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Patients with chronic obstructive pulmonary disease (COPD) experience respiratory symptoms, which impair quality of life.,This pooled analysis of two Phase III studies assessed the impact of aclidinium/formoterol on patients with COPD categorized by symptom status.,Data were pooled from two 24-week, randomized, placebo-controlled studies of twice-daily aclidinium/formoterol 400/12 µg in moderate-to-severe COPD (ACLIFORM [NCT01462942] and AUGMENT [NCT01437397]).,These post hoc analyses evaluated the efficacy of aclidinium/formoterol versus placebo or monotherapies in patients defined as less/more symptomatic by a) Evaluating Respiratory Symptoms (E-RS™) score ≥10/<10 and b) Baseline Dyspnea Index score <7/≥7.,Endpoints included trough and 1-hour morning postdose forced expiratory volume in 1 second (FEV1), Transition Dyspnea Index, E-RS total score, early-morning and nighttime symptom severity, early-morning limitation of activities, and exacerbation rate.,Data for 3,394 patients were analyzed (mean age: 63.5 years; 60.5% male).,In both definitions of less and more symptomatic patients, aclidinium/formoterol improved 1-hour morning postdose FEV1 from baseline at week 24 versus placebo (P<0.001) and both monotherapies (P<0.05).,Aclidinium/formoterol improved trough FEV1 from baseline in both groups versus placebo (P<0.05) and formoterol (P<0.05); improvements were greater in more symptomatic patients.,Improvements versus aclidinium were also observed in more symptomatic patients (P<0.05).,Aclidinium/formoterol improved dyspnea, early-morning symptom severity, and limitation of activities versus placebo in both less and more symptomatic patients (P<0.001).,In more symptomatic patients, aclidinium/formoterol also improved E-RS total score and severity of nighttime symptoms from baseline versus placebo and one or both monotherapies (P<0.05).,The rate of moderate/severe exacerbations was reduced with aclidinium/formoterol versus placebo in more symptomatic patients.,Aclidinium/formoterol 400/12 µg provided consistent improvements in bronchodilation and symptoms versus monotherapies and reduced exacerbations versus placebo in more symptomatic patients with moderate-to-severe COPD, regardless of the definition used.,Furthermore, patients with a low symptom burden achieved benefits with aclidinium/formoterol versus monotherapies in postdose FEV1, dyspnea, and early-morning symptoms. | Chronic obstructive pulmonary disease (COPD) has traditionally been considered an inexorably progressive disease, associated with a constant increase of symptoms that occur as the forced expiratory volume in 1 second (FEV1) worsens, only intermittently interrupted by exacerbations.,However, this paradigm has been challenged in recent decades by the available evidence.,Recent studies have pointed out that COPD-related symptoms are not consistently perceived by patients in the same way, showing not only seasonal variation, but also changes in symptom perception during a week or even within a single day.,According to the available data, patients experience the biggest increase in respiratory symptoms during the first hours of the early morning, followed by the nighttime.,This variation over time is of considerable importance, since it impacts on daily life activities and health-related quality of life, as measured by a recently developed ad hoc questionnaire.,Additionally, recent clinical trials have suggested that the use of rapid-onset long-acting bronchodilators may have an impact on morning symptoms, despite their current use as maintenance treatment for a determined period.,Although this hypothesis is to be validated in future long-term clinical trials comparing fast-onset versus slow-onset inhaled drugs in COPD, it may bring forward a new concept of long-term bronchodilator therapy.,At the present time, the two available long-acting, fast-onset bronchodilators used in the treatment of COPD are formoterol and the recently marketed indacaterol.,Newer drugs have also been shown to have a rapid onset of action in preclinical studies.,Health care professionals caring for COPD patients should consider this variation in the perception of symptoms during their clinical interview as a potential new target in the long-term treatment plan. | 1 |
Adherence to medication among individuals with chronic obstructive pulmonary disease (COPD) is suboptimal and has negative impacts on survival and health care costs.,No systematic review has examined the effectiveness of interventions designed to improve medication adherence.,Electronic databases Medline and Cochrane were searched using a combination of MeSH and keywords.,Eligible studies were interventions with a primary or secondary aim to improve medication adherence among individuals with COPD published in English.,Included studies were assessed for methodological quality using the Effective Practice and Organisation of Care (EPOC) criteria.,Of the 1,186 papers identified, seven studies met inclusion criteria.,Methodological quality of the studies was variable.,Five studies identified effective interventions.,Strategies included: brief counselling; monitoring and feedback about inhaler use through electronic medication delivery devices; and multi-component interventions consisting of self-management and care co-ordination delivered by pharmacists and primary care teams.,Further research is needed to establish the most effective and cost effective interventions.,Special attention should be given to increasing patient sample size and using a common measure of adherence to overcome methodological limitations.,Interventions that involve caregivers and target the healthcare provider as well as the patient should be further explored. | Exacerbations of chronic obstructive pulmonary disease (COPD) lead to significant increases in resource utilization and cost to the health care system.,COPD patients with chronic bronchitis and a history of exacerbations pose an additional burden to the system.,This study examined health care utilization and cost among these patients.,For this retrospective analysis, data were extracted from a large national health plan with a predominantly Medicare population.,This study involved patients who were aged 40-89 years, had been enrolled continuously for 24 months or more, had at least two separate insurance claims for COPD with chronic bronchitis (International Classification