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Current recommendations to consider initiation of palliative care (PC) in COPD patients are often based on an expected poor prognosis.,However, this approach is not evidence-based, and which and when COPD patients should start PC is controversial.,We aimed to assess whether current suggested recommendations for initiating PC were sufficiently reliable.,We identified prognostic variables proposed in the literature for initiating PC; then, we ascertained their relationship with 1-year mortality, and finally, we validated their utility in our cohort of 697 patients hospitalized for COPD exacerbation.,From 24 articles of 499 screened, we selected 20 variables and retrieved 48 original articles in which we were able to calculate the relationship between each of them and 1-year mortality.,The number of studies where 1-year mortality was detailed for these variables ranged from 9 for previous hospitalizations or FEV1 ≤30% to none for albumin ≤25 mg/dL.,The percentage of 1-year mortality in the literature for these variables ranged from 5% to 60%.,In the validation cohort study, the prevalence of these proposed variables ranged from 8% to 64%; only 10 of the 18 variables analyzed in our cohort reached statistical significance with Cox regression analysis, and none overcame an area under the curve ≥0.7.,We conclude that none of the suggested criteria for initiating PC based on an expected poor vital prognosis in COPD patients in the short or medium term offers sufficient reliability, and consequently, they should be avoided as exclusive criteria for considering PC or at least critically appraised. | 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 |
Patients with chronic obstructive pulmonary disease (COPD) often experience depression and anxiety, but little information is available regarding Chinese patients with these conditions.,The present study assessed depression and anxiety in Chinese patients with COPD.,A case-controlled study was designed with 1100 patients with COPD enrolled in the case group and1100 residents without COPD and respiratory symptoms selected as the control group.,Anxiety and depression in both groups were evaluated using the Hospital Anxiety and Depression Scale (HADS).,The body mass index,degree of airflow obstruction, dyspnea, and exercise capacity (BODE ) index was used to assess COPD severity.,Binary logistic regression models were used to test the association between anxiety and depression.,The patients with COPD were more likely than controls to experience depression (cases, HADS 10.5 ± 3.6, prevalence 35.7%; controls, HADS 8.7 ± 2.7, prevalence 7.2%) and anxiety (cases, HADS 10.4 ± 3.1, prevalence 18.3%; controls, HADS 8.6 ± 2.1, prevalence 5.3%).,Subjects with anxious and depressive symptoms had poorer health outcomes including a higher BODE index, a shorter 6-minute-walk distance (6MWD), more dyspnea, and a higher St George’s respiratory questionnaire (SGRQ) score.,The prevalence of anxious and depressive symptoms increased with increasing BODE scores.,On the basis of binary logistic regression, the BODE index was significantly correlated with anxiety (OR = 1.47, p < 0.001) and depression (OR = 1.51, p < 0.001).,Anxious and depressive symptoms were also associated with several factors including younger age, female sex, higher education level, lower household income and history of smoking.,This study confirmed the high prevalence of anxiety and depression in Chinese outpatients with COPD.,Patients with COPD who had anxiety and/or depression had a poorer health-related quality of life.,Chinese Clinical Trials Registration(ChiCTR-TRC-12001958) | COPD is currently the fourth cause of morbidity and mortality in the developed world.,Patients with COPD experience a progressive deterioration and disability, which lead to a worsening in their health-related quality of life (HRQoL).,The aim of this work is to assess the Health-Related Quality of Life (HRQoL) of patients with stable COPD followed in primary care and to identify possible predictors of disease.,It is a multicenter, epidemiological, observational, descriptive study.,Subjects of both sexes, older than 40 years and diagnosed of COPD at least 12 months before starting the study were included.,Sociodemographic data, severity of disease, comorbidity, and use of health resources in the previous 12 months were collected.,All patients were administered a generic quality-of-life questionnaire, the SF-12, that enables to calculate two scores, the physical (PCS-12) and the mental (MCS-12) component summary scores.,10,711 patients were evaluated (75.6% men, 24.4% women), with a mean age of 67.1 years (SD 9.66).,The mean value of FEV1 was 35.9 ± 10.0%.,Mean PCS-12 and MCS-12 scores were 36.0 ± 9.9 and 48.3 ± 10.9, respectively.,Compared to the reference population, patients with COPD had a reduction of PCS-12, even in mild stages of the disease.,The correlation with FEV1 was higher for PCS-12 (r = 0.38) than for MCS-12 (r = 0.12).,Predictors for both HRQoL components were sex, FEV1, use of oxygen therapy, and number of visits to emergency rooms and hospital admissions.,Other independent predictors of PCS-12 were age, body mass index and educational level.,Patients with stable COPD show a reduction of their HRQoL, even in mild stages of the disease.,The factors determining the HRQoL include sex, FEV1, use of oxygen therapy, and number of visits to emergency rooms and hospital admissions. | 1 |
Chronic obstructive pulmonary disease (COPD) exacerbations have a negative impact on the quality of life of patients and the evolution of the disease.,We have investigated the prognostic value of several health-related quality of life questionnaires to predict the appearance of a composite event (new ambulatory or emergency exacerbation, hospitalization, or death) over a 1-year follow-up.,This was a multicenter, prospective, observational study.,Patients completed four questionnaires after recovering from an exacerbation (COPD Assessment Test [CAT], a Clinical COPD Questionnaire [CCQ], COPD Severity Score [COPDSS], and Airways Questionnaire [AQ20]).,Patients were followed-up until the appearance of the composite event or for 1 year, whichever came first.,A total of 497 patients were included in the study.,The majority of them were men (89.7%), with a mean age of 68.7 (SD 9.2) years, and a forced expiratory volume in 1 second of 47.1% (SD 17.5%).,A total of 303 (61%) patients experienced a composite event.,Patients with an event had worse mean scores of all questionnaires at baseline compared to patients without event: CAT=12.5 vs 11.3 (P=0.028); CCQ=2.2 vs 1.9 (P=0.013); COPDSS=12.3 vs 10.9 (P=0.001); AQ20=8.3 vs 7.5 (P=0.048).,In the multivariate analysis, only previous history of exacerbations and CAT score ≥13.5 were significant risk factors for the composite event.,A CAT score ≥13.5 increased the predictive value of previous exacerbations with an area under the receiver operating characteristic curve of 0.864 (95% CI: 0.829-0.899; P=0.001).,The predictive value of previous exacerbations significantly increased only in one of the four trialled questionnaires, namely in the CAT questionnaire.,However, previous history of exacerbations was the strongest predictor of the composite event. | Utilizing data from the Continuing to Confront COPD (chronic obstructive pulmonary disease) International Physician Survey, this study aimed to describe physicians’ knowledge and application of the GOLD (Global initiative for chronic Obstructive Lung Disease) Global Strategy for the Diagnosis, Management and Prevention of COPD diagnosis and treatment recommendations and compare performance between primary care physicians (PCPs) and respiratory specialists.,Physicians from 12 countries were sampled from in-country professional databases; 1,307 physicians (PCP to respiratory specialist ratio three to one) who regularly consult with COPD, emphysema, or chronic bronchitis patients were interviewed online, by telephone or face to face.,Physicians were questioned about COPD risk factors, prognosis, diagnosis, and treatment, including knowledge and application of the GOLD global strategy using patient scenarios.,Physicians reported using spirometry routinely (PCPs 82%, respiratory specialists 100%; P<0.001) to diagnose COPD and frequently included validated patient-reported outcome measures (PCPs 67%, respiratory specialists 81%; P<0.001).,Respiratory specialists were more likely than PCPs to report awareness of the GOLD global strategy (93% versus 58%, P<0.001); however, when presented with patient scenarios, they did not always perform better than PCPs with regard to recommending GOLD-concordant treatment options.,The proportion of PCPs and respiratory specialists providing first- or second-choice treatment options concordant with GOLD strategy for a GOLD B-type patient was 38% versus 67%, respectively.,For GOLD C and D-type patients, the concordant proportions for PCPs and respiratory specialists were 40% versus 38%, and 57% versus 58%, respectively.,This survey of physicians in 12 countries practicing in the primary care and respiratory specialty settings showed high awareness of COPD-management guidelines.,Frequent use of guideline-recommended COPD diagnostic practices was reported; however, gaps in the application of COPD-treatment recommendations were observed, warranting further evaluation to understand potential barriers to adopt guideline recommendations. | 1 |
Despite the availability of national and international guidelines, evidence suggests that chronic obstructive pulmonary disease (COPD) treatment is not always prescribed according to recommendations.,This study evaluated the current management of patients with COPD using a large UK primary-care database.,This analysis used electronic patient records and patient-completed questionnaires from the Optimum Patient Care Research Database.,Data on current management were analyzed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group and presence or absence of a concomitant asthma diagnosis, in patients with a COPD diagnosis at ≥35 years of age and with spirometry results supportive of the COPD diagnosis.,A total of 24,957 patients were analyzed, of whom 13,557 (54.3%) had moderate airflow limitation (GOLD Stage 2 COPD).,The proportion of patients not receiving pharmacologic treatment for COPD was 17.0% in the total COPD population and 17.7% in the GOLD Stage 2 subset.,Approximately 50% of patients in both cohorts were receiving inhaled corticosteroids (ICS), either in combination with a long-acting β2-agonist (LABA; 26.7% for both cohorts) or a LABA and a long-acting muscarinic antagonist (LAMA; 23.2% and 19.9%, respectively).,ICS + LABA and ICS + LABA + LAMA were the most frequently used treatments in GOLD Groups A and B.,Of patients without concomitant asthma, 53.7% of the total COPD population and 50.2% of the GOLD Stage 2 subset were receiving ICS.,Of patients with GOLD Stage 2 COPD and no exacerbations in the previous year, 49% were prescribed ICS.,A high proportion of GOLD Stage 2 COPD patients were symptomatic on their current management (36.6% with modified Medical Research Council score ≥2; 76.4% with COPD Assessment Test score ≥10).,COPD is not treated according to GOLD and National Institute for Health and Care Excellence recommendations in the UK primary-care setting.,Some patients receive no treatment despite experiencing symptoms.,Among those on treatment, most receive ICS irrespective of severity of airflow limitation, asthma diagnosis, and exacerbation history.,Many patients on treatment continue to have symptoms. | 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) 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. | Chronic obstructive pulmonary disease (COPD) is a highly prevalent condition associated with a high health care resource consumption and health care expenditures, driven mainly by exacerbations-related hospitalizations.,Telemedicine has been proposed as a mean for timely detection of exacerbation, but the available evidence is inadequate to provide conclusive information on its efficacy.,The aim of this study is to evaluate the efficacy of a telemonitoring system in reducing COPD-related hospitalizations in an elderly population with COPD.,This is a parallel arms, randomized trial including patients aged 65 or older with COPD in GOLD stages II and III enrolled in a Pulmonary Medicine outpatient facility.,Patients were randomly assigned to receive a non-invasive system able to telemonitor vital signs (oxygen saturation, heart rate, near-body temperature, overall physical activity) or standard care, and were followed up for 9 months.,The outcome measures were the number of exacerbations and exacerbation-related hospitalization.,Fifty patients were included in the telemonitoring group and 49 in the control group.,The incidence rate of respiratory events was 28/100 person/years in the telemonitoring group vs. 42/100 person/years in the control group (incidence rate ratio: 0.67, 95% CI: 0.32 - 1.36).,The corresponding figures for hospital admissions where 13/100 person/years and 20/100 person/years, respectively (IRR: 0.66, 95% CI: 0.21 - 1.86).,In our study, COPD patients followed up with the aid of a multiparametric remote monitoring system experienced a lower rate of exacerbations and COPD-related hospitalizations compared to patients followed up using the standard model of care.,These results need to be replicated in larger studies before they can be applied to the general COPD population.,Trial registration number: NCT01481506 (clinicaltrials.gov).,Funding: co-financed by Lazio Region and Intersistemi Inc. | 1 |
Indacaterol is a novel, inhaled, once-daily, ultra-long-acting β2-agonist for the treatment of chronic obstructive pulmonary disease (COPD).,This randomized, double-blind study compared the bronchodilator efficacy of indacaterol with that of placebo and tiotropium in patients with moderate-to-severe COPD.,In an incomplete-block, multi-dose, three-period, crossover design, patients received three of the following four treatments: indacaterol 150 μg, indacaterol 300 μg, tiotropium 18 μg and placebo, each once-daily for 14 days.,Each treatment period was separated by a 14-day washout.,Study drug was supplied daily by blinded, third party study personnel to maintain blinding of patients and investigators.,The primary efficacy variable was trough forced expiratory volume in one second (FEV1) at 24 h post-dose after 14 days.,The study was powered to demonstrate non-inferiority of indacaterol to tiotropium for this variable.,A total of 169 patients were randomized (mean age 65 years); 153 (90.5%) completed.,Trough FEV1 after 14 days with indacaterol 150 μg and 300 μg was statistically and clinically superior to placebo, with differences (95% CI) of 170 (120-220) and 150 (100-200) mL respectively (both p < 0.001).,For this endpoint, both doses of indacaterol not only met the criterion for non-inferiority compared with tiotropium, but also achieved numerically higher values, with differences versus tiotropium of 40 and 30 mL for indacaterol 150 and 300 μg, respectively.,At 5 min post-dose on Day 1, the mean FEV1 for both indacaterol doses was significantly higher than placebo (by 120 and 130 mL for indacaterol 150 and 300 μg, respectively; p < 0.001) and tiotropium (by 80 mL for both doses; p < 0.001).,Adverse events were reported by similar proportions of patients: 31.4%, 29.5%, 28.3% and 28.5% for indacaterol 150 μg and 300 μg, tiotropium and placebo treatments, respectively.,Once-daily indacaterol provided clinically and statistically significant 24-h bronchodilation.,Indacaterol was at least as effective as tiotropium, with a faster onset of action (within 5 min) on the first day of dosing.,Indacaterol should prove useful in patients with moderate-to-severe COPD, for whom treatment with one or more classes of long-acting bronchodilator is recommended.,ClinicalTrials.gov: NCT00615459, EudraCT number: 2007-004071-19 | 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 |
Airway bacterial dysbiosis is a feature of chronic obstructive pulmonary disease (COPD).,However, there is limited comparative data of the lung microbiome between healthy smokers, non-smokers and COPD.,We compared the 16S rRNA gene-based sputum microbiome generated from pair-ended Illumina sequencing of 124 healthy subjects (28 smokers and 96 non-smokers with normal lung function), with single stable samples from 218 COPD subjects collected from three UK clinical centres as part of the COPDMAP consortium.,In healthy subjects Firmicutes, Bacteroidetes and Actinobacteria were the major phyla constituting 88% of the total reads, and Streptococcus, Veillonella, Prevotella, Actinomyces and Rothia were the dominant genera.,Haemophilus formed only 3% of the healthy microbiome.,In contrast, Proteobacteria was the most dominant phylum accounting for 50% of the microbiome in COPD subjects, with Haemophilus and Moraxella at genus level contributing 25 and 3% respectively.,There were no differences in the microbiome profile within healthy and COPD subgroups when stratified based on smoking history.,Principal coordinate analysis on operational taxonomic units showed two distinct clusters, representative of healthy and COPD subjects (PERMANOVA, p = 0·001).,The healthy and COPD sputum microbiomes are distinct and independent of smoking history.,Our results underline the important role for Gammaproteobacteria in COPD. | Levels of iron and iron-related proteins including ferritin are higher in the lung tissue and lavage fluid of individuals with chronic obstructive pulmonary disease (COPD), when compared to healthy controls.,Whether more iron in the extracellular milieu of the lung associates with distinct clinical phenotypes of COPD, including increased exacerbation susceptibility, is unknown.,We measured iron and ferritin levels in the bronchoalveolar lavage fluid (BALF) of participants enrolled in the SubPopulations and InteRmediate Outcome Measures In COPD (SPIROMICS) bronchoscopy sub-study (n = 195).,BALF Iron parameters were compared to systemic markers of iron availability and tested for association with FEV1 % predicted and exacerbation frequency.,Exacerbations were modelled using a zero-inflated negative binomial model using age, sex, smoking, and FEV1 % predicted as clinical covariates.,BALF iron and ferritin were higher in participants with COPD and in smokers without COPD when compared to non-smoker control participants but did not correlate with systemic iron markers.,BALF ferritin and iron were elevated in participants who had COPD exacerbations, with a 2-fold increase in BALF ferritin and iron conveying a 24% and 2-fold increase in exacerbation risk, respectively.,Similar associations were not observed with plasma ferritin.,Increased airway iron levels may be representative of a distinct pathobiological phenomenon that results in more frequent COPD exacerbation events, contributing to disease progression in these individuals. | 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. | 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 |
To evaluate outcomes of the Clinical Chronic obstructive pulmonary disease (COPD) Questionnaire (CCQ) in patients with advanced COPD admitted for a post-acute pulmonary rehabilitation (PR) programme and to relate (change in) health status to lung function, degree of dyspnoea and (change in) functional capacity.,This is a prospective observational study in patients with advanced COPD admitted for a post-acute PR programme in a skilled nursing facility.,Health status (CCQ) and functional capacity were measured before and after rehabilitation.,Health status measured by the CCQ was severely impaired and showed significant and clinically relevant improvement during the post-acute PR programme.,Moderate to strong correlations were found between CCQ scores and functional capacity on admission and at discharge.,Moderate correlations were found between improvement in CCQ scores and improvement in functional capacity.,No correlation was found between CCQ scores and lung function (forced expiratory volume in 1 s % predicted).,Health status measured by the CCQ improves following a post-acute PR programme in patients with advanced COPD and correlates with improvement in functional capacity.,These results suggest that the CCQ is sensitive to change in response to PR in this specific group of patients. | Reduced physical activity is an important feature of Chronic Obstructive Pulmonary Disease (COPD).,Various activity monitors are available but their validity is poorly established.,The aim was to evaluate the validity of six monitors in patients with COPD.,We hypothesized triaxial monitors to be more valid compared to uniaxial monitors.,Thirty-nine patients (age 68±7years, FEV1 54±18%predicted) performed a one-hour standardized activity protocol.,Patients wore 6 monitors (Kenz Lifecorder (Kenz), Actiwatch, RT3, Actigraph GT3X (Actigraph), Dynaport MiniMod (MiniMod), and SenseWear Armband (SenseWear)) as well as a portable metabolic system (Oxycon Mobile).,Validity was evaluated by correlation analysis between indirect calorimetry (VO2) and the monitor outputs: Metabolic Equivalent of Task [METs] (SenseWear, MiniMod), activity counts (Actiwatch), vector magnitude units (Actigraph, RT3) and arbitrary units (Kenz) over the whole protocol and slow versus fast walking.,Minute-by-minute correlations were highest for the MiniMod (r = 0.82), Actigraph (r = 0.79), SenseWear (r = 0.73) and RT3 (r = 0.73).,Over the whole protocol, the mean correlations were best for the SenseWear (r = 0.76), Kenz (r = 0.52), Actigraph (r = 0.49) and MiniMod (r = 0.45).,The MiniMod (r = 0.94) and Actigraph (r = 0.88) performed better in detecting different walking speeds.,The Dynaport MiniMod, Actigraph GT3X and SenseWear Armband (all triaxial monitors) are the most valid monitors during standardized physical activities.,The Dynaport MiniMod and Actigraph GT3X discriminate best between different walking speeds. | 1 |
Chronic obstructive pulmonary disease (COPD) is a multisystem disease that resembles the accumulation of multiple impairments seen in aging.,A comprehensive geriatric assessment (CGA) captures multisystem deficits, from which a frailty index (FI) can be derived.,We hypothesized that patients with COPD would be frailer than a comparator group free from respiratory disease.,In this cross-sectional analysis, the CGA questionnaire was completed and used to derive an FI in 520 patients diagnosed with COPD and 150 comparators.,All subjects were assessed for lung function, body composition, 6-minute walking distance (6MWD), and handgrip strength.,Patients completed validated questionnaires on health-related quality of life and respiratory symptoms.,Patients and comparators were similar in age, gender, and body mass index, but patients had a greater mean ± SD FI 0.16 ± 0.08 than comparators 0.05 ± 0.03.,In patients, a stepwise linear regression 6MWD (β = −0.43), number of comorbidities (β = −0.38), handgrip (β = −0.11), and number of exacerbations (β = 0.11) were predictors of frailty (all p < 0.01).,This large study suggests patients with COPD are frailer than comparators.,The FI derived from the CGA captures the deterioration of multiple systems in COPD and provides an overview of impairments, which may identify individuals at increased risk of morbidity and mortality in COPD. | Frailty is a state of increased risk of unfavorable outcomes when exposed to stressors, and COPD is one of the several chronic illnesses associated with the condition.,However, few studies have been conducted regarding the prevalence of COPD and its related factors in Southeast Asia.,The objectives of this study were to determine the prevalence of frailty in COPD patients and to identify the associated factors in these populations.,A cross-sectional study of COPD patients who attended a COPD clinic was conducted from May 2015 to December 2016.,Baseline characteristics were collected, and the diagnosis of frailty was based on the FRAIL (fatigue, resistance, ambulation, illnesses, and loss of weight) scale.,Descriptive statistics were used to analyze baseline data.,Factors associated with frailty were analyzed using univariate and multivariate regression analyses.,The results showed that the prevalence rates of frailty and pre-frailty were 6.6% (eight out of 121 cases) and 41.3% (50 out of 121 cases), respectively, among COPD patients.,Fatigue was the most common component of the FRAIL scale that was found more frequently in frail patients than in non-frail patients (odds ratio [OR] 91.9).,Factors associated with frailty according to multivariate analyses were comorbid cancer (adjusted OR [AOR] 45.8), at least two instances of nonelective admission over the past 12 months (AOR 112.5), high waist circumference (WC) (AOR 1.3), and presence of sarcopenia (AOR 29.5).,In conclusion, frailty affected 6.6% of stable COPD patients.,Cancer, two or more instances of nonelective hospitalization over the past 12 months, high WC, and presence of sarcopenia were associated with frailty.,Early identification and intervention in high-risk patients is recommended to prevent or delay the adverse outcomes of frailty. | 1 |
C-reactive protein (CRP) measurement has proven valuable for detecting exacerbations, but its usefulness in predicting etiology remains controversial.,Likewise, its potential value as a marker of severity, which is well established in patients with pneumonia, remains unproven in chronic obstructive pulmonary disease (COPD) exacerbations.,A cohort study of 118 patients with severe COPD and acute infectious exacerbations were included and followed up over 1 year.,Episodes of exacerbations meeting Anthonisen’s criteria type I-II were evaluated, analyzing the etiology and inflammatory response as measured by CRP in blood.,A total of 380 episodes were recorded.,Full microbiological analysis was available in 265 samples.,Haemophilus influenzae was the most commonly isolated bacteria and rhinovirus the most common virus.,Median CRP levels from the 265 episodes were higher in the cases with positive cultures for bacteria (58.30 mg/L, interquartile range [IQR] 21.0-28.2) than in episodes only positive for viruses (37.3 mg/L, IQR 18.6-79.1) and cases negative for any microorganism (36.4 mg/L, IQR 10.8-93.7) (P<0.014).,H. influenzae and Streptococcus pneumoniae reached the highest CRP levels of 74.5 mg/L (IQR 23.9-167.9) and 74.1 mg/L (IQR 42.0-220.7), respectively.,In the 380 exacerbations studied, 227 (~60%) were community-managed, while 153 (~40%) required hospital admission.,In the multivariate analysis to assess the influence of inflammatory response on exacerbation severity, baseline hypercapnia (odds ratio [OR]: 2.70, 95% confidence interval [CI]: 1.46-4.9) and CRP levels >100 mg/L (OR: 4.23, 95% CI: 2.12-8.44) were independent predictors after adjustment for baseline characteristics.,CRP level was higher in bacterial infections, especially when H. influenzae and S. pneumoniae were isolated.,CRP values >100 mg/L were associated with a fourfold increased risk of hospital admission.,Therefore, CRP blood levels may be a useful biomarker in the management of exacerbations appearing in patients with severe disease. | Chronic obstructive pulmonary disease (COPD) exacerbations are the leading cause of hospital admission and death among chronic bronchitis (CB) patients.,This study estimated annual COPD exacerbation rates, related costs, and their predictors among patients treated for CB.,This was a retrospective study using claims data from the HealthCore Integrated Research Database (HIRDSM).,The study sample included CB patients aged ≥ 40 years with at least one inpatient hospitalization or emergency department visit or at least two office visits with CB diagnosis from January 1, 2004 to May 31, 2011, at least two pharmacy fills for COPD medications during the follow-up year, and ≥2 years of continuous enrollment.,COPD exacerbations were categorized as severe or moderate.,Annual rates, costs, and predictors of exacerbations during follow-up were assessed.,A total of 17,382 individuals treated for CB met the selection criteria (50.6% female; mean ± standard deviation age 66.7 ± 11.4 years).,During the follow-up year, the mean ± standard deviation number of COPD maintenance medication fills was 7.6 ± 6.3; 42.6% had at least one exacerbation and 69.5% of patients with two or more exacerbations during the 1 year prior to the index date (baseline period) had any exacerbation during the follow-up year.,The mean ± standard deviation cost per any exacerbation was $269 ± $748 for moderate and $18,120 ± $31,592 for severe exacerbation.,The number of baseline exacerbations was a significant predictor of the number of exacerbations and exacerbation costs during follow-up.,Exacerbation rates remained high among CB patients despite treatment with COPD maintenance medications.,New treatment strategies, designed to reduce COPD exacerbations and associated costs, should focus on patients with high prior-year exacerbations. | 1 |
The recognition of asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) as a distinct phenotype of COPD or asthma has increased.,Although ACO has worse clinical features than non-ACO COPD, limited information is available on long-term outcomes of lung function decline for ACO and non-ACO COPD.,COPD patients with at least 3 years of follow-up were selected from the Korean Obstructive Lung Disease cohort.,ACO was defined based on 3 major criteria: 1) airflow limitation in individuals 40 years of age and older, 2) ≥10 pack-years of smoking history, and 3) a history of asthma or bronchodilator response of > 400 mL in forced expiratory volume in 1 s (FEV1) at baseline; and at least 1 minor criterion: 1) history of atopy or allergic rhinitis, 2) two separated bronchodilator responses of ≥12% and 200 mL in FEV1, or 3) peripheral blood eosinophils ≥300 cells/μL.,Lung function decline was compared using a linear mixed effects model for longitudinal data with random intercept and random slope.,Among 239 patients, 47 were diagnosed with ACO (19.7%).,During the follow-up period, change in smoking status, use of inhaled corticosteroids (ICS) and long-acting β2-agonists or ICS and at least 2 exacerbations per year were similar between patients with non-ACO COPD and ACO.,Over a median follow-up duration of 5.8 years, patients with non-ACO COPD experienced a faster annual decline in pre-bronchodilator FEV1 than patients with ACO (− 29.3 ml/year vs. -13.9 ml/year, P = 0.042), which was persistent after adjustment for confounders affecting lung function decline.,Patients with ACO showed favorable longitudinal changes in lung function compared to COPD patients over a median follow-up of 5.8 years.,The online version of this article (10.1186/s12931-018-0737-8) contains supplementary material, which is available to authorized users. | 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 |
Epigenetic modification is one of most important mechanisms underlying the pathogenesis of chronic obstructive pulmonary disease (COPD).,The purpose of this study was to determine whether histone acetyltransferase binding to ORC1 (HBO1) can protect against cigarette smoke (CS)-induced cell apoptosis and sustain normal histone acetylation in COPD.,Human lung tissue samples were obtained from patients who underwent lung resection.,The emphysema mouse model and HBO1 overexpressing mice were each established by intraperitoneal injection with cigarette smoke extract (CSE) or intratracheal lentiviral vectors instillation.,TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays were used to assess apoptotic ratio in mice.,The apoptosis of human bronchial epithelial cells (HBECs) was assayed by flow cytometry.,HBO1, B-cell lymphoma-2 (BCL-2), and H3K14ac protein expression were detected by Western blotting.,HBO1 mRNA expression was measured by quantitative real-time polymerase chain reaction.,Protein expression of HBO1 was decreased significantly in lung tissue from COPD patients and CSE-treated emphysema mouse models.,Overexpression of HBO1 attenuated CSE-induced emphysematous changes, as well as apoptosis in the lungs of COPD mice.,In vitro, the HBO1 protein degraded in a time- and dose-dependent course with CSE treatment.,With flow cytometry, we proved that HBO1 could reverse the apoptosis of HBECs induced by CSE.,Furthermore, HBO1 overexpression promoted the expression of anti-apoptotic BCL-2 protein and enhanced H3K14 acetylation in airway epithelial cells.,These findings demonstrate that the key histone modulator HBO1 plays a protective role in COPD pathogenesis that may shed light on potential therapeutic targets to inhibit the progress of COPD. | Endothelial progenitor cells (EPCs) might play a protective role in COPD.,The aim of this study was to investigate whether intratracheal allogeneic transplantation of bone-marrow-derived EPCs would attenuate the development of smoking-induced COPD in mice.,Isolated mononuclear cells from the bone marrow of C57BL/6J mice were cultured in endothelial cell growth medium-2 for 10 days, yielding EPCs.,A murine model of COPD was established by passive 90-day exposure of cigarette smoke.,On day 30, EPCs or phosphate-buffered saline alone was administered into the trachea.,On day 90, EPCs or 30 μL phosphate-buffered saline alone was administered into the trachea, and on day 120, inflammatory cells, antioxidant activity, apoptosis, matrix metalloproteinase (MMP)-2, and MMP-9 were measured.,After EPC treatment, the lung function of the mice had improved compared with the untreated mice.,Mean linear intercept and destructive index were reduced in the EPCs-treated group compared with the untreated group.,In addition, the EPCs-treated mice exhibited less antioxidant activity in bronchoalveolar lavage fluid compared with the untreated mice.,Moreover, decreased activities of MMP-2, MMP-9, and TUNEL-positive cells in lung tissues were detected in EPCs-treated mice.,Intratracheal transplantation of EPCs attenuated the development of pulmonary emphysema and lung function disorder probably by alleviating inflammatory infiltration, decelerating apoptosis, inhibiting proteolytic enzyme activity, and improving antioxidant activity. | 1 |
As of 11 July, 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic has infected over 12.7 million people around the world and caused more than 560,000 deaths [1].,Given the devastating impact that COVID-19 can have on the lung, it is natural to fear for patients with underlying COPD.,Estimating their excess risk for contracting COVID-19 and, in particular, its more severe respiratory manifestations has been a challenging exercise in this pandemic for various reasons.,First, the reporting on cases has concentrated on hospitalised and intensive care unit (ICU) patients, rather than on mild, outpatient cases.,This is in part also due to the variability in testing strategies across the world, where some nations with stricter testing requirements and scarce testing resources have focused on testing only those requiring hospitalisation.,COPD patients have increased risk of severe pneumonia and poor outcomes when they develop COVID-19.,This may be related to poor underlying lung reserves or increased expression of ACE-2 receptor in small airways.https://bit.ly/37dSB8l | Like M.,Rossato and co-workers, we too have been struck by the relative underrepresentation of current smokers in cohorts of coronavirus disease 2019 (COVID-19) patients, particularly in light of our recent findings that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor angiotensin-converting enzyme II (ACE-2) is upregulated in the airway epithelium of this population [1].,China [2], Italy (as reported by M.,Rossato and co-workers), and now New York City [3] have all reported current smoking rates below those of their respective general populations.,The reason for this is a mystery.,One possible explanation is misclassification of smoking status owing to under-reporting of smoking in these cohorts.,Another is that smokers may be taking medications that may offer some protection against COVID-19 (e.g. certain inhalers).,Smoking and COPD are risk factors for severe COVID-19https://bit.ly/2KJxAbp | 1 |
Guideline recommendations for chronic obstructive pulmonary disease (COPD) are based on the results of large pharmaceutically-sponsored COPD studies (LPCS).,There is a paucity of data on disease characteristics at the primary care level, while the majority of COPD patients are treated in primary care.,We aimed to evaluate the external validity of six LPCS (ISOLDE, TRISTAN, TORCH, UPLIFT, ECLIPSE, POET-COPD) on which current guidelines are based, in relation to primary care COPD patients, in order to inform future clinical practice guidelines and trials.,Baseline data of seven primary care databases (n = 3508) from Europe were compared to baseline data of the LPCS.,In addition, we examined the proportion of primary care patients eligible to participate in the LPCS, based on inclusion criteria.,Overall, patients included in the LPCS were younger (mean difference (MD)-2.4; p = 0.03), predominantly male (MD 12.4; p = 0.1) with worse lung function (FEV1% MD -16.4; p<0.01) and worse quality of life scores (SGRQ MD 15.8; p = 0.01).,There were large differences in GOLD stage distribution compared to primary care patients.,Mean exacerbation rates were higher in LPCS, with an overrepresentation of patients with ≥1 and ≥2 exacerbations, although results were not statistically significant.,Our findings add to the literature, as we revealed hitherto unknown GOLD I exacerbation characteristics, showing 34% of mild patients had ≥1 exacerbations per year and 12% had ≥2 exacerbations per year.,The proportion of primary care patients eligible for inclusion in LPCS ranged from 17% (TRISTAN) to 42% (ECLIPSE, UPLIFT).,Primary care COPD patients stand out from patients enrolled in LPCS in terms of gender, lung function, quality of life and exacerbations.,More research is needed to determine the effect of pharmacological treatment in mild to moderate patients.,We encourage future guideline makers to involve primary care populations in their recommendations. | The aim of this study was to evaluate the association between health-related quality of life (HRQL) and disease severity using lung function measures.,A survey was performed in subjects with COPD in Sweden. 168 subjects (70 women, mean age 64.3 years) completed the generic HRQL questionnaire, the Short Form 36 (SF-36), the disease-specific HRQL questionnaire; the St George's Respiratory Questionnaire (SGRQ), and the utility measure, the EQ-5D.,The subjects were divided into four severity groups according to FEV1 per cent of predicted normal using two clinical guidelines: GOLD and BTS.,Age, gender, smoking status and socio-economic group were regarded as confounders.,The COPD severity grades affected the SGRQ Total scores, varying from 25 to 53 (GOLD p = 0.0005) and from 25 to 45 (BTS p = 0.0023).,The scores for SF-36 Physical were significantly associated with COPD severity (GOLD p = 0.0059, BTS p = 0.032).,No significant association were noticed for the SF-36, Mental Component Summary scores and COPD severity.,Scores for EQ-5D VAS varied from 73 to 37 (GOLD I-IV p = 0.0001) and from 73 to 50 (BTS 0-III p = 0.0007).,The SGRQ Total score was significant between age groups (p = 0.0047).,No significant differences in HRQL with regard to gender, smoking status or socio-economic group were noticed.,The results show that HRQL in COPD deteriorates with disease severity and with age.,These data show a relationship between HRQL and disease severity obtained by lung function. | 1 |
