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Interactions between spirometry and patient-reported outcomes in COPD are not well understood.,This systematic review and study-level analysis investigated the relationship between changes in FEV1 and changes in health status with bronchodilator therapy.,Six databases (to October 2009) were searched to identify studies with long-acting bronchodilator therapy reporting FEV1 and health status, dyspnoea or exacerbations.,Mean and standard deviations of treatment effects were extracted for each arm of each study.,Relationships between changes in trough FEV1 and outcomes were assessed using correlations and random-effects regression modelling.,The primary outcome was St George's Respiratory Questionnaire (SGRQ) total score.,Thirty-six studies (≥3 months) were included.,Twenty-two studies (23,654 patients) with 49 treatment arms each contributing one data point provided SGRQ data.,Change in trough FEV1 and change in SGRQ total score were negatively correlated (r = -0.46, p < 0.001); greater increases in FEV1 were associated with greater reductions (improvements) in SGRQ.,The correlation strengthened with increasing study duration from 3 to 12 months.,Regression modelling indicated that 100 mL increase in FEV1 (change at which patients are more likely to report improvement) was associated with a statistically significant reduction in SGRQ of 2.5 (95% CI 1.9, 3.1), while a clinically relevant SGRQ change (4.0) was associated with 160.6 (95% CI 129.0, 211.6) mL increase in FEV1.,The association between change in FEV1 and other patient-reported outcomes was generally weak.,Our analyses indicate, at a study level, that improvement in mean trough FEV1 is associated with proportional improvements in health status. | Clinical trials of tiotropium have principally recruited patients from secondary care with more severe chronic obstructive pulmonary disease (COPD), and typically had included limitation of concomitant medication.,In primary care, which is the most common setting for COPD management, many patients may have milder disease, and also may take a broad range of concomitant medication.,This randomised, placebo-controlled, parallel-group, 12-week, 44-centre study investigated the efficacy (trough forced expiratory volume in 1 second [FEV1] response) and safety of additional treatment with once-daily tiotropium 18 μg via the HandiHaler® in a primary care COPD population (tiotropium: N = 191, FEV1 = 1.25 L [47.91% predicted]; placebo: N = 183, FEV1 = 1.32 L [49.86% predicted]).,Secondary endpoints included: trough forced vital capacity (FVC) response, weekly use of rescue short-acting β-agonist, and exacerbation of COPD (complex of respiratory symptoms/events of >3 days in duration requiring a change in treatment).,Treatment effects were determined using non-parametric analysis.,At Week 12, median improvement in trough FEV1 response with tiotropium versus placebo was 0.06 L (p = 0.0102).,The improvement was consistent across baseline treatment and COPD severity.,Median improvement in FVC at 2, 6 and 12 weeks was 0.12 L (p < 0.001).,The percentage of patients with ≥1 exacerbation was reduced (tiotropium 9.5%; placebo 17.9%; p = 0.0147), independent of disease severity.,Rescue medication usage was significantly reduced in the tiotropium group compared with placebo.,Adverse event profile was consistent with previous studies.,Tiotropium provides additional benefits to usual primary care management in a representative COPD population.,The identifier is: NCT00274079. | 1 |
Chronic obstructive pulmonary disease (COPD) is now the fourth leading cause of death in the world, and it continues to increase in developing countries.,The World Health Organization expects COPD to be the third most common cause of death in the world by 2020.,Effective and continuous postdischarge care can help patients to maintain good health.,The use of electronic health records (EHRs) as an element of community health care is new technology in China.,The aim of this study was to develop and evaluate a Web-based coaching program using EHRs for physical function and health-related quality of life for patients with COPD in China.,A randomized controlled trial was conducted from 2008 to 2015 at two hospitals.,The control group received routine care and the intervention group received routine care with the addition of the Web-based coaching program using EHRs.,These were used to manage patients’ demographic and clinical variables, publish relevant information, and have communication between patients and health care providers.,Participants were not blinded to group assignment.,The effects of the intervention were evaluated by lung function, including percent of forced expiratory volume in 1 second (FEV1%), percent of forced vital capacity (FVC%), peak expiratory flow (PEF), maximum midexpiratory flow; St George’s Respiratory Questionnaire (SGRQ); Modified Medical Research Council Dyspnea Scale (MMRC); and 6-Minute Walk Test (6MWT).,Data were collected before the program, and at 1, 3, 6, and 12 months after the program.,Of the 130 participants, 120 (92.3%) completed the 12-month follow-up program.,There were statistically significant differences in lung function (FEV1%: F1,4=5.47, P=.002; FVC%: F1,4=3.06, P=.02; PEF: F1,4=12.49, P<.001), the total score of SGRQ (F1,4=23.30, P<.001), symptoms of SGRQ (F1,4=12.38, P<.001), the activity of SGRQ (F1,4=8.35, P<.001), the impact of SGRQ (F1,4=12.26, P<.001), MMRC (F1,4=47.94, P<.001), and 6MWT (F1,4=35.54, P<.001) between the two groups with the variation of time tendency.,The Web-based coaching program using EHRs in China appears to be useful for patients with COPD when they are discharged from hospital into the community.,It promotes the sharing of patients’ medical information by hospital and community nurses, and achieves dynamic management and follow-up analysis for patients’ disease.,In addition, this program can postpone the decreasing rate of lung function, improve quality of life, decrease dyspnea, and increase physical capacity. | 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 |
Aims of this cross-sectional study were to assess health status and care dependency in patients with advanced chronic obstructive pulmonary disease (COPD) or chronic heart failure (CHF) and to identify correlates of an impaired health status.,The following outcomes were assessed in outpatients with advanced COPD (n = 105) or CHF (n = 80): clinical characteristics; general health status (EuroQol-5 Dimensions (EQ-5D); Assessment of Quality of Life instrument (AQoL); Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)); disease-specific health status (St.,Georges Respiratory Questionnaire (SGRQ), Minnesota Living with Heart Failure Questionnaire (MLHFQ)); physical mobility (timed ‘Up and Go’ test); and care dependency (Care Dependency Scale).,Patients with advanced COPD or CHF have an impaired health status and may be confronted with care dependency.,Multiple regression analyses have shown that physical and psychological symptoms, care dependency and number of drugs were correlated with impaired health status in advanced COPD or CHF, while demographic and clinical characteristics like age, gender, disease severity and co-morbidities were not correlated.,Clinical care should regularly assess symptom burden and care dependency to identify patients with advanced COPD or CHF at risk for an impaired health status. | The aims of this study were: (1) to compare the discriminative ability of a disease-specific instrument, the St.,George's Respiratory Questionnaire (SGRQ) to generic instruments (i.e., EQ-5D and SF-36); and (2), to evaluate the strength of associations among clinical and health-related quality of life (HRQL) measures in chronic obstructive pulmonary disease (COPD).,We analyzed data collected from 120 COPD patients in a Veterans Affairs hospital.,Patients self-completed two generic HRQL measures (EQ-5D and SF-36) and the disease-specific SGRQ.,The ability of the summary scores of these HRQL measures to discriminate COPD disease severity based on Global Obstructive Lung Disease (GOLD) stage was assessed using relative efficiency ratios (REs).,Strength of correlation was used to further evaluate associations between clinical and HRQL measures.,Mean total scores for PCS-36, EQ-VAS and SGRQ were significantly lower for the more severe stages of COPD (p < 0.05).,Using SGRQ total score as reference, the summary scores of the generic measures (PCS-36, MCS-36, EQ index, and EQ-VAS) all had REs of <1.,SGRQ exhibited a stronger correlation with clinical measures than the generic summary scores.,For instance, SGRQ was moderately correlated with FEV1 (r = 0.43), while generic summary scores had trivial levels of correlation with FEV1 (r < 0.2).,The SGRQ demonstrated greater ability to discriminate among different levels of severity stages of COPD than generic measures of health, suggestive that SGRQ may provide COPD studies with greater statistical power than EQ-5D and SF-36 summary scores to capture meaningful differences in clinical severity. | 1 |
Many patients with chronic obstructive pulmonary disease (COPD) continue to experience exacerbations despite receiving standard-of-care treatments.,Novel approaches to COPD treatment focus on understanding and targeting molecular mechanisms of airway inflammation, airway obstruction, remodeling and lung destruction.,Several identified phenotypes and endotypes of COPD will pave the future path for a more personalized approach to therapy.,Although well known to be associated with neutrophilic inflammation, COPD may also be driven by eosinophilic inflammation both at stable states and during exacerbation.,Targeting eosinophilic inflammation has been successful in managing severe eosinophilic asthma and may hold promise in certain phenotypes of COPD.,The most promising biologic treatments at an advanced stage of development are agents blocking interleukin (IL)-5 or its receptor.,This review examines our current understanding of the eosinophilic inflammation in COPD and the rationale for IL-5 targeting agents. | The immunopathology of chronic obstructive pulmonary disease (COPD) is based on the innate and adaptive inflammatory immune responses to the chronic inhalation of cigarette smoking.,In the last quarter of the century, the analysis of specimens obtained from the lower airways of COPD patients compared with those from a control group of age-matched smokers with normal lung function has provided novel insights on the potential pathogenetic role of the different cells of the innate and acquired immune responses and their pro/anti-inflammatory mediators and intracellular signalling pathways, contributing to a better knowledge of the immunopathology of COPD both during its stable phase and during its exacerbations.,This also has provided a scientific rationale for new drugs discovery and targeting to the lower airways.,This review summarises and discusses the immunopathology of COPD patients, of different severity, compared with control smokers with normal lung function. | 1 |
The extent of the survival benefit of augmentation therapy for alpha-1 antitrypsin deficiency (AATD) in individuals with advanced COPD is difficult to define.,We performed a retrospective analysis using all available data from the observational registry of individuals with severe deficiency of alpha-1 antitrypsin (AAT) conducted by the NHLBI investigators.,Individuals (N=1129) with severe deficiency of AAT were evaluated for mortality using all data sources and stratified by 10% increments of baseline forced expiratory volume in 1 second (FEV1) percent predicted and by augmentation therapy status (ever receiving versus never receiving).,Kaplan-Meier survival curves were constructed for each of the deciles comparing survival in treated vs non-treated groups.,A multivariable model was performed to define the correlates of survival in individuals with FEV1 <30% predicted.,Amongst all subjects, augmentation was associated with improved survival (p<0.0001).,Among the individuals ever receiving augmentation therapy, survival was better than for those not receiving augmentation at all 10% increments of FEV1% predicted from 10% to 60% (P values <0.05 in all deciles).,In subgroups of participants with hyperinflation defined as residual volume (RV)>120% predicted and in subgroups of participants with reduced diffusing capacity for carbon monoxide (DLCO) <70% predicted, there was significantly better survival for those ever receiving augmentation therapy than for those who never received augmentation (p<0.001).,A multivariable analysis showed that mortality benefit is influenced by age, DLCO % predicted, and augmentation therapy.,There is a survival benefit from augmentation therapy in AATD between FEV1 values in the 10-60% predicted range.,Screening and treatment of AATD patients should therefore not be limited by the severity of illness as defined by FEV1. | Alpha 1 antitrypsin deficiency is a hereditary condition characterized by low alpha 1 proteinase inhibitor (also known as alpha 1 antitrypsin [AAT]) serum levels.,Reduced levels of AAT allow abnormal degradation of lung tissue, which may ultimately lead to the development of early-onset emphysema.,Intravenous infusion of AAT is the only therapeutic option that can be used to maintain levels above the protective threshold.,Based on its biochemical efficacy, AAT replacement therapy was approved by the US Food and Drug administration in 1987.,However, there remained considerable interest in selecting appropriate outcome measures that could confirm clinical efficacy in a randomized controlled trial setting.,Using computed tomography as the primary measure of decline in lung density, the capacity for intravenously administered AAT replacement therapy to slow and modify the course of disease progression was demonstrated for the first time in the Randomized, Placebo-controlled Trial of Augmentation Therapy in Alpha-1 Proteinase Inhibitor Deficiency (RAPID) trial.,Following these results, an expert review forum was held at the European Respiratory Society to discuss the findings of the RAPID trial program and how they may change the landscape of alpha 1 antitrypsin emphysema treatment.,This review summarizes the results of the RAPID program and the implications for clinical considerations with respect to diagnosis, treatment and management of emphysema due to alpha 1 antitrypsin deficiency. | 1 |
COPD is among the major causes of death, and it is associated with several comorbid conditions.,Chronic kidney disease (CKD) is frequently diagnosed in older people living in Western societies and could impact COPD patients’ mortality.,We evaluated the relationship between burden of comorbidities, CKD, and mortality in a population-based cohort of patients discharged with a diagnosis of COPD.,A longitudinal cohort study was conducted evaluating 27,272 COPD patients.,Recruitment of COPD subjects and identification of CKD and other comorbidities summarized by the Charlson comorbidity index (CCI) were based on claims data coded according to the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM).,Severity of COPD was classified by hospital diagnosis or exemption from medical charges due to respiratory failure or previous hospitalizations for COPD.,The impact of comorbidities on survival was assessed by Cox regression.,Less than 40% of patients were still alive at the end of a median follow-up of 37 months (17 months for patients who died and 56 months for those alive at the end of follow-up).,After adjustment for age, gender, and severity score of COPD, CKD (hazard ratio =1.36, 95% confidence interval 1.30-1.42) independently from comorbidities summarized by the CCI was a significant risk factor for mortality.,In spite of limitations due to the use of claims data, long-term survival of COPD patients was heavily affected by the presence of CKD and other comorbidities. | Objective To evaluate the safety of benzodiazepines and opioids in patients with very severe chronic obstructive pulmonary disease (COPD).,Design Population based longitudinal consecutive cohort study.,Setting Centres prescribing long term oxygen therapy in Sweden.,Patients 2249 patients starting long term oxygen therapy for COPD in Sweden between 2005 and 2009 in the national Swedevox Register.,Main outcome measures Effects of benzodiazepines and opioids on rates of admission to hospital and mortality, adjusted for age, sex, arterial blood gases, body mass index (BMI), performance status, previous admissions, comorbidities, and concurrent drugs.,Results 1681 (76%) patients were admitted to hospital, and 1129 (50%) died under observation.,No patient was lost to follow-up.,Benzodiazepines and opioids were not associated with increased admission: hazard ratio 0.98 (95% confidence interval, 0.87 to 1.10) and 0.98 (0.86 to 1.10), respectively.,Benzodiazepines were associated with increased mortality (1.21, 1.05 to 1.39) with a dose response trend.,Opioids also had a dose response relation with mortality: lower dose opioids (≤30 mg oral morphine equivalents a day) were not associated with increased mortality (1.03, 0.84 to 1.26) in contrast with higher dose opioids (1.21, 1.02 to 1.44).,Concurrent benzodiazepines and opioids in lower doses were not associated with increased admissions (0.86, 0.53 to 1.42) or mortality (1.25, 0.78 to 1.99).,Associations were not modified by being naive to the drugs or by hypercapnia.,Conclusions Lower dose opioids are not associated with increased admissions or deaths in patients with COPD and might be safe for symptom reduction in severe respiratory disease. | 1 |
Mortality rate is high in patients with chronic obstructive pulmonary disease (COPD).,Our aim was to investigate long-term mortality and associated risk factors in COPD patients previously hospitalized for a COPD exacerbation.,A total of 256 patients from the Nordic countries were followed for 8.7 ± 0.4 years after the index hospitalization in 2000-2001.,Prior to discharge, the St George’s Respiratory Questionnaire was administered and data on therapy and comorbidities were obtained.,Information on long-term mortality was obtained from national registries in each of the Nordic countries.,In total, 202 patients (79%) died during the follow up period, whereas 54 (21%) were still alive.,Primary cause of death was respiratory (n = 116), cardiovascular (n = 43), malignancy (n = 28), other (n = 10), or unknown (n = 5).,Mortality was related to older age, with a hazard risk ratio (HRR) of 1.75 per 10 years, lower forced expiratory volume in 1 second (FEV1) (HRR 0.80), body mass index (BMI) <20 kg/m2 (HRR 3.21), and diabetes (HRR 3.02).,Older age, lower BMI, and diabetes were related to both respiratory and cardiovascular mortality.,An association was also found between lower FEV1 and respiratory mortality, whereas mortality was not significantly associated with therapy, anxiety, or depression.,Almost four out of five patients died within 9 years following an admission for COPD exacerbation.,Increased mortality was associated with older age, lower lung function, low BMI, and diabetes, and these factors should be taken into account when making clinical decisions about patients who have been admitted to hospital for a COPD exacerbation. | Chronic obstructive pulmonary disease (COPD) is characterised by pulmonary and systemic inflammation which flare-up during episodes of acute exacerbation (AECOPD).,Given the role of Toll-like receptors (TLRs) in the induction of inflammatory responses we investigated the involvement of TLRs in COPD pathogenesis.,The expression of TLR-2, TLR-4 and CD14 in monocytes was analyzed by flow cytometry.,To study the functional responses of these receptors, monocytes were stimulated with peptidoglycan or lipopolysaccharide and the amounts of TNFα and IL-6 secreted were determined by ELISA.,We found that the expression of TLR-2 was up-regulated in peripheral blood monocytes from COPD patients, either clinically stable or during AECOPD, as compared to never smokers or smokers with normal lung function.,Upon stimulation with TLR-2 ligand monocytes from COPD patients secreted increased amounts of cytokines than similarly stimulated monocytes from never smokers and smokers.,In contrast, the expressions of TLR-4 and CD14 were not significantly different between groups, and the response to lipopolysaccharide (a TLR-4 ligand) stimulation was not significantly different either.,At discharge from hospital TLR-2 expression was down-regulated in peripheral blood monocytes from AECOPD patients.,This could be due to the treatment with systemic steroids because, in vitro, steroids down-regulated TLR-2 expression in a dose-dependent manner.,Finally, we demonstrated that IL-6, whose plasma levels are elevated in patients, up-regulated in vitro TLR-2 expression in monocytes from never smokers.,Our results reveal abnormalities in TLRs expression in COPD patients and highlight its potential relationship with systemic inflammation in these patients. | 1 |
Patients with COPD have frequent exacerbations.,The role of respiratory viral infection is just emerging.,We wished to determine prospectively the incidence of viral infection in exacerbated and stable COPD patients as well as smokers who do not have airways obstruction.,Stable and exacerbated COPD patients were recruited along with a group of patients who had smoked but who did not have any airways obstruction.,Spirometry was performed and sputum specimens were tested for a range of 12 different respiratory viruses using PCR.,One hundred and thirty-six patients with exacerbations of COPD, 68 stable COPD patients and 16 non-obstructed smokers were recruited.,A respiratory virus was detected in 37% of exacerbations, 12% of stable COPD patients and 12% of non-obstructed smokers, p < 0.0005.,Rhinovirus was most frequently detected.,The symptom of fever was associated with virus detection, p < 0.05.,Infection with more than one virus was only found in the exacerbated COPD patients.,Respiratory viral infection is associated with exacerbations of COPD.,Rhinovirus was the most common infecting agent identified and in two cases human metapneumovirus was also detected.,Dual infections were only seen amongst those patients admitted to hospital with acute exacerbations of COPD.,Viruses were more commonly detected in those with more severe airways disease. | The inflammatory responses and associated clinical severity of COPD exacerbations are greatly variable, and the determinants of these factors are poorly understood.,We examined the hypothesis that bacteria and viruses may modulate this heterogeneity and that interactions between bacterial and viral infection may affect changes in airway bacterial load and the clinical features and inflammatory responses of exacerbations in patients with COPD.,Prospective cohort study.,Outpatient Department, London Chest Hospital, London, UK.,Thirty-nine patients with COPD.,We prospectively studied 56 COPD exacerbations, obtaining clinical data and paired sputum and serum samples at baseline and exacerbation.,Qualitative and quantitative microbiology, polymerase chain reaction detection for rhinovirus, and estimation of cytokine levels by enzyme-linked immunosorbent assay were performed.,A total of 69.6% of exacerbations were associated with a bacterial pathogen, most commonly Haemophilus influenzae.,Rhinovirus was identified in 19.6% of exacerbations.,The rise in bacterial load at exacerbation correlated with the rise in sputum interleukin (IL)-8 (r = 0.37, p = 0.022) and fall in FEV1 (r = 0.35, p = 0.048).,Exacerbations with both rhinovirus and H influenzae had higher bacterial loads (108.56 cfu/mL vs 108.05cfu/mL, p = 0.018) and serum IL-6 (13.75 pg/mL vs 6.29 pg/mL, p = 0.028) than exacerbations without both pathogens.,In exacerbations with both cold symptoms (a marker of putative viral infection) and a bacterial pathogen, the FEV1 fall was greater (20.3% vs 3.6%, p = 0.026) and symptom count was higher (p = 0.019) than those with a bacterial pathogen alone.,The clinical severity and inflammatory responses in COPD exacerbations are modulated by the nature of the infecting organism: bacterial and viral pathogens interact to cause additional rises in inflammatory markers and greater exacerbation severity. | 1 |
High-intensity noninvasive ventilation (NIV) has been shown to improve outcomes in stable chronic obstructive pulmonary disease patients.,However, there is insufficient knowledge about whether with this more controlled ventilatory mode optimal respiratory muscle unloading is provided without an increase in patient-ventilator asynchrony (PVA).,Ten chronic obstructive pulmonary disease patients on home mechanical ventilation were included.,Four different ventilatory settings were investigated in each patient in random order, each for 15 min, varying the inspiratory positive airway pressure and backup breathing frequency.,With surface electromyography (EMG), activities of the intercostal muscles, diaphragm, and scalene muscles were determined.,Furthermore, pressure tracings were derived simultaneously in order to assess PVA.,Compared to spontaneous breathing, the most pronounced decrease in EMG activity was achieved with the high-pressure settings.,Adding a high breathing frequency did reduce EMG activity per breath, while the decrease in EMG activity over 1 min was comparable with the high-pressure, low-frequency setting.,With high backup breathing frequencies less breaths were pressure supported (25% vs 97%).,PVAs occurred more frequently with the low-frequency settings (P=0.017).,High-intensity NIV might provide optimal unloading of respiratory muscles, without undue increases in PVA. | Noninvasive ventilation (NIV) improves gas-exchange and symptoms in selected chronic obstructive pulmonary disease (COPD) patients with hypercapnic respiratory failure.,We hypothesized NIV reverses respiratory failure by one or all of increased ventilatory response to carbon-dioxide, reduced respiratory muscle fatigue, or improved pulmonary mechanics.,Nineteen stable COPD patients (forced expiratory volume in one second 35% predicted) were studied at baseline (D0), 5-8 days (D5) and 3 months (3M) after starting NIV.,Ventilator use was 6.2 (3.7) hours per night at D5 and 3.4 (1.6) at 3M (p = 0.12).,Mean (SD) daytime arterial carbon-dioxide tension (PaCO2) was reduced from 7.4 (1.2) kPa to 7.0 (1.1) kPa at D5 and 6.5 (1.1) kPa at 3M (p = 0.001).,Total lung capacity decreased from 107 (28) % predicted to 103 (28) at D5 and 103 (27) % predicted at 3M (p = 0.035).,At D5 there was an increase in the hypercapnic ventilatory response and some volitional measures of inspiratory and expiratory muscle strength, but not isolated diaphragmatic strength whether assessed by volitional or nonvolitional methods.,These findings suggest decreased gas trapping and increased ventilatory sensitivity to CO2 are the principal mechanism underlying improvements in gas-exchange in patients with COPD following NIV.,Changes in some volitional but not nonvolitional muscle strength measures may reflect improved patient effort. | 1 |
Current evidence suggests that roflumilast is efficacious in treating COPD, especially in preventing the acute exacerbation of COPD.,This study was designed to evaluate the clinical effects and safety of roflumilast in the treatment of stable COPD using randomized clinical trial (RCT) data.,A MEDLINE, EMBASE, and Cochrane Controlled Trials Register search was carried out.,RCTs reporting the treatment effects of roflumilast in COPD were identified.,Relevant data were extracted and a meta-analysis was performed.,A total of nine articles and 13 RCT studies were identified.,Overall, 29.1% of the subjects in the roflumilast group showed evidence of exacerbation.,The corresponding figure was 32.2% in the placebo group.,According to pooled analysis, the use of roflumilast reduced COPD exacerbations in comparison to placebo (odds ratio [OR] =0.82, 95% confidence interval [CI] =0.75-0.9).,The quality of life and spirometry were improved.,For patients receiving baseline pre-bronchodilators, their average forced expiratory volume in the first second showed evidence of change when they took roflumilast (64.88 mL; 95% CI =54.09-75.66).,Those who took placebo showed no evidence of change.,Similar result was observed in patients receiving baseline (54.49 mL; 95% CI =44.04-64.94).,As for the safety of roflumilast treatment, the overall cumulative incidence of adverse drug reaction was 54.2% in the roflumilast group and 48.2% in the placebo group (OR =1.36, 95% CI =1.13-1.65).,The adverse effects included diarrhea, headache, nausea, weight loss, and insomnia.,The efficacy of roflumilast in the prevention of acute exacerbation of COPD is obvious.,Roflumilast is proved to be able to improve spirometry of COPD patients.,The adverse drug reaction did not increase significantly in the roflumilast group compared with the control group.,COPD patients can benefit from roflumilast therapy.,However, our results are limited by the cohort design of the selected studies and the degree of heterogeneity among them; hence, more randomized trials are needed to further support this conclusion. | Despite the benefits of beta-blockers in patients with established or sub-clinical coronary artery disease, their use in patients with chronic obstructive pulmonary disease (COPD) has been controversial.,Currently, no systematic review has examined the impact of beta-blockers on mortality in COPD.,We systematically searched electronic bibliographic databases including MEDLINE, EMBASE and Cochrane Library for clinical studies that examine the association between beta-blocker use and all cause mortality in patients with COPD.,Risk ratios across studies were pooled using random effects models to estimate a pooled relative risk across studies.,Publication bias was assessed using a funnel plot.,Our search identified nine retrospective cohort studies that met the study inclusion criteria.,The pooled relative risk of COPD related mortality secondary to beta-blocker use was 0.69 (95% CI: 0.62-0.78; I2=82%).,The results of this review are consistent with a protective effect of beta-blockers with respect to all cause mortality.,Due to the observational nature of the included studies, the possibility of confounding that may have affected these results cannot be excluded.,The hypothesis that beta blocker therapy might be of benefit in COPD needs to be evaluated in randomised controlled trials. | 1 |
Prediction of future exacerbations of chronic obstructive pulmonary disease (COPD) is a major concern for long-term management of this disease.,To determine which of three multidimensional assessment systems (the body mass index, obstruction, dyspnea, and exercise capacity [BODE] index; dyspnea, obstruction, smoking, exacerbations [DOSE] index; or age, dyspnea, obstruction [ADO] index) is superior for predicting exacerbations.,This was a 2-year prospective cohort study of COPD patients.,Pulmonary function tests, the 6-minute walk distance (6MWD), Modified Medical Respiratory Council (MMRC) dyspnea scores, chest computed-tomography measurements, and body composition were analyzed, and predictions of exacerbation by the three assessment systems were compared.,Among 183 patients who completed the study, the mean annual exacerbation rate was 0.57 events per patient year, which correlated significantly with lower predicted forced expiratory volume in 1 second (FEV1) (P < 0.001), lower transfer coefficient of the lung for carbon monoxide (%DLco/VA) (P = 0.021), lesser 6MWD (P = 0.016), higher MMRC dyspnea score (P = 0.001), higher DOSE index (P < 0.001), higher BODE index (P = 0.001), higher ADO index (P = 0.001), and greater extent of emphysema (P = 0.002).,For prediction of exacerbation, the areas under the curves were larger for the DOSE index than for the BODE and ADO indices (P < 0.001).,Adjusted multiple logistic regression identified the DOSE index as a significant predictor of risk of COPD exacerbation.,In this study, the DOSE index was a better predictor of exacerbations of COPD when compared with the BODE and ADO indices. | A growing number of prognostic indices for chronic obstructive pulmonary disease (COPD) is developed for clinical use.,Our aim is to identify, summarize and compare all published prognostic COPD indices, and to discuss their performance, usefulness and implementation in daily practice.,We performed a systematic literature search in both Pubmed and Embase up to September 2010.,Selection criteria included primary publications of indices developed for stable COPD patients, that predict future outcome by a multidimensional scoring system, developed for and validated with COPD patients only.,Two reviewers independently assessed the index quality using a structured screening form for systematically scoring prognostic studies.,Of 7,028 articles screened, 13 studies comprising 15 indices were included.,Only 1 index had been explored for its application in daily practice.,We observed 21 different predictors and 7 prognostic outcomes, the latter reflecting mortality, hospitalization and exacerbation.,Consistent strong predictors were FEV1 percentage predicted, age and dyspnoea.,The quality of the studies underlying the indices varied between fairly poor and good.,Statistical methods to assess the predictive abilities of the indices were heterogenic.,They generally revealed moderate to good discrimination, when measured.,Limitations: We focused on prognostic indices for stable disease only and, inevitably, quality judgment was prone to subjectivity.,We identified 15 prognostic COPD indices.,Although the prognostic performance of some of the indices has been validated, they all lack sufficient evidence for implementation.,Whether or not the use of prognostic indices improves COPD disease management or patients' health is currently unknown; impact studies are required to establish this. | 1 |
Use of inhaled corticosteroids (ICS) increases the risk of pneumonia in chronic obstructive pulmonary disease (COPD), but the magnitude of risk with different ICS remains unclear.,A post hoc analysis of the 4-year UPLIFT® trial to assess whether pneumonia risk differed by type of ICS (fluticasone propionate [FP], other ICS, or no ICS) in permanent users (defined by use until end of study) or in users at baseline (sensitivity analysis).,For the permanent-users analysis, 825 patients receiving FP throughout the trial, 825 patients receiving other ICS and 825 patients not receiving ICS were matched on relevant baseline features 1:1:1.,A significantly greater risk of pneumonia was observed for FP versus no ICS: the hazard ratio (HR) for risk of pneumonia was 1.33 (95% confidence interval [CI] 1.00, 1.75; p = 0.046) and the rate ratio (RR) was 1.58 (95% CI 1.05, 2.37; p = 0.028).,A greater risk was also found for FP versus other ICS: HR 1.28 (95% CI 0.97, 1.68; p = 0.078) and RR 1.48 (95% CI 1.00, 2.19; p = 0.049).,A higher proportion of patients on FP were hospitalized with pneumonia (7.9%) versus other ICS (6.7%) or no ICS (5.9%).,Whilst other ICS use was associated with the highest number of fatal pneumonia events, the total number of fatal pneumonia incidents was low.,A similar pattern was observed in the sensitivity analyses, which included 4002 patients on different treatments at baseline (FP, other ICS, and no ICS) and considered potential switches during the study.,The results support existing evidence of an increased pneumonia risk with FP use compared with other ICS and no ICS use in patients with COPD.,Healthcare professionals should evaluate the risk-benefit ratio of using ICS when making treatment decisions with their patients.,Post hoc analysis of UPLIFT®.,ClinicalTrials.gov number: NCT00144339.,Retrospectively registered September 2, 2005.,The online version of this article (10.1186/s12931-018-0874-0) contains supplementary material, which is available to authorized users. | An association between chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) has been described, mainly due to smoking and corticosteroid use.,Whether inhaled corticosteroid (ICS) therapy is associated with an increased risk of TB remains unclear.,We selected COPD cases by using six diagnostic scenarios and control subjects from a nationwide health insurance database, and applied time-dependent Cox regression analysis to identify the risk factors for TB.,Among 1,000,000 beneficiaries, 23,594 COPD cases and 47,188 non-COPD control subjects were selected.,Cox regression analysis revealed that age, male gender, diabetes mellitus, end-stage renal disease, and cirrhosis, as well as COPD (hazard ratio = 2.468 [2.205-2.762]) were independent risk factors for TB.,Among the COPD cases, those who developed TB received more oral corticosteroids and oral β-agonists.,Time-dependent Cox regression analysis revealed that age, male gender, diabetes mellitus, low income, oral corticosteroid dose, and oral β-agonist dose, but not ICS dose, were independent risk factors for TB.,The identified risk factors and their hazard ratios were similar among the COPD cases selected using different scenarios.,Keeping a high suspicion and regularly monitoring for the development of pulmonary TB in COPD patients are necessary, especially for those receiving higher doses of oral corticosteroids and other COPD medications.,Although ICS therapy has been shown to predispose COPD patients to pneumonia in large randomized clinical trials, it does not increase the risk of TB in real world practice. | 1 |
Real-world prescription pathways leading to triple therapy (TT) (inhaled corticosteroid [ICS] plus long-acting β2-agonist bronchodilator [LABA] plus long-acting muscarinic antagonist) differ from Global initiative for chronic Obstructive Lung Disease [GOLD] and National Institute for Health and Care Excellence treatment recommendations.,This study sets out to identify COPD patients without asthma receiving TT, and determine the pathways taken from diagnosis to the first prescription of TT.,This was a historical analysis of COPD patients without asthma from the Optimum Patient Care Research Database (387 primary-care practices across the UK) from 2002 to 2010.,Patient disease severity was classified using GOLD 2013 criteria.,Data were analyzed to determine prescribing of TT before, at, and after COPD diagnosis; the average time taken to receive TT; and the impact of lung function grade, modified Medical Research Council dyspnea score, and exacerbation history on the pathway to TT.,During the study period, 32% of patients received TT.,Of these, 19%, 28%, 37%, and 46% of patients classified as GOLD A, B, C, and D, respectively, progressed to TT after diagnosis (P<0.001).,Of all patients prescribed TT, 25% were prescribed TT within 1 year of diagnosis, irrespective of GOLD classification (P=0.065).,The most common prescription pathway to TT was LABA plus ICS.,It was observed that exacerbation history did influence the pathway of LABA plus ICS to TT.,Real life UK prescription data demonstrates the inappropriate prescribing of TT and confirms that starting patients on ICS plus LABA results in the inevitable drift to overuse of TT.,This study highlights the need for dissemination and implementation of COPD guidelines to physicians, ensuring that patients receive the recommended therapy. | A variety of large randomized controlled trials (RCT’s) evaluating pharmacotherapy in chronic obstructive pulmonary disease (COPD) patients does exist.,One of the drugs that has been tested is the new long-acting anticholinergic glycopyrronium bromide.,As the generalizability of results from RCT’s is questionable we designed a longitudinal, prospective non-interventional study (DACCORD) of two years duration plus two years extension with at least 6000 participants in approximately 500 primary and secondary care practices in Germany (within the new established COPD National Prospective Registry), to assess patient reported outcomes (PRO’s), lung function, adherence and drug safety.,To circumvent the hurdle of inappropriate COPD diagnosis in a non-interventional trial, patients have to fulfill the inclusion criteria of the COPD disease management program (DMP) of the German statutory health insurances.,Patient management should follow the German national COPD guidelines, which are based on Global Initiative for Chronic Obstructive Lung Disease 2007 (GOLD) report.,Labels of prescribed drugs should also be taken into account.,Patients received treatment as part of their standard care: at the discretion of the investigator patients were included in one of two arms.,A: standard care with glycopyrronium containing regimen, and arm B: standard care without glycopyrronium.,For 2016 we expect important results regarding longitudinal development of PRO’s including exacerbations, lung function, adherence and side effects.,We also investigate applicability of the new GOLD staging system in usual care.,Data on diagnostic and treatment modalities in current German primary and secondary care, as well as pharmaco-economic data will be generated.,1.,German Register for non-interventional studies: http://www.vfa.de/de/arzneimittel-forschung/datenbanken-zu-arzneimitteln/nisdb.,2.,EMA EnCePP http://www.encepp.eu/. | 1 |