of Diseases, Ninth Revision, Clinical Modification code 491.xx), and had pharmacy claims for COPD maintenance medications between January 1, 2007, and March 31, 2009.,Two years of data were examined for each patient; the index date was defined as the first occurrence of COPD.,Baseline characteristics were obtained from the first year of data, with health outcomes tracked in the second year.,Severe exacerbation was defined by COPD-related hospitalization or death; moderate exacerbation was defined by oral or parenteral corticosteroid use.,Adjusted numbers of exacerbations and COPD-related costs per patient were estimated controlling for demographic and clinical characteristics.,The final study sample involved 8554 patients; mean age was 70.1 ± 8.6 years and 49.8% of the overall population had exacerbation, 13.9% had a severe exacerbation only, 29.1% had a moderate exacerbation only, and 6.8% had both a severe and moderate exacerbation.,COPD-related mean annual costs were $4069 (all figures given in US dollars) for the overall population and $6381 for patients with two or more exacerbations.,All-cause health care costs were $18,976 for the overall population and $23,901 for patients with history of two or more exacerbations.,Severity of exacerbations, presence of cardiovascular disease, diabetes, and long-term oxygen use were associated with higher adjusted costs.,The results indicate that despite treatment with maintenance medications, COPD patients continue to have exacerbations resulting in higher costs.,New medications and disease management interventions are warranted to reduce the severity and frequency of exacerbations and the related cost impact of the disease. | 1 |
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death by disease worldwide and has a 30-day readmission rate of 22.6%.,In 2015, COPD was added to the Medicare Hospital Readmission Reductions Program.,The objective of this paper was to survey the current medical technologies for remote patient monitoring (RPM) tools that forecast COPD exacerbations in order to reduce COPD readmissions.,We searched literature and digital health news to find commercially available RPM devices focused on predicting COPD exacerbations.,These technologies were reviewed and compared according to four criteria: forecasting ability, cost, ease of use, and appearance.,A rating system was developed to facilitate the evaluation process.,As of June 2019, a list of handheld and hands-free devices was compiled.,We compared features and found substantial variations.,Devices that ranked higher on all criteria tended to have a high or unlisted price.,Commonly mass-marketed devices like the pulse oximeter and spirometer surprisingly fulfilled the least criteria.,The COPD RPM technologies with most technological promise and compatibility with daily living appear to have high or unlisted prices.,Consumers and providers need better access to product information to make informed decisions. | Adherence to medication among individuals with chronic obstructive pulmonary disease (COPD) is suboptimal and has negative impacts on survival and health care costs.,No systematic review has examined the effectiveness of interventions designed to improve medication adherence.,Electronic databases Medline and Cochrane were searched using a combination of MeSH and keywords.,Eligible studies were interventions with a primary or secondary aim to improve medication adherence among individuals with COPD published in English.,Included studies were assessed for methodological quality using the Effective Practice and Organisation of Care (EPOC) criteria.,Of the 1,186 papers identified, seven studies met inclusion criteria.,Methodological quality of the studies was variable.,Five studies identified effective interventions.,Strategies included: brief counselling; monitoring and feedback about inhaler use through electronic medication delivery devices; and multi-component interventions consisting of self-management and care co-ordination delivered by pharmacists and primary care teams.,Further research is needed to establish the most effective and cost effective interventions.,Special attention should be given to increasing patient sample size and using a common measure of adherence to overcome methodological limitations.,Interventions that involve caregivers and target the healthcare provider as well as the patient should be further explored. | 1 |
Single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 μg has been shown to improve lung function and health status, and reduce exacerbations, versus budesonide/formoterol in patients with chronic obstructive pulmonary disease (COPD).,We evaluated the non-inferiority of single-inhaler FF/UMEC/VI versus FF/VI + UMEC using two inhalers.,Eligible patients with COPD (aged ≥40 years; ≥1 moderate/severe exacerbation in the 12 months before screening) were randomized (1:1; stratified by the number of long-acting bronchodilators [0, 1 or 2] per day during run-in) to receive 24-week FF/UMEC/VI 100/62.5/25 μg and placebo or FF/VI 100/25 μg + UMEC 62.5 μg; all treatments/placebo were delivered using the ELLIPTA inhaler once-daily in the morning.,Primary endpoint: change from baseline in trough forced expiratory volume in 1 s (FEV1) at Week 24.,The non-inferiority margin for the lower 95% confidence limit was set at − 50 mL.,A total of 1055 patients (844 [80%] of whom were enrolled on combination maintenance therapy) were randomized to receive FF/UMEC/VI (n = 527) or FF/VI + UMEC (n = 528).,Mean change from baseline in trough FEV1 at Week 24 was 113 mL (95% CI 91, 135) for FF/UMEC/VI and 95 mL (95% CI 72, 117) for FF/VI + UMEC; the between-treatment difference of 18 mL (95% CI -13, 50) confirmed FF/UMEC/VI’s was considered non-inferior to FF/VI + UMEC.,At Week 24, the proportion of responders based on St George’s Respiratory Questionnaire Total score was 50% (FF/UMEC/VI) and 51% (FF/VI + UMEC); the proportion of responders based on the Transitional Dyspnea Index focal score was similar (56% both groups).,A similar proportion of patients experienced a moderate/severe exacerbation in the FF/UMEC/VI (24%) and FF/VI + UMEC (27%) groups; the hazard ratio for time to first moderate/severe exacerbation with FF/UMEC/VI versus FF/VI + UMEC was 0.87 (95% CI 0.68, 1.12).,The incidence of adverse events was comparable in both groups (48%); the incidence of serious adverse events was 10% (FF/UMEC/VI) and 11% (FF/VI + UMEC).,Single-inhaler triple therapy (FF/UMEC/VI) is non-inferior to two inhalers (FF/VI + UMEC) on trough FEV1 change from baseline at 24 weeks.,Results were similar on all other measures of efficacy, health-related quality of life, and safety.,GSK study CTT200812; ClinicalTrials.gov NCT02729051 (submitted 31 March 2016). | This study is an analysis of a pilot COPD clinical audit that evaluated adherence to guidelines for patients with COPD in a stable disease phase during a routine visit in specialized secondary care outpatient clinics in order to identify the variables associated with the decision to step-up or step-down pharmacological treatment.,This study was a pilot clinical audit performed at hospital outpatient respiratory clinics in the region of Andalusia, Spain (eight provinces with over eight million inhabitants), in which 20% of centers in the area (catchment population 3,143,086 inhabitants) were invited to participate.,Treatment changes were evaluated in terms of the number of prescribed medications and were classified as step-up, step-down, or no change.,Three backward stepwise binominal multivariate logistic regression analyses were conducted to evaluate variables associated with stepping up, stepping down, and inhaled corticosteroids discontinuation.,The present analysis evaluated 565 clinical records (91%) of the complete audit.,Of those records, 366 (64.8%) cases saw no change in pharmacological treatment, while 99 patients (17.5%) had an increase in the number of drugs, 55 (9.7%) had a decrease in the number of drugs, and 45 (8.0%) noted a change to other medication for a similar therapeutic scheme.,Exacerbations were the main factor in stepping up treatment, as were the symptoms themselves.,In contrast, rather than symptoms, doctors used forced expiratory volume in 1 second and previous treatment with long-term antibiotics or inhaled corticosteroids as the key determinants to stepping down treatment.,The majority of doctors did not change the prescription.,When changes were made, a number of related factors were noted.,Future trials must evaluate whether these therapeutic changes impact clinically relevant outcomes at follow-up. | 1 |
The combination of asthma and chronic obstructive pulmonary disease (COPD), or ACOS is a recently defined syndrome.,The epidemiology of the condition is poorly described and previous research has suggested ACOS is associated with worse outcomes than either condition alone.,We therefore decided to complete a systematic review of the published literature.,This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta- Analyses guidelines.,A structured search was performed in the PubMed, Embase, and Medline databases up to Feb 2015 to identify studies reporting incidence, prevalence, health care utilization, morbidity, or mortality in COPD and asthma.,A total of 19 studies were included in the present study.,The pooled prevalence of overlap among COPD was 27% (95% CI: 0.16-0.38, p<0.0001) and 28% (95% CI: 0.09-0.47, p = 0.0032) in the population and hospital-based studies, respectively.,We found no significant difference between ACOS and COPD in terms of gender, smoking status, lung function and 6mWD.,However, in comparison to subject with only COPD, ACOS subjects were significantly younger, had higher BMI, healthcare utilization, and lower HRQoL.,ACOS is a common condition that exists in a substantial proportion of subjects with COPD.,ACOS represents a distinct clinical phenotype with more frequent exacerbations, hospitalization, worse health-related quality of life, and higher healthcare costs than either disease alone.,There is a critical need to better define the management and treatment of this syndrome. | 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 |
Inhaled corticosteroids (ICS) are widely used and recommended to treat chronic obstructive pulmonary disease (COPD).,While generally considered safe, several studies demonstrated an increased risk of pneumonia with the use of ICS in COPD patients.,Although all ICS indicated for COPD carry the class labeling warning of increased pneumonia risk, evidence suggests an intraclass difference in the risk of pneumonia between inhaled budesonide and fluticasone.,To date, systematic reviews of direct-comparison studies have not been performed to assess if an intraclass difference exists.,This review investigated whether there is an intraclass difference in risk of pneumonia between inhaled fluticasone and budesonide, the 2 most commonly used ICS in COPD.,A search of the medical literature was conducted in PubMed and Embase for the time period of 01/01/69-05/31/19.,The search strategy combined terms that defined the patient/disease type, exposures, outcome, and the study/publication type.,Descriptive and comparative statistics reported for fluticasone- and budesonide-containing products in each study, including data for pneumonia event subgroups, were extracted and reported by dose, seriousness, or practice setting.,Controlled clinical trials and observational studies meeting the inclusion criteria were assessed for methodologic quality by using the appropriate tool from the list of study quality assessment tools developed by the National Institutes of Health.,The summary relative risk (RR) ratio across 5 included studies (57,199 patients) was 1.13 (95% CI: 1.09-1.19), representing a 13.5% increased risk of pneumonia among fluticasone users compared to budesonide users.,Similarly, summary RR ratio for serious pneumonia implied a 14.4% increased risk of serious pneumonia among fluticasone users compared to budesonide users (pooled RR: 1.14; 95% CI: 1.09-1.20).,There is likely a clinically important intraclass difference in the risk of pneumonia between fluticasone- and budesonide-containing inhaled medications in COPD. | Whether the use of inhaled corticosteroids (ICSs) in patients with COPD can protect from osteoporosis remains undetermined.,The aim of this study is to assess the incidence of osteoporosis in patients with COPD with ICS use and without.,This is a retrospective cohort and population-based study in which we extracted newly diagnosed female patients with COPD between 1997 and 2009 from Taiwan’s National Health Insurance (TNHI) database between 1996 and 2011 (International Classification of Diseases, Ninth Revision - Clinical Modification [ICD-9-CM] 491, 492, 496).,The patients with COPD were defined by the presence of two or more diagnostic codes for