Randomised, double-blind, controlled trials are considered the gold standard for evaluating a pharmacological agent, as they minimise any potential bias.,However, it is not always possible to perform double-blind trials, particularly for medications delivered via specific devices, e.g. inhalers.,In such cases, open-label studies can be employed instead.,Methods used to minimise any potential bias introduced by open-label study design include randomisation, crossover study design, and objective measurements of primary efficacy and safety variables.,Concise reviews analysing the effect of blinding procedures of comparator drugs on outcomes in respiratory trials are limited.,Here, we compare data from different chronic obstructive pulmonary disease trials with once-daily indacaterol versus a blinded or non-blinded comparator.,The clinical trial programme for indacaterol, a once-daily, long-acting β2-agonist, used tiotropium as a comparator either in an open-label or blinded fashion.,Data from these studies showed that the effects of tiotropium were consistent for forced expiratory volume in 1 second, an objective measure, across blinded and non-blinded studies.,The data were consistent with previous studies of double-blind tiotropium, suggesting that the open-label use of tiotropium did not introduce treatment bias.,The effect of tiotropium on subjective measures (St George’s Respiratory Questionnaire; transition dyspnoea index) varied slightly across blinded and non-blinded studies, indicating that minimal bias was introduced by using open-label tiotropium.,Importantly, the studies used randomised, open-label tiotropium patients to treatment allocation, a method shown to minimise bias to a greater degree than blinding.,In conclusion, it is important when reporting a clinical trial to be transparent about who was blinded and how the blinding was performed; if the design is open-label, additional efforts must be made to minimise risk of bias.,If these recommendations are followed, and the data are considered in the full knowledge of any potential sources of bias, results with tiotropium suggest that data from open-label studies can provide valuable and credible evidence of the effects of therapy. | To compare efficacy of indacaterol to that of fixed-dose combination (FDC) formoterol and budesonide (FOR/BUD) and FDC salmeterol and fluticasone (SAL/FP) for the treatment of chronic obstructive pulmonary disease (COPD) based on the available randomized clinical trials (RCTs).,Fifteen placebo-controlled RCTs were included that evaluated: indacaterol 150 μg (n = 5 studies), indacaterol 300 μg (n = 4), FOR/BUD 9/160 μg (n = 2), FOR/BUD 9/320 μg (n = 3), SAL/FP 50/500 μg (n = 5), and SAL/FP 50/250 μg (n = 1).,Outcomes of interest were trough forced expiratory volume in 1 second (FEV1), total scores for St.,George’s Respiratory Questionnaire (SGRQ), and transition dyspnea index (TDI).,All trials were analyzed simultaneously using a Bayesian network meta-analysis and relative treatment effects between all regimens were obtained.,Treatment-by-covariate interactions were included where possible to improve the similarity of the trials.,Indacaterol 150 μg resulted in a higher change from baseline (CFB) in FEV1 at 12 weeks compared to FOR/BUD 9/160 μg (difference in CFB 0.11 L [95% credible intervals: 0.08, 0.13]) and FOR/BUD 9/320 μg (0.09 L [0.06, 0.11]) and was comparable to SAL/FP 50/250 μg (0.02 L [−0.04, 0.08]) and SAL/FP 50/500 μg (0.03 L [0.00, 0.06]).,Similar results were observed for indacaterol 300 μg at 12 weeks and indacaterol 150/300 μg at 6 months.,Indacaterol 150 μg demonstrated comparable improvement in SGRQ total score at 6 months versus FOR/BUD (both doses), and SAL/FP 50/500 μg (−2.16 point improvement [−4.96, 0.95]).,Indacaterol 150 and 300 μg demonstrated comparable TDI scores versus SAL/FP 50/250 μg (0.21 points (−0.57, 0.99); 0.39 [−0.39, 1.17], respectively) and SAL/FP 50/500 μg at 6 months.,Indacaterol monotherapy is expected to be at least as good as FOR/BUD (9/320 and 9/160 μg) and comparable to SAL/FP (50/250 and 50/500 μg) in terms of lung function.,Indacaterol is also expected to be comparable to FOR/BUD (9/320 and 9/160 μg) and SAL/FP 50/500 μg in terms of health status and to SAL/FP (50/250 and 50/500 μg) in terms of breathlessness. | 1 |
Current guidelines recommend inhaled pharmacologic therapy as the preferred route of administration for treating COPD.,Bronchodilators (β2-agonists and antimuscarinics) are the mainstay of pharmacologic therapy in patients with COPD, with long-acting agents recommended for patients with moderate to severe symptoms or those who are at a higher risk for COPD exacerbations.,Dry powder inhalers and pressurized metered dose inhalers are the most commonly used drug delivery devices, but they may be inadequate in various clinical scenarios (eg, the elderly, the cognitively impaired, and hospitalized patients).,As more drugs become available in solution formulations, patients with COPD and their caregivers are becoming increasingly satisfied with nebulized drug delivery, which provides benefits similar to drugs delivered by handheld inhalers in both symptom relief and improved quality of life.,This article reviews recent innovations in nebulized drug delivery and the important role of nebulized therapy in the treatment of COPD. | A nebulized formulation of formoterol, Perforomist®, 20 μg/2 ml, has been available since 2007 for the maintenance treatment of chronic obstructive pulmonary disease (COPD).,We review the safety and efficacy data obtained during its development.,In a dose-finding study, formoterol inhalation solution (FFIS) was similar to the formoterol originator, Foradil® 12 μg DPI (FA) in patients with COPD.,In a 12-week efficacy study, FFIS manifested a rapid onset of action and FEV1 peak, AUC0-12, and trough levels similar to FA.,No loss of efficacy, tachyphylaxis, was observed over 12 weeks of regular administration.,In placebo-controlled studies in COPD patients receiving maintenance tiotropium, the addition of FFIS significantly augmented bronchodilation over the 6-week treatment duration, signifying that nebulized formoterol can further improve lung function in patients who are receiving tiotropium without an observed increase in adverse reactions.,The safety profile of FFIS during 12-week and 1-year studies revealed adverse events that were similar to those of placebo and FA.,Cardiac rhythm studies, including frequent ECGs and Holter monitoring, did not indicate any increase in rate or rhythm disturbances greater than placebo or FA.,We conclude that maintenance use of Perforomist® is appropriate for patients with COPD who require or prefer a nebulizer for management of their disease. | 1 |
Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.,Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks.,Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.,In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment.,Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies.,Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg.,Incidence of adverse events was comparable between the FDCs and the mono-components.,These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.,Lung function and symptomatic benefits of daily tiotropium+olodaterol fixed-dose combination in moderate to very severe COPDhttp://ow.ly/DIKiY | Chronic obstructive pulmonary disease (COPD) is a preventable and treatable lung disease characterized by airflow limitation that is not fully reversible.,In a significant proportion of patients with COPD, reduced lung elastic recoil combined with expiratory flow limitation leads to lung hyperinflation during the course of the disease.,Development of hyperinflation during the course of COPD is insidious.,Dynamic hyperinflation is highly prevalent in the advanced stages of COPD, and new evidence suggests that it also occurs in many patients with mild disease, independently of the presence of resting hyperinflation.,Hyperinflation is clinically relevant for patients with COPD mainly because it contributes to dyspnea, exercise intolerance, skeletal muscle limitations, morbidity, and reduced physical activity levels associated with the disease.,Various pharmacological and nonpharmacological interventions have been shown to reduce hyperinflation and delay the onset of ventilatory limitation in patients with COPD.,The aim of this review is to address the more recent literature regarding the pathogenesis, assessment, and management of both static and dynamic lung hyperinflation in patients with COPD.,We also address the influence of biological sex and obesity and new developments in our understanding of hyperinflation in patients with mild COPD and its evolution during progression of the disease. | 1 |
Acute exacerbation of chronic obstructive pulmonary disease (COPD) is a leading cause of hospitalizations and readmissions in the US.,Reducing the frequency of hospital readmission is a high priority of US health care organizations and government agencies.,This study evaluated the risk factors associated with readmissions among commercially insured adults aged 40-65 years in the US who were hospitalized for COPD.,This retrospective cohort study used anonymized claims data from the Truven Health MarketScan® Commercial Claims and Encounters database.,The patients included were aged 40-65 years, had an index hospitalization with a primary diagnosis of COPD between July 1, 2008 and June 30, 2010 (continuously enrolled 12 months before and after), and were alive at hospital discharge.,Patients with cystic fibrosis or tuberculosis or who were transferred to another inpatient facility after hospital discharge were excluded.,All readmissions regardless of diagnosis, and separately a subset of all readmissions that had COPD as a primary or secondary diagnosis (COPD-related), were examined.,Univariate descriptive statistics and multivariable regression methods were used.,Of the 18,568 patients with index COPD hospitalizations, 6,095 (32.83%) met the eligibility criteria.,Of those, 503 (8.25%) were readmitted within the first 30 days post-index hospitalization and 2,527 (41.46%) within the first year (COPD-related 340 [5.58%] and 1,681 [27.58%], respectively).,The median time to the first readmission post initial discharge was 4.0 months, with a mean of 5.0 ± 3.4 months.,Multivariable regression analyses showed that comorbid conditions and health care utilization in the pre-index period were significant predictors for readmission both 30 and 90 days following index hospitalization.,A relatively high readmission rate was observed for patients aged 40-65 years.,The results suggest that attention to patient comorbidities and pre-index/index health care service utilization may help identify hospitalized COPD patients at higher risk for readmission. | As many other European healthcare systems the Danish healthcare system (DHS) has targeted chronic condition care in its reform efforts.,Benchmarking is a valuable tool to identify areas for improvement.,Prior work indicates that chronic care coordination is poor in the DHS, especially in comparison with care in Kaiser Permanente (KP), an integrated delivery system based in the United States.,We investigated population rates of hospitalisation and readmission rates for ambulatory care sensitive, chronic medical conditions in the two systems.,Using a historical cohort study design, age and gender adjusted population rates of hospitalisations for angina, heart failure, chronic obstructive pulmonary disease, and hypertension, plus rates of 30-day readmission and mortality were investigated for all individuals aged 65+ in the DHS and KP.,DHS had substantially higher rates of hospitalisations, readmissions, and mean lengths of stay per hospitalisation, than KP had.,For example, the adjusted angina hospitalisation rates in 2007 for the DHS and KP respectively were 1.01/100 persons (95%CI: 0.98-1.03) vs.,0.11/100 persons (95%CI: 0.10-0.13/100 persons); 21.6% vs.,9.9% readmission within 30 days (OR = 2.53; 95% CI: 1.84-3.47); and mean length of stay was 2.52 vs.,1.80 hospital days.,Mortality up through 30 days post-discharge was not consistently different in the two systems.,There are substantial differences between the DHS and KP in the rates of preventable hospitalisations and subsequent readmissions associated with chronic conditions, which suggest much opportunity for improvement within the Danish healthcare system.,Reductions in hospitalisations also could improve patient welfare and free considerable resources for use towards preventing disease exacerbations.,These conclusions may also apply for similar public systems such as the US Medicare system, the NHS and other systems striving to improve the integration of care for persons with chronic conditions. | 1 |
Frailty is a state of increased vulnerability that has a significant risk of unfavorable outcomes such as increased dependency and/or death, but little is known about frailty in people with chronic obstructive pulmonary disease (COPD).,We aimed to determine the prevalence of frailty in COPD patients and to identify the associated risk factors.,Two hundred fifty-seven COPD patients enrolled from primary care in Greece between 2015 and 2016.,Physicians used structured interviews to collect cross-sectional data including demographics, medical history, symptoms and COPD Assessment Tool (CAT) or modified Medical Research Council Dyspnea scale (mMRC) score.,Patients were classified into severity groups according to GOLD 2017 guidelines.,Participants completed the The Frail Non-Disabled (FiND) questionnaire, exploring the frailty and disability domains.,In the present analyses, frail patients with and without mobility disability were pooled and were compared to non-frail patients.,Factors associated with frailty were analyzed using univariate and multivariate logistic regression.,Mean (SD) age was 65 (12.3) with 79% males.,The majority of patients suffered with frailty (82%) of which 76.8% had mobility disability.,84.2% were married/with partner and 55.4% retired.,55.6% were current smokers.,Uncontrolled disease (≥10 CAT score) was reported in 91.1% and 37.2% of patients had ≥2 exacerbations in the past year.,Dyspnea (38%) and cough (53.4%) were the main symptoms.,Main comorbidities were hypertension (72.9%), hyperlipidaemia (24.6%) and diabetes (11%).,Risk of frailty was significantly increased with age (OR; 95%CI: 1.05; 1.02-1.08), hypertension (2.25; 1.14-4.45), uncontrolled disease (≥10 CAT score 4.65; 1.86-11.63, ≥2 mMRC score 5.75 (2.79-11.85) or ≥ 2 exacerbations 1.73; 1.07-2.78), smoking cessation (ex compared to current smokers: 2.37; 1.10-5.28) and GOLD status (B&D compared to A&C groups: CAT-based 4.65; 1.86-11.63; mMRC-based: 5.75; 2.79-11.85).,In multivariate regression smoking cessation and GOLD status remained significant.,Gender, body mass index, occupational or marital status, symptoms and other comorbidities were not significant.,Frailty with mobility disability is common in COPD patients and severity of disease increases the risk.,It is possible that frail patients are more likely to quit smoking perhaps because of their disability and uncontolled disease.,Routine assessment of frailty in addition to COPD control may allow early interventions for preventing or delaying progression of frailty and improvement in COPD disease. | Frailty is a state of increased risk of unfavorable outcomes when exposed to stressors, and COPD is one of the several chronic illnesses associated with the condition.,However, few studies have been conducted regarding the prevalence of COPD and its related factors in Southeast Asia.,The objectives of this study were to determine the prevalence of frailty in COPD patients and to identify the associated factors in these populations.,A cross-sectional study of COPD patients who attended a COPD clinic was conducted from May 2015 to December 2016.,Baseline characteristics were collected, and the diagnosis of frailty was based on the FRAIL (fatigue, resistance, ambulation, illnesses, and loss of weight) scale.,Descriptive statistics were used to analyze baseline data.,Factors associated with frailty were analyzed using univariate and multivariate regression analyses.,The results showed that the prevalence rates of frailty and pre-frailty were 6.6% (eight out of 121 cases) and 41.3% (50 out of 121 cases), respectively, among COPD patients.,Fatigue was the most common component of the FRAIL scale that was found more frequently in frail patients than in non-frail patients (odds ratio [OR] 91.9).,Factors associated with frailty according to multivariate analyses were comorbid cancer (adjusted OR [AOR] 45.8), at least two instances of nonelective admission over the past 12 months (AOR 112.5), high waist circumference (WC) (AOR 1.3), and presence of sarcopenia (AOR 29.5).,In conclusion, frailty affected 6.6% of stable COPD patients.,Cancer, two or more instances of nonelective hospitalization over the past 12 months, high WC, and presence of sarcopenia were associated with frailty.,Early identification and intervention in high-risk patients is recommended to prevent or delay the adverse outcomes of frailty. | 1 |
Chronic obstructive pulmonary disease (COPD) is set to become the third most frequent cause of death and also the third largest cause of global morbidity by 2020.,In China, where the population is aging rapidly, COPD has become one of the leading causes of disability and a large economic burden.,An epidemiological assessment of the COPD in China is required, with a focus on the number of cases living with disease, main determinants of the disease and time trends.,We systematically searched large Chinese bibliographic databases and English databases to identify spirometry-based epidemiological studies of the prevalence of COPD in China diagnosed according to GOLD criteria.,We estimated age- and gender-specific prevalence of COPD using a multilevel mixed-effect logistic regression.,We also presented the time trends of COPD between 1990 and 2010 by age, gender and setting (urban vs rural).,In 1990, the prevalence of COPD ranged from 0.49% (95% CI = 0.29-0.85) in <20 years group to 20.95% (95% CI = 14.04-27.04) in> = 80 years group, and the crude prevalence for China was 2.70% (95% CI = 1.86-3.51).,In 2010, the prevalence in <20 years was 0.55% (95% CI = 0.37-1.04) and in> = 80 years was 22.89% (95% CI = 18.13-28.96), with the crude prevalence for China of 3.84% (95% CI = 3.30-4.77).,The COPD prevalence in males was about two-fold higher than in females, and it increased with increasing age.,Between 1990-2010, the total number of Chinese people living with COPD increased by 66.73%, from 30.90 million (95% CI = 21.28-40.02) in 1990 to 51.52 million (95% CI = 44.26-63.93) in 2010.,This increase was most striking in middle age, and greater in females than in males from 30 years up to 64 years.,Our estimates, which used an independent approach to acquiring data and development of analytical methods, and were based on a more complete data set, are remarkably similar to those produced recently by the GBD 2013 collaboration, differing by only about 5% in the estimated number of COPD cases in 1990 and by 1% in 2010.,COPD is a highly prevalent disease in China and its importance is growing steadily.,The number of people living with COPD has increased substantially between 1990 and 2010.,COPD is more frequent in males and in rural areas.,Optimised primary and secondary prevention and treatment is urgently needed to counter this growing trend.,Improved epidemiological studies will be required to assist development of more effective strategies of prevention and treatment of COPD in China in the next decade and beyond. | Early identification of patients with a prolonged stay due to acute exacerbation of chronic obstructive pulmonary disease (COPD) may reduce risk of adverse event and treatment costs.,This study aimed to identify predictors of prolonged stay after acute exacerbation of COPD based on variables on admission; the study also looked to establish a prediction model for length of stay (LOS).,We extracted demographic and clinical data from the medical records of 599 patients discharged after an acute exacerbation of COPD between March 2006 and December 2008 at Oslo University Hospital, Aker.,We used logistic regression analyses to assess predictors of a length of stay above the 75th percentile and assessed the area under the receiving operating characteristic curve to evaluate the model’s performance.,We included 590 patients (54% women) aged 73.2±10.8 years (mean ± standard deviation) in the analyses.,Median LOS was 6.0 days (interquartile range [IQR] 3.5-11.0).,In multivariate analysis, admission between Thursday and Saturday (odds ratio [OR] 2.24 [95% CI 1.60-3.51], P<0.001), heart failure (OR 2.26, 95% CI 1.34-3.80), diabetes (OR 1.90, 95% CI 1.07-3.37), stroke (OR 1.83, 95% CI 1.04-3.21), high arterial PCO2 (OR 1.26 [95% CI 1.13-1.41], P<0.001), and low serum albumin level (OR 0.92 [95% CI 0.87-0.97], P=0.001) were associated with a LOS >11 days.,The statistical model had an area under the receiver operating characteristic curve of 0.73.,Admission between Thursday and Saturday, heart failure, diabetes, stroke, high arterial PCO2, and low serum albumin level were associated with a prolonged LOS.,These findings may help physicians to identify patients that will need a prolonged LOS in the early stages of admission.,However, the predictive model exhibited suboptimal performance and hence is not ready for clinical use. | 1 |
Non-typeable Haemophilus influenzae (NTHi) is a key pathogen in COPD, being associated with airway inflammation and risk of exacerbation.,Why some patients are susceptible to colonisation is not understood.,We hypothesised that this susceptibility may be due to a deficiency in mucosal humoral immunity.,The aim of our study (NCT01701869) was to quantify the amount and specificity of antibodies against NTHi in the lungs and the associated risk of infection and inflammation in health and COPD.,Phlebotomy, sputum induction and bronchoscopy were performed on 24 mild-to-moderate COPD patients and 8 age and smoking-matched controls.,BAL (Bronchoalveolar lavage) total IgG1, IgG2, IgG3, IgM and IgA concentrations were significantly increased in COPD patients compared to controls.,NTHi was detected in the lungs of 7 of the COPD patients (NTHi+ve-29%) and these patients had a higher median number of previous exacerbations than NTHi-ve patients as well as evidence of increased systemic inflammation.,When comparing NTHi+ve versus NTHi-ve patients we observed a decrease in the amount of both total IgG1 (p = 0.0068) and NTHi-specific IgG1 (p = 0.0433) in the BAL of NTHi+ve patients, but no differences in total IgA or IgM.,We observed no evidence of decreased IgG1 in the serum of NTHi+ve patients, suggesting this phenomenon is restricted to the airway.,Furthermore, the NTHi+ve patients had significantly greater levels of IL-1β (p = 0.0003), in BAL than NTHi-ve COPD patients.This study indicates that the presence of NTHi is associated with reduced levels and function of IgG1 in the airway of NTHi-colonised COPD patients.,This decrease in total and NTHI-specific IgG1 was associated with greater systemic and airway inflammation and a history of more frequent exacerbations and may explain the susceptibility of some COPD patients to the impacts of NTHi. | Exposure to cigarette smoking can increase the risk of cancers and cardiovascular and pulmonary diseases.,However, the underlying mechanisms of how smoking contributes to disease risks are not completely understood.,Epigenome-wide association studies (EWASs), mostly in non-Asian populations, have been conducted to identify smoking-associated methylation alterations at individual probes.,There are few data on regional methylation changes in relation to smoking.,Few data link differential methylation in blood to differential gene expression in lung tissue.,We identified 108 significant (false discovery rate (FDR) < 0.05) differentially methylated probes (DMPs) and 87 significant differentially methylated regions (DMRs) (multiple-testing corrected p < 0.01) in current compared to never smokers from our EWAS of cotinine-validated smoking in blood DNA from a Korean chronic obstructive pulmonary disease cohort (n = 100 including 31 current, 30 former, and 39 never smokers) using Illumina HumanMethylation450 BeadChip.,Of the 108 DMPs (FDR < 0.05), nine CpGs were statistically significant based on Bonferroni correction and 93 were novel including five that mapped to loci previously associated with smoking.,Of the 87 DMRs, 66 were mapped to novel loci.,Methylation correlated with urine cotinine levels in current smokers at six DMPs, with pack-years in current smokers at six DMPs, and with duration of smoking cessation in former smokers at eight DMPs.,Of the 143 genes to which our significant DMPs or DMRs annotated, gene expression levels at 20 genes were associated with pack-years in lung tissue transcriptome data of smokers (Asan Biobank, n = 188).,Our study of differential methylation in Koreans confirmed previous findings from non-Asian populations and revealed novel loci in relation to smoking.,Smoking-related differential methylation in blood is associated with gene expression in lung tissue, an important target of adverse health effects of smoking, supporting the potential functional importance of methylation in smoking-related disease.,The online version of this article (doi:10.1186/s13148-016-0266-6) contains supplementary material, which is available to authorized users. | 1 |
Integrated disease management with self-management for Chronic Obstructive Pulmonary Disease (COPD) is effective to improve clinical outcomes. eHealth can improve patients’ involvement to be able to accept and maintain a healthier lifestyle.,Eventhough there is mixed evidence of the impact of eHealth on quality of life (QoL) in different settings.,The primary aim of the e-Vita-COPD-study was to investigate the effect of use of eHealth patient platforms on disease specific QoL of COPD patients.,We evaluated the impact of an eHealth platform on disease specific QoL measured with the clinical COPD questionnaire (CCQ), including subscales of symptoms, functional state and mental state.,Interrupted time series (ITS) design was used to collect CCQ data at multiple time points.,Multilevel linear regression modelling was used to compare trends in CCQ before and after the intervention.,Of 742 invited COPD patients, 244 signed informed consent.,For the analyses, we only included patients who actually used the eHealth platform (n = 123).,The decrease of CCQ-symptoms was 0.20% before the intervention and 0.27% after the intervention; this difference in slopes was statistically significant (P = 0.027).,The decrease of CCQ-mental was 0.97% before the intervention and after the intervention there was an increase of 0.017%; this difference was statistically significant (P = 0.01).,No significant difference was found in the slopes of CCQ (P = 0.12) and CCQ-function (P = 0.11) before and after the intervention.,The e-Vita eHealth platform had a potential beneficial impact on the CCQ-symptoms of COPD patients, but not on functional state.,The CCQ-mental state remained stable after the intervention, but this was a deterioration compared to the improving situation before the start of the eHealth platform.,Therefore, health care providers should be aware that, although symptoms improve, there might be a slight increase in anxiety and depression after introducing an eHealth intervention to support self-management.,Our study is registered in the Dutch Trial Register (national registration of clinical trails, mandatory for publication) with number NTR4098 and can be found at http://www.trialregister.nl/trial/3936.,Date registered: 2013-07-31.,First participant: 2014-01-01.,The online version of this article (10.1186/s12931-019-1110-2) contains supplementary material, which is available to authorized users. | Outcomes for patients with chronic respiratory diseases remain poor despite the development of novel therapies.,In part, this reflects the fact that adherence to therapy is low and clinicians lack accurate methods to assess this issue.,Digital technologies hold promise to overcome these barriers to care.,For example, algorithmic analysis of large amounts of information collected on health status and treatment use, along with other disease relevant information such as environmental data, can be used to help guide personalised interventions that may have a positive health impact, such as establishing habitual and correct inhaler use.,Novel approaches to data analysis also offer the possibility of statistical algorithms that are better able to predict exacerbations, thereby creating opportunities for preventive interventions that may adapt therapy as disease activity changes.,To realise these possibilities, digital approaches to disease management should be supported by strong evidence, have a solid infrastructure, be designed collaboratively as clinically effective and cost-effective systems, and reflect the needs of patients and healthcare providers.,Regulatory standards for digital interventions and strategies to handle the large amounts of data generated are also needed.,This review highlights the opportunities provided by digital technologies for managing patients with respiratory diseases.,Digital technologies hold promise to improve adherence and personalise care in patients with respiratory diseaseshttp://ow.ly/WjTz30m71ZW | 1 |
NVA237 (glycopyrronium bromide) is a once-daily long-acting muscarinic antagonist (LAMA) in development for chronic obstructive pulmonary disease (COPD).,The GLycopyrronium bromide in COPD airWays clinical Study 2 (GLOW2) evaluated the efficacy and safety of NVA237 in moderate-to-severe COPD over 52 weeks.,Patients were randomised 2:1:1 to NVA237 50 μg, placebo or open-label tiotropium 18 μg for 52 weeks.,Primary end-point was trough forced expiratory volume in 1 s (FEV1) at 12 weeks.,1,066 patients were randomised, 810 completed the study.,At week 12, trough FEV1 increased significantly by 97 mL with NVA237 (95% CI 64.6-130.2; p<0.001) and 83 mL with tiotropium (95% CI 45.6-121.4; p<0.001).,Compared with placebo, NVA237 produced significant improvements in dyspnoea (Transition Dyspnoea Index at week 26; p=0.002) and health status (St George's Respiratory Questionnaire at week 52; p<0.001).,NVA237 significantly reduced the risk of moderate-to-severe COPD exacerbations by 34% (p=0.001) and the use of rescue medication (p=0.039), versus placebo.,NVA237-placebo and tiotropium-placebo differences were comparable for all outcomes.,Safety profiles were similar across groups.,NVA237 50 μg provided significant improvements in lung function, dyspnoea, health status, exacerbations and rescue medication use, versus placebo, and was comparable to tiotropium.,NVA237 can potentially be an alternative choice of LAMA for COPD patients. | NVA237 is a once-daily dry-powder formulation of the long-acting muscarinic antagonist glycopyrronium bromide in development for the treatment of chronic obstructive pulmonary disease (COPD).,The glycopyrronium bromide in COPD airways clinical study 1 (GLOW1) evaluated the efficacy, safety and tolerability of NVA237 in patients with moderate-to-severe COPD.,Patients with COPD with a smoking history of ≥ 10 pack-years, post-bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and ≥ 30% predicted normal and FEV1/forced vital capacity < 0.70 were enrolled.,Patients were randomized to double-blind treatment with NVA237 50 μg once daily or placebo for 26 weeks with inhaled/intranasal corticosteroids or H1 antagonists permitted in patients stabilized on them prior to study entry.,The primary outcome measure was trough FEV1 at Week 12.,A total of 822 patients were randomized to NVA237 (n = 552) or placebo (n = 270).,Least squares mean (± standard error) trough FEV1 at Week 12 was significantly higher in patients receiving NVA237 (1.408 ± 0.0105 L), versus placebo (1.301 ± 0.0137 L; treatment difference 108 ± 14.8 mL, p < 0.001).,Significant improvements in trough FEV1 were apparent at the end of Day 1 and sustained through Week 26.,FEV1 was significantly improved in the NVA237 group versus placebo throughout the 24-hour periods on Day 1 and at Weeks 12 and 26, and at all other visits and timepoints.,Transition dyspnoea index focal scores and St.,George's Respiratory Questionnaire scores were significantly improved with NVA237 versus placebo at Week 26, with treatment differences of 1.04 (p < 0.001) and-2.81 (p = 0.004), respectively.,NVA237 significantly reduced the risk of first moderate/severe COPD exacerbation by 31% (p = 0.023) and use of rescue medication by 0.46 puffs per day (p = 0.005), versus placebo.,NVA237 was well tolerated and had an acceptable safety profile, with a low frequency of cardiac and typical antimuscarinic adverse effects.,Once-daily NVA237 was safe and well tolerated and provided rapid, sustained improvements in lung function, improvements in dyspnoea, and health-related quality of life, and reduced the risk of exacerbations and the use of rescue medication.,ClinicalTrials.gov: NCT01005901 | 1 |
The gait abnormalities were linked to the balance deficits in the previous studies.,However, the deviations in the gait parameters in COPD are currently not known.,The study aims to compare gait parameters, static and dynamic balance, and risk of falls in COPD with those in non-COPD individuals.,Fourty-two patients with COPD aged 45 years and gender-matched control subjects were included in the study.,Gait parameters were assessed by Win-Track gait analyzer, the static balance was assessed by posturography, and the dynamic balance was assessed by the time up and go test.,The fear of falls was assessed by Falls Efficacy Scale.,COPD individuals had decreased static and dynamic balance as assessed by posturography (p < 0.05) and TUG (p < 0.01), respectively.,A significant difference in swing duration (p=0.004) and also increased risk of falls (p < 0.01) was observed in COPD patients as compared to non-COPD individuals.,COPD individuals have increased swing duration, reduced static and dynamic balance, and increased fear of falls as compared to non-COPD individuals. | Chronic obstructive pulmonary disease (COPD) is a disease associated with dyspnea, fatigue, and exercise intolerance.,The degree of functional debility and level of exercise capacity greatly influences quality of life and mortality in patients with COPD, and the measures of exercise capacity are to be an integral part of patient assessment but often not feasible in routine daily practice, resulting in likely suboptimal care.,There is a need for simple ways to identify functional decline in the clinical setting in order to guide resources to preventive interventions or proper care, including palliative care.,Gait speed, or measuring how long it takes for a patient to walk a short distance, takes very little time and space, and can serve as a candidate measure of physical function in COPD.,Gait speed has been shown to be an indicator of disability, health care utilization, and survival in older adults.,It is a simple, reliable, and feasible measure to perform in the clinic and has been promoted as the next vital sign, providing insight into patients’ functional capacity.,Gait speed is mainly determined by exercise capacity but reflects global well-being as it captures many of the multisystemic effects of disease severity in COPD rather than pulmonary impairment alone.,It is an excellent screening measure for exercise capacity and frailty; in COPD, the usual gait speed (4-m course with rolling start) has been very accurate in identifying clinically relevant benchmarks of the 6-minute walk test, poor (<350 m) and very poor (<200 m) 6-minute walk test distances.,A specific cut-off point of 0.8 m · s−1 had a positive predictive value of 69% and negative predictive value of 98% in predicting very poor exercise capacity.,The increasing evidence on gait speed is promising as a simple test that can inform the clinician about many important functional aspects of the COPD patient.,Further work will likely show the strength of gait speed as a predictive marker of hospitalizations, re-admissions, and mortality.,Instead of relying on the “eyeball test” regarding the patient’s frailty or exercise capacity, a gait speed in its simplicity represents a much more solid assessment.,Furthermore, repeat measures over serial clinic visits may show a pattern and further guide a change in therapy, whether it be medications, rehabilitation, or even initiation of palliative care discussions. | 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. | Alterations in the composition of the lung microbiome associated with adverse clinical outcomes, known as dysbiosis, have been implicated with disease severity and exacerbations in COPD.,To characterise longitudinal changes in the lung microbiome in the AERIS study (Acute Exacerbation and Respiratory InfectionS in COPD) and their relationship with associated COPD outcomes.,We surveyed 584 sputum samples from 101 patients with COPD to analyse the lung microbiome at both stable and exacerbation time points over 1 year using high-throughput sequencing of the 16S ribosomal RNA gene.,We incorporated additional lung microbiology, blood markers and in-depth clinical assessments to classify COPD phenotypes.,The stability of the lung microbiome over time was more likely to be decreased in exacerbations and within individuals with higher exacerbation frequencies.,Analysis of exacerbation phenotypes using a Markov chain model revealed that bacterial and eosinophilic exacerbations were more likely to be repeated in subsequent exacerbations within a subject, whereas viral exacerbations were not more likely to be repeated.,We also confirmed the association of bacterial genera, including Haemophilus and Moraxella, with disease severity, exacerbation events and bronchiectasis.,Subtypes of COPD have distinct bacterial compositions and stabilities over time.,Some exacerbation subtypes have non-random probabilities of repeating those subtypes in the future.,This study provides insights pertaining to the identification of bacterial targets in the lung and biomarkers to classify COPD subtypes and to determine appropriate treatments for the patient.,Results, NCT01360398. | 1 |