The objective of the study is to develop a scoring system for predicting a 90-day re-exacerbation in hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,A total of 176 consecutive hospitalized patients with AECOPD were included.,The sociodemographic characteristics, status before acute exacerbation (AE), presentations of and treatment for the current AE, and the re-exacerbation in 90 days after discharge from hospital were collected.,The re-exacerbation rate in 90 days was 48.9% (86 out of 176).,It was associated with the degree of lung function impairment (Global initiative for chronic Obstructive Lung Disease [GOLD] grades), frequency of AE in the previous year, and parameters of the current AE, including pleural effusion, use of accessory respiratory muscles, inhaled long-acting β-2-agonists, inhaled corticosteroids, controlled oxygen therapy, noninvasive mechanical ventilation, and length of hospital stay, but was not associated with body mass index, modified Medical Research Council scale, or chronic obstructive pulmonary disease assessment test.,A subgroup of ten variables was selected and developed into the re-exacerbation index scoring system (age grades, GOLD grades, AE times in the previous year, pleural effusion, use of accessory respiratory muscles, noninvasive mechanical ventilation, controlled oxygen therapy, inhaled long-acting β-2-agonists and inhaled corticosteroids, and length of hospital stay).,The re-exacerbation index showed good discrimination for re-exacerbation, with a C-statistic of 0.750 (P<0.001).,A comprehensive assessment integrating parameters of stable chronic obstructive pulmonary disease, clinical presentations at exacerbation, and treatment showed a strong predictive capacity for short-term outcome in patients with AECOPD.,Further studies are required to verify these findings. | This study was conducted to describe the different antibiotics that are used in the home management of chronic obstructive pulmonary disease (COPD) exacerbations and to estimate the failure rates following the initiation of the antibiotic.,A cohort study was conducted.,Patients enrolled in a COPD home management program were included in the analysis.,Failure rates were defined as an additional prescription of an antibiotic, an emergency room visit, or a hospitalization for a COPD exacerbation in the 30 days following the initiation of the antibiotic.,A total of 1180 episodes of antibiotic treatment were analyzed.,Overall, 348 episodes led to a failure (29.5%).,The most frequently used antibiotics were cefuroxime (45.9%) and ciprofloxacin (21.1%).,This project demonstrates that a wide range of antibiotics were prescribed to our population of COPD patients with a moderate to severe form of the disease.,Many treatment failures (about 30%) occurred in the 30-day period following the initiation of the home therapy with an antibiotic.,Clinicians should be aware of this high failure rate when managing mild exacerbations of COPD at home. | 1 |
Focusing on the advanced non-small cell lung cancer (NSCLC) patients without driver mutations can elucidate the clinical impact of COPD on treatment outcomes.,The present study evaluated the effects of COPD on the overall survival of driver mutation-negative NSCLC patients undergoing conventional chemotherapy as the first-line treatment.,Medical records of stage IIIB and IV NSCLC patients from January 2008 to December 2015 from six university hospitals were reviewed.,The total study population consisted of 197 patients; 92 (46.7%) were COPD patients and 105 (53.3%) were non-COPD patients.,The median survival in the non-COPD group was 11.5 months, compared to 9.2 months in the COPD group.,Univariate analysis showed that old age (>70 years), high Eastern Cooperative Oncology Group status score (2-3), squamous cell histology, and COPD were risk factors for mortality.,The presence of COPD was a significant prognostic factor in univariate analysis (hazard ratio [HR], 1.402; p=0.037), but not in multivariate analysis (HR, 1.275; p=0.144).,Subgroup analysis of 143 smokers showed that COPD was a significant prognostic factor on multivariate analysis (HR, 1.726; p=0.006).,In 154 stage IV patients, COPD was also a prognostic factor in multivariate analysis (HR, 1.479; p=0.039).,COPD had a negative impact on overall survival in the stage IV NSCLC and smoker NSCLC patients who underwent conventional chemotherapy. | The reticular basement membrane (Rbm) in smokers and especially smokers with COPD is fragmented with "clefts" containing cells staining for the collagenase matrix-metalloproteinase-9 (MMP-9) and fibroblast protein, S100A4.,These cells are also present in the basal epithelium.,Such changes are likely hallmarks of epithelial mesenchymal transition (EMT).,We aimed to confirm the epithelial origin of these Rbm cells, and to exclude potential confounding by infiltrating inflammatory cells.,Endobronchial biopsy sections from 17 COPD current smokers, with documented Rbm splitting and cellularity were stained for neutrophil elastase (neutrophil marker), CD68 (macrophage/mature fibroblasts), CD4+/CD8+ T lymphocytes, CD19 (B-cells), CD11c (dendritic cells/inflammatory cells), and S100 (Langerhans cells).,The number of cells in the Rbm and epithelium staining for these "inflammatory" cell markers were then compared to numbers staining for S100A4, "a documented EMT epitope".,Slides were double stained for S100A4 and cytokeratin(s).,In the basal epithelium significantly more cells stained for S100A4 compared to infiltrating macrophages, fibroblasts or immune cells: median, 26 (21.3 - 37.3) versus 0 (0 - 9.6) per mm, p < 0.003.,Markedly more S100A4 staining cells were also observed in the Rbm compared to infiltrating macrophages, neutrophils, fibroblasts or immune cells or any sub-type: 58 (37.3 - 92.6) versus 0 (0 - 4.8) cells/mm Rbm, p < 0.003.,Cells in the basal epithelium 26 (21.3 - 37.3) per mm) and Rbm (5.9 (2.3 - 13.8) per mm) frequently double stained for both cytokeratin and S100A4.,These data provide additional support for active EMT in COPD airways. | 1 |
The aim of the study was to determine the nutritional status and anthropometric values in a group of patients with COPD and to examine the relationship between these factors and disease severity.,A total of 105 COPD patients were included in this cross-sectional study.,The patients underwent spirometric exmination.,Mini nutritional assessment form was applied, and the anthropometric values of the patients were measured by bioelectrical impedance method.,Nutrient registration forms were given using a 3-day, 24-hour recall method to assess the nutrient uptake.,COPD severity was determined using the Global Initiative for Chronic Obstructive Lung Disease criteria, and the correlations between nutritional status and disease severity parameters were measured.,The prevalence of malnutrition in our patients with COPD was found to be 17%.,Spirometric parameters were found to be significantly lower in patients with low body mass index (BMI) and malnutrition.,As the modified Medical Research Council dyspnea scale score increased, the frequency of malnutrition increased (P=0.002).,Positive significant correlation was found between spirometric variables and muscle mass and fat external tissue volume of the patients.,Patients receiving higher protein content in diet showed a better muscle mass amount (P<0.001).,Our study results confirmed that malnutrition is an important and frequently encountered problem in COPD patients, and spirometric values of the patients with malnourishment and with low BMI are significantly lower.,We think that nutritional status should be evaluated in every COPD patient, and nutritional intake should be tailored individually. | Neutrophil to lymphocyte ratio (NLR) in peripheral blood is a useful systemic inflammatory response biomarker.,However, NLR has not been studied in patients with chronic obstructive pulmonary disease (COPD).,This study was aimed to evaluate the usefulness of NLR in patients with COPD.,NLR was prospectively measured and compared in patients with COPD exacerbation (n = 59), patients with stable COPD (n = 61), and healthy controls (n = 28).,NLR in patients with COPD exacerbation was repeatedly measured in the convalescent period.,The correlation between NLR and clinical parameters was evaluated, and the predictors for respiratory hospitalization were analyzed by multivariate logistic regression.,NLR values were significantly higher in patients with COPD exacerbation compared with stable COPD patients and controls (12.4 ± 10.6, 2.4 ± 0.7, 1.4 ± 0.5, respectively; p < 0.001).,NLR was significantly decreased during the convalescent period in patients with COPD exacerbation (4.5 ± 4.6 vs.,11.5 ± 8.8, p < 0.001).,NLR exhibited a significant correlation with the body mass index, degree of airway obstruction, dyspnea, and exercise capacity (BODE) index, the 6-minute walk test, and the modified Medical Research Council scale.,NLR ≥ 2.8 was an independent predictor with a borderline significance for respiratory hospitalization (odds ratio, 2.083; p = 0.079).,Body mass index and forced expiratory volume in 1 second were independent predictors for respiratory hospitalization.,NLR is a straightforward and effective biomarker of COPD exacerbation that may serve as a predictor for respiratory hospitalization in patients with COPD. | 1 |
Patients with severe chronic obstructive pulmonary disease (COPD) are at increased risk of infection by P. aeruginosa.,The specific role of bronchiectasis in both infection and chronic colonization by this microorganism in COPD, however, remains ill defined.,To evaluate the prevalence and risk factors for P. aeruginosa recovery from sputum in outpatients with severe COPD, characterizing P. aeruginosa isolates by pulsed-field gel electrophoresis (PFGE) and focusing on the influence of bronchiectasis on chronic colonization in these patients.,A case-cohort study of 118 patients with severe COPD attended at a Respiratory Day Unit for an acute infectious exacerbation and followed up over one year.,High-resolution CT scans were performed during stability for bronchiectasis assessment and sputum cultures were obtained during exacerbation and stability in all patients.,P. aeruginosa isolates were genotyped by PFGE.,Determinants of the recovery of P. aeruginosa in sputum and chronic colonization by this microorganism were assessed by multivariate analysis.,P. aeruginosa was isolated from 41 of the 118 patients studied (34.7%).,Five of these 41 patients (12.2%) with P. aeruginosa recovery fulfilled criteria for chronic colonization.,In the multivariate analysis, the extent of bronchiectasis (OR 9.8, 95% CI: 1.7 to 54.8) and the number of antibiotic courses (OR 1.7, 95% CI: 1.1 to 2.5) were independently associated with an increased risk of P. aeruginosa isolation.,Chronic colonization was unrelated to the presence of bronchiectasis (p=0.75).,In patients with chronic colonization the isolates of P. aeruginosa retrieved corresponded to the same clones during the follow-up, and most of the multidrug resistant isolates (19/21) were harbored by these patients.,The main risk factors for P. aeruginosa isolation in severe COPD were the extent of bronchiectasis and exposure to antibiotics.,Over 10% of these patients fulfilled criteria for chronic colonization by P. aeruginosa and showed clonal persistence, independently of the presence of bronchiectasis. | The purpose of this study was to investigate the clinical efficacy and safety of a fixed-dose combination of mometasone furoate/formoterol fumarate (MF/F) administered via a metered-dose inhaler in subjects with moderate-to-very severe chronic obstructive pulmonary disease (COPD).,This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension.,Subjects (n = 1196), at least 40 years old, were current or ex-smokers randomized to twice-daily inhaled MF/F 400/10 μg, MF/F 200/10 μg, MF 400 μg, F 10 μg, or placebo.,The trial’s co-primary endpoints were mean changes from baseline, as area under the curve (AUC), in forced expiratory volume (FEV1) over 0-12 hours (AUC0-12 h FEV1) with MF/F versus MF, and in morning (AM) pre-dose (trough) FEV1 with MF/F versus F after 13 weeks of treatment.,Key secondary endpoints were the effects of MF/F on respiratory health status using the Saint George’s Respiratory Questionnaire (SGRQ), symptom-free nights, partly stable COPD at 26 weeks, and time to first COPD exacerbation.,The largest improvements in AUC0-12 h FEV1 were observed with MF/F 400/10 μg and MF/F 200/10 μg.,Serial spirometry results demonstrated that bronchodilator effects with MF/F occurred rapidly (within 5 minutes), persisted for 12 hours after dosing, and were sustained over the 26-week treatment period.,Similar findings were observed for AM pre-dose FEV1, for which effects were further investigated, excluding subjects whose AM FEV1 data were incorrectly collected after 2 days from the last dose of study treatment.,Improvements in SGRQ scores surpassed the minimum clinically important difference of more than four units with both MF/F treatments.,At 26 weeks, no notable between-treatment differences in the occurrence and nature of adverse events (AEs) were reported.,No unexpected AEs were observed.,Overall, 90 subjects reported AEs considered to be treatment-related, the most common of which were lenticular opacities, dysphonia, and oral candidiasis.,In conclusion, MF/F treatments improved lung function and respiratory health status, reduced exacerbations, and were well tolerated in subjects with moderate-to-very severe COPD. | 1 |
Objective To assess the effect of second generation, home based telehealth on health related quality of life, anxiety, and depressive symptoms over 12 months in patients with long term conditions.,Design A study of patient reported outcomes (the Whole Systems Demonstrator telehealth questionnaire study; baseline n=1573) was nested in a pragmatic, cluster randomised trial of telehealth (the Whole Systems Demonstrator telehealth trial, n=3230).,General practice was the unit of randomisation, and telehealth was compared with usual care.,Data were collected at baseline, four months (short term), and 12 months (long term).,Primary intention to treat analyses tested treatment effectiveness; multilevel models controlled for clustering by general practice and a range of covariates.,Analyses were conducted for 759 participants who completed questionnaire measures at all three time points (complete case cohort) and 1201 who completed the baseline assessment plus at least one other assessment (available case cohort).,Secondary per protocol analyses tested treatment efficacy and included 633 and 1108 participants in the complete case and available case cohorts, respectively.,Setting Provision of primary and secondary care via general practices, specialist nurses, and hospital clinics in three diverse regions of England (Cornwall, Kent, and Newham), with established integrated health and social care systems.,Participants Patients with chronic obstructive pulmonary disease (COPD), diabetes, or heart failure recruited between May 2008 and December 2009.,Main outcome measures Generic, health related quality of life (assessed by physical and mental health component scores of the SF-12, and the EQ-5D), anxiety (assessed by the six item Brief State-Trait Anxiety Inventory), and depressive symptoms (assessed by the 10 item Centre for Epidemiological Studies Depression Scale).,Results In the intention to treat analyses, differences between treatment groups were small and non-significant for all outcomes in the complete case (0.480≤P≤0.904) or available case (0.181≤P≤0.905) cohorts.,The magnitude of differences between trial arms did not reach the trial defined, minimal clinically important difference (0.3 standardised mean difference) for any outcome in either cohort at four or 12 months.,Per protocol analyses replicated the primary analyses; the main effect of trial arm (telehealth v usual care) was non-significant for any outcome (complete case cohort 0.273≤P≤0.761; available case cohort 0.145≤P≤0.696).,Conclusions Second generation, home based telehealth as implemented in the Whole Systems Demonstrator Evaluation was not effective or efficacious compared with usual care only.,Telehealth did not improve quality of life or psychological outcomes for patients with chronic obstructive pulmonary disease, diabetes, or heart failure over 12 months.,The findings suggest that concerns about potentially deleterious effect of telehealth are unfounded for most patients.,Trial Registration ISRCTN43002091. | Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD).,We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.,This retrospective analysis of data from the 4-year UPLIFT® (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo.,Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0, >0-1, >1-2, and >2).,Spirometry and the St George’s Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry).,In total, 5992 patients (mean age 65 years, 75% male) were randomized.,Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV1) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units).,Corresponding rates of decline in postbronchodilator FEV1 (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium).,Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium).,The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium).,The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations.,Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD.,Increasing rates of hospitalized exacerbations are associated with increasing risk of death. | 1 |
The prognostic role of the arterial blood gas tension of carbon dioxide (PaCO2) in severe Chronic Obstructive Pulmonary Disease (COPD) remains unknown.,The aim of this study was to estimate the association between PaCO2 and mortality in oxygen-dependent COPD.,National prospective study of patients starting long-term oxygen therapy (LTOT) for COPD in Sweden between October 1, 2005 and June 30, 2009, with all-cause mortality as endpoint.,The association between PaCO2 while breathing air, PaCO2 (air), and mortality was estimated using Cox regression adjusted for age, sex, arterial blood gas tension of oxygen (PaO2), World Health Organization performance status, body mass index, comorbidity, and medications.,Of 2,249 patients included, 1,129 (50%) died during a median 1.1 years (IQR 0.6-2.0 years) of observation.,No patient was lost to follow-up.,PaCO2 (air) independently predicted adjusted mortality (p < 0.001).,The association with mortality was U-shaped, with the lowest mortality at approximately PaCO2 (air) 6.5 kPa and increased mortality at PaCO2 (air) below 5.0 kPa and above 7.0 kPa.,In oxygen-dependent COPD, PaCO2 (air) is an independent prognostic factor with a U-shaped association with mortality. | The Clinical COPD Questionnaire (CCQ) measures health status and can be used to assess health-related quality of life (HRQL).,We investigated whether CCQ is also associated with mortality.,Some 1111 Swedish primary and secondary care chronic obstructive pulmonary disease (COPD) patients were randomly selected.,Information from questionnaires and medical record review were obtained in 970 patients.,The Swedish Board of Health and Welfare provided mortality data.,Cox regression estimated survival, with adjustment for age, sex, heart disease, and lung function (for a subset with spirometry data, n = 530).,Age and sex-standardized mortality ratios were calculated.,Over 5 years, 220 patients (22.7%) died.,Mortality risk was higher for mean CCQ ≥ 3 (37.8% died) compared with mean CCQ < 1 (11.4%), producing an adjusted hazard ratio (HR) (and 95% confidence interval [CI]) of 3.13 (1.98 to 4.95).,After further adjustment for 1 second forced expiratory volume (expressed as percent of the European Community for Steel and Coal reference values ), the association remained (HR 2.94 [1.42 to 6.10]).,The mortality risk was higher than in the general population, with standardized mortality ratio (and 95% CI) of 1.87 (1.18 to 2.80) with CCQ < 1, increasing to 6.05 (4.94 to 7.44) with CCQ ≥ 3.,CCQ is predictive of mortality in COPD patients.,As HRQL and mortality are both important clinical endpoints, CCQ could be used to target interventions. | 1 |
It is difficult to assess the impact of multiple comorbidities on clinical outcomes in chronic obstructive pulmonary disease (COPD).,In this study, we aimed to investigate exacerbation-associated comorbidities, determine whether the number of comorbidities is an independent risk factor for exacerbation, and identify other exacerbation-associated factors in a Korean COPD population using a nationwide population-based cohort.,This study focused on severe exacerbations that required hospitalisation or emergency room visits.,The National Health Insurance Service-National Sample Cohort, version 2.0, data sampled between 2002 and 2015 were analysed.,Data from two years after the diagnosis of COPD were analysed for each participant (N = 12,554, entire cohort).,Moreover, 42% of the participants underwent additional health examinations (N = 5306, health-screening cohort).,Fifteen comorbidities that were previously reported as risk factors for exacerbations were examined.,A logistic regression model was used to analyse association with exacerbations.,Asthma (1.57 [1.39-1.76] and 1.24 [1.06-1.44]), lung cancer (1.84 [1.30-2.59] and 2.28 [1.54-3.37]), and heart failure (1.39 [1.16-1.67] and 1.52 [1.18-1.97]) were associated with exacerbation in both cohorts (odds ratio [95% confidence interval] in the entire cohort and health-screening cohort, respectively).,The number of comorbidities was an independent risk factor, and old age, male sex, low body mass index, and current smoking were also independent risk factors.,High cholesterol levels and body mass index exerted protective effects against exacerbation.,The number of comorbidities, certain comorbidities such as asthma, lung cancer and heart failure, and low BMI were associated with an increased risk of severe exacerbation in COPD patients. | It is unclear whether various bronchodilator reversibility (BDR) criteria affect the prognosis of chronic obstructive pulmonary disease (COPD).,The aim of this study is to evaluate the impact of positive BDR defined according to various BDR criteria on the risk of severe acute exacerbation (AE) in COPD patients.,Patients from four prospective COPD cohorts in South Korea who underwent follow-up for at least 1 year were enrolled in this study.,The assessed BDR criteria included the Global Initiative for Chronic Obstructive Lung Disease (GOLD), American Thoracic Society (ATS), American College of Chest Physicians, (ACCP), major criteria of the Spanish definition of asthma-COPD overlap syndrome (ACOS), criteria compatible with ACOS in the Global Initiative for Asthma (GINA), and European Respiratory Society (ERS).,The rate of patients with severe AE who required hospitalization within 1 year due to BDR results according to each set of criteria was analyzed using logistic regression models.,Among a total of 854 patients, the BDR-positive cases varied according to the criteria used.,There was a 3.5% positive BDR rate according to GINA and a 29.9% rate according to the ATS criteria.,Positive BDR according to the GOLD criteria was significantly associated with a decreased risk of severe AE (adjusted odds ratio (aOR) = 0.38; 95% Confidence interval (CI) = 0.15-0.93).,This result remained statistically significant even in a sensitivity analysis that included only participants with a smoking history of at least 10 pack-years and in the analysis for the propensity score-matched participants.,Among different criteria for positive BDR, the use of the GOLD ones was significantly associated with a decreased risk of severe AE in COPD patients.,Increase use of ICS/LABA may have affected this relationship.,The online version of this article (doi:10.1186/s12931-017-0587-9) contains supplementary material, which is available to authorized users. | 1 |
Parametric response mapping (PRM) of paired CT lung images has been shown to improve the phenotyping of COPD by allowing for the visualization and quantification of non-emphysematous air trapping component, referred to as functional small airways disease (fSAD).,Although promising, large variability in the standard method for analyzing PRMfSAD has been observed.,We postulate that representing the 3D PRMfSAD data as a single scalar quantity (relative volume of PRMfSAD) oversimplifies the original 3D data, limiting its potential to detect the subtle progression of COPD as well as varying subtypes.,In this study, we propose a new approach to analyze PRM.,Based on topological techniques, we generate 3D maps of local topological features from 3D PRMfSAD classification maps.,We found that the surface area of fSAD (SfSAD) was the most robust and significant independent indicator of clinically meaningful measures of COPD.,We also confirmed by micro-CT of human lung specimens that structural differences are associated with unique SfSAD patterns, and demonstrated longitudinal feature alterations occurred with worsening pulmonary function independent of an increase in disease extent.,These findings suggest that our technique captures additional COPD characteristics, which may provide important opportunities for improved diagnosis of COPD patients. | The term ‘emphysema’ is generally used in a morphological sense, and therefore imaging modalities have an important role in diagnosing this disease.,In particular, high resolution computed tomography (HRCT) is a reliable tool for demonstrating the pathology of emphysema, even in subtle changes within secondary pulmonary lobules.,Generally, pulmonary emphysema is classified into three types related to the lobular anatomy: centrilobular emphysema, panlobular emphysema, and paraseptal emphysema.,In this pictorial review, we discuss the radiological - pathological correlation in each type of pulmonary emphysema.,HRCT of early centrilobular emphysema shows an evenly distributed centrilobular tiny areas of low attenuation with ill-defined borders.,With enlargement of the dilated airspace, the surrounding lung parenchyma is compressed, which enables observation of a clear border between the emphysematous area and the normal lung.,Because the disease progresses from the centrilobular portion, normal lung parenchyma in the perilobular portion tends to be preserved, even in a case of far-advanced pulmonary emphysema.,In panlobular emphysema, HRCT shows either panlobular low attenuation or ill-defined diffuse low attenuation of the lung.,Paraseptal emphysema is characterized by subpleural well-defined cystic spaces.,Recent topics related to imaging of pulmonary emphysema will also be discussed, including morphometry of the airway in cases of chronic obstructive pulmonary disease, combined pulmonary fibrosis and pulmonary emphysema, and bronchogenic carcinoma associated with bullous lung disease. | 1 |
Respiratory symptoms are increasingly recognized as an important consideration in COPD management.,Understanding the links between the time(s) of day symptoms are experienced and overall symptom burden could support personalized management strategies.,This real-world study aimed to establish the association between the time of day of symptoms and the burden on patients using validated patient-reported outcomes, health care resource utilization, and physician-perceived impact of COPD on patients’ lives.,Analyses used data from four waves (2012, 2013, 2014, and 2016) of the Respiratory Disease Specific Programme: cross-sectional surveys of patients with COPD in Germany, Italy, Spain, and the UK.,Patients were classified by their physicians as having symptoms in the morning (M), daytime (D), and/or nighttime (N) in the 4 weeks before entering the Disease Specific Programme.,Outcomes included health care resource utilization, work productivity and activity impairment, COPD Assessment Test, EuroQol 5-dimension 3-level questionnaire with visual analog scale, and Jenkins Sleep Evaluation Questionnaire.,In total, 8,844 patients were included, and 8,185 had evaluable time-of-day symptom data.,Physicians reported that in the previous 4 weeks, 25% of patients experienced no symptoms, 16% D only, 17% M/D only, 6% D/N only, 4% M, N, or M/N only, and 32% M/D/N.,In general, patients with M/D/N symptoms utilized more health care resources in the previous 12 months, had more prior exacerbations, and reported worse activity impairment, health status, and sleep than other symptom groups, whereas patients with symptoms at any time of the day utilized more resources, experienced more exacerbations, and reported worse health status than patients with no symptoms during the 4 weeks before entering the survey.,Patients experiencing morning, daytime, and nighttime symptoms experience a greater disease burden than those in other groups.,An individualized approach to COPD treatment based on the timing and persistence of symptoms may improve outcomes for these patients. | Patients with chronic obstructive pulmonary disease (COPD) exhibit poor sleep quality and consider morning as the worst time of day for their symptoms.,While work has been done to characterize nighttime (NT) and early morning (EM) symptoms in various populations, the impact and factors associated with NT/EM symptoms among patients with COPD in the United States is not well understood.,Commercially insured patients aged ≥40 years with one or more medical claim for COPD and one or more pharmacy claim for COPD maintenance medication were identified from the HealthCore Integrated Research Database between September 1, 2010 and August 31, 2011.,Consenting respondents were asked whether they had COPD symptoms on at least three nights or at least three mornings during the past week.,Respondents were then either assigned to one of three symptom groups to complete the survey or excluded if their predefined group quota limit had been met.,Survey completers completed the survey with questions about COPD symptoms and other commonly used patient-reported outcome measures.,Respondents with NT/EM symptoms were asked about the frequency, severity, and impact of the symptoms on sleep, morning activities, and anxiety levels.,Among respondents with symptoms, 73.1% of respondents with NT symptoms (N=376) and 83% of respondents with EM symptoms (N=506) experienced at least three distinct types of symptoms over the past week, with cough being the most frequently reported symptom.,Approximately half of respondents with NT or EM symptoms perceived their symptoms as moderate to very severe, with a majority reporting their symptoms affected their NT sleep and morning activities, and more than half felt anxious due to their symptoms.,Multinomial logistic regression showed COPD patients with both or either NT/EM symptoms were associated with poorer health status compared to those without.,Improved disease management may reduce NT/EM symptoms and improve health status in patients with COPD. | 1 |
Information concerning how climate and atmospheric pollutants affects physical activity in COPD patients is lacking and might be valuable in determining when physical activity should be encouraged.,Seventy-three stable COPD patients recorded on daily diary cards worsening of respiratory symptoms, peak expiratory flow rate, hours spent outside the home and the number of steps taken per day.,Pedometry data was recorded on 16,478 days, an average of 267 days per patient (range 29-658).,Daily data for atmospheric PM10 and ozone (O3) were obtained for Bloomsbury Square, Central London from the Air Quality Information Archive databases.,Daily weather data were obtained for London Heathrow from the British Atmospheric Data Archive.,Colder weather below 22.5 °C, reduced daily step count by 43.3 steps day per°C (95 % CI 2.14 to 84.4; p = 0.039) and activity was lower on rainy than dry days (p = 0.002) and on overcast compared to sunny days (p < 0.001).,Daily step count was 434 steps per day lower on Sunday than Saturday (p < 0.001) and 353 steps per day lower on Saturday than Friday (p < 0.001).,After allowance for these effects, higher O3 levels decreased activity during the whole week (-8 steps/ug/m3; p = 0.005) and at weekends (-7.8 steps/ug/m3; p = 0.032).,Whilst, during the week PM10 reduced activity (p = 0.018) but not during the weekend.,Inactivity of COPD patients is greatest on cold, wet and overcast days and at the weekends.,This study also provides evidence of an independent effect of atmospheric pollution at high levels.,The online version of this article (doi:10.1186/s12931-015-0229-z) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) is characterized by a persistent blockage of airflow, prompting episodes of shortness of breath, commonly leading to hospitalization.,Hospitalization may lead to a decline in physical activity following discharge.,Physical activity has been shown to improve symptoms of COPD and reduce readmissions, and to decrease morbidity and mortality.,This study aims to explore, from the perspectives of people with COPD, the barriers to and enablers of participation in physical activity following hospitalization for COPD.,This study had a qualitative descriptive design and included semistructured interviews with 28 adult COPD patients who had been admitted to hospital with a primary diagnosis of exacerbation of COPD.,A plethora of barriers to but fewer enablers of participation in physical activity and pulmonary rehabilitation were identified for this cohort of people.,The main barriers identified were health-related (comorbidities, COPD symptoms, and physical injury or illness) environment-related (weather, transport, and finance), and self-related.,The main enabling factors reported were access to health professionals and equipment, social support, routine and extracurricular activities, personal goals and motivation, and the effect of physical activity and “feeling better”.,This research provides a snapshot of the barriers to and enablers of physical activity and pulmonary rehabilitation in people with COPD.,It is evident that there are significant barriers which hinder the ability of people with COPD to undertake and continue participation in physical activity and pulmonary rehabilitation.,While there are some enablers that may counter these barriers, it is clear that health professionals dealing with people suffering from COPD need to actively recognize and address barriers to physical activity and pulmonary rehabilitation.,Hospital admission may create an opportunity for implementation of interventions promoting physical activity (such as referral to pulmonary rehabilitation), which may assist in reducing hospital readmission, as well as decreasing morbidity and mortality. | 1 |
For chronic obstructive pulmonary disease (COPD), the role of physical activity in reducing COPD mortality and heart loading and in extending life expectancy remains unclear.,Participants in comprehensive medical screening were recruited with spirometry on everyone.,We analyzed physical activity volume calculated from intensity, duration and frequency of self-reported exercise history.,Deaths were identified from the National Death File.,The impacts of physical activity on mortality, heart rate and life expectancy were analyzed.,Among the cohort of 483,603 adults, 32,535 had spirometry-determined COPD, indicating an adjusted national prevalence of 11.4% (male) and 9.8% (female).,On the average, COPD increased all-cause mortality with a hazard ratio of 1.44 and loss of 6.0 years in life expectancy.,Almost two thirds (65%) of the causes of deaths were extra-pulmonary, such as cardiovascular disease, diabetes, cancer and kidney diseases.,In addition, COPD was associated with increases in heart rate proportionate to its severity, which led to higher mortality.,Participants with COPD who were fully active physically could reduce mortality and have improved heart rates as compared with those without physical activity.,In addition, their life expectancy could be extended close to those of the no COPD but inactive cohort.,Fully active physical activity can help patients with COPD overcome most of the mortality risks, decrease heart rate, and achieve a life expectancy close to that of patients without COPD.,The effectiveness of physical activity on COPD is facilitated by its systemic nature beyond lung disease. | Study of the causes of the reduced levels of physical activity in patients with COPD has been scarce and limited to biological factors.,To assess the relationship between novel socio-environmental factors, namely dog walking, grandparenting, neighbourhood deprivation, residential surrounding greenness and residential proximity to green or blue spaces, and amount and intensity of physical activity in COPD patients.,This cross-sectional study recruited 410 COPD patients from five Catalan municipalities.,Dog walking and grandparenting were assessed by questionnaire.,Neighbourhood deprivation was assessed using the census Urban Vulnerability Index, residential surrounding greenness by the satellite-derived Normalized Difference Vegetation Index, and residential proximity to green or blue spaces as living within 300 m of such a space.,Physical activity was measured during 1 week by accelerometer to assess time spent on moderate-to-vigorous physical activity (MVPA) and vector magnitude units (VMU) per minute.,Patients were 85% male, had a mean (SD) age of 69 (9) years, and post-bronchodilator FEV1 of 56 (17) %pred.,After adjusting for age, sex, socio-economic status, dyspnoea, exercise capacity and anxiety in a linear regression model, both dog walking and grandparenting were significantly associated with an increase both in time in MVPA (18 min/day (p<0.01) and 9 min/day (p<0.05), respectively) and in physical activity intensity (76 VMU/min (p=0.05) and 59 VMUs/min (p<0.05), respectively).,Neighbourhood deprivation, surrounding greenness and proximity to green or blue spaces were not associated with physical activity.,Dog walking and grandparenting are associated with a higher amount and intensity of physical activity in COPD patients.,Pre-results, NCT01897298. | 1 |
