatment and/or history of severe exacerbations.,COPD/CB patients with history of severe exacerbations and high use of COPD medication experienced a significantly increased rate of severe exacerbations and healthcare resource utilization during the one-year follow-up.,The online version of this article (10.1186/s12890-018-0573-0) contains supplementary material, which is available to authorized users. | Daily diaries are often used to collect data on disease activity, but are burdensome and compliance may be poor.,Their use in chronic obstructive pulmonary disease (COPD) and impact on the prevention and treatment of exacerbations is poorly researched.,We investigated diary-keeping in COPD and ascertained items that best predicted emergency attendances for exacerbations.,Participants in the active limb of a clinical trial in COPD kept daily diaries rating breathlessness, cough, sputum, physical activity, and use of reliever medication.,Data on 55 participants, 67% of whom were female, showed that overall compliance with diary-keeping was 62%.,Participants educated to primary school level only had lower compliance (P = 0.05).,Twenty patients had at least one emergency attendance, in whom the relative risk of an acute exacerbation for an increase in item score rose from six days prior to hospitalization, most sharply in the last two days.,Even for optimal combinations of items, the positive predictive value was poor, the best combination being cough, activity level, and inhaler use.,Good compliance can be achieved using daily diaries in COPD, although this is worse in those with a poor educational level.,Diary-keeping is not accurate in predicting acute exacerbations, but could be substantially simplified without loss of efficiency. | 1 |
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. | The alveolar compartment, the fundamental gas exchange unit in the lung, is critical for tissue oxygenation and viability.,We explored hepatocyte growth factor (HGF), a pleiotrophic cytokine that promotes epithelial proliferation, morphogenesis, migration, and resistance to apoptosis, as a candidate mediator of alveolar formation and regeneration.,Mice deficient in the expression of the HGF receptor Met in lung epithelial cells demonstrated impaired airspace formation marked by a reduction in alveolar epithelial cell abundance and survival, truncation of the pulmonary vascular bed, and enhanced oxidative stress.,Administration of recombinant HGF to tight-skin mice, an established genetic emphysema model, attenuated airspace enlargement and reduced oxidative stress.,Repair in the TSK/+ mouse was punctuated by enhanced akt and stat3 activation.,HGF treatment of an alveolar epithelial cell line not only induced proliferation and scattering of the cells but also conferred protection against staurosporine-induced apoptosis, properties critical for alveolar septation.,HGF promoted cell survival was attenuated by akt inhibition.,Primary alveolar epithelial cells treated with HGF showed improved survival and enhanced antioxidant production.,In conclusion, using both loss-of-function and gain-of-function maneuvers, we show that HGF signaling is necessary for alveolar homeostasis in the developing lung and that augmentation of HGF signaling can improve airspace morphology in murine emphysema.,Our studies converge on prosurvival signaling and antioxidant protection as critical pathways in HGF-mediated airspace maintenance or repair.,These findings support the exploration of HGF signaling enhancement for diseases of the airspace. | 1 |
The World Health Organisation reported COPD to be the third leading cause of death globally in 2019, and in 2020, the most common cause of cancer death was lung cancer; when these linked conditions are added together they come near the top of the leading causes of mortality.,The cell-biological program termed epithelial-to-mesenchymal transition (EMT) plays an important role in organ development, fibrosis and cancer progression.,Over the past decade there has emerged a substantial literature that also links EMT specifically to the pathophysiology of chronic obstructive pulmonary disease (COPD) as primarily an airway fibrosis disease; COPD is a recognised strong independent risk factor for the development of lung cancer, over and above the risks associated with smoking.,In this review, our primary focus is to highlight these linkages and alert both the COPD and lung cancer fields to these complex interactions.,We emphasise the need for inter-disciplinary attention and research focused on the likely crucial roles of EMT (and potential for its inhibition) with recognition of its strategic place mechanistically in both COPD and lung cancer.,As part of this we discuss the future potential directions for novel therapeutic opportunities, including evidence-based strategic repurposing of currently used familiar/approved medications. | Chronic obstructive pulmonary disease (COPD) and lung cancer, closely related to smoking, are major lung diseases affecting millions of individuals worldwide.,The generated gas mixture of smoking is proved to contain about 4,500 components such as carbon monoxide, nicotine, oxidants, fine particulate matter, and aldehydes.,These components were considered to be the principle factor driving the pathogenesis and progression of pulmonary disease.,A large proportion of lung cancer patients showed a history of COPD, which demonstrated that there might be a close relationship between COPD and lung cancer.,In the early stages of smoking, lung barrier provoked protective response and DNA repair are likely to suppress these changes to a certain extent.,In the presence of long-term smoking exposure, these mechanisms seem to be malfunctioned and lead to disease progression.,The infiltration of inflammatory cells to mucosa, submucosa, and glandular tissue caused by inhaled cigarette smoke is responsible for the destruction of matrix, blood supply shortage, and epithelial cell death.,Conversely, cancer cells have the capacity to modulate the proliferation of epithelial cells and produce of new vascular networks.,Comprehension understanding of mechanisms responsible for both pathologies is necessary for the prevention and treatment of COPD and lung cancer.,In this review, we will summarize related articles and give a glance of possible mechanism between cigarette smoking induced COPD and lung cancer. | 1 |
This study utilized a validated combination of a COPD Population Screener (COPD-PS) questionnaire and a handheld spirometric device as a screening tool for patients at high risk of COPD, such as smokers.,The study aimed to investigate and pilot the feasibility and application of this combined assessment, which we termed the “VitalQPlus”, as a screening tool for the early detection of COPD, especially in primary care settings.,This was a cross-sectional study screening potentially undiagnosed COPD patients using a validated five-item COPD-PS questionnaire together with a handheld spirometric device.,Patients were recruited from selected Malaysian government primary care health centers.,Of the total of 83 final participants, only 24.1% (20/83) were recruited from Perak and Penang (peninsular Malaysia) compared to 75.9% (63/83) from Sabah (Borneo region).,Our dual assessment approach identified 8.4% of the surveyed patients as having potentially undiagnosed COPD.,When only the Vitalograph COPD-6 screening tool was used, 15.8% of patients were detected with a forced expiratory volume in 1 second/forced expiratory volume in 6 seconds (FEV1/FEV6) ratio at <0.75, while 35.9% of patients were detected with the COPD-PS questionnaire.,These findings suggested that this dual assessment approach has a greater