The distance of 6-minute walk test (D6MWT) has been widely used in the assessment of functional status in patients with COPD, while very little attention has been paid to the role of steps of 6-minute walk test (S6MWT).,The purpose of this study was to investigate the relationship between S6MWT and other physiologic parameters of COPD.,Seventy patients with stable COPD were enrolled consecutively in this cross-sectional study.,Pulmonary function tests, including spirometry, impulse oscillometry (IOS) and the single-breath diffusing capacity of the lungs for carbon monoxide (DLCO), were carried out at rest.,Quality of life was assessed by health-related quality of life (HRQoL) questionnaires, including modified Medical Research Council dyspnea scale (mMRC), St George’s Respiratory Questionnaire, Chronic Obstructive Pulmonary Disease Assessment Test (CAT) and Clinical Chronic Obstructive Pulmonary Questionnaire.,Both steps and distance were measured in the following 6-minute walk test (6MWT).,Both S6MWT and D6MWT showed significant correlation with spirometry, IOS, DLCO parameters and HRQoL questionnaires score.,Both pre- and post-6MWT inspiratory capacity showed significant correlation with S6MWT (ρ=0.338, P=0.004; ρ=0.359, P=0.002, respectively), whereas did not correlate with D6MWT (ρ=0.145, P=0.230; ρ=0.160, P=0.189, respectively).,In stepwise multiple regression analysis, mMRC grade, age and CAT score remained as significant predictors in the final model for D6MWT (adjusted R2=0.445, P<0.01).,DLCO and CAT score remained as significant predictors in the final model for S6MWT (adjusted R2=0.417, P<0.01).,S6MWT is efficient in the evaluation of functional status and quality of life in COPD and has significant correlation with various parameters indicating disease severity.,Additionally, S6MWT might be better in predicting lung hyperinflation in COPD compared with D6MWT. | Sustained bronchodilation using inhaled medications in moderate to severe chronic obstructive pulmonary disease (COPD) grades 2 and 3 (Global Initiative for Chronic Obstructive Lung Disease guidelines) has been shown to have clinical benefits on long-term symptom control and quality of life, with possible additional benefits on disease progression and longevity.,Aggressive diagnosis and treatment of symptomatic COPD is an integral and pivotal part of COPD management, which usually begins with primary care physicians.,The current standard of care involves the use of one or more inhaled bronchodilators, and depending on COPD severity and phenotype, inhaled corticosteroids.,There is a wide range of inhaler devices available for delivery of inhaled medications, but suboptimal inhaler use is a common problem that can limit the clinical effectiveness of inhaled therapies in the real-world setting.,Patients’ comorbidities, other physical or mental limitations, and the level of inhaler technique instruction may limit proper inhaler use.,This paper presents information that can overcome barriers to proper inhaler use, including issues in device selection, steps in correct technique for various inhaler devices, and suggestions for assessing and monitoring inhaler techniques.,Ensuring proper inhaler technique can maximize drug effectiveness and aid clinical management at all grades of COPD. | 1 |
Asthma and chronic obstructive pulmonary disease (COPD) can be debilitating conditions adversely affecting a person's quality of life.,Effective treatments are available, but common errors in the use of inhalers compound the issue of disease control.,The beliefs and concerns of a patient can also have an impact on treatment adherence, the consequences of which are diminished disease control and the occurrence of exacerbations.,Once a treatment has been prescribed, it is often nurses who manage the patient long-term, and they may even be the main care provider.,This puts nurses in a key position to monitor inhaler technique, communicate with the patient to improve adherence, and even suggest alternative treatments if the patient and therapy are incompatible.,This review examines the central role that nurses play in disease management and emphasizes how effective inhaler education can make a difference to disease control.,Good communication between the nurse and patient is vital if this is to be achieved.,Recent updates to asthma and COPD guidelines are reviewed, and key resources available to help manage patients are highlighted.,Finally, with regard to inhaler education, we reconsider the nursing keystones of “Know it,” “Show it,” “Teach it,” and “Review it.” | 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. | 1 |
Chronic obstructive pulmonary disease (COPD) is a multifaceted condition that cannot be fully described by the severity of airway obstruction.,The limitations of spirometry and clinical history have prompted researchers to investigate a multitude of surrogate biomarkers of disease for the assessment of patients, prediction of risk, and guidance of treatment.,The aim of this review is to provide a comprehensive summary of observations for a selection of recently investigated pulmonary inflammatory biomarkers (Surfactant protein D (SP-D), Club cell protein 16 (CC-16), and Pulmonary and activation-regulated chemokine (PARC/CCL-18)) and systemic inflammatory biomarkers (C-reactive protein (CRP) and fibrinogen) with COPD.,The relevance of these biomarkers for COPD is discussed in terms of their biological plausibility, their independent association to disease and hard clinical outcomes, their modification by interventions, and whether changes in clinical outcomes are reflected by changes in the biomarker. | Exacerbations of COPD (ECOPD) represent a major burden for patients and health care systems.,Innovative sampling techniques have led to the identification of several pulmonary biomarkers.,Although some molecules are promising, their usefulness in clinical practice is not yet established.,Medline and Highwire databases were used to identify studies evaluating pulmonary sampled biomarkers in ECOPD.,We combined 3 terms for ECOPD, 3 for biomarkers and 6 for the sampling method.,Seventy-nine studies were considered eligible for inclusion in the review and were analyzed further.,Pulmonary biomarkers sampled with non-invasive, semi-invasive and invasive methods were evaluated for their potential to illustrate the disease’s clinical course, to correlate to clinical variables and to predict clinical outcomes, ECOPD etiology and response to treatment.,According to published data several pulmonary biomarkers assessed in ECOPD have the potential to illustrate the natural history of disease through the modification of their levels.,Among the clinically relevant molecules, those that have been studied the most and appear to be promising are spontaneous and induced sputum biomarkers for reflecting clinical severity and symptomatic recovery, as well as for directing towards an etiological diagnosis.,Current evidence on the clinical usefulness of exhaled breath condensate and bronchoalveolar lavage biomarkers in ECOPD is limited.,In conclusion, pulmonary biomarkers have the potential to provide information on the mechanisms underlying ECOPD, and several correlate with clinical variables and outcomes.,However, on the basis of published evidence, no single molecule is adequately validated for wide clinical use.,Clinical trials that incorporate biomarkers in decisional algorithms are required. | 1 |
Pulmonary rehabilitation is a cornerstone of care for COPD but uptake of traditional centre-based programmes is poor.,We assessed whether home-based pulmonary rehabilitation, delivered using minimal resources, had equivalent outcomes to centre-based pulmonary rehabilitation.,A randomised controlled equivalence trial with 12 months follow-up.,Participants with stable COPD were randomly assigned to receive 8 weeks of pulmonary rehabilitation by either the standard outpatient centre-based model, or a new home-based model including one home visit and seven once-weekly telephone calls from a physiotherapist.,The primary outcome was change in 6 min walk distance (6MWD).,We enrolled 166 participants to receive centre-based rehabilitation (n=86) or home-based rehabilitation (n=80).,Intention-to-treat analysis confirmed non-inferiority of home-based rehabilitation for 6MWD at end-rehabilitation and the confidence interval (CI) did not rule out superiority (mean difference favouring home group 18.6 m, 95% CI −3.3 to 40.7).,At 12 months the CI did not exclude inferiority (−5.1 m, −29.2 to 18.9).,Between-group differences for dyspnoea-related quality of life did not rule out superiority of home-based rehabilitation at programme completion (1.6 points, −0.3 to 3.5) and groups were equivalent at 12 months (0.05 points, −2.0 to 2.1).,The per-protocol analysis showed the same pattern of findings.,Neither group maintained postrehabilitation gains at 12 months.,This home-based pulmonary rehabilitation model, delivered with minimal resources, produced short-term clinical outcomes that were equivalent to centre-based pulmonary rehabilitation.,Neither model was effective in maintaining gains at 12 months.,Home-based pulmonary rehabilitation could be considered for people with COPD who cannot access centre-based pulmonary rehabilitation.,NCT01423227, clinicaltrials.gov. | Comprehensive multidisciplinary pulmonary rehabilitation is vital in the management of chronic obstructive pulmonary disease (COPD) and is considered for any stage of the disease.,Rehabilitation programmes are often centre-based and organised in groups.,However, the distance from the patient’s home to the centre and lack of transportation may hinder participation.,Rehabilitation at home can improve access to care for patients regardless of disease severity.,We had previously studied the technology usability and acceptability of a comprehensive home rehabilitation programme designed for patients with very severe COPD receiving long-term oxygen therapy.,The acceptability of such comprehensive home programmes for those with less severe COPD, who may be less homebound, is not known.,The aims of this feasibility study were to assess patient acceptability of the delivery mode and components of a comprehensive pulmonary rehabilitation programme for any stage of COPD, as well as the technology usability, patient outcomes and economic aspects.,Ten participants with COPD in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade I-IV were enrolled in a 9-week home programme and divided into two rehabilitation groups, with five patients in each group.,The programme included exercise training and self-management education in online groups of patients, and individual online consultations.,The patients also kept a digital health diary.,To assess the acceptability of the programme, the patients were interviewed after the intervention using a semi-structured interview guide.,In addition the number of sessions attended was observed.,The usability of the technology was assessed using interviews and the System Usability Scale questionnaire.,The St George’s Respiratory Questionnaire (SGRQ) was used to measure health-related quality of life.,The mode of delivery and the components of the programme were well accepted by the patients.,The programme provided an environment for learning from both healthcare professionals and peers, for asking questions and discussing disease-related issues and for group exercising.,The patients considered that it facilitated health-enhancing behaviours and social interactions with a social group formed among the participants.,Even participants who were potentially less homebound appreciated the home group and social aspects of the programme.,The participants found the technology easy to learn and use.,The acceptability and usability results were consistent with those in our previous study of patients with very severe COPD.,Only the mean change in the SGRQ total score of −6.53 (CI 95 % −0.38 to −12.68, p = 0.04) indicates a probable clinically significant effect.,Economic calculations indicated that the cost of the programme was feasible.,The results of this study indicate that comprehensive pulmonary rehabilitation delivered in home-based online groups may be feasible in COPD.,The mode of delivery and components of the programme appeared to be acceptable across patients with different disease severity.,The results in terms of patient outcomes are inconclusive, and further assessment is needed. | 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. | None of the drugs currently available for chronic obstructive pulmonary disease (COPD) are able to reduce the progressive decline in lung function which is the hallmark of this disease.,Smoking cessation is the only intervention that has proved effective.,The current pharmacological treatment of COPD is symptomatic and is mainly based on bronchodilators, such as selective β2-adrenergic agonists (short- and long-acting), anticholinergics, theophylline, or a combination of these drugs.,Glucocorticoids are not generally recommended for patients with stable mild to moderate COPD due to their lack of efficacy, side effects, and high costs.,However, glucocorticoids are recommended for severe COPD and frequent exacerbations of COPD.,New pharmacological strategies for COPD need to be developed because the current treatment is inadequate. | 1 |
Relationships between airway inflammation and respiratory potentially pathogenic microorganisms (PPMs) quantified using quantitative polymerase chain reaction (qPCR) in subjects with COPD are unclear.,Our aim was to evaluate mediators of airway inflammation and their association with PPMs in subjects with COPD at stable state and during exacerbations.,Sputum from 120 stable subjects with COPD was analyzed for bacteriology (colony-forming units; total 16S; and qPCR targeting Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae), differential cell counts, and inflammatory mediators using the Meso-Scale Discovery Platform.,Subjects were classified as colonized if any PPM was identified above the threshold of detection by qPCR.,Symptoms were quantified using the visual analog scale.,At stable state, 60% of subjects were qPCR positive for H influenzae, 48% for M catarrhalis, and 28% for S pneumoniae.,Elevated sputum concentrations of IL-1β, IL-10, and tumor necrosis factor (TNF)-α were detected in samples qPCR positive for either H influenzae or M catarrhalis.,Bacterial loads of H influenzae positively correlated with IL-1β, IL-8, IL-10, TNF-α, and symptoms; and M catarrhalis correlated with IL-10 and TNF-α.,H influenzae qPCR bacterial load was an independent predictor of sputum TNF-α and IL-1β.,In 55 subjects with paired exacerbation data, qPCR bacterial load fold change at exacerbation in M catarrhalis but not H influenzae correlated to changes in sputum TNF-α and IL-1β concentrations.,At stable state, H influenzae is associated with increased airway inflammation in COPD.,The relationship between bacterial load changes of specific pathogens and airway inflammation at exacerbation and recovery warrants further investigation. | The percentage of neutrophils in sputum are increased in COPD patients, and may therefore be a biomarker of airway inflammation.,We studied the relationships between sputum neutrophils and FEV1, health status, exacerbation rates, systemic inflammation and emphysema, and long term variability at 1 year.,Sputum samples were obtained from 488 COPD patients within the ECLIPSE cohort. 359 samples were obtained at baseline, and 297 after 1 year. 168 subjects provided samples at both visits.,Serum interleukin-6 (IL-6), IL-8, surfactant protein D and C-reactive protein levels were measured by immunoassays.,Low-dose CT scans evaluated emphysema.,Sputum neutrophil % increased with GOLD stage.,There was a weak association between % sputum neutrophils and FEV1 % predicted (univariate r2 = 0.025 and 0.094 at baseline and year 1 respectively, p < 0.05 after multivariate regression).,Similar weak but significant associations were observed between neutrophil % and health status measured using the St Georges Respiratory Questionairre.,There were no associations between neutrophils and exacerbation rates or emphysema.,Associations between sputum neutrophils and systemic biomarkers were non-significant or similarly weak.,The mean change over 1 year in neutrophil % was an increase of 3.5%.,Sputum neutrophil measurements in COPD are associated weakly with FEV1 % predicted and health status.,Sputum neutrophil measurements were dissociated from exacerbation rates, emphysema and systemic inflammation. | 1 |
BMP and activin membrane-bound inhibitor (BAMBI) is postulated to inhibit or modulate transforming growth factor β (TGF-β) signaling.,Furthermore, strong upregulation of BAMBI expression following in vitro infection of chronic obstructive pulmonary disease (COPD) lung tissue has been demonstrated.,In this study, we investigated whether TGF-β/BAMBI pathway is associated with COPD.,Blood samples were obtained from 27 healthy controls (HC), 24 healthy smokers (HS) and 29 COPD patients.,Elevated Th17/Treg ratios, and increased levels of BAMBI protein and mRNA (in plasma and CD4+ T cells respectively), were observed in COPD compared with HC and HS.,BAMBI expression was first observed on human CD4+ T cells, with a typical membrane-bound pattern.,The enhanced plasma BAMBI levels in COPD positively correlated with the increased plasma TGF-β1 levels and Th17/Treg ratio.,Together, an impaired TGF-β/BAMBI pathway may promote the inflammation leading to Th17/Treg imbalance, which is a new mechanism in smokers who develop COPD. | Chronic obstructive pulmonary disease (COPD) is characterized by progressive worsening of airflow limitation associated with abnormally inflamed airways in older smokers.,Despite correlative evidence for a role for tumor necrosis factor-alpha in the pathogenesis of COPD, the anti-tumor necrosis factor-alpha, infliximab did not show clinical efficacy in a double-blind, placebo-controlled, phase II clinical trial.,This study sought to evaluate the systemic inflammatory profile associated with COPD and to assess the impact of tumor necrosis factor neutralization on systemic inflammation.,Serum samples (n = 234) from the phase II trial were collected at baseline and after 24 weeks of placebo or infliximab.,Additionally, baseline serum samples were obtained from an independent COPD cohort (n = 160) and 2 healthy control cohorts (n = 50; n = 109).,Serum concentrations of a broad panel of inflammation-associated analytes were measured using a 92-analyte multiplex assay.,Twenty-five proteins were significantly elevated and 2 were decreased in COPD, including highly elevated CD40 ligand, brain-derived neurotrophic factor, epidermal growth factor, acute-phase proteins, and neutrophil-associated proteins.,This profile was largely independent of smoking status, age, and clinical phenotype.,The majority of these associations of serum analytes with COPD are novel findings.,Increased serum creatine kinase-muscle/brain and myoglobin correlated modestly with decreased forced expiratory volume at 1 second, suggesting cardiac involvement.,Infliximab did not affect this systemic inflammatory profile.,A robust systemic inflammatory profile was associated with COPD.,This profile was generally independent of disease severity.,Because anti-tumor necrosis factor-alpha did not influence systemic inflammation, how to control the underlying pathology beyond symptom suppression remains unclear.,ClinicalTrials.gov, No.: NCT00056264. | 1 |
Chronic obstructive pulmonary disease (COPD) is a multi-component disease characterised by airflow limitation and airway inflammation.,Exacerbations of COPD have a considerable impact on the quality of life, daily activities and general well-being of patients and are a great burden on the health system.,Thus, the aims of COPD management include not only relieving symptoms and preventing disease progression but also preventing and treating exacerbations.,Attention towards the day-to-day burden of the disease is also required in light of evidence that suggests COPD may be variable throughout the day with morning being the time when symptoms are most severe and patients’ ability to perform regular morning activities the most problematic.,While available therapies improve clinical symptoms and decrease airway inflammation, they do not unequivocally slow long-term progression or address all disease components.,With the burden of COPD continuing to increase, research into new and improved treatment strategies to optimise pharmacotherapy is ongoing - in particular, combination therapies, with a view to their complementary modes of action enabling multiple components of the disease to be addressed.,Evidence from recent clinical trials indicates that triple therapy, combining an anticholinergic with an inhaled corticosteroid and a long-acting β2-agonist, may provide clinical benefits additional to those associated with each treatment alone in patients with more severe COPD.,This article reviews the evidence for treatment strategies used in COPD with a focus on combination therapies and introduces the 3-month CLIMB study (Evaluation of Efficacy and Safety of Symbicort as an Add-on Treatment to Spiriva in Patients With Severe COPD) which investigated the potential treatment benefits of combining tiotropium with budesonide/formoterol in patients with COPD with regard to lung function, exacerbations, symptoms and morning activities. | The combination of inhaled corticosteroids and long-acting β2-adrenoceptor agonists is increasingly used in chronic obstructive pulmonary disease (COPD).,Recently, we have demonstrated that combination of salmeterol and fluticasone propionate (FP) additionally suppress the production of IL-8 by human monocyte.,In this study, the molecular mechanism behind the effectiveness of this combination therapy is investigated in human neutrophils.,Human neutrophils were preincubated with salmeterol or FP or the combination.,The amount of interleukin-8 (IL-8), elastase and matrix metalloproteinases (MMP)-2 and -9 releases, and reactive oxygen species (ROS) generation and expression of MAP kinase phosphatase (MKP-1) and glucocorticoid receptor (GR) were determined.,Cigarette smoke medium (CSM) induces an increased expression of CXC receptors and the production of ROS that may explain the strong production of IL-8 by neutrophils.,The expression of CXC receptors, the production of ROS, and the release of elastase and MMP-2 and -9 were not influenced by salmeterol, FP, or the combination.,Interestingly, the combination therapy had an additive suppressive effect on the CSM-induced production of IL-8.,The latter could be explained by an increased mRNA expression of MKP-1, the GR and an increased translocation of the GR to the nucleus.,This leads eventually to suppression of both the NF-κB and MAPK pathways and, hence, to less IL-8 production by the neutrophil.,These data are in support for the use of a combination therapy in COPD patients. | 1 |
Chronic obstructive pulmonary disease (COPD) is responsible for significant morbidity and mortality worldwide.,We evaluated the characteristics of stable COPD patients in the pulmonology clinics of seven Asian cities and also evaluated whether the exposure to biomass fuels and dusty jobs were related to respiratory symptoms, airflow limitation, and quality of life in the COPD patients.,This cross-sectional observational study recruited 922 COPD patients from seven cities of Asia.,The patients underwent spirometry and were administered questionnaires about their exposure to cigarette smoking, biomass fuels, and dusty jobs in addition to respiratory symptoms and health related quality of life.,Of the patients, there appeared to be variations from city to city in the history of exposure to biomass fuels and dusty jobs and also in respiratory symptoms of cough, phlegm, wheeze, and dyspnea.,These symptoms were more frequent in those COPD patients with a history of exposure to biomass fuels than without and those with a history of exposure to dusty jobs than without (P < 0.01 for all comparisons).,Airflow limitation was more severe in those COPD patients with a history of exposure to biomass fuels than without (52.2% predicted versus 55.9% of post-bronchodilator forced expiratory volume in 1 second [FEV1], P = 0.009); quality of life was poorer in those with exposure to biomass fuels than without (40.4 versus 36.2 of the St George’s Respiratory Questionnaire [SGRQ] total score, P = 0.001).,Airflow limitation was more severe in those COPD patients with a history of exposure to dusty jobs than without (51.2% predicted versus 57.3% of post-bronchodilator FEV1, P < 0.001); quality of life was poorer in those with dusty jobs than without (41.0 versus 34.6 of SGRQ score, P = 0.006).,In Asian cities, the characteristics of COPD patients vary and the history of exposure to biomass fuels or dusty jobs was related to frequency of symptoms, severe airflow limitation, and poor quality of life. | Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and responses to therapies are highly variable.,The aim of this study was to identify the predictors of pulmonary function response to 3 months of treatment with salmeterol/fluticasone in patients with COPD.,A total of 127 patients with stable COPD from the Korean Obstructive Lung Disease (KOLD) Cohort, which were prospectively recruited from June 2005 to September 2009, were analyzed retrospectively.,The prediction models for the FEV1, FVC and IC/TLC changes after 3 months of treatment with salmeterol/fluticasone were constructed by using multiple, stepwise, linear regression analysis.,The prediction model for the FEV1 change after 3 months of treatment included wheezing history, pre-bronchodilator FEV1, post-bronchodilator FEV1 change and emphysema extent on CT (R = 0.578).,The prediction models for the FVC change after 3 months of treatment included pre-bronchodilator FVC, post-bronchodilator FVC change (R = 0.533), and those of IC/ TLC change after 3 months of treatment did pre-bronchodilator IC/TLC and post-bronchodilator FEV1 change (R = 0.401).,Wheezing history, pre-bronchodilator pulmonary function, bronchodilator responsiveness, and emphysema extent may be used for predicting the pulmonary function response to 3 months of treatment with salmeterol/fluticasone in patients with COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) management remains challenging due to the high heterogeneity of clinical symptoms and the complex pathophysiological basis of the disease.,Airflow limitation, diagnosed by spirometry, remains the cornerstone of the diagnosis.,However, the calculation of the forced expiratory volume in the first second (FEV1) alone, has limitations in uncovering the underlying complexity of the disease.,Incorporating additional pulmonary function tests (PFTs) in the everyday clinical evaluation of COPD patients, like resting volume, capacity and airway resistance measurements, diffusion capacity measurements, forced oscillation technique, field and cardiopulmonary exercise testing and muscle strength evaluation, may prove essential in tailoring medical management to meet the needs of such a heterogeneous patient population.,We aimed to provide a comprehensive overview of the available PFTs, which can be incorporated into the primary care physician’s practice to enhance the efficiency of COPD management. | Patients with chronic obstructive pulmonary disease (COPD) are at risk of exacerbations and pneumonia; how the risk factors interact is unclear.,This post-hoc, pooled analysis included studies of COPD patients treated with inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) combinations and comparator arms of ICS, LABA, and/or placebo.,Backward elimination via Cox’s proportional hazards regression modelling evaluated which combination of risk factors best predicts time to first (a) pneumonia, and (b) moderate/severe COPD exacerbation.,Five studies contributed: NCT01009463, NCT01017952, NCT00144911, NCT00115492, and NCT00268216.,Low body mass index (BMI), exacerbation history, worsening lung function (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage), and ICS treatment were identified as factors increasing pneumonia risk.,BMI was the only pneumonia risk factor influenced by ICS treatment, with ICS further increasing risk for those with BMI <25 kg/m2.,The modelled probability of pneumonia varied between 3 and 12% during the first year.,Higher exacerbation risk was associated with a history of exacerbations, poorer lung function (GOLD stage), female sex and absence of ICS treatment.,The influence of the other exacerbation risk factors was not modified by ICS treatment.,Modelled probabilities of an exacerbation varied between 31 and 82% during the first year.,The probability of an exacerbation was considerably higher than for pneumonia.,ICS reduced exacerbations but did not influence the effect of risks associated with prior exacerbation history, GOLD stage, or female sex.,The only identified risk factor for ICS-induced pneumonia was BMI <25 kg/m2.,Analyses of this type may help the development of COPD risk equations. | 1 |
Blood eosinophil counts and history of exacerbations have been proposed as predictors of patients with chronic obstructive pulmonary disease (COPD) who may benefit from triple therapy (inhaled corticosteroid, long-acting β2-agonist and long-acting muscarinic antagonist).,In a retrospective cohort analysis we examined the profiles of COPD patients from the UK Clinical Practice Research Datalink (CPRD) and US Optum Clinformatics™ Data Mart (Optum) databases with reference to exacerbation frequency and blood eosinophil distribution.,Of the 31,437 (CPRD) and 383,825 (Optum) patients with COPD, 15,364 (CPRD) and 139,465 (Optum) met the eligibility criteria and were included.,Among patients with ≥2 exacerbations and available eosinophil counts in the baseline period (CPRD, n = 3089 and Optum, n = 13414), 17.0 and 13.3% respectively had eosinophil counts ≥400 cells/μL.,Patients with ≥2 exacerbations or eosinophil count ≥400 cells/μL during first year, exacerbated at least once (CPRD, 82.8% vs Optum, 80.6%) or continued to have eosinophil count ≥300 cells/μL (76.8% vs 76.5%), respectively in the follow-up year.,In both years, a higher variability in the number of exacerbations and eosinophil count was observed in patients with one exacerbation and eosinophil counts between 300 and 400 cells/μL; patients with eosinophil count < 150 cells/μL had the lowest variability.,Approximately 10% patients had both ≥2 exacerbations and eosinophil count ≥300 cells/μL across the databases.,A high variability in blood eosinophil counts over two consecutive years was observed in UK and US patients with COPD and should be considered while making treatment decisions.,A small proportion of COPD patients had frequent exacerbations and eosinophil count ≥300 cells/μL.,The online version of this article (10.1186/s12931-019-1130-y) contains supplementary material, which is available to authorized users. | Exacerbations are important outcomes in COPD both from a clinical and an economic perspective.,Most studies investigating predictors of exacerbations were performed in COPD patients participating in pharmacological clinical trials who usually have moderate to severe airflow obstruction.,This study was aimed to investigate whether predictors of COPD exacerbations depend on the COPD population studied.,A network of COPD health economic modelers used data from five COPD data sources - two population-based studies (COPDGene® and The Obstructive Lung Disease in Norrbotten), one primary care study (RECODE), and two studies in secondary care (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoint and UPLIFT) - to estimate and validate several prediction models for total and severe exacerbations (= hospitalization).,The models differed in terms of predictors (depending on availability) and type of model.,FEV1% predicted and previous exacerbations were significant predictors of total exacerbations in all five data sources.,Disease-specific quality of life and gender were predictors in four out of four and three out of five data sources, respectively.,Age was significant only in the two studies including secondary care patients.,Other significant predictors of total exacerbations available in one database were: presence of cough and wheeze, pack-years, 6-min walking distance, inhaled corticosteroid use, and oxygen saturation.,Predictors of severe exacerbations were in general the same as for total exacerbations, but in addition low body mass index, cardiovascular disease, and emphysema were significant predictors of hospitalization for an exacerbation in secondary care patients.,FEV1% predicted, previous exacerbations, and disease-specific quality of life were predictors of exacerbations in patients regardless of their COPD severity, while age, low body mass index, cardiovascular disease, and emphysema seem to be predictors in secondary care patients only. | 1 |
Previous studies have established a higher prevalence of vitamin D deficiency in patients with COPD, but the relationship between vitamin D levels and COPD exacerbations remains controversial.,In addition, the effect of vitamin D levels on imaging characteristics remains mostly unexplored.,Using cross-sectional and longitudinal follow up data from the COPDGene Study, we assessed the association between vitamin D levels on respiratory symptoms, exacerbations, and imaging characteristics.,We hypothesized that vitamin D deficiency will be associated with worse respiratory-related outcomes.,Current and former smokers between ages 45-80 were enrolled the COPDGene Study.,Subjects completed questionnaires, spirometry, six-minute walk test, and chest computed tomography scans.,A subset of subjects had measurement of serum concentration of 25-hydroxyvitamin D (25(OH)D).,Vitamin D deficiency was defined as serum concentration less than 20 ng/mL.,Longitudinal follow up was conducted via a web-based or telephone questionnaire.,Vitamin D levels were measured on 1544 current and former smokers, of which 981 subjects had sufficient vitamin D levels and 563 subjects had vitamin D deficiency.,Subjects with vitamin D deficiency were younger with increased likelihood of being African American, being current smokers, having a lower percent predicted FEV1, and having COPD.,Vitamin D deficiency was associated with worse quality of life, increased dyspnea, decreased exercise tolerance, and increased frequency of severe exacerbations.,Vitamin D deficiency was also associated with increased segmental airway wall thickness on chest CT scans.,Vitamin D deficiency was associated with increased respiratory symptoms, decreased functional status, increased frequency of severe exacerbations, as well as airway wall thickening on chest CT scans.,Further research is needed to determine the potential impact of vitamin D supplementation to improve disease outcomes. | Although observational studies suggest positive vitamin D-lung function associations, randomized trials are inconsistent.,We examined effects of vitamin D supplementation on lung function.,We recruited 442 adults (50-84 years, 58% male) into a randomized, double-blinded, placebo-controlled trial.,Participants received, for 1.1 years (median; range = 0.9-1.5 years), either (1) vitamin D3 200,000 IU, followed by monthly 100,000 IU doses (n = 226); or (2) placebo monthly (n = 216).,At baseline and follow-up, spirometry yielded forced expiratory volume in 1 s (FEV1; primary outcome).,Mean (standard deviation) 25-hydroxyvitamin D increased from 61 (24) nmol/L at baseline to 119 (45) nmol/L at follow-up in the vitamin D group, but was unchanged in the placebo group.,There were no significant lung function improvements (vitamin D versus placebo) in the total sample, vitamin D-deficient participants or asthma/chronic obstructive pulmonary disease (COPD) participants.,However, among ever-smokers (n = 217), the mean (95% confidence interval) FEV1 increase in the vitamin D versus placebo was 57 (4, 109) mL (p = 0.03).,FEV1 increases were larger among vitamin D-deficient ever-smokers (n = 54): 122 (8, 236) mL (p = 0.04).,FEV1 improvements were largest among ever-smokers with asthma/COPD (n = 60): 160 (53, 268) mL (p = 0.004).,Thus, vitamin D supplementation did not improve lung function among everyone, but benefited ever-smokers, especially those with vitamin D deficiency or asthma/COPD. | 1 |