Club cell protein (CC16) is expressed primarily by club cells possesses anti-inflammatory properties and is located in the bronchiolar epithelium.,Previous studies have demonstrated that CC16 deficiency is associated with the progression of chronic obstructive pulmonary disease (COPD).,In the present study, the therapeutic effects of recombinant rat CC16 protein in mice with COPD were examined and the underlying mechanisms investigated.,A total of 30 adult male C57/BL6 mice were randomly divided into three groups (10 mice/group).,A mouse COPD model was generated by exposing 20 mice to cigarette smoke (CS) for 24 weeks.,A total of 10 mice were treated intranasally with rCC16 (2.5 µg/g body weight) and control mice were exposed to normal room air.,Results indicated that rCC16 treatment ameliorated pathological damage in the lungs and reduced the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8, which were induced by CS exposure.,After rCC16 administration, endogenous CC16 was upregulated and the body weight of COPD mice was increased, whereas the opposite was observed in CS-exposed mice.,Additionally, rCC16 treatment inhibited the DNA binding of NF-κB/p65 in lung tissues and reduced nuclear translocation of NF-κB/p65 in BALF and epithelial cells.,Moreover, rCC16 treatment lead to a decrease in the total number of BALF cells, including macrophages, which was elevated in COPD mice.,In conclusion, the present results demonstrate that rCC16 has therapeutic effects on COPD by downregulating pro-inflammatory factors via the NF-κB pathway. | 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 |
Little is known about whether there is any sex effect on chronic obstructive lung disease (COPD) exacerbations.,This study is intended to describe the possible sex-associated differences in exacerbation profile in COPD patients.,A total of 384 COPD patients who were hospitalized due to exacerbation were evaluated retrospectively for their demographics and previous and current exacerbation characteristics.,The study was conducted on 109 (28%) female patients and 275 (72%) male patients.,The mean age was 68.30±10.46 years.,Although females had better forced expiratory volume in 1 second and near-normal forced vital capacity, they had much impaired arterial blood gas levels (partial oxygen pressure [PO2] was 36.28 mmHg vs 57.93 mmHg; partial carbon dioxide pressure [PCO2] was 45.97 mmHg vs 42.49 mmHg; P=0.001), indicating severe exacerbation with respiratory failure.,More females had two exacerbations and two hospitalizations, while more men had one exacerbation and one hospitalization.,Low adherence to treatment and pulmonary embolism were more frequent in females.,Females had longer time from the onset of symptoms till the admission and longer hospitalization duration than males.,Comorbidities were less in number and different in women (P<0.05).,Women were undertreated and using more oral corticosteroids.,Current data showed that female COPD patients might be more prone to have severe exacerbations, a higher number of hospitalizations, and prolonged length of stay for hospitalization.,They have a different comorbidity profile and might be undertreated for COPD. | Hospital readmission for acute exacerbation of COPD (AECOPD) occurs in up to 30% of patients, leading to excess morbidity and poor survival.,Physiological risk factors predict readmission, but the impact of modifiable psychosocial risk factors remains uncertain.,We aimed to evaluate whether psychosocial risk factors independently predict readmission for AECOPD in patients referred to early discharge services (EDS).,This prospective cohort study included 79 patients with AECOPD cared for by nurse led EDS in the UK, and followed up for 12 months.,Data on lung function, medical comorbidities, previous hospital admissions, medications, and sociodemographics were collected at baseline; St George's Respiratory Questionnaire (SGRQ), Hospital Anxiety and Depression Scale (HADS), and social support were measured at baseline, 3 and 12-months.,Exploratory multivariate models were fitted to identify psychosocial factors associated with readmission adjusted for known confounders.,26 patients were readmitted within 90 days and 60 patients were readmitted at least once during follow-up.,Depression at baseline predicted readmission adjusted for sociodemographics and forced expiratory volume in 1 second (odds ratio 1.30, 95% CI 1.06 to 1.60, p = 0.013).,Perceived social support was not significantly associated with risk of readmission.,Home ownership was associated with the total number of readmissions (B = 0.46, 95% CI -0.86 to -0.06, p = 0.024).,Compared with those not readmitted, readmitted patients had worse SGRQ and HADS scores at 12 months.,Depressive symptoms and socioeconomic status, but not perceived social support, predict risk of readmission and readmission frequency for AECOPD in patients cared for by nurse-led EDS.,Future work on reducing demand for unscheduled hospital admissions could include the design and evaluation of interventions aimed at optimising the psychosocial care of AECOPD patients managed at home. | 1 |
Occupational asthma and chronic obstructive pulmonary disease (COPD) are associated with the airway inflammatory process.,The aim of this study was to compare the sputum and serum markers of inflammation in patients with occupational asthma and COPD.,The study group included 20 patients with stable COPD, 24 patients with asthma, and 22 healthy subjects.,Interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, matrix metalloproteinase (MMP)-9 levels in serum and induced sputum as well as fibrinogen and CRP in serum were determined in all the subjects.,Higher concentrations of IL-1β, IL-6, TNF-α, and MMP-9 in induced sputum and an increased concentration of acute-phase proteins in serum were observed in COPD patients compared with healthy subjects.,Higher concentrations of IL-1β and MMP-9 in induced sputum and a higher concentration of C-reactive protein (CRP) were detected in COPD patients than in asthmatic subjects.,Never smokers with COPD had significantly higher levels of IL-1β and MMP-9 in induced sputum than never smoker controls.,There was no significant difference between the serum and sputum levels of cytokines and MMP-9 of never smokers and smokers with COPD.,Higher concentrations of IL-1β and MMP-9 in induced sputum and a higher concentration of CRP in serum allow distinguishing between biomarker profiles of COPD patients and asthmatic patients.,Occupational exposure induces a systemic proinflammatory state with increased levels of acute-phase proteins in stable COPD patients.,MMP-9 and IL-1β concentrations are increased in induced sputum of never smokers with COPD, which is associated with occupational exposure. | 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 |
During most COPD exacerbations, patients continue to live in the community but there is little information on changes in activity during exacerbations due to the difficulties of obtaining recent, prospective baseline data.,Patients recorded on daily diary cards any worsening in respiratory symptoms, peak expiratory flow (PEF) and the number of steps taken per day measured with a Yamax Digi-walker pedometer.,Exacerbations were defined by increased respiratory symptoms and the number of exacerbations experienced in the 12 months preceding the recording of daily step count used to divide patients into frequent (> = 2/year) or infrequent exacerbators.,The 73 COPD patients (88% male) had a mean (±SD) age 71(±8) years and FEV1 53(±16)% predicted.,They recorded pedometer data on a median 198 days (IQR 134-353).,At exacerbation onset, symptom count rose by 1.9(±1.3) and PEF fell by 7(±13) l/min.,Mean daily step count fell from 4154(±2586) steps/day during a preceding baseline week to 3673(±2258) step/day during the initial 7 days of exacerbation (p = 0.045).,Patients with larger falls in activity at exacerbation took longer to recover to stable level (rho = −0.56; p < 0.001).,Recovery in daily step count was faster (median 3.5 days) than for exacerbation symptoms (median 11 days; p < 0.001).,Recovery in step count was also faster in untreated compared to treated exacerbation (p = 0.030).,Daily step count fell faster over time in the 40 frequent exacerbators, by 708 steps/year, compared to 338 steps/year in 33 infrequent exacerbators (p = 0.002).,COPD exacerbations reduced physical activity and frequent exacerbations accelerate decline in activity over time. | To study patients’ levels of exercise activity and the clinical characteristics that relate to physical activity and inactivity among patients with chronic obstructive pulmonary disease (COPD).,A postal questionnaire was administered to 719 patients with COPD in 2010; patients were recruited from the Helsinki and Turku University Central Hospitals in Finland and have been followed since 2005.,The questionnaire asked participants about their exercise routines and other daily activities, potential restrictions to exercise, health-related quality of life, and subjective sensations of dyspnea upon exertion.,A total of 50% of the participants reported exercising > 2 times a week throughout the year.,The proportion of the exercise inactive patients increased in parallel with disease progression, but the participants exhibited great variation in the degree of activity as well as in sport choices.,Year-round activity was better maintained among patients who exercised both indoors and outdoors.,Training activity was significantly correlated with patients’ reported subjective dyspnea (r = 0.32, P < 0.001), health-related quality of life (r = 0.25, P < 0.001), mobility score (r = 0.37, P < 0.001), and bronchial obstruction (r = 0.18, P < 0.001).,Active patients did not differ from inactive patients in terms of sex, age, smoking status, somatic comorbidities, or body mass index.,Irrespective of the level of severity of patients’ COPD, the most significant barrier to exercising was the subjective sensation of dyspnea.,When a patient with COPD suffers from dyspnea and does not have regular exercise routines, the patient will most likely benefit from an exercise program tailored to his or her physical capabilities. | 1 |
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. | Airway surface dehydration, caused by an imbalance between secretion and absorption of ions and fluid across the epithelium and/or increased epithelial mucin secretion, impairs mucociliary clearance.,Recent evidence suggests that this mechanism may be implicated in chronic obstructive pulmonary disease (COPD).,However, the role of airway surface dehydration in the pathogenesis of cigarette smoke (CS)-induced COPD remains unknown.,We aimed to investigate in vivo the effect of airway surface dehydration on several CS-induced hallmarks of COPD in mice with airway-specific overexpression of the β-subunit of the epithelial Na+ channel (βENaC).,βENaC-Tg mice and wild-type (WT) littermates were exposed to air or CS for 4 or 8 weeks.,Pathological hallmarks of COPD, including goblet cell metaplasia, mucin expression, pulmonary inflammation, lymphoid follicles, emphysema and airway wall remodelling were determined and lung function was measured.,Airway surface dehydration in βENaC-Tg mice aggravated CS-induced airway inflammation, mucin expression and destruction of alveolar walls and accelerated the formation of pulmonary lymphoid follicles.,Moreover, lung function measurements demonstrated an increased compliance and total lung capacity and a lower resistance and hysteresis in βENaC-Tg mice, compared to WT mice.,CS exposure further altered lung function measurements.,We conclude that airway surface dehydration is a risk factor that aggravates CS-induced hallmarks of COPD. | 1 |
Patients with COPD experience lower airway and systemic inflammation, and an accelerated decline in FEV1.,There is no evidence on whether this inflammation changes over time, or if it is associated with a faster decline in FEV1.,A cohort of 148 COPD patients (100 men) was monitored daily for a median of 2.91 years (interquartile range [IQR], 2.1 to 4.8).,At recruitment, median age was 68.5 years (IQR, 62.5 to 73.6) and FEV1 as percentage of predicted (FEV1%Pred) was 38.5% (IQR, 27.7 to 50.3).,During the study, the patients experienced 1,389 exacerbations, a median of 2.52/yr (IQR, 1.48 to 3.96) and FEV1 declined by 40.2 mL/yr or as FEV1%Pred by 1.5%/yr.,Concerning inflammatory markers, sputum interleukin (IL)-6 rose by 9 pg/mL/yr, sputum neutrophil count rose by 1.64 × 106 cells per gram sputum per year, an plasma fibrinogen rose by 0.10 g/L/yr (all p < 0.05).,Patients with frequent exacerbations (≥ 2.52/yr) had a faster rise over time in plasma fibrinogen and sputum IL-6 of 0.063 g/L/yr (p = 0.046, n = 130) and 29.5 pg/mL/yr (p < 0.001, n = 98), respectively, compared to patients with infrequent exacerbations (< 2.52/yr).,Using the earliest stable (nonexacerbation) measured marker, patients whose IL-6 exceeded the group median had a faster FEV1%Pred decline of 0.42%/yr (p = 0.018).,Similarly, a high neutrophil count or fibrinogen were associated with a faster FEV1%Pred decline of 0.97%/yr (p = 0.001) and 0.40%/yr (p = 0.014), respectively.,In COPD, airway and systemic inflammatory markers increase over time; high levels of these markers are associated with a faster decline in lung function. | Currently available long-acting inhaled bronchodilators (tiotropium, salmeterol, formoterol) have demonstrated beneficial effects on exacerbations in placebo-controlled trials.,However, there have been no direct comparisons of these drugs with exacerbations as the primary outcome and consequently COPD treatment guidelines do not indicate a preference for either bronchodilator.,Therefore, an international, randomized, double-blind, double-dummy, parallel-group clinical trial has been designed to investigate the comparative efficacy of 2 long-acting bronchodilators tiotropium 18 μg daily and salmeterol 50 μg bid on exacerbations.,The trial will include at least 6800 randomized patients with diagnosis of COPD, ≥ 10 pack-year history of smoking, post-bronchodilator FEV1 ≤ 70% predicted, and a history of exacerbations in the previous year.,The primary endpoint is time to first COPD exacerbation.,Secondary endpoints include number of exacerbations and time to premature discontinuation of trial medication.,The trial has been designed to address several of the challenges in studying exacerbations in a controlled trial by a symptom and event-based definition of exacerbations, frequent follow-up contacts, selection of time to first event as the primary endpoint and using exposure adjusted analysis when examining number of events.,Other challenges in designing exacerbation trials such as differential discontinuation and follow-up of discontinued patients are discussed. | 1 |
To explore the relationship between the blood eosinophil concentrations in the early stage and mortality in critically ill patients with acute exacerbation of chronic obstructive pulmonary disease.,Patient data were extracted from the MIMIC-III V1.4 database.,Only the acute exacerbation of chronic obstructive pulmonary disease patients with the first measurement time of blood eosinophil concentrations (%) between 24 hours before admission and 24 hours after admission was included.,The logistic regression model was used to analyze the association between eosinophil and outcomes.,1019 patients were included in the study.,Two multivariate regression models were built.,The adjusted odds ratio of in-hospital mortality, in-ICU mortality, hospital length of stay and ICU length of stay for initial blood eosinophil concentrations in model 1 (adjusted for SAPS Ⅱ, cardiac arrhythmias, solid tumor, metastatic cancer, liver disease, neutrophils) were 0.792 (95% CI: 0.643-0.976, p=0.028), 0.812 (95% CI: 0.645-1.022, p=0.076), 0.847 (95% CI: 0.772-0.930, p=0.001) and 0.914 (95% CI: 0.836-1.000, p=0.049) respectively.,Meanwhile, in model 2 (adjusted for SOFA score, age, cardiac arrhythmias, solid tumor, metastatic cancer, liver disease, neutrophils) ORs were 0.785 (95% CI: 0.636-0.968, p=0.024), 0.807 (95% CI: 0.641-1.016, p=0.068), 0.854 (95% CI: 0.778-0.939, p=0.001) and 0.917 (95% CI: 0.838-1.004, p=0.060) respectively.,The area under the ROC curve for eosinophil initial was 0.608 (95% CI: 0.559-0.657).,The discriminatory eosinophil thresholds were 0.35% (sensitivity=0.59, specificity=0.61) for in-hospital mortality.,Increased blood eosinophils were associated with decreased in-hospital mortality and shorten hospital length of stay in critically ill patients with acute exacerbation of chronic obstructive pulmonary disease.,A discriminatory eosinophil threshold of 0.35% for mortality was found, but further studies were needed to verify it. | Coronavirus disease 2019 (COVID-19) is an evolving infectious disease that dramatically spread all over the world in the early part of 2020.,No studies have yet summarized the potential severity and mortality risks caused by COVID-19 in patients with chronic obstructive pulmonary disease (COPD), and we update information in smokers.,We systematically searched electronic databases from inception to March 24, 2020.,Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.,Study quality was assessed using a modified version of the Newcastle-Ottawa Scale.,We synthesized a narrative from eligible studies and conducted a meta-analysis using a random-effects model to calculate pooled prevalence rates and 95% confidence intervals (95%CI).,In total, 123 abstracts were screened and 61 full-text manuscripts were reviewed.,A total of 15 studies met the inclusion criteria, which included a total of 2473 confirmed COVID-19 patients.,All studies were included in the meta-analysis.,The crude case fatality rate of COVID-19 was 7.4%.,The pooled prevalence rates of COPD patients and smokers in COVID-19 cases were 2% (95% CI, 1%-3%) and 9% (95% CI, 4%-14%) respectively.,COPD patients were at a higher risk of more severe disease (risk of severity = 63%, (22/35) compared to patients without COPD 33.4% (409/1224) [calculated RR, 1.88 (95% CI, 1.4-2.4)].,This was associated with higher mortality (60%).,Our results showed that 22% (31/139) of current smokers and 46% (13/28) of ex-smokers had severe complications.,The calculated RR showed that current smokers were 1.45 times more likely [95% CI: 1.03-2.04] to have severe complications compared to former and never smokers.,Current smokers also had a higher mortality rate of 38.5%.,Although COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD.,Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate.,Effective preventive measures are required to reduce COVID-19 risk in COPD patients and current smokers. | 1 |
The landmark study of Fletcher and Peto on the natural history of tobacco smoke-related chronic airflow obstruction suggested that decline in the forced expiratory volume in the first second (FEV1) in chronic obstructive pulmonary disease (COPD) is slow at the beginning, becoming faster with more advanced disease.,The present authors reviewed spirometric data of COPD patients included in the placebo arms of recent clinical trials to assess the lung function decline of each stage, defined according to the severity of airflow obstruction as proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.,In large COPD populations the mean rate of FEV1 decline in GOLD stages II and III is between 47 and 79 mL/year and 56 and 59 mL/year, respectively, and lower than 35 mL/year in GOLD stage IV.,Few data on FEV1 decline are available for GOLD stage I.,Hence, the loss of lung function, assessed as expiratory airflow reduction, seems more accelerated and therefore more relevant in the initial phases of COPD.,To have an impact on the natural history of COPD, it is logical to look at the effects of treatment in the earlier stages. | Socioeconomic status is likely an independent risk factor for Chronic Obstructive Pulmonary Disease (COPD), but little research has been done in China to study this association in a nationwide sample.,We used data from the 2007 China Chronic Disease Risk Factor Surveillance of 49,363 Chinese men and women aged 15-69 years to examine the association between the prevalence of self-reported physician diagnosed COPD and socioeconomic status defined by both educational level and annual household income.,Multivariable logistic regression modelling was performed with adjustement for potential confounders.,Both low educational attainment and low household income were independently associated with higher risk of physician-diagnosed COPD.,Compared to subjects with high educational level, subjects with low educational level had a significantly increased risk of COPD (OR 1.67, 95%CI 1.32-2.13, p for trend< 0.001 for urban, OR 1.76, 95%CI 1.34-2.30, p for trend < 0.001 for rural) after adjusting for age, sex, smoking status, passive smoking and geographic regions.,Similarly increased risk was observed for household income and COPD in urban (OR 1.64, 95%CI 1.28-2.09, P for trend< 0.001) but not rural areas.,Among never smokers, low educational level and household income were still associated with a significant higher prevalence of COPD (OR 1.77, 95%CI 1.40-2.25, OR 1.31, 95%CI 1.05-1.62).,Removal of those with asthma diagnosis did not alter the observed associations.,Socioeconomic status is a risk factor for self-reported physician-diagnosed COPD independently of current or passive smoking.,Prospective studies are needed in China to better understand the association between socioeconomic status and COPD. | 1 |
Pulmonary tuberculosis (PTB) is associated with many forms of chronic lung disease including the development of chronic airflow obstruction (AFO).,However, the nature, evolution and mechanisms responsible for the AFO after PTB are poorly understood.,The aim of this study was to examine the progression of changes in lung physiology in patients treated for PTB.,Immunocompetent, previously healthy, adult patients receiving ambulatory treatment for a first episode of tuberculosis were prospectively followed up with serial lung physiology and quantitative computed tomography (CT) lung scans performed at diagnosis of tuberculosis, 2, 6, 12 and 18 months during and after the completion of treatment.,Forty-nine patients (median age 26 years; 37.2% males) were included, and 43 were studied.,During treatment, lung volumes improved and CT fibrosis scores decreased, but features of AFO and gas trapping emerged, while reduced diffusing capacity (DLco) seen in a majority of patients persisted.,Significant increases in total lung capacity (TLC) by plethysmography were seen in the year following treatment completion (median change 5.9% pred., P<0.01) and were driven by large increases in residual volume (RV) (median change +19%pred., P<0.01) but not inspiratory capacity (IC; P=0.41).,The change in RV/TLC correlated with significant progression of radiological gas trapping after treatment (P=0.04) but not with emphysema scores.,One year after completing treatment, 18.6% of patients had residual restriction (total lung capacity, TLC <80%pred), 16.3% had AFO, 32.6% had gas trapping (RV/TLC>45%), and 78.6% had reduced DLco.,Simple spirometry alone does not fully reveal the residual respiratory impairments resulting after a first episode of PTB.,Changes in physiology evolve after treatment completion, and these findings when taken together, suggest emergence of gas trapping after treatment likely caused by progression of small airway pathology during the healing process. | Tuberculosis-associated COPD (T-COPD) has clinical characteristics similar to those of smoking-associated COPD (S-COPD), such as dyspnea, sputum production, and acute exacerbation (AE).,However, the degree of systemic inflammation and prognosis might be different because of difference in the pathophysiology.,The aim of this study was to compare the lung function, systemic inflammatory markers, and their impacts on AE in patients with S-COPD and T-COPD.,We performed a multicenter cross-sectional cohort study.,We evaluated clinical characteristics, pulmonary function tests, levels of inflammatory markers, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and IL-6, and the association of these markers with AE in patients with S-COPD and T-COPD.,Patients with T-COPD included more women and had lesser smoking history and higher St George Respiratory Questionnaire score than did patients with S-COPD.,Although the FEV1 of both groups was similar, FVC, vital capacity, total lung capacity, and functional residual capacity were lower in patients with T-COPD than in those with S-COPD.,CRP, ESR, and IL-6 levels were significantly higher in patients with T-COPD compared to patients with S-COPD.,According to a multivariate logistic regression analysis, FEV1 was a significant factor predicting AE in S-COPD, and IL-6 was a significant factor predicting AE in T-COPD.,IL-6 level greater than 2.04 pg/mL was a cutoff for predicting exacerbation of T-COPD (sensitivity 84.8%, specificity 59.3%, P<0.001).,Patients with T-COPD have higher levels of inflammatory markers, and IL-6 has a predictive value for AE in T-COPD. | 1 |
IMPACT, a 52-week, randomised, double-blind trial, assessed the efficacy and safety of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus FF/VI or UMEC/VI in patients with symptomatic COPD and a history of exacerbations.,Subgroup analyses assessed whether the efficacy of FF/UMEC/VI versus FF/VI or UMEC/VI and UMEC/VI versus FF/VI varies according to prior exacerbation history, and the combined effects of exacerbation history and blood eosinophil counts.,Three subgroups were defined: single moderate (1 moderate/no severe; n=3056 (30%)), frequent moderate (≥2 moderate/no severe; n=4628 (45%)) and severe (≥1 severe/any moderate; n=2671 (26%)).,End-points included annual on-treatment moderate/severe exacerbation rate (pre-specified), lung function and health status (both post-hoc).,Moderate/severe exacerbation rates (reduction % (95% CI)) were reduced in the FF/UMEC/VI group versus FF/VI (single moderate 20% (10-29), frequent moderate 11% (2-19), severe 17% (7-26)) and versus UMEC/VI (single moderate 18% (5-29), frequent moderate 29% (21-37), severe 26% (14-35)).,Moderate/severe exacerbation rates were reduced in the FF/VI group versus UMEC/VI in the frequent moderate subgroup; a numerical reduction was observed in the severe subgroup (single moderate 2% (−12-18), frequent moderate 21% (11-29), severe 11% (−3-22)).,Moderate/severe exacerbation rates were lower in the FF/VI group compared with UMEC/VI in patients with higher eosinophil counts.,FF/UMEC/VI improved lung function and health status versus both dual therapies irrespective of exacerbation subgroup.,UMEC/VI improved lung function versus FF/VI in all subgroups.,Triple therapy was more effective than dual regardless of exacerbation history, consistent with results in the intent-to-treat population.,Comparisons between dual therapies were influenced by prior exacerbation history and eosinophil counts.,FF/UMEC/VI shows benefits vs FF/VI and UMEC/VI across multiple endpoints irrespective of exacerbation history.,Exacerbation history and eosinophils influenced the comparison between UMEC/VI and FF/VI, and eosinophils that between FF/UMEC/VI and UMEC/VI.http://bit.ly/2SHu2ey | To evaluate risk factors associated with exacerbation frequency in primary care.,Information on exacerbations of chronic obstructive pulmonary disease (COPD) has mainly been generated by secondary care-based clinical cohorts.,Retrospective observational cohort study.,Electronic medical records database (England and Wales).,58 589 patients with COPD aged ≥40 years with COPD diagnosis recorded between 1 April 2009 and 30 September 2012, and with at least 365 days of follow-up before and after the COPD diagnosis, were identified in the Clinical Practice Research Datalink.,Mean age: 69 years; 47% female; mean forced expiratory volume in 1s 60% predicted.,Data on moderate or severe exacerbation episodes defined by diagnosis and/or medication codes 12 months following cohort entry were retrieved, together with demographic and clinical characteristics.,Associations between patient characteristics and odds of having none versus one, none versus frequent (≥2) and one versus frequent exacerbations over 12 months follow-up were evaluated using multivariate logistic regression models.,During follow-up, 23% of patients had evidence of frequent moderate-to-severe COPD exacerbations (24% one; 53% none).,Independent predictors of increased odds of having exacerbations during the follow-up, either frequent episodes or one episode, included prior exacerbations, increasing dyspnoea score, increasing grade of airflow limitation, females and prior or current history of several comorbidities (eg, asthma, depression, anxiety, heart failure and cancer).,Primary care-managed patients with COPD at the highest risk of exacerbations can be identified by exploring medical history for the presence of prior exacerbations, greater COPD disease severity and co-occurrence of other medical conditions. | 1 |
Variation in ADAM33 has been shown to be important in the development of asthma and altered lung function.,This relationship however, has not been investigated in the population susceptible to COPD; long term tobacco smokers.,We evaluated the association between polymorphisms in ADAM33 gene with COPD and lung function in long term tobacco smokers.,Caucasian subjects, at least 50 year old, who smoked ≥ 20 pack-years (n = 880) were genotyped for 25 single nucleotide polymorphisms (SNPs) in ADAM33.,COPD was defined as an FEV1/FVC ratio < 70% and percent-predicted (pp)FEV1 < 75% (n = 287).,The control group had an FEV1/FVC ratio ≥ 70% and ppFEV1 ≥ 80% (n = 311) despite ≥ 20 pack years of smoking.,Logistic and linear regressions were used for the analysis.,Age, sex, and smoking status were considered as potential confounders.,Five SNPs in ADAM33 were associated with COPD (Q-1, intronic: p < 0.003; S1, Ile → Val: p < 0.003; S2, Gly → Gly: p < 0.04; V-1 intronic: p < 0.002; V4, in 3' untranslated region: p < 0.007).,Q-1, S1 and V-1 were also associated with ppFEV1, FEV1/FVC ratio and ppFEF25-75 (p values 0.001 - 0.02).,S2 was associated with FEV1/FVC ratio (p < 0.05).,The association between S1 and residual volume revealed a trend toward significance (p value < 0.07).,Linkage disequilibrium and haplotype analyses suggested that S1 had the strongest degree of association with COPD and pulmonary function abnormalities.,Five SNPs in ADAM33 were associated with COPD and lung function in long-term smokers.,Functional studies will be needed to evaluate the biologic significance of these polymorphisms in the pathogenesis of COPD. | Pulmonary function measures obtained by spirometry are used to diagnose chronic obstructive pulmonary disease (COPD) and are highly heritable.,We conducted genome-wide association (GWA) analyses (Affymetrix 100K SNP GeneChip) for measures of lung function in the Framingham Heart Study.,Ten spirometry phenotypes including percent of predicted measures, mean spirometry measures over two examinations, and rates of change based on forced expiratory volume in one second (FEV1), forced vital capacity (FVC), forced expiratory flow from the 25th to 75th percentile (FEF25-75), the FEV1/FVC ratio, and the FEF25-75/FVC ratio were examined.,Percent predicted phenotypes were created using each participant's latest exam with spirometry.,Predicted lung function was estimated using models defined in the set of healthy never-smokers, and standardized residuals of percent predicted measures were created adjusting for smoking status, pack-years, and body mass index (BMI).,All modeling was performed stratified by sex and cohort.,Mean spirometry phenotypes were created using data from two examinations and adjusting for age, BMI, height, smoking and pack-years.,Change in pulmonary function over time was studied using two to four examinations with spirometry to calculate slopes, which were then adjusted for age, height, smoking and pack-years.,Analyses were restricted to 70,987 autosomal SNPs with minor allele frequency ≥ 10%, genotype call rate ≥ 80%, and Hardy-Weinberg equilibrium p-value ≥ 0.001.,A SNP in the interleukin 6 receptor (IL6R) on chromosome 1 was among the best results for percent predicted FEF25-75.,A non-synonymous coding SNP in glutathione S-transferase omega 2 (GSTO2) on chromosome 10 had top-ranked results studying the mean FEV1 and FVC measurements from two examinations.,SNPs nearby the SOD3 and vitamin D binding protein genes, candidate genes for COPD, exhibited association to percent predicted phenotypes.,GSTO2 and IL6R are credible candidate genes for association to pulmonary function identified by GWA.,These and other observed associations warrant replication studies.,This resource of GWA results for pulmonary function measures is publicly available at . | 1 |
The COVID-19 pandemic has impacted specialty chronic obstructive pulmonary disease (COPD) care.,We examined the degree to which care has moved to remote approaches, eliciting clinician and patient perspectives on what is appropriate for ongoing remote delivery.,Using an online research platform, we conducted a survey and consensus-building process involving clinicians and patients with COPD.,Fifty-five clinicians and 19 patients responded.,The majority of clinicians felt able to assess symptom severity (n=52, 95%), reinforce smoking cessation (n=46, 84%) and signpost to other healthcare resources (n=44, 80%).,Patients reported that assessing COPD severity and starting new medications were being addressed through remote care.,Forty-three and 31 respondents participated in the first and second consensus-building rounds, respectively.,When asked to rate the appropriateness of using remote delivery for specific care activities, respondents reached consensus on 5 of 14 items: collecting information about COPD and overall health status (77%), providing COPD education and developing a self-management plan (74%), reinforcing smoking cessation (81%), deciding whether patients should seek in-person care (72%) and initiating a rescue pack (76%).,Adoption of remote care delivery appears high, with many care activities partially or completely delivered remotely.,Our work identifies strengths and limitations of remote care delivery. | Singing for lung health (SLH) is a popular arts-in-health activity for people with long-term respiratory conditions.,Participants report biopsychosocial benefits, however, research on impact is limited.,The ‘SLH: Improving Experiences of Lung Disease trial’, a randomised controlled, single (assessor) blind, trial of 12 weeks SLH versus usual care for people with chronic obstructive pulmonary disease (COPD) (n=120) was setup to help to address this.,The first group (n=18, nine singing and nine controls) started face-to-face (five sessions) before changing to online delivery (seven sessions) due to COVID-19-related physical distancing measures.,As such, the experience of this group is here reported as a pilot study to inform further research in this area.,We conducted semistructured interviews and thematic analysis regarding barriers, facilitators and key considerations for transitioning from face-to-face to online delivery.,Pilot quantitative outcomes include attendance, premeasures and postmeasures of quality of life and disease impact (Short Form 36 Health Survey, COPD Assessment Test score), breathlessness (Medical Research Council breathlessness scale, Dyspnoea-12), depression (Patient Health Questionnaire-9, PHQ-9), anxiety (Generalised Anxiety Disorder-7), balance confidence (Activity specific Balance Confidence, ABC scale) and physical activity (clinical visit PROactive physical activity in COPD tool, combining subjective rating and actigraphy).,Attendance was 69% overall, (90% of the face-to-face sessions, 53% online sessions).,Analysis of semistructured interviews identified three themes regarding participation in SLH delivered face to face and online, these where (1) perceived benefits; (2) digital barriers (online) and (3) digital facilitators (online).,Findings were summarised into key considerations for optimising transitioning singing groups from face-to-face to online delivery.,Pilot quantitative data suggested possible improvements in depression (treatment effect −4.78 PHQ-9 points, p<0.05, MCID 5) and balance confidence (treatment effect +17.21 ABC scale points, p=0.04, MCID 14.2).,This study identifies key considerations regarding the adaptation of SLH from face-to-face to online delivery.,Pilot data suggest online group singing for people with COPD may deliver benefits related to reducing depression and improved balance confidence. | 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. | Objective: This study aimed to investigate the quantitative effects of outdoor air pollution, represented by 10 µg/m3 increment of PM10, on chronic obstructive pulmonary disease in China, United States and European Union through systematic review and meta-analysis.,Methods: Publications in English and Chinese from PubMed and EMBASE were selected.,The Cochrane Review Handbook of Generic Inverse Variance was used to synthesize the pooled effects on incidence, prevalence, mortality and hospital admission.,Results: Outdoor air pollution contributed to higher incidence and prevalence of COPD.,Short-term exposure was associated with COPD mortality increased by 6%, 1% and 1% in the European Union, the United States and China, respectively (p < 0.05).,Chronic PM exposure produced a 10% increase in mortality.,In a short-term exposure to 10 µg/m3 PM10 increment COPD mortality was elevated by 1% in China (p < 0.05) and hospital admission enrollment was increased by 1% in China, 2% in United States and 1% in European Union (p < 0.05).,Conclusions: Outdoor air pollution contributes to the increasing burdens of COPD.10 µg/m3 increase of PM10 produced significant condition of COPD death and exacerbation in China, United States and European Union.,Controlling air pollution will have substantial benefit to COPD morbidity and mortality. | 1 |
Since the Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups A-D were introduced, the lung function changes according to group have been evaluated rarely.,We investigated the rate of decline in annual lung function in patients categorized according to the 2014 GOLD guidelines.,Patients with COPD included in the Korean Obstructive Lung Disease (KOLD) prospective study, who underwent yearly postbronchodilator spirometry at least three times, were included.,The main outcome was the annual decline in postbronchodilator forced expiratory volume in 1 second (FEV1), which was analyzed by random-slope and random-intercept mixed linear regression.,A total 175 participants were included.,No significant postbronchodilator FEV1 decline was observed between the groups (−34.4±7.9 [group A]; −26.2±9.4 [group B]; −22.7±16.0 [group C]; and −24.0±8.7 mL/year [group D]) (P=0.79).,The group with less symptoms (−32.3±7.2 vs −25.0±6.5 mL/year) (P=0.44) and the low risk group (−31.0±6.1 vs −23.6±7.7 mL/year) (P=0.44) at baseline showed a more rapid decline in the postbronchodilator FEV1, but the trends were not statistically significant.,However, GOLD stages classified by FEV1 were significantly related to the annual lung function decline.,There was no significant difference in lung function decline rates according to the GOLD groups.,Prior classification using postbronchodilator FEV1 predicts decline in lung function better than does the new classification. | Little is known about factors that determine health status decline in clinical trials of COPD.,To examine health status changes over 3 years in the TORCH study of salmeterol+fluticasone propionate (SFC) vs. salmeterol alone, fluticasone propionate alone or placebo.,St George's Respiratory Questionnaire (SGRQ) was administered at baseline then every 6 months.,Data from 4951 patients in 28 countries were available.,SFC produced significant improvements over placebo in all three SGRQ domains during the study: (Symptoms -3.6 [95% CI -4.8, -2.4], Activity -2.8 [95% CI -3.9, -1.6], Impacts -3.2 [95% CI -4.3, -2.1]) but the pattern of change over time differed between domains.,SGRQ deteriorated faster in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages III & IV relative to GOLD stage II (p < 0.001).,There was no difference in the relationship between deterioration in SGRQ Total score and forced expiratory volume in one second (FEV1) decline (as % predicted) in men and women.,Significantly faster deterioration in Total score relative to FEV1 % predicted was seen in older patients (≥ 65 years) and there was an age-related change in Total score that was independent of change in FEV1.,The relationship between deterioration in FEV1 and SGRQ did not differ in different world regions, but patients in Asia-Pacific showed a large improvement in score that was unrelated to FEV1 change.,In addition to treatment effects, health status changes in clinical trials may be influenced by demographic and disease-related factors.,Deterioration in health status appears to be fastest in older persons and those with severe airflow limitation.,ClinicalTrials.gov: NCT00268216 | 1 |