chance of identifying potentially undiagnosed COPD patients compared to the Vitalograph COPD-6 or COPD-PS questionnaire when used alone.,Our findings show that patients with more symptoms (scores of ≥5) yielded twice the percentage of outcomes of FEV1/FEV6 <0.75 compared to patients with fewer COPD symptoms (scores <5).,With the availability of a simple screening questionnaire and the COPD-6, there is an opportunity easily to make patients more aware of their lung symptoms and to encourage the provision of early treatment.,The proposed dual assessment approach, which we termed the VitalQPlus, may play a profound role in the early diagnosis of COPD, which is crucial in improving the clinical management of the disease. | COPD has a profound impact on daily life, yet remains underdiagnosed and undertreated.,We set out to develop a brief, reliable, self-scored questionnaire to identify individuals likely to have COPD.,COPD-PS™ development began with a list of concepts identified for inclusion using expert opinion from a clinician working group comprised of pulmonologists (n = 5) and primary care clinicians (n = 5).,A national survey of 697 patients was conducted at 12 practitioner sites.,Logistic regression identified items discriminating between patients with and without fixed airflow obstruction (AO, postbronchodilator FEV1/FVC < 70%).,ROC analyses evaluated screening accuracy, compared scoring options, and assessed concurrent validity.,Convergent and discriminant validity were assessed via COPD-PS and SF-12v2 score correlations.,For known-groups validation, COPD-PS differences between clinical groups were tested.,Test-retest reliability was evaluated in a 20% sample.,Of 697 patients surveyed, 295 patients met expert review criteria for spirometry performance; 38% of these (n = 113) had results indicating AO.,Five items positively predicted AO (p < 0.0001): breathlessness, productive cough, activity limitation, smoking history, and age.,COPD-PS scores accurately classified AO status (area under ROC curve = 0.81) and reliable (r = 0.91).,Patients with spirometry indicative of AO scored significantly higher (6.8, SD = 1.9; p < 0.0001) than patients without AO (4.0, SD = 2.3).,Higher scores were associated with more severe AO, bronchodilator use, and overnight hospitalization for breathing problems.,With the prevalence of COPD in the studied cohort, a score on the COPD-PS of greater than five was associated with a positive predictive value of 56.8% and negative predictive value of 86.4%.,The COPD-PS accurately classified physician-reported COPD (AUC = 0.89).,The COPD-PS is a brief, accurate questionnaire that can identify individuals likely to have COPD. | 1 |
This study was performed to examine acute exacerbation of COPD (AECOPD) during pulmonary rehabilitation (PR) and the usefulness of multidimensional indices (MIs) to predict AECOPD at enrolment in PR.,A 4-week PR program (PRP) was implemented for 125 consecutive patients with COPD.,At baseline and PRP completion, we recorded the FEV1, 6-minute walk test, peak work rate at cardiopulmonary testing, modified Medical Research Council score, and COPD Assessment Test (CAT) score.,The risk of AECOPDs at baseline was assessed using the body mass index, airway obstruction, dyspnea, Exercise capacity (BODE), dyspnea, obstruction, smoking, exacerbation (DOSE), and score to predict short-term risk of COPD exacerbations (SCOPEX) MIs.,Thirty-two episodes of AECOPD occurred.,The COPD status was worse in patients with than without AECOPD at baseline (lower FEV1, 6-minute walk test, and peak work rate; higher modified Medical Research Council and CAT scores).,The sensitivities of the BODE, DOSE, and SCOPEX MIs to predict the occurrence of AECOPD during PRP were 78.1%, 21.9%, and 84.4%, and the specificities were 73.6%, 87.1%, and 51.6%, respectively.,The BODE and SCOPEX MIs help to predict the exacerbation risk during PR. | COPD is now widely recognized as a complex heterogeneous syndrome, having both pulmonary and extrapulmonary features.,In clinical practice, the diagnosis of COPD is based on the presence of chronic airflow limitation, as assessed by post-bronchodilator spirometry.,The severity of the airflow limitation, as measured by percent predicted FEV1, provides important information to the physician to enable optimization of management.,However, in order to accurately assess the complexity of COPD, there need to be other measures made beyond FEV1.,At present, there is a lack of reliable and simple blood biomarkers to confirm and further assess the diagnosis of COPD.,However, it is possible to identify patients who display different phenotypic characteristics of COPD that relate to clinically relevant outcomes.,Currently, validated phenotypes of COPD include alpha-1 antitrypsin deficiency, and “frequent exacerbators”.,Recently, a definition and assessment of a new phenotype comprising patients with overlapping features of asthma and COPD has been suggested and is known as “asthma COPD overlap syndrome”.,Several other phenotypes have been proposed, but require validation against clinical outcomes.,Defining phenotypes requires the assessment of multiple factors indicating disease severity, its impact, and its activity.,Recognition and validation of COPD phenotypes has an important role to play in the selection of evidence-based targeted therapy in the future management of COPD, but regardless of the diagnostic terms, patients with COPD should be assessed and treated according to their individual treatable characteristics. | 1 |
Chronic obstructive pulmonary disease (COPD) is widely underdiagnosed.,A number of studies have evaluated the accuracy of screening tests for COPD, but their findings have not been formally summarised.,We therefore sought to determine and compare the diagnostic accuracy of such screening tests in primary care.,Systematic review and meta-analysis of the diagnostic accuracy of screening tests for COPD confirmed by spirometry in primary care.,We searched MEDLINE, EMBASE and other bibliographic databases from 1997 to 2013 for diagnostic accuracy studies that evaluated 1 or more index tests in primary care among individuals aged ≥35 years with no prior diagnosis of COPD.,Bivariate meta-analysis of sensitivity and specificity was performed where appropriate.,Methodological quality was assessed independently by 2 reviewers using the QUADAS-2 tool.,10 studies were included. 8 assessed screening questionnaires (the COPD Diagnostic Questionnaire (CDQ) was the most evaluated, n=4), 4 assessed handheld flow meters (eg, COPD-6) and 1 assessed their combination.,Among ever smokers, the CDQ (score threshold ≥19.5; n=4) had a pooled sensitivity of 64.5% (95% CI 59.9% to 68.8%) and specificity of 65.2% (52.9% to 75.8%), and handheld flow meters (n=3) had a sensitivity of 79.9% (95% CI 74.2% to 84.7%) and specificity of 84.4% (68.9% to 93.0%).,Inadequate blinding between index tests and spirometry was the main risk of bias.,Handheld flow meters demonstrated higher test accuracy than the CDQ for COPD screening in primary care.,The choice of alternative screening tests within whole screening programmes should now be fully evaluated.,CRD42012002074. | Underdiagnosis of chronic obstructive pulmonary disease (COPD) in primary care can be improved by a more efficient screening strategy.,To evaluate a three-step method of screening for COPD consisting of an initial short questionnaire followed by measurement of forced expiratory volume in 1s/forced expiratory volume in 6s (FEV1/FEV6) using an inexpensive pocket spirometer in those with high risk, and diagnostic quality spirometry in those with a low FEV1/FEV6.,We analysed two related Mexico City cross-sectional samples.,The 2003 Mexico City PLATINO survey (n=542) was used to develop a short questionnaire to determine the risk of COPD and a 2010 survey (n=737) additionally used a pocket spirometer.,The discriminatory power of the two instruments was assessed with receiver operator characteristic (ROC) curves using three COPD definitions.,The developed COPD scale included two variables from a simple questionnaire and, in ROC analysis, an area under the curve (AUC) between 0.64 and 0.77 was found to detect COPD.,The pocket spirometer had an AUC between 0.85 and 0.88 to detect COPD.,Using the COPD scale as a first screening step excluded 35-48% of the total population from further testing at the cost of not detecting 8-18% of those with COPD.,Using the pocket spirometer and sending those with a FEV1/FEV6<0.80 for diagnostic quality spirometry is very efficient, and substantially improved the positive predictive value at the cost of not detecting one-third of COPD cases.,A three-step screening strategy for COPD substantially reduces the need for spirometry testing when only a COPD scale is used for screening. | 1 |
Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants.,We have previously identified iron-responsive element binding protein 2 (IRP2) as an important COPD susceptibility gene, with IRP2 protein increased in the lungs of individuals with COPD.,Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD.,By integrating RIP-Seq, RNA-Seq, gene expression and functional enrichment clustering analysis, we identified IRP2 as a regulator of mitochondrial function in the lung.,IRP2 increased mitochondrial iron loading and cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD.,Frataxin-deficient mice with higher mitochondrial iron loading had impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas synthesis of cytochrome c oxidase (Sco2)-deficient mice with reduced COX were protected from CS-induced pulmonary inflammation and impairment of MCC.,Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD.,Mitochondrial iron chelation also alleviated CS-impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD. | Patients with chronic obstructive pulmonary disease (COPD) exhibit dominant features of chronic bronchitis, emphysema, and/or asthma, with a common phenotype of airflow obstruction.,COPD pulmonary physiology reflects the sum of pathological changes in COPD, which can occur in large central airways, small peripheral airways, and the lung parenchyma.,Quantitative or high-resolution computed tomography is used as a surrogate measure for assessment of disease progression.,Different biological or molecular markers have been reported that reflect the mechanistic or pathogenic triad of inflammation, proteases, and oxidants and correspond to the different aspects of COPD histopathology.,Similar to the pathogenic triad markers, genetic variations or polymorphisms have also been linked to COPD-associated inflammation, protease-antiprotease imbalance, and oxidative stress.,Furthermore, in recent years, there have been reports identifying aging-associated mechanistic markers as downstream consequences of the pathogenic triad in the lungs from COPD patients.,For this review, the authors have limited their discussion to a review of mechanistic markers and genetic variations and their association with COPD histopathology and disease status. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality.,COPD is typified by persistent, progressive airflow limitation and a range of respiratory and systemic symptoms such as breathlessness, coughing, wheezing, depression, anxiety, general fatigue, and sleeping difficulties.,Despite receiving treatment for COPD, many patients suffer from regular symptoms that affect their daily lives and lead to increased morbidity.,These symptoms vary in severity, frequency, and type, and can occur at any time throughout the 24-h day, with over half of patients with COPD experiencing symptoms in the morning, during the day, and at nighttime.,Despite the prevalence of symptoms, patient and physician perception of the impact of COPD symptoms on patients’ lives is not always in concordance.,Dual bronchodilator therapy with a long-acting muscarinic antagonist (LAMA) and long-acting beta agonist (LABA) has the potential to treat the symptoms of COPD in addition to improving lung function.,This review therefore examines the burden of symptoms experienced throughout the day by patients with COPD and the evidence for combined LAMA/LABA treatment in terms of symptom management.,As patients with COPD experience varying symptoms throughout the course of their disease, the role of tailoring treatment to the individual needs of the patient is also examined.,We conclude that the symptoms of COPD are troublesome, variable, can occur during all parts of the 24-h day, and have a substantial impact on patients’ health status and quality of life.,In order to provide effective, patient-orientated care, patients with COPD should be evaluated on the basis of lung function, the frequency of symptoms, and patient-perceived impact of symptoms on their lives.,Therapy should be chosen carefully based on individualized assessment, ensuring personalization to the individual needs of the patient. | Epicardial adipose tissue (EAT) has been shown to be a non-invasive marker that predicts the progression of cardiovascular disease (CVD).,It has been reported that the EAT volume is increased in patients with chronic obstructive pulmonary disease (COPD).,However, little is known about which phenotypes of COPD are associated with increased EAT.,One hundred and eighty smokers who were referred to the clinic were consecutively enrolled.,A chest CT was used for the quantification of the emphysematous lesions, airway lesions, and EAT.,These lesions were assessed as the percentage of low attenuation volume (LAV%), the square root of airway wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) and the EAT area, respectively.,The same measurements were made on 225 Vietnamese COPD patients to replicate the results.,Twenty-six of the referred patients did not have COPD, while 105 were diagnosed as having COPD based on a FEV1/FVC<0.70.,The EAT area was significantly associated with age, BMI, FEV1 (%predicted), FEV1/FVC, self-reported hypertension, self-reported CVD, statin use, LAV%, and √Aaw at Pi10 in COPD patients.,The multiple regression analyses showed that only BMI, self-reported CVD and √Aaw at Pi10 were independently associated with the EAT area (R2 = 0.51, p<0.0001).,These results were replicated in the Vietnamese population.,The EAT area is independently associated with airway wall thickness.,Because EAT is also an independent predictor of CVD risk, these data suggest a mechanistic link between the airway predominant form of COPD and CVD. | 1 |