Objective: The objective was to assess the effects of a nasal restriction device for inspiratory muscle training, called Feelbreathe®, added to a rehabilitation program (RP) on exercise capacity, quality of life, dyspnea and inspiratory muscle strength in patients with stable COPD.,Methods: Patients were randomized into three groups, one performed a supervised RP using the Feelbreathe® device (FB group), the second group developed the same RP with oronasal breathing without FB (ONB group) and the third was the control group (CG).,We evaluated inspiratory muscle strength (PImax), dyspnea (mMRC), quality of life (CAT) and exercise capacity (6MWT) before and after 8-week of RP.,Results: A total of 16 patients completed the study, seven in FB group, five in ONB group and four in the CG.,After the RP, the FB group showed a significant increase in PImax (93.3 ± 19.1 vs.,123.0 ± 15.8 mmHg) and in the 6MWT distance (462.9 ± 71.8 m vs.,529.1 ± 50.1 m) and a decrease in the CAT score (9.7 ± 6.5 vs.,5.9 ± 6.0) and in the mMRC dyspnea score.,FB provides greater improvement in PImax, dyspnea, quality of life and 6MWT than ONB.,Conclusions: The Feelbreathe® device provides greater improvements in quality of life, dyspnea, exercise capacity and inspiratory muscle strength compared to patients that did not use it. | It is known that respiratory muscles undergo adaptation in response to overload stimuli during exercise training in stable COPD patients, thus resulting in significant increase of respiratory muscle function as well as the individual’s improvements.,The present article reviews the most updated evidence with regard to the use of respiratory muscle training (RMT) methods in COPD patients.,Basically, three types of RMT (resistive training, pressure threshold loading, and normocapnic hyperpnea) have been reported.,Frequency, duration, and intensity of exercise must be carefully considered for a training effect.,In contrast with the plentitude of existing data inherent to inspiratory muscle training (IMT), literature is still lacking in showing clinical and physiological studies related to expiratory muscle training (EMT).,In particular, while it seems that IMT is slightly superior to EMT in providing additional benefits other than respiratory muscle function such as a reduction in dyspnea, both the effects and the safety of EMT is still to be definitively elucidated in patients with COPD. | 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. | Chronic Obstructive Pulmonary Disease (COPD) influences different aspects of patient’s health-related quality of life (HRQL).,While disease-specific HRQL instruments focus on symptoms and functional impairments, generic instruments cover a broader view on health.,This study compares the generic EQ-5D-3 L and two disease-specific questionnaires (St.-George’s Respiratory Questionnaire (SGRQ-C), COPD Assessment Test (CAT)) in a comprehensive spectrum of COPD disease grades with particular attention on comorbidities and assesses the discriminative abilities of these instruments.,Using data from the baseline visit of the German COPD cohort COSYCONET, mean HRQL scores in different COPD grades were compared by linear regression models adjusting for age, sex, education, smoking status, BMI, and low vs. high number of comorbidities or a list of several self-reported comorbid conditions.,Discriminative abilities of HRQL instruments to differentiate between COPD grades were assessed by standardized mean differences.,In 2,291 subjects in COPD GOLD grades 1-4 EQ-5D-3 L utility, EQ-5D VAS, SGRQ, and CAT were found able to discriminate between COPD grades, with some limitations for the EQ-5D utility in mild disease.,Both generic and disease-specific HRQL instruments reflected the burden of comorbid conditions.,The SGRQ showed the best discrimination between COPD grades and was less influenced by comorbidities, while EQ-5D utility put a higher weight on comorbid conditions.,For all instruments, psychiatric disorders and peripheral artery disease showed the strongest negative associations with HRQL.,All HRQL instruments considered reflect considerable impairment of HRQL in COPD patients, worsening with increasing COPD grade and number of comorbidities.,Findings may support clinical assessment, choice of HRQL instrument in future studies, and parameterization of decision-analytic models.,The online version of this article (doi:10.1186/s12890-016-0238-9) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) represents a major health problem in Central and Eastern European (CEE) countries; however, there are no data regarding clinical phenotypes of these patients in this region.,Participation in the Phenotypes of COPD in Central and Eastern Europe (POPE) study was offered to stable patients with COPD in a real-life setting.,The primary aim of this study was to assess the prevalence of phenotypes according to predefined criteria.,Secondary aims included analysis of differences in symptom load, comorbidities and pharmacological treatment.,3362 patients with COPD were recruited in 10 CEE countries. 63% of the population were nonexacerbators, 20.4% frequent exacerbators with chronic bronchitis, 9.5% frequent exacerbators without chronic bronchitis and 6.9% were classified as asthma-COPD overlap.,Differences in the distribution of phenotypes between countries were observed, with the highest heterogeneity observed in the nonexacerbator cohort and the lowest heterogeneity observed in the asthma-COPD cohort.,There were statistically significant differences in symptom load, lung function, comorbidities and treatment between these phenotypes.,The majority of patients with stable COPD in CEE are nonexacerbators; however, there are distinct differences in surrogates of disease severity and therapy between predefined COPD phenotypes.,Distinct phenotypes of COPD in Central and Eastern Europe have differences in symptoms, comorbidities and treatmenthttp://ow.ly/oMZI307ndr5 | The combination of asthma and chronic obstructive pulmonary disease (COPD), or ACOS is a recently defined syndrome.,The epidemiology of the condition is poorly described and previous research has suggested ACOS is associated with worse outcomes than either condition alone.,We therefore decided to complete a systematic review of the published literature.,This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta- Analyses guidelines.,A structured search was performed in the PubMed, Embase, and Medline databases up to Feb 2015 to identify studies reporting incidence, prevalence, health care utilization, morbidity, or mortality in COPD and asthma.,A total of 19 studies were included in the present study.,The pooled prevalence of overlap among COPD was 27% (95% CI: 0.16-0.38, p<0.0001) and 28% (95% CI: 0.09-0.47, p = 0.0032) in the population and hospital-based studies, respectively.,We found no significant difference between ACOS and COPD in terms of gender, smoking status, lung function and 6mWD.,However, in comparison to subject with only COPD, ACOS subjects were significantly younger, had higher BMI, healthcare utilization, and lower HRQoL.,ACOS is a common condition that exists in a substantial proportion of subjects with COPD.,ACOS represents a distinct clinical phenotype with more frequent exacerbations, hospitalization, worse health-related quality of life, and higher healthcare costs than either disease alone.,There is a critical need to better define the management and treatment of this syndrome. | 1 |
Pulmonary diseases [asthma, chronic obstructive pulmonary disease (COPD), and tuberculosis (TB)] are associated with lung cancer mortality.,However, the relationship between coexisting pulmonary diseases and survival in patients with lung squamous cell carcinoma (SqCC) has not been well defined.,Patients newly diagnosed with SqCC between 2003 and 2008 were identified by linking the National Health Insurance Research Database and Taiwan Cancer Registry Database.,Cases with SqCC were followed up until death, loss to follow-up, or study end in 2010.,Information on health status, date of death and the main causes of death was ascertained from the National Death Registry Database.,Cox proportional hazard regression was used to calculate the hazard ratio (HR) of coexisting asthma, COPD and/or TB.,During the study period, a total of 5406 cases with SqCC were enrolled.,For all cause-mortality, HRs were 1.08 [95% confidence interval (CI), 0.99-1.18], 1.04 (95% CI, 0.97-1.12), and 1.14 (95% CI, 1.00-1.31) for individuals with asthma, COPD, and TB, respectively.,Specifically, among men with coexisting pulmonary diseases, the HRs were 1.56 (95% CI, 1.23-1.97) and 1.11 (95% CI, 1.00-1.24) for individuals with asthma+COPD+TB and asthma+COPD, respectively.,Among male patients with stage III SqCC, HRs were 3.41 (95%CI, 1.27-9.17) and 1.65 (95%CI, 1.10-2.47) for individuals with asthma+TB and asthma+COPD+TB, respectively.,Among male patients with stage IV SqCC, HRs were 1.40 (95%CI, 1.00-1.97) and 1.25 (95%CI, 1.03-1.52) for individuals with asthma+ COPD+TB and asthma.,Among female patients with stage I and II, HR was 0.19 (95%CI, 005-0.77) for individuals with asthma.,Coexisting pulmonary diseases increased the risk of mortality from SqCC in male patients.,For female patients with early stage SqCC, pre-existing asthma decreased mortality.,These patients deserve greater attention while undergoing cancer treatment. | Lung cancer and chronic obstructive pulmonary disease (COPD) share a common risk factor in cigarette smoking and a large portion of patients with lung cancer suffer from COPD synchronously.,We therefore hypothesized that COPD is an independent risk factor for lung cancer.,Our aim was to investigate the intrinsic linkage of COPD (or emphysema, chronic bronchitis and asthma) and lung cancer.,The present hospital-based case-control study included 1,069 patients with newly diagnosed lung cancer and 1,132 age frequency matched cancer-free controls.,The odds ratios (ORs) for the associations between each previous pulmonary disease and lung cancer were estimated with logistic regression models, adjusting for age, sex, family history of cancer, BMI and pack year smoking.,In meta-analysis, the pooled effects of previous pulmonary diseases were analyzed with random effects models; and stratification analyses were conducted on smoking status and ethnicity.,In the case-control study, previous COPD was associated with the odds for increased risk of lung cancer (OR = 1.29, 95% confidence interval [CI] = 1.00∼1.68); so were emphysema (OR = 1.55, 95%CI = 1.03∼2.32) and chronic bronchitis (OR = 1.22, 95%CI = 0.99∼1.67); while asthma was associated with odds for decreased risk of lung cancer (OR = 0.29, 95%CI = 0.16∼0.53).,These associations were more pronounced in smokers (P<.05 for all strata), but not in non-smokers.,In meta-analysis, 35 studies (22,010 cases and 44,438 controls) were identified.,COPD was significantly associated with the odds for increased risk of lung cancer (pooled OR = 2.76; 95% CI = 1.85-4.11), so were emphysema (OR = 3.02; 95% CI = 2.41-3.79) and chronic bronchitis (OR = 1.88; 95% CI = 1.49-2.36); and these associations were more pronounced in smokers than in non-smokers (P<.001 respectively).,No significant association was observed for asthma.,Previous COPD could increase the risk of lung cancer, especially in smokers. | 1 |
Little is known about the microbiota shift induced by exacerbation in chronic obstructive pulmonary disease (COPD) patients.,The sputa microbiota of COPD patients was evaluated when clinically stable and during acute exacerbations of the disease.,Sputa microbiota was analyzed using 16S ribosomal RNA gene pyrosequencing and quantitative polymerase chain reaction-based pathogen detection.,Nine COPD patients were enrolled.,Pyrosequencing of 16S rRNA genes identified 2,267 unique bacterial operational taxonomic units.,Principal microbiota shifts during exacerbation were in either Proteobacteria, Firmicutes or Bacteroidetes.,Streptococcus and Moraxella levels were detected during exacerbation in severe (Global Initiative for Chronic Obstructive Lung Disease 3) COPD patients.,Most of the clinically-important genera found in the sputum with the pyrosequencing of 16S rRNA gene correlated with specific quantitative polymerase chain reactions for bacteria while respiratory viruses were nearly absent.,Sputum microbiotas of exacerbated COPD patients are complex.,This pilot study shows a clear shift in the microbiota of patients during exacerbation.,The nature of this shift varies from patient to patient in such a way that the treatment should be patient-specific.,Further studies are needed to establish the impact of microbial exacerbations on the pulmonary microbiota. | To investigate the respiratory infectious phenotypes and their impact on length of stay (LOS) and the COPD Assessment Test (CAT) Scale in acute exacerbation of COPD (AECOPD).,We categorized 81 eligible patients into bacterial infection, viral infection, coinfection, and non-infectious groups.,The respiratory virus examination was determined by a liquid bead array xTAG Respiratory Virus Panel in pharyngeal swabs, while bacterial infection was studied by conventional sputum culture.,LOS and CAT as well as demographic information were recorded.,Viruses were detected in 38 subjects, bacteria in 17, and of these, seven had both.,Influenza virus was the most frequently isolated virus, followed by enterovirus/rhinovirus, coronavirus, bocavirus, metapneumovirus, parainfluenza virus types 1, 2, 3, and 4, and respiratory syncytial virus.,Bacteriologic analyses of sputum showed that Pseudomonas aeruginosa was the most common bacteria, followed by Acinetobacter baumannii, Klebsiella, Escherichia coli, and Streptococcus pneumoniae.,The longest LOS and the highest CAT score were detected in coinfection group.,CAT score was positively correlated with LOS.,Respiratory infection is a common causative agent of exacerbations in COPD.,Respiratory coinfection is likely to be a determinant of more severe acute exacerbations with longer LOS.,CAT score may be a predictor of longer LOS in AECOPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is a complex multi-component disorder characterized by progressive irreversible respiratory symptoms and extrapulmonary comorbidities, including anxiety-depression and mild cognitive impairment (MCI).,However, the prevalence of these impairments is still uncertain, due to non-optimal screening methods.,This observational cross-sectional multicentre study aimed to evaluate the prevalence of anxiety-depressive symptoms and MCI in COPD patients, identify the most appropriate cognitive tests to screen MCI, and investigate specific cognitive deficits in these patients and possible predictive factors.,Sixty-five stable COPD inpatients (n = 65, aged 69.9±7.6 years, mainly stage III-IV GOLD) underwent the following assessments: Hospital Anxiety and Depression Scale (HADS), Geriatric Depression Scale (GDS) or Beck Depression Inventory-II (BDI-II), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and a complete neuropsychological battery (ENB-2) including different cognitive domains (attention, memory, executive functions, and perceptive and praxis abilities).,Moderate-severe anxiety was present in 18.5% of patients and depressive symptoms in 30.7%.,The prevalence of MCI varied according to the test: 6.2% (MMSE), 18.5% (MoCA) and 50.8% (ENB-2).,In ENB-2, patients performed significantly worse compared to Italian normative data on digit span (5.11±0.9 vs.,5.52±1.0, p = 0.0004), trail making test-B (TMT-B) (176.31±99.5 vs.,135.93±58.0, p = 0.004), overlapping pictures (26.03±8.9 vs.,28.75±8.2, p = 0.018) and copy drawing (1.370.6 vs.,1.61±0.5, p = 0.002).,At logistic regression analysis, only COPD severity (p = 0.012, odds ratio, OR, 4.4 [95% CI: 1.4-14.0]) and anxiety symptoms (p = 0.026, OR 4.6 [1.2-17.7]) were significant and independent predictors of the deficit in copy drawing, which assesses visuospatial and praxis skills.,Given the prevalence of neuropsychological impairments in COPD patients, the routine adoption in rehabilitation of screening tools for mood and cognitive function, including digit span, TMT-B and copy drawing, may be useful to detect psychosocial comorbidities and personalize the rehabilitative program. | Exacerbations of chronic obstructive pulmonary disease (COPD) are the third largest cause of emergency hospital admissions in the UK.,This systematic literature review explored the relationship between the hospitalization rates and the COPD comorbidities, anxiety, and depression.,The Centre for Research Dissemination’s framework for systematic reviews was followed using search terms relating to COPD, anxiety, depression, and hospital admission.,Papers identified were assessed for relevance and quality, using a suitable Critical Appraisal Skills Programme tool and Mixed Methods Assessment Tool.,Twenty quantitative studies indicated that anxiety and depression led to a statistically significant increase in the likelihood of COPD patients being hospitalized.,These comorbidities also led to an increased length of stay and a greater risk of mortality postdischarge.,Other significant factors included lower Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise scores, female gender, lower socioeconomic status, poorer patient perceived quality of life, increased severity of lung function, and less improvement in dyspnea from admission to discharge.,It was also highlighted that only 27%-33% of those with depression were being treated for it.,Four qualitative studies revealed that patients saw anxiety and depression as a major factor that affected their ability to cope with and self-manage their condition.,Findings from the systematic review have highlighted a need for better recognition and treatment of anxiety and depression amongst individuals with COPD.,Ongoing research will develop and test strategies for promoting better management and self-management as a means of reducing hospital admissions. | 1 |
Dyspnea is a defining symptom in the classification and treatment of chronic obstructive pulmonary disease (COPD).,However, the degree of variation in burden among symptomatic COPD patients and the possible correlates of burden remain unclear.,This study was conducted to characterize patients in Europe currently being treated for COPD according to the level of dyspnea in terms of sociodemographics, health-related quality of life, work productivity impairment, and health care resource use assessed by patient reports.,Data were derived from the 5-EU 2013 National Health and Wellness Survey (N=62,000).,Respondents aged ≥40 years who reported currently using a prescription for COPD were grouped according to their level of dyspnea as per the Global Initiative for Chronic Obstructive Lung Disease guidelines and compared on health status (revised Short Form 36 [SF-36]v2), work impairment (Work Productivity and Activity Impairment questionnaire), and number of health care visits in the past 6 months using generalized linear models with appropriate distributions and link functions.,Of the 768 respondents who met the inclusion criteria, 245 (32%) were considered to have higher dyspnea (equivalent to modified Medical Research Council score ≥2).,Higher dyspnea was associated with decrements ranging from 3.9 to 8.2 points in all eight domains of the SF-36 health profile after adjustment for sociodemographics, general health characteristics, and length of COPD diagnosis; mental component summary scores and Short Form-6D health utility scores were lower by 3.5 and 0.06 points, respectively.,Adjusted mean activity impairment (55% vs 37%, P<0.001) and number of emergency room visits (0.61 vs 0.40, P=0.030) were higher in patients with greater dyspnea.,Many European patients with COPD continue to experience dyspnea despite treatment and at levels associated with notable impairments in the patients’ ability to function across a multitude of domains.,These patients may benefit from more intense treatment of their symptoms. | Utilizing data from the Continuing to Confront COPD (chronic obstructive pulmonary disease) International Physician Survey, this study aimed to describe physicians’ knowledge and application of the GOLD (Global initiative for chronic Obstructive Lung Disease) Global Strategy for the Diagnosis, Management and Prevention of COPD diagnosis and treatment recommendations and compare performance between primary care physicians (PCPs) and respiratory specialists.,Physicians from 12 countries were sampled from in-country professional databases; 1,307 physicians (PCP to respiratory specialist ratio three to one) who regularly consult with COPD, emphysema, or chronic bronchitis patients were interviewed online, by telephone or face to face.,Physicians were questioned about COPD risk factors, prognosis, diagnosis, and treatment, including knowledge and application of the GOLD global strategy using patient scenarios.,Physicians reported using spirometry routinely (PCPs 82%, respiratory specialists 100%; P<0.001) to diagnose COPD and frequently included validated patient-reported outcome measures (PCPs 67%, respiratory specialists 81%; P<0.001).,Respiratory specialists were more likely than PCPs to report awareness of the GOLD global strategy (93% versus 58%, P<0.001); however, when presented with patient scenarios, they did not always perform better than PCPs with regard to recommending GOLD-concordant treatment options.,The proportion of PCPs and respiratory specialists providing first- or second-choice treatment options concordant with GOLD strategy for a GOLD B-type patient was 38% versus 67%, respectively.,For GOLD C and D-type patients, the concordant proportions for PCPs and respiratory specialists were 40% versus 38%, and 57% versus 58%, respectively.,This survey of physicians in 12 countries practicing in the primary care and respiratory specialty settings showed high awareness of COPD-management guidelines.,Frequent use of guideline-recommended COPD diagnostic practices was reported; however, gaps in the application of COPD-treatment recommendations were observed, warranting further evaluation to understand potential barriers to adopt guideline recommendations. | 1 |
This paper proposes a mathematical framework for understanding how the structural changes in the COPD lung reflect in model parameters.,The core of the analysis is a correlation between the heterogeneity in the lung as COPD degree changes (GOLD II, III and IV) and the nonlinearity index evaluated using the forced oscillation technique.,A low frequency evaluation of respiratory impedance models and nonlinearity degree is performed since changes in tissue mechanics are related to viscoelastic properties.,Simulation analysis of our model indicates a good correlation to expected changes in heterogeneity and nonlinear effects.,A total of 43 COPD diagnosed patients are evaluated, distributed as GOLD II (18), GOLD III (15) and GOLD IV (10).,Experimental data supports the claims and indicate that the proposed model and index for nonlinearity is well-suited to capture COPD structural changes. | Recent studies have provided evidence for a link between leptin and tumor necrosis factor-alpha (TNF-α).,Insulin-like growth factor I (IGF-I) mediates the metabolic effects of growth hormone (GH).,The GH axis is believed to be suppressed in chronic obstructive pulmonary disease (COPD).,The aim of this study is to find out whether acute exacerbations of COPD are followed by changes in plasma leptin and insulin-like growth factor I (IGF-I) levels and furthermore, whether these changes are related to systemic inflammation.,We measured serum leptin, IGF-I, TNF-α, interleukin 1β (IL-1β), interleukin 6 (IL-6) and interleukin 8 (IL-8) levels in 52 COPD patients with acute exacerbation on admission to hospital (Day 1) and two weeks later (Day 15). 25 healthy age-matched subjects served as controls.,COPD patients were also divided into two subgroups (29 with chronic bronchitis and 23 with emphysema).,Serum leptin and IGF-I were measured by radioimmunoassay and TNF-α, IL-1β, IL-6 and IL-8 were measured by ELISA.,Serum leptin levels were significantly higher and serum IGF-I levels significantly lower in COPD patients on Day 1 than in healthy controls (p < 0.001).,A positive correlation was observed between leptin and TNF-α on Day 1 (r = 0.620, p < 0.001).,Emphysematous patients had significantly lower IGF-I levels compared to those with chronic bronchitis both on Day 1 and Day 15 (p = 0.003 and p < 0.001 respectively).,Inappropriately increased circulating leptin levels along with decreased IGF-I levels occured during acute exacerbations of COPD.,Compared to chronic bronchitis, patients with emphysema had lower circulating IGF-I levels both at the onset of the exacerbation and two weeks later. | 1 |
Pulmonary rehabilitation (PR) is an effective, key standard treatment for people with COPD.,Nevertheless, low participant uptake, insufficient attendance and high drop-out rates are reported.,Investigation is warranted of the benefits achieved through alternative approaches, such as pulmonary tele-rehabilitation (PTR).,To investigate whether PTR is superior to conventional PR on 6 min walk distance (6MWD) and secondarily on respiratory symptoms, quality of life, physical activity and lower limb muscle function in patients with COPD and FEV1 <50% eligible for routine hospital-based, outpatient PR.,In this single-blinded, multicentre, superiority randomised controlled trial, patients were assigned 1:1 to 10 weeks of groups-based PTR (60 min, three times weekly) or conventional PR (90 min, two times weekly).,Assessments were performed by blinded assessors at baseline, end of intervention and at 22 weeks’ follow-up from baseline.,The primary analysis was based on the intention-to-treat principle.,The primary outcome was change in 6MWD from baseline to 10 weeks; 134 participants (74 females, mean±SD age 68±9 years, FEV1 33%±9% predicted, 6MWD 327±103 metres) were included and randomised.,The analysis showed no between-group differences for changes in 6MWD after intervention (9.2 metres (95% CI: −6.6 to 24.9)) or at 22 weeks’ follow-up (−5.3 metres (95% CI: −28.9 to 18.3)).,More participants completed the PTR intervention (n=57) than conventional PR (n=43) (χ2 test p<0.01).,PTR was not superior to conventional PR on the 6MWD and we found no differences between groups.,As more participants completed PTR, supervised PTR would be relevant to compare with conventional PR in a non-inferiority design.,Trial registration number,ClinicalTrials.gov (NCT02667171), 28 January 2016. | Chronic obstructive pulmonary disease (COPD) is a highly prevalent condition associated with a high health care resource consumption and health care expenditures, driven mainly by exacerbations-related hospitalizations.,Telemedicine has been proposed as a mean for timely detection of exacerbation, but the available evidence is inadequate to provide conclusive information on its efficacy.,The aim of this study is to evaluate the efficacy of a telemonitoring system in reducing COPD-related hospitalizations in an elderly population with COPD.,This is a parallel arms, randomized trial including patients aged 65 or older with COPD in GOLD stages II and III enrolled in a Pulmonary Medicine outpatient facility.,Patients were randomly assigned to receive a non-invasive system able to telemonitor vital signs (oxygen saturation, heart rate, near-body temperature, overall physical activity) or standard care, and were followed up for 9 months.,The outcome measures were the number of exacerbations and exacerbation-related hospitalization.,Fifty patients were included in the telemonitoring group and 49 in the control group.,The incidence rate of respiratory events was 28/100 person/years in the telemonitoring group vs. 42/100 person/years in the control group (incidence rate ratio: 0.67, 95% CI: 0.32 - 1.36).,The corresponding figures for hospital admissions where 13/100 person/years and 20/100 person/years, respectively (IRR: 0.66, 95% CI: 0.21 - 1.86).,In our study, COPD patients followed up with the aid of a multiparametric remote monitoring system experienced a lower rate of exacerbations and COPD-related hospitalizations compared to patients followed up using the standard model of care.,These results need to be replicated in larger studies before they can be applied to the general COPD population.,Trial registration number: NCT01481506 (clinicaltrials.gov).,Funding: co-financed by Lazio Region and Intersistemi Inc. | 1 |
Inflammation increases during exacerbations of COPD, but only a few studies systematically assessed these changes.,Better identification of these changes will increase our knowledge and potentially guide therapy, for instance by helping with quicker distinction of bacterially induced exacerbations from other causes.,To identify which inflammatory parameters increase during COPD exacerbations compared to stable disease, and to compare bacterial and non-bacterial exacerbations.,In 45 COPD patients (37 male/8 female, 21 current smokers, mean age 65, FEV1 52% predicted, pack years 38) sputum was collected during a stable phase and subsequently during an exacerbation.,Sputum total cell counts (9.0 versus 7.9 × 106/mL), eosinophils (0.3 versus 0.2 × 106/mL), neutrophils (6.1 versus 5.8 × 106/mL), and lymphocytes (0.07 versus 0.02 × 106/mL) increased significantly during an exacerbation compared to stable disease.,A bacterial infection was demonstrated by culture in 8 sputum samples obtained during an exacerbation.,These exacerbations had significantly increased sputum total cell and neutrophil counts, leukotriene-B4, myeloperoxidase, interleukin-8 and interleukin-6, and tumor necrosis factor-α (TNF-α) levels, and were also associated with more systemic inflammation compared to exacerbations without a bacterial infection.,Sputum TNF-α level during an exacerbation had the best test characteristics to predict a bacterial infection.,Sputum eosinophil, neutrophil, and lymphocyte counts increase during COPD exacerbations.,The increase in systemic inflammation during exacerbations seems to be limited to exacerbations caused by bacterial infections of the lower airways.,Sputum TNF-α is a candidate marker for predicting airway bacterial infection. | Irreversible airflow obstruction in Chronic Obstructive Pulmonary Disease (COPD) is thought to result from airway remodelling associated with aberrant inflammation.,Patients who experience frequent episodes of acute deterioration in symptoms and lung function, termed exacerbations, experience a faster decline in their lung function, and thus over time greater disease severity However the mechanisms by which these episodes may contribute to decreased lung function are poorly understood.,This study has prospectively examined changes in sputum levels of inflammatory cells, MMP-9 and TIMP-1 during exacerbations comparing with paired samples taken prior to exacerbation.,Nineteen COPD patients ((median, [IQR]) age 69 [63 to 74], forced expiratory volume in one second (FEV1) 1.0 [0.9 to1.2], FEV1% predicted 37.6 [27.3 to 46.2]) provided sputa at exacerbation.,Of these, 12 were paired with a samples collected when the patient was stable, a median 4 months [2 to 8 months] beforehand.,MMP-9 levels increased from 10.5 μg/g [1.2 to 21.1] prior to exacerbation to 17.1 μg/g [9.3 to 48.7] during exacerbation (P < 0.01).,TIMP-1 levels decreased from 3.5 μg/g [0.6 to 7.8] to 1.5 μg/g [0.3 to 4.9] (P = 0.16).,MMP-9/TIMP-1 Molar ratio significantly increased from 0.6 [0.2 to 1.1] to 3.6 [2.0 to 25.3] (P < 0.05).,Neutrophil, eosinophil and lymphocyte counts all showed significant increase during exacerbation compared to before (P < 0.05).,Macrophage numbers remained level.,MMP-9 levels during exacerbation showed highly significant correlation with both neutrophil and lymphocyte counts (Rho = 0.7, P < 0.01).,During exacerbation, increased inflammatory burden coincides with an imbalance of the proteinase MMP-9 and its cognate inhibitor TIMP-1.,This may suggest a pathway connecting frequent exacerbations with lung function decline. | 1 |
Singing is an increasingly popular activity for people with chronic obstructive pulmonary disease (COPD).,Research to date suggests that ‘Singing for Lung Health’ may improve various health measures, including health-related quality-of-life.,Singing and breathing are closely linked processes affecting one another.,In this narrative review, we explore the physiological rationale for ‘Singing for Lung Health’ as an intervention, focusing on the abnormalities of pulmonary mechanics seen in COPD and how these might be impacted by singing.,The potential beneficial physiological mechanisms outlined here require further in-depth evaluation. | Chronic obstructive pulmonary disease (COPD) is a common, preventable disease of airflow limitation that accounts for the third leading deaths of any disease process in the worldwide.,Health benefits of liuzijue qigong (LQG) on patients with stable COPD has been assessed.,This study was designed to perform a systemic review and meta-analysis of the effect of Liuzijue breathing exercise on patients with stable COPD.,Published articles from 1970 to December 2020 were conducted using electronic searches.,Two independents reviewers conducted data extraction.,The Cochrane risk of bias assessment tool was used to evaluate the quality of the included studies.,A total of 16 eligible trials with 1039 patients with stable COPD were identified.,Compared with control group, the pool meta-analysis of LQG showed a significant improvement in forced expiratory volume in one second (FEV1) (MD = −0.16, 95% CI [0.09, 0.23], P < .00001), FEV1% (MD = 9.71, 95% CI [8.44, 10.98], P < .00001), the ratio of forced expiratory volume to forced vital capacity in the first second (FEV1/FVC [%]) (MD = 4.81, 95% CI [2.12, 7.51], P = .0005), 6 minutes walking distance (6MWD) (MD = 21.89, 95% CI [14.67, 29.11], P < .00001), health-related quality of life (SMD = −0.84, 95% CI [−1.12,-0.55], P < .00001) and modified medical research council dyspnea scale (mMRC) (MD = −0.73, 95% CI [−0.96, −0.50], P < .00001).,The observed effect was more pronounced for short term and medium-term duration interventions of study.,It also showed improvements in the secondary outcome measures by LQG.,In this systematic review and meta-analysis, LQG can improve lung ventilation function, exercise endurance and health-related quality of life of patients with stable COPD.,This study is a systematic review and it does not involve harming to the rights of participants.,Ethical approval will not be require for this study.,The research results may be published in a peer-reviewed journals. | 1 |
Objective To determine whether supported self management in chronic obstructive pulmonary disease (COPD) can reduce hospital readmissions in the United Kingdom.,Design Randomised controlled trial.,Setting Community based intervention in the west of Scotland.,Participants Patients admitted to hospital with acute exacerbation of COPD.,Intervention Participants in the intervention group were trained to detect and treat exacerbations promptly, with ongoing support for 12 months.,Main outcome measures The primary outcome was hospital readmissions and deaths due to COPD assessed by record linkage of Scottish Morbidity Records; health related quality of life measures were secondary outcomes.,Results 464 patients were randomised, stratified by age, sex, per cent predicted forced expiratory volume in 1 second, recent pulmonary rehabilitation attendance, smoking status, deprivation category of area of residence, and previous COPD admissions.,No difference was found in COPD admissions or death (111/232 (48%) v 108/232 (47%); hazard ratio 1.05, 95% confidence interval 0.80 to 1.38).,Return of health related quality of life questionnaires was poor (n=265; 57%), so that no useful conclusions could be made from these data.,Pre-planned subgroup analysis showed no differential benefit in the primary outcome relating to disease severity or demographic variables.,In an exploratory analysis, 42% (75/150) of patients in the intervention group were classified as successful self managers at study exit, from review of appropriateness of use of self management therapy.,Predictors of successful self management on stepwise regression were younger age (P=0.012) and living with others (P=0.010).,COPD readmissions/deaths were reduced in successful self managers compared with unsuccessful self managers (20/75 (27%) v 51/105 (49%); hazard ratio 0.44, 0.25 to 0.76; P=0.003).,Conclusion Supported self management had no effect on time to first readmission or death with COPD.,Exploratory subgroup analysis identified a minority of participants who learnt to self manage; this group had a significantly reduced risk of COPD readmission, were younger, and were more likely to be living with others.,Trial registration Clinical trials NCT 00706303. | Despite optimal pharmacological therapy and pulmonary rehabilitation, patients with COPD continue to be breathless.,There is a need to develop additional strategies to alleviate symptoms.,Learning to sing requires control of breathing and posture and might have benefits that translate into daily life.,To test this hypothesis we performed a randomised controlled trial, comparing a six week course of twice weekly singing classes to usual care, in 28 COPD patients.,The experience of singing was assessed in a qualitative fashion, through interviews with a psychologist.,In addition, we surveyed patients with chronic respiratory conditions who participated in a series of open singing workshops.,In the RCT, the physical component score of the SF36 improved in the singers (n = 15) compared to the controls (n = 13); +7.5(14.6) vs. -3.8(8.4) p = 0.02.,Singers also had a significant fall in HAD anxiety score; -1.1(2.7) vs.,+0.8(1.7) p = 0.03.,Singing did not improve single breath counting, breath hold time or shuttle walk distance.,In the qualitative element, 8 patients from the singing group were interviewed.,Positive effects on physical sensation, general well-being, community/social support and achievement/efficacy emerged as common themes. 150 participants in open workshops completed a questionnaire. 96% rated the workshops as "very enjoyable" and 98% thought the workshop had taught them something about breathing in a different way. 81% of attendees felt a "marked physical difference" after the workshop.,Singing classes can improve quality of life measures and anxiety and are viewed as a very positive experience by patients with respiratory disease; no adverse consequences of participation were observed.,Current Controlled Trials - ISRCTN17544114. | 1 |