Reduced physical activity is an important feature of Chronic Obstructive Pulmonary Disease (COPD).,Various activity monitors are available but their validity is poorly established.,The aim was to evaluate the validity of six monitors in patients with COPD.,We hypothesized triaxial monitors to be more valid compared to uniaxial monitors.,Thirty-nine patients (age 68±7years, FEV1 54±18%predicted) performed a one-hour standardized activity protocol.,Patients wore 6 monitors (Kenz Lifecorder (Kenz), Actiwatch, RT3, Actigraph GT3X (Actigraph), Dynaport MiniMod (MiniMod), and SenseWear Armband (SenseWear)) as well as a portable metabolic system (Oxycon Mobile).,Validity was evaluated by correlation analysis between indirect calorimetry (VO2) and the monitor outputs: Metabolic Equivalent of Task [METs] (SenseWear, MiniMod), activity counts (Actiwatch), vector magnitude units (Actigraph, RT3) and arbitrary units (Kenz) over the whole protocol and slow versus fast walking.,Minute-by-minute correlations were highest for the MiniMod (r = 0.82), Actigraph (r = 0.79), SenseWear (r = 0.73) and RT3 (r = 0.73).,Over the whole protocol, the mean correlations were best for the SenseWear (r = 0.76), Kenz (r = 0.52), Actigraph (r = 0.49) and MiniMod (r = 0.45).,The MiniMod (r = 0.94) and Actigraph (r = 0.88) performed better in detecting different walking speeds.,The Dynaport MiniMod, Actigraph GT3X and SenseWear Armband (all triaxial monitors) are the most valid monitors during standardized physical activities.,The Dynaport MiniMod and Actigraph GT3X discriminate best between different walking speeds. | Persons with Chronic Obstructive Pulmonary Disease (COPD), performing some level of regular physical activity, have a lower risk of both COPD-related hospital admissions and mortality.,COPD patients of all stages seem to benefit from exercise training programs, thereby improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue.,Physical inactivity, which becomes more severe with increasing age, is a point of concern in healthy older adults.,COPD might worsen this scenario, but it is unclear to what degree.,This literature review aims to present the extent of the impact of COPD on objectively-measured daily physical activity (DPA).,The focus is on the extent of the impact that COPD has on duration, intensity, and counts of DPA, as well as whether the severity of the disease has an additional influence on DPA.,A literature review was performed in the databases PubMed [MEDLINE], Picarta, PEDRO, ISI Web of Knowledge and Google scholar.,After screening, 11 studies were identified as being relevant for comparison between COPD patients and healthy controls with respect to duration, intensity, and counts of DPA.,Four more studies were found to be relevant to address the subject of the influence the severity of the disease may have on DPA.,The average percentage of DPA of COPD patients vs. healthy control subjects for duration was 57%, for intensity 75%, and for activity counts 56%.,Correlations of DPA and severity of the disease were low and/or not significant.,From the results of this review, it appears that patients with COPD have a significantly reduced duration, intensity, and counts of DPA when compared to healthy control subjects.,The intensity of DPA seems to be less affected by COPD than duration and counts.,Judging from the results, it seems that severity of COPD is not strongly correlated with level of DPA.,Future research should focus in more detail on the relation between COPD and duration, intensity, and counts of DPA, as well as the effect of disease severity on DPA, so that these relations become more understandable. | 1 |
Chronic obstructive pulmonary disease (COPD) features chronic inflammatory reactions of both intra- and extrapulmonary nature.,Moreover, COPD is associated with abnormal glucose and lipid metabolism in patients, which influences the prognosis and chronicity of this disease.,Abnormal glucose and lipid metabolism are also closely related to inflammation processes.,Further insights into the interactions of inflammation and glucose and lipid metabolism might therefore inspire novel therapeutic interventions to promote lung rehabilitation.,Chemerin, as a recently discovered adipokine, has been shown to play a role in inflammatory response and glucose and lipid metabolism in many diseases (including COPD).,Chemerin recruits inflammatory cells to sites of inflammation during the early stages of COPD, leading to endothelial barrier dysfunction, early vascular remodeling, and angiogenesis.,Moreover, it supports the recruitment of antigen-presenting cells that guide immune cells as part of the body's inflammatory responses.,Chemerin also regulates metabolism via activation of its cognate receptors.,Glucose homeostasis is affected via effects on insulin secretion and sensitivity, and lipid metabolism is changed by increased transformation of preadipocytes to mature adipocytes through chemerin-binding receptors.,Controlling chemerin signaling may be a promising approach to improve various aspects of COPD-related dysfunction.,Importantly, several studies indicate that chemerin expression in vivo is influenced by exercise.,Although available evidence is still limited, therapeutic alterations of chemerin activity may be a promising target of therapeutic approaches aimed at the rehabilitation of COPD patients based on exercises.,In conclusion, chemerin plays an essential role in COPD, especially in the inflammatory responses and metabolism, and has a potential to become a target for, and a biomarker of, curative mechanisms underlying exercise-mediated lung rehabilitation. | Little is known about airway remodelling in bronchial biopsies (BB) in smokers and chronic obstructive pulmonary disease (COPD).,We conducted an initial pilot study comparing BB from COPD patients with nonsmoking controls.,This pilot study suggested the presence of reticular basement membrane (Rbm) fragmentation and altered vessel distribution in COPD.,To determine whether Rbm fragmentation and altered vessel distribution in BB were specific for COPD we designed a cross-sectional study and stained BB from 19 current smokers and 14 ex-smokers with mild to moderate COPD and compared these to 15 current smokers with normal lung function and 17 healthy and nonsmoking subjects.,Thickness of the Rbm was not significantly different between groups; although in COPD this parameter was quite variable.,The Rbm showed fragmentation and splitting in both current smoking groups and ex-smoker COPD compared with healthy nonsmokers (p < 0.02); smoking and COPD seemed to have additive effects.,Rbm fragmentation correlated with smoking history in COPD but not with age.,There were more vessels in the Rbm and fewer vessels in the lamina propria in current smokers compared to healthy nonsmokers (p < 0.05).,The number of vessels staining for vascular endothelial growth factor (VEGF) in the Rbm was higher in both current smoker groups and ex-smoker COPD compared to healthy nonsmokers (p < 0.004).,In current smoker COPD VEGF vessel staining correlated with FEV1% predicted (r = 0.61, p < 0.02).,Airway remodelling in smokers and mild to moderate COPD is associated with fragmentation of the Rbm and altered distribution of vessels in the airway wall.,Rbm fragmentation was also present to as great an extent in ex-smokers with COPD.,These characteristics may have potential physiological consequences. | 1 |
Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD).,The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.,In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.,At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints).,Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint).,All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.,Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk.,Aclidinium/formoterol may be an effective treatment for patients with COPD.,ClinicalTrials.gov: NCT01462942.,The online version of this article (doi:10.1186/1471-2466-14-178) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) represents a significant cause of global morbidity and mortality, with a substantial economic impact.,Recent changes in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidance refined the classification of patients for treatment using a combination of spirometry, assessment of symptoms, and/or frequency of exacerbations.,The aim of treatment remains to reduce existing symptoms while decreasing the risk of future adverse health events.,Long-acting bronchodilators are the mainstay of therapy due to their proven efficacy.,GOLD guidelines recommend combining long-acting bronchodilators with differing mechanisms of action if the control of COPD is insufficient with monotherapy, and recent years have seen growing interest in the additional benefits that combination of long-acting muscarinic antagonists (LAMAs), typified by tiotropium, with long-acting β2-agonists (LABAs), such as formoterol and salmeterol.,Most studies have examined free combinations of currently available LAMAs and LABAs, broadly showing a benefit in terms of lung function and other patient-reported outcomes, although evidence is limited at present.,Several once- or twice-daily fixed-dose LAMA/LABA combinations are under development, most involving newly developed monotherapy components.,This review outlines the existing data for LAMA/LABA combinations in the treatment of COPD, summarizes the ongoing trials, and considers the evidence required to inform the role of LAMA/LABA combinations in treatment of this disease. | 1 |
Chronic obstructive pulmonary disease (COPD) is one of the main contributors to the global burden of disease.,The aim of this systematic review was to quantify the disease burden of COPD in China and to determine the risk factors of the disease.,The number of studies included in the review was 47 with an average quality assessment score of 7.70 out of 10.,Reported COPD prevalence varied between 1.20% and 8.87% in different provinces/cities across China.,The prevalence rate of COPD was higher among men (7.76%) than women (4.07%).,The disease was more prevalent in rural areas (7.62%) than in urban areas (6.09%).,The diagnostic rate of COPD patients in China varied from 23.61% to 30.00%.,The percentage of COPD patients receiving outpatient treatment was around 50%, while the admission rate ranged between 8.78% and 35.60%.,Tobacco exposure and biomass fuel/solid fuel usage were documented as two important risk factors of COPD.,COPD ranked among the top three leading causes of death in China.,The direct medical cost of COPD ranged from 72 to 3,565 USD per capita per year, accounting for 33.33% to 118.09% of local average annual income.,The most commonly used scales for the assessment of quality of life (QoL) included Saint George Respiratory Questionnaire, Airways Questionnaire 20, SF-36, and their revised versions.,The status of QoL was worse among COPD patients than in non-COPD patients, and COPD patients were at higher risks of depression.,The COPD burden in China was high in terms of economic burden and QoL.,In view of the high smoking rate and considerable concerns related to air pollution and smog in China, countermeasures need to be taken to improve disease prevention and management to reduce disease burdens raised by COPD. | Wnt signaling pathways are tightly controlled under a physiological condition, under which they play key roles in many biological functions, including cell fate specification and tissue regeneration.,Increasing lines of evidence recently demonstrated that a dysregulated activation of Wnt signaling, particularly the Wnt/β-catenin signaling, was involved in the pathogenesis of chronic pulmonary diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).,In this respect, Wnt signaling interacts with other cellular signaling pathways to regulate the initiation and pathogenic procedures of airway inflammation and remodeling, pulmonary myofibroblast proliferation, epithelial-to-mesenchymal transition (EMT), and development of emphysema.,Intriguingly, Wnt/β-catenin signaling is activated in IPF; an inhibition of this signaling leads to an alleviation of pulmonary inflammation and fibrosis in experimental models.,Conversely, Wnt/β-catenin signaling is inactivated in COPD tissues, and its reactivation results in an amelioration of airspace enlargement with a restored alveolar epithelial structure and function in emphysema models.,These studies thus imply distinct mechanisms of Wnt/β-catenin signaling in the pathogenesis of these two chronic pulmonary diseases, indicating potential targets for COPD and IPF treatments.,This review article aims to summarize the involvement and pathogenic roles of Wnt signaling pathways in the COPD and IPF, with a focus on the implication of Wnt/β-catenin signaling as underlying mechanisms and therapeutic targets in these two incurable diseases. | 1 |
Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD).,The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.,In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.,At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints).,Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint).,All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.,Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk.,Aclidinium/formoterol may be an effective treatment for patients with COPD.,ClinicalTrials.gov: NCT01462942.,The online version of this article (doi:10.1186/1471-2466-14-178) contains supplementary material, which is available to authorized users. | Sleep quality is often poor in patients with chronic obstructive pulmonary disease (COPD).,A cross-sectional European survey investigated the prevalence of night-time symptoms in COPD to evaluate the level of disconnect between physician and patient perceptions of the presence of night-time symptoms, and to compare the characteristics of patients with and without night-time symptoms.,A total of 251 primary care physicians and 251 respiratory specialists completed record forms on 2,807 patients with COPD.,The forms captured information on patient demographics, lung function, COPD severity, and symptoms.,Patients completed questionnaires on the time of day when their COPD symptoms bothered them, and the impact of COPD on their ability to get up in the morning and on sleep.,Data were compared between groups (those with and without night-time symptoms) using t-tests or Wilcoxon signed rank tests.,The kappa statistic was used to assess the level of disconnect between physician and patient perceptions of the impact of night-time symptoms.,Most patients (78%) reported night-time disturbance.,Patients with night-time symptoms experienced more daytime breathlessness (mean modified Medical Research Council dyspnea scale score 2.4 versus 1.1) and exacerbations in the previous 12 months (mean 1.7 versus 0.4), and received more maintenance therapy (mean of 2.8 versus 2.3 products) than those without.,Concordance between the frequency of physician-reported (67.9% of patients) and patient-reported (68.5% of patients) night-time symptoms was good.,Physicians significantly underestimated the impact of COPD on the patient’s ability to get up in the morning and on sleep (fair-moderate agreement).,Physician-reported night-time symptoms were present for 41.2% of patients who could be categorized by Global initiative for chronic Obstructive Lung Disease (GOLD) group (n=937), increasing from 20.9% of those in the low-risk group to 77.4% of those in the high-riskgroup.,Patients with COPD experience night-time symptoms regardless of GOLD group, that impact on their ability to get up in the morning and on their sleep quality. | 1 |
Rationale: In the phase III, 52-week ETHOS (Efficacy and Safety of Triple Therapy in Obstructive Lung Disease) trial in chronic obstructive pulmonary disease (COPD) (NCT02465567), triple therapy with budesonide/glycopyrrolate/formoterol fumarate (BGF) significantly reduced all-cause mortality compared with glycopyrrolate/formoterol fumarate (GFF).,However, 384 of 8,509 patients were missing vital status at Week 52 in the original analyses.,Objectives: To assess the robustness of the ETHOS mortality findings after additional data retrieval for patients missing Week 52 vital status in the original analyses.,Methods: Patients with moderate to very severe COPD and prior history of exacerbation received twice-daily dosing with 320/18/9.6 μg of BGF (BGF 320), 160/18/9.6 μg of BGF (BGF 160), 18/9.6 μg of GFF, or 320/9.6 μg of budesonide/formoterol fumarate (BFF) (all delivered via a single metered-dose Aerosphere inhaler).,Time to death (all-cause) was a prespecified secondary endpoint.,Measurements and Main Results: In the final retrieved dataset, which included Week 52 vital status for 99.6% of the intent-to-treat population, risk of death with BGF 320 was significantly lower than GFF (hazard ratio, 0.51; 95% confidence interval, 0.33-0.80; unadjusted P = 0.0035).,There were no significant differences in mortality when comparing BGF 320 with BFF (hazard ratio, 0.72; 95% confidence interval, 0.44-1.16; P = 0.1721), nor were significant differences observed when comparing BGF 160 against either dual comparator.,Results were similar when the first 30, 60, or 90 days of treatment were excluded from the analysis.,Deaths from cardiovascular causes occurred in 0.5%, 0.8%, 1.4%, and 0.5% of patients in the BGF 320, BGF 160, GFF, and BFF groups, respectively.,Conclusions: Using final retrieved vital status data, triple therapy with BGF 320 reduced the risk of death compared with GFF, but was not shown to significantly reduce the risk of death compared with BFF, in patients with COPD.,Triple therapy containing a lower dose of inhaled corticosteroid (BGF 160) was not shown to significantly reduce the risk of death compared with the dual therapy comparators. | Salbutamol and ipratropium bromide improve lung function in patients with chronic obstructive pulmonary disease (COPD).,However, their bronchodilating effect has not yet been compared in the central and distal airways.,Functional imaging using computational fluid dynamics offers the possibility of making such a comparison.,The objective of this study was to assess the effects of salbutamol and ipratropium bromide on the geometry and computational fluid dynamics-based resistance of the central and distal airways.,Five patients with Global Initiative for Chronic Obstructive Lung Disease Stage III COPD were randomized to a single dose of salbutamol or ipratropium bromide in a crossover manner with a 1-week interval between treatments.,Patients underwent lung function testing and a multislice computed tomography scan of the thorax that was used for functional imaging.,Two hours after dosing, the patients again underwent lung function tests and repeat computed tomography.,Lung function parameters, including forced expiratory volume in 1 second, vital capacity, overall airway resistance, and specific airway resistance, changed significantly after administration of each product.,On functional imaging, the bronchodilating effect was greater in the distal airways, with a corresponding drop in airway resistance, compared with the central airways.,Salbutamol and ipratropium bromide were equally effective at first glance when looking at lung function tests, but when viewed in more detail with functional imaging, hyporesponsiveness could be shown for salbutamol in one patient.,Salbutamol was more effective in the other patients.,This pilot study gives an innovative insight into the modes of action of salbutamol and ipratropium bromide in patients with COPD, using the new techniques of functional imaging and computational fluid dynamics. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) are progressively limited in their ability to undertake normal everyday activities by a combination of exertional dyspnoea and peripheral muscle weakness.,COPD is characterised by expiratory flow limitation, resulting in air trapping and lung hyperinflation.,Hyperinflation increases acutely under conditions such as exercise or exacerbations, with an accompanying sharp increase in the intensity of dyspnoea to distressing and intolerable levels.,Air trapping, causing increased lung hyperinflation, can be present even in milder COPD during everyday activities.,The resulting activity-related dyspnoea leads to a vicious spiral of activity avoidance, physical deconditioning, and reduced quality of life, and has implications for the early development of comorbidities such as cardiovascular disease.,Various strategies exist to reduce hyperinflation, notably long-acting bronchodilator treatment (via reduction in flow limitation and improved lung emptying) and an exercise programme (via decreased respiratory rate, reducing ventilatory demand), or their combination.,Optimal bronchodilation can reduce exertional dyspnoea and increase a patient's ability to exercise, and improves the chance of successful outcome of a pulmonary rehabilitation programme.,There should be a lower threshold for initiating treatments appropriate to the stage of the disease, such as long-acting bronchodilators and an exercise programme for patients with mild-to-moderate disease who experience persistent dyspnoea. | Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone.,The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.,In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair®/Pressair®)*.,Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV1 (FDCs versus formoterol).,Secondary endpoints were change from baseline in St.,George’s Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24.,Safety and tolerability were also assessed.,At study end, improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001).,Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC.,Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively.,All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies.,Treatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo.,Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD.,Clinicaltrials.gov NCT01437397.,*Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the US as Pressair® and Genuair® within all other licensed territories.,The online version of this article (doi:10.1186/s12931-014-0123-0) contains supplementary material, which is available to authorized users. | 1 |
The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally. | In this study, we analyzed maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) values in a stable COPD population compared with normal subjects.,We evaluated the possible correlation between functional maximal respiratory static pressures and functional and anthropometric parameters at different stages of COPD.,Furthermore, we considered the possible correlation between airway obstruction and MIP and MEP values.,110 patients with stable COPD and 21 age-matched healthy subjects were enrolled in this study.,Patients were subdivided according to GOLD guidelines: 31 mild, 39 moderate and 28 severe.,Both MIP and MEP were lower in patients with severe airway impairment than in normal subjects.,Moreover, we found a correlation between respiratory muscle function and some functional and anthropometric parameters: FEV1 (forced expiratory volume in one second), FVC (forced vital capacity), PEF (peak expiratory flow), TLC (total lung capacity) and height.,MIP and MEP values were lower in patients with severe impairment than in patients with a slight reduction of FEV1.,The measurement of MIP and MEP indicates the state of respiratory muscles, thus providing clinicians with a further and helpful tool in monitoring the evolution of COPD. | 1 |
Self-management interventions for chronic obstructive pulmonary disease (COPD) can improve quality of life, reduce hospital admissions, and improve symptoms.,However, many factors impede engagement for patients and practitioners.,Qualitative research, with its focus on subjective experience, can provide invaluable insights into such factors.,Therefore, a systematic review and synthesis of qualitative evidence on COPD self-management from the perspective of patients, carers, and practitioners was conducted.,Following a systematic search and screening, 31 studies were appraised and data extracted for analysis.,This review found that patients can adapt to COPD; however, learning to self-manage is often a protracted process.,Emotional needs are considerable; frustration, depression, and anxiety are common.,In addition, patients can face an assortment of losses and limitations on their lifestyle and social interaction.,Over time, COPD can consume their existence, reducing motivation.,Support from family can prove vital, yet tinged with ambivalence and burden.,Practitioners may not have sufficient time, resources, or appropriate skills or confidence to provide effective self-management support, particularly in regard to patients’ psychosocial needs.,This can compound patients’ capability to engage in self-management.,For COPD self-management to be effective, patients’ psychosocial needs must be prioritised alongside medication and exacerbation management.,In addition, patients’ personal beliefs regarding COPD and its management should be reviewed periodically to avoid problematic behaviours and enhance positive adaptions to the disease.,Patients with COPD are not a homogenous group and no one intervention will prove effective for all.,Finally, practitioners require greater education, training, and support to successfully assist patients. | Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities.,COPD exacerbations and comorbidities contribute to the overall severity in individual patients.,Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age.,Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations.,However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide.,This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale.,Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases.,All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases.,In this review, we focus on the major comorbidities that affect COPD patients.,We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs.,We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity. | 1 |
The role of the ATP binding cassette transporter A1 (ABCA1) in maintaining cellular lipid homeostasis in cardiovascular disease is well established.,More recently, the important beneficial role played by ABCA1 in modulating pathogenic disease mechanisms, such as inflammation, in a broad range of chronic conditions has been realised.,These studies position ABCA1 as a potential therapeutic target in a diverse range of diseases where inflammation is an underlying cause.,Chronic respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD) are driven by inflammation, and as such, there is now a growing recognition that we need a greater understanding of the signaling pathways responsible for regulation of ABCA1 expression in this clinical context.,While the signaling pathways responsible for cholesterol-mediated ABCA1 expression have been clearly delineated through decades of studies in the atherosclerosis field, and thus far appear to be translatable to the respiratory field, less is known about the cholesterol-independent signaling pathways that can modulate ABCA1 expression in inflammatory lung disease.,This review will identify the various signaling pathways and ligands that are associated with the regulation of ABCA1 expression and may be exploited in future as therapeutic targets in the setting of chronic inflammatory lung diseases. | Past studies have shown that mean values of Interleukin-6 (IL-6) and C-reactive protein (CRP) do not change significantly in COPD patients over a one-year period.,However, longer period follow-up studies are still lacking.,Thus, the aim of this study is to evaluate plasma CRP and IL-6 concentration over three years in COPD patients and to test the association between these inflammatory mediators and disease outcome markers.,A cohort of 77 outpatients with stable COPD was evaluated at baseline, and 53 (mean FEV1, 56% predicted) were included in the prospective study.,We evaluated Interleukin-6 (IL-6), C-reactive protein (CRP), six-minute walking distance (6MWD), and body mass index (BMI) at baseline and after three years.,Plasma concentration of IL-6 was measured by high sensitivity ELISA, and CRP was obtained by high sensitivity particle-enhanced immunonephelometry.,IL-6 increased significantly after 3 years compared to baseline measurements [0.8 (0.5-1.3) vs 2.4 (1.3-4.4) pg/ml; p < 0.001] and was associated with worse 6MWD performance.,In the Cox regression, increased IL-6 at baseline was associated with mortality [Hazard Ratio (95% CI) = 2.68 (0.13, 1.84); p = 0.02].,CRP mean values did not change [5 (1.6-7.9) vs 4.7 (1.7-10) pg/L; p = 0.84], although eleven patients (21%) presented with changes >3 mg/L in CRP after 3 years.,The systemic inflammatory process, evaluated by IL-6, seems to be persistent, progressive and associated with mortality and worse physical performance in COPD patients.,No.:NCT00605540 | 1 |
Asthma and chronic obstructive pulmonary disease (COPD), chronic airway inflammatory diseases characterized by airflow limitation, have different etiologies and pathophysiologies.,Asthma-COPD Overlap (ACO) has recently been used for patients with mixed asthma and COPD.,The pathophysiological mechanisms of ACO have not been clearly understood due to the lack of an appropriate murine model.,To investigate its pathophysiology, we examined a murine model by allergen challenge in surfactant protein‐D (SP‐D)‐deficient mice that spontaneously developed pulmonary emphysema.,SP‐D‐deficient mice were sensitized and challenged by ovalbumin (OVA).,Lungs and bronchoalveolar lavage fluid (BALF) were collected for analysis, and static lung compliance and airway hyperresponsiveness (AHR) were measured 48 h after the last OVA challenge.,In SP‐D‐deficient, naïve, or OVA‐challenged mice, the mean linear intercept and static lung compliance were increased compared with wild‐type (WT) mice.,There was no significant difference in goblet cell hyperplasia and the gene expression of Mucin 5AC (MUC5AC) between SP‐D‐deficient and WT OVA‐challenged mice.,In SP‐D‐deficient OVA‐challenged mice, airway hyperresponsiveness was significantly enhanced despite the lower eosinophil count and the concentration of interleukin (IL)‐5 and IL‐13 in BALF compared with WT OVA‐challenged mice at 120 ventilations per minute.,When mice were ventilated at a lower ventilation frequency of 100 ventilations per minute, elevated airway hyperresponsiveness in SP‐D‐deficient OVA‐challenged mice was diminished.,This model of emphysematous change with allergic airway inflammation raises the possibility that frequency‐dependent airway hyperresponsiveness may be involved in the pathophysiology of ACO. | Asthma-COPD ovelap (ACO) is an umbrella term that encompasses patients with COPD and eosinophilic inflammation (e-COPD) and smoking asthmatics with non-fully reversible airflow obstruction (SA).,We compared the clinical characteristics and the inflammatory profile of e-COPD and SA.,Patients classified as e-COPD were older and more often male and showed significantly impaired pulmonary function (likely explained by a heavier smoking habit).,On the contrary, SA had more atopic features, more reversibility of airflow obstruction and higher IgE levels.,The concentrations of IL-5, IL-13, IL-8, IL-6, TNF-α, IL17 in serum were similar between the 2 groups.,However, Th2-related biomarkers (periostin, FeNO and blood eosinophils) shower higher median values in e-COPD patients.,Our findings reinforce the notion that ACO is a heterogeneous disorder and, as a consequence, it might be unacceptable to offer the same treatment for two related but different conditions. | 1 |
This study aims to (1) examine the variation in implementation of a 2-year chronic obstructive pulmonary disease (COPD) management programme called RECODE, (2) analyse the facilitators and barriers to implementation and (3) investigate the influence of this variation on health outcomes.,Implementation variation among the 20 primary-care teams was measured directly using a self-developed scale and indirectly through the level of care integration as measured with the Patient Assessment of Chronic Illness Care (PACIC) and the Assessment of Chronic Illness Care (ACIC).,Interviews were held to obtain detailed information regarding the facilitators and barriers to implementation.,Multilevel models were used to investigate the association between variation in implementation and change in outcomes.,The teams implemented, on average, eight of the 19 interventions, and the specific package of interventions varied widely.,Important barriers and facilitators of implementation were (in)sufficient motivation of healthcare provider and patient, the high starting level of COPD care, the small size of the COPD population per team, the mild COPD population, practicalities of the information and communication technology (ICT) system, and hurdles in reimbursement.,Level of implementation as measured with our own scale and the ACIC was not associated with health outcomes.,A higher level of implementation measured with the PACIC was positively associated with improved self-management capabilities, but this association was not found for other outcomes.,There was a wide variety in the implementation of RECODE, associated with barriers at individual, social, organisational and societal level.,There was little association between extent of implementation and health outcomes. | Several diseases commonly co-exist with chronic obstructive pulmonary disease (COPD), especially in elderly patients.,This study aimed to investigate whether there is an association between COPD severity and the frequency of comorbidities in stable COPD patients.,In this multicenter, cross-sectional study, patients with spirometric diagnosis of COPD attended to by internal medicine departments throughout Spain were consecutively recruited by 225 internal medicine specialists.,The severity of airflow obstruction was graded using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and data on demographics, smoking history, comorbidities, and dyspnea were collected.,The Charlson comorbidity score was calculated.,Eight hundred and sixty-six patients were analyzed: male 93%, mean age 69.8 (standard deviation [SD] 9.7) years and forced vital capacity in 1 second 42.1 (SD 17.7)%.,Even, the mean (SD) Charlson score was 2.2 (2.2) for stage I, 2.3 (1.5) for stage II, 2.5 (1.6) for stage III, and 2.7 (1.8) for stage IV (P=0.013 between stage I and IV groups), independent predictors of Charlson score in the multivariate analysis were age, smoking history (pack-years), the hemoglobin level, and dyspnea, but not GOLD stage.,COPD patients attended to in internal medicine departments show high scores of comorbidity.,However, GOLD stage was not an independent predictor of comorbidity. | 1 |
Inhaled drug delivery is the cornerstone treatment for asthma and chronic obstructive pulmonary disease (COPD).,However, use of inhaler devices can be challenging, potentially leading to critical errors in handling that can significantly reduce drug delivery to the lungs and effectiveness of treatment.,A systematic review was conducted to define ‘critical’ errors and their impact on health outcomes and resource use between 2004 and 2016, using key search terms for inhaler errors in asthma and COPD (Search-1) and associated health-economic and patient burden (Search-2).,Search-1 identified 62 manuscripts, 47 abstracts, and 5 conference proceedings (n = 114 total).,Search-2 identified 9 studies.,We observed 299 descriptions of critical error.,Age, education status, previous inhaler instruction, comorbidities and socioeconomic status were associated with worse handling error frequency.,A significant association was found between inhaler errors and poor disease outcomes (exacerbations), and greater health-economic burden.,We have shown wide variations in how critical errors are defined, and the evidence shows an important association between inhaler errors and worsened health outcomes.,Given the negative impact diminished disease outcomes impose on resource use, our findings highlight the importance of achieving optimal inhaler technique, and a need for a consensus on defining critical and non-critical errors.,The online version of this article (10.1186/s12931-017-0710-y) contains supplementary material, which is available to authorized users. | With the current wealth of new inhalers available and insurance policy driven inhaler switching, the need for insights in optimal education on inhaler use is more evident than ever.,We aimed to systematically review educational inhalation technique interventions, to assess their overall effectiveness, and identify main drivers of success.,Medline, Embase and CINAHL databases were searched for randomised controlled trials on educational inhalation technique interventions.,Inclusion eligibility, quality appraisal (Cochrane’s risk of bias tool) and data extraction were performed by two independent reviewers.,Regression analyses were performed to identify characteristics contributing to inhaler technique improvement.,Thirty-seven of the 39 interventions included (95%) indicated statistically significant improvement of inhaler technique.,However, average follow-up time was relatively short (5 months), 28% lacked clinical relevant endpoints and all lacked cost-effectiveness estimates.,Poor initial technique, number of inhalation procedure steps, setting (outpatient clinics performing best), and time elapsed since intervention (all, p < 0.05), were shown to have an impact on effectiveness of the intervention, explaining up to 91% of the effectiveness variation.,Other factors, such as disease (asthma vs. chronic obstructive pulmonary disease), education group size (individual vs. group training) and inhaler type (dry powder inhalers vs. pressurised metered dose inhalers) did not play a significant role.,Notably, there was a trend (p = 0.06) towards interventions in adults being more effective than those in children and the intervention effect seemed to wane over time.,In conclusion, educational interventions to improve inhaler technique are effective on the short-term.,Periodical intervention reinforcement and longer follow-up studies, including clinical relevant endpoints and cost-effectiveness, are recommended. | 1 |