Inflammatory biomarkers, including cytokines, are associated with COPD, but the association of particular circulating cytokines with systemic pathology remains equivocal.,To investigate this, we developed a protein microarray system to detect multiple cytokines in small volumes of serum.,Fourteen cytokines were measured in serum from never-smokers, ex-smokers, current smokers, and COPD patients (GOLD stages 1-3).,Certain individual circulating cytokines (particularly TNFα and IL-1β) were significantly elevated in concentration in the serum of particular COPD patients (and some current/ex-smokers without COPD) and may serve as markers of particularly significant systemic inflammation.,However, numerous circulating cytokines were raised such that their combined, but not individual, elevation was significantly associated with severity of disease, and these may be further indicators of, and contributors to, the systemic inflammatory manifestations of COPD.,The coelevation of numerous circulating cytokines in COPD is consistent with the insidious development, chronic nature, and systemic comorbidities of the disease. | Exacerbations of COPD (ECOPD) represent a major burden for patients and health care systems.,Innovative sampling techniques have led to the identification of several pulmonary biomarkers.,Although some molecules are promising, their usefulness in clinical practice is not yet established.,Medline and Highwire databases were used to identify studies evaluating pulmonary sampled biomarkers in ECOPD.,We combined 3 terms for ECOPD, 3 for biomarkers and 6 for the sampling method.,Seventy-nine studies were considered eligible for inclusion in the review and were analyzed further.,Pulmonary biomarkers sampled with non-invasive, semi-invasive and invasive methods were evaluated for their potential to illustrate the disease’s clinical course, to correlate to clinical variables and to predict clinical outcomes, ECOPD etiology and response to treatment.,According to published data several pulmonary biomarkers assessed in ECOPD have the potential to illustrate the natural history of disease through the modification of their levels.,Among the clinically relevant molecules, those that have been studied the most and appear to be promising are spontaneous and induced sputum biomarkers for reflecting clinical severity and symptomatic recovery, as well as for directing towards an etiological diagnosis.,Current evidence on the clinical usefulness of exhaled breath condensate and bronchoalveolar lavage biomarkers in ECOPD is limited.,In conclusion, pulmonary biomarkers have the potential to provide information on the mechanisms underlying ECOPD, and several correlate with clinical variables and outcomes.,However, on the basis of published evidence, no single molecule is adequately validated for wide clinical use.,Clinical trials that incorporate biomarkers in decisional algorithms are required. | 1 |
Acute exacerbations, which are a significant cause of mortality and morbidity, adversely affect chronic obstructive pulmonary disease (COPD) prognosis by accelerating loss of lung function.,It is important to know the microorganisms that commonly cause exacerbations in the patient groups classified according to clinical and functional characteristics for fast and accurate treatment of acute exacerbations.,The last Global Initiative for Chronic Obstructive Lung Disease (GOLD) publication recommended a new staging system containing obstruction degree, frequency of exacerbations, and quality of life questionnaires.,This study is designed to analyze the relationship between the bacteria isolated in acute exacerbations and new GOLD stages.,Potentially pathogenic bacteria (PPB) isolation with culture and polymerase chain reaction methods were obtained from 114 acute exacerbation COPD patients, classified into A, B, C, and D groups by analyzing the forced expiratory volume in 1 second (FEV1) value, COPD Assessment Test (CAT) score, and exacerbation frequency according to the new GOLD staging system.,There was a significant correlation between exacerbation frequency and PPB isolation (P=0.002).,There was no relationship between GOLD stage, FEV1, and CAT score with PPB isolation.,The isolated bacteria diversity and mixed infection frequency were higher in the GOLD stage D group.,Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii were isolated only from D group patients.,Bacterial infection may cause an acute exacerbation equally in each stage for COPD.,The difference in bacterial etiology is more related to exacerbation frequency than FEV1 and CAT scores for an acute exacerbation.,Determining exacerbation frequency is significant for treatment success in empirical antibiotic selection. | To review and summarize existing literature on the indirect burden of chronic obstructive pulmonary disease (COPD) in the US.,Medline, Scopus, and OvidSP databases were searched using defined search terms to identify relevant studies.,Eligible studies were published in English between January 2000 and April 2012 and calculated the indirect burden of COPD in a US population in terms of prevalence, incidence or costs of productivity loss, disability, morbidity, or mortality.,Of 53 studies identified, eleven met eligibility criteria, with data years spanning 1987-2009.,Estimates of workforce participation range from 56% to 69% among individuals with COPD and from 65% to 77% among individuals without COPD.,Approximately 13%-18% of those with COPD are limited in the amount or type of work they can do and one-third or more experience general activity limitation.,Estimates of restricted activity days range from 27-63 days per year.,Estimates of mean annual sick leave and/or disability days among employed individuals with COPD range from 1.3-19.4 days.,Estimates of bed confinement range from 13-32 days per year.,Estimated mean annual indirect costs were $893-$2,234/person (US dollars) with COPD ($1,521-$3,348 in 2010 [US dollars]) and varied with the population studied, specific cost outcomes, and economic inputs.,In studies that assessed total (direct and indirect) costs, indirect costs accounted for 27%-61% of total costs, depending on the population studied.,COPD is associated with substantial indirect costs.,The disease places a burden on employers in terms of lost productivity and associated costs and on individuals in terms of lost income related to absenteeism, activity limitation, and disability.,Consideration of indirect as well as direct costs is necessary to gain a more complete view of the societal burden of COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is widely underdiagnosed, but the most effective approach for identifying these patients is unknown.,The aim of this study was to summarise and compare the effectiveness of different case finding approaches for undiagnosed COPD in primary care.,A systematic review of primary studies of any design evaluating case finding strategies for COPD in primary care among individuals aged ⩾35 years with no prior diagnosis was conducted.,Medline, Embase and other bibliographic databases were searched from 1997 to 2013, and methodological quality was assessed using standard tools.,Results were described and meta-analysis of the uptake and yield from different approaches was performed where there was sufficient homogeneity.,Three randomised controlled trials (RCTs), 1 controlled trial and 35 uncontrolled studies were identified that assessed the identification of new cases of COPD through systematic case finding.,A range of approaches were used including pre-screening with questionnaires (n=13) or handheld flow meters (n=5) or direct invitation to diagnostic spirometry (n=30).,Overall, any approach identified more undiagnosed COPD compared with usual care.,Targeting those at higher risk (e.g., smokers) and pre-screening (e.g., using questionnaires) is likely to increase the yield.,However, studies were heterogeneous and were limited by a lack of comparison groups, inadequate reporting and diversity in the definition of COPD, which limited our ability to draw firm conclusions.,There is extensive heterogeneity among studies evaluating case finding strategies for COPD, with few RCTs.,Well-conducted RCTs comparing case finding approaches are needed to identify the most effective target population, recruitment strategy and screening tests, using a clinical definition of COPD, and addressing the limitations highlighted in this review.,There is also a need to evaluate the impact of case finding on clinical care and patient outcomes. | COPD has a profound impact on daily life, yet remains underdiagnosed and