COPD within 12 months on either inpatient or outpatient service claims submitted to TNHI.,Patients were excluded if they were younger than 40 years or if osteoporosis had been diagnosed prior to the diagnosis of COPD and cases of asthma (ICD-9 CM code 493.,X) before the index date.,These enrolled patients were followed up till 2011, and the incidence of osteoporosis was determined.,The Cox proportional hazards regression model was also used to estimate hazard ratios (HRs) for incidences of lung cancer.,Totally, 10,723 patients with COPD, including ICS users (n=812) and nonusers (n=9,911), were enrolled.,The incidence rate of osteoporosis per 100,000 person years is 4,395 in nonusers and 2,709 in ICS users (HR: 0.73, 95% confidence interval [CI]: 0.63-084).,The higher ICS dose is associated with lower risk of osteoporosis (0 mg to ≤20 mg, HR: 0.84, 95% CI: 0.69-1.04; >20 mg to ≤60 mg, HR: 0.78, 95% CI: 0.59-1.04; and >60 mg, HR: 0.72, 95% CI: 0.55-0.96; P for trend =0.0023) after adjusting for age, income, and medications.,The cumulative osteoporosis probability significantly decreased among the ICS users when compared with the nonusers (P<0.001).,Female patients with COPD using ICS have a dose-response protective effect for osteoporosis. | 1 |
Self-management support for chronic obstructive pulmonary disease (COPD) patients is recommended by UK national guidelines, but extent of implementation is unknown.,We aimed to describe self-management behaviour and support among COPD patients and explore behaviour associated with having a self-management plan.,We undertook cross-sectional analysis of self-reported data from diagnosed COPD patients in the Birmingham COPD Cohort study.,Questionnaire items relevant to self-management behaviour, knowledge of COPD, receipt of self-management plans and advice from healthcare professionals were examined.,Multiple regression models were used to identify behaviour associated with having a self-management plan.,One-thousand seventy-eight participants (676 males, 62.7%, mean age 69.8 (standard deviation 9.0) years) were included.,The majority reported taking medications as instructed (940, 94.0%) and receiving annual influenza vaccinations (962, 89.2%).,Only 400 (40.4%) participants had self-management plans, 538 (49.9%) reported never having received advice on diet/exercise and 110 (42.7%) current smokers had been offered practical help to stop smoking in the previous year.,General knowledge about COPD was moderate (mean total Bristol COPD Knowledge Questionnaire score: 31.5 (standard deviation 10.7); max score 65), corresponding to 48.5% of questions answered correctly.,Having a self-management plan was positively associated with self-reported adherence to medication (odds ratio 3.10, 95% confidence interval 1.43 to 6.72), attendance at a training course (odds ratio 2.72, 95% confidence interval 1.81 to 4.12), attendance at a support group (odds ratio 6.28, 95% confidence interval 2.96 to 13.35) and better disease knowledge (mean difference 4.87, 95% confidence interval 3.16 to 6.58).,Primary care healthcare professionals should ensure more widespread implementation of individualised self-management plans for all patients and improve the lifestyle advice provided.,Health professionals should ensure all patients with chronic lung disease receive individualized self-management plans and lifestyle advice.,UK national guidelines state that patients with chronic obstructive pulmonary disease (COPD) should receive personalized self-management plans and comprehensive support to help them manage their disease.,Ainee Khan and colleagues at the University of Birmingham analyzed patient questionnaire data gathered during the Birmingham COPD Cohort study to explore self-management behavior, receipt of self-management plans and advice, and patient knowledge of COPD.,Of 1,078 participants, only 400 had self-management plans, and less than half reported receiving lifestyle advice or support.,Those with plans were more likely to adhere to medication, had greater knowledge about COPD and were more likely to attend support groups and training courses.,The authors recommend carefully-planned, wider implementation of COPD self-management plans and associated support. | Chronic obstructive pulmonary disease (COPD) is one of the top five major causes of morbidity and mortality worldwide.,Despite worldwide health care efforts, costs, and medical research, COPD figures demonstrate a continuously increasing tendency in mortality.,This is contrary to other top causes of death, such as neoplasm, accidents, and cardiovascular disease.,A major factor affecting COPD-related mortality is the acute exacerbation of COPD (AECOPD).,Exacerbations and comorbidities contribute to the overall severity in individual patients.,Despite the underestimation by the physicians and the patients themselves, AECOPD is a really devastating event during the course of the disease, similar to acute myocardial infarction in patients suffering from coronary heart disease.,In this review, we focus on the evidence that supports the claim that AECOPD is the “stroke of the lungs”.,AECOPD can be viewed as: a Semicolon or disease’s full-stop period, Triggering a catastrophic cascade, usually a Relapsing and Overwhelming event, acting as a Killer, needing Emergent treatment. | 1 |
Psychiatric symptoms of anxiety, depression and cognitive dysfunction often occur in patients suffering from somatic conditions such as asthma and chronic obstructive pulmonary disease (COPD) which constitute a major and growing public health problem.,In the present study we therefore aimed at analyzing depressive symptoms as well as symptoms of anxiety and cognitive problems in patients with mild to moderate asthma and COPD. 59 participants-17 with asthma, 24 with COPD and 18 healthy controls were enrolled.,Depressiveness was assessed with the beck depression inventory (BDI); anxiety symptoms were measured with the State-Trait Anxiety Inventory Part 1 and 2, and cognitive function levels were estimated with the Trail Making Test Part A and B.,A score above the threshold indicative for depression was found by 33 % (n = 8) of COPD patients, 29 % (n = 5) of asthma patients compared to 0.05 % (n = 1) of the control group.,Clinically relevant anxiety levels were found in 42 % (n = 10) of the COPD group, 41 % (n = 7) of the asthma patients and 17 % (n = 3) of the controls.,Patients with COPD performed significantly