Chronic obstructive pulmonary disease (COPD) is one of the most common chronic respiratory diseases with high morbidity and mortality.,It has become the fifth most burdened and the third most deadly disease in the global economy and increases year by year.,The prevention and treatment of COPD are urgent.,Smoking is the main and most common risk factor for COPD.,Cigarette smoke (CS) contains a large number of toxic substances, can cause a series of changes in the trachea, lung tissue, pulmonary blood vessels, and promotes the occurrence and development of COPD.,In recent years, the development of epigenetics and molecular biology have provided new guidance for revealing the pathogenesis, diagnosis, and treatment of diseases.,The latest research indicates that pulmonary vascular endothelial cell apoptosis initiates and participates in the pathogenesis of COPD.,In this review, we summarize the current research on the epigenetic mechanisms and molecular biology of CS-induced pulmonary vascular endothelial cell apoptosis in COPD, providing a new research direction for pathogenesis of COPD and a new target for the diagnosis, treatment, and prevention of COPD. | The purpose of this study was to evaluate the association of serum lymphocyte level with several clinical parameters in COPD.,The study population included 451 COPD patients from the Korean Obstructive Lung Disease cohort study.,Serum lymphocyte level was measured every year along with various clinical parameters, such as lung function, 6-min walking (6 MW) distance, quality of life using COPD assessment test (CAT) and St.,George's Respiratory Questionnaire (SGRQ) scores, exacerbations, and survival.,Serum lymphocyte level less than 20% was considered as a low lymphocyte level.,Normal lymphocyte and low lymphocyte groups comprised of 409 (90.7%) and 42 (9.3%) patients, respectively.,Clustered analysis showed that patients in low lymphocyte group had a lower post-bronchodilator forced expiratory volume in 1 s % predicted (estimated mean = − 5.70%; P = 0.001), a lower forced vital capacity % predicted (estimated mean = − 5.63%; P = 0.005), a shorter 6 MW distance (estimated mean = − 41.31 m; P < 0.001), a higher CAT score (estimated mean = 2.62; P = 0.013), and a higher SGRQ score (estimated mean = 10.10; P < 0.001).,Serum lymphocyte level was not associated with frequent acute exacerbations nor mortality.,Low serum lymphocyte group showed poorer pulmonary function, lower 6 MW distance, and worse quality of life.,Serum lymphocyte levels could be a simple and widely available predictive marker for variable clinical outcomes in COPD patients. | 1 |
Phase III studies demonstrated efficacy and safety of nebulized glycopyrrolate inhalation solution (GLY) in subjects with COPD.,Secondary analyses were performed to examine the effect of background long-acting beta2-agonist (LABA) use on the efficacy and safety of nebulized GLY.,In two 12-week placebo-controlled studies (GOLDEN 3 and GOLDEN 4) and one 48-week, open-label active-controlled study (GOLDEN 5), a total of 2,379 subjects were stratified by background LABA use (LABA-yes: n=861; LABA-no: n=1,518) and randomized to placebo vs GLY 25 or 50 µg twice daily, or GLY 50 µg twice daily vs tiotropium (TIO) 18 µg once daily.,Lung function, patient-reported outcomes, exacerbations, and safety were assessed.,Compared with placebo, pooled data from the 12-week studies showed significant improvements from baseline with GLY 25 and 50 µg across LABA subgroups in trough FEV1 (LABA-yes: 0.101 and 0.110 L; LABA-no: 0.092 and 0.101 L, respectively; P<0.001) and St George’s Respiratory Questionnaire total score (SGRQ; LABA-yes: −2.957 and −3.888; LABA-no: −3.301 and −2.073, respectively; P<0.05).,Incidence of treatment-emergent adverse events (TEAEs) was similar in LABA subgroups, and lower in GLY 25 µg vs placebo.,In the 48-week active-controlled study, GLY and TIO both showed improvement from baseline across LABA subgroups in FEV1 (LABA-yes: 0.106 and 0.092 L; LABA-no: 0.096 and 0.096 L, respectively) and in SGRQ total score (LABA-yes: −5.190 and −3.094; LABA-no: −4.368 and −4.821, respectively).,Incidence of TEAEs was similar between GLY and TIO, and across LABA subgroups.,Exacerbation rates were similar across treatments and LABA subgroups, and cardiovascular events of special interest were more frequent in the LABA-no subgroup.,Nebulized GLY, combined with LABA, did not generate any additional safety signals.,Nebulized GLY demonstrated efficacy and was well tolerated up to 48 weeks in subjects with COPD with/without background LABA. | Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone.,The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.,In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair®/Pressair®)*.,Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV1 (FDCs versus formoterol).,Secondary endpoints were change from baseline in St.,George’s Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24.,Safety and tolerability were also assessed.,At study end, improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001).,Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC.,Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively.,All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies.,Treatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo.,Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD.,Clinicaltrials.gov NCT01437397.,*Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the US as Pressair® and Genuair® within all other licensed territories.,The online version of this article (doi:10.1186/s12931-014-0123-0) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) is a debilitating disease affecting patients in daily life, both physically and emotionally.,Symptoms such as dyspnea and muscle fatigue, lead to exercise intolerance, which, together with behavioral issues, trigger physical inactivity, a key feature of COPD.,Physical inactivity is associated with adverse clinical outcomes, including hospitalization and all-cause mortality.,Increasing activity levels is crucial for effective management strategies and could lead to improved long-term outcomes.,In this review we summarize objective and subjective instruments for evaluating physical activity and focus on interventions such as pulmonary rehabilitation or bronchodilators aimed at increasing activity levels.,To date, only limited evidence exists to support the effectiveness of these interventions.,We suggest that a multimodal approach comprising pulmonary rehabilitation, pharmacotherapy, and counselling programs aimed at addressing emotional and behavioural aspects of COPD may be an effective way to increase physical activity and improve health status in the long term. | The GOLD guidelines suggest that the presence of a post-bronchodilator forced expiratory volume in one second (FEV1) < 80% of the predicted value in combination with a FEV1/forced vital capacity (FVC) < 70% confirms the diagnosis of COPD.,Limited data exist regarding the accuracy of these criteria to distinguish between COPD and asthma.,The aim of this study therefore was to investigate the diagnostic value of post-bronchodilator lung function parameters in obstructive lung disease.,The pulmonary function tests of 43 (22 = COPD, 21 = asthma) patients with similar baseline characteristics were evaluated (baseline FEV1 were 55.7% ± 7.6%, and 59.3% ± 8.4% predicted for COPD and asthma, respectively).,Bronchodilator responsiveness (BDR) was calculated according to three recognized pulmonary function test criteria.,The first criteria, post-bronchodilator FEV1 < 80% of the predicted value in combination with a post-bronchodilator FEV1/FVC ratio of <70%, had an accuracy of 70% to diagnose COPD.,This combination was very sensitive (100%) in diagnosing COPD, but it was not specific (38%).,The second BDR criteria, defined as an increase of <12% and 200 mL of initial FEV1 and criterion number 3, an increase of < 9% of predicted FEV1, were less sensitive (55% and 59%, respectively), but more specific (81% and 76% respectively) to diagnose COPD.,Our findings suggest that the current recommended spirometric indices are not optimal in differentiating between COPD and asthma. | 1 |
Individuals with a single Z mutation in the SERPINA1 gene that codes for alpha-1 antitrypsin (AAT) are at increased risk for COPD if they have ever-smoked.,Whether additional variants alter the risk for COPD in this population remains unknown.,To determine whether additional SERPINA1 variants impact COPD development in a previously identified MZ (carrier) cohort.,Individuals with prior MZ results and AAT serum level <16uM were recruited from the Alpha-1 Coded Testing study and Alpha-1 Foundation Research Registry.,Participants completed smoking history, demographics, and COPD Severity Score (Range 0-33) using REDCap data capture.,At-home finger-stick tests were performed for next generation sequencing (NGS) at the Biocerna LLC laboratory.,A genetic counselor reviewed records and interviewed participants with additional variants by NGS.,A Wilcoxon Rank Sum test was used to assess correlation between variants and the COPD severity score.,A second SERPINA1 variant of known or possible significance was identified in 6 (5.8%) participants.,One each of ZZ, SZ, FZ, ZSmunich, ZM2obernburg, and Z/c.922G>T genotypes were identified.,ZZ, SZ, and FZ are known pathogenic genotypes.,Smunich is a likely pathogenic variant.,M2obernburg and c.922G>T are variants of uncertain significance.,The ZZ individual was on augmentation therapy when determined MZ by protease inhibitor (Pi) phenotyping; the others had limited targeted genotyping with MZ results.,These six participants with biallelic variants had positive COPD severity scores >1.,Presence of additional variants was not significantly associated with COPD symptoms in this small sample size.,Some diagnosed MZ individuals instead have biallelic variants.,Larger studies are needed to determine COPD-risk liability of variants.,Accurate diagnosis impacts medical management and familial risk assessment.,Pi phenotyping can be confounded by augmentation therapy and liver transplantation.,Because a normal M allele may be reported in the absence of tested mutation(s) in AATD genotyping, clinicians should consider clinical circumstances and laboratory methods when selecting and interpreting AATD tests.,Advanced testing, including NGS, may be beneficial for select individuals with prior MZ results.,This study was registered with clinicaltrials.gov (NCT NCT02810327). | The alpha-1 antitrypsin (AAT) haplotype Pi*S, when inherited along with the Pi*Z haplotype to form a Pi*SZ genotype, can be associated with pulmonary emphysema in regular smokers, and less frequently with liver disease, panniculitis, and systemic vasculitis in a small percentage of people, but this connection is less well established.,Since the detection of cases can allow the application of preventive measures in patients and relatives with this congenital disorder, the objective of this study was to update the prevalence of the SZ genotype to achieve accurate estimates of the number of Pi*SZ subjects worldwide, based on studies performed according to the following criteria: 1) samples representative of the general population, 2) AAT phenotyping characterized by adequate methods, and 3) selection of studies with reliable results assessed with a coefficient of variation calculated from the sample size and 95% confidence intervals.,Studies fulfilling these criteria were used to develop tables and maps with an inverse distance-weighted (IDW) interpolation method, to provide numerical and geographical information of the Pi*SZ distribution worldwide.,A total of 262 cohorts from 71 countries were included in the analysis.,With the data provided by these cohorts, a total of 1,490,816 Pi*SZ were estimated: 708,792 in Europe; 582,984 in America and Caribbean; 85,925 in Africa; 77,940 in Asia; and 35,176 in Australia and New Zealand.,Remarkably, the IDW interpolation maps predicted the Pi*SZ prevalence throughout the entire world even in areas lacking real data.,These results may be useful to plan strategies for future research, diagnosis, and management of affected individuals. | 1 |
This real world study evaluated the effectiveness of switching to closed triple therapy from mono/dual combination or open triple therapy in patients with chronic obstructive pulmonary disease (COPD).,We conducted this retrospective study at a single medical center from December 2014 to September 2020.,Patients with COPD who were stepped up to triple therapy were enrolled.,We analyzed the duration from initial COPD management to open or closed triple therapy and identified the clinical predictors of the patients who needed triple therapy early.,We also evaluated the effectiveness of triple therapy after switching from initial management, and closed triple therapy after switching from open triple therapy.,A total 115 COPD patients who were stepped up to triple therapy from initial treatment were analyzed.,The duration from initial treatment to triple therapy was 22.4 months.,The baseline peripheral blood eosinophil counts of the patients who switched to triple therapy early (n=63, less than 22 months) and those who switched to triple therapy later (n=52, more than 22 months) were similar (489.6 vs 434.5 cells/uL; p=0.589).,After univariate and multivariate analysis, the patients who were older had more acute exacerbations (AEs) in the previous year, asthma and COPD overlap (ACO), and initial dual bronchodilator therapy were stepped up to triple therapy early.,The FEV1 of the patients was significantly increased after switching to open triple therapy from mono bronchodilator therapy.,In addition, switching from initial or open triple therapy to closed triple therapy significantly reduced the incidence of AEs.,COPD patients with high blood eosinophilia, older age, more AEs in the previous year, ACO, and initial dual bronchodilator therapy were stepped up to triple therapy early.,Triple therapy showed improvements in lung function of most patients switching from mono bronchodilator therapy.,After switching to closed triple therapy further reduced the incidence of AEs. | Current practice guidelines for the treatment of COPD recommend the use of combined inhaled corticosteroids and long-acting bronchodilators in severe and very severe patients (GOLD stages III and IV).,The aim of this study was to evaluate, through a simulation model, the economic consequences of this recommendation in Italy.,We developed a cost-effectiveness analysis (CEA) on five alternative therapeutic strategies (salmeterol/fluticasone, SF; formoterol/budesonide, FB; salmeterol alone, S; fluticasone alone, F; control, C).,Published data on the Italian COPD population and efficacy data from international reference trials were fitted in a disease progression model based on a Markov chain representing severity stages and death.,The yearly total direct costs of treating COPD patients in Italy was estimated at approximately €7 billion, with a mean cost per patient per year of around €2450.,Mean survival of the cohort is 11.5 years.,The C and F strategies were dominated (ie, are associated with worse outcomes and higher costs) by all alternatives.,SF and FB were the most effective strategies, with a slight clinical superiority of SF, but they were also marginally more expensive than S.,Incremental cost-effectiveness of SF vs S was €679.5 per avoided exacerbation and €3.3 per symptom-free day.,Compared with current practice, the recommended use of combined inhaled corticosteroids and long-acting bronchodilators for severe and very severe COPD patients has the potential for improving clinical outcomes without increasing healthcare costs. | 1 |
Epithelial-to-mesenchymal transition (EMT), which involves changes in cellular morphology of highly polarized epithelial cells and the gain of mesenchymal cell phenotype with migratory and invasive capacities, is implicated in smoking-related chronic obstructive pulmonary disease (COPD).,However, the interactions of fibroblasts and epithelial cells and the participation of fibroblasts in the EMT processes in COPD are poorly understood.,Here, we investigated the hypothesis that EMT is active in human bronchial epithelial (HBE) cells of COPD patients, and that mediators secreted by lung fibroblasts from COPD patients induce EMT.,Primary HBE cells from normal subjects and COPD patients were purchased from LONZA.,HLFs were derived from resected lung obtained from normal (N) and COPD (D) subjects and their conditioned medium (CM) was collected after 2-day culture in serum-free medium.,The expression of epithelial and mesenchymal markers as well as EMT-related transcription factors in lung biopsies, and in HBE cells following stimulation with CM from both normal human lung fibroblasts (NHLF) and COPD human lung fibroblasts (DHLF) was evaluated by immunohistochemistry, qRT-PCR and western blot.,Basal mRNA expression of mesenchymal markers and EMT-related transcription factors were increased in DHBE cells compared to normal human bronchial epithelial cells (NHBE) cells as well as in COPD lungs.,CM from NHLF significantly induced vimentin expression in both NHBE and COPD human bronchial epithelial cells (DHBE) cells, but only increased N-cadherin expression in DHBE cells.,CM from NHLF significantly induced Twist1 and Twist2 expression in NHBE cells and increased Snai2 (Slug) expression in DHBE cells.,While CM from NHLF had no effect on such EMT markers, CM from DHLF significantly increased the protein expression of E-cadherin and vimentin in NHBE cells compared to control.,N-cadherin expression was upregulated to a greater degree in NHBE cells than DHBE cells.,Only CM from DHLF significantly increased E-/N-cadherin ratio in DHBE cells.,Our results suggest that DHBE cells have partially undergone EMT under baseline conditions.,DHLF-CM promoted EMT in NHBE, suggesting that interactions between fibroblast and epithelial cells may play an important role in the EMT process in COPD. | We recently reported that epithelial-mesenchymal transition (EMT) is active in the airways in chronic obstructive pulmonary disease (COPD), suggesting presence of an active profibrotic and promalignant stroma.,With no data available on potential treatment effects, we undertook a blinded analysis of inhaled corticosteroids (ICS) effects versus placebo on EMT markers in previously obtained endobronchial biopsies in COPD patients, as a “proof of concept” study.,Assessment of the effects of inhaled fluticasone propionate (FP; 500 μg twice daily for 6 months) versus placebo in 34 COPD patients (23 on fluticasone propionate and eleven on placebo).,The end points were epidermal growth factor receptor (EGFR; marker of epithelial activation) and the biomarkers of EMT: reticular basement membrane (Rbm) fragmentation (“hallmark” structural marker), matrix metalloproteinase-9 (MMP-9) cell expression, and S100A4 expression in basal epithelial and Rbm cells (mesenchymal transition markers).,Epithelial activation, “clefts/fragmentation” in the Rbm, and changes in the other biomarkers all regressed on ICS, at or close to conventional levels of statistical significance.,From these data, we have been able to nominate primary and secondary end points and develop power calculations that would be applicable to a definitive prospective study.,Although only a pilot “proof of concept” study, this trial provided strong suggestive support for an anti-EMT effect of ICS in COPD airways.,A larger and fully powered prospective study is now indicated as this issue is likely to be extremely important.,Such studies may clarify the links between ICS use and better clinical outcomes and protection against lung cancer in COPD. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are defined as sustained worsening of a patient’s condition beyond normal day-to-day variations that is acute in onset, and that may also require a change in medication and/or hospitalization.,Exacerbations have a significant and prolonged impact on health status and outcomes, and negative effects on pulmonary function.,A significant proportion of exacerbations are unreported and therefore left untreated, leading to a poorer prognosis than those treated.,COPD exacerbations are heterogeneous, and various phenotypes have been proposed which differ in biologic basis, prognosis, and response to therapy.,Identification of biomarkers could enable phenotype-driven approaches for the management and prevention of exacerbations.,For example, several biomarkers of inflammation can help to identify exacerbations most likely to respond to oral corticosteroids and antibiotics, and patients with a frequent exacerbator phenotype, for whom preventative treatment is appropriate.,Reducing the frequency of exacerbations would have a beneficial impact on patient outcomes and prognosis.,Preventative strategies include modification of risk factors, treatment of comorbid conditions, the use of bronchodilator therapy with long-acting β2-agonists or long-acting muscarinic antagonists, and inhaled corticosteroids.,A better understanding of the mechanisms underlying COPD exacerbations will help to optimize use of the currently available and new interventions for preventing and treating exacerbations. | Histone acetyltransferases (HAT) and histone deacetylases (HDAC) are enzymes that upregulate and down-regulate pro-inflammatory gene transcription respectively.,HDAC2 is required by corticosteroids to switch off activated inflammatory genes and is reduced in lung macrophages in COPD.,We have shown that COPD patients have increased steroid resistant CD28null (senescent) pro-inflammatory T and NKT-like peripheral blood cells (particularly CD8+ subsets) and we hypothesized that these changes would be associated with a loss of HDAC2 from these senescent pro-inflammatory lymphocytes.,Blood was collected from 10 COPD and 10 aged-matched controls.,Intracellular pro-inflammatory cytokines, IFNγ and TNFα, and expression of CD28, HDAC2 and HAT, were determined in lymphocyte subsets in the presence of ± 5 mg/ml theophylline (HDAC2 activator), 10 μM prednisolone and 2.5 ng/ml cyclosporine A (immunosuppressant), using flow cytometry.,There was a loss of HDAC2 from CD28null CD8+ T and NKT-like cells in COPD.,There was a significant negative correlation between HDAC2 expression and the percentage of CD28null CD8+ T and NKT-like cells producing IFNγ or TNFα in all subjects (eg, COPD: R = −.763, p < 0.001 for T-cell IFNγ).,There was a synergistic upregulation of HDAC2 and associated decrease in pro-inflammatory cytokine production in CD28nullCD8+ T and NKT-like cells in the presence of 5 mg/L theophylline + 10−6 M prednisolone or 2.5 ng/mL cyclosporine A (CsA).,Lymphocyte senescence in COPD is associated with loss of HDAC2 in CD28nullCD8+ T and NKT-like cells.,Alternative treatment options such as combined theophylline with low-dose CsA, that inhibit these pro-inflammatory cells, may reduce systemic inflammation in COPD. | 1 |
Dry powder inhalers (DPIs) are often used in asthma and chronic obstructive pulmonary disease (COPD) therapies.,Using the discrete choice experiment (DCE) methodology, this study conducted in France was designed to assess patients’ preferences for different attributes of DPIs.,Attributes of DPIs were defined based on a literature review, patient focus group discussions and interviews with healthcare professionals (qualitative phase of the study).,An online survey was then conducted among French patients with asthma or COPD to elicit patient preferences and willingness to pay (WTP) for these attributes using the DCE methodology (quantitative phase).,A fractional factorial design including three blocks of 12 choice sets was created.,Each choice set comprised three alternatives: two fictitious inhalers and the patient’s current inhaler.,Marginal utilities were estimated using a ranked ordered logit model.,Interactions between attributes and disease (asthma or COPD) were tested.,Six DPI attributes were defined based on the qualitative phase: ease of use/fool-proof priming; accurate and easy-to-read dose counter; dose confirmation; hygiene of the mouthpiece; flexibility of the device handling; ability to use the inhaler with breathing difficulties.,Overall, 201 patients with asthma and 93 with COPD were included in the online survey.,Patients with asthma placed most value on an inhaler that requires one step for dose preparation (WTP €4.83 [95% CI: €3.77-€5.90], relative to an inhaler requiring four steps) and one that could be used during episodes of breathing difficulties (WTP €4.49 [95% CI: €2.95-€6.02]).,Patients with COPD placed most value on an inhaler that could be used during episodes of breathing difficulties (WTP €7.70 [95% CI: €5.65-€9.76]) and on the accuracy of the dose counter (WTP €5.87 [95% CI: €3.98-€ 7.77]).,This study suggests that asthma and COPD patients would be willing to change their inhaler if they were offered the option of a new inhaler with improved characteristics and they place a high value on an inhaler with ease of use during breathing difficulty episodes.,The online version of this article (doi:10.1186/s12890-017-0439-x) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,COPD is characterized by poor treatment adherence, and patient medication preferences may contribute to adherence.,A discrete choice experiment with an internet panel drawn from the USA was used to evaluate preference and willingness to pay (WTP) of COPD patients for long-acting maintenance medications.,Key attributes derived from earlier qualitative research (brief literature review and focus groups) with COPD patients on maintenance therapy included symptom relief, speed of feeling medication start to work, inhaler ease of use, rescue medication use, side effects, and monthly out-of-pocket co-pay.,Patients were presented with hypothetical medications with different profiles and asked which they preferred.,Utilities and marginal WTP in monthly co-pay dollars were estimated for all patients and by severity.,Utilities for 515 participants were in the expected direction and highest for the most favorable attribute levels.,Each attribute evaluated was important, and participants were willing to pay a premium to obtain each benefit.,On average, WTP was as high as $US64 for complete symptom relief, $US59 for no side effects, $US32 to rarely use rescue medication, $US16 for a quick and easy to use inhaler, and $US13 for feeling medication work quickly (within 5 min; average WTP $US18/month for patients with severe/very severe COPD).,As expected, efficacy and safety were most valued by patients; however, this study showed that other COPD medication attributes, such as rescue medication, ease of use, and feeling medication work quickly, are also important in patient preferences. | 1 |
Chronic obstructive pulmonary disease (COPD) produces skeletal muscle atrophy and weakness, leading to impairments of exercise performance.,The mechanical work needed for movement execution is also provided by the passive tension developed by musculoarticular connective tissue.,To verify whether COPD affects this component, the passive viscoelastic properties of the knee joint were evaluated in 11 patients with COPD and in 11 healthy individuals.,The levels of stiffness and viscosity were assessed by means of the pendulum test, consisting in a series of passive leg oscillations.,In addition, to explore the contribution of passive tension in the mechanical output of a simple motor task, voluntary leg flexion-extension movements were performed.,Patients with COPD showed a statistically significant reduction in stiffness and viscosity compared to controls.,Voluntary execution of flexion-extension movements revealed that the electromyographic activity of the Rectus Femoris and Biceps Femoris was lower in patients than in controls, and the low viscoelastic tension in the patients conditioned the performance of active movements.,These results provide novel insights on the mechanism responsible for the movement impairments associated with COPD. | Chronic obstructive pulmonary disease (COPD) is an increasingly prevalent lung disease linked to dysfunctional balance and an increased risk of falls.,The Balance Evaluation Systems Test (BESTest) evaluates the six underlying subcomponents of functional balance.,The aim of this study was to determine the specific balance subcomponents and cut-off scores that discriminate between fallers and non-fallers with COPD to guide fall risk assessment and prevention.,A secondary analysis of cross-sectional data from two prior studies in COPD was performed.,Independent samples t-tests were used to explore the differences in the BESTest sub-system scores between fallers and non-fallers.,Receiver operating characteristic curves were used to determine the optimal subcomponent cut-off scores that identified fallers, and the area under the curve (AUC) was used to assess test accuracy.,Data from 72 subjects with COPD (mean age, 70.3 ± 7.4y; mean forced expiratory volume in 1 second, 38.9 ± 15.8% predicted) were analyzed.,Two BESTest subcomponents, stability limits/verticality (fallers: 75.4%, non-fallers: 83.8%; p=0.002) and postural responses (fallers: 67.5%, non-fallers: 79.7%; p=0.008) distinguished between fallers and non-fallers.,Stability limits/verticality had an AUC of 0.70 and optimal cut-off score of 73.8% for identifying fallers; postural responses had an AUC of 0.67 and optimal cut-off score of 69.4%.,The stability limits/verticality and postural responses subcomponents of the BESTest distinguished between fallers and non-fallers with COPD.,The stability limits/verticality subcomponent can also be used to identify whether an individual with COPD is at risk of falling using a cut-off score of 73.8%.,These findings suggest that specific subcomponents of balance could be targeted to optimize fall risk assessment and prevention in COPD. | 1 |
The objective of this study was to identify the necessary features of pulmonary telerehabilitation (P-TR) from the perspectives of individuals living with chronic lung disease and health care professionals (HCPs) who deliver pulmonary rehabilitation (PR).,Focus groups were carried out with patients (n = 26) and HCPs (n = 26) to elicit and explore their opinions about the critical elements of in-person PR and ideas for how these elements could be supported using technology.,A questionnaire was used to assess technology use, PR experience, and general health status.,Four key elements of PR were identified as critical to P-TR: the social aspect of PR; communicating with HCPs for education and support; using biosensors for monitoring and promoting self-knowledge; and the evolution of support with progress over time.,A range of technology-enabled devices and programs were suggested as means to recreate aspects of these integral elements.,Consultations with patients and HCPs suggest that users are interested in technology and want to ensure it recreates the important aspects of PR.,Patients and HCPs identified similar key elements for P-TR.,The opinions and suggestions of patients and HCPs should be the driving force of innovation if P-TR is to succeed in improving health outcomes. | Chronic obstructive pulmonary disease (COPD) is an obstructive and progressive airway disease associated with an important reduction in daily physical activity and psychological problems that contribute to the patient’s disability and poor health-related quality of life (HRQoL).,Nowadays, pulmonary rehabilitation (PR) plays an essential role in the management of symptomatic patients with COPD, by breaking the vicious circle of dyspnea-decreased activity-deconditioning-isolation.,Indeed the main benefits of comprehensive PR programs for patients with COPD include a decrease in symptoms (dyspnea and fatigue), improvements in exercise tolerance and HRQoL, reduction of health care utilization (particularly bed-days), as well as an increase in physical activity.,Several randomized studies and meta-analyses greatly established the benefits of PR, which additionally, is recommended in a number of influential guidelines.,This review aimed to highlight the impact of PR on COPD patients, focusing on the clinical usefulness of PR, which provides patients a good support for change. | 1 |
For patients with COPD, physical activity (PA) is recommended as the core component of pulmonary rehabilitation, but there is lack of a validated questionnaire for assessing the PA effectively.,To evaluate the reliability and validity of the Chinese version of Physical Activity Scale for the Elderly (PASE-C) in patients with COPD.,A cross-sectional study was conducted with 167 outpatients aged 60 years or older with COPD.,Test−retest reliability and internal consistency were calculated by intraclass correlation coefficient (ICC) and Cronbach’s coefficient α, respectively.,Validity was evaluated by correlation with the International Physical Activity Questionnaire-Short (IPAQ-S), data of pedometer, Self-Efficacy for Managing Chronic Disease 6-Item Scale (SES6), Hospital Anxiety and Depression Scale (HADS), Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), grip strength, and disease characteristics.,The PASE-C had an excellent seven-day test−retest reliability (ICC=0.98) and an acceptable internal consistency (Cronbach’s α=0.71).,The content validity was supported by an item-content validity index, a scale-content validity index/universal agreement, and a scale-content validity index/average value of 0.70-1, 0.70, and 0.93, respectively.,Concurrent validity was tested by correlation with IPAQ-S (r=0.651).,Criterion validity was confirmed by correlation with the walking steps (r=0.611) and energy expenditure (r=0.493).,For construct validity, PASE-C had correlations with SES6 (r=0.396), HADS for depression (r=−0.234), seven subscales of SF-36 (r=0.182-0.525), grip strength (r=0.341), and disease characteristics including the duration of COPD (r=−0.215), modified British Medical Research Council scale (r=−0.354), forced expiratory volume in one second as percentage of predicted (r=0.307), and Global Initiative for Chronic Obstructive Lung Disease grade (r=−0.264), with a good construct validity (all P<0.05).,The PASE-C has acceptable reliability and validity for patients aged 60 years or older with COPD, and it can be used as a valid tool to measure the PA of patients with COPD in the People’s Republic of China. | Multiple factors can influence the severity of chronic obstructive pulmonary disease (COPD) and the functioning of patients with COPD, such as personal characteristics and systemic manifestations.,To evaluate the different factors that can influence the activity and psychosocial impact domains of the Saint George's Respiratory Questionnaire (SGRQ) in COPD patients.,Participants, recruited in a university-based hospital, responded to the SGRQ, and in addition, personal, anthropometric, and clinical data were collected.,The study was approved by the Institutional Ethics Committee.,Data were analyzed using multiple linear regression models, with the SGRQ activity and psychosocial impact scores as outcome variables, and 10 explanatory variables (age, gender, forced expiratory volume in the first second - FEV1, smoking load, body mass index, oxygen therapy, associated diseases, regular physical activity, participation in a formal rehabilitation program, and SGRQ symptoms score) were considered.,The best regression model for predicting the SGRQ activity score (r2=0.477) included gender, FEV1, and SGRQ symptoms.,In contrast, the predictive model with the highest proportion of explained variance in psychosocial impact score (r2=0.426) included the variables gender, oxygen therapy, and SGRQ symptoms.,The results indicate that the outcomes, while based on functioning parameters in COPD patients, could be partly explained by the personal and clinical factors analyzed, especially by the symptoms assessed by the SGRQ.,Thus, it appears that the health conditions of these patients cannot be described by isolated variables, including pulmonary function parameters. | 1 |
Chronic obstructive pulmonary disease is one of the leading causes of morbidity and mortality worldwide and a growing healthcare problem.,Identification of modifiable risk factors for prevention and treatment of COPD is urgent, and the scientific community has begun to pay close attention to diet as an integral part of COPD management, from prevention to treatment.,This review summarizes the evidence from observational and clinical studies regarding the impact of nutrients and dietary patterns on lung function and COPD development, progression, and outcomes, with highlights on potential mechanisms of action.,Several dietary options can be considered in terms of COPD prevention and/or progression.,Although definitive data are lacking, the available scientific evidence indicates that some foods and nutrients, especially those nutraceuticals endowed with antioxidant and anti-inflammatory properties and when consumed in combinations in the form of balanced dietary patterns, are associated with better pulmonary function, less lung function decline, and reduced risk of COPD.,Knowledge of dietary influences on COPD may provide health professionals with an evidence-based lifestyle approach to better counsel patients toward improved pulmonary health. | ► Nrf2 anti-oxidant function is impaired when HDAC activity is inhibited.,► HDAC inhibition decreases Nrf2 protein stability.,► HDAC2 is involved in reduced Nrf2 stability and both correlate in COPD samples.,► HDAC inhibition increases Nrf2 acetylation.,Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes.,However, where high levels of oxidative stress are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although the molecular mechanism for this defect is uncertain.,Here, we show that down-regulation of histone deacetylase (HDAC) 2 causes Nrf2 instability, resulting in reduced anti-oxidant gene expression and increase sensitivity to oxidative stress.,Although Nrf2 protein was clearly stabilized after hydrogen peroxide (H2O2) stimulation in a bronchial epithelial cell line (BEAS2B), Nrf2 stability was decreased and Nrf2 acetylation increased in the presence of an HDAC inhibitor, trichostatin A (TSA).,TSA also reduced Nrf2-regulated heme-oxygenase-1 (HO-1) expression in these cells, and this was confirmed in acute cigarette-smoke exposed mice in vivo.,HDAC2 knock-down by RNA interference resulted in reduced H2O2-induced Nrf2 protein stability and activity in BEAS2B cells, whereas HDAC1 knockdown had no effect.,Furthermore, monocyte-derived macrophages obtained from healthy volunteers (non-smokers and smokers) and COPD patients showed a significant correlation between HDAC2 expression and Nrf2 expression (r = 0.92, p < 0.0001).,Thus, reduced HDAC2 activity in COPD may account for increased Nrf2 acetylation, reduced Nrf2 stability and impaired anti oxidant defences. | 1 |
Pulmonary rehabilitation (PR), delivered as a supervised multidisciplinary program including exercise training, is one of the cornerstones in the chronic obstructive pulmonary disease (COPD) management.,We performed a systematic review and meta-analysis to assess the effect on mortality of a supervised early PR program, initiated during or within 4 weeks after hospitalization with an acute exacerbation of COPD compared with usual post-exacerbation care or no PR program.,Secondary outcomes were days in hospital, COPD related readmissions, health-related quality of life (HRQoL), exercise capacity (walking distance), activities of daily living (ADL), fall risk and drop-out rate.,We identified randomized trials through a systematic search using MEDLINE, EMBASE and Cocharne Library and other sources through October 2017.,Risk of bias was assessed regarding randomization, allocation sequence concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases using the Cochrane Risk of Bias tool.,We included 13 randomized trials (801 participants).,Our meta-analyses showed a clinically relevant reduction in mortality after early PR (4 trials, 319 patients; RR = 0.58 (95% CI: [0.35 to 0.98])) and at the longest follow-up (3 trials, 127 patients; RR = 0.55 (95% CI: [0.12 to 2.57])).,Early PR reduced number of days in hospital by 4.27 days (1 trial, 180 patients; 95% CI: [− 6.85 to − 1.69]) and hospital readmissions (6 trials, 319 patients; RR = 0.47 (95% CI: [0.29 to 0.75])).,Moreover, early PR improved HRQoL and walking distance, and did not affect drop-out rate.,Several of the trials had unclear risk of bias in regard to the randomization and blinding, for some outcome there was also a lack of power.,Moderate quality of evidence showed reductions in mortality, number of days in hospital and number of readmissions after early PR in patients hospitalized with a COPD exacerbation.,Long-term effects on mortality were not statistically significant, but improvements in HRQoL and exercise capacity appeared to be maintained for at least 12 months.,Therefore, we recommend early supervised PR to patients with COPD-related exacerbations.,PR should be initiated during hospital admission or within 4 weeks after hospital discharge.,The online version of this article (10.1186/s12890-018-0718-1) contains supplementary material, which is available to authorized users. | Since the introduction of the Quality and Outcomes framework, there has been some evidence of improvement in the management of chronic obstructive pulmonary disease (COPD) patients in the United Kingdom through increasing rates of smoking cessation advice and immunisations against influenza.,However, it is unknown whether disease-specific management criteria, disease outcomes and diagnosis have improved.,To describe changes in the management and outcomes of patients with COPD in UK general practice between 2000 and 2009.,The study was done on a retrospective cohort using data from The Health Improvement Network UK primary care database.,We calculated age at diagnosis of COPD and death, total number of short-term oral corticosteroid courses and consultations, and proportion of patients with very severe COPD and on triple inhaled therapy for each year between 2000 and 2009.,We identified 92,576 patients with COPD.,The mean age at COPD diagnosis decreased from 68.1 years in 2000 to 66.7 years in 2009.,The mean age at death increased from 78.2 years in 2000 to 78.8 years in 2009.,The number of prescribed courses of oral corticosteroids increased from 0.6 in 2000 to 0.8 in 2009.,The number of consultations increased from 9.4 in 2004 to 11.3 in 2009.,The risk of having very severe COPD decreased from 9.4% in 2004 to 6.8% in 2009.,The likelihood of patients with very severe COPD receiving triple therapy increased from 25% in 2004 to 59% in 2009.,The trends suggest that management and outcomes observed in patients with COPD may have improved since the year 2000. | 1 |