Patients with symptoms of both asthma and chronic obstructive pulmonary disease (COPD) may be classified with the term asthma-COPD overlap (ACO).,ACO is of considerable interest as it is currently poorly characterised and has been associated with worse health outcomes and higher healthcare costs compared with COPD or asthma alone.,Patients with ACO in Asia remain poorly described, and there is limited information regarding their resource utilisation compared with patients with asthma or COPD only.,This study investigated the characteristics, disease burden and medical resource utilisation of patients with ACO in Taiwan.,This was a retrospective cohort study of patients identified from National Health Insurance (NHI) claims data in Taiwan in 2009-2011.,Patients were classified into incident ACO, COPD or asthma cohorts according to International Classification of Disease, ninth revision, clinical modification codes in claims.,Eligible patients were ≥40 years of age with 12 months’ continuous enrolment in the NHI programme pre- and post-index date (date of the first relevant medical claim).,Patients with ACO (N = 22,328) and COPD (N = 69,648) were older and more likely to be male than those with asthma (N = 50,293).,Patients with ACO had more comorbidities and exacerbations, with higher medication use: short-acting β2-agonist prescriptions ranged from 30.4% of patients (asthma cohort) to 43.6% (ACO cohort), and inhaled corticosteroid/long-acting β2-agonist combination prescriptions ranged from 11.1% (COPD cohort) to 35.0% (ACO cohort) in the 12 months following index.,Patients with ACO generally had the highest medication costs of any cohort (long-acting muscarinic antagonist costs ranged from $227/patient [asthma cohort] to $349/patient [ACO cohort]); they also experienced more respiratory-related hospital visits than patients with asthma or COPD (mean outpatient/inpatient visits per patient post-index: 9.1/1.9 [ACO cohort] vs 5.7/1.4 [asthma cohort] and 6.4/1.7 [COPD cohort]).,Patients with ACO in Taiwan experience a greater disease burden with greater healthcare resource utilisation, and higher costs, than patients with asthma or COPD alone.,The online version of this article (10.1186/s12890-017-0571-7) contains supplementary material, which is available to authorized users. | Patients with asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) and cardiovascular diseases (CVDs) share common risk factors.,However, the association between ACOS and the incidence of CVDs has not been reported.,This study investigated the relationship between CVDs and ACOS in the general population.,Data were obtained from Taiwan’s National Health Insurance Research Database for the period 2000 to 2010.,The ACOS cohort comprised patients (n=5814) who had received a diagnosis of asthma and COPD.,The non-ACOS cohort comprised patients who had not received a diagnosis of asthma or COPD and were matched to the ACOS cohort (2:1) by age, sex and index date (n=11 625).,The cumulative incidence of CVDs-coronary artery disease (CAD), cardiac dysrhythmia (CD) and heart failure (HF)-was calculated.,Cox proportional regression analysis was employed to examine the relationship between ACOS and CVDs.,After adjustment for multiple confounding factors-age, sex, comorbidities and medications-patients with ACOS were associated with a significantly higher risk of CVDs; the adjusted HRs (aHRs; 95% CI) for CAD, CD and HF were 1.62 (1.50 to 1.76), 1.44 (1.30 to 1.61) and 1.94 (1.73 to 2.19), respectively, whereas those of beta-blockers treatment for CAD, CD and HF were 1.19 (0.92 to 1.53), 0.90 (0.56 to 1.45) and 0.82 (0.49 to 1.38).,The aHR of atenolol treatment for CD was 1.72 (1.01 to 2.93).,The aHRs (95% CIs) of ACOS without acute exacerbation of COPD (AE-COPD) for CAD, CD and HF were 1.85 (1.70 to 2.01), 1.57 (1.40 to 1.77) and 2.07 (1.82 to 2.35), respectively.,ACOS was associated with higher CVD risk, even without the presence of previous comorbidities or AE-COPD.,No significant differences in CVD events were observed in the ACOS cohort using beta-blockers, except for those using atenolol for treating CD. | 1 |
COPD exacerbations requiring hospitalization increase morbidity and mortality.,Although most COPD exacerbations are neutrophilic, approximately 10%-25% of exacerbations are eosinophilic.,We aimed to evaluate mortality and outcomes of eosinophilic and non-eosinophilic COPD exacerbations and identify new biomarkers that predict survival.,A retrospective observational cohort study was carried out in a tertiary teaching hospital from January 1, 2014 to November 1, 2014.,All COPD patients hospitalized with exacerbations were enrolled in the study at their initial hospitalization and followed-up for 6 months after discharge.,Electronic data were collected from the hospital database.,Subjects’ characteristics, hemogram parameters, CRP levels, neutrophil-to-lymphocyte ratio (NLR), platelet-to-mean platelet volume ratio on admission and discharge, length of hospital stay (days), readmissions, and mortality were recorded.,Patients were grouped according to peripheral blood eosinophil (PBE) levels: Group 1, >2% PBE, eosinophilic; Group 2, non-eosinophilic ≤2%.,Patient survival after hospital discharge was evaluated by Kaplan-Meier survival analysis.,A total of 1,704 patients hospitalized with COPD exacerbation were included.,Approximately 20% were classified as eosinophilic.,Six-month mortality was similar in eosinophilic and non-eosinophilic groups (14.2% and 15.2%, respectively); however, the hospital stay length and readmission rate were longer and higher in the non-eosinophilic group (P<0.001 and P<0.01, respectively).,CRP and NLR were significantly higher in the non-eosinophilic group (both P<0.01).,The platelet-to-mean platelet volume ratio was not different between the two groups.,Cox regression analysis showed that survival was negatively influenced by elevated CRP (P<0.035) and NLR (P<0.001) in the non-eosinophilic group.,Non-eosinophilic patients with COPD exacerbations with high CRP and NLR values had worse outcomes than eosinophilic patients.,PBE and NLR can be helpful markers to guide treatment decisions. | COPD exacerbations requiring intensive care unit (ICU) admission have a major impact on morbidity and mortality.,Only 10%-25% of COPD exacerbations are eosinophilic.,To assess whether eosinophilic COPD exacerbations have better outcomes than non-eosinophilic COPD exacerbations in the ICU.,This retrospective observational cohort study was conducted in a thoracic, surgery-level III respiratory ICU of a tertiary teaching hospital for chest diseases from 2013 to 2014.,Subjects previously diagnosed with COPD and who were admitted to the ICU with acute respiratory failure were included.,Data were collected electronically from the hospital database.,Subjects’ characteristics, complete blood count parameters, neutrophil to lymphocyte ratio (NLR), delta NLR (admission minus discharge), C-reactive protein (CRP) on admission to and discharge from ICU, length of ICU stay, and mortality were recorded.,COPD subjects were grouped according to eosinophil levels (>2% or ≤2%) (group 1, eosinophilic; group 2, non-eosinophilic).,These groups were compared with the recorded data.,Over the study period, 647 eligible COPD subjects were enrolled (62 [40.3% female] in group 1 and 585 [33.5% female] in group 2).,Group 2 had significantly higher C-reactive protein, neutrophils, NLR, delta NLR, and hemoglobin, but a lower lymphocyte, monocyte, and platelet count than group 1, on admission to and discharge from the ICU.,Median (interquartile range) length of ICU stay and mortality in the ICU in groups 1 and 2 were 4 days (2-7 days) vs 6 days (3-9 days) (P<0.002), and 12.9% vs 24.9% (P<0.034), respectively.,COPD exacerbations with acute respiratory failure requiring ICU admission had a better outcome with a peripheral eosinophil level >2%.,NLR and peripheral eosinophilia may be helpful indicators for steroid and antibiotic management. | 1 |
Reports regarding gender-related differences in COPD expression have provided conflicting results.,In the French Initiatives BPCO real-world cohort, which contained 688 patients (146 women) when data were extracted, women were matched with men (1:3 ratio: n = 107:275) on age (5-year intervals) and FEV1 (5% predicted intervals) and comparisons were performed using univariate logistic regressions.,For a given age and level of airflow obstruction, women with COPD had higher BOD scores due to more pronounced dyspnea and lower BMI, suggesting worse prognosis, and were more likely to exhibit anxiety, suggesting the need for specific assessment and care. | 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 |
How to identify the optimum switch point of sequential invasive and noninvasive ventilation is the focus of clinical attention on the patients suffering from acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated by acute respiratory failure (ARF).,This study aims to explore the clinical significance of taking the change rate of procalcitonin (PCT) as identifying the timing of weaning on the mechanical ventilation for the patients of AECOPD followed by ARF as a complication.,There were altogether 140 patients of AECOPD complicated with ARF, who were randomly selected and divided into a study group and a control group respectively.,A change rate of serum PCT level exceeding 50% was taken as the switch point selection of tracheal intubation removal for the patients of the study group, while the ‘pulmonary infection control (PIC) window’ was done for those in the control group.,With CRP, IL-6, TNF-a, PaCO2, PaO2, and Lac having been detected before and after treatment to them all, clinical indexes were obtained and compared between these two groups.,The CRP, TNF-a, and IL-6 levels of the patients in the study group after treatment (p < 0.05) were lower than those in the control group.,There was no significant difference in PaCO2, PaO2, and Lac between these two groups before and after treatment (p > 0.05).,Even so, some other indexes available for the study group of patients were found to be lower than those for the control group (p < 0.05) in the following aspects: duration of invasive ventilation support, total time of mechanical ventilation support, incidence rate of ventilator-associated pneumonia, 48-hour reintubation rate, incidence rate of upper gastrointestinal bleeding, hospitalization time of critical respiratory illness, total hospitalization time, RICU treatment cost, total treatment cost, and mortality.,It is preferable to take the change rate of PCT level exceeding 50% as the switch point of weaning time in sequential mechanical ventilation rather than the PIC window.,Abbreviations,AECOPD: acute exacerbation of chronic obstructive pulmonary disease; ARF: acute respiratory failure; PCT: procalcitonin; PaO2: the oxygen partial pressure; PaCO2: the partial pressure of carbon dioxide; TNF-a: serum tumor necrosis factor-a; IL-6: interleukin-6; CRP: serum C-reactive protein; PIC window: pulmonary infection control window; RICU: respiration and intensive care unit | Background and Objectives: The incidence of postoperative delirium (POD) in patients with chronic obstructive pulmonary disease (COPD) is unclear.,It seems that postoperative respiratory problems that may occur in COPD patients, including prolonged mechanical ventilation or respiratory-tract infections, may contribute to the development of delirium.,The aim of the study was to identify a relationship between COPD and the occurrence of delirium after cardiac surgery and the impact of these combined disorders on postoperative mortality.,Materials and Methods: We performed an analysis of data collected from 4151 patients undergoing isolated coronary artery bypass grafting (CABG) in a tertiary cardiac-surgery center between 2012 and 2018.,We included patients with a clinical diagnosis of COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.,The primary endpoint was postoperative delirium; Confusion Assessment Method in the Intensive Care Unit (CAM-ICU) was used for delirium assessment.,Results: Final analysis included 283 patients with COPD, out of which 65 (22.97%) were diagnosed with POD.,Delirious COPD patients had longer intubation time (p = 0.007), more often required reintubation (p = 0.019), had significantly higher levels of C-reactive protein (CRP) three days after surgery (p = 0.009) and were more often diagnosed with pneumonia (p < 0.001).,The CRP rise on day three correlated positively with the occurrence of postoperative pneumonia (r = 0.335, p = 0.005).,The probability of survival after CABG was significantly lower in COPD patients with delirium (p < 0.001).,Conclusions: The results of this study confirmed the relationship between chronic obstructive pulmonary disease and the incidence of delirium after cardiac surgery.,The probability of survival in COPD patients undergoing CABG who developed postoperative delirium was significantly decreased. | 1 |
Introduction: Poor oral health has been implicated as an independent risk factor for the development of COPD, but few studies have evaluated the association between oral health and COPD exacerbations.,We aimed to determine if poor oral health is associated with COPD exacerbations and/or worse respiratory health.,Methods: We performed a case-control study of oral health among COPD exacerbators and non-exacerbators.,Cases (exacerbators) had experienced ≥1 exacerbation in the previous 12 months, while controls (non-exacerbators) had no exacerbations in the previous 24 months.,We excluded those with <4 teeth.,We evaluated the global oral health assessment, Oral Health Impact Profile (OHIP-5), dental symptoms/habits, and St.,George’s Respiratory Questionnaire (SGRQ).,In a subset, we performed blinded dental exams to measure bleeding on probing, probing depth, clinical attachment loss, periodontitis severity, plaque index, gingival index, and carries risk.,We evaluated associations between oral health and COPD exacerbations using logistic regression.,Linear regression was used to assess relationships between oral health and SGRQ scores.,Results: Screened non-exacerbators (n=118) were significantly more likely to have <4 teeth, compared to screened exacerbators (n=100) (44% vs 30%, respectively; p=0.046).,After excluding those with <4 teeth, there were 70 cases and 66 controls.,Self-reported oral health and objective dental exam measures did not vary significantly between cases vs controls.,However, the odds of severe COPD exacerbations requiring hospitalizations and/or emergency department visits trended higher in those with worse dental exam compared to those with better dental exam.,Worse OHIP-5 was strongly associated with worse SGRQ scores.,Conclusions: Oral health status was not related to COPD exacerbations, but was associated with self-reported respiratory health.,Non-exacerbators were more likely to be edentate or have ≤4 teeth compared to exacerbators.,Larger studies are needed to address oral health as a potential method to improve respiratory health in patients with COPD. | The Global Initiative defines COPD for chronic obstructive lung disease as an entirely preventable and treatable disease characterized by sputum production, bacterial colonisation, neutrophilic bronchial airway inflammation and poor health status.,The World Health Organization (WHO) estimates that COPD will become the fourth-most common cause of death worldwide, just behind ischemic heart disease, cerebrovascular disease and HIV/AIDS, by 2030.,The aim of this study was to determine the main structure feature of sputum potentially pathogenic microorganisms in subjects with COPD during the clinical stable state.,We employed a molecular genetics-based investigation of the bacteria community, including DNA isolation, PCR amplification and DGGE profiling.,PCR-denaturing gradient gel electrophoresis (DGGE) with universal primers targeting the V3 region of the 16S rRNA gene was employed to characterize the overall COPD patient sputum microbiota composition, and some excised gel bands were cloned for sequencing.,Real-time PCR was further utilized to quantitatively analyze the subpopulation of microbiota using group-specific primers targeting Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa.,The DGGE profiles of two groups displayed significant differences between COPD and healthy groups (P < 0.05).,Real-time PCR revealed significant increases of Streptococcus pneumoniae, Klebsiella pneumoniae and Pseudomonas aeruginosa (P < 0.05) in the COPD group compared with the healthy group.,This study revealed strong relationship between alterations of sputum microbiota and COPD.,By determining the content of several types of bacteria, we can provide evidence to aid in the diagnosis and treatment of COPD. | 1 |
A genetic contribution to develop chronic obstructive pulmonary disease (COPD) is well established.,However, the specific genes responsible for enhanced risk or host differences in susceptibility to smoke exposure remain poorly understood.,The goal of this review is to provide a comprehensive literature overview on the genetics of COPD, highlight the most promising findings during the last few years, and ultimately provide an updated COPD gene list.,Candidate gene studies on COPD and related phenotypes indexed in PubMed before January 5, 2012 are tabulated.,An exhaustive list of publications for any given gene was looked for.,This well-documented COPD candidate-gene list is expected to serve many purposes for future replication studies and meta-analyses as well as for reanalyzing collected genomic data in the field.,In addition, this review summarizes recent genetic loci identified by genome-wide association studies on COPD, lung function, and related complications.,Assembling resources, integrative genomic approaches, and large sample sizes of well-phenotyped subjects is part of the path forward to elucidate the genetic basis of this debilitating disease. | Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability worldwide.,The Global Burden of Disease study has concluded that COPD will become the third leading cause of death worldwide by 2020, and will increase its ranking of disability-adjusted life years lost from 12th to 5th.,Acute exacerbations of COPD (AECOPD) are associated with impaired quality of life and pulmonary function.,More frequent or severe AECOPDs have been associated with especially markedly impaired quality of life and a greater longitudinal loss of pulmonary function.,COPD and AECOPDs are characterized by an augmented inflammatory response.,Macrolide antibiotics are macrocyclical lactones that provide adequate coverage for the most frequently identified pathogens in AECOPD and have been generally included in published guidelines for AECOPD management.,In addition, they exert broad-ranging, immunomodulatory effects both in vitro and in vivo, as well as diverse actions that suppress microbial virulence factors.,Macrolide antibiotics have been used to successfully treat a number of chronic, inflammatory lung disorders including diffuse panbronchiolitis, asthma, noncystic fibrosis associated bronchiectasis, and cystic fibrosis.,Data in COPD patients have been limited and contradictory but the majority hint to a potential clinical and biological effect.,Additional, prospective, controlled data are required to define any potential treatment effect, the nature of this effect, and the role of bronchiectasis, baseline colonization, and other cormorbidities. | 1 |
A combination therapy with inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA) is recommended in severe chronic obstructive pulmonary disease (COPD) patients experiencing frequent exacerbations.,Currently, there are five ICS/LABA combination products available on the market.,The purpose of this study was to systematically review the efficacy of various ICS/LABA combinations with a network meta-analysis.,Several databases and manufacturer’s websites were searched for relevant clinical trials.,Randomized control trials, at least 12 weeks duration, comparing an ICS/LABA combination with active control or placebo were included.,Moderate and severe exacerbations were chosen as the outcome assessment criteria.,The primary analyses were conducted with a Bayesian Markov chain Monte Carlo method.,Most of the ICS/LABA combinations reduced moderate-to-severe exacerbations as compared with placebo and LABA, but none of them reduced severe exacerbations.,However, many studies excluded patients receiving long-term oxygen therapy.,Moderate-dose ICS was as effective as high-dose ICS in reducing exacerbations when combined with LABA.,ICS/LABA combinations had a class effect with regard to the prevention of COPD exacerbations.,Moderate-dose ICS/LABA combination therapy would be sufficient for COPD patients when indicated.,The efficacy of ICS/LABA combination therapy appeared modest and had no impact in reducing severe exacerbations.,Further studies are needed to evaluate the efficacy of ICS/LABA combination therapy in severely affected COPD patients requiring long-term oxygen therapy. | The expression of HDAC2 is reported as reduced in chronic obstructive pulmonary disease (COPD).,We assessed HDAC2 expression within the airways of smokers and subjects with COPD and effects of inhaled corticosteroids (ICS), using immuno-histology to contrast with previous molecular methodology.,Endobronchial biopsies (ebb) from current smokers with COPD (COPD-CS; n = 15), ex-smokers with COPD (COPD-ES; n = 17), smokers with normal lung function (NS; n = 16) and normal controls (NC; n = 9) were immunostained for HDAC2.,A double-blinded, randomized, placebo-controlled 6 months intervention study assessed effects of ICS on HDAC2 in 34 COPD subjects.,There was no difference in epithelial HDAC2 staining in all groups.,There was a significant reduction in total cell numbers in the lamina propria (LP) in COPD-CS and NS (p<0.05).,LP cellularity correlated inversely with smoking history in COPD-CS (R = −0.8, p<0.003).,HDAC2 expression increased markedly in NS (p<0.001); in contrast COPD-CS was associated with suppressed signal (p<0.03), while normal in COPD-ES.,ICS did not affect HDAC2 cell staining.,Our findings suggest that airway HDAC2 expression is increased in the LP by smoking itself, but is reduced in COPD.,Ex-smokers have normalised HDAC2 cell expression, but ICS had no effect.,The paper emphasise the pit-falls of relying on molecular data alone to define airway changes.,Clinical Trial Registration Information:,The Australian New Zealand Clinical Trials Registry (ANZCTR),ACTRN12612001111864 | 1 |
The GOLD report provides a framework for classifying COPD in a way that reflects its clinical impact and allows treatment recommendations.,The GOLD 2017 proposes a new classification whereby patients are grouped as A-D according to their symptoms and history of exacerbations.,However, the clinical characteristics and outcomes in these patients are not well documented.,In this prospective observational study, we analyzed data from the Ishinomaki COPD Network Registry.,All patients with stable COPD were classified into the four groups defined by GOLD 2017.,The patient demographics, clinical characteristics, number of exacerbations, and mortality rate during 1 year of follow-up were compared between the groups.,Four hundred and one patients with stable COPD were identified.,There were 240 patients (59.9%) in group A, 122 (30.4%) in group B, 16 (4.0%) in group C, and 23 (5.7%) in group D.,Patients in groups B, C, and D had ORs of 2.95, 3.92, and 5.45, respectively, for risk of exacerbation relative to group A.,Groups C and D experienced exacerbations more frequently, including exacerbations leading to hospital admission, than groups A and B (both P<0.001) during the 1-year follow-up period.,Patients with a high risk of exacerbation (groups C and D) had a lower body mass index, showed more symptoms, used more respiratory medications, and had more severe airflow limitation than patients at low risk of exacerbation (groups A and B).,Mortality was not different between the high-risk and low-risk groups.,The results of our study provide evidence that the GOLD 2017 classification identifies patients with COPD at risk of exacerbations, including those requiring hospitalization, but has a poor ability to predict mortality. | Recent recommendations from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) position inhaled corticosteroids (ICS) for use in chronic obstructive pulmonary disease (COPD) patients experiencing exacerbations (≥ 2 or ≥ 1 requiring hospitalisation); i.e.,GOLD groups C and D.,However, it is known that ICS is frequently prescribed for patients with less severe COPD.,Potential drivers of inappropriate ICS use may be historical clinical guidance or a belief among physicians that intervening early with ICS would improve outcomes and reduce resource use.,The objective of this study was to compare healthcare resource use in the UK for COPD patients in GOLD groups A and B (0 or 1 exacerbation not resulting in hospitalisation) who have either been prescribed an ICS-containing regimen or a non-ICS-containing regimen.,Linked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) database were used.,For the study period (1 July 2005 to 30 June 2015) a total 4009 patients met the inclusion criteria; 1745 receiving ICS-containing therapy and 2264 receiving non-ICS therapy.,Treatment groups were propensity score-matched to account for potential confounders in the decision to prescribe ICS, leaving 1739 patients in both treatment arms.,Resource use was assessed in terms of frequency of healthcare practitioner (HCP) interactions and rescue therapy prescribing.,Treatment acquisition costs were not assessed.,Results showed no benefit associated with the addition of ICS, with numerically higher all-cause HCP interactions (72,802 versus 69,136; adjusted relative rate: 1.07 [p = 0.061]) and rescue therapy prescriptions (24,063 versus 21,163; adjusted relative rate: 1.05 [p = 0.212]) for the ICS-containing group compared to the non-ICS group.,Rate ratios favoured the non-ICS group for eight of nine outcomes assessed.,Outcomes were similar for subgroup analyses surrounding potential influential parameters, including patients with poorer lung function (FEV1 < 50% predicted), one prior exacerbation or elevated blood eosinophils.,These data suggest that ICS use in GOLD A and B COPD patients is not associated with a benefit in terms of healthcare resource use compared to non-ICS bronchodilator-based therapy; using ICS according to GOLD recommendations may offer an opportunity for improving patient care and reducing resource use.,The online version of this article (10.1186/s12931-018-0767-2) contains supplementary material, which is available to authorized users. | 1 |
Cigarette smoke (CS) is the leading risk factor to develop COPD.,Therefore, the pathologic effects of whole CS on the differentiation of primary small airway epithelial cells (SAEC) were investigated, using cells from three healthy donors and three COPD patients, cultured under ALI (air-liquid interface) conditions.,The analysis of the epithelial physiology demonstrated that CS impaired barrier formation and reduced cilia beat activity.,Although, COPD-derived ALI cultures preserved some features known from COPD patients, CS-induced effects were similarly pronounced in ALI cultures from patients compared to healthy controls.,RNA sequencing analyses revealed the deregulation of marker genes for basal and secretory cells upon CS exposure.,The comparison between gene signatures obtained from the in vitro model (CS vs. air) with a published data set from human epithelial brushes (smoker vs. non-smoker) revealed a high degree of similarity between deregulated genes and pathways induced by CS.,Taken together, whole cigarette smoke alters the differentiation of small airway basal cells in vitro.,The established model showed a good translatability to the situation in vivo.,Thus, the model can help to identify and test novel therapeutic approaches to restore the impaired epithelial repair mechanisms in COPD, which is still a high medical need. | The receptor for advanced glycation end products (RAGE) is a multiligand signal transduction receptor that can initiate and perpetuate inflammation.,Its soluble isoform (sRAGE) acts as a decoy receptor for RAGE ligands, and is thought to afford protection against inflammation.,With the present study, we aimed at determining whether circulating sRAGE is correlated with emphysema and chronic cor pulmonale in chronic obstructive pulmonary disease (COPD).,In 200 COPD patients and 201 age- and sex-matched controls, we measured lung function by spirometry, and sRAGE by ELISA method.,We also measured the plasma levels of two RAGE ligands, N-epsilon-carboxymethyl lysine and S100A12, by ELISA method.,In the COPD patients, we assessed the prevalence and severity of emphysema by computed tomography (CT), and the prevalence of chronic cor pulmonale by echocardiography.,Multiple quantile regression was used to assess the effects of emphysema, chronic cor pulmonale, smoking history, and comorbid conditions on the three quartiles of sRAGE.,sRAGE was significantly lower (p = 0.007) in COPD patients (median 652 pg/mL, interquartile range 484 to 1076 pg/mL) than in controls (median 869 pg/mL, interquartile range 601 to 1240 pg/mL), and was correlated with the severity of emphysema (p < 0.001), the lower the level of sRAGE the greater the degree of emphysema on CT.,The relationship remained statistically significant after adjusting for smoking history and comorbid conditions.,In addition, sRAGE was significantly lower in COPD patients with chronic cor pulmonale than in those without (p = 0.002).,Such difference remained statistically significant after adjusting for smoking history, comorbidities, and emphysema severity.,There was no significant difference in the plasma levels of the two RAGE ligands between cases and controls.,sRAGE is significantly lower in patients with COPD than in age- and sex-matched individuals without airflow obstruction.,Emphysema and chronic cor pulmonale are independent predictors of reduced sRAGE in COPD. | 1 |
Acknowledgement of COPD underdiagnosis and misdiagnosis in primary care can contribute to improved disease diagnosis.,PUMA is an international primary care study in Argentina, Colombia, Venezuela and Uruguay.,To assess COPD underdiagnosis and misdiagnosis in primary care and identify factors associated with COPD underdiagnosis in this setting.,COPD was defined as post-bronchodilator (post-BD) forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) <0.70 and the lower limit of normal (LLN).,Prior diagnosis was self-reported physician diagnosis of emphysema, chronic bronchitis, or COPD.,Those patients with spirometric COPD were considered to have correct prior diagnosis, while those without spirometric criteria had misdiagnosis.,Individuals with spirometric criteria without previous diagnosis were considered as underdiagnosed.,1,743 patients were interviewed, 1,540 completed spirometry, 309 (post-BD FEV1/FVC <0.70) and 226 (LLN) had COPD.,Underdiagnosis using post-BD FEV1/FVC <0.70 was 77% and 73% by LLN.,Overall, 102 patients had a prior COPD diagnosis, 71/102 patients (69.6%) had a prior correct diagnosis and 31/102 (30.4%) had a misdiagnosis defined by post-BD FEV1/FVC ≥0.70.,Underdiagnosis was associated with higher body mass index (≥30 kg/m2), milder airway obstruction (GOLD I-II), black skin color, absence of dyspnea, wheezing, no history of exacerbations or hospitalizations in the past-year.,Those not visiting a doctor in the last year or only visiting a GP had more risk of underdiagnosis.,COPD underdiagnosis (65.8%) and misdiagnosis (26.4%) were less prevalent in those with previous spirometry.,COPD underdiagnosis is a major problem in primary care.,Availability of spirometry should be a priority in this setting. | Guidelines on COPD diagnosis and management encourage primary care physicians to detect the disease at an early stage and to treat patients according to their condition and needs.,Problems in guideline implementation include difficulties in diagnosis, using spirometry and the disputed role of reversibility testing.,These lead to inaccurate diagnostic registers and inadequacy of administered treatments.,This study represents an audit of COPD diagnosis and management in primary care practices in Devon.,Six hundred and thirty two patients on COPD registers in primary care practices were seen by a visiting Respiratory Specialist Nurse.,Diagnoses were made according to the NICE guidelines.,Reversibility testing was carried out either routinely or based on clinical indication in two sub-samples.,Dyspnoea was assessed.,Data were entered into a novel IT-based software which computed guideline-based treatment recommendations.,Current and recommended treatments were compared.,Five hundred and eighty patients had spirometry.,Diagnoses of COPD were confirmed in 422 patients (73%).,Thirty nine patients were identified as asthma only, 94 had normal spirometry, 23 were restrictive and 2 had a cardiac disorder.,Reversibility testing changed diagnosis of 11% of patients with airflow obstruction, and severity grading in 18%.,Three quarters of patients with COPD had been offered practical help with smoking cessation.,Short and long-acting anticholinergics and long acting beta-2 agonists had been under-prescribed; in 15-18% of patients they were indicated but not received.,Inhaled steroids had been over-prescribed (recommended in 17%; taken by 60%), whereas only 4% of patients with a chronic productive cough were receiving mucolytics.,Pulmonary rehabilitation was not available in some areas and was under-used in other areas.,Diagnostic registers of COPD in primary care contain mistakes leading to inaccurate prevalence estimates and inappropriate treatment decisions.,Use of pre-bronchodilator readings for diagnosis overestimates the prevalence and severity in a significant minority, thus post bronchodilator readings should be used.,Management of stable COPD does often not correspond to guidelines.,The IT system used in this study has the potential to improve diagnosis and management of COPD in primary care. | 1 |
Aging is an important risk factor for most chronic diseases.,Patients with COPD develop more comorbidities than non-COPD subjects.,We hypothesized that the development of comorbidities characteristically affecting the elderly occur at an earlier age in subjects with the diagnosis of COPD.,We included all subjects carrying the diagnosis of COPD (n = 27,617), and a similar number of age and sex matched individuals without the diagnosis, extracted from the 727,241 records of individuals 40 years and older included in the EpiChron Cohort (Aragon, Spain).,We compared the cumulative number of comorbidities, their prevalence and the mortality risk between both groups.,Using network analysis, we explored the connectivity between comorbidities and the most influential comorbidities in both groups.,We divided the groups into 5 incremental age categories and compared their comorbidity networks.,We then selected those comorbidities known to affect primarily the elderly and compared their prevalence across the 5 age groups.,In addition, we replicated the analysis in the smokers’ subgroup to correct for the confounding effect of cigarette smoking.,Subjects with COPD had more comorbidities and died at a younger age compared to controls.,Comparison of both cohorts across 5 incremental age groups showed that the number of comorbidities, the prevalence of diseases characteristic of aging and network’s density for the COPD group aged 56-65 were similar to those of non-COPD 15 to 20 years older.,The findings persisted after adjusting for smoking.,Multimorbidity increases with age but in patients carrying the diagnosis of COPD, these comorbidities are seen at an earlier age. | 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 |
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. | 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 |
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. | Pulmonary rehabilitation has short-term benefits on dyspnea, exercise capacity and quality of life in COPD, but evidence suggests these do not always translate to increased daily physical activity on a patient level.,This is attributed to a limited understanding of the determinants of physical activity maintenance following pulmonary rehabilitation.,This systematic review of qualitative research was conducted to understand COPD patients’ perceived facilitators and barriers to physical activity following pulmonary rehabilitation.,Electronic databases of published data, non-published data, and trial registers were searched to identify qualitative studies (interviews, focus groups) reporting the facilitators and barriers to physical activity following pulmonary rehabilitation for people with COPD.,Thematic synthesis of qualitative data was adopted involving line-by-line coding of the findings of the included studies, development of descriptive themes, and generation of analytical themes.,Fourteen studies including 167 COPD patients met the inclusion criteria.,Seven sub-themes were identified as influential to physical activity following pulmonary rehabilitation.,These included: intentions, self-efficacy, feedback of capabilities and improvements, relationship with health care professionals, peer interaction, opportunities following pulmonary rehabilitation and routine.,These encapsulated the facilitators and barriers to physical activity following pulmonary rehabilitation and were identified as sub-themes within the three analytical themes, which were beliefs, social support, and the environment.,The findings highlight the challenge of promoting physical activity following pulmonary rehabilitation in COPD and provide complementary evidence to aid evaluations of interventions already attempted in this area, but also adds insight into future development of interventions targeting physical activity maintenance in COPD. | 1 |