worse on the TMT than other groups.,Psychoemotional state and cognitive functions were found to be correlated with exposure to tobacco smoke (measured in pack-years) and airway obstruction (measured with FEV1).,In conclusion, patients with mild to moderate asthma and COPD exhibit significantly higher levels of depressive and anxiety symptoms as well as cognitive dysfunctions than controls.,The prevalence of these symptoms is related to the amount of exposure to tobacco smoke and the severity of airflow obstruction. | Pulmonary rehabilitation (PR) is a multidisciplinary program of care for patients with chronic obstructive pulmonary disease (COPD) with the goal of improving the functional capacity and quality of life, as well as maintaining the clinical stability of COPD sufferers.,However, not all patients are available for such a program despite discomfort with their condition.,The aim of this study was to evaluate the effects of a home-based PR (HBPR) program on functional ability, quality of life, and respiratory muscle strength and endurance.,Patients with COPD according to the Global Initiative of Chronic Obstructive Lung Disease were randomized (double-blind) into two groups.,One group performed a protocol at home with aerobic and muscle strength exercises and was called the intervention group; the other group received only instructions to perform breathing and stretching exercises, characterizing it as the control group (CG).,We assessed the following variables at baseline and 2 months: exercise tolerance (incremental shuttle walk test and upper limb test), respiratory muscle (strength and endurance test), and health-related quality of life (Airways Questionnaire 20).,There were no significant changes after the intervention in either of the two groups in exercise tolerance and quality of life.,However, the intervention group had improved respiratory endurance compared with the CG, while the CG presented a decrease in the load sustained by the respiratory muscles after the HBPR.,A program of HBPR with biweekly supervision (although not enough to provide significant improvements in physical capacity or quality of life) played an important role in maintaining the stability of the clinical features of patients with COPD; the patients had no worsening of symptoms during the intervention period according to the daily log. | 1 |
The Spanish Guidelines for COPD (GesEPOC) describe four clinical phenotypes: non-exacerbator (NE), asthma-COPD overlap syndrome (ACO), frequent exacerbator with emphysema (EE), and exacerbator with chronic bronchitis (ECB).,The objective of this study was to determine the frequency of COPD phenotypes, their clinical characteristics, and the availability of diagnostic tools to classify COPD phenotypes in clinical practice.,This study was an epidemiological, cross-sectional, and multi-centered study.,Patients ≥40 years old with a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio of <0.7 and who were smokers or former smokers (with at least 10 pack-years) were included.,The availability of diagnostic tools to classify COPD phenotypes was assessed by an ad hoc questionnaire.,A total of 647 patients (294 primary care [PC], 353 pulmonology centers) were included.,Most patients were male (80.8%), with a mean age (SD) of 68.2 (9.2) years, mean post-bronchodilator FEV1 was 53.2% (18.9%) and they suffered a mean of 2.2 (2.1) exacerbations in the last year.,NE was the most frequent phenotype (47.5%) found, followed by ECB (29.1%), EE (17.0%), and ACO (6.5%).,Significant differences between the four phenotypes were found regarding age; sex; body mass index; FEV1; body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE)/body mass index, airflow obstruction, dyspnea and exacerbations (BODEx) index; modified Medical Research Council dyspnea scale; respiratory symptoms; comorbidi-ties; hospitalizations; and exacerbations in the last year.,Physicians considered that >80% of the diagnostic tools needed to classify COPD phenotypes were available, with the exception of computed tomography (26.9%) and carbon monoxide transfer test (13.5%) in PC, and sputum eosinophilia count in PC and pulmonology centers (40.4% and 49.4%, respectively).,In Spanish clinical practice, almost half of the patients with COPD presented with NE phenotype.,The prevalence of ACO according to the Spanish consensus definition was very low.,In general, physicians indicated that they had the necessary tools for diagnosing COPD phenotypes. | Chronic obstructive pulmonary disease (COPD) imposes a substantial burden on individuals with the disease, which can include a range of symptoms (breathlessness, cough, sputum production, wheeze, chest tightness) of varying severities.,We present an overview of the biomedical literature describing reported relationships between COPD symptoms and disease burden in terms of quality of life, health status, daily activities, physical activity, sleep, comorbid anxiety, and depression, as well as risk of exacerbations and disease prognosis.,In addition, the substantial variability of COPD symptoms encountered (morning, daytime, and nighttime) is addressed and their implications for disease burden considered.,The findings from this narrative review, which mainly focuses on real-world and observational studies, demonstrate the impact of COPD symptoms on the burden of disease and that improved recognition and understanding of their impact is central to alleviating this burden. | 1 |
H. haemolyticus is often misidentified as NTHi due to their close phylogenetic relationship.,Differentiating between the two is important for correct identification and appropriate treatment of infective organism and to ensure any role of H. haemolyticus in disease is not being overlooked.,Speciation however is not completely reliable by culture and PCR methods due to the loss of haemolysis by H. haemolyticus and the heterogeneity of NTHi.,Haemophilus isolates from COPD as part of the AERIS study (ClinicalTrials - NCT01360398) were speciated by analysing sequence data for the presence of molecular markers.,Further investigation into the genomic relationship was carried out using average nucleotide identity and phylogeny of allelic and genome alignments.,Only 6.3% were identified as H. haemolyticus.,Multiple in silico methods were able to distinguish H. haemolyticus from NTHi.,However, no single gene target was found to be 100% accurate.,A group of omp2 negative NTHi were observed to be phylogenetically divergent from H. haemolyticus and remaining NTHi.,The presence of an atypical group from a geographically and disease limited set of isolates supports the theory that the heterogeneity of NTHi may provide a genetic continuum between NTHi and H. haemolyticus. | 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. | 1 |