undertreated.,We set out to develop a brief, reliable, self-scored questionnaire to identify individuals likely to have COPD.,COPD-PS™ development began with a list of concepts identified for inclusion using expert opinion from a clinician working group comprised of pulmonologists (n = 5) and primary care clinicians (n = 5).,A national survey of 697 patients was conducted at 12 practitioner sites.,Logistic regression identified items discriminating between patients with and without fixed airflow obstruction (AO, postbronchodilator FEV1/FVC < 70%).,ROC analyses evaluated screening accuracy, compared scoring options, and assessed concurrent validity.,Convergent and discriminant validity were assessed via COPD-PS and SF-12v2 score correlations.,For known-groups validation, COPD-PS differences between clinical groups were tested.,Test-retest reliability was evaluated in a 20% sample.,Of 697 patients surveyed, 295 patients met expert review criteria for spirometry performance; 38% of these (n = 113) had results indicating AO.,Five items positively predicted AO (p < 0.0001): breathlessness, productive cough, activity limitation, smoking history, and age.,COPD-PS scores accurately classified AO status (area under ROC curve = 0.81) and reliable (r = 0.91).,Patients with spirometry indicative of AO scored significantly higher (6.8, SD = 1.9; p < 0.0001) than patients without AO (4.0, SD = 2.3).,Higher scores were associated with more severe AO, bronchodilator use, and overnight hospitalization for breathing problems.,With the prevalence of COPD in the studied cohort, a score on the COPD-PS of greater than five was associated with a positive predictive value of 56.8% and negative predictive value of 86.4%.,The COPD-PS accurately classified physician-reported COPD (AUC = 0.89).,The COPD-PS is a brief, accurate questionnaire that can identify individuals likely to have COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is one global disease.,Lung function gradually declines.,Medication does not fully reverse the airflow limitation.,Qigong’s role in COPD rehabilitation has been assessed.,We aimed to assess the effects of Qigong practised by COPD patients.,Eligible articles were obtained through a systematic search.,The databased were search on October 8, 2017, and the date range of the searches in the electronic databases had no upper limit.,The Cochrane risk-of-bias tool was used to evaluate the quality of the eligible studies.,Mean differences with 95% confidence intervals were utilized to analyse the results.,Ten included studies contained 993 participants.,Statistical improvements occurred in the 6-min walk distance (6MWD) (MD, 30.57 m; 95% CI, 19.61-41.53 m; P < 0.00001); forced expiratory volume in 1 s (FEV1) (MD, 0.32 L; 95% CI, 0.09-0.56 L; P < 0.001); forced vital capacity rate of 1 s (FEV1/FVC) (MD, 2.66%; 95% CI, 1.32-2.26%; P = 0.0001); forced expiratory volume in 1 s/predicted (FEV1/pre) (MD, 6.04; CI, 2.58-9.5; P = 0.006); Monitored Functional Task Evaluation (MD, 0.88; 95% CI, 0.78-0.99; P < 0.00001); COPD Assessment Test for exercise (MD, − 5.54; 95% CI, − 9.49 to − 1.59; P = 0.006); Short Form-36 Health Quality Survey (SF-36)-General Health (MD, 5.22; 95% CI, 3.65-6.80; P < 0.00001); and Short Form-36 Health Quality Survey (SF-36)-Mental Health (MD, − 1.21; 95% CI, − 2.75 to 0.33; P = 0.12).,In this meta-analysis of RCTs between ten included studies, we found that Qigong can improve COPD patients in lung function, exercise capacity and quality of life who were in the stable stage.,The online version of this article (10.1186/s12906-019-2639-9) contains supplementary material, which is available to authorized users. | Objective: This study is the first meta-analysis investigating the rehabilitative effects of Wuqinxi for patients with chronic obstructive pulmonary disease (COPD).,Methods: Five electronic databases (PubMed, Web of Science, Scopus, CNKI, and Wanfang) from inception until early November 2018 were searched.,All randomized controlled trials (RCT) using Wuqinxi as the main intervention component were included for meta-analysis.,The pooled effect sizes (Standardized mean difference, SMD) were calculated to determine the magnitude of the Wuqinxi intervention effect.,Moderator analysis was only conducted for total training time.,Results: Overall results of the meta-analysis indicated that Wuqinxi exercise significantly improved exercise capability (SMD = 1.18, 95% CI 0.53 to 1.84, e < 0.001, I2 = 84.97%), FEV1 (SMD = 0.44, 95% CI 0.12 to 0.77, e < 0.001, I2 = 33.77%), FEV1% (SMD = 0.59, 95% CI 0.24 to 0.93, e < 0.001, I2 = 63.79%), FEV1/FVC (SMD = 0.65, 95% CI 0.37 to 0.93, e = 0.006, I2 = 44.32%) and CCQ (SMD = 1.23, 95% CI 0.31 to 2.14, e = 0.01, I2 = 93.32%).,Conclusions: With no occurrence of adverse event, clinicians could try to incorporate Wuqinxi exercise into their first-line rehabilitation regime for COPD patients. | 1 |
Quantifying the improvements in lower limb or quadriceps muscle mass following resistance training (RT), is an important outcome measure in COPD.,Ultrasound is a portable, radiation free imaging technique that can measure the size of superficial muscles belonging to the quadriceps group such as the rectus femoris, but has not been previously used in COPD patients following RT.,We compared the responsiveness of ultrasound derived measures of quadriceps mass against dual energy x-ray absorptiometry (DEXA), in patients with COPD and healthy controls following a programme of high intensity knee extensor RT.,Portable ultrasound was used to assess the size of the dominant quadriceps in 45 COPD patients and 19 healthy controls-before, during, and after 8 weeks of bilateral high intensity isokinetic knee extensor RT.,Scanning was performed at the mid-thigh region, and 2 indices of quadriceps mass were measured-rectus femoris cross-sectional area (RFcsa) and quadriceps muscle thickness (Qt).,Thigh lean mass (Tdexa) was determined by DEXA.,Training resulted in a significant increase in Tdexa, RFcsa and Qt in COPD patients [5.7%, 21.8%, 12.1% respectively] and healthy controls [5.4%, 19.5%, 10.9 respectively].,The effect size for the changes in RFcsa (COPD= 0.77; Healthy=0.83) and Qt (COPD=0.36; Healthy=0.78) were greater than the changes in Tdexa (COPD=0.19; Healthy=0.26) following RT.,Serial ultrasound measurements of the quadriceps can detect changes in muscle mass in response to RT in COPD.,The technique has good reproducibility, and may be more sensitive to changes in muscle mass when compared to DEXA.,http://www.controlled-trials.com (Identifier: ISRCTN22764439) | Many patients with chronic obstructive pulmonary disease (COPD) suffer from exercise intolerance.,In about 40% of the patients exercise capacity is limited by alterations in skeletal muscle rather than pulmonary problems.,Indeed, COPD is often associated with muscle wasting and a slow-to-fast shift in fiber type composition resulting in weakness and an earlier onset of muscle fatigue, respectively.,Clearly, limiting muscle wasting during COPD benefits the patient by improving the quality of life and also the chance of survival.,To successfully combat muscle wasting and remodeling during COPD a clear understanding of the causes and mechanisms is needed.,Disuse, hypoxemia, malnutrition, oxidative stress and systemic inflammation may all cause muscle atrophy.,Particularly when systemic inflammation is elevated muscle wasting becomes a serious complication.,The muscle wasting may at least partly be due to an increased activity of the ubiquitin proteasome pathway and apoptosis.,However, it might well be that an impaired regenerative potential of the muscle rather than the increased protein degradation is the crucial factor in