The combination of aclidinium bromide, a long-acting anticholinergic, and formoterol fumarate, a long-acting beta2-agonist (400/12 μg twice daily) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease (COPD), and is approved in the European Union as a maintenance treatment.,The effect of this combination on symptoms of COPD and exacerbations is less well established.,We examined these outcomes in a pre-specified analysis of pooled data from two 24-week, double-blind, parallel-group, active- and placebo-controlled, multicentre, randomised Phase III studies (ACLIFORM and AUGMENT).,Patients ≥40 years with moderate to severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <70 % and FEV1 ≥30 % but <80 % predicted normal) were randomised (ACLIFORM: 2:2:2:2:1; AUGMENT: 1:1:1:1:1) to twice-daily aclidinium/formoterol 400/12 μg or 400/6 μg, aclidinium 400 μg, formoterol 12 μg or placebo via Genuair™/Pressair®.,Dyspnoea (Transition Dyspnoea Index; TDI), daily symptoms (EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [E-RS] questionnaire), night-time and early-morning symptoms, exacerbations (Healthcare Resource Utilisation [HCRU] and EXACT definitions) and relief-medication use were assessed.,The pooled intent-to-treat population included 3394 patients.,Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 (all p < 0.05).,Over 24 weeks, significant improvements in E-RS total score, overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with aclidinium/formoterol 400/12 μg versus placebo and both monotherapies (all p < 0.05).,The rate of moderate or severe HCRU exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg compared with placebo (p < 0.05) but not monotherapies; the rate of EXACT-defined exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg versus placebo (p < 0.01) and aclidinium (p < 0.05).,Time to first HCRU or EXACT exacerbation was longer with aclidinium/formoterol 400/12 μg compared with placebo (all p < 0.05) but not the monotherapies.,Relief-medication use was reduced with aclidinium/formoterol 400/12 μg versus placebo and aclidinium (p < 0.01).,Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo, aclidinium and formoterol in patients with moderate to severe COPD.,Furthermore, aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo.,NCT01462942 and NCT01437397 (ClinicalTrials.gov),The online version of this article (doi:10.1186/s12931-015-0250-2) contains supplementary material, which is available to authorized users. | Inhaled long-acting bronchodilators are the mainstay of pharmacotherapy for chronic obstructive pulmonary disease (COPD).,Both the twice-daily long-acting β2-adrenoceptor agonists (LABAs) salmeterol and formoterol and the once-daily LABA indacaterol are indicated for use in COPD.,This review examines current evidence for the safety of LABAs in COPD, focusing on their effect on exacerbations and deaths.,We searched PubMed for placebo-controlled studies evaluating long-term (≥24 weeks) use of formoterol, salmeterol, or indacaterol in patients with stable COPD, published between January 1990 and September 2012.,We summarized data relating to exacerbations and adverse events, particularly events related to COPD.,From 20 studies examined (8774 LABA-treated patients), there was no evidence of an association between LABA treatment and increased exacerbations, COPD-related adverse events, or deaths.,Where analyzed as an efficacy outcome, LABA treatment was generally associated with significant or numerical reductions in COPD exacerbations compared with placebo.,Incidences of COPD-related adverse events were similar for active and placebo treatments.,The incidence of adverse events typically associated with the β2-agonist drug class such as skeletal muscle tremors and palpitations was low (often <1% of patients), and there were no reports of increased incidence of cardiac arrhythmias.,The systemic effects of β2-adrenoceptor stimulation, such as high glucose and potassium levels, were considered minor.,Current evidence from clinical studies of the safety and tolerability profile of LABAs supports their long-term use in COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is a serious, yet preventable and treatable, disease.,The success of its treatment relies largely on the proper implementation of recommendations, such as the recently released Global Strategy for Diagnosis, Management, and Prevention of COPD (GOLD 2011, of late December 2011).,The primary objective of this study was to examine the extent to which GOLD 2011 is being used correctly among Czech respiratory specialists, in particular with regard to the correct classification of patients.,The secondary objective was to explore what effect an erroneous classification has on inadequate use of inhaled corticosteroids (ICS).,In order to achieve these goals, a multi-center, cross-sectional study was conducted, consisting of a general questionnaire and patient-specific forms.,A subjective classification into the GOLD 2011 categories was examined, and then compared with the objectively computed one.,Based on 1,355 patient forms, a discrepancy between the subjective and objective classifications was found in 32.8% of cases.,The most common reason for incorrect classification was an error in the assessment of symptoms, which resulted in underestimation in 23.9% of cases, and overestimation in 8.9% of the patients' records examined.,The specialists seeing more than 120 patients per month were most likely to misclassify their condition, and were found to have done so in 36.7% of all patients seen.,While examining the subjectively driven ICS prescription, it was found that 19.5% of patients received ICS not according to guideline recommendations, while in 12.2% of cases the ICS were omitted, contrary to guideline recommendations.,Furthermore, with consideration to the objectively-computed classification, it was discovered that 15.4% of patients received ICS unnecessarily, whereas in 15.8% of cases, ICS were erroneously omitted.,It was therefore concluded that Czech specialists tend either to under-prescribe or overuse inhaled corticosteroids. | The relationship between prior health care utilization and respiratory medication prescriptions in an unselected population of patients with COPD is not known.,We determined the prescribed respiratory medications and respiratory and nonrespiratory health care encounters in 523 Veterans with COPD at the Cincinnati Veterans Affairs Medical Center between 2000 and 2005.,Prescribed treatments were compared with the GOLD guidelines and each patient was classified as receiving less medications than recommended in the guidelines (<G), medications according to the guidelines (=G), or more medications than recommended (>G).,Respiratory medications were <G for 54%, =G in 33%, and >G for 14% of the patients studied.,For GOLD stages 1 and 2, <G patients had the fewest and >G patients the most prior respiratory encounters during a 12 month period (0.31 ± 0.073 (0.21, 0.47), 0.75 ± 0.5 (0.37, 1.5), 1.1 ± 0.27 (0.74, 1.6) visits/person/year, <G, =G, >G, respectively, mean + standard error of mean (SEM) (95% confidence limits) 2 degrees of freedom (df) ANOVA P < 0.001 for prescription effect).,For GOLD stages 3 and 4, <G was associated with significantly fewer prior respiratory visits than was =G (0.78 ± 0.11 (0.6, 1.0) and 2.4 ± 0.47 (1.9, 3.1) visits/person/year, respectively, P < 0.001).,There were no differences in nonrespiratory health care visits for GOLD stages 1 and 2 by prescription level (3.1 ± 0.24 (2.6, 3.5), 3.1 ± 0.46 (2.1, 4.6) and 4.1 ± 0.55 (3.3, 5.1) visits/person/year, <G, =G, >G respectively, 2 df ANOVA P = 0.096) or for GOLD stages 3 and 4 (3.6 ± 0.25 (3.2, 4.1) and 4.0 ± 0.44 (3.3, 4.9) visits/person/year, <G and =G, respectively, P = 0.36).,Respiratory medications prescribed for an unselected population with a broad range of COPD severity complied poorly with the GOLD pharmacologic treatment guidelines but correlated with the number of prior respiratory health care visits. | 1 |
The objective of this study is to evaluate whether a chronic obstructive pulmonary disease (COPD) self-management education program with coaching of a case manager improves patient-related outcomes and leads to practice changes in primary care.,COPD patients from six family medicine clinics (FMCs) participated in a 1-year educational program offered by trained case managers who focused on treatment adherence, inhaler techniques, smoking cessation, and the use of an action plan for exacerbations.,Health-care utilization, health-related quality of life (HRQL), treatment adherence, inhaler technique, and COPD knowledge were assessed at each visit with validated questionnaires.,We also evaluated whether the use of spirometry and the assessment of individual patient needs led to a more COPD-targeted treatment by primary care physicians, based on changes in prescriptions for COPD (medication, immunization, and written action plan).,Fifty-four patients completed the follow-up visits and were included in the analysis.,The number of unscheduled physician visits went from 40 the year before intervention to 17 after 1 year of educational intervention (p = 0.033).,Emergency room visits went from five to two and hospitalizations from two to three (NS).,Significant improvements were observed in HRQL (p = 0.0001), treatment adherence (p = 0.025), adequate inhaler technique (p < 0.0001), and COPD knowledge (p < 0.001).,Primary care physicians increased their prescriptions for long-acting bronchodilators with/without inhaled corticosteroid, flu immunizations, and COPD action plans in the event patient had an exacerbation.,The COPD self-management educational intervention in FMCs reduced unscheduled visits to the clinic and improved patients’ quality of life, self-management skills, and knowledge.,The program had a positive impact on COPD-related practices by primary care physicians in the FMCs. | 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 |
Uptake of nutritional supplementation during pulmonary rehabilitation (PR) for people with chronic obstructive pulmonary disease (COPD) has been limited by an absence of rigorous evidence-based studies supporting use.,The objective was to report and summarise the current evidence supporting the use of nutritional supplementation to improve outcomes during PR in stable COPD patients.,A systematic search was conducted up to 7 August 2019 (registration number CRD42018089142).,The preferred reporting items for systematic reviews and meta-analyses guidelines were used.,Six databases were included: Medical Literature Analysis and Retrieval System Online or MEDLARS Online, Allied and Complementary Medicine Database, the Cochrane Database of Systematic Reviews, Excerpta Medica dataBASE, Cumulative Index of Nursing and Allied Health Literature and Web of Science.,This systematic search generated 580 initial matches, of which 22 studies (917 COPD participants) met the pre-specified criteria and were included.,Sixteen of 19 studies that used nutritional supplements in addition to PR did not show additional benefit compared to PR alone when measuring exercise capacity.,Nutritional supplements significantly increased body weight in 7 of 11 studies.,Body mass index increased significantly in two of six studies.,Handgrip strength did not improve, while quadriceps muscle strength significantly improved in 3 of 11 studies.,Four of eight studies showed a significant improvement in inspiratory muscle function.,Only 2 of 14 studies demonstrated a significant improvement in quality of life with supplementation in addition to PR.,There remains insufficient evidence on the effect of nutritional supplementation on improving outcomes during PR in patients with COPD due to heterogeneity in supplements, outcome measures and PR programmes.,Therefore, controversy remains and further research is needed. | Computed tomography (CT) phenotypic characterization helps in understanding the clinical diversity of chronic obstructive pulmonary disease (COPD) patients, but its clinical relevance and its relationship with functional features are not clarified.,Volumetric capnography (VC) uses the principle of gas washout and analyzes the pattern of CO2 elimination as a function of expired volume.,The main variables analyzed were end-tidal concentration of carbon dioxide (ETCO2), Slope of phase 2 (Slp2), and Slope of phase 3 (Slp3) of capnogram, the curve which represents the total amount of CO2 eliminated by the lungs during each breath.,To investigate, in a group of patients with severe COPD, if the phenotypic analysis by CT could identify different subsets of patients, and if there was an association of CT findings and functional variables.,Sixty-five patients with COPD Gold III-IV were admitted for clinical evaluation, high-resolution CT, and functional evaluation (spirometry, 6-minute walk test [6MWT], and VC).,The presence and profusion of tomography findings were evaluated, and later, the patients were identified as having emphysema (EMP) or airway disease (AWD) phenotype.,EMP and AWD groups were compared; tomography findings scores were evaluated versus spirometric, 6MWT, and VC variables.,Bronchiectasis was found in 33.8% and peribronchial thickening in 69.2% of the 65 patients.,Structural findings of airways had no significant correlation with spirometric variables.,Air trapping and EMP were strongly correlated with VC variables, but in opposite directions.,There was some overlap between the EMP and AWD groups, but EMP patients had signicantly lower body mass index, worse obstruction, and shorter walked distance on 6MWT.,Concerning VC, EMP patients had signicantly lower ETCO2, Slp2 and Slp3.,Increases in Slp3 characterize heterogeneous involvement of the distal air spaces, as in AWD.,Visual assessment and phenotyping of CT in COPD patients is feasible and may help identify functional and clinically different subsets of patients.,VC may provide useful information about the heterogeneous involvement of lung structures in COPD. | 1 |
Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma.,In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017.,Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex.,Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases.,We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs.,In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9-584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990.,Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia.,The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically.,Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8-7·2] of all deaths), behind cardiovascular diseases and neoplasms.,Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578-4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%.,However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%).,In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD.,In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes.,Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world.,Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions.,Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men.,Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region.,Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990.,Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis.,Bill & Melinda Gates Foundation. | Reduced physical activity (PA) in patients with COPD is associated with a poor prognosis.,Increasing PA is a key therapeutic target, but thus far few strategies have been found effective in this patient group.,To investigate the effectiveness of a 12-week semiautomated telecoaching intervention on PA in patients with COPD in a multicentre European randomised controlled trial.,343 patients from six centres, encompassing a wide spectrum of disease severity, were randomly allocated to either a usual care group (UCG) or a telecoaching intervention group (IG) between June and December 2014.,This 12-week intervention included an exercise booklet and a step counter providing feedback both directly and via a dedicated smartphone application.,The latter provided an individualised daily activity goal (steps) revised weekly and text messages as well as allowing occasional telephone contacts with investigators.,PA was measured using accelerometry during 1 week preceding randomisation and during week 12.,Secondary outcomes included exercise capacity and health status.,Analyses were based on modified intention to treat.,Both groups were comparable at baseline in terms of factors influencing PA.,At 12 weeks, the intervention yielded a between-group difference of mean, 95% CI (lower limit - upper limit; ll-ul) +1469, 95% CI (971 to 1965) steps/day and +10.4, 95% CI (6.1 to 14.7) min/day moderate PA; favouring the IG (all p≤0.001).,The change in 6-min walk distance was significantly different (13.4, 95% CI (3.40 to 23.5) m, p<0.01), favouring the IG.,In IG patients, an improvement could be observed in the functional state domain of the clinical COPD questionnaire (p=0.03) compared with UCG.,Other health status outcomes did not differ.,The amount and intensity of PA can be significantly increased in patients with COPD using a 12-week semiautomated telecoaching intervention including a step counter and an application installed on a smartphone.,NCT02158065. | 1 |
The Global Initiative of Chronic Obstructive Lung Disease (GOLD) guidelines define chronic obstructive pulmonary disease (COPD) in subjects with FEV1/FVC <0.7.,However, the use of this fixed ratio may result in over-diagnosis of COPD in the elderly, especially with mild degree of COPD.,The lower limit of normal (LLN) can be used to minimize the potential misclassification.,The aim of this study was to evaluate the impact of different definitions of airflow obstruction (LLN or fixed ratio of FEV1/FVC) on the estimated prevalence of COPD in a population-based sample.,We compared the prevalence of COPD and its difference diagnosed by different methods using either fixed ratio (FEV1/FVC <0.7) or LLN criterion (FEV1/FVC below LLN).,Among the 4,816 subjects who had performed spirometry, 2,728 subjects met new ATS/ERS spirometry criteria for acceptability and repeatability.,The prevalence of COPD was 10.9% (14.7% in men, 7.2% in women) by LLN criterion and 15.5% (21.8% in men, 9.1% in women) by fixed ratio of FEV1/FVC among subjects older than 45 yr.,The difference of prevalence between LLN and fixed ratio of FEV1/FVC was even higher among subjects with age ≥65, 14.9% and 31.1%, respectively.,In conclusion, the prevalence of COPD by LLN criterion was significantly lower in elderly compared to fixed ratio of FEV1/FVC.,Implementing LLN criterion instead of fixed ratio of FEV1/FVC may reduce the risk of over-diagnosis of COPD in elderly people. | 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. | 1 |
The most commonly applied treatment for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is a 5-day course of high-dose systemic corticosteroids.,However, this treatment has not been shown to reduce mortality and can potentially have serious side effects.,Recent research has shown that, presumably, only a subgroup of COPD patients identifieable by blood eosinophil count benefit from a rescue course of prednisolone.,By applying a biomarker-guided strategy, the aim of this study is to determine whether it is possible to reduce the use of systemic corticosteroids in AECOPD without influencing the outcome.,This is an ongoing prospective multicenter randomized controlled open label trial comprising 320 patients with AECOPD recruited from four hospitals in Denmark.,The patients are randomized 1:1 to either standard care or eosinophil-guided corticosteroid-sparing therapy where prednisolone is not administered if the daily blood sampling reveals an eosinophil level below 0.3 × 109 cells/L.,The primary endpoint is length of hospital stay within 14 days after recruitment.,The secondary endpoints are treatment failure, 30-day mortality rate, COPD related re-admission rate, change in FEV1, and a number of adverse effect measures obtained within 3 months after the index hospitalisation date related to corticosteroid usage.,This will be a very large RCT providing knowledge about the effectiveness of individualized biomarker-guided corticosteroid therapy in hospitalised patients with AECOPD.,Clinicaltrials.gov, NCT02857842, 02-august-2016.,Clinicaltrialregister.eu: Classification Code: 10,010,953, 02-marts-2016. | The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.,The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada.,Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified.,The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.,The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively.,The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th.,The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first.,Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.,The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation.,Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality. | 1 |
The St.,George’s Respiratory Questionnaire (SGRQ) and chronic obstructive pulmonary disease (COPD) assessment test (CAT) are the measures used to assess health status.,This study aims to examine the responsiveness of these tools by severity of dyspnoea category in patients with COPD.,Forty-nine COPD patients who underwent a 12-week pulmonary rehabilitation (PR) programme were assessed at baseline, 12 weeks and at 28-week follow-up.,Patients were categorized into two groups by severity of dyspnoea category (i.e. mild to moderate (modified Medical Research Council (mMRC) 1-2) and severe to very severe (mMRC 3-4)) using the mMRC dyspnoea scale.,Effect size (ES) was computed as estimates of responsiveness.,The SGRQ demonstrated greater responsiveness by total sample (SGRQ, ES = 0.87; CAT, ES = 0.75) and for the mMRC 3-4 category (SGRQ, ES = 0.91; CAT, ES = 0.76) on completion of PR.,At 28-week follow-up, overall comparable responsiveness of the CAT and SGRQ was identified by total sample (SGRQ, ES = 0.75; CAT, ES = 0.74) and by severity of dyspnoea category.,The symptom, impact and activity domains of the SGRQ showed good responsiveness, with greater ESs obtained overall for the mMRC 3-4 category.,On completion of PR, the SGRQ demonstrates a greater responsiveness with COPD patients, especially in relation to the mMRC 3-4 category, while both the CAT and SGRQ show comparable responsiveness on follow-up. | Chronic Obstructive Pulmonary Disease (COPD) influences different aspects of patient’s health-related quality of life (HRQL).,While disease-specific HRQL instruments focus on symptoms and functional impairments, generic instruments cover a broader view on health.,This study compares the generic EQ-5D-3 L and two disease-specific questionnaires (St.-George’s Respiratory Questionnaire (SGRQ-C), COPD Assessment Test (CAT)) in a comprehensive spectrum of COPD disease grades with particular attention on comorbidities and assesses the discriminative abilities of these instruments.,Using data from the baseline visit of the German COPD cohort COSYCONET, mean HRQL scores in different COPD grades were compared by linear regression models adjusting for age, sex, education, smoking status, BMI, and low vs. high number of comorbidities or a list of several self-reported comorbid conditions.,Discriminative abilities of HRQL instruments to differentiate between COPD grades were assessed by standardized mean differences.,In 2,291 subjects in COPD GOLD grades 1-4 EQ-5D-3 L utility, EQ-5D VAS, SGRQ, and CAT were found able to discriminate between COPD grades, with some limitations for the EQ-5D utility in mild disease.,Both generic and disease-specific HRQL instruments reflected the burden of comorbid conditions.,The SGRQ showed the best discrimination between COPD grades and was less influenced by comorbidities, while EQ-5D utility put a higher weight on comorbid conditions.,For all instruments, psychiatric disorders and peripheral artery disease showed the strongest negative associations with HRQL.,All HRQL instruments considered reflect considerable impairment of HRQL in COPD patients, worsening with increasing COPD grade and number of comorbidities.,Findings may support clinical assessment, choice of HRQL instrument in future studies, and parameterization of decision-analytic models.,The online version of this article (doi:10.1186/s12890-016-0238-9) contains supplementary material, which is available to authorized users. | 1 |
Current treatment strategies to stratify exacerbation risk rely on history of ≥2 events in the previous year.,To understand year-to-year variability and factors associated with consistent exacerbations over time, we present a prospective analysis of the SPIROMICS cohort.,We analyzed SPIROMICS participants with COPD and three years of prospective data (n=1,105).,We classified participants according to yearly exacerbation frequency.,Stepwise logistic regression compared factors associated with individuals experiencing ≥1 AECOPD in every year for three years versus none.,During three years follow-up, 48·7% of participants experienced at least one AECOPD, while the majority (51·3%) experienced none.,Only 2·1% had ≥2 AECOPD in each year.,An inconsistent pattern (both years with and years without AECOPD) was common (41·3% of the group), particularly among GOLD stages 3 and 4 subjects (56·1%).,In logistic regression, consistent AECOPD (≥1 event per year for three years) as compared to no AECOPD were associated with higher baseline symptom burden assessed with the COPD Assessment Test, previous exacerbations, greater evidence of small airway abnormality by computed tomography, lower Interleukin-15 (IL-15) and elevated Interleukin-8 (IL-8).,Although AECOPD are common, the exacerbation status of most individuals varies markedly from year to year.,Among participants who experienced any AECOPD over three years, very few repeatedly experienced ≥2 events/year.,In addition to symptoms and history of exacerbations in the prior year, we identified several novel biomarkers associated with consistent exacerbations, including CT-defined small airway abnormality, IL-15 and IL-8. | Patients with COPD show a significant reduction of the lobar hyperinflation at the functional residual capacity level in the patients who improved >120 mL in forced expiratory volume in 1 second (FEV1) after 6 months of treatment with roflumilast in addition to inhaled corticosteroids (ICSs)/long-acting beta-2 agonists (LABAs)/long-acting muscarinic antagonists (LAMAs).,Functional respiratory imaging was used to quantify lobar hyperinflation, blood vessel density, ventilation, aerosol deposition, and bronchodilation.,To investigate the exact mode of action of roflumilast, correlations between lobar and global measures have been tested using a mixed-model approach with nested random factors and Pearson correlation, respectively.,The reduction in lobar hyperinflation appears to be associated with a larger blood vessel density in the respective lobes (t=−2.154, P=0.040); lobes with a higher percentage of blood vessels reduce more in hyperinflation in the responder group.,Subsequently, it can be observed that lobes that reduce in hyperinflation after treatment are better ventilated (t=−5.368, P<0.001).,Functional respiratory imaging (FRI)-based aerosol deposition showed that enhanced ventilation leads to more peripheral particle deposition of ICS/LABA/LAMA in the better-ventilated areas (t=2.407, P=0.024).,Finally, the study showed that areas receiving more particles have increased FRI-based bronchodilation (t=2.564, P=0.017), leading to an increase in FEV1 (R=0.348, P=0.029).,The study demonstrated that orally administered roflumilast supports the reduction of regional hyperinflation in areas previously undertreated by inhalation medication.,The local reduction in hyperinflation induces a redistribution of ventilation and aerosol deposition, leading to enhanced efficacy of the concomitant ICS/LABA/LAMA therapy.,FRI appears to be a sensitive tool to describe the mode of action of novel compounds in chronic obstructive pulmonary disease.,Future studies need to confirm the enhanced sensitivity and the potential of FRI parameters to act as surrogates for clinically relevant, but more difficult to measure, end points such as exacerbations. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of worsening of symptoms, leading to substantial morbidity and mortality.,COPD exacerbations are associated with increased airway and systemic inflammation and physiological changes, especially the development of hyperinflation.,They are triggered mainly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation.,Some patients are particularly susceptible to exacerbations, and show worse health status and faster disease progression than those who have infrequent exacerbations.,Several pharmacological interventions are effective for the reduction of exacerbation frequency and severity in COPD such as inhaled steroids, long-acting bronchodilators, and their combinations.,Non-pharmacological therapies such as pulmonary rehabilitation, self-management, and home ventilatory support are becoming increasingly important, but still need to be studied in controlled trials.,The future of exacerbation prevention is in assessment of optimum combinations of pharmacological and non-pharmacological therapies that will result in improvement of health status, and reduction of hospital admission and mortality associated with COPD. | Measurements of eosinophils in induced sputum and fractional exhaled nitric oxide (FeNO) are noninvasive biomarkers for assessing airway inflammation phenotypes in chronic obstructive pulmonary disease (COPD).,Nevertheless, the clinical application of the correlation between FeNO levels and sputum eosinophilia is controversial.,The study aimed to investigate the correlation and predictive relationship between FeNO levels and sputum eosinophils in patients with COPD exacerbation.,It also examined the relationship between FeNO levels and blood eosinophil percentage.,A total of 163 patients with COPD exacerbation were included in the cross-sectional study.,All patients underwent the following on the same day: FeNO test, spirometry, bronchodilator reversibility test, induced sputum, and routine blood test.,They were classified as eosinophilic group or noneosinophilic group based on sputum eosinophilic percentage (≥2.5%)/FeNO levels (≥32 parts per billion [ppb]).,FeNO levels and blood eosinophilic percentage were higher in patients with sputum eosinophilia (n=62) compared to those without (31.35 ppb versus 21.43 ppb, P=0.015; 2.71% versus 0.98%, P<0.0001, respectively).,Sputum eosinophilic percentage was higher with raised FeNO (n=34) compared to those with FeNO <32 ppb (5.12% versus 3.12%, P=0.007).,Eosinophils in induced sputum correlated with both FeNO levels (ρ=0.221, P=0.005) and blood eosinophilic percentage (ρ=0.399, P<0.001).,There was no relationship between FeNO and blood eosinophilic percentage.,Blood eosinophilic percentage was predictive of sputum eosinophilia (95% confidence interval [CI] =0.65-0.81, P<0.001) at a cutoff point of 0.65% (sensitivity =73%, specificity =61.3%).,FeNO levels were predictive of sputum eosinophilia (95% CI =0.53-3,071, P=0.012) at a cutoff point of 17.5 ppb (sensitivity =65.1%, specificity =56.4%).,The clinical relevance of this study provides evidence that inflammatory biomarkers, including sputum eosinophilic percentage, FeNO level, and blood eosinophilic percentage, can be used to positively diagnose eosinophilic COPD.,The FeNO level and blood eosinophilic counts/percentage, which determine an optimal cutoff for sputum eosinophilia, need more studies. | 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. | Exercise limitation, dynamic hyperinflation, and exertional dyspnea are key features of symptomatic chronic obstructive pulmonary disease (COPD).,We assessed the effects of glycopyrronium bromide (NVA237), a once-daily, long-acting muscarinic antagonist, on exercise tolerance in patients with moderate to severe COPD.,Patients were randomized to a cross-over design of once-daily NVA237 50 μg or placebo for 3 weeks, with a 14-day washout.,Exercise endurance, inspiratory capacity (IC) during exercise, IC and expiratory volumes from spirometry, plethysmographic lung volumes, leg discomfort and dyspnea under exercise (Borg scales), and transition dyspnea index were measured on Days 1 and 21 of treatment.,The primary endpoint was endurance time during a submaximal constant-load cycle ergometry test on Day 21.,A total of 108 patients were randomized to different treatment groups (mean age, 60.5 years; mean post-bronchodilator, forced expiratory volume in 1 second [FEV1] 57.1% predicted).,Ninety-five patients completed the study.,On Day 21, a 21% difference in endurance time was observed between patients treated with NVA237 and those treated with placebo (P < 0.001); the effect was also significant from Day 1, with an increase of 10%.,Dynamic IC at exercise isotime and trough FEV1 showed significant and clinically relevant improvements from Day 1 of treatment that were maintained throughout the study.,This was accompanied by inverse decreases in residual volume and functional residual capacity.,NVA237 was superior to placebo (P < 0.05) in decreasing leg discomfort (Borg CR10 scale) on Day 21 and exertional dyspnea on Days 1 and 21 (transition dyspnea index and Borg CR10 scale at isotime).,The safety profile of NVA237 was similar to that of the placebo.,NVA237 50 μg once daily produced immediate and significant improvement in exercise tolerance from Day 1.,This was accompanied by sustained reductions in lung hyperinflation (indicated by sustained and significant improvements in IC at isotime), and meaningful improvements in trough FEV1 and dyspnea.,Improvements in exercise endurance increased over time, suggesting that mechanisms beyond improved lung function may be involved in enhanced exercise tolerance.,(ClinicalTrials.gov Identifier: NCT01154127). | 1 |
Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) can lead to high frequencies and rates of hospitalization and mortality.,Macrolides are a class of antibiotics that possess both antimicrobial and anti-inflammatory properties.,Since the occurrence of AECOPDs is associated with aggravation of airway inflammation and bacterial infections, prophylactic macrolide treatment may be an effective approach towards the prevention of AECOPDs.,We systemically searched the PubMed, Embase and Cochrane Library databases to identify randomized controlled trials (RCTs) that evaluated the effect of prophylactic macrolide therapy on the prevention of AECOPDs.,The primary outcomes were the total number of patients with one or more exacerbations as well as the rate of exacerbations per patient per year.,Nine RCTs comprising 1666 patients met the inclusion criteria.,Pooled evidence showed macrolides could reduce the frequency of exacerbations in patients with COPD by both unweighted (RR = 0.70; 95% CI: 0.56-0.87; P < 0.01) and weighted approaches (RR = 0.58, 95% CI: 0.43-0.78, P < 0.01).,Subgroup analysis showed only 6-12 months of erythromycin or azithromycin therapy could be effective.,Moreover, among studies with 6-12 months of azithromycin therapy, both the daily dosing regimen and the intermittent regimen significantly reduced exacerbation rates.,The overall number of hospitalizations and the all-cause rate of death were not significantly different between the treatment and control groups.,A tendency for more adverse events was found in the treatment groups (OR = 1.55, 95%CI: 1.003-2.39, P = 0.049).,Our results suggest 6-12 months erythromycin or azithromycin therapy could effectively reduce the frequency of exacerbations in patients with COPD.,However, Long-term treatment may bring increased adverse events and the emergence of macrolide-resistance.,A recommendation for the prophylactic use of macrolide therapy should weigh both the advantages and disadvantages. | Although chronic obstructive pulmonary disease (COPD) is a major global health burden there is a lack of patient awareness of disease severity, particularly in relation to exacerbations.,We conducted a global patient survey using an innovative, internet-based methodology to gain insight into patient perceptions of COPD and exacerbations in a real-world sample typical of today’s working-age COPD population.,Two thousand patients with COPD (53%), chronic bronchitis (52%) and/or emphysema (22%) from 14 countries completed an online questionnaire developed by the authors.,The Medical Research Council (MRC) breathlessness scale was used to delineate symptom severity.,Over three quarters of patients (77%) had experienced an exacerbation, with 27% of MRC 1 and 2 patients and 52% of MRC 3, 4 and 5 patients requiring hospitalization as a result of an exacerbation.,While a majority of MRC 1 and 2 patients (51%) reported being back to normal within a few days of an exacerbation, 23% of MRC 3, 4 and 5 patients took several weeks to return to normal and 6% never fully recovered.,A high proportion of patients (39%) took a ‘wait and see’ approach to exacerbations.,Despite the high prevalence of exacerbations and their negative impact on quality of life, 73% of MRC 1 and 2 patients and 64% of MRC 3, 4 and 5 patients felt that they had control of their COPD.,However, 77% of all patients were worried about their long-term health, and 38% of MRC 1 and 2 patients and 59% of MRC 3, 4 and 5 patients feared premature death due to COPD.,To reduce the adverse effects of COPD on patients’ quality of life and address their fears for the future, we need better patient education and improved prevention and treatment of exacerbations. | 1 |
Pooled data were analyzed to evaluate the safety and tolerability of indacaterol, a once-daily inhaled long-acting β2-agonist for chronic obstructive pulmonary disease (COPD).,Data were pooled from clinical studies of 3-12 months’ duration in patients with moderate-to-severe COPD receiving double-blind indacaterol 75 μg (n = 449), 150 μg (n = 2611), 300 μg (n = 1157), or 600 μg once daily (n = 547); formoterol 12 μg twice daily (n = 556); salmeterol 50 μg twice daily (n = 895); placebo (n = 2012); or tiotropium 18 μg once daily, given open label or blinded (n = 1214).,Outcomes were adverse events, serious adverse events and deaths, plasma potassium, blood glucose, and QTc interval and vital signs.,The commonest adverse events with indacaterol were COPD worsening, nasopharyngitis, and headache; most cases were mild or moderate and incidence was generally similar to placebo and other active treatments.,The risk of acute respiratory serious adverse events (leading to hospitalization, intubation, or death) was not significantly increased with any of the active treatments compared with placebo.,COPD exacerbation rates (analyzed in the intent-to-treat population) were significantly reduced with all active treatments versus placebo.,Hazard ratios versus placebo for major cardiovascular adverse events were <1 for all indacaterol doses.,Notable values for vital signs and measures of systemic β2-adrenoceptor activity were rare with indacaterol.,The number of deaths adjusted per patient-year was lower with indacaterol (all doses combined) than with placebo (relative risk 0.21 [95% confidence interval 0.07-0.660], P = 0.008).,Indacaterol has a good profile of safety and tolerability that is appropriate for the maintenance treatment of patients with COPD. | Two 1-year studies evaluated the long-term efficacy and safety of tiotropium 5 or 10 μg versus placebo, inhaled via the Respimat® Soft Mist™ Inhaler (SMI).,The two studies were combined and had 4 co-primary endpoints (trough FEV1 response, Mahler Transition Dyspnea Index [TDI] and St George’s Respiratory Questionnaire scores all at week 48, and COPD exacerbations per patient-year).,A total of 1990 patients with COPD participated (mean FEV1: 1.09 L).,The mean trough FEV1 response of tiotropium 5 or 10 μg relative to placebo was 127 or 150 mL, respectively (both P < 0.0001).,The COPD exacerbation rate was significantly lower with tiotropium 5 μg (RR = 0.78; P = 0.002) and tiotropium 10 μg (RR = 0.73; P = 0.0008); the health-related quality of life and Mahler TDI co-primary endpoints were significantly improved with both doses (both P < 0.0001).,Adverse events were generally balanced except anticholinergic class effects, which were more frequent with active treatment.,Fatal events occurred in 2.4% (5 μg), 2.7% (10 μg), and 1.6% (placebo) of patients; these differences were not significant.,Tiotropium Respimat® SMI 5 μg demonstrated sustained improvements in patients with COPD relative to placebo and similar to the 10 μg dose but with a lower frequency of anticholinergic adverse events. | 1 |