Corticosteroid resistance is a major barrier to effective treatment of COPD.,We have shown that the resistance is associated with decreased expression of glucocorticoid receptor (GCR) by senescent CD28nullCD8+ pro-inflammatory lymphocytes in peripheral blood of COPD patients.,GCR must be bound to molecular chaperones heat shock proteins (Hsp) 70 and Hsp90 to acquire a high-affinity steroid binding conformation, and traffic to the nucleus.,We hypothesized a loss of Hsp70/90 from these lymphocytes may further contribute to steroid resistance in COPD.,Blood was collected from COPD (n = 10) and aged-matched controls (n = 10).,To assess response to steroids, cytotoxic mediators, intracellular pro-inflammatory cytokines, CD28, GCR, Hsp70 and Hsp90 were determined in T and NKT-like cells in the presence of ± 10 μM prednisolone and 2.5 ng/mL cyclosporine A (binds to GCR-Hsp70/90 complex) using flow cytometry, western blot and fluorescence microscopy.,A loss of expression of Hsp90 and GCR from CD28null CD8+ T and NKT-like cells in COPD was noted (Hsp70 unchanged).,Loss of Hsp90 expression correlated with the percentage of CD28null CD8+ T and NKT-like cells producing IFNγ or TNFα in all subjects (eg, COPD: R = −0.763, p = 0.007 for T-cell IFNγ).,Up-regulation of Hsp90 and associated decrease in pro-inflammatory cytokine production was found in CD28nullCD8+ T and NKT-like cells in the presence of 10 μM prednisolone and 2.5 ng/mL cyclosporine A.,Loss of Hsp90 from cytotoxic/pro-inflammatory CD28nullCD8+ T and NKT-like cells could contribute to steroid resistance in COPD.,Combination prednisolone and low-dose cyclosporine A therapy inhibits these pro-inflammatory cells and may reduce systemic inflammation in COPD. | Pro-inflammatory/cytotoxic T cells (IFNγ, TNFα, granzyme B+) are increased in the peripheral circulation in COPD.,NKT-like and NK cells are effector lymphocytes that we have also shown to be major sources of pro-inflammatory cytokines and granzymes.,P-glycoprotein 1 (Pgp1) is a transmembrane efflux pump well characterised in drug resistant cancer cells.,We hypothesized that Pgp1 would be increased in peripheral blood T, NKT-like and NK cells in patients with COPD, and that this would be accompanied by increased expression of IFNγ, TNFα and granzyme B.,We further hypothesized that treatment with cyclosporine A, a Pgp1 inhibitor, would render cells more sensitive to treatment with corticosteroids.,Pgp1, granzyme B, IFNγ and TNFα expression were measured in peripheral blood T, NK and NKT-like cells from COPD patients and control subjects (± cyclosporine A and prednisolone) following in vitro stimulation and results correlated with uptake of efflux dye Calcein-AM using flow cytometry.,There was increased Pgp1 expression by peripheral blood T, NKT-like and NK cells co-expressing IFNγ, TNFα and granzyme B in COPD patients compared with controls (e.g.,%IFNγ/Pgp1 T, NKT-like, NK for COPD (Control): 25(6), 54(27), 39(23)).,There was an inverse correlation between Pgp1 expression and Calcein-AM uptake.,Treatment with 2.5 ng/ml cylosporin A and10-6 M prednisolone resulted in synergistic inhibition of pro-inflammatory cytokines in Pgp1 + cells (p < 0.05 for all).,Treatment strategies that target Pgp1 in T, NKT-like and NK cells may reduce systemic inflammatory mediators in COPD and improve patient morbidity. | 1 |
Quantifying physical activity in chronic obstructive pulmonary disease (COPD) is important as physical inactivity is related to poor health outcomes.,This study analyzed the relationship between patients’ self-reported daily walking time and relevant characteristics related to COPD severity.,Pooled analysis was performed on data from four observational studies on which daily walking time was gathered from a personal interview.,Patients were classified as physically inactive if walking time was <30 min/day.,Walking times were described and compared according to several markers of disease severity.,The mean daily walking time of 5,969 patients was 66 (standard deviation [SD] 47) min/day; 893 (15%) patients were inactive.,A linear dose-response relationship was observed between walking time and the modified Medical Research Council (mMRC) dyspnea score, admissions, COPD assessment test (CAT), body mass index, airway obstruction, dyspnea, exacerbation (BODEx) index, and Charlson index (P<0.001).,Daily walking times were lower in patients classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) B and D (P<0.001).,Often, inactive patients had mMRC or Charlson index >3, post-bronchodilator forced expiratory volume in the first second <30% predicted, at least one hospitalization for COPD, classified as GOLD B or D, BODEx >4, and CAT score >30.,Lower self-reported walking times are related to worse markers of disease severity in COPD. | Chronic obstructive pulmonary disease (COPD) imposes a substantial burden on individuals with the disease, which can include a range of symptoms (breathlessness, cough, sputum production, wheeze, chest tightness) of varying severities.,We present an overview of the biomedical literature describing reported relationships between COPD symptoms and disease burden in terms of quality of life, health status, daily activities, physical activity, sleep, comorbid anxiety, and depression, as well as risk of exacerbations and disease prognosis.,In addition, the substantial variability of COPD symptoms encountered (morning, daytime, and nighttime) is addressed and their implications for disease burden considered.,The findings from this narrative review, which mainly focuses on real-world and observational studies, demonstrate the impact of COPD symptoms on the burden of disease and that improved recognition and understanding of their impact is central to alleviating this burden. | 1 |
There is currently no comprehensive tool to assess the functional health literacy (HL) skills of chronic airway disease (CAD) patients.,The purpose of this article is to describe the development of a new HL measure, the Vancouver Airways Health Literacy Tool (VAHLT).,The tool was developed through the following phases: (1) Tool conceptualization, consisting of: (A) a systematic review (SR), (B) focus group sessions with CAD patients to understand barriers and facilitators to CAD management, (C) a survey with key-informants to obtain strategies to mitigate self-management barriers and validate patient-derived topics, and (D) respiratory physicians’ review of the topics; (2) Scenario and item development; and (3) Tool testing and content validation.,The SR identified the lack of a valid HL measurement tool for CAD patients.,Patients provided an initial shortlist of disease-related self-care topics.,Key-informants helped to finalize topics for inclusion.,Respiratory physicians and patients contributed to the development of a scenario-based questionnaire, which was refined during three rounds of testing to develop a 44-item instrument comprising nine self-management passages.,We highlight the holistic process of integrating information from the literature with knowledge gained from key stakeholders into our tool framework.,Our approach to stakeholder engagement may be of interest to researchers developing similar tools, and could facilitate the development and testing of HL-based interventions to ultimately improve patient outcomes and reduce the burden on the healthcare system. | Health literacy (HL) is a person’s ability to practically apply a wide range of cognitive and non-cognitive skills in health-related decisions.,HL includes five domains: navigate/access, understand, communicate, evaluate, and use of health information and services.,Currently, no tool accurately captures and measures HL in adult patients with asthma and COPD, while utilizing all 5-HL domains.,Develop a comprehensive functional-based measurement tool for adult asthma and/or COPD patients, while assessing HL on routine actions required to manage their chronic respiratory condition(s).,We developed our HL tool based on a conceptualization of the link between HL and asthma and COPD management, during needs assessment stage including; a systematic review, which was followed by patient-oriented focus groups, and key-informant and respirologist interviews.,Preliminary face and content validation were obtained by patients’ and health professionals’ input prior to the pretesting stage.,The needs assessment information enabled us to develop passages in scenario-format and corresponding items to assess HL core domains, in addition to numeracy skills, across nine self-management topics: peak flow meters, prednisone use, pulmonary rehabilitation, action plans, flu shots, inhaler technique, lifestyle (nutrition and exercise), trigger control, and map navigation.,The tool was pretested with asthma and COPD patients to assess its relevance, clarity, and difficulty.,Our systematic review identified the deficiencies of existing HL tools that assessed the HL skills of asthma and COPD patients.,The patient-oriented focus groups (n=93) enabled us to identify self-management topics and develop items for our proposed HL tool, which were enriched by input from 45 key informants (eg, policy makers, clinicians, etc.) and 17 respiratory physicians.,Preliminary pretesting with a new cohort of participants (36 asthma and COPD patients and 39 key informants) aided in the refinement and finalized our tool.,The modified tool included passages and corresponding items related to asthma and COPD management was pretested with 75 asthma/COPD patients who completed the questionnaire and provided their feedback on the clarity, relevance, and difficulty of the tool.,The main barrier to self-management pertained to “communication” skills.,The flu shot was the most relevant topic (91.2%), while map navigation was the least relevant (63.9%).,Action plans were the most difficult topic, where only 55% knew when to utilize their action plans.,Numeracy items challenged COPD patients the most.,We summarized findings from the development and preliminary testing stages of a new asthma/COPD HL tool.,This tool will now be validated with a new cohort of patients.,Knowledge gained in this study has been applied to the final version of the tool, which is currently being validated. | 1 |
This study aimed to generate real-world evidence to assess the burden of comorbidities in COPD patients, to effectively manage these patients and optimize the associated healthcare resource allocation.,ARCTIC is a large, real-world, retrospective cohort study conducted in Swedish COPD patients using electronic medical record data collected between 2000 and 2014.,These patients were studied for prevalence of various comorbidities and for association of these comorbidities with exacerbations, mortality, and healthcare costs compared with an age-, sex-, and comorbidities-matched non-COPD reference population.,A total of 17,479 patients with COPD were compared with 84,514 non-COPD reference population.,A significantly higher prevalence of various comorbidities was observed in COPD patients 2 years post-diagnosis vs. reference population, with the highest percentage increase observed for cardiovascular diseases (81.8% vs.,30.7%).,Among the selected comorbidities, lung cancer was relatively more prevalent in COPD patients vs. reference population (relative risk, RR = 5.97, p < 0.0001).,Ischemic heart disease, hypertension, depression, anxiety, sleep disorders, osteoporosis, osteoarthritis, and asthma caused increased mortality rates in COPD patients.,Comorbidities that were observed to be significantly associated with increased number of severe exacerbations in COPD patients included heart failure, ischemic heart disease, depression/anxiety, sleep disorders, osteoporosis, lung cancer, and stroke.,The cumulative healthcare costs associated with comorbidities over 2 years after the index date were observed to be significantly higher in COPD patients (€27,692) vs. reference population (€5141) (p < 0.0001).,The data support the need for patient-centered treatment strategies and targeted healthcare resource allocation to reduce the humanistic and economic burden associated with COPD comorbidities.,Co-existing conditions should be taken into consideration when treating patients with chronic lung disease to ensure coherent and cost-effective disease management.,In a large-scale study of the Swedish population, Björn Ställberg at Uppsala University and co-workers analyzed electronic medical records spanning fourteen years for 17,479 patients with chronic obstructive pulmonary disease (COPD) and compared their health status with 84,514 age-, sex- and comorbidity-matched non-COPD members of the population.,Patients with COPD were significantly more likely to suffer from co-morbidities two years after initial diagnosis than their non-COPD counterparts, with cardiovascular diseases being the most common comorbidities.,Lung cancer, hypertension, depression and sleep disorders were among other comorbidities more prevalent in the COPD population.,These data support the need for fully integrated, targeted healthcare to reduce mortality and the economic burden associated with COPD. | Within telehealth there are a number of domains relevant to pulmonary care: telemonitoring, teleassistance, telerehabilitation, teleconsultation and second opinion calls.,In the last decade, several studies focusing on the effects of various telemanagement programs for patients with chronic obstructive pulmonary disease (COPD) have been published but with contradictory findings.,From the literature, the best telemonitoring outcomes come from programs dedicated to aged and very sick patients, frequent exacerbators with multimorbidity and limited community support; programs using third-generation telemonitoring systems providing constant analytical and decisionmaking support (24 h/day, 7 days/week); countries where strong community links are not available; and zones where telemonitoring and rehabilitation can be delivered directly to the patient’s location.,In the near future, it is expected that telemedicine will produce changes in work practices, cultural attitudes and organization, which will affect all professional figures involved in the provision of care.,The key to optimizing the use of telemonitoring is to correctly identify who the ideal candidates are, at what time they need it, and for how long.,The time course of disease progression varies from patient to patient; hence identifying for each patient a ‘correct window’ for initiating telemonitoring could be the correct solution.,In conclusion, as clinicians, we need to identify the specific challenges we face in delivering care, and implement flexible systems that can be customized to individual patients’ requirements and adapted to our diverse healthcare contexts. | 1 |
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. | The traditional classification of COPD, which relies solely on spirometry, fails to account for the complexity and heterogeneity of the disease.,Phenotyping is a method that attempts to derive a single or combination of disease attributes that are associated with clinically meaningful outcomes.,Deriving phenotypes entails the use of cluster analyses, and helps individualize patient management by identifying groups of individuals with similar characteristics.,We aimed to systematically review the literature for studies that had derived such phenotypes using unsupervised methods.,Two independent reviewers systematically searched multiple databases for studies that performed validated statistical analyses, free of definitive pre-determined hypotheses, to derive phenotypes among patients with COPD.,Data were extracted independently.,9156 citations were retrieved, of which, 8 studies were included.,The number of subjects ranged from 213 to 1543.,Most studies appeared to be biased: patients were more likely males, with severe disease, and recruited in tertiary care settings.,Statistical methods used to derive phenotypes varied by study.,The number of phenotypes identified ranged from 2 to 5.,Two phenotypes, with poor longitudinal health outcomes, were common across multiple studies: young patients with severe respiratory disease, few cardiovascular co-morbidities, poor nutritional status and poor health status, and a phenotype of older patients with moderate respiratory disease, obesity, cardiovascular and metabolic co-morbidities.,The recognition that two phenotypes of COPD were often reported may have clinical implications for altering the course of the disease.,This review also provided important information on limitations of phenotype studies in COPD and the need for improvement in future studies.,The online version of this article (doi:10.1186/s12931-015-0208-4) contains supplementary material, which is available to authorized users. | 1 |
To establish a database network for the study of alpha-1 antitrypsin deficiency (AATD) and compare the results to CT lung density as the most direct measure of emphysema.,A central electronic database was established to permit the upload of anonymised patient data from remote sites.,Prospectively collected CT data were recorded onto disc, anonymised, analysed at the coordinating centre and compared with the clinical features of the disease.,Tertiary referral centres with expertise in the management of AATD focused on academic Biomedical Research Units and Wellcome Clinical Research Facilities.,Data were collected from 187 patients over 1 year from eight UK academic sites.,This included patient demographics, postbronchodilator physiology, health status and CT.,Analysis was undertaken at the coordinating centre in Birmingham.,Patient recruitment in the 12 months reached 94% of target (set at 200) covering the whole spectrum of the disease from those with normal lung function to very severe chronic obstructive lung disease.,CT scan suitable for analysis was available from 147 (79%) of the patients.,CT density, analysed as the threshold for the lowest 15% of lung voxels, showed statistically significant relationships with the objective physiological parameters of lung function as determined by spirometric Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity staging (p<0.001) and carbon monoxide gas transfer (p<0.01).,Density also correlated with subjective measures of quality of life (p=0.02).,Establishment of the network for data collection and its transfer was highly successful facilitating future collaboration for the study of this rare disease and its management.,CT densitometry correlated well with the objective clinical features of the disease supporting its role as the specific marker of the associated emphysema and its severity.,Correlations with subjective measures of health, however, were generally weak indicating other factors play a role. | Severe alpha 1-antitrypsin (AAT) deficiency (genotype PiZZ) is a well-known risk factor for COPD.,A cohort of PiZZ and PiSZ individuals was identified by the Swedish national neonatal AAT screening program in 1972-1974 and followed up regularly since birth.,Our aim was to study the lung function, respiratory symptoms and health status at the age of 38 years in comparison with a random sample of control subjects selected from the population registry.,The study group included 120 PiZZ, 46 PiSZ and 164 control subjects (PiMM), who answered a questionnaire on smoking habits and symptoms and the Saint George Respiratory Questionnaire (SGRQ) on quality of life.,A total of 89 PiZZ, 33 PiSZ and 92 PiMM subjects underwent spirometry.,Four percent of the PiZZ, 2% of the PiSZ and 12% of the control subjects were current smokers (P=0.008), and 17% of the PiZZ, 9% of the PiSZ and 21% of the control subjects had stopped smoking.,The PiZZ current smokers had a significantly higher (ie, poorer) median activity score according to the SGRQ than the PiZZ never-smokers (P=0.032).,The PiMM current smokers had significantly higher activity score (P<0.001), symptom score (P<0.001), and total score (P=0.001) according to the SGRQ than the PiMM never-smokers.,The PiZZ current smokers had a significantly lower postbronchodilator forced expiratory volume in 1 second (FEV1)% of predicted value (P=0.019) and FEV1/forced vital capacity (FVC) ratio (P=0.032) than the PiZZ never-smokers.,The proportion of subjects with a FEV1/FVC ratio of <0.70, indicating COPD, was significantly higher in the PiZZ current smokers than in the PiZZ never-smokers (P=0.001).,Among the PiSZ and PiMM subjects, the differences in lung function between the smoking subgroups were insignificant.,PiZZ current smokers were found to have signs of COPD before 40 years of age.,Smoking is less common among the AAT-deficient subjects identified by neonatal screening than among their peers in the general population. | 1 |
To estimate patient- and episode-level direct costs of chronic obstructive pulmonary disease (COPD) among commercially insured patients in the US.,In this retrospective claims-based analysis, commercial enrollees with evidence of COPD were grouped into five mutually exclusive cohorts based on the most intensive level of COPD-related care they received in 2006, ie, outpatient, urgent outpatient (outpatient care in addition to a claim for an oral corticosteroid or antibiotic within seven days), emergency department (ED), standard inpatient admission, and intensive care unit (ICU) cohorts.,Patient- level COPD-related annual health care costs, including patient- and payer-paid costs, were compared among the cohorts.,Adjusted episode-level costs were calculated.,Of the 37,089 COPD patients included in the study, 53% were in the outpatient cohort, 37% were in the urgent outpatient cohort, 3% were in the ED cohort, and the standard admission and ICU cohorts together comprised 6%.,Mean (standard deviation, SD) annual COPD-related health care costs (2008 US$) increased across the cohorts (P < 0.001), ranging from $2003 ($3238) to $43,461 ($76,159) per patient.,Medical costs comprised 96% of health care costs for the ICU cohort.,Adjusted mean (SD) episode-level costs were $305 ($310) for an outpatient visit, $274 ($336) for an urgent outpatient visit, $327 ($65) for an ED visit, $9745 ($2968) for a standard admission, and $33,440 for an ICU stay.,Direct costs of COPD-related care for commercially insured patients are driven by hospital stays with or without ICU care.,Exacerbation prevention resulting in reduced need for inpatient care could lower costs. | Acute exacerbations may cause deteriorations in the health status of subjects with chronic obstructive pulmonary disease (COPD).,The present study prospectively evaluated the effects of such exacerbations on the health status and pulmonary function of subjects with COPD over a 6-month period, and examined whether those subjects showed a steeper decline in their health status versus those subjects without exacerbations.,A total of 156 subjects with COPD (mean age 71.4 ± 6.3 years) were included in the analysis.,At baseline and after 6 months, their pulmonary function and health status were evaluated using the Chronic Respiratory Disease Questionnaire (CRQ) and the St.,George's Respiratory Questionnaire (SGRQ).,An acute exacerbation was defined as a worsening of respiratory symptoms requiring the administration of systemic corticosteroids or antibiotics, or both.,Forty-eight subjects experienced one or more exacerbations during the 6-month study period, and showed a statistically and clinically significant decline in Symptom scores on the SGRQ, whereas subjects without exacerbations did not show a clinically significant decline.,Logistic multiple regression analyses confirmed that the exacerbations significantly influenced the Fatigue and Mastery domains of the CRQ, and the Symptoms in the SGRQ.,Twelve subjects with frequent exacerbations demonstrated a more apparent decline in health status.,Although pulmonary function did not significantly decline during the 6-month period, acute exacerbations were responsible for a decline in health status.,To minimize deteriorations in health status, one must prevent recurrent acute exacerbations and reduce the exacerbation frequencies in COPD subjects. | 1 |
The COVID-19 pandemic is associated with severe pneumonia and acute respiratory distress syndrome leading to death in susceptible individuals.,For those who recover, post-COVID-19 complications may include development of pulmonary fibrosis.,Factors contributing to disease severity or development of complications are not known.,Using computational analysis with experimental data, we report that idiopathic pulmonary fibrosis (IPF)- and chronic obstructive pulmonary disease (COPD)-derived lung fibroblasts express higher levels of angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2 entry and part of the renin-angiotensin system that is antifibrotic and anti-inflammatory.,In preclinical models, we found that chronic exposure to cigarette smoke, a risk factor for both COPD and IPF and potentially for SARS-CoV-2 infection, significantly increased pulmonary ACE2 protein expression.,Further studies are needed to understand the functional implications of ACE2 on lung fibroblasts, a cell type that thus far has received relatively little attention in the context of COVID-19. | The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) a pandemic [1].,COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,COVID-19 displays symptoms ranging from mild to severe (pneumonia) that can lead to death in some individuals [2-4].,As of 18 April 2020, there have been 2 280 945 cases of COVID-19 worldwide and 156 354 deaths [5].,SARS-CoV-2 uses the angiotensin-converting enzyme II (ACE-2) as the cellular entry receptor [6].,While the virus can infect individuals of any age, to date, most of the severe cases have been described in those >55 years of age and with significant comorbidities, such as COPD [7].,Here, we determined whether patients with COPD have increased expression of ACE-2 in bronchial epithelial cells in the lower respiratory tract.,Smokers and those with COPD have increased airway expression of ACE-2, which is the entry receptor for the COVID-19 virus.,This may explain the increased risk of severe COVID-19 in these subpopulations and highlight the importance of smoking cessation.https://bit.ly/3bC29es | 1 |
Serum procalcitonin levels have been used as a biomarker of invasive bacterial infection and recently have been advocated to guide antibiotic therapy in patients with chronic obstructive pulmonary disease (COPD).,However, rigorous studies correlating procalcitonin levels with microbiologic data are lacking.,Acute exacerbations of COPD (AECOPD) have been linked to viral and bacterial infection as well as noninfectious causes.,Therefore, we evaluated procalcitonin as a predictor of viral versus bacterial infection in patients hospitalized with AECOPD with and without evidence of pneumonia.,Adults hospitalized during the winter with symptoms consistent with AECOPD underwent extensive testing for viral, bacterial, and atypical pathogens.,Serum procalcitonin levels were measured on day 1 (admission), day 2, and at one month.,Clinical and laboratory features of subjects with viral and bacterial diagnoses were compared.,In total, 224 subjects with COPD were admitted for 240 respiratory illnesses.,Of these, 56 had pneumonia and 184 had AECOPD alone.,A microbiologic diagnosis was made in 76 (56%) of 134 illnesses with reliable bacteriology (26 viral infection, 29 bacterial infection, and 21 mixed viral bacterial infection).,Mean procalcitonin levels were significantly higher in patients with pneumonia compared with AECOPD.,However, discrimination between viral and bacterial infection using a 0.25 ng/mL threshold for bacterial infection in patients with AECOPD was poor.,Procalcitonin is useful in COPD patients for alerting clinicians to invasive bacterial infections such as pneumonia but it does not distinguish bacterial from viral and noninfectious causes of AECOPD. | The identification of biological markers in order to assess different aspects of COPD is an area of growing interest.,The objective of this study was to investigate whether levels of procalcitonin (PCT), C-reactive protein (CRP), and neopterin in COPD patients could be useful in identifying the etiological origin of the exacerbation and assessing its prognosis.,We included 318 consecutive COPD patients: 46 in a stable phase, 217 undergoing an exacerbation, and 55 with pneumonia.,A serum sample was collected from each patient at the time of being included in the study.,A second sample was also collected 1 month later from 23 patients in the exacerbation group.,We compared the characteristics, biomarker levels, microbiological findings, and prognosis in each patient group.,PCT and CRP were measured using an immunofluorescence assay.,Neopterin levels were measured using a competitive immunoassay.,PCT and CRP showed significant differences among the three patient groups, being higher in patients with pneumonia, followed by patients with exacerbation (P < 0.0001).,For the 23 patients with paired samples, PCT and CRP levels decreased 1 month after the exacerbation episode, while neopterin increased.,Neopterin showed significantly lower levels in exacerbations with isolation of pathogenic bacteria, but no differences were found for PCT and CRP.,No significant differences were found when comparing biomarker levels according to the Gram result: PCT (P = 0.191), CRP (P = 0.080), and neopterin (P = 0.109).,However, median values of PCT and CRP were high for Streptococcus pneumoniae, Staphylococcus aureus, and enterobacteria.,All biomarkers were higher in patients who died within 1 month after the sample collection than in patients who died later on.,According to our results, biomarker levels vary depending on the clinical status.,However, the identification of the etiology of infectious exacerbation by means of circulating biomarkers is encouraging, but its main disadvantage is the absence of a microbiological gold standard, to definitively demonstrate their value.,High biomarker levels during an exacerbation episode correlate with the short-term prognosis, and therefore their measurement can be useful for COPD management. | 1 |
The burden of chronic obstructive pulmonary disease (COPD) is high.,Health benefits can be gained in primary care by early detection and preventive measures.,To compare the effectiveness of two strategies for population-based early detection of COPD, taking into account different socioeconomic status (SES) settings.,Practices were randomised on strategy and stratified on SES setting.,The Respiratory Health Screening Questionnaire (RHSQ) was distributed to all participants.,In the practice-managed condition, the practice was responsible for the whole procedure, while in the patient-managed condition, patients were responsible for calculating their RHSQ risk score and applying for a spirometry test.,The main outcome measure was the rate of COPD diagnoses after screening.,More new COPD patients were detected in the practice-managed condition (36%) than in the patient-managed condition (18%).,In low SES practices, more high-risk patients were found (16%) than in moderate-to-high SES practices (9%).,Recalculated for a standard Dutch practice (2,350 patients), the yield would be 8.9 new COPD diagnoses, which is a 20% increase of known cases.,The practice-managed variant of this screening procedure shows a substantial yield of new COPD diagnoses for both low and moderate-to-high SES practices. | COPD is uniquely situated as a chronic disease at the beginning of the 21st century; it is not only an established major cause of mortality and morbidity but is increasing in prevalence despite current medical interventions.,In addition COPD is not a stable disease but its natural history is punctuated by periods of acute deterioration or exacerbations.,Exacerbations generate considerable additional morbidity and mortality, and directly affect patients’ quality of life.,However, despite significant advances in understanding and treating this disease, exacerbations continue to be the major cause of COPD-associated hospitalization, and provision for their management incurs considerable health care costs.,This review will consider the current management of COPD exacerbations and how new clinical strategies may improve outcome of these important clinical events. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of worsening of symptoms, leading to substantial morbidity and mortality.,COPD exacerbations are associated with increased airway and systemic inflammation and physiological changes, especially the development of hyperinflation.,They are triggered mainly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation.,Some patients are particularly susceptible to exacerbations, and show worse health status and faster disease progression than those who have infrequent exacerbations.,Several pharmacological interventions are effective for the reduction of exacerbation frequency and severity in COPD such as inhaled steroids, long-acting bronchodilators, and their combinations.,Non-pharmacological therapies such as pulmonary rehabilitation, self-management, and home ventilatory support are becoming increasingly important, but still need to be studied in controlled trials.,The future of exacerbation prevention is in assessment of optimum combinations of pharmacological and non-pharmacological therapies that will result in improvement of health status, and reduction of hospital admission and mortality associated with COPD. | Recent studies have indicated that arginase, which converts l-arginine into l-ornithine and urea, may play an important role in the pathogenesis of various pulmonary disorders.,In asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis, increased arginase activity in the airways may contribute to obstruction and hyperresponsiveness of the airways by inducing a reduction in the production of bronchodilatory nitric oxide (NO) that results from its competition with constitutive (cNOS) and inducible (iNOS) NO synthases for their common substrate.,In addition, reduced l-arginine availability to iNOS induced by arginase may result in the synthesis of both NO and the superoxide anion by this enzyme, thereby enhancing the production of peroxynitrite, which has procontractile and pro-inflammatory actions.,Increased synthesis of l-ornithine by arginase may also contribute to airway remodelling in these diseases. l-Ornithine is a precursor of polyamines and l-proline, and these metabolic products may promote cell proliferation and collagen production, respectively.,Increased arginase activity may also be involved in other fibrotic disorders of the lung, including idiopathic pulmonary fibrosis.,Finally, through its action of inducing reduced levels of vasodilating NO, increased arginase activity has been associated with primary and secondary forms of pulmonary hypertension.,Drugs targeting the arginase pathway could have therapeutic potential in these diseases. | 1 |
Although traffic exposure has been associated with the development of COPD, the role of particulate matter <10 μm in aerodynamic diameter (PM10) in the pathogenesis of COPD is not yet fully understood.,We assessed the 1-year effect of exposure to PM10 on the pathogenesis of COPD in a retrospective cohort study.,We recruited 53 subjects with COPD stages III and IV and 15 healthy controls in a hospital in Taiwan.,We estimated the 1-year annual mean levels of PM10 at all residential addresses of the cohort participants.,Changes in PM10 for the 1-year averages in quintiles were related to diffusion capacity of the lung for carbon monoxide levels (r=−0.914, P=0.029), changes in the pulse oxygen saturation (ΔSaO2; r=−0.973, P=0.005), receptor for advanced glycation end-products (r=−0.881, P=0.048), interleukin-6 (r=0.986, P=0.002), ubiquitin (r=0.940, P=0.017), and beclin 1 (r=0.923, P=0.025) in COPD.,Next, we observed that ubiquitin was correlated with ΔSaO2 (r=−0.374, P=0.019).,Beclin 1 was associated with diffusion capacity of the lung for carbon monoxide (r=−0.362, P=0.028), ΔSaO2 (r=−0.354, P=0.032), and receptor for advanced glycation end-products (r=−0.471, P=0.004).,Autophagy may be an important regulator of the PM10-related pathogenesis of COPD, which could cause deterioration in the lung diffusion capacity and oxygen saturation. | Chronic obstructive pulmonary disease (COPD) is a multicomponent condition that is characterised by airflow obstruction that is not fully reversible and is a major global cause of morbidity and mortality.,The most widely used marker of disease severity and progression is FEV1.,However, FEV1 correlates poorly with both symptoms and other measures of disease progression and thus there is an urgent need for other biological markers to better characterise individuals with COPD.,Fibrinogen is an acute phase plasma protein that has emerged as a promising biomarker in COPD.,Here we review the current clinical evidence linking fibrinogen with COPD and its associated co-morbidities and discuss its potential utility as a biomarker.,Searches for appropriate studies were undertaken on PubMed using search terms fibrinogen, COPD, emphysema, chronic bronchitis, FEV1, cardiovascular disease, exacerbation and mortality.,There is strong evidence of an association between fibrinogen and the presence of COPD, the presence and frequency of exacerbations and with mortality.,Fibrinogen is associated with disease severity but does not predict lung function decline, a measure used as a surrogate for disease activity.,The role of fibrinogen in identifying inflammatory co morbidities, particularly cardiovascular disease, remains unclear.,Fibrinogen is reduced by p38 mitogen-activated protein kinase inhibitors in individuals with stable disease and by oral corticosteroids during exacerbations.,Fibrinogen is likely to be a useful biomarker to stratify individuals with COPD into those with a high or low risk of future exacerbations and may identify those with a higher risk of mortality. | 1 |