the loss of muscle mass during COPD with a high degree of systemic inflammation.,Finally, we briefly discuss the various treatments and rehabilitation strategies available to control muscle wasting and fatigue in patients with COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by frequent exacerbation phenotypes independent of disease stage.,Increasing evidence shows that the microbiota plays a role in disease progression and severity, but long-term and international multicenter assessment of the variations in viral and bacterial communities as drivers of exacerbations are lacking.,Two-hundred severe COPD patients from Europe and North America were followed longitudinally for 3 years.,We performed nucleic acid detection for 20 respiratory viruses and 16S ribosomal RNA gene sequencing to evaluate the bacterial microbiota in 1179 sputum samples collected at stable, acute exacerbation and follow-up visits.,Similar viral and bacterial taxa were found in patients from the USA compared to Bulgaria and Czech Republic but their microbiome diversity was significantly different (P < 0.001) and did not impact exacerbation rates.,Virus infection was strongly associated with exacerbation events (P < 5E-20).,Human rhinovirus (13.1%), coronavirus (5.1%) and influenza virus (3.6%) constitute the top viral pathogens in triggering exacerbation.,Moraxella and Haemophilus were 5-fold and 1.6-fold more likely to be the dominating microbiota during an exacerbation event.,Presence of Proteobacteria such as Pseudomonas or Staphylococcus amongst others, were associated with exacerbation events (OR > 0.17; P < 0.02) but more strongly associated with exacerbation frequency (OR > 0.39; P < 4E-10), as confirmed by longitudinal variations and biotyping of the bacterial microbiota, and suggesting a role of the microbiota in sensitizing the lung.,This study highlights bacterial taxa in lung sensitization and viral triggers in COPD exacerbations.,It provides a global overview of the diverse targets for drug development and explores new microbiome analysis methods to guide future patient management applications. | Sphingolipid bioactivities in the respiratory airways and the roles of the proteins that handle them have been extensively investigated.,Gas or inhaled particles or microorganisms come into contact with mucus components, epithelial cells, blood barrier, and immune surveillance within the airways.,Lung structure and functionality rely on a complex interplay of polar and hydrophobic structures forming the surfactant layer and governing external-internal exchanges, such as glycerol-phospholipids sphingolipids and proteins.,Sphingolipids act as important signaling mediators involved in the control of cell survival and stress response, as well as secreted molecules endowed with inflammation-regulatory activities.,Most successful respiratory infection and injuries evolve in the alveolar compartment, the critical lung functional unit involved in gas exchange.,Sphingolipid altered metabolism in this compartment is closely related to inflammatory reaction and ceramide increase, in particular, favors the switch to pathological hyperinflammation.,This short review explores a few mechanisms underlying sphingolipid involvement in the healthy lung (surfactant production and endothelial barrier maintenance) and in a selection of lung pathologies in which the impact of sphingolipid synthesis and metabolism is most apparent, such as acute lung injury, or chronic pathologies such as cystic fibrosis and chronic obstructive pulmonary disease. | 1 |
The SERPINA1, SERPINA3, and SERPINE2 genes, which encode antiproteases, have been proposed to be susceptible genes for of chronic obstructive pulmonary disease (COPD) and related phenotypes.,Whether they are associated with emphysema is not known.,Twelve previously reported single nucleotide polymorphisms (SNPs) in SERPINA1 (rs8004738, rs17751769, rs709932, rs11832, rs1303, rs28929474, and rs17580), SERPINA3 (rs4934, rs17473, and rs1800463), and SERPINE2 (rs840088 and rs975278) were genotyped in samples obtained from 1,335 consecutive autopsies of elderly Japanese people.,The association between these SNPs and the severity of emphysema, as assessed using macroscopic scores, was determined.,Emphysema of more than moderate degree was detected in 189 subjects (14.1%) and showed a significant gender difference (males, 20.5% and females, 7.0%; p < 0.0001).,Among the 12 examined SNPs, only rs975278 in the SERPINE2 gene was positively associated with emphysema.,Unlike the major alleles, homozygous minor alleles of rs975278 were associated with emphysema (odds ratio (OR) = 1.54; 95% confidence interval (CI) = 1.02-2.30; p = 0.037) and the association was very prominent in smokers (OR = 2.02; 95% CI = 1.29-3.15; p = 0.002).,SERPINE2 may be a risk factor for the development of emphysema and its association with emphysema may be stronger in smokers. | Recent studies have proposed that the serine protease inhibitor E2 (SERPINE2) was a novel susceptibility gene for chronic obstructive pulmonary disease (COPD) in Caucasians.,However, this issue still remained controversial.,Additional evidences from populations with different environments and/or genetic backgrounds, such as East Asian, would be helpful to elucidate the issue.,In this study, five proposed causal SNPs in SERPINE2 were genotyped in 327 COPD patients and 349 controls, all of which belonged to the Han population sampled from Southwest China.,The frequency of each SNP was compared both individually and in combination between patients and controls.,The potential relationship between these SNPs and severity of COPD was also investigated.,Three SNPs (rs3795877, rs6747096, and rs3795879) showed complete linkage disequilibrium (r2 = 1), and the minor allele frequencies were 13.0% and 12.9% in case and control cohorts, respectively, with no significant difference observed (P = 0.96).,We also failed to observe any significant correlation between these SNPs and COPD severity (P = 0.67).,The other two SNPs (rs7579646 and rs840088) also presented a similar pattern.,Moreover, four major haplotypes were observed in our sample but none showed a significant difference between case and control groups (P > 0.1).,Our results failed to obtain the evidence that these SNPs in SERPINE2 contributed to the COPD susceptibility in the Han Chinese population. | 1 |
CD56+ natural killer (NK) and CD56+ T cells, from sputum or bronchoalveolar lavage of subjects with chronic obstructive pulmonary disease (COPD) are more cytotoxic to highly susceptible NK targets than those from control subjects.,Whether the same is true in lung parenchyma, and if NK activity actually contributes to emphysema progression are unknown.,To address these questions, we performed two types of experiments on lung tissue from clinically-indicated resections (n = 60).,First, we used flow cytometry on fresh single-cell suspension to measure expression of cell-surface molecules (CD56, CD16, CD8, NKG2D and NKp44) on lung lymphocytes and of the 6D4 epitope common to MICA and MICB on lung epithelial (CD326+) cells.,Second, we sequentially isolated CD56+, CD8+ and CD4+ lung lymphocytes, co-cultured each with autologous lung target cells, then determined apoptosis of individual target cells using Annexin-V and 7-AAD staining.,Lung NK cells (CD56+ CD3−) and CD56+ T cells (CD56+ CD3+) were present in a range of frequencies that did not differ significantly between smokers without COPD and subjects with COPD.,Lung NK cells had a predominantly “cytotoxic” CD56+ CD16+ phenotype; their co-expression of CD8 was common, but the percentage expressing CD8 fell as FEV1 % predicted decreased.,Greater expression by autologous lung