Genetic factors play a role in chronic obstructive pulmonary disease (COPD) but are poorly understood.,A number of candidate genes have been proposed on the basis of the pathogenesis of COPD.,These include the matrix metalloproteinase (MMP) genes which play a role in tissue remodelling and fit in with the protease - antiprotease imbalance theory for the cause of COPD.,Previous genetic studies of MMPs in COPD have had inadequate coverage of the genes, and have reported conflicting associations of both single nucleotide polymorphisms (SNPs) and SNP haplotypes, plausibly due to under-powered studies.,To address these issues we genotyped 26 SNPs, providing comprehensive coverage of reported SNP variation, in MMPs- 1, 9 and 12 from 977 COPD patients and 876 non-diseased smokers of European descent and evaluated their association with disease singly and in haplotype combinations.,We used logistic regression to adjust for age, gender, centre and smoking history.,Haplotypes of two SNPs in MMP-12 (rs652438 and rs2276109), showed an association with severe/very severe disease, corresponding to GOLD Stages III and IV.,Those with the common A-A haplotype for these two SNPs were at greater risk of developing severe/very severe disease (p = 0.0039) while possession of the minor G variants at either SNP locus had a protective effect (adjusted odds ratio of 0.76; 95% CI 0.61 - 0.94).,The A-A haplotype was also associated with significantly lower predicted FEV1 (42.62% versus 44.79%; p = 0.0129).,This implicates haplotypes of MMP-12 as modifiers of disease severity. | Recent studies have proposed that the serine protease inhibitor E2 (SERPINE2) was a novel susceptibility gene for chronic obstructive pulmonary disease (COPD) in Caucasians.,However, this issue still remained controversial.,Additional evidences from populations with different environments and/or genetic backgrounds, such as East Asian, would be helpful to elucidate the issue.,In this study, five proposed causal SNPs in SERPINE2 were genotyped in 327 COPD patients and 349 controls, all of which belonged to the Han population sampled from Southwest China.,The frequency of each SNP was compared both individually and in combination between patients and controls.,The potential relationship between these SNPs and severity of COPD was also investigated.,Three SNPs (rs3795877, rs6747096, and rs3795879) showed complete linkage disequilibrium (r2 = 1), and the minor allele frequencies were 13.0% and 12.9% in case and control cohorts, respectively, with no significant difference observed (P = 0.96).,We also failed to observe any significant correlation between these SNPs and COPD severity (P = 0.67).,The other two SNPs (rs7579646 and rs840088) also presented a similar pattern.,Moreover, four major haplotypes were observed in our sample but none showed a significant difference between case and control groups (P > 0.1).,Our results failed to obtain the evidence that these SNPs in SERPINE2 contributed to the COPD susceptibility in the Han Chinese population. | 1 |
COPD, asthma, and asthma-COPD overlap increase health care resource consumption, predominantly because of hospitalization for exacerbations and also increased visits to general practitioners (GPs) or specialists.,Little information is available regarding this in the primary care setting.,To describe the prevalence and number of GP and specialist visits for any cause or due to exacerbations in patients with COPD, asthma, and asthma-COPD overlap.,COPD was defined as post-bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio <0.70; asthma was defined as prior medical diagnosis, wheezing in the last 12 months, or wheezing plus reversibility (post-bronchodilator FEV1 or FVC increase ≥200 mL and ≥12%); asthma-COPD overlap was defined as post-bronchodilator FEV1/FVC <0.70 plus prior asthma diagnosis.,Health care utilization was evaluated as GP and/or specialist visits in the previous year.,Among the 1,743 individuals who completed the questionnaire, 1,540 performed acceptable spirometry.,COPD patients had a higher prevalence of any medical visits to any physician versus those without COPD (37.2% vs 21.8%, respectively) and exacerbations doubled the number of visits.,The prevalence of any medical visits to any physician was also higher in asthma patients versus those without asthma (wheezing: 47.2% vs 22.7%; medical diagnosis: 54.6% vs 21.6%; wheezing plus reversibility: 46.2% vs 23.8%, respectively).,Asthma patients with exacerbations had twice the number of visits versus those without an exacerbation.,The number of visits was higher (2.8 times) in asthma-COPD overlap, asthma (1.9 times), or COPD (1.4 times) patients versus those without these respiratory diseases; the number of visits due to exacerbation was also higher (4.9 times) in asthma-COPD overlap, asthma (3.5 times), and COPD (3.8 times) patients.,COPD, asthma, and asthma-COPD overlap increase the prevalence of medical visits and, therefore, health care resource utilization.,Attempts to reduce health care resource use in these patients require interventions aimed at preventing exacerbations. | In patients with COPD, self-management skills are important to reduce the impact of exacerbations.,However, both detection and adequate response to exacerbations appear to be difficult for some patients.,Little is known about the underlying process of exacerbation-related self-management.,Therefore, the objective of this study was to identify and explain the underlying process of exacerbation-related self-management behavior.,A qualitative study using semi-structured in-depth interviews was performed according to the grounded theory approach, following a cyclic process in which data collection and data analysis alternated.,Fifteen patients (male n=8; age range 59-88 years) with mild to very severe COPD were recruited from primary and secondary care settings in the Netherlands, in 2015.,Several patterns in exacerbation-related self-management behavior were identified, and a conceptual model describing factors influencing exacerbation-related self-management was developed.,Acceptance, knowledge, experiences with exacerbations, perceived severity of symptoms and social support were important factors influencing exacerbation-related self-management.,Specific factors influencing recognition of exacerbations were heterogeneity of exacerbations and habituation to symptoms.,Feelings of fear, perceived influence on exacerbation course, patient beliefs, ambivalence toward treatment, trust in health care providers and self-empowerment were identified as specific factors influencing self-management actions.,This study provided insight into factors influencing exacerbation-related self-management behavior in COPD patients.,The conceptual model can be used as a framework for health care professionals providing self-management support.,In the development of future self-management interventions, factors influencing the process of exacerbation-related self-management should be taken into account. | 1 |
Lung hyperinflation contributes to dyspnea, morbidity and mortality in chronic obstructive pulmonary disease (COPD).,The inspiratory-to-total lung capacity (IC/TLC) ratio is a measure of lung hyperinflation and is associated with exercise intolerance.,However, knowledge of its effect on longitudinal change in the 6-min walk distance (6MWD) in patients with COPD is scarce.,We aimed to study whether the IC/TLC ratio predicts longitudinal change in 6MWD in patients with COPD.,This prospective cohort study included 389 patients aged 40-75 years with clinically stable COPD in Global Initiative for Chronic Obstructive Lung Disease stages II-IV.,The 6MWD was measured at baseline, and after one and 3 years.,We performed generalized estimating equation regression analyses to examine predictors for longitudinal change in 6MWD.,Predictors at baseline were: IC/TLC ratio, age, gender, pack years, fat mass index (FMI), fat-free mass index (FFMI), number of exacerbations within 12 months prior to inclusion, Charlson index for comorbidities, forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and light and hard self-reported physical activity.,Reduced IC/TLC ratio (p < 0.001) was a statistically significant predictor for decline in 6MWD.,With a 0.1-unit decrease in baseline IC/TLC ratio, the annual decline in 6MWD was 12.7 m (p < 0.001).,Study participants with an IC/TLC ratio in the upper quartiles maintained their 6MWD from baseline to year 3, while it was significantly reduced for the patients with an IC/TLC ratio in the lower quartiles.,Absence of light and hard physical activity, increased age and FMI, decreased FEV1 and FVC, more frequent exacerbations and higher Charlson comorbidity index were also predictors for lower 6MWD at any given time, but did not predict higher rate of decline over the timespan of the study.,Our findings demonstrated that patients with less lung hyperinflation at baseline maintained their functional exercise capacity during the follow-up period, and that it was significantly reduced for patients with increased lung hyperinflation. | Specific resistance loops appear in different shapes influenced by different resistive properties of the airways, yet their descriptive ability is compressed to a single parameter - its slope.,We aimed to develop new parameters reflecting the various shapes of the loop and to explore their potential in the characterisation of obstructive airways diseases.,Our study included 134 subjects: Healthy controls (N = 22), Asthma with non-obstructive lung function (N = 22) and COPD of all disease stages (N = 90).,Different shapes were described by geometrical and second-order transfer function parameters.,Our parameters demonstrated no difference between asthma and healthy controls groups, but were significantly different (p < 0.0001) from the patients with COPD.,Grouping mild COPD subjects by an open or not-open shape of the resistance loop revealed significant differences of loop parameters and classical lung function parameters.,Multiple logistic regression indicated RV/TLC as the only predictor of loop opening with OR = 1.157, 95% CI (1.064-1.267), p-value = 0.0006 and R2 = 0.35.,Inducing airway narrowing in asthma gave equal shape measures as in COPD non-openers, but with a decreased slope (p < 0.0001).,This study introduces new parameters calculated from the resistance loops which may correlate with different phenotypes of obstructive airways diseases. | 1 |
Tiotropium bromide has been widely used in clinical practice, while theophylline is another treatment option for chronic obstructive pulmonary disease (COPD).,However, only a few relevant studies have investigated the long-term outcomes and efficacy of both in patients with COPD.,We evaluated the effects of tiotropium and low-dose theophylline on stable COPD patients of groups B and D.,Eligible participants (n = 170) were randomized and received either tiotropium 18 µg once daily with theophylline 100 mg twice daily (Group I) or tiotropium 18 µg once daily (Group II) for 6 months.,COPD assessment test (CAT), modified Medical Research Council (mMRC) dyspnea scores and pulmonary function tests were measured before randomization and during the treatment.,After 6 months of treatment, the CAT scores in both groups decreased significantly (11.41 ± 3.56 and 11.08 ± 3.05, p < 0.0001).,The changes of CAT (p = 0.028) and mMRC scores (p = 0.049) between the two groups differed after 1 month of treatment.,In Group I, forced expiratory flow after 25% of the FVC% predicted (MEF25% pred) was significantly improved after 3 months (4.84 ± 8.73%, p < 0.0001) and 6 months (6.21 ± 8.65%, p < 0.0001).,There was a significant difference in small airway function tests (MEF50% pred, MEF25% pred, and MMEF% pred) between the two groups after 6 month of treatment (p = 0.003, p < 0.0001, and p = 0.021, respectively).,Tiotropium combined with low-dose theophylline significantly improved the symptoms and general health of patients with stable COPD of groups B and D after 6 months of follow-up.,Additionally, this therapy also improved the indicators of small airway function.,Chinese Clinical Trial Registry (Registry ID: ChiCTR1800019027).,The online version of this article (10.1007/s12325-018-0831-9) contains supplementary material, which is available to authorized users. | The aim of this paper was to propose key steps for community pharmacist integration into a patient care pathway for chronic obstructive pulmonary disease (COPD) management.,A literature search was conducted to identify publications focusing on the role of the community pharmacist in identification and management of COPD.,The literature search highlighted evidence supporting an important role for pharmacists at each of the four key steps in the patient care pathway for COPD management.,Step 1 (primary prevention): pharmacists are ideally placed to provide information on disease awareness and risk prevention campaigns, and to encourage lifestyle interventions, including smoking cessation.,Step 2 (early detection/case finding): pharmacists are often the first point of contact between the patient and the healthcare system and can therefore play an important role in the early identification of patients with COPD.,Step 3 (management and ongoing support): pharmacists can assist patients by providing advice and education on dosage, inhaler technique, treatment expectations and the importance of adherence, and by supporting self‐management, including recognition and treatment of COPD exacerbations.,Step 4 (review and follow‐up): pharmacists can play an important role in monitoring adherence and ongoing inhaler technique in patients with COPD.,In summary, pharmacists are ideally positioned to play a vital role in all key stages of an integrated COPD patient care pathway from early disease detection to the support of management plans, including advice and counselling regarding medications, inhaler technique and treatment adherence.,Areas requiring additional consideration include pharmacist training, increasing awareness of the pharmacist role, administration and reimbursement, and increasing physician-pharmacist collaboration. | 1 |
Chronic obstructive pulmonary disease (COPD) is a major global health problem.,It results from chronic inflammation and causes irreversible airway damage.,Levels of different serum cytokines could be surrogate biomarkers for inflammation and lung function in COPD.,We aimed to determine the serum levels of different biomarkers in COPD patients, the association between cytokine levels and various prognostic parameters, and the key pathways/networks involved in stable COPD.,In this study, serum levels of 48 cytokines were examined by multiplex assays in 30 subjects (control, n=9; COPD, n=21).,Relationships between serum biomarkers and forced expiratory volume in 1 second, peak oxygen uptake, body mass index, dyspnea score, and smoking were assessed.,Enrichment pathways and network analyses were implemented, using a list of cytokines showing differential expression between healthy controls and patients with COPD by Cytoscape and GeneGo Metacore™ software (Thomson-Reuters Corporation, New York, NY, USA).,Concentrations of cutaneous T-cell attracting chemokine, eotaxin, hepatocyte growth factor, interleukin 6 (IL-6), IL-16, and stem cell factor are significantly higher in COPD patients compared with in control patients.,Notably, this study identifies stem cell factor as a biomarker for COPD.,Multiple regression analysis predicts that cutaneous T-cell-attracting chemokine, eotaxin, IL-6, and stem cell factor are inversely associated with forced expiratory volume in 1 second and peak oxygen uptake change, whereas smoking is related to eotaxin and hepatocyte growth factor changes.,Enrichment pathways and network analyses reveal the potential involvement of specific inflammatory and immune process pathways in COPD.,Identified network interaction and regulation of different cytokines would pave the way for deeper insight into mechanisms of the disease process. | Osteoporosis is common in patients with COPD but the likely multi-factorial causes contributing to this condition (e.g. sex, age, smoking, therapy) mask the potential contribution from elements related to COPD.,In order to study osteoporosis and bone mineral density (BMD) related to COPD, we studied a well-defined group of patients and controls.,BMD, forced expiratory volume in one second (FEV1), circulating bone biomarkers and biochemistry were determined in 30 clinically stable male ex-smokers with confirmed COPD and 15 age matched "ex-smoker" male controls.,None of the patients were on inhaled corticosteroids or received more than one short course of steroids.,Mean (SD) FEV1% predicted of patients was 64(6)%, the majority having Global Initiative for Chronic Obstructive Lung Disease (GOLD) II airflow obstruction.,There were 5/30 patients and 1/15 controls who were osteoporotic, while a further 17 patients and 5 controls were osteopenic.,The BMD at the hip was lower in patients than controls, but not at the lumbar spine.,Mean values of procollagen type 1 amino-terminal propeptide and osteocalcin, both markers of bone formation, and Type 1 collagen β C-telopeptide, a marker of bone resorption, were similar between patients and controls.,However, all bone biomarkers were inversely related to hip BMD in patients (r = -0.51, r = -0.67, r = -0.57, p < 0.05) but did not relate to lumbar spine BMD.,25-OH Vitamin D was lower in patients.,Men with COPD had a greater prevalence of osteoporosis and osteopenia than age matched male controls, with a marked difference in BMD at the hip.,Bone biomarkers suggest increased bone turnover. | 1 |
The polygenic nature of complex diseases offers potential opportunities to utilize network-based approaches that leverage the comprehensive set of protein-protein interactions (the human interactome) to identify new genes of interest and relevant biological pathways.,However, the incompleteness of the current human interactome prevents it from reaching its full potential to extract network-based knowledge from gene discovery efforts, such as genome-wide association studies, for complex diseases like chronic obstructive pulmonary disease (COPD).,Here, we provide a framework that integrates the existing human interactome information with experimental protein-protein interaction data for FAM13A, one of the most highly associated genetic loci to COPD, to find a more comprehensive disease network module.,We identified an initial disease network neighborhood by applying a random-walk method.,Next, we developed a network-based closeness approach (CAB) that revealed 9 out of 96 FAM13A interacting partners identified by affinity purification assays were significantly close to the initial network neighborhood.,Moreover, compared to a similar method (local radiality), the CAB approach predicts low-degree genes as potential candidates.,The candidates identified by the network-based closeness approach were combined with the initial network neighborhood to build a comprehensive disease network module (163 genes) that was enriched with genes differentially expressed between controls and COPD subjects in alveolar macrophages, lung tissue, sputum, blood, and bronchial brushing datasets.,Overall, we demonstrate an approach to find disease-related network components using new laboratory data to overcome incompleteness of the current interactome. | The coexistence of COPD and asthma is widely recognized but has not been well described.,This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma.,We performed a cross-sectional study comparing subjects with COPD and asthma to subjects with COPD alone in the COPDGene Study.,119 (13%) of 915 subjects with COPD reported a history of physician-diagnosed asthma.,These subjects were younger (61.3 vs 64.7 years old, p = 0.0001) with lower lifetime smoking intensity (43.7 vs 55.1 pack years, p = 0.0001).,More African-Americans reported a history of asthma (33.6% vs 15.6%, p < 0.0001).,Subjects with COPD and asthma demonstrated worse disease-related quality of life, were more likely to have had a severe COPD exacerbation in the past year, and were more likely to experience frequent exacerbations (OR 3.55 [2.19, 5.75], p < 0.0001).,Subjects with COPD and asthma demonstrated greater gas-trapping on chest CT.,There were no differences in spirometry or CT measurements of emphysema or airway wall thickness.,Subjects with COPD and asthma represent a relevant clinical population, with worse health-related quality of life.,They experience more frequent and severe respiratory exacerbations despite younger age and reduced lifetime smoking history.,ClinicalTrials.gov: NCT00608764 | 1 |
COPD is a multifactorial disease caused by environmental determinants as well as genetic risk factors.,The prevalence and mortality of COPD continue to increase, and underdiagnosis of COPD remains a critical issue.,Previous reports investigated promising microRNAs (miRNAs) to reveal the molecular mechanism for the development of COPD; however, diagnostic and therapeutic markers for COPD have not yet been found.,For this study, 20 representative COPD patients were separated into four groups based on increasing severity (A, B, C, and D) and compared to six healthy controls.,Small RNA profiles of peripheral leukocytes were differentially expressed miRNAs (analyzed via next-generation sequencing) were validated via quantitative reverse transcriptase-polymerase chain reaction.,Compared to healthy controls, 19 differentially expressed miRNAs were found in COPD patients.,For all COPD groups, miR-3177-3p was downregulated, while 17 miRNAs were upregulated.,Furthermore, the results revealed 21 differentially expressed miRNAs, of which miR-183-5p was continually downregulated from A to B to D.,Between respective bronchodilator reversibility positive and negative groups of COPD different groups (A, B, C, and D), 10 miRNAs were differentially expressed, while miR-100-5p was upregulated in the negative groups.,In conclusion, miR-106b-5p, miR-125a-5p, miR-183-5p, and miR-100-5p are central for the development of COPD.,The severity of COPD was attenuated by miR-106b-5p, thus suggesting this miRNA as potential target for disease treatment. | A core feature of chronic obstructive pulmonary disease (COPD) is the accelerated decline in forced expiratory volume in one second (FEV1).,The recent Groningen and Leiden Universities study of Corticosteroids in Obstructive Lung Disease (GLUCOLD) study suggested that particular phenotypes of COPD benefit from fluticasone±salmeterol by reducing the rate of FEV1 decline, yet the underlying mechanisms are unknown.,Whole-genome gene expression profiling using the Affymetrix Gene ST array (V.1.0) was performed on 221 bronchial biopsies available from 89 COPD patients at baseline and after 6 and 30 months of fluticasone±salmeterol and placebo treatment in GLUCOLD.,Linear mixed effects modelling revealed that the expression of 138 genes decreased, whereas the expression of 140 genes significantly upregulated after both 6 and 30 months of treatment with fluticasone±salmeterol versus placebo.,A more pronounced treatment-induced change in the expression of 50 and 55 of these 278 genes was associated with a lower rate of decline in FEV1 and Saint George Respiratory Questionnaire, respectively.,Genes decreasing with treatment were involved in pathways related to cell cycle, oxidative phosphorylation, epithelial cell signalling, p53 signalling and T cell signalling.,Genes increasing with treatment were involved in pathways related to focal adhesion, gap junction and extracellular matrix deposition.,Finally, the fluticasone-induced gene expression changes were enriched among genes that change in the airway epithelium in smokers with versus without COPD in an independent data set.,The present study suggests that gene expression in biological pathways of COPD is dynamic with treatment and reflects disease activity.,This study opens the gate to targeted and molecular phenotype-driven therapy of COPD. | 1 |
Greece has one of the highest rates of smoking and chronic obstructive pulmonary disease (COPD) in Europe.,The study aimed to record both the disease characteristics among a sample of Greek COPD patients and the nationwide rates of newly diagnosed COPD cases.,In this noninterventional, epidemiological cross-sectional study, a representative nationwide sample of 45 respiratory centers provided data on the following: 1) the demographic and clinical characteristics of COPD patients and 2) newly diagnosed COPD cases monitored over a period of 6 months by each physician.,Data from 6,125 COPD patients were collected.,Advanced age (median age: 68 years), male predominance (71.3%), largely overweight status with median body mass index (BMI) =27.5 kg/m2, high percentage of current and ex-smokers (89.8%), and presence of comorbidities (81.9%) were evident in the sample.,According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 criteria, majority of the COPD patients had moderate or severe airflow limitation (61%).,Severity of airflow limitation was significantly associated with older age, male sex, obesity, ex-smoking status, and presence of comorbidity (all P-values <0.001).,A total of 61.3% of the patients received medication, mostly bronchodilators (64.4%) and fixed-dose combinations of long-acting β2-agonists and inhaled corticosteroids (39.9%), while 35.9% reported taking medication on demand.,The majority (81.1%) of patients reported a preference for fewer inhalations of their bronchodilator therapy.,Based on the mixed-effect Poisson model, the rate of newly diagnosed COPD cases was estimated to be 18.2% (95% confidence interval: 14.9-22.3) per pulmonologist/3 months.,Of those newly diagnosed, the majority of patients had mild or moderate airflow limitation (78.2%).,The Greek Obstructive Lung Disease Epidemiology and health ecoNomics study reflected the real-life profile of COPD patients and provided evidence on the profile of new COPD cases in Greece.,Various demographic factors were delineated, which can assist in designing more effective diagnostic and management strategies for COPD in Greece. | To investigate the magnitude of barriers in access to health services for chronic patients and the socioeconomic and demographic characteristics that affect them.,A cross-sectional study was conducted in 1,594 chronic patients suffering from diabetes, hypertension, COPD and Alzheimer.,Logistic regression analyses were carried out in order to explore the factors related to economic and geographical barriers in access, as well as the determinants of barriers due to waiting lists.,A total of 25% of chronic patients face geographical barriers while 63.5% and 58.5% of them are in front of economic and waiting list barriers, respectively.,Unemployed, low-income and low-educated are more likely to face economic barriers in access.,Moreover, women, low-income patients, and patients with lower health status are more likely to be in front of geographical barriers.,In addition, the probability of waiting lists occurrence is greater for unemployed, employees and low income patients.,Barriers in access can be mainly attributed to income decrease and unemployment.,In this context, health policy measures are essential for removing barriers in access.,Otherwise, inequalities may increase and chronic patients’ health status will be deteriorated.,These consequences imply adverse effects on health expenditure. | 1 |
Chronic obstructive pulmonary disease (COPD) and lung cancer, closely related to smoking, are major lung diseases affecting millions of individuals worldwide.,The generated gas mixture of smoking is proved to contain about 4,500 components such as carbon monoxide, nicotine, oxidants, fine particulate matter, and aldehydes.,These components were considered to be the principle factor driving the pathogenesis and progression of pulmonary disease.,A large proportion of lung cancer patients showed a history of COPD, which demonstrated that there might be a close relationship between COPD and lung cancer.,In the early stages of smoking, lung barrier provoked protective response and DNA repair are likely to suppress these changes to a certain extent.,In the presence of long-term smoking exposure, these mechanisms seem to be malfunctioned and lead to disease progression.,The infiltration of inflammatory cells to mucosa, submucosa, and glandular tissue caused by inhaled cigarette smoke is responsible for the destruction of matrix, blood supply shortage, and epithelial cell death.,Conversely, cancer cells have the capacity to modulate the proliferation of epithelial cells and produce of new vascular networks.,Comprehension understanding of mechanisms responsible for both pathologies is necessary for the prevention and treatment of COPD and lung cancer.,In this review, we will summarize related articles and give a glance of possible mechanism between cigarette smoking induced COPD and lung cancer. | Chronic obstructive pulmonary disease (COPD) is associated with increased lung cancer risk.,We evaluated the association of statin use with lung cancer risk in COPD patients and identified which statins possess the highest chemopreventive potential.,After adjustment for age, sex, CCI, diabetes, hypertension, dyslipidemia, urbanization level, and monthly income according to propensity scores, lung cancer risk in the statin users was lower than that in the statin nonusers (adjusted hazard ratio [aHR] = 0.37).,Of the individual statins, lovastatin and fluvastatin did not reduce lung cancer risk significantly.,By contrast, lung cancer risk in patients using rosuvastatin, simvastatin, atorvastatin, and pravastatin was significantly lower than that in statin nonusers (aHRs = 0.41, 0.44, 0.52, and 0.58, respectively).,Statins dose-dependently reduced lung cancer risk in all subgroups and the main model with additional covariates (nonstatin drug use).,The study cohort comprised all patients diagnosed with COPD at health care facilities in Taiwan (n = 116,017) between January 1, 2001 and December 31, 2012.,Our final study cohort comprised 43,802 COPD patients: 10,086 used statins, whereas 33,716 did not.,Patients were followed up to assess lung cancer risk or protective factors.,In addition, we also considered demographic characteristics, namely age, sex, comorbidities (diabetes, hypertension, dyslipidemia, and Charlson comorbidity index [CCI]), urbanization level, monthly income, and nonstatin drug use.,The index date of statin use was the COPD confirmation date.,To examine the dose-response relationship, we categorized statin use into four groups in each cohort: < 28, 28-90, 91-365, and > 365 cumulative defined daily doses (cDDDs).,Patients receiving < 28 cDDDs were defined as nonstatin users.,Statins dose-dependently exert a significant chemopreventive effect against lung cancer in COPD patients.,Rosuvastatin, simvastatin, and atorvastatin exhibited the highest chemopreventive potential. | 1 |
Drugs for inhalation are the cornerstone of therapy in obstructive lung disease.,We have observed that up to 75 % of patients do not perform a correct inhalation technique.,The inability of patients to correctly use their inhaler device may be a direct consequence of insufficient or poor inhaler technique instruction.,The objective of this study is to test the efficacy of two educational interventions to improve the inhalation techniques in patients with Chronic Obstructive Pulmonary Disease (COPD).,This study uses both a multicenter patients´ preference trial and a comprehensive cohort design with 495 COPD-diagnosed patients selected by a non-probabilistic method of sampling from seven Primary Care Centers.,The participants will be divided into two groups and five arms.,The two groups are: 1) the patients´ preference group with two arms and 2) the randomized group with three arms.,In the preference group, the two arms correspond to the two educational interventions (Intervention A and Intervention B) designed for this study.,In the randomized group the three arms comprise: intervention A, intervention B and a control arm.,Intervention A is written information (a leaflet describing the correct inhalation techniques).,Intervention B is written information about inhalation techniques plus training by an instructor.,Every patient in each group will be visited six times during the year of the study at health care center.,Our hypothesis is that the application of two educational interventions in patients with COPD who are treated with inhaled therapy will increase the number of patients who perform a correct inhalation technique by at least 25 %.,We will evaluate the effectiveness of these interventions on patient inhalation technique improvement, considering that it will be adequate and feasible within the context of clinical practice.,Current Controlled Trials ISRTCTN15106246 | Although medical treatment of COPD has advanced, nonadherence to medication regimens poses a significant barrier to optimal management.,Underuse, overuse, and improper use continue to be the most common causes of poor adherence to therapy.,An average of 40%-60% of patients with COPD adheres to the prescribed regimen and only 1 out of 10 patients with a metered dose inhaler performs all essential steps correctly.,Adherence to therapy is multifactorial and involves both the patient and the primary care provider.,The effect of patient instruction on inhaler adherence and rescue medication utilization in patients with COPD does not seem to parallel the good results reported in patients with asthma.,While use of a combined inhaler may facilitate adherence to medications and improve efficacy, pharmacoeconomic factors may influence patient’s selection of both the device and the regimen.,Patient’s health beliefs, experiences, and behaviors play a significant role in adherence to pharmacological therapy.,This manuscript reviews important aspects associated with medication adherence in patients with COPD and identifies some predictors of poor adherence. | 1 |
AMPLIFY assessed the efficacy and safety of aclidinium bromide/formoterol fumarate (AB/FF) vs its monocomponents and tiotropium (TIO) in patients with moderate-to-very severe symptomatic COPD (NCT02796677).,In this 24-week, Phase III, double-dummy, active-controlled study, symptomatic patients (COPD Assessment Test score ≥10) were randomized to twice-daily AB/FF 400/12 µg, AB 400 µg, or FF 12 µg, or once-daily TIO 18 µg.,Co-primary endpoints were change from baseline at week 24 in 1-hour morning post-dose FEV1 (AB/FF vs AB) and in pre-dose (trough) FEV1 (AB/FF vs FF).,Non-inferiority of AB vs TIO in pre-dose FEV1 was also an objective.,Normalized area under the curve (AUC)0-3/3 h FEV1 and nighttime and early morning symptoms were also assessed.,A subgroup participated in a 24-hour serial spirometry sub-study.,A total of 1,594 patients were randomized; 566 entered the sub-study.,At week 24, 1-hour post-dose FEV1 significantly improved with AB/FF vs AB, FF, and TIO (84, 84, and 92 mL; all P<0.0001).,AB/FF significantly improved trough FEV1 vs FF (55 mL, P<0.001) and AB was non-inferior to TIO.,AB/FF significantly improved AUC0-3/3 h FEV1 vs all comparators (P<0.0001) and provided significant improvements in early morning symptoms vs TIO.,The 24-hour spirometry demonstrated significantly greater improvements with AB/FF in AUC12-24/12 h vs all comparators, and in AUC0-24/24 h vs FF or TIO at week 24.,In patients with moderate-to-very severe symptomatic COPD, twice-daily AB/FF significantly improved lung function vs monocomponents and TIO, and early morning symptom control vs TIO. | To determine the efficacy and safety of glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI 36/9.6, 36/7.2, 18/9.6, 9/9.6 µg) using innovative co-suspension delivery technology, compared with glycopyrrolate (GP) MDI 36 µg and formoterol fumarate (FF) MDI 9.6 µg, in patients with moderate-to-severe COPD.,In this Phase IIb, randomized, double-blind, balanced incomplete-block, two-period, cross-over study (NCT01349816), patients received treatment twice-daily for 7 days.,The primary efficacy endpoint was forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 12 hours (AUC0-12) on Day 7.,Secondary efficacy endpoints were peak change from baseline in FEV1 through 2 hours; time to onset of action (≥10% improvement in mean FEV1); proportion of patients achieving ≥12% improvement in FEV1 on Day 1; peak change from baseline in inspiratory capacity (IC) on Days 1 and 7; change from baseline in morning pre-dose FEV1; peak change from baseline in FEV1 through 6 hours; and change from baseline in mean evening 12-hour post-dose trough FEV1 on Day 7.,Safety was assessed.,All 185 randomized patients received treatment.,All doses of GFF MDI significantly improved the primary endpoint compared with GP MDI 36 µg (all P≤0.0137).,For peak change in FEV1 and IC and time to onset of action secondary endpoints, ≥2 doses of GFF MDI demonstrated superiority to GP MDI 36 µg.,No significant differences were observed between GFF MDI and FF MDI 9.6 µg for primary and secondary endpoints.,The incidence of adverse events was similar between treatments.,While all doses of GFF MDI were superior to GP MDI 36 µg for the primary end-point, in this study neither superiority of GFF MDI to FF MDI 9.6 µg nor a clear dose-response was observed.,All treatments were well tolerated with no unexpected safety findings. | 1 |