One hundred million deaths were caused by tobacco in the 20th century, and it is estimated that there will be up to one billion deaths attributed to tobacco use in the 21st century.,Chronic obstructive pulmonary disease (COPD) is rapidly becoming a global public health crisis with smoking being recognized as its most important causative factor.,The most effective available treatment for COPD is smoking cessation.,There is mounting evidence that the rate of progression of COPD can be reduced when patients at risk of developing the disease stop smoking, while lifelong smokers have a 50% probability of developing COPD during their lifetime.,More significantly, there is also evidence that the risk of developing COPD falls by about half with smoking cessation.,Several pharmacological interventions now exist to aid smokers in cessation; these include nicotine replacement therapy, bupropion, and varenicline.,All pharmacotherapies for smoking cessation are more efficacious than placebo, with odds ratios of about 2.,Pharmacologic therapy should be combined with nonpharmacologic (behavioral) therapy.,Unfortunately, despite the documented efficacy of these agents, the absolute number of patients who are abstinent from smoking at 12 months of follow-up is low. | Few studies have investigated the independent effects of occupational exposures and smoking on chronic bronchitis and airflow obstruction.,We assessed the association between lifetime occupational exposures and airflow obstruction in a cross-sectional survey in an urban-industrial area of Catalonia, Spain.,We interviewed 576 subjects of both sexes aged 20-70 years (response rate 80%) randomly selected from census rolls, using the ATS questionnaire.,Forced spirometry was performed by 497 subjects according to ATS normative.,Lifetime occupational exposure to dust, gases or fumes was reported by 52% of the subjects (63% in men, 41% in women).,Textile industry was the most frequently reported job in relation to these exposures (39%).,Chronic cough, expectoration and wheeze were more prevalent in exposed subjects with odds ratios ranging from 1.7 to 2.0 being highest among never-smokers (2.1 to 4.3).,Lung function differences between exposed and unexposed subjects were dependent on duration of exposure, but not on smoking habits.,Subjects exposed more than 15 years to dusts, gases or fumes had lower lung function values (FEV1 -80 ml, 95% confidence interval (CI) -186 to 26; MMEF -163 ml, CI -397 to 71; FEV1/FVC ratio -1.7%, CI -3.3 to -0.2) than non-exposed.,Chronic bronchitis symptoms and airflow obstruction are associated with occupational exposures in a population with a high employment in the textile industry.,Lung function impairment was related to the duration of occupational exposure, being independent of the effect of smoking. | 1 |
The aim of the study was to determine the expression profile of long noncoding RNAs (lncRNAs) in CD4+ T cells from COPD patients and explore the clinical value of the lncRNAs.,First, microarray analysis was performed.,Differentially expressed lncRNAs were validated by quantitative real-time reverse transcription-PCR (qRT-PCR) in samples from 56 patients with acute exacerbations of COPD (AECOPD), 56 patients with stable COPD, and 35 healthy controls.,Meanwhile, the clinical value was tested by receiver operating characteristic curve analysis.,The functions of lncRNAs were analyzed by the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database.,The potential target genes that might be regulated by NR-026690 and ENST00000447867 were identified by the lncRNA-mRNA network and competing endogenous RNA network.,The transcriptional expression level of rap guanine nucleotide exchange factor 3 (RAPGEF3) was tested by qRT-PCR.,The correlation of the expression between NR-026690, ENST00000447867, and RAPGEF3 was analyzed by Spearman’s correlation test.,We found that the relative expression levels of ENST00000447867 and NR-026690 in the CD4+ T cells of AECOPD patients were significantly higher than in the stable COPD patients and control subjects by microarray and qRT-PCR validation.,The transcriptional expression level of RAPGEF3 in the CD4+ T cells was significantly higher in the AECOPD group compared to the control group (P<0.01) and the stable COPD group (P<0.05).,RAPGEF3 expression was positively associated with NR-026690 (r=0.4925, P<0.01) and ENST00000447867 (r=0.4065, P<0.01).,NR-026690 and ENST00000447867 might be potential biomarkers for COPD.,They might affect RAPGEF3 as miRNA sponges to regulate COPD development. | Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation.,Autophagy is a degradative process involving lysosomal turnover of cellular components, though its role in human diseases remains unclear.,Increased autophagy was observed in lung tissue from COPD patients, as indicated by electron microscopic analysis, as well as by increased activation of autophagic proteins (microtubule-associated protein-1 light chain-3B, LC3B, Atg4, Atg5/12, Atg7).,Cigarette smoke extract (CSE) is an established model for studying the effects of cigarette smoke exposure in vitro.,In human pulmonary epithelial cells, exposure to CSE or histone deacetylase (HDAC) inhibitor rapidly induced autophagy.,CSE decreased HDAC activity, resulting in increased binding of early growth response-1 (Egr-1) and E2F factors to the autophagy gene LC3B promoter, and increased LC3B expression.,Knockdown of E2F-4 or Egr-1 inhibited CSE-induced LC3B expression.,Knockdown of Egr-1 also inhibited the expression of Atg4B, a critical factor for LC3B conversion.,Inhibition of autophagy by LC3B-knockdown protected epithelial cells from CSE-induced apoptosis.,Egr-1 −/− mice, which displayed basal airspace enlargement, resisted cigarette-smoke induced autophagy, apoptosis, and emphysema.,We demonstrate a critical role for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke exposure in vitro and in vivo.,The induction of autophagy at early stages of COPD progression suggests novel therapeutic targets for the treatment of cigarette smoke induced lung injury. | 1 |
Female smokers have increased risk of chronic obstructive pulmonary disease (COPD) compared with male smokers who have a similar history of cigarette smoke exposure.,We have shown previously that chronic smoke exposure for 6 months leads to increased airway wall remodeling in female C57BL/6 mice compared with male C57BL/6 mice.,These differences, however, were not evident in female ovariectomized mice exposed to cigarette smoke.,Herein, we report on the pulmonary function test results from the flexiVent system, which was used to determine the potential functional consequences of the histologic changes observed in these mice.,We found that tissue damping (G) was increased in female compared to male or ovariectomized female mice after smoke exposure.,At low oscillating frequencies, complex input resistance (Zrs) and impedance (Xrs) of the respiratory system was increased and decreased, respectively, in female but not in male or ovariectomized female mice after smoke exposure.,Quasistatic pressure-volume curves revealed a reduction in inspiratory capacity in female mice but not in male or ovariectomized female mice after smoke exposure.,The remaining lung function measurements including quasistatic compliance were similar amongst all groups.,This is the first study characterizing a sexual dimorphism in respiratory functional properties in a mouse model of COPD.,These findings demonstrate that increased airway remodeling in female mice following chronic smoke exposure is associated with increased tissue resistance in the peripheral airways.,These data may explain the importance of female sex hormones and the increased risk of airway disease in female smokers. | Systemic inflammation is present in chronic obstructive pulmonary disease (COPD).,A whey peptide-based enteral diet reduce inflammation in patients with COPD, but its effect on COPD development has not been determined.,On the other hand, it is known that short chain fatty acids (SCFAs), which are produced by micro-flora in the gut, attenuates bronchial asthma in mice model.,Mice with elastase-induced emphysema were fed with 1 of 3 diets (control diet, whey peptide-based enteral diet, or standard enteral diet) to determine the effects of whey peptide-based enteral diet on emphysema and on cecal SCFAs.,The whey peptide-based enteral diet group exhibited fewer emphysematous changes; significantly lower total cell counts in bronchoalveolar lavage fluid (BALF); and significantly higher cecal SCFA levels than either the control or standard enteral diet groups.,The total cell count was inversely correlated with total cecal SCFA levels in these three diet groups.,The whey peptide-based enteral diet attenuates elastase-induced emphysema through the suppression of inflammation in the lung.,This may be related to the increase in cecal SCFA. | 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. | Because pulmonary embolism (PE) and COPD exacerbation have similar presentations and symptoms, PE can be overlooked in COPD patients.,Our objective was to determine the prevalence of PE during COPD exacerbation and to describe the clinical aspects in COPD patients diagnosed with PE.,This was a prospective study conducted at a university hospital in the city of Ankara, Turkey.,We included all COPD patients who were hospitalized due to acute exacerbation of COPD between May of 2011 and May of 2013.,All patients underwent clinical risk assessment, arterial blood gas analysis, chest CT angiography, and Doppler ultrasonography of the lower extremities.,In addition, we measured D-dimer levels and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels.,We included 172 patients with COPD.,The prevalence of PE was 29.1%.,The patients with pleuritic chest pain, lower limb asymmetry, and high NT-pro-BNP levels were more likely to develop PE, as were those who were obese or immobile.,Obesity and lower limb asymmetry were independent predictors of PE during COPD exacerbation (OR = 4.97; 95% CI, 1.775-13.931 and OR = 2.329; 95% CI, 1.127-7.105, respectively).,The prevalence of PE in patients with COPD exacerbation was higher than expected.,The association between PE and COPD exacerbation should be considered, especially in patients who are immobile or obese.,Visto que a embolia pulmonar (EP) e a exacerbação da DPOC têm apresentação e sintomas comuns, o diagnóstico de EP pode ser negligenciado nesses pacientes.,Nosso objetivo foi determinar a prevalência de EP durante a exacerbação da DPOC e descrever os aspectos clínicos em portadores de DPOC diagnosticados com EP.,Estudo prospectivo conduzido em um hospital universitário na cidade de Ancara, Turquia.,Entre maio de 2011 e maio de 2013, todos os pacientes hospitalizados por exacerbação aguda da DPOC foram incluídos no estudo.,Todos os pacientes foram submetidos a avaliação de risco clínico, gasometria arterial, angiotomografia de tórax e ultrassonografia Doppler de membros inferiores.,Além disso, foram medidos os níveis de dímero-D e de N-terminal pro-brain natriuretic peptide (NT-pro-BNP).,Foram incluídos 172 pacientes com DPOC.,A prevalência de EP foi de 29,1 %.,Os pacientes com DPOC e dor torácica pleurítica, assimetria de membros inferiores e altos níveis de NT-pro-BNP, assim como aqueles que estavam obesos ou imobilizados, apresentavam maior probabilidade de desenvolver EP.,Obesidade e assimetria de membros inferiores foram preditores independentes de EP nos pacientes com exacerbação da DPOC (OR = 4,97; IC95%, 1,775-13,931 e OR = 2,329; IC95% CI, 1,127-7,105, respectivamente).,A prevalência de EP em pacientes com exacerbação da DPOC foi maior que a esperada.,A associação entre EP e exacerbação da DPOC deve ser considerada nesses pacientes, especialmente naqueles imobilizados ou obesos. | 1 |
Non-typeable Haemophilus influenzae (NTHi) is an ubiquitous commensal-turned-pathogen that colonises the respiratory mucosa in airways diseases including Chronic Obstructive Pulmonary Disease (COPD).,COPD is a progressive inflammatory syndrome of the lungs, encompassing chronic bronchitis that is characterised by mucus hypersecretion and impaired mucociliary clearance and creates a static, protective, humid, and nutrient-rich environment, with dysregulated mucosal immunity; a favourable environment for NTHi colonisation.,Several recent large COPD cohort studies have reported NTHi as a significant and recurrent aetiological pathogen in acute exacerbations of COPD.,NTHi proliferation has been associated with increased hospitalisation, disease severity, morbidity and significant lung microbiome shifts.,However, some cohorts with patients at different severities of COPD do not report that NTHi is a significant aetiological pathogen in their COPD patients, indicating other obligate pathogens including Moraxella catarrhalis, Streptococcus pneumoniae and Pseudomonas aeruginosa as the cause.,NTHi is an ubiquitous organism across healthy non-smokers, healthy smokers and COPD patients from childhood to adulthood, but it currently remains unclear why NTHi becomes pathogenic in only some cohorts of COPD patients, and what behaviours, interactions and adaptations are driving this susceptibility.,There is emerging evidence that biofilm-phase NTHi may play a significant role in COPD.,NTHi displays many hallmarks of the biofilm lifestyle and expresses key biofilm formation-promoting genes.,These include the autoinducer-mediated quorum sensing system, epithelial- and mucus-binding adhesins and expression of a protective, self-produced polymeric substance matrix.,These NTHi biofilms exhibit extreme tolerance to antimicrobial treatments and the immune system as well as expressing synergistic interspecific interactions with other lung pathogens including S. pneumoniae and M. catarrhalis.,Whilst the majority of our understanding surrounding NTHi as a biofilm arises from otitis media or in-vitro bacterial monoculture models, the role of NTHi biofilms in the COPD lung is now being studied.,This review explores the evidence for the existence of NTHi biofilms and their impact in the COPD lung.,Understanding the nature of chronic and recurrent NTHi infections in acute exacerbations of COPD could have important implications for clinical treatment and identification of novel bactericidal targets. | Infection-related exacerbations of respiratory diseases are a major health concern; thus understanding the mechanisms driving them is of paramount importance.,Despite distinct inflammatory profiles and pathological differences, asthma and COPD share a common clinical facet: raised airway ATP levels.,Furthermore, evidence is growing to suggest that infective agents can cause the release of extracellular vesicle (EVs) in vitro and in bodily fluids.,ATP can evoke the P2X7/caspase 1 dependent release of IL-1β/IL-18 from EVs; these cytokines are associated with neutrophilia and are increased during exacerbations.,Thus we hypothesized that respiratory infections causes the release of EVs in the airway and that the raised ATP levels, present in respiratory disease, triggers the release of IL-1β/IL-18, neutrophilia and subsequent disease exacerbations.,To begin to test this hypothesis we utilised human cell-based assays, ex vivo murine BALF, in vivo pre-clinical models and human samples to test this hypothesis.,Data showed that in a murine model of COPD, known to have increased airway ATP levels, infective challenge causes exacerbated inflammation.,Using cell-based systems, murine models and samples collected from challenged healthy subjects, we showed that infection can trigger the release of EVs.,When exposed to ATP the EVs release IL-1β/IL-18 via a P2X7/caspase-dependent mechanism.,Furthermore ATP challenge can cause a P2X7 dependent increase in LPS-driven neutrophilia.,This preliminary data suggests a possible mechanism for how infections could exacerbate respiratory diseases and may highlight a possible signalling pathway for drug discovery efforts in this area. | 1 |
Based on blood and sputum samples, up to 40% of patients with COPD have eosinophilic inflammation; however, there is little epidemiology data characterizing the health care burden within this sub-population.,Given that COPD-attributable medical costs in the USA are predicted to approach $50 billion by 2020, we analyzed the effect of blood eosinophil counts and exacerbations on health care resource utilization and costs.,This cross-sectional study used electronic medical records and insurance claims data from the Reliant Medical Group (January 2011-December 2015).,Eligible patients were ≥40 years of age, continuously enrolled during the year of interest (2012, 2013, 2014, or 2015), had ≥1 COPD-related code in the preceding year, and documented maintenance therapy use.,Patients with ≥1 blood eosinophil count recorded were stratified into 2 cohorts: <150 cells/µL and ≥150 cells/µL.,Endpoints included demographics, clinical characteristics, health care resource utilization, and costs.,The impact of blood eosinophil count and exacerbation patterns on health care resource utilization and costs was assessed with multivariate analyses.,On average, 2,832 eligible patients were enrolled annually, of whom ~28% had ≥1 eosinophil count recorded during the year.,The ≥150 cells/µL cohort had numerically higher all-cause and COPD-related health care resource utilization and cost each year compared with the <150 cells/µL cohort, but varied by service and year.,Among patients with exacerbations, the ≥150 cells/µL cohort exhibited significantly higher COPD-related costs compared with the <150 cells/µL cohort.,Blood eosinophil counts may be a useful biomarker for burden of disease in a subgroup of patients with COPD. | We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy.,Three studies of ≥1-year duration met the inclusion criteria.,Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%).,At baseline, 57-75% of patients had ≥2% blood eosinophils.,Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level.,For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001).,No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively).,In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo).,No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ.,Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations. | 1 |
The therapeutic value of inhaled corticosteroids (ICSs) for COPD is limited.,In published RCTs, ICS could be withdrawn in COPD patients without increasing exacerbation risk when bronchodilator treatment is optimized.,Here we report on the feasibility and risks of ICS withdrawal in Dutch general practice for COPD patients without an indication for ICSs.,In our pragmatic trial, general practitioners decided autonomously which of their COPD patients on ICS treatment could stop this, how this was done, and whether additional bronchodilator therapy was needed.,We recruited 62 COPD patients (58 analysed) who were eligible for ICS withdrawal in 79 practices.,In 32 patients (55.2%, 95% CI: 42.5-67.3%) ICS was withdrawn successfully, 19 (32.8%, 95% CI: 22.1-45.6%) restarted ICS treatment within six months, 12 patients (20.7%, 95% CI: 12.3-32.8%) had a moderate exacerbation, and one patient had a severe exacerbation.,ICS withdrawal was successful in just over half of the patients with COPD without an indication for ICS. | To prevent unnecessary use of inhaled corticosteroids (ICS), ICS treatment should only be started when the diagnostic process of asthma and COPD is completed.,Little is known about the chronological order between these diagnoses and the start of ICS.,We performed a retrospective cohort study, based on electronic medical records of 178 Dutch general practices, to explore the temporal relations between starting continuous use of ICS and receiving a diagnosis of asthma and/or COPD.,The database included information of patients who were registered with a diagnosis of asthma and/or COPD in one of the practices during January 1, 2012 and December 31, 2013.,Two or more successive prescriptions of ICS within 6 months were considered as continuous ICS treatment.,The chronological order of events based on available dates were analysed using descriptive analyses.,For 8507 patients with asthma, 4024 patients with COPD, and 801 patients with asthma-COPD overlap (ACO), the order of events could be analysed.,In total, 1857 (14.4%) patients started ICS prior to their diagnosis, 11.5, 20.8, and 10.0% of patients with asthma, COPD, and ACO, respectively.,In 53.4% of the patients, the first prescription of ICS was a combination inhaler with a long-acting bronchodilator.,In this real-life primary care cohort, one in seven patients started ICS treatment prior to their diagnosis and approximately half of the patients started with a combination inhaler.,Our findings suggest that there is relevant room for improvement in the pharmaceutical management of patients with these chronic respiratory diseases. | 1 |
Alterations in microRNA (miRNA) expression may contribute to COPD pathogenesis.,In COPD, lung fibroblast repair functions are altered in multiple ways, including extracellular mediator release.,Our prior study revealed miR-503 expression is decreased in COPD lung fibroblasts, although the exact role played by miR-503 is undetermined.,The current study examined a role of miR-503 in cytokine, growth factor and fibronectin production by lung fibroblasts from patients with and without COPD.,Primary adult lung fibroblasts were isolated from patients with or without COPD.,MiR-503 expression and interleukin (IL)-6, -8, PGE2, HGF, KGF, VEGF and fibronectin release were examined with or without inflammatory cytokines, IL-1β and tumor necrosis factor (TNF)-α.,MiR-503 expression was decreased in COPD lung fibroblasts.,The expression of miR-503 was positively correlated with %FVC, %FEV1, and %DLco as well as IL-6, -8, PGE2, HGF, KGF, and VEGF in the absence or presence of IL-1ß/TNF-α.,In addition, IL-8 and VEGF release from COPD lung fibroblasts were increased compared to those from control.,Exogenous miR-503 inhibited VEGF release from primary adult and fetal lung fibroblasts but not IL-8 release.,As expected, COPD fibroblasts proliferated more slowly than control fibroblasts.,MiR-503 did not affect proliferation of either control or COPD lung fibroblasts.,MiR-503 inhibition of VEGF protein production and mRNA was mediated by direct binding to the 3’ untranslated region of VEGF mRNA.,Endogenous miR-503 was differently regulated by exogenous stimulants associated with COPD pathogenesis, including IL-1ß/TNF-α, TGF-ß1 and PGE2.,Endogenous miR-503 inhibition augmented VEGF release by IL-1ß/TNF-α and TGF-ß1 but not by PGE2, demonstrating selectivity of miR-503 regulation of VEGF.,In conclusions, reduced miR-503 augments VEGF release from lung fibroblasts from patients with COPD.,Since VEGF contributes to disturbed vasculature in COPD, altered miR-503 production might play a role in modulating fibroblast-mediated vascular homeostasis in COPD. | COPD is an abnormal inflammatory response characterized by decreased expression of TLR2 in patients, which is suggested to induce invasive pulmonary aspergillosis (IPA).,MicroRNAs (miRNAs) have been shown to play important roles in the pathogenesis of human respiratory system disorders.,Therefore, the aim of this study was to identify the miRNAs involved in the regulation of TLR2 signaling in COPD.,miRNA microarray analysis was performed to screen for the dysregulated miRNAs in alveolar macrophages (AMs) isolated from COPD rats.,The interaction between these miRNAs and TLR2 gene was predicted using miRBase and validated using dual luciferase assay.,Based on the analysis, a novel miR-344b-1-3p was identified as a novel modulator of TLR2 gene.,Then, the mechanism through which miR-344b-1-3p regulated TLR2 expression was explored using cigarette smoke extract (CSE)-pretreated NR8383 cells.,Moreover, by subjecting CSE-pretreated NR8383 cells to Pam3CSK4, the effect of miR-344b-1-3p on NF-κB activity and other important mediators of COPD, including IRAK-1, ERK, TNF-α, IL-1β, and MIP-2, was also assessed.,COPD rat model was successfully induced by smoke inhalation.,Among the 11 upregulated miRNAs in AMs from COPD rats, miR-344b-1-3p was predicted to be a novel miRNA targeting TLR2 gene.,In the CSE pretreated NR8383 cells exposed to Pam3CSK4, miR-344b-1-3p inhibition increased the expression levels of TLR2, TNF-α, and IL-1β and decreased the expression levels of MIP-2.,In addition, the phosphorylation of IRAK-1, IκBα, and IRK was augmented by miR-344b-1-3p inhibition.,Findings outlined in this study suggest that miR-344b-1-3p was an effective modulator of TLR2 gene, which can be employed as a promising therapeutic and preventive target of IPA in COPD patients. | 1 |
To evaluate the impact that the distribution of emphysema has on clinical and functional severity in patients with COPD.,The distribution of the emphysema was analyzed in COPD patients, who were classified according to a 5-point visual classification system of lung CT findings.,We assessed the influence of emphysema distribution type on the clinical and functional presentation of COPD.,We also evaluated hypoxemia after the six-minute walk test (6MWT) and determined the six-minute walk distance (6MWD).,Eighty-six patients were included.,The mean age was 65.2 ± 12.2 years, 91.9% were male, and all but one were smokers (mean smoking history, 62.7 ± 38.4 pack-years).,The emphysema distribution was categorized as obviously upper lung-predominant (type 1), in 36.0% of the patients; slightly upper lung-predominant (type 2), in 25.6%; homogeneous between the upper and lower lung (type 3), in 16.3%; and slightly lower lung-predominant (type 4), in 22.1%.,Type 2 emphysema distribution was associated with lower FEV1, FVC, FEV1/FVC ratio, and DLCO.,In comparison with the type 1 patients, the type 4 patients were more likely to have an FEV1 < 65% of the predicted value (OR = 6.91, 95% CI: 1.43-33.45; p = 0.016), a 6MWD < 350 m (OR = 6.36, 95% CI: 1.26-32.18; p = 0.025), and post-6MWT hypoxemia (OR = 32.66, 95% CI: 3.26-326.84; p = 0.003).,The type 3 patients had a higher RV/TLC ratio, although the difference was not significant.,The severity of COPD appears to be greater in type 4 patients, and type 3 patients tend to have greater hyperinflation.,The distribution of emphysema could have a major impact on functional parameters and should be considered in the evaluation of COPD patients.,Avaliar o impacto que a distribuição do enfisema tem na gravidade clínica e funcional em pacientes com DPOC.,A distribuição do enfisema foi analisada em pacientes com DPOC, que foram classificados de acordo com um sistema de classificação visual de cinco pontos a partir de achados de TC de tórax.,Avaliou-se a influência do tipo de distribuição do enfisema na apresentação funcional e clínica da DPOC.,Hipoxemia após o teste da caminhada de seis minutos (TC6) foi também avaliada e a distância percorrida (DTC6) foi determinada.,Foram incluídos 86 pacientes.,A média de idade foi de 65,2 ± 12,2 anos, 91,9% eram homens, e todos menos um eram fumantes (média de carga tabágica, 62,7 ± 38,4 anos-maço).,A distribuição do enfisema foi categorizada como obviamente predominante no pulmão superior (tipo 1), em 36,0% dos pacientes; levemente predominante no pulmão superior (tipo 2), em 25,6%; homogêneo entre o pulmão superior e inferior (tipo 3), em 16,3%; e levemente predominante no pulmão inferior (tipo 4), em 22,1%.,A distribuição do enfisema do tipo 2 foi associada a menores valores de VEF1, CVF, relação VEF1/CVF e DLCO.,Em comparação com os pacientes do tipo 1, os do tipo 4 apresentaram maior probabilidade de ter VEF1 < 65% do previsto (OR = 6,91, IC95%: 1,43-33,45; p = 0,016), DTC6 < 350 m (OR = 6,36, IC95%: 1,26-32,18; p = 0,025),e hipoxemia após o TC6 (OR = 32,66, IC95%: 3,26-326,84; p = 0,003).,Os pacientes do tipo 3 tiveram uma relação VR/CPT maior, embora sem diferença significativa.,A gravidade da DPOC parece ser maior nos pacientes do tipo 4, e os do tipo 3 tendem a apresentar maior hiperinsuflação.,A distribuição do enfisema pode ter um impacto importante nos parâmetros funcionais e deve ser considerada na avaliação de pacientes com DPOC. | Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) is associated with rapid decline in lung function, poorer health-related quality-of-life outcomes, and frequent exacerbations, compared to COPD alone.,Although the numbers of patients with ACOS have increased, there is little established evidence regarding diagnostic criteria and treatment options.,Thus, the aim of our study was to clarify the clinical, physiological, and radiological features of patients with ACOS.,We examined a total of 100 patients with COPD and 40 patients with ACOS, who were selected based on clinical criteria.,All patients underwent baseline testing, including a COPD assessment test, pulmonary function tests, and multidetector row computed tomography imaging.,Percentage of low attenuation volume, percentage of wall area, and percentage of total cross-sectional area of pulmonary vessels less than 5 mm2 (%CSA <5) were determined using multidetector row computed tomography.,ACOS patients were administered a fixed dose of budesonide/formoterol (160/4.5 μg, two inhalations; twice daily) for 12 weeks, after which the ACOS patients underwent multidetector row computed tomography to measure the same parameters.,At baseline, the ACOS patients and COPD patients had a similar degree of airflow limitation, vital capacity, and residual volume.,ACOS patients had higher COPD assessment test scores, percentage of wall area, and %CSA <5 than COPD patients.,Compared to baseline, budesonide/formoterol treatment significantly increased the forced expiratory volume in 1 second and decreased the degree of airway wall thickness (percentage of wall area) as well as pulmonary microvascular density (%CSA <5) in ACOS patients.,Our results suggest that ACOS is characterized by an airway lesion-dominant phenotype, in contrast to COPD.,Higher %CSA <5 might be a characteristic feature of ACOS. | 1 |
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities.,COPD exacerbations and comorbidities contribute to the overall severity in individual patients.,Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age.,Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations.,However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide.,This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale.,Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases.,All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases.,In this review, we focus on the major comorbidities that affect COPD patients.,We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs.,We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity. | Nutritional depletion is an important manifestation of chronic obstructive pulmonary disease (COPD), which has been related to systemic inflammation.,It remains unclear to what degree airway inflammation contributes to the presence or progression of nutritional depletion.,To determine whether airway inflammation and lung bacterial colonization are related to nutritional status or predict progressive weight loss and muscle atrophy in patients with COPD.,Body composition using dual energy X-ray absorptiometry, indices of airway inflammation, and bacterial colonization were measured in 234 COPD patients.,Systemic inflammation was assessed from serum C reactive protein (CRP) and circulating total and differential leukocyte counts.,Nutritional depletion was defined as a body mass index (BMI) less than 21 kg/m2 and/or fat-free mass index (FFMI) less than 15 or 17 kg/m2 in women and men, respectively.,FFMI was calculated as the fat-free mass (FFM) corrected for body surface area.,Measurements were repeated in 94 patients after a median 16-month follow-up.,Regression analysis was used to assess the relationships of weight change and FFM change with indices of bacterial colonization and airway and systemic inflammation.,Nutritional depletion occurred in 37% of patients.,Lung function was worsened in patients with nutritional depletion compared to those without (forced expiratory volume in 1 second 1.17 L versus 1.41 L, mean difference 0.24, 95% confidence interval 0.10 to 0.38, P<0.01).,There were no differences in airway inflammation and bacterial colonization in patients with and without nutritional depletion.,At baseline, BMI correlated positively with serum CRP (rs=0.14, P=0.04).,Change in weight and change in FFM over time could not be predicted from baseline patient characteristics.,Nutritional depletion and progressive muscle atrophy are not related to airway inflammation or bacterial colonization.,Overspill of pulmonary inflammation is not a key driver of muscle atrophy in COPD. | 1 |
Identifying patients at risk of exacerbations and managing them appropriately to reduce this risk represents an important clinical challenge.,Numerous treatments have been assessed for the prevention of exacerbations and their efficacy may differ by patient phenotype.,Given their centrality in the treatment of COPD, there is strong rationale for maximizing bronchodilation as an initial strategy to reduce exacerbation risk irrespective of patient phenotype.,Therefore, in patients assessed as frequent exacerbators (>1 exacerbation/year) we propose initial bronchodilator treatment with a long-acting muscarinic antagonist (LAMA)/ long-acting β2-agonist (LABA).,For those patients who continue to experience >1 exacerbation/year despite maximal bronchodilation, we advocate treating according to patient phenotype.,Based on currently available data on adding inhaled corticosteroids (ICS) to a LABA, ICS might be added to a LABA/LAMA combination in exacerbating patients who have an asthma-COPD overlap syndrome or high blood eosinophil counts, while in exacerbators with chronic bronchitis, consideration should be given to treating with a phosphodiesterase (PDE)-4 inhibitor (roflumilast) or high-dose mucolytic agents.,For those patients who experience frequent bacterial exacerbations and/or bronchiectasis, addition of mucolytic agents or a macrolide antibiotic (e.g. azithromycin) should be considered.,In all patients at risk of exacerbations, pulmonary rehabilitation should be included as part of a comprehensive management plan.,The online version of this article (doi:10.1186/s12931-016-0425-5) contains supplementary material, which is available to authorized users. | Telehealth is an approach to disease management, which may hold the potential of improving some of the features associated with COPD, including positive impact on disease progression, and thus possibly limiting further reduction in quality of life (QoL).,Our objective was, therefore, to summarize studies addressing the impact of telehealth on QoL in patients with COPD.,Systematic review.,A series of systematic searches were carried out using the following databases: PubMed, EMBASE, Cochrane Controlled Trials Register, and ClinicalTrials.gov (last updated November 2015).,A predefined search algorithm was utilized with the intention to capture all results related to COPD, QoL, and telehealth published since year 2000.,Primary outcome was QoL, assessed by validated measures.,Out of the 18 studies fulfilling the criteria for inclusion in this review, three studies found statistically significant improvements in QoL for patients allocated to telemedical interventions.,However, all of the other included studies found no statistically significant differences between control and telemedical intervention groups in terms of QoL.,Telehealth does not make a strong case for itself when exclusively looking at QoL as an outcome, since statistically significant improvements relative to control groups have been observed only in few of the available studies.,Nonetheless, this does not only rule out the possibility that telehealth is superior to standard care with regard to other outcomes but also seems to call for more research, not least in large-scale controlled trials. | 1 |
Pulmonary hypertension and exercise-induced oxygen desaturation (EID) influence acute exacerbation of COPD.,Computed tomography (CT)-detected pulmonary artery (PA) enlargement is independently associated with acute COPD exacerbations.,Associations between PA to aorta (PA:A) ratio and EID in patients with COPD have not been reported.,We hypothesized that the PA:A ratio correlated with EID and that results of the 6-minute walk test (6MWT) would be useful for predicting the risk associated with PA:A >1.,We retrospectively measured lung function, 6MWT, emphysema area, and PA enlargement on CT in 64 patients with COPD.,The patients were classified into groups with PA:A ≤1 and >1.,Receiver-operating characteristic curves were used to determine the threshold values with the best cutoff points to predict patients with PA:A >1.,The PA:A >1 group had lower forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1:FVC ratio, diffusion capacity of lung carbon monoxide, 6MW distance, and baseline peripheral oxygen saturation (SpO2), lowest SpO2, highest modified Borg scale results, percentage low-attenuation area, and history of acute COPD exacerbations ≤1 year, and worse BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise) index results (P<0.05).,Predicted PA:A >1 was determined for SpO2 during 6MWT (best cutoff point 89%, area under the curve 0.94, 95% confidence interval 0.88-1).,SpO2 <90% during 6MWT showed a sensitivity of 93.1, specificity of 94.3, positive predictive value of 93.1, negative predictive value of 94.3, positive likelihood ratio of 16.2, and negative likelihood ratio of 0.07.,Lowest SpO2 during 6MWT may predict CT-measured PA:A, and lowest SpO2 <89% during 6MWT is excellent for detecting pulmonary hypertension in COPD. | New parameters in the 6-minute walk test (6MWT) are required for comprehensive analysis of exercise capacity in patients with chronic obstructive pulmonary disease (COPD).,The aim of the present study was to apply a novel index, the desaturation distance ratio (DDR), to clinical research on COPD as an estimate of exercise capacity and to examine whether DDR is a potential parameter for manifold analysis of exercise capacity in patients with COPD.,A total of 41 patients with COPD (median age [interquartile range] =75 [68-79] years; and body mass index [BMI] =22.3 [19.4-23.8] kg/m2) participated in the study.,The 6MWT was performed along with anthropometric measurements and a pulmonary function test.,The “desaturation area” was measured as the total area above the curve created using peripheral oxygen saturation (SpO2) values observed at each minute during the 6MWT.,Then the DDR was calculated as the ratio of the desaturation area to the 6-minute walk distance (6MWD).,The 6MWD was 370 (328-445) m, and the decline in SpO2 values (ΔSpO2) was −5.0% (−8.0% to −1.5%).,The DDR correlated modestly with baseline pulmonary function in patients with COPD (forced expiratory volume in 1 second [% of predicted value]: r=−0.658, P<0.001; and diffusing capacity of the lung for carbon monoxide [DLCO]: r=−0.470, P=0.002), comparable with the findings of the 6MWD.,The DDR correlated well with ΔSpO2 (r=−0.656, P<0.001) and with the increase in subjective sense of dyspnea during the 6MWT, as assessed by Borg scale scores (ΔBorg) (r=0.486, P=0.001), in contrast with the 6MWD, which was not significantly correlated with ΔSpO2 and ΔBorg scale scores.,The DDR is more informative for manifold analysis of exercise capacity associated with oxygen desaturation and subsequent sense of dyspnea by exercise in patients with COPD. | 1 |