epithelial cells of the NKG2D ligands, MICA/MICB, but not expression by lung CD56+ cells of the activating receptor NKG2D, correlated inversely with FEV1 % predicted.,Lung CD56+ lymphocytes, but not CD4+ or CD8+ conventional lung T cells, rapidly killed autologous lung cells without additional stimulation.,Such natural cytotoxicity was increased in subjects with severe COPD and was unexplained in multiple regression analysis by age or cancer as indication for surgery.,These data show that as spirometry worsens in COPD, CD56+ lung lymphocytes exhibit spontaneous cytotoxicity of autologous structural lung cells, supporting their potential role in emphysema progression.,ClinicalTrials.gov NCT00281229 | Cigarette smoking is the main risk factor for the development of chronic obstructive pulmonary disease (COPD), a major cause of morbidity and mortality worldwide.,Despite this, the cellular and molecular mechanisms that contribute to COPD pathogenesis are still poorly understood.,The objective of this study was to assess IL-1 α and β expression in COPD patients and to investigate their respective roles in perpetuating cigarette smoke-induced inflammation.,Functional studies were pursued in smoke-exposed mice using gene-deficient animals, as well as blocking antibodies for IL-1α and β.,Here, we demonstrate an underappreciated role for IL-1α expression in COPD.,While a strong correlation existed between IL-1α and β levels in patients during stable disease and periods of exacerbation, neutrophilic inflammation was shown to be IL-1α-dependent, and IL-1β- and caspase-1-independent in a murine model of cigarette smoke exposure.,As IL-1α was predominantly expressed by hematopoietic cells in COPD patients and in mice exposed to cigarette smoke, studies pursued in bone marrow chimeric mice demonstrated that the crosstalk between IL-1α+ hematopoietic cells and the IL-1R1+ epithelial cells regulates smoke-induced inflammation.,IL-1α/IL-1R1-dependent activation of the airway epithelium also led to exacerbated inflammatory responses in H1N1 influenza virus infected smoke-exposed mice, a previously reported model of COPD exacerbation.,This study provides compelling evidence that IL-1α is central to the initiation of smoke-induced neutrophilic inflammation and suggests that IL-1α/IL-1R1 targeted therapies may be relevant for limiting inflammation and exacerbations in COPD. | 1 |
Despite a well-recognised burden of disabling physical symptoms compounded by co-morbidities, psychological distress and social isolation, the needs of people with severe chronic obstructive pulmonary disease (COPD) are typically poorly addressed.,To assess the effectiveness of interventions designed to deliver holistic care for people with severe COPD.,We searched 11 biomedical databases, three trial repositories (January 1990-March 2012; no language restrictions) and contacted international experts to locate published, unpublished and in-progress randomised controlled trials (RCTs), quasi-RCTs and controlled clinical trials (CCTs) that investigated holistic interventions to support patients with severe COPD in any healthcare context.,The primary outcome was health-related quality of life (HRQoL).,Quality assessment and data extraction followed Cochrane Collaboration methodology.,We used a piloted data extraction sheet and undertook narrative synthesis.,From 2,866 potentially relevant papers, we identified three trials: two RCTs (from United States and Australia), and one CCT (from Thailand): total 216 patients.,Risk of bias was assessed as moderate in two studies and high in the third.,All the interventions were led by nurses acting in a co-ordinating role (e.g. facilitating community support in Thailand, providing case-management in the USA, or co-ordinating inpatient care in Australia).,HRQoL improved significantly in the Thai CCT compared to the (very limited) usual care (p<0.001), in two sub-domains in the American trial, but showed no significant changes in the Australian trial.,Exercise tolerance, dyspnoea, and satisfaction with care also improved in the Thai trial.,Some 15 years after reports first highlighted the unmet needs of people with severe COPD, we have been unable to find robust trial evidence about interventions that can address those needs.,There is an urgent need to develop and evaluate holistic care interventions designed improve HRQoL for people with severe COPD.,PROSPERO (CRD42012002430). | Background: Chronic obstructive pulmonary disease (COPD) is a disease of increasing significance in terms of economic and social burden due to its increasing prevalence and high costs.,Direct costs of COPD are mostly associated with hospitalization expenditures.,In this study, our objective was to investigate the costs of hospitalization and factors affecting these costs in patients hospitalized due to acute exacerbation of COPD (AECOPD).,Methods: A total of 284 patients hospitalized AECOPD were included in the study.,Data were examined retrospectively using the electronic hospital charts.,Results: Mean duration of hospitalization was 11.38 ± 6.94 days among study patients.,Rates of admission to the intensive care unit, initiation of non-invasive mechanical ventilation (NIMV) and invasive mechanical ventilation (MIV) were 37.3% (n=106), 44.4% (n=126) and 18.3% (n=52) respectively.,The rate of mortality was 14.8% (n=42).,Mean cost of a single patient hospitalized for an AECOPD was calculated as $1765 ± 2139.,Mean cost of admission was $889 ± 533 in standard ward, and $2508 ± 2857 in intensive care unit (ICU).,The duration of hospitalization, a FEV1% predicted value below 30%, having smoked 40 package-years or more, the number of co-morbidities, NIMV, IMV, ICU, exitus and the number of hospitalizations in the past year were among the factors that increased costs significantly.,Hospital acquired pneumonia, chronic renal failure and anemia also increased the costs of COPD significantly.,Conclusion: The costs of treatment increase with the severity of COPD or with progression to a higher stage.,Efforts and expenditures aimed at preventing COPD exacerbations might decrease the costs in COPD. | 1 |
The role of vitamin D (VitD) in calcium and bone homeostasis is well described.,In the last years, it has been recognized that in addition to this classical function, VitD modulates a variety of processes and regulatory systems including host defense, inflammation, immunity, and repair.,VitD deficiency appears to be frequent in industrialized countries.,Especially patients with lung diseases have often low VitD serum levels.,Epidemiological data indicate that low levels of serum VitD is associated with impaired pulmonary function, increased incidence of inflammatory, infectious or neoplastic diseases.,Several lung diseases, all inflammatory in nature, may be related to activities of VitD including asthma, COPD and cancer.,The exact mechanisms underlying these data are unknown, however, VitD appears to impact on the function of inflammatory and structural cells, including dendritic cells, lymphocytes, monocytes, and epithelial cells.,This review summarizes the knowledge on the classical and newly discovered functions of VitD, the molecular and cellular mechanism of action and the available data on the relationship between lung disease and VitD status. | The management of COPD is complex and patient adherence to treatment recommendations is known to be poor.,In this paper the methods used for evaluating adherence in COPD are compared.,Self-reporting has satisfactory reliability and offers a cheap, simple and easy method for assessing adherent behaviors.,Unlike the objective measures of adherence such as electronic monitoring, self-reporting helps in identifying the reasons for nonadherence, which in turn would be useful in addressing adherence issues.,Patients do not follow their treatment recommendations either intentionally or unintentionally.,Intentional deviations are driven by patient beliefs and experiences about illness and treatment, which are in turn influenced by social and cultural factors.,Unintentional deviations are often due to cognitive impairment and lack of routines.,Factors associated with adherence in COPD have been explained using the Becker-Maiman model.,Strategies for overcoming nonadherence have to be formulated based on the nature and reasons for nonadherence.,In the event of unintentional nonadherence, the use of adherence aids like Dosette boxes, calendar packs and reminders should be promoted.,Understanding patient beliefs and experiences, patient education focusing on the pathology of COPD and the role of treatment, periodic monitoring and reinforcement are critical for overcoming the barriers of intentional nonadherence. | 1 |