Oxidative stress (OS) plays a key role in the muscle impairment and exercise capacity of COPD patients.,However, the literature reveals that systemic OS markers show great heterogeneity, which may hinder the prescription of effective antioxidant supplementation.,This study therefore aimed to identify OS markers imbalance of COPD patients, relative to validated normal reference values, and to investigate the possibility of systemic OS profiles.,We measured systemic enzymatic/nonenzymatic antioxidant and lipid peroxidation (LP) levels in 54 stable COPD patients referred for a rehabilitation program.,The main systemic antioxidant deficits in these patients concerned vitamins and trace elements.,Fully 89% of the COPD patients showed a systemic antioxidant imbalance which may have caused the elevated systemic LP levels in 69% of them.,Interestingly, two patient profiles (clusters 3 and 4) had a more elevated increase in LP combined with increased copper and/or decreased vitamin C, GSH, and GPx.,Further analysis revealed that the systemic LP level was higher in COPD women and associated with exercise capacity.,Our present data therefore support future supplementations with antioxidant vitamins and trace elements to improve exercise capacity, but COPD patients will probably show different positive responses. | Recent studies described association between chronic obstructive pulmonary disease (COPD) and increased risk of cardiovascular diseases (CVD).,In their analysis none of these studies accounted for sociodemographic factors, health behaviors, and patient comorbidities simultaneously.,To study whether COPD diagnosis is an independent risk factor for CVD.,Subjects aged 40 years and older (N = 18,342) from the sample adult file of the 2002 National Health Interview Survey (NHIS) were included in the analysis.,Chi-squared tests and odds ratios (OR) were utilized to compare the data.,Multiple logistic regression was employed to analyze the association between COPD and CVD with simultaneous control for sociodemographic factors (age, gender, race, marital status, education, income), health behaviors (tobacco use, alcohol consumption, physical activity), and patient comorbidities (diabetes, hypertension, high cholesterol, and obesity).,The analysis employed NHIS sampling weights to generate data representative of the entire US population.,The COPD population had increased prevalence of CVD (56.5% vs 25.6%; P < 0.0001).,Adjusted logistic regression showed that COPD patients (N = 958) were at higher risk of having coronary heart disease (OR = 2.0, 95% CI: 1.5-2.5), angina (OR = 2.1, 95% CI: 1.6-2.7), myocardial infarction (OR = 2.2, 95% CI: 1.7-2.8), stroke (OR = 1.5, 95% CI: 1.1-2.1), congestive heart failure (OR = 3.9, 95% CI: 2.8-5.5), poor circulation in lower extremities (OR = 2.5, 95% CI: 2.0-3.0), and arrhythmia (OR = 2.4, 95% CI: 2.0-2.8).,Overall, the presence of COPD increased the odds of having CVD by a factor of 2.7 (95% CI: 2.3-3.2).,These findings support the conclusion that COPD is an independent risk factor for CVD. | 1 |
The rate of obesity is increasing in Asia, but the clinical impact of body mass index (BMI) on the outcome of chronic obstructive pulmonary disease (COPD) remains unknown.,We aimed to assess this impact while focusing on the risk of exacerbation, health-care utilization, and medical costs.,We examined 43,864 subjects registered in the Korean National Health and Nutrition Examination Survey (KNHANES) database from 2007 to 2012, and linked the data of COPD patients who had mild to moderate airflow obstruction (n = 1,320) to National Health Insurance (NHI) data.,COPD was confirmed by spirometry.,BMI was used to stratify patients into four categories: underweight (BMI <18.5 kg/m2), normal range (18.5-22.9 kg/m2), overweight (23-24.9 kg/m2), and obese (≥25 kg/m2).,Of the 1,320 patients with COPD with mild to moderate airflow obstruction, 27.8% had a BMI ≥25 kg/m2.,Compared with normal-weight patients, obese patients tended to experience fewer exacerbations (incidence rate ratio [IRR] 0.88; 95% CI 0.77-0.99; P = 0.04), although this association was not significant in a multivariable analysis.,COPD-related health-care utilization and medical expenses were higher among underweight patients than the other groups.,After adjustment, the risk of COPD-related hospitalization was highest among underweight and higher among overweight patients vs normal-weight patients (adjusted IRRs: 7.12, 1.00, 1.26, and 1.02 for underweight, normal, overweight, and obese groups, respectively; P = 0.01).,Decreased weight tends to negatively influence prognosis of COPD with mild to moderate airflow obstruction, whereas higher BMI was not significantly related to worse outcomes. | Chronic bronchitis and previous exacerbations are both well-known risk factors for new exacerbations, impaired health-related quality of life, and increased mortality in COPD.,The aim of the study was to characterize the phenotype of concurrent chronic bronchitis and frequent exacerbation in severe COPD.,Information on patient characteristics, comorbidity, and exacerbations from the previous year (total number and number requiring hospitalization) was collected from 373 patients with stage III and IV COPD attending 27 secondary care respiratory units in Sweden.,Logistic regression used chronic bronchitis and frequent exacerbations (≥2 exacerbations or ≥1 hospitalized exacerbations in the previous year) as response variables.,Stratification and interaction analyses examined effect modification by sex.,Chronic bronchitis was associated with current smoking (adjusted odds ratio [OR] [95% CI], 2.75 [1.54-4.91]; P=0.001), frequent exacerbations (OR [95% CI], 1.93 [1.24-3.01]; P=0.004), and musculoskeletal symptoms (OR [95% CI], 1.74 [1.05-2.86]; P=0.031), while frequent exacerbations were associated with lung function (forced expiratory volume in 1 second as a percentage of predicted value [FEV1% pred]) (OR [95% CI] 0.96 [0.94-0.98]; P=0.001) and chronic bronchitis (OR [95% CI] 1.73 [1.11-2.68]; P=0.015).,The phenotype with both chronic bronchitis and frequent exacerbations was associated with FEV1% pred (OR [95% CI] 0.95 [0.92-0.98]; P=0.002) and musculoskeletal symptoms (OR [95% CI] 2.55 [1.31-4.99]; P=0.006).,The association of smoking with the phenotype of chronic bronchitis and exacerbations was stronger in women than in men (interaction, P=0.040).,Musculoskeletal symptoms and low lung function are associated with the phenotype of combined chronic bronchitis and frequent exacerbations in severe COPD.,In women, current smoking is of specific importance for this phenotype.,This should be considered in clinical COPD care. | 1 |
Heme oxygenase-1 (HO-1) plays a protective role as an antioxidant in the lung, and HO-1 gene promoter polymorphism has been shown to be associated with the severity and prognosis of COPD patients.,N-acetylcysteine (NAC), an antioxidant/mucous modifier, has shown an uncertain benefit in COPD patients.,We hypothesized that this polymorphism could be associated with the effectiveness of oral NAC.,A total of 368 patients with COPD were recruited and the polymorphisms of their HO-1 gene promoter were classified into three subclasses according to the number of (GT)n repeats, as previously reported: class S (<27 (GT)n repeats), class M (27-32 (GT)n repeats), and class L (>32 (GT)n repeats).,These subjects were then classified as L+ group (with the L allele: L/L, L/M, L/S) and L− group (without the L allele: M/M, M/S, S/S).,All the patients were allocated to standard therapy plus NAC 600 mg bid over a 1-year period and were observed over that year.,The L− group saw improvements in forced expiratory volume in 1 second (FEV1) (from 1.44±0.37 to 1.58±0.38, P=0.04) and FEV1% predicted (from 56.6±19.2 to 59.7±17.2, P=0.03).,No improvement was found in forced vital capacity of each group and the decline of forced vital capacity in both of the groups was not statistical significant.,The number of yearly COPD exacerbations of the L− group was 1.5±0.66 which was lower than the 2.1±0.53 of the L+ group (P<0.01).,For the changes of St George’s Respiratory Questionnaire (SGRQ) score, only the activity score of the L− group was more significant than that of the L+ group (P=0.02).,The improvement of the outcome of 6-minute walking distance test in L− group (from 290.1±44.9 meters to 309.7±46.9 m) was higher than that in the L+ group (from 289.7±46.2 m to 300.3±44.2 m) (P=0.03).,A 600 mg bid oral NAC treatment for 1-year on COPD patients without the L allele can improve the FEV1, FEV1% predicted, the SGRQ activity score, and the result of 6-minute walking distance test, and the exacerbation rate of the L allele carrier in COPD patients is much higher than in the COPD patients without the L allele. | The prevalence of metabolic syndrome in COPD patients and its impact on patient related outcomes has been little studied.,We evaluated the prevalence of metabolic syndrome and clinical and functional characteristics in patients with COPD and healthy subjects.,228 COPD patients and 156 healthy subjects were included.,Metabolic syndrome was defined using criteria of the IDF.,In all patients spirometry, body composition, functional exercise performance, and mood and health status were assessed.,Groups were stratified for BMI and gender.,Metabolic syndrome was present in 57% of the COPD patients and 40% of the healthy subjects.,After stratification for BMI, presence of metabolic syndrome in patients with a BMI ≥25 kg/m2 was higher than in healthy peers.,Patients with metabolic syndrome and a BMI <25 kg/m2 had higher BMI, fat free mass index and bone mineral density, and a lower 6MWD than the BMI matched patients without metabolic syndrome.,Spirometry, maximal ergometry, mood and health status, and blood gases were not different between those groups.,In COPD patients with metabolic syndrome self-reported co-morbidities and medication use were higher than in those without.,Metabolic syndrome is more prevalent in overweight or obese COPD patients than in BMI matched healthy subjects.,Metabolic syndrome did not additionally impact patients' functional outcomes, but did impact the prevalence of co-morbidities. | 1 |
Chronic obstructive pulmonary disease (COPD) is frequent and often coexists with other diseases.,The aim of this study was to quantify the prevalence of COPD and related chronic comorbidity among patients aged over 40 years visiting family practices in an area of Madrid.,An observational, descriptive, cross-sectional study was conducted in a health area of the Madrid Autonomous Region (Comunidad Autónoma de Madrid).,The practice population totalled 198,670 persons attended by 129 Family Physicians (FPs), and the study population was made up of persons over the age of 40 years drawn from this practice population.,Patients were deemed to have COPD if this diagnosis appeared on their clinical histories.,Prevalence of COPD; prevalence of a further 25 chronic diseases in patients with COPD; and standardised prevalence ratios, were calculated.,Prevalence of COPD in family medicine was 3.2% (95% CI 3.0-3.3) overall, 5.3% among men and 1.4% among women; 90% of patients presented with comorbidity, with a mean of 4 ± 2.04 chronic diseases per patient, with the most prevalent related diseases being arterial hypertension (52%), disorders of lipid metabolism (34%), obesity (25%), diabetes (20%) and arrhythmia (15%).,After controlling for age and sex, the observed prevalence of the following ten chronic diseases was higher than expected: heart failure; chronic liver disease; asthma; generalised artherosclerosis; osteoporosis; ischaemic heart disease; thyroid disease; anxiety/depression; arrhythmia; and obesity.,Patients with COPD, who are frequent in family practice, have a complex profile and pose a clinical and organisational challenge to FPs. | We investigated a large population of patients with chronic obstructive pulmonary disease (COPD) to determine their frequency of medication use and patterns of pharmacotherapy.,Medical and pharmacy claims data were retrospectively analyzed from 19 health plans (>7.79 million members) across the US.,Eligible patients were aged ≥40 years, continuously enrolled during July 2004 to June 2005, and had at least one inpatient or at least two outpatient claims coded for COPD.,As a surrogate for severity of illness, COPD patients were stratified by complexity of illness using predefined International Classification of Diseases, Ninth Revision, Clinical Modification, Current Procedural Terminology, Fourth Edition, and Healthcare Common Procedure Coding System codes.,A total of 42,565 patients with commercial insurance and 8507 Medicare patients were identified.,Their mean age was 54.7 years and 74.8 years, and 48.7% and 46.9% were male, respectively.,In total, 66.3% of commercial patients (n = 28,206) were not prescribed any maintenance COPD pharmacotherapy (59.1% no medication; 7.2% inhaled short-acting β2-agonist only).,In the Medicare population, 70.9% (n = 6031) were not prescribed any maintenance COPD pharmacotherapy (66.0% no medication; 4.9% short-acting β2-agonist only).,A subset of patients classified as high-complexity were similarly undertreated, with 58.7% (5358/9121) of commercial and 68.8% (1616/2350) of Medicare patients not prescribed maintenance COPD pharmacotherapy.,Only 18.0% and 9.8% of diagnosed smokers in the commercial and Medicare cohorts had a claim for a smoking cessation intervention and just 16.6% and 23.5%, respectively, had claims for an influenza vaccination.,This study highlights a high degree of undertreatment of COPD in both commercial and Medicare patients, with most patients receiving no maintenance pharmacotherapy or influenza vaccination. | 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. | Although T cells, especially CD8+, have been implicated in chronic obstructive pulmonary disease (COPD) pathogenesis, their role during acute exacerbations (AE-COPD) is uncertain.,We recruited subjects with COPD and a history of previous AE-COPD and studied them quarterly to collect blood and spontaneously expectorated sputum while stable.,During exacerbations (defined by a change in symptoms plus physician diagnosis and altered medications), we collected blood and sputum before administering antibiotics or steroids.,We used flow cytometry to identify leukocytes in peripheral blood, plus Luminex® analysis or ELISA to determine levels of inflammatory biomarkers in serum and sputum supernatants.,Of 33 enrolled subjects, 13 participated in multiple stable visits and had ≥1 AE-COPD visit, yielding 18 events with paired data.,Flow cytometric analyses of peripheral blood demonstrated decreased CD4+ and CD8+ T cells during AE-COPD (both absolute and as a percentage of all leukocytes) and significantly increased granulocytes, all of which correlated significantly with serum C-reactive protein (CRP) concentrations.,No change was observed in other leukocyte populations during AE-COPD, although the percentage of BDCA-1+ dendritic cells expressing the activation markers CD40 and CD86 increased.,During AE-COPD, sICAM-1, sVCAM-1, IL-10, IL-15 and GDF-15 increased in serum, while in sputum supernatants, CRP and TIMP-2 increased and TIMP-1 decreased.,The decrease in CD4+ and CD8+ T cells (but not other lymphocyte subsets) in peripheral blood during AE-COPD may indicate T cell extravasation into inflammatory sites or organized lymphoid tissues.,GDF-15, a sensitive marker of cardiopulmonary stress that in other settings independently predicts reduced long-term survival, is acutely increased in AE-COPD.,These results extend the concept that AE-COPD are systemic inflammatory events to which adaptive immune mechanisms contribute.,NCT00281216, ClinicalTrials.gov.,The online version of this article (doi:10.1186/s12931-015-0251-1) contains supplementary material, which is available to authorized users. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) often experience depression and anxiety, but little information is available regarding Chinese patients with these conditions.,The present study assessed depression and anxiety in Chinese patients with COPD.,A case-controlled study was designed with 1100 patients with COPD enrolled in the case group and1100 residents without COPD and respiratory symptoms selected as the control group.,Anxiety and depression in both groups were evaluated using the Hospital Anxiety and Depression Scale (HADS).,The body mass index,degree of airflow obstruction, dyspnea, and exercise capacity (BODE ) index was used to assess COPD severity.,Binary logistic regression models were used to test the association between anxiety and depression.,The patients with COPD were more likely than controls to experience depression (cases, HADS 10.5 ± 3.6, prevalence 35.7%; controls, HADS 8.7 ± 2.7, prevalence 7.2%) and anxiety (cases, HADS 10.4 ± 3.1, prevalence 18.3%; controls, HADS 8.6 ± 2.1, prevalence 5.3%).,Subjects with anxious and depressive symptoms had poorer health outcomes including a higher BODE index, a shorter 6-minute-walk distance (6MWD), more dyspnea, and a higher St George’s respiratory questionnaire (SGRQ) score.,The prevalence of anxious and depressive symptoms increased with increasing BODE scores.,On the basis of binary logistic regression, the BODE index was significantly correlated with anxiety (OR = 1.47, p < 0.001) and depression (OR = 1.51, p < 0.001).,Anxious and depressive symptoms were also associated with several factors including younger age, female sex, higher education level, lower household income and history of smoking.,This study confirmed the high prevalence of anxiety and depression in Chinese outpatients with COPD.,Patients with COPD who had anxiety and/or depression had a poorer health-related quality of life.,Chinese Clinical Trials Registration(ChiCTR-TRC-12001958) | COPD patients may be at increased risk for vitamin D (25(OH)D) deficiency, but risk factors for deficiency among COPD patients have not been extensively reported.,Serum 25(OH)D levels were measured by liquid chromatography double mass spectrometry in subjects aged 40-76 years from Western Norway, including 433 COPD patients (GOLD stage II-IV) and 325 controls.,Levels <20 ng/mL defined deficiency.,Season, sex, age, body mass index (BMI), smoking, GOLD stage, exacerbation frequency, arterial oxygen tension (PaO2), respiratory symptoms, depression (CES-D score≥16), comorbidities (Charlson score), treatment for osteoporosis, use of inhaled steroids, and total white blood count were examined for associations with 25(OH)D in both linear and logistic regression models.,COPD patients had an increased risk for vitamin D deficiency compared to controls after adjustment for seasonality, age, smoking and BMI.,Variables associated with lower 25(OH)D levels in COPD patients were obesity ( = −6.63), current smoking ( = −4.02), GOLD stage III- IV ( = −4.71, = −5.64), and depression ( = −3.29).,Summertime decreased the risk of vitamin D deficiency (OR = 0.22).,COPD was associated with an increased risk of vitamin D deficiency, and important disease characteristics were significantly related to 25(OH)D levels. | 1 |
Inhaled corticosteroids (ICS) are known to increase the risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD).,It is unclear whether the risk of pneumonia varies for different inhaled agents, particularly fluticasone and budesonide, and increases with the dose and long-term duration of use.,We formed a new-user cohort of patients with COPD treated during 1990-2005.,Subjects were identified using the Quebec health insurance databases and followed through 2007 or until a serious pneumonia event, defined as a first hospitalisation for or death from pneumonia.,A nested case-control analysis was used to estimate the rate ratio (RR) of serious pneumonia associated with current ICS use, adjusted for age, sex, respiratory disease severity and comorbidity.,The cohort included 163 514 patients, of which 20 344 had a serious pneumonia event during the 5.4 years of follow-up (incidence rate 2.4/100/year).,Current use of ICS was associated with a 69% increase in the rate of serious pneumonia (RR 1.69; 95% CI 1.63 to 1.75).,The risk was sustained with long-term use and declined gradually after stopping ICS use, disappearing after 6 months (RR 1.08; 95% CI 0.99 to 1.17).,The rate of serious pneumonia was higher with fluticasone (RR 2.01; 95% CI 1.93 to 2.10), increasing with the daily dose, but was much lower with budesonide (RR 1.17; 95% CI 1.09 to 1.26).,ICS use by patients with COPD increases the risk of serious pneumonia.,The risk is particularly elevated and dose related with fluticasone.,While residual confounding cannot be ruled out, the results are consistent with those from recent randomised trials. | Seasonal variations in the acute exacerbation of chronic obstructive pulmonary disease (COPD) have been reported.,However, the influence of air temperature and other meteorological factors on COPD exacerbation remains unclear.,National Health Insurance registry data from January 1, 1999 to December 1, 2009 and meteorological variables from the Taiwan Central Weather Bureau for the same period were analyzed.,A case-crossover study design was used to investigate the association between COPD exacerbation and meteorological variables.,A total of 16,254 cases who suffered from COPD exacerbation were enrolled.,We found that a 1°C decrease in air temperature was associated with a 0.8% increase in the exacerbation rate on event-days (95% confidence interval (CI), 1.015-1.138, p = 0.015).,With a 5°C decrease in mean temperature, the cold temperature (28-day average temperature) had a long-term effect on the exacerbation of COPD (odds ratio (OR), 1.106, 95% CI 1.063-1.152, p<0.001).,In addition, elderly patients and those who did not receive inhaled medication tended to suffer an exacerbation when the mean temperature dropped 5°C.,Higher barometric pressure, more hours of sunshine, and lower humidity were associated with an increase in COPD exacerbation.,This study demonstrated the effect of cold temperatures on the COPD exacerbation rate.,Elderly patients and those without inhaled medicine before the exacerbation event were affected significantly by lower mean temperatures.,A more comprehensive program to prevent cold stress in COPD patients may lead to a reduction in the exacerbations rate of COPD. | 1 |
Data examining the characteristics of patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD) and associated hospitalisations and mortality are scarce.,Post-hoc analysis of the Prevention Of Exacerbations with Tiotropium in COPD (POET-COPD) trial, targeting exacerbations as the primary endpoint.,Patients were classified as non-, infrequent, and frequent exacerbators (0, 1, or ≥ 2 exacerbations during study treatment), irrespective of study treatment.,A multivariate Cox regression model assessed the effect of covariates on time to first exacerbation.,In total, 7376 patients were included in the analysis: 63.5% non-exacerbators, 22.9% infrequent, 13.6% frequent exacerbators.,Factors significantly associated with exacerbation risk were age, sex, body mass index, COPD duration and severity, smoking history, baseline inhaled corticosteroid use, and preceding antibiotic or systemic corticosteroid courses.,Frequent exacerbators had greater severity and duration of COPD, received more pulmonary medication, and ≥ 2 systemic corticosteroid or antibiotic courses in the preceding year, and were more likely to be female and ex-smokers.,The small proportion of frequent exacerbators (13.6%) accounted for 56.6% of exacerbation-related hospitalisations, which, overall, were associated with a three-fold increase in mortality.,The frequent exacerbator phenotype was closely associated with exacerbation-related hospitalisations, and exacerbation-related hospitalisations were associated with poorer survival.,NCT00563381; Study identifier: BI 205.389. | Chronic obstructive lung disease (COPD) exacerbations are a significant cause of morbidity and mortality.,Data regarding factors which causes or prevents exacerbations is very limited.,The aim of this systematic review is to summarize the results from available studies to identify potential risk factors for hospital admission and/or re-admission among patients experiencing COPD exacerbations.,We undertook a systematic review of the literature.,Potential studies were identified by searching the electronic databases: PubMed, EMBASE, BIOSIS, CINAHL, PsycINFO, Cochrane library, reference lists in trial reports, and other relevant articles.,Seventeen articles that met the predefined inclusion criteria were identified.,Heterogeneity of study designs, risk factors and outcomes restrict the result to only a systematic review and precluded a formal meta-analysis.,In this review, three predictive factors: previous hospital admission, dyspnea and oral corticosteroids were all found to be significant risk factors of readmissions and variables including using long term oxygen therapy, having low health status or poor health related quality of life and not having routine physical activity were all associated with an increased risk of both admission and readmission to hospital.,There are a number of potential modifiable factors that are independently associated with a higher risk of COPD exacerbation requiring admission/readmission to the hospital.,Identifying these factors and the development of targeted interventions could potentially reduce the number and severity of such exacerbations. | 1 |
To study exposure-response relations between cumulative organic dust exposure and incident chronic obstructive pulmonary disease (COPD) among subjects employed in the Danish farming and wood industry.,We studied exposure-response relations between cumulative organic dust exposure and incident COPD (1997-2013) among individuals born during 1950-1977 in Denmark ever employed in the farming or wood industry (n=1 75 409).,Industry-specific employment history (1964-2007), combined with time-dependent farming and wood industry-specific exposure matrices defined cumulative exposure.,We used logistic regression analysis with discrete survival function adjusting for age, sex and calendar year.,Adjustment for smoking status was explored in a subgroup of 4023 with smoking information available.,Cumulative organic dust exposure was inversely associated with COPD (adjusted rate ratios (RRadj (95% CIs) of 0.90 (0.82 to 0.99), 0.76 (0.69 to 0.84) and 0.52 (0.47 to 0.58) for intermediate-low, intermediate-high and high exposure quartiles, respectively, compared with the lowest exposure quartile).,Lagging exposure 10 years was not consistently suggestive of an association between cumulative exposure and COPD; RRadj (95% CI): 1.05 (0.94 to 1.16), 0.92 (0.83 to 1.02) and 0.63 (0.56 to 0.70).,Additional stratification by duration of employment showed no clear association between organic dust exposure and COPD except for the longer exposed (15-40 years) where an inverse association was indicated.,Subgroup analyses showed that smoking had no impact on exposure-response estimates.,Our findings show no increased risk of COPD with increasing occupational exposure to organic dust in the farming or wood industry.,Potential residual confounding by smoking can, however, not be ruled out. | Never smokers comprise a substantial proportion of patients with COPD.,Their characteristics and possible risk factors in this population are not yet well defined.,We analyzed data from 14 countries that participated in the international, population-based Burden of Obstructive Lung Disease (BOLD) study.,Participants were aged ≥ 40 years and completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors.,A diagnosis of COPD was based on the postbronchodilator FEV1/FVC ratio, according to current GOLD (Global Initiative for Obstructive Lung Disease) guidelines.,In addition to this, the lower limit of normal (LLN) was evaluated as an alternative threshold for the FEV1/FVC ratio.,Among 4,291 never smokers, 6.6% met criteria for mild (GOLD stage I) COPD, and 5.6% met criteria for moderate to very severe (GOLD stage II+) COPD.,Although never smokers were less likely to have COPD and had less severe COPD than ever smokers, never smokers nonetheless comprised 23.3% (240/1,031) of those classified with GOLD stage II+ COPD.,This proportion was similar, 20.5% (171/832), even when the LLN was used as a threshold for the FEV1/FVC ratio.,Predictors of COPD in never smokers include age, education, occupational exposure, childhood respiratory diseases, and BMI alterations.,This multicenter international study confirms previous evidence that never smokers comprise a substantial proportion of individuals with COPD.,Our data suggest that, in addition to increased age, a prior diagnosis of asthma and, among women, lower education levels are associated with an increased risk for COPD among never smokers. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular morbidity and mortality.,Elevated arterial stiffness, measured by aortic pulse wave velocity (aPWV), is a cardiovascular risk surrogate and is potentially modifiable by inhaled corticosteroid/long-acting beta2-agonist combinations in patients with COPD.,The effects of once-daily inhaled fluticasone furoate/vilanterol (FF/VI) 100/25 µg, VI 25 µg, versus placebo on arterial stiffness in patients with COPD and baseline aPWV ≥11.0 m/s were investigated in a 24-week, multicenter, double-blind, randomized, stratified (by COPD exacerbation history), parallel-group, placebo-controlled trial.,Eligible patients were ≥40 years old, with ≥10 pack-year smoking history, forced expiratory volume in 1 s (FEV1)/forced vital capacity ≤0.70, and post-bronchodilator FEV1 ≤70% of predicted.,Patients with a major cardiovascular event in the previous 6 months/current severe heart failure/uncontrolled hypertension were excluded.,Primary endpoint is change from baseline in aPWV after 24 weeks of treatment.,Safety analyses included adverse events (AEs).,The intent-to-treat population included 430 patients: FF/VI (n=135), VI (n=154), and placebo (n=141).,Patients were predominantly male (79%) and Asian or White (each 48%), with a mean age of 68.5 years (standard deviation [SD] =7.9), percentage predicted post-bronchodilator FEV1 50.1% (SD =13.3), and aPWV 13.26 m/s (SD =2.22) at screening.,At 24 weeks, mean (standard error [SE]) changes from baseline in aPWV were −1.75 m/s (SE =0.26, FF/VI), −1.95 m/s (SE =0.24, VI), and −1.97 m/s (SE =0.28, placebo).,AEs occurred in 57% (FF/VI), 51% (VI), and 41% (placebo) of patients.,No differences were observed in aPWV-adjusted mean change from baseline for FF/VI 100/25 µg, compared with placebo. | None of the drugs currently available for chronic obstructive pulmonary disease (COPD) are able to reduce the progressive decline in lung function which is the hallmark of this disease.,Smoking cessation is the only intervention that has proved effective.,The current pharmacological treatment of COPD is symptomatic and is mainly based on bronchodilators, such as selective β2-adrenergic agonists (short- and long-acting), anticholinergics, theophylline, or a combination of these drugs.,Glucocorticoids are not generally recommended for patients with stable mild to moderate COPD due to their lack of efficacy, side effects, and high costs.,However, glucocorticoids are recommended for severe COPD and frequent exacerbations of COPD.,New pharmacological strategies for COPD need to be developed because the current treatment is inadequate. | 1 |
N6‐methyladenosine (m6A) RNA methylation, the most prevalent internal chemical modification of mRNA, has been reported to participate in the progression of various tumours via the dynamic regulation of m6A RNA methylation regulators.,However, the role of m6A RNA methylation regulators in chronic obstructive pulmonary disease (COPD) has never been reported.,This study aimed to determine the expression and potential functions of m6A RNA methylation regulators in COPD.,Four gene expression data sets were acquired from Gene Expression Omnibus.,Gene ontology function, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, weighted correlation network analysis and protein‐protein interaction network analysis were performed.,The correlation analyses of m6A RNA methylation regulators and key COPD genes were also performed.,We found that the mRNA expressions of IGF2BP3, FTO, METTL3 and YTHDC2, which have the significant associations with some key genes enriched in the signalling pathway and biological processes that promote the development progression of COPD, are highly correlated with the occurrence of COPD.,In conclusion, six central m6A RNA methylation regulators could contribute to the occurrence of COPD.,This study provides important evidence for further examination of the role of m6A RNA methylation in COPD. | Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide.,Genetic risk loci provide novel insights into disease pathogenesis.,We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium.,We identified 82 loci with P-value < 5 × 10−8; 47 were previously described in association with either COPD or population-based lung function.,Of the remaining 35 novel loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium.,Using gene expression and regulation data, we identified enrichment for loci in lung tissue, smooth muscle and several lung cell types.,We found 14 COPD loci shared with either asthma or pulmonary fibrosis.,COPD genetic risk loci clustered into groups of quantitative imaging features and comorbidity associations.,Our analyses provide further support to the genetic susceptibility and heterogeneity of COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations.,This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE).,We studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers.,In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography.,COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function.,Co-morbidities were more prevalent in COPD patients than in controls, and occurred to the same extent irrespective of the GOLD stage.,The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, presence of co-morbidity, exercise capacity and number of exacerbations reported in the year before the study.,The distribution of these variables within each GOLD stage was wide.,Even in subjects with severe airflow obstruction, a substantial proportion did not report symptoms, exacerbations or exercise limitation.,The amount of emphysema increased with GOLD severity.,The prevalence of bronchiectasis was low (4%) but also increased with GOLD stage.,Some gender differences were also identified.,The clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease. | Recent reports indicate that over the next decade rates of chronic obstructive pulmonary disease (COPD) in women will exceed those in men in the western world, though in most jurisdictions, women continue to smoke less compared with men.,Whether female adult smokers are biologically more susceptible to COPD is unknown.,This study reviewed the available evidence to determine whether female adult smokers have a faster decline in forced expiratory volume in one second (FEV1) compared with male adult smokers and whether age modifies the relationship between cigarette smoke and lung function decline.,A systematic review and a meta-analysis was performed of population-based cohort studies that had a follow-up period of at least 3 years, measured FEV1 on at least two different time points, and presented FEV1 data stratified by gender and smoking status in adults.,Of the 646 potentially relevant articles, 11 studies met these criteria and were included in the analyses (N = 55 709 participants).,There was heterogeneity in gender-related results across the studies.,However, on average current smokers had a faster annual decline rate in FEV1% predicted compared with never and former smokers.,Female current smokers had with increasing age a significantly faster annual decline in FEV1% predicted than male current smokers (linear regression analysis, R2 = 0.56; p = 0.008).,Age did not materially affect the rate of decline in FEV1% predicted in male and female former and never smokers (p = 0.775 and p = 0.326, respectively).,As female smokers age, they appear to experience an accelerated decline in FEV1% predicted compared with male smokers.,Future research powered specifically on gender-related changes in lung function is needed to confirm these early findings. | 1 |
Gastroesophageal reflux disease (GERD) is one of the most common causes of chronic cough and a potential risk factor for exacerbation of chronic obstructive pulmonary disease (COPD).,The aim of this study was to investigate the prevalence and risk factors of GERD in patients with COPD and association between GERD and COPD exacerbation.,Data were collected from the National Health Insurance Database of Korea.,The subjects were 40 years old and older, who had COPD as primary or secondary diagnosis codes and utilized health care resource to receive prescriptions of COPD medication at least twice in 2009.,Univariate logistic regression was performed to understand the relationship between COPD and GERD, and multiple logistic regression analysis was performed with adjustment for several confounding factors.,The prevalence of GERD in COPD patients was 28% (39,987/141,057).,Old age, female gender, medical aid insurance type, hospitalization, and emergency room (ER) visit were associated with GERD.,Most of COPD medications except inhaled muscarinic antagonists were associated with GERD.,The logistic regression analysis showed that the presence of GERD was associated with increased risk of hospitalization (OR 1.54, CI 1.50 to 1.58, p<0.001) and frequent ER visits (OR 1.55, CI 1.48 to 1.62, p<0.001).,The prevalence of GERD in patients with COPD was high.,Old age, female gender, medical aid insurance type, and many COPD medications except inhaled muscarinic antagonists were associated with GERD.,The presence of GERD was associated with COPD exacerbation. | The aim of this study is to quantify the burden of chronic obstructive pulmonary disease (COPD) - incidence, prevalence, and mortality - and identify trends in Australia, Canada, France, Germany, Italy, Japan, The Netherlands, Spain, Sweden, the United Kingdom, and the United States of America.,A structured literature search was performed (January 2000 to September 2010) of PubMed and EMBASE, identifying English-language articles reporting COPD prevalence, incidence, or mortality.,Of 2838 articles identified, 299 full-text articles were reviewed, and data were extracted from 133 publications.,Prevalence data were extracted from 80 articles, incidence data from 15 articles, and mortality data from 58 articles.,Prevalence ranged from 0.2%-37%, but varied widely across countries and populations, and by COPD diagnosis and classification methods.,Prevalence and incidence were greatest in men and those aged 75 years and older.,Mortality ranged from 3-111 deaths per 100,000 population.,Mortality increased in the last 30-40 years; more recently, mortality decreased in men in several countries, while increasing or stabilizing in women.,Although COPD mortality increased over time, rates declined more recently, likely indicating improvements in COPD management.,In many countries, COPD mortality has increased in women but decreased in men.,This may be explained by differences in smoking patterns and a greater vulnerability in women to the adverse effects of smoking.,Point your SmartPhone at the code above.,If you have a QR code reader the video abstract will appear.,Or use: http://dvpr.es/Nl3LKT | 1 |
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