Identifying patients at risk of exacerbations and managing them appropriately to reduce this risk represents an important clinical challenge.,Numerous treatments have been assessed for the prevention of exacerbations and their efficacy may differ by patient phenotype.,Given their centrality in the treatment of COPD, there is strong rationale for maximizing bronchodilation as an initial strategy to reduce exacerbation risk irrespective of patient phenotype.,Therefore, in patients assessed as frequent exacerbators (>1 exacerbation/year) we propose initial bronchodilator treatment with a long-acting muscarinic antagonist (LAMA)/ long-acting β2-agonist (LABA).,For those patients who continue to experience >1 exacerbation/year despite maximal bronchodilation, we advocate treating according to patient phenotype.,Based on currently available data on adding inhaled corticosteroids (ICS) to a LABA, ICS might be added to a LABA/LAMA combination in exacerbating patients who have an asthma-COPD overlap syndrome or high blood eosinophil counts, while in exacerbators with chronic bronchitis, consideration should be given to treating with a phosphodiesterase (PDE)-4 inhibitor (roflumilast) or high-dose mucolytic agents.,For those patients who experience frequent bacterial exacerbations and/or bronchiectasis, addition of mucolytic agents or a macrolide antibiotic (e.g. azithromycin) should be considered.,In all patients at risk of exacerbations, pulmonary rehabilitation should be included as part of a comprehensive management plan.,The online version of this article (doi:10.1186/s12931-016-0425-5) contains supplementary material, which is available to authorized users. | The purpose of this analysis was to compare health care costs and utilization among COPD patients who had long-acting beta-2 agonist (LABA) OR long-acting muscarinic antagonist (LAMA); LABA AND LAMA; or LABA, LAMA, AND inhaled corticosteroid (ICS) prescription claims.,This was a 12 month pre-post, retrospective analysis using COPD patients in a national administrative insurance database.,Propensity score and exact matching were used to match patients 1:1:1 between the LABA or LAMA (formoterol, salmeterol, or tiotropium), LABA and LAMA (tiotropium/formoterol or tiotropium/salmeterol), and LABA, LAMA and ICS (bronchodilators plus steroid) groups.,Post-period comparisons were evaluated with analysis of covariance.,Costs were evaluated from a commercial payer perspective.,A total of 523 patients were matched using 29 pre-period variables (e.g., demographics, medication exposure).,Post-match assessments indicated balance among the cohorts.,COPD-related costs differed among groups (LABA or LAMA $2,051 SE = 91; LABA and LAMA $2,823 SE = 62; LABA, LAMA and ICS $3,546 SE = 89; all p < .0001) with the differences driven by study medication costs.,However, non-study COPD medication costs were higher for the LABA or LAMA therapy group ($911 SE = 91) compared to the LABA and LAMA therapy group ($668 SE = 58; p = 0.0238) and non-study respiratory medications were approximately $100 greater for the LABA or LAMA therapy group relative to both LABA and LAMA (p = .0018) and LABA, LAMA, and ICS (p = .0071) therapy groups.,While there was no observed difference in outpatient costs, there was a slightly higher number of outpatient visits per patient in the LABA and LAMA (25.5 SE = 0.9, p = 0.0070) relative to the LABA or LAMA therapy group (22.3 SE = 0.8) and higher utilization (89.7% of patients) with COPD visits in the LABA and LAMA therapy group relative to both the LABA or LAMA (73.8%; p < .0001) and LABA, LAMA and ICS therapy groups (85.3; p = 0.0305).,Significant cost differences driven mainly by pharmaceuticals were observed among LABA or LAMA, LABA and LAMA and LABA, LAMA and ICS therapies.,A COPD-related cost offset was observed from single bronchodilator to two bronchodilators.,Addition of an ICS with two bronchodilators resulted in higher treatment costs without reduction in other COPD-related costs compared with two bronchodilators. | 1 |
As lung function declines rapidly in the early stages of chronic obstructive pulmonary disease (COPD), the effects of bronchodilators in patients with moderate disease and those who have not previously received maintenance therapy are of interest.,OTEMTO® 1 and 2 were two replicate, 12-week, Phase III studies investigating the benefit of tiotropium + olodaterol on lung function and quality of life in patients with moderate to severe disease.,Post hoc analyses were performed to assess the benefits for patients according to disease severity and treatment history.,Four subgroup analyses were performed: Global initiative for chronic Obstructive Lung Disease (GOLD) 2/3, GOLD A/B/C/D, treatment naive/not treatment naive and receiving inhaled corticosteroids (ICS) at baseline/not receiving ICS at baseline.,Primary end points were change in forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h response, change in trough FEV1 and St George’s Respiratory Questionnaire (SGRQ) total score.,Transition Dyspnoea Index (TDI) focal score was a secondary end point, and SGRQ and TDI responder analyses were further end points; all were assessed at 12 weeks.,In all subgroups, patients receiving tiotropium + olodaterol responded better overall than those receiving tiotropium monotherapy.,Improvements with tiotropium + olodaterol over placebo or tiotropium monotherapy were noted across GOLD 2/3 and GOLD A/B/C/D; however, improvements in SGRQ total score were most evident in the GOLD B subgroup.,Moreover, lung-function outcomes were generally greater in those patients who had been receiving previous long-acting bronchodilator and/or ICS maintenance treatment.,These data suggest that tiotropium + olodaterol should be considered as a treatment option in patients with moderate COPD who are initiating maintenance therapy, as well as those with more severe disease.,ClinicalTrials.gov: NCT01964352 and NCT02006732.,The online version of this article (doi:10.1186/s12931-016-0387-7) contains supplementary material, which is available to authorized users. | Interactions between spirometry and patient-reported outcomes in COPD are not well understood.,This systematic review and study-level analysis investigated the relationship between changes in FEV1 and changes in health status with bronchodilator therapy.,Six databases (to October 2009) were searched to identify studies with long-acting bronchodilator therapy reporting FEV1 and health status, dyspnoea or exacerbations.,Mean and standard deviations of treatment effects were extracted for each arm of each study.,Relationships between changes in trough FEV1 and outcomes were assessed using correlations and random-effects regression modelling.,The primary outcome was St George's Respiratory Questionnaire (SGRQ) total score.,Thirty-six studies (≥3 months) were included.,Twenty-two studies (23,654 patients) with 49 treatment arms each contributing one data point provided SGRQ data.,Change in trough FEV1 and change in SGRQ total score were negatively correlated (r = -0.46, p < 0.001); greater increases in FEV1 were associated with greater reductions (improvements) in SGRQ.,The correlation strengthened with increasing study duration from 3 to 12 months.,Regression modelling indicated that 100 mL increase in FEV1 (change at which patients are more likely to report improvement) was associated with a statistically significant reduction in SGRQ of 2.5 (95% CI 1.9, 3.1), while a clinically relevant SGRQ change (4.0) was associated with 160.6 (95% CI 129.0, 211.6) mL increase in FEV1.,The association between change in FEV1 and other patient-reported outcomes was generally weak.,Our analyses indicate, at a study level, that improvement in mean trough FEV1 is associated with proportional improvements in health status. | 1 |
There is a need for novel anti-inflammatory therapies to treat COPD.,The liver X receptor (LXR) is a nuclear hormone receptor with anti-inflammatory properties.,We investigated LXR gene and protein expression levels in alveolar macrophages and whole lung tissue from COPD patients and controls, the effect of LXR activation on the suppression of inflammatory mediators from LPS stimulated COPD alveolar macrophages, and the effect of LXR activation on the induction of genes associated with alternative macrophage polarisation.,The levels of LXR mRNA were significantly increased in whole lung tissue extracts in COPD patients and smokers compared to non-smokers.,The expression of LXR protein was significantly increased in small airway epithelium and alveolar epithelium in COPD patients compared to controls.,No differences in LXR mRNA and protein levels were observed in alveolar macrophages between patient groups.,The LXR agonist GW3965 significantly induced the expression of the LXR dependent genes ABCA1 and ABCG1 in alveolar macrophage cultures.,In LPS stimulated alveolar macrophages, GW3965 suppressed the production of CXCL10 and CCL5, whilst stimulating IL-10 production.,GW3965 did not significantly suppress the production of TNFα, IL-1β, or CXCL8.,Our major finding is that LXR activation has anti-inflammatory effects on CXC10, CCL5 and IL-10 production from alveolar macrophages. | Patients with bronchitis type of chronic obstructive pulmonary disease (COPD) have raised vascular endothelial growth factor (VEGF) levels in induced sputum.,This has been associated with the pathogenesis of COPD through apoptotic and oxidative stress mechanisms.,Since, chronic airway inflammation is an important pathological feature of COPD mainly initiated by cigarette smoking, aim of this study was to assess smoking as a potential cause of raised airway VEGF levels in bronchitis type COPD and to test the association between VEGF levels in induced sputum and airway inflammation in these patients.,14 current smokers with bronchitis type COPD, 17 asymptomatic current smokers with normal spirometry and 16 non-smokers were included in the study.,VEGF, IL-8, and TNF-α levels in induced sputum were measured and the correlations between these markers, as well as between VEGF levels and pulmonary function were assessed.,The median concentrations of VEGF, IL-8, and TNF-α were significantly higher in induced sputum of COPD patients (1,070 pg/ml, 5.6 ng/ml and 50 pg/ml, respectively) compared to nonsmokers (260 pg/ml, 0.73 ng/ml, and 15.4 pg/ml, respectively, p < 0.05) and asymptomatic smokers (421 pg/ml, 1.27 ng/ml, p < 0.05, and 18.6 pg/ml, p > 0.05, respectively).,Significant correlations were found between VEGF levels and pack years (r = 0.56, p = 0.046), IL-8 (r = 0.64, p = 0.026) and TNF-α (r = 0.62, p = 0.031) levels both in asymptomatic and COPD smokers (r = 0.66, p = 0.027, r = 0.67, p = 0.023, and r = 0.82, p = 0.002, respectively).,No correlation was found between VEGF levels in sputum and pulmonary function parameters.,VEGF levels are raised in the airways of both asymptomatic and COPD smokers.,The close correlation observed between VEGF levels in the airways and markers of airway inflammation in healthy smokers and in smokers with bronchitis type of COPD is suggestive of VEGF as a marker reflecting the inflammatory process that occurs in smoking subjects without alveolar destruction. | 1 |
Umeclidinium (UMEC; long-acting muscarinic antagonist) plus vilanterol (VI; long-acting beta2 agonist [LABA]) and the LABA/inhaled corticosteroid fluticasone propionate/salmeterol (FP/SAL) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD).,This 12-week, multicentre, double-blind, parallel-group, double-dummy study compared the efficacy and safety of these treatments in symptomatic patients with moderate-to-severe COPD with no exacerbations in the year prior to enrolment.,Patients (n = 717) were randomised 1:1 to once-daily UMEC/VI 62.5/25 mcg or twice-daily FP/SAL 500/50 mcg.,Endpoints included 0-24 h weighted mean (wm) forced expiratory volume in 1 s (FEV1) (Day 84; primary), trough FEV1 (Day 85; secondary), other lung function endpoints, symptoms, quality of life (QoL) and safety.,Improvements with UMEC/VI versus FP/SAL were 0.080 L (95 % confidence interval: 0.046-0.113; wmFEV1) and 0.090 L (0.055-0.125; trough FEV1) (both p < 0.001).,UMEC/VI statistically significantly improved all other lung function measures versus FP/SAL.,Both treatments demonstrated a clinically meaningful improvement in symptoms (Transition Dyspnoea Index ≥1 unit) and QoL (St George’s Respiratory Questionnaire Total score ≥4 unit decrease from baseline) over 12 weeks.,The incidence of adverse events was 28 % (UMEC/VI) and 29 % (FP/SAL); nasopharyngitis and headache were most common.,Once-daily UMEC/VI 62.5/25 mcg over 12 weeks resulted in significant and sustained improvements in lung function versus twice-daily FP/SAL 500/50 mcg in patients with moderate-to-severe COPD and with no exacerbations in the year prior to enrolment.,NCT01822899 Registration date: March 28, 2013,The online version of this article (doi:10.1186/s12890-015-0092-1) contains supplementary material, which is available to authorized users. | Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone.,The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.,In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair®/Pressair®)*.,Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV1 (FDCs versus formoterol).,Secondary endpoints were change from baseline in St.,George’s Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24.,Safety and tolerability were also assessed.,At study end, improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001).,Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC.,Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively.,All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies.,Treatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo.,Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD.,Clinicaltrials.gov NCT01437397.,*Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the US as Pressair® and Genuair® within all other licensed territories.,The online version of this article (doi:10.1186/s12931-014-0123-0) contains supplementary material, which is available to authorized users. | 1 |
The aetiology of acute exacerbations of COPD (AECOPD) is incompletely understood.,Understanding the relationship between chronic bacterial airway infection and viral exposure may explain the incidence and seasonality of these events.,In this prospective, observational cohort study (NCT01360398), patients with COPD aged 40-85 years underwent sputum sampling monthly and at exacerbation for detection of bacteria and viruses.,Results are presented for subjects in the full cohort, followed for 1 year.,Interactions between exacerbation occurrence and pathogens were investigated by generalised estimating equation and stratified conditional logistic regression analyses.,The mean exacerbation rate per patient-year was 3.04 (95% CI 2.63 to 3.50).,At AECOPD, the most common bacterial species were non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis, and the most common virus was rhinovirus.,Logistic regression analyses (culture bacterial detection) showed significant OR for AECOPD occurrence when M. catarrhalis was detected regardless of season (5.09 (95% CI 2.76 to 9.41)).,When NTHi was detected, the increased risk of exacerbation was greater in high season (October-March, OR 3.04 (1.80 to 5.13)) than low season (OR 1.22 (0.68 to 2.22)).,Bacterial and viral coinfection was more frequent at exacerbation (24.9%) than stable state (8.6%).,A significant interaction was detected between NTHi and rhinovirus presence and AECOPD risk (OR 5.18 (1.92 to 13.99); p=0.031).,AECOPD aetiology varies with season.,Rises in incidence in winter may be driven by increased pathogen presence as well as an interaction between NTHi airway infection and effects of viral infection.,Results, NCT01360398. | Gas trapping quantified on chest CT scans has been proposed as a surrogate for small airway disease in COPD.,We sought to determine if measurements using paired inspiratory and expiratory CT scans may be better able to separate gas trapping due to emphysema from gas trapping due to small airway disease.,Smokers with and without COPD from the COPDGene Study underwent inspiratory and expiratory chest CT scans.,Emphysema was quantified by the percent of lung with attenuation < −950HU on inspiratory CT.,Four gas trapping measures were defined: (1) Exp−856, the percent of lung < −856HU on expiratory imaging; (2) E/I MLA, the ratio of expiratory to inspiratory mean lung attenuation; (3) RVC856-950, the difference between expiratory and inspiratory lung volumes with attenuation between −856 and −950 HU; and (4) Residuals from the regression of Exp−856 on percent emphysema.,In 8517 subjects with complete data, Exp−856 was highly correlated with emphysema.,The measures based on paired inspiratory and expiratory CT scans were less strongly correlated with emphysema.,Exp−856, E/I MLA and RVC856-950 were predictive of spirometry, exercise capacity and quality of life in all subjects and in subjects without emphysema.,In subjects with severe emphysema, E/I MLA and RVC856-950 showed the highest correlations with clinical variables.,Quantitative measures based on paired inspiratory and expiratory chest CT scans can be used as markers of small airway disease in smokers with and without COPD, but this will require that future studies acquire both inspiratory and expiratory CT scans. | 1 |
Asthma-COPD overlap (ACO) is a term that encompasses patients with characteristics of two conditions, smoking asthmatics or COPD patients with asthma-like features such as high bronchodilator response or blood eosinophil count ≥300 cells/μL.,The aim of this study was to compare the different phenotypes inside the ACO definition in a real-life population cohort.,We analyzed patients from the MAJORICA cohort who had a diagnosis of asthma and/or COPD based on current guidelines, laboratory data in 2014 and follow-up until 2015.,Prevalence of ACO according to the different criteria, demographic, clinical and functional characteristics, prescriptions and use of health resources data were compared between three groups.,We included 603 patients.,Prevalence of smoking asthmatics was 14%, COPD patients with high bronchodilator response 1.5% and eosinophilic COPD patients 12%.,Smoking asthmatics were younger and used more rescue inhalers, corticosteroids and health resources.,Conversely, eosinophilic COPD patients were older than the other groups, often treated with corticosteroids and had lower use of health resources.,Most of the COPD patients with high bronchodilator response were included in the eosinophilic COPD group.,ACO includes two conditions (smoking asthmatics and eosinophilic COPD patients) with different medication requirement and prognosis that should not be pooled together.,Use of ≥300 blood eosinophils/μL as a treatable trait should be recommended. | Inhaled corticosteroids (ICSs) are a mainstay of COPD treatment for patients with a history of exacerbations.,Initial studies evaluating their use as monotherapy failed to show an effect on rate of pulmonary function decline in COPD, despite improvements in symptoms and reductions in exacerbations.,Subsequently, ICS use in combination with long-acting β2-agonists (LABAs) was shown to provide improved reductions in exacerbations, lung function, and health status.,ICS-LABA combination therapy is currently recommended for patients with a history of exacerbations despite treatment with long-acting bronchodilators alone.,The presence of eosinophilic bronchial inflammation, detected by high blood eosinophil levels or a history of asthma or asthma-COPD overlap, may define a population of patients in whom ICSs may be of particular benefit.,Prospective clinical studies to determine an appropriate threshold of eosinophil levels for predicting the beneficial effects of ICSs are needed.,Further study is also required in COPD patients who continue to smoke to assess the impact of cell- and tissue-specific changes on ICS responsiveness.,The safety profile of ICSs in COPD patients is confounded by comorbidities, age, and prior use of systemic corticosteroids.,The risk of pneumonia in patients with COPD is increased, particularly with more advanced age and worse disease severity.,ICS-containing therapy also has been shown to increase pneumonia risk; however, differences in study design and the definition of pneumonia events have led to substantial variability in risk estimates, and some data indicate that pneumonia risk may differ by the specific ICS used.,In summary, treatment with ICSs has a role in dual and triple therapy for COPD to reduce exacerbations and improve symptoms.,Careful assessment of COPD phenotypes related to risk factors, triggers, and comorbidities may assist in individualizing treatment while maximizing the benefit-to-risk ratio of ICS-containing COPD treatment. | 1 |
The use of a simple screening questionnaire to detect persistent airflow obstruction (AO) in COPD may facilitate the early, accurate diagnosis of COPD in general practice settings.,This study developed an original persistent AO questionnaire for screening individuals with COPD in a general Japanese population.,A working group was established to generate initial draft questionnaire items about COPD.,Eligible subjects aged 40 and older living in Japan were solicited to participate in a health checkup from 2014 to 2015.,In study I, 2,338 subjects who fully completed the initial draft questionnaire and who had valid spirometry measurements were statistically analyzed to determine the final questionnaire items as a COPD screening questionnaire (COPD-Q).,Persistent AO was defined as a post-bronchodilator FEV1/FVC <0.70.,In study II, the working group analyzed the weighted scores for individual items and established a cutoff point for the COPD-Q based on the data of 2,066 subjects in the Hisayama study.,Receiver operating characteristic (ROC) curves were used to examine the ability of the COPD-Q to discriminate between subjects with and without AO.,The five-item COPD-Q was established based on 19 initial draft items in study I and the weighted scores of individual items.,The overall area under the ROC curve for the COPD-Q was 0.796 (95% confidence interval, 0.707-0.788).,A cutoff of 4 points resulted in a sensitivity of 71.0% and a specificity of 70.1%.,The positive predictive value was 10.8%, and the negative predictive value was 97.9%.,The crude odds ratio of the COPD-Q for AO was 5.8.,The five-item COPD-Q is a useful questionnaire for diagnosing persistent AO in a general Japanese population and is expected to be an effective first-stage screening tool for detecting COPD. | Chronic obstructive pulmonary disease (COPD) is widely underdiagnosed, but the most effective approach for identifying these patients is unknown.,The aim of this study was to summarise and compare the effectiveness of different case finding approaches for undiagnosed COPD in primary care.,A systematic review of primary studies of any design evaluating case finding strategies for COPD in primary care among individuals aged ⩾35 years with no prior diagnosis was conducted.,Medline, Embase and other bibliographic databases were searched from 1997 to 2013, and methodological quality was assessed using standard tools.,Results were described and meta-analysis of the uptake and yield from different approaches was performed where there was sufficient homogeneity.,Three randomised controlled trials (RCTs), 1 controlled trial and 35 uncontrolled studies were identified that assessed the identification of new cases of COPD through systematic case finding.,A range of approaches were used including pre-screening with questionnaires (n=13) or handheld flow meters (n=5) or direct invitation to diagnostic spirometry (n=30).,Overall, any approach identified more undiagnosed COPD compared with usual care.,Targeting those at higher risk (e.g., smokers) and pre-screening (e.g., using questionnaires) is likely to increase the yield.,However, studies were heterogeneous and were limited by a lack of comparison groups, inadequate reporting and diversity in the definition of COPD, which limited our ability to draw firm conclusions.,There is extensive heterogeneity among studies evaluating case finding strategies for COPD, with few RCTs.,Well-conducted RCTs comparing case finding approaches are needed to identify the most effective target population, recruitment strategy and screening tests, using a clinical definition of COPD, and addressing the limitations highlighted in this review.,There is also a need to evaluate the impact of case finding on clinical care and patient outcomes. | 1 |
Sputum induction is a non-invasive method for obtaining measurements of inflammation in the airways.,Whether spontaneously sampled sputum can be a valid surrogate is unknown.,The aim of this study was to compare levels of six inflammatory markers in sputum pairs consisting of induced and spontaneous sputum sampled on the same consultation either in a stable state or during exacerbations of chronic obstructive pulmonary disease (COPD).,433 COPD patients aged 40-76, Global initiative for chronic Obstructive Lung Disease (GOLD) stage II-IV were enrolled in 2006/07 and followed every six months for three years. 356 patients were followed for potential exacerbations.,Interleukin-6, interleukin-8, interleukin-18, interferon gamma-inducible protein-10, monokine induced by gamma interferon and tumor necrosis factor-alpha (IL-6, IL-8, IL-18, IP-10, MIG and TNF-α) were measured by bead based multiplex immunoassay in 60 paired sputum samples from 45 patients.,Albumin was measured by enzyme immunoassay, for concentration correction.,Culturing for bacterial growth was performed on 24 samples.,Bland-Altman plots were used to assess agreement.,The paired non-parametric Wilcoxon signed-rank test, the non-parametric Spearman’s rank correlation test and Kruskal-Wallis test were used for statistical analyses.,For all analyses, a p-value < 0.05 was considered significant.,Agreement between the two measurements was generally low for all six markers.,TNF-α was significantly higher in spontaneous sputum at exacerbations (p = 0.002) and trending higher at the steady state (p = 0.06).,Correlation coefficients between the levels of markers in induced and spontaneous sputum varied between 0.58 (IL-18) to 0.83 (IP-10).,In spontaneous sputum IL-18 and MIG were higher in ex-smokers (p < 0.05).,The levels of all markers were higher in GOLD stage III & IV except for IL-6 in spontaneous sputum and IL-18 in induced sputum, compared with GOLD stage II, although not statistically significant.,In spontaneous sputum the levels of IL-6 were significantly higher if Haemophilus influenzae (HI) was not cultured.,We observed a low agreement and significant differences in inflammatory markers between induced and spontaneous sputum, both at steady state and exacerbations.,We recommend considering sampling method when reporting on inflammatory markers in sputum. | The bronchial microbiome in severe COPD during stability and exacerbation in patients chronically colonised by Pseudomonas aeruginosa (PA), has not been defined.,Our objective was to determine the characteristics of the bronchial microbiome of severe COPD patients colonised and not colonised by P. aeruginosa and its changes during exacerbation.,COPD patients with severe disease and frequent exacerbations were categorised according to chronic colonisation by P. aeruginosa.,Sputum samples were obtained in stability and exacerbation, cultured, and analysed by 16S rRNA gene amplification and pyrosequencing.,Sixteen patients were included, 5 of them showing chronic colonisation by P. aeruginosa.,Pseudomonas genus had significantly higher relative abundance in stable colonised patients (p = 0.019), but no significant differences in biodiversity parameters were found between the two groups (Shannon, 3 (2-4) vs 3 (2-3), p = 0.699; Chao1, 124 (77-159) vs 140 (115-163), p = 0.364).,In PA-colonised patients bronchial microbiome changed to a microbiome similar to non-PA-colonised patients during exacerbations.,An increase in the relative abundance over 20 % during exacerbation was found for Streptococcus, Pseudomonas, Moraxella, Haemophilus, Neisseria, Achromobacter and Corynebacterium genera, which include recognised potentially pathogenic microorganisms, in 13 patients colonised and not colonised by P. aeruginosa with paired samples.,These increases were not identified by culture in 5 out of 13 participants (38.5 %).,Stable COPD patients with severe disease and PA-colonised showed a similar biodiversity to non-PA-colonised patients, with a higher relative abundance of Pseudomonas genus in bronchial secretions.,Exacerbation in severe COPD patients showed the same microbial pattern, independently of previous colonisation by P. aeruginosa.,The online version of this article (doi:10.1007/s10096-013-2044-0) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) is a common, highly debilitating disease of the airways, primarily caused by smoking.,Chronic inflammation and structural remodelling are key pathological features of this disease, in part caused by the aberrant function of airway smooth muscle (ASM) cells under the regulation of transforming growth factor (TGF)‐β. miRNA are short, noncoding gene transcripts involved in the negative regulation of specific target genes, through their interactions with mRNA.,Previous studies have proposed that mRNA‐145 (miR‐145) may interact with SMAD3, an important downstream signalling molecule of the TGF‐β pathway.,TGF‐β was used to stimulate primary human ASM cells isolated from healthy nonsmokers, healthy smokers and COPD patients.,This resulted in a TGF‐β‐dependent increase in CXCL8 and IL‐6 release, most notably in the cells from COPD patients.,TGF‐β stimulation increased SMAD3 expression, only in cells from COPD patients, with a concurrent increased miR‐145 expression.,Regulation of miR‐145 was found to be negatively controlled by pathways involving the MAP kinases, MEK‐1/2 and p38 MAPK.,Subsequent, overexpression of miR‐145 (using synthetic mimics) in ASM cells from patients with COPD suppressed IL‐6 and CXCL8 release, to levels comparable to the nonsmoker controls.,Therefore, this study suggests that miR‐145 negatively regulates pro‐inflammatory cytokine release from ASM cells in COPD by targeting SMAD3. | Cigarette smoke is a major risk factor for chronic obstructive pulmonary disease (COPD), an inflammatory lung disorder.,COPD is characterized by an increase in CD8+ T cells within the central and peripheral airways.,We hypothesized that the CD8+ T cells in COPD patients have increased Toll-like receptor (TLR) expression compared to control subjects due to the exposure of cigarette smoke in the airways.,Endobronchial biopsies and peripheral blood were obtained from COPD patients and control subjects.,TLR4 and TLR9 expression was assessed by immunostaining of lung tissue and flow cytometry of the peripheral blood.,CD8+ T cells isolated from peripheral blood were treated with or without cigarette smoke condensate (CSC) as well as TLR4 and TLR9 inhibitors.,PCR and western blotting were used to determine TLR4 and TLR9 expression, while cytokine secretion from these cells was detected using electrochemiluminescence technology.,No difference was observed in the overall expression of TLR4 and TLR9 in the lung tissue and peripheral blood of COPD patients compared to control subjects.,However, COPD patients had increased TLR4 and TLR9 expression on lung CD8+ T cells.,Exposure of CD8+ T cells to CSC resulted in an increase of TLR4 and TLR9 protein expression.,CSC exposure also caused the activation of CD8+ T cells, resulting in the production of IL-1β, IL-6, IL-10, IL-12p70, TNFα and IFNγ.,Furthermore, inhibition of TLR4 or TLR9 significantly attenuated the production of TNFα and IL-10.,Our results demonstrate increased expression of TLR4 and TLR9 on lung CD8+ T cells in COPD.,CD8+ T cells exposed to CSC increased TLR4 and TLR9 levels and increased cytokine production.,These results provide a new perspective on the role of CD8+ T cells in COPD. | 1 |
Observational studies using case-control designs have showed an increased risk of pneumonia associated with inhaled corticosteroid (ICS)-containing medications in patients with chronic obstructive pulmonary disease (COPD).,New-user observational cohort designs may minimize biases associated with previous case-control designs.,To estimate the association between ICS and pneumonia among new users of ICS relative to inhaled long-acting bronchodilator (LABD) monotherapy.,Pneumonia events in COPD patients ≥45 years old were compared among new users of ICS medications (n = 11,555; ICS, ICS/long-acting β2-agonist [LABA] combination) and inhaled LABD monotherapies (n = 6,492; LABA, long-acting muscarinic antagonists) using Cox proportional hazards models, with propensity scores to adjust for confounding.,Setting: United Kingdom electronic medical records with linked hospitalization and mortality data (2002-2010).,New users were censored at earliest of: pneumonia event, death, changing/discontinuing treatment, or end of follow-up.,Outcomes: severe pneumonia (primary) and any pneumonia (secondary).,Following adjustment, new use of ICS-containing medications was associated with an increased risk of pneumonia hospitalization (n = 322 events; HR = 1.55, 95% CI: 1.14, 2.10) and any pneumonia (n = 702 events; HR = 1.49, 95% CI: 1.22, 1.83).,Crude incidence rates of any pneumonia were 48.7 and 30.9 per 1000 person years among the ICS-containing and LABD cohorts, respectively.,Excess risk of pneumonia with ICS was reduced when requiring ≥1 month or ≥ 6 months of new use.,There was an apparent dose-related effect, with greater risk at higher daily doses of ICS.,There was evidence of channeling bias, with more severe patients prescribed ICS, for which the analysis may not have completely adjusted.,The results of this new-user cohort study are consistent with published findings; ICS were associated with a 20-50% increased risk of pneumonia in COPD, which reduced with exposure time.,This risk must be weighed against the benefits when prescribing ICS to patients with COPD. | 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 |
Chronic obstructive pulmonary disease (COPD) is the cause of substantial economic and social burden.,We investigated trends in hospitalizations for acute exacerbation of COPD in Beijing, China, from 2009 to 2017.,Investigations were conducted using data from the discharge records of inpatients that were given a primary diagnosis of acute exacerbation of COPD.,The dataset was a retrospective review of information collected from electronic medical records and included 315,116 admissions (159,368 patients).,Descriptive analyses and multivariate regressions were used to investigate trends in per admission and per capita expenditures, as well as other potential contributing factors.,The mean per admission expenditures increased from 19,760 CNY ($2893, based on USD/CNY=6.8310) in 2009 to 20,118 CNY ($2980) in 2017 (a growth rate of 0.11%).,However, the per capita expenditures increased from 23,716 CNY ($3472) in 2009 to 31,000 CNY ($4538) in 2017 (a growth rate of 1.7%).,In terms of per admission expenditures, drug costs accounted for 52.9% of the total expenditures in 2009 and dropped to 39.4% in 2017 (P trend < 0.001).,The mean length of stay (LOS) decreased from 16.0 days to 13.5 days (P trend < 0·001).,Age, gender, COPD type, LOS, and hospital level were all associated with per admission and per capita expenditures.,Relatively stable per admission expenditures along with the decline in drug costs and LOS reflect the effectiveness of cost containment on some indicators in China’s health care reform.,However, the increase in hospitalization expenditures per capita calls for better policies for controlling hospitalizations, especially multiple admissions. | Little is known about whether there is any sex effect on chronic obstructive lung disease (COPD) exacerbations.,This study is intended to describe the possible sex-associated differences in exacerbation profile in COPD patients.,A total of 384 COPD patients who were hospitalized due to exacerbation were evaluated retrospectively for their demographics and previous and current exacerbation characteristics.,The study was conducted on 109 (28%) female patients and 275 (72%) male patients.,The mean age was 68.30±10.46 years.,Although females had better forced expiratory volume in 1 second and near-normal forced vital capacity, they had much impaired arterial blood gas levels (partial oxygen pressure [PO2] was 36.28 mmHg vs 57.93 mmHg; partial carbon dioxide pressure [PCO2] was 45.97 mmHg vs 42.49 mmHg; P=0.001), indicating severe exacerbation with respiratory failure.,More females had two exacerbations and two hospitalizations, while more men had one exacerbation and one hospitalization.,Low adherence to treatment and pulmonary embolism were more frequent in females.,Females had longer time from the onset of symptoms till the admission and longer hospitalization duration than males.,Comorbidities were less in number and different in women (P<0.05).,Women were undertreated and using more oral corticosteroids.,Current data showed that female COPD patients might be more prone to have severe exacerbations, a higher number of hospitalizations, and prolonged length of stay for hospitalization.,They have a different comorbidity profile and might be undertreated for COPD. | 1 |
In contemporary guidelines for the management of Chronic Obstructive Pulmonary Disease (COPD), the history of acute exacerbations plays an important role in the choice of long-term inhaled therapies.,This study aimed at evaluating population-level trends of filled inhaled prescriptions over the time course of COPD and their relation to the history of exacerbations.,We used administrative health databases in British Columbia, Canada (1997-2015), to create a retrospective incident cohort of individuals with diagnosed COPD.,We quantified long-acting inhaled medication prescriptions within each year of follow-up and documented their trend over the time course of COPD.,Using generalized linear models, we investigated the association between the frequent exacerbator status (≥2 moderate or ≥1 severe exacerbation(s) in the previous 12 months) and filling a prescription after a physician visit.,132,004 COPD patients were included (mean age 68.6, 49.2% female).,The most common medication class during the first year of diagnosis was inhaled corticosteroids (ICS, used by 49.9%), followed by long-acting beta-2 adrenoreceptor agonists (LABA, 31.8%).,Long-acting muscarinic receptor antagonists (LAMA) were the least commonly prescribed (10.4%).,ICS remained the most common prescription throughout follow-up, being used by approximately 50% of patients during each year.,39.0% of patients received combination inhaled therapies in their first year of diagnosis, with ICS+LABA being the most common (30.7%).,The association with exacerbation history was the most pronounced for triple therapy with an odds ratio (OR) of 2.68 for general practitioners and 2.02 for specialists (p<0.001 for both).,Such associations were generally stronger among GPs compared with specialists, with the exception of monotherapy with LABA or ICS.,We documented low utilization of monotherapies (specifically LAMA) and high utilization of combination therapies (particularly ICS containing).,Specialists were less likely to consider exacerbation history in the choice of inhaled therapies compared with GPs. | Severe exacerbations of COPD, ie, those leading to hospitalization, have profound clinical implications for patients and significant economic consequences for society.,The prevalence and burden of severe COPD exacerbations remain high, despite recognition of the importance of exacerbation prevention and the availability of new treatment options.,Severe COPD exacerbations are associated with high mortality, have negative impact on quality of life, are linked to cardiovascular complications, and are a significant burden on the health-care system.,This review identified risk factors that contribute to the development of severe exacerbations, treatment options (bronchodilators, antibiotics, corticosteroids [CSs], oxygen therapy, and ventilator support) to manage severe exacerbations, and strategies to prevent readmission to hospital.,Risk factors that are amenable to change have been highlighted.,A number of bronchodilators have demonstrated successful reduction in risk of severe exacerbations, including long-acting muscarinic antagonist or long-acting β2-agonist mono- or combination therapies, in addition to vaccination, mucolytic and antibiotic therapy, and nonpharmacological interventions, such as pulmonary rehabilitation.,Recognition of the importance of severe exacerbations is an essential step in improving outcomes for patients with COPD.,Evidence-based approaches to prevent and manage severe exacerbations should be implemented as part of targeted strategies for disease management. | 1 |
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