Clinically Important Deterioration (CID) is a novel composite measure to assess treatment effect in chronic obstructive pulmonary disease (COPD).,We examined the performance and utility of CID in assessing the effect of inhaled corticosteroids (ICS) in COPD.,This post-hoc analysis of four budesonide/formoterol (BUD/FORM) studies comprised 3576 symptomatic moderate-to-very-severe COPD patients with a history of exacerbation.,Analysis of time to first CID event (exacerbation, deterioration in forced expiratory volume in 1 second [FEV1] or worsening St George’s Respiratory Questionnaire [SGRQ] score) was completed using Cox proportional hazards models.,The proportion of patients with ≥1 CID in the four studies ranged between 63 and 77% and 69-84% with BUD/FORM and FORM, respectively, with an average 25% reduced risk of CID with BUD/FORM.,All components contributed to the CID event rate.,Experiencing a CID during the first 3 months was associated with poorer outcomes (lung function, quality of life, symptoms and reliever use) and increased risk of later CID events.,The effect of BUD/FORM versus FORM in reducing CID risk was positively associated with the blood eosinophil count.,Our findings suggest that BUD/FORM offers protective effects for CID events compared with FORM alone, with the magnitude of the effect dependent on patients’ eosinophil levels.,CID may be an important tool for evaluation of treatment effect in a complex, multifaceted, and progressive disease like COPD, and a valuable tool to allow for shorter and smaller future outcome predictive trials in early drug development. | Minimizing the risk of disease progression and exacerbations is the key goal of COPD management, as these are well-established indicators of poor COPD prognosis.,We developed a novel composite end point assessing three important aspects (lung function, health status, and exacerbations) of worsening in COPD.,The objective was to determine whether dual bronchodilation with umeclidinium/vilanterol (UMEC/VI) reduces clinically important deteriorations (CIDs) in COPD versus placebo or bronchodilator monotherapy.,This study is a post hoc analysis of two 24-week trials comparing UMEC/VI 62.5/25 µg with UMEC 62.5 µg, VI 25 µg, or placebo (Study A; NCT01313650), or UMEC/VI 62.5/25 µg with tiotropium (TIO) 18 µg (Study B; NCT01777334) in patients with symptomatic COPD, without a history of frequent exacerbations.,Deterioration was assessed as the time to a first CID, a composite measure defined as a decrease of ≥100 mL in trough forced expiratory volume in 1 second or ≥4-unit increase in St George’s Respiratory Questionnaire total score or an on-treatment moderate-to-severe COPD exacerbation.,In Study A, fewer patients experienced a first CID with UMEC/VI (44%) versus UMEC (50%), VI (56%), and placebo (75%).,The risk of a first CID was reduced with UMEC/VI (hazard ratio [HR]: 0.37 [95% confidence interval, CI: 0.30, 0.45]), UMEC (HR: 0.46 [95% CI: 0.38, 0.56]), and VI (HR: 0.55 [95% CI: 0.45, 0.66]; all P<0.001) versus placebo, and with UMEC/VI versus UMEC (HR: 0.80 [95% CI: 0.65, 0.97]; P<0.05) and versus VI (HR: 0.67 [95% CI: 0.55, 0.81]; P<0.001).,In Study B, fewer patients experienced a first CID with UMEC/VI (41%) versus TIO (59%).,UMEC/VI reduced the risk of a first composite CID by 43% versus TIO (HR: 0.57 [95% CI: 0.47, 0.69]; P<0.001).,This exploratory analysis, using a new assessment of clinical deterioration in COPD, revealed that a majority of symptomatic patients with low exacerbation risk experienced a deterioration during the 24-week study periods.,UMEC/VI reduces the risk of a first CID versus placebo or bronchodilator monotherapy. | 1 |
Long-term maintenance therapy for COPD is evolving rapidly.,Dual bronchodilation with new long-acting muscarinic antagonist and long-acting beta-agonist (LAMA/LABA) fixed dose combination inhalers were introduced over the past 2 years.,In clinical trials, these inhalers significantly improved lung function (trough forced expiratory volume in 1 second), patient-reported outcomes, and quality of life measures compared with placebo, their respective monocomponents, and tiotropium.,The recorded adverse events of these new inhalers were also similar to those of their monocomponents or placebo.,There are concerns regarding long-term complications (weight gain, osteoporosis, cataract) and increased risk of community-acquired pneumonia with the use of inhaled corticosteroids (ICS).,The new LAMA/LABA inhalers could potentially reduce the use of ICS as part and parcel of maintenance therapy in COPD.,Recent studies compared these LAMA/LABA inhalers with ICS/LABA combination inhalers in moderate-to-severe COPD.,The results are promising and favor the LAMA/LABA inhalers, especially in the longer duration trials.,Furthermore, there is a clearer picture emerging as to the subgroup of COPD patients who may be able to successfully switch from their current ICS/LABA therapy to these new LAMA/LABA inhalers. | Increasing evidence suggests pharmacological treatments may impact on overall survival in Chronic Obstructive Pulmonary Disease (COPD) patients.,Individual clinical trials are rarely powered to detect mortality differences between treatments and may not include all treatment options relevant to healthcare decision makers.,A systematic review was conducted to identify RCTs of COPD treatments reporting mortality; evidence was synthesised using network meta-analysis (NMA).,The analysis included 40 RCTs; a quantitative indirect comparison between 14 treatments using data from 55,220 patients was conducted.,The analysis reported two treatments reducing all-cause mortality; salmeterol/fluticasone propionate combination (SFC) was associated with a reduction in mortality versus placebo in the fixed effects (HR 0.79; 95 % Crl 0.67, 0.94) but not the random effects model (0.79; 0.56, 1.09).,Indacaterol was associated with a reduction in mortality versus placebo in fixed (0.28; 0.08 to 0.85) and random effects (0.29; 0.08, 0.89) models.,Mean estimates and credible intervals for hazard ratios for indacaterol versus placebo are based on a small number of events; estimates may change when the results of future studies are included.,These results were maintained across a variety of assumptions and provide evidence that SFC and indacaterol may lead to improved survival in COPD patients.,Results of an NMA of COPD treatments suggest that SFC and indacaterol may reduce mortality.,Further research is warranted to strengthen this conclusion.,The online version of this article (doi:10.1186/s12890-015-0138-4) contains supplementary material, which is available to authorized users. | 1 |
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