Exercise is an important countermeasure to limb muscle dysfunction in COPD.,The two major training modalities in COPD rehabilitation, endurance training (ET) and resistance training (RT), may both be efficient in improving muscle strength, exercise capacity, and health-related quality of life, but the effects on quadriceps muscle characteristics have not been thoroughly described.,Thirty COPD patients (forced expiratory volume in 1 second: 56% of predicted, standard deviation [SD] 14) were randomized to 8 weeks of ET or RT.,Vastus lateralis muscle biopsies were obtained before and after the training intervention to assess muscle morphology and metabolic and angiogenic factors.,Symptom burden, exercise capacity (6-minute walking and cycle ergometer tests), and vascular function were also assessed.,Both training modalities improved symptom burden and exercise capacity with no difference between the two groups.,The mean (SD) proportion of glycolytic type IIa muscle fibers was reduced after ET (from 48% [SD 11] to 42% [SD 10], P<0.05), whereas there was no significant change in muscle fiber distribution with RT.,There was no effect of either training modality on muscle capillarization, angiogenic factors, or vascular function.,After ET the muscle protein content of phosphofructokinase was reduced (P<0.05) and the citrate synthase content tended increase (P=0.08) but no change was observed after RT.,Although both ET and RT improve symptoms and exercise capacity, ET induces a more oxidative quadriceps muscle phenotype, counteracting muscle dysfunction in COPD. | Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are highly prevalent and associated with a large symptom burden, that is compounded in a dual HF-COPD diagnosis.,Yoga has potential benefit for symptom relief; however functional impairment hinders access to usual yoga classes.,We developed a Tele-Yoga intervention and evaluated it in a controlled pilot trial.,This paper reports on the appropriateness and acceptability of the intervention and the evaluation design.,A controlled, non-randomised trial was conducted of an 8-week Tele-Yoga intervention versus an educational control (information leaflets mailed to participants with one phone call a week).,Biweekly one-hour Tele-Yoga classes were implemented via multipoint videoconferencing that connected participants to live classes via an Internet connection to their televisions.,Semi-structured qualitative interviews were conducted with participants post study exit to explore reasons for and experiences of participating, including views of study outcome measures and physiological tests.,Transcribed interviews were analysed using thematic content analysis.,Fifteen people participated in the pilot study (7 in the intervention group, 8 in the control).,Of these, 12 participants were interviewed, 6 in each group, mean age 71.2 years (SD 10.09); 3 were male.,Themes are reported in the following categories: acceptability and appropriateness of the intervention, potential active ingredients of the intervention, acceptability and appropriateness of the control, participation in the research, and acceptability of the testing procedures.,The intervention was acceptable and appropriate: the intervention group reported enjoying yoga and valuing the home-based aspect and participants described a high symptom burden and social isolation.,However, technological problems resulted in poor video-streaming quality for some participants.,Potential active ingredients included physical postures, breathing exercises and guidance in relaxation and meditation.,The educational control intervention was acceptable and appropriate, with participants reporting little effect on their well-being and no impact on mechanisms hypothesised to explain yoga’s effectiveness.,The questionnaires and home physiological testing were acceptable to participants.,Tele-Yoga is an acceptable and appropriate intervention in people with HF and COPD and further research is warranted to refine the technology used in its delivery.,Findings provide guidance for researchers working in tele-interventions, yoga, and similar populations.,ClinicalTrials.gov Identifier: NCT02078739 (4 March 2014). | 1 |
A significant proportion of patients with chronic obstructive pulmonary disease (COPD) remain undiagnosed.,Characterizing these patients can increase our understanding of the ‘hidden’ burden of COPD and the effectiveness of case detection interventions.,We conducted a systematic review and meta-analysis to compare patient and disease factors between patients with undiagnosed persistent airflow limitation and those with diagnosed COPD.,We searched MEDLINE and EMBASE for observational studies of adult patients meeting accepted spirometric definitions of COPD.,We extracted and pooled summary data on the proportion or mean of each risk factor among diagnosed and undiagnosed patients (unadjusted analysis), and coefficients for the adjusted association between risk factors and diagnosis status (adjusted analysis).,Two thousand eighty-three records were identified through database searching and 16 articles were used in the meta-analyses.,Diagnosed patients were less likely to have mild (v. moderate to very severe) COPD (odds ratio [OR] 0.30, 95%CI 0.24-0.37, 6 studies) in unadjusted analysis.,This association remained significant but its strength was attenuated in the adjusted analysis (OR 0.72, 95%CI 0.58-0.89, 2 studies).,Diagnosed patients were more likely to report respiratory symptoms such as wheezing (OR 3.51, 95%CI 2.19-5.63, 3 studies) and phlegm (OR 2.16, 95% CI 1.38-3.38, 3 studies), had more severe dyspnea (mean difference in modified Medical Research Council scale 0.52, 95%CI 0.40-0.64, 3 studies), and slightly greater smoking history than undiagnosed patients.,Patient age, sex, current smoking status, and the presence of coughing were not associated with a previous diagnosis.,Undiagnosed patients had less severe airflow obstruction and fewer respiratory symptoms than diagnosed patients.,The lower disease burden in undiagnosed patients may significantly delay the diagnosis of COPD.,The online version of this article (10.1186/s12931-018-0731-1) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) has traditionally been considered an inexorably progressive disease, associated with a constant increase of symptoms that occur as the forced expiratory volume in 1 second (FEV1) worsens, only intermittently interrupted by exacerbations.,However, this paradigm has been challenged in recent decades by the available evidence.,Recent studies have pointed out that COPD-related symptoms are not consistently perceived by patients in the same way, showing not only seasonal variation, but also changes in symptom perception during a week or even within a single day.,According to the available data, patients experience the biggest increase in respiratory symptoms during the first hours of the early morning, followed by the nighttime.,This variation over time is of considerable importance, since it impacts on daily life activities and health-related quality of life, as measured by a recently developed ad hoc questionnaire.,Additionally, recent clinical trials have suggested that the use of rapid-onset long-acting bronchodilators may have an impact on morning symptoms, despite their current use as maintenance treatment for a determined period.,Although this hypothesis is to be validated in future long-term clinical trials comparing fast-onset versus slow-onset inhaled drugs in COPD, it may bring forward a new concept of long-term bronchodilator therapy.,At the present time, the two available long-acting, fast-onset bronchodilators used in the treatment of COPD are formoterol and the recently marketed indacaterol.,Newer drugs have also been shown to have a rapid onset of action in preclinical studies.,Health care professionals caring for COPD patients should consider this variation in the perception of symptoms during their clinical interview as a potential new target in the long-term treatment plan. | 1 |
COPD (chronic obstructive pulmonary disease) is a major incurable global health burden and will become the third largest cause of death in the world by 2020.,It is currently believed that an exaggerated inflammatory response to inhaled irritants, in particular cigarette smoke, causes progressive airflow limitation.,This inflammation, where macrophages, neutrophils and T-cells are prominent, leads to oxidative stress, emphysema, small airways fibrosis and mucus hypersecretion.,The mechanisms and mediators that drive the induction and progression of chronic inflammation, emphysema and altered lung function are poorly understood.,Current treatments have limited efficacy in inhibiting chronic inflammation, do not reverse the pathology of disease and fail to modify the factors that initiate and drive the long-term progression of disease.,Therefore there is a clear need for new therapies that can prevent the induction and progression of COPD.,Animal modelling systems that accurately reflect disease pathophysiology continue to be essential to the development of new therapies.,The present review highlights some of the mouse models used to define the cellular, molecular and pathological consequences of cigarette smoke exposure and whether they can be used to predict the efficacy of new therapeutics for COPD. | Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies.,To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552).,Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years.,We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation.,Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p<0.001) and exacerbation frequency (1.5 (1.5) vs.,0.9 (1.1) per year, p<0.001) compared to non-inflamed ones.,As a descriptive study our results show associations but do not prove causality.,Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice.,Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment. | 1 |
Severe exacerbations of COPD are commonly associated with hyperglycaemia, which predicts adverse outcomes.,Metformin is a well-established anti-hyperglycaemic agent in diabetes mellitus, possibly augmented with anti-inflammatory effects, but its effects in COPD are unknown.,We investigated accelerated metformin therapy in severe COPD exacerbations, primarily to confirm or refute an anti-hyperglycaemic effect, and secondarily to explore its effects on inflammation and clinical outcome.,This was a multicentre, randomised, double-blind, placebo-controlled trial testing accelerated metformin therapy in non-diabetic patients, aged ≥35 years, hospitalised for COPD exacerbations.,Participants were assigned in a 2:1 ratio to 1 month of metformin therapy, escalated rapidly to 2 g/day, or matched placebo.,The primary end point was mean in-hospital blood glucose concentration.,Secondary end points included the concentrations of fructosamine and C reactive protein (CRP), and scores on the COPD Assessment Test and Exacerbations of Chronic Pulmonary Disease Tool.,52 participants (mean (±SD) age 67±9 years) were randomised (34 to metformin, 18 to placebo).,All were included in the primary end point analysis.,The mean blood glucose concentrations in the metformin and placebo groups were 7.1±0.9 and 8.0±3.3 mmol/L, respectively (difference −0.9 mmol/L, 95% CI −2.1 to +0.3; p=0.273).,No significant between-group differences were observed on any of the secondary end points.,Adverse reactions, particularly gastrointestinal effects, were more common in metformin-treated participants.,Metformin did not ameliorate elevations in blood glucose concentration among non-diabetic patients admitted to hospital for COPD exacerbations, and had no detectable effect on CRP or clinical outcomes.,ISRCTN66148745 and NCT01247870. | Genotoxic stress, such as by exposure to bromodeoxyuridine (BrdU) and cigarette smoke, induces premature cell senescence.,Recent evidence indicates that cellular senescence of various types of cells is accelerated in COPD patients.,However, whether the senescence of airway epithelial cells contributes to the development of airway diseases is unknown.,The present study was designed to test the hypothesis that premature senescence of airway epithelial cells (Clara cells) impairs repair processes and exacerbates inflammation after airway injury.,C57/BL6J mice were injected with the Clara-cell-specific toxicant naphthalene (NA) on days 0, 7, and 14, and each NA injection was followed by a daily dose of BrdU on each of the following 3 days, during which regenerating cells were allowed to incorporate BrdU into their DNA and to senesce.,The p38 MAPK inhibitor SB202190 was injected 30 minutes before each BrdU dose.,Mice were sacrificed at different times until day 28 and lungs of mice were obtained to investigate whether Clara cell senescence impairs airway epithelial regeneration and exacerbates airway inflammation.,NCI-H441 cells were induced to senesce by exposure to BrdU or the telomerase inhibitor MST-312.,Human lung tissue samples were obtained from COPD patients, asymptomatic smokers, and nonsmokers to investigate whether Clara cell senescence is accelerated in the airways of COPD patients, and if so, whether it is accompanied by p38 MAPK activation.,BrdU did not alter the intensity of the airway epithelial injury or inflammation after a single NA exposure.,However, after repeated NA exposure, BrdU induced epithelial cell (Clara cell) senescence, as demonstrated by a DNA damage response, p21 overexpression, increased senescence-associated β-galactosidase activity, and growth arrest, which resulted in impaired epithelial regeneration.,The epithelial senescence was accompanied by p38 MAPK-dependent airway inflammation.,Senescent NCI-H441 cells impaired epithelial wound repair and secreted increased amounts of pro-inflammatory cytokines in a p38 MAPK-dependent manner.,Clara cell senescence in COPD patients was accelerated and accompanied by p38 MAPK activation.,Senescence of airway epithelial cells impairs repair processes and exacerbates p38 MAPK-dependent inflammation after airway injury, and it may contribute to the pathogenesis of COPD. | 1 |
COPD is one of the leading causes of morbidity and mortality worldwide.,Although medication counseling interventions by pharmacists have been found to support the management of COPD, little is known about pharmacists’ knowledge concerning COPD and regular practices and perceptions concerning medication counseling of COPD patients.,The purpose of this study was to research these topics among Finnish community pharmacists.,In January 2017, an electronic survey was e-mailed to Finnish community pharmacies (n=741) via the Association of the Finnish Pharmacies.,One pharmacist from each pharmacy, preferably a specialist in asthma, was invited to answer the survey.,Completed responses were received from 263 pharmacists (response rate =35%), of whom 196 pharmacists were specialists in asthma.,Response rate among asthma pharmacists was 42%.,Pharmacists were positive about their role in medication counseling and in support of the self-management of COPD patients.,COPD-related knowledge was self-assessed as being good and was on a good level in respect of basic facts.,However, almost half (46%) of the pharmacists did not know that COPD is considered a national public health issue, and ~50% of the pharmacists were not familiar with the current care guideline on COPD.,Medication counseling was found to be more medicinal product-driven and less advisory concerning lifestyle changes such as smoking cessation and physical exercise.,Although the pharmacists’ knowledge of COPD was good on general topics, there were some gaps in their knowledge on the current care guideline and status of the disease.,Pharmacists should more systematically individually target medication counseling according to patients’ needs.,In addition, lifestyle treatments, including smoking cessation and physical exercise, should be part of the medication counseling. | Case finding of patients at risk of COPD by community pharmacists could identify a substantial number of people with undiagnosed COPD, but little is known about the feasibility and effectiveness of pharmacy-based COPD case finding using microspirometry.,The objective of this study was to assess the feasibility and effectiveness of COPD case-finding service provided by community pharmacists, utilizing a combination of risk assessment questionnaire and microspirometry.,A 6-month service was conducted in 21 community pharmacies in Australia.,Pharmacists trained in COPD case finding, including lung function test (LFT), invited their patients aged ≥35 years with a history of smoking and/or respiratory symptoms to participate.,High-risk patients were identified via a COPD risk assessment questionnaire (Initial Screening Questionnaire [ISQ]) and underwent LFT.,Pharmacists referred patients with a forced expiratory volume in 1 second (FEV1)/forced expiratory volume in 6 seconds (FEV6) ratio <0.75 to their general practitioner (GP) for further assessment and diagnosis.,In all, 91 of 167 (54%) patients had an ISQ score >3 indicating high COPD risk.,Of the 157 patients who were able to complete LFT, 61 (39%) had an FEV1/FEV6 ratio of <0.75 and were referred to their GP.,Patients with high ISQ symptoms scores (>3) were at a significantly higher risk of an FEV1/FEV6 ratio of <0.75, compared to patients with fewer COPD symptoms.,A total of 15 (10%) patients were diagnosed with COPD by their GP.,Another eight (5%) patients were diagnosed with other medical conditions and 87% of these were initiated on treatment.,Although only half of all screened patients lived in regional areas, 93% of those diagnosed with COPD were from regional areas.,A brief community pharmacy-based COPD case-finding service utilizing the ISQ, LFT and GP referral is feasible and may lead to identification and diagnosis of a substantial number of people with COPD.,This might be an important strategy for reducing the burden of COPD, particularly for those living in rural locations. | 1 |
Cigarette smoke (CS)-induced mitochondrial damage with increased reactive oxygen species (ROS) production has been implicated in COPD pathogenesis by accelerating senescence.,Mitophagy may play a pivotal role for removal of CS-induced damaged mitochondria, and the PINK1 (PTEN-induced putative kinase 1)-PARK2 pathway has been proposed as a crucial mechanism for mitophagic degradation.,Therefore, we sought to investigate to determine if PINK1-PARK2-mediated mitophagy is involved in the regulation of CS extract (CSE)-induced cell senescence and in COPD pathogenesis.,Mitochondrial damage, ROS production, and cell senescence were evaluated in primary human bronchial epithelial cells (HBEC).,Mitophagy was assessed in BEAS-2B cells stably expressing EGFP-LC3B, using confocal microscopy to measure colocalization between TOMM20-stained mitochondria and EGFP-LC3B dots as a representation of autophagosome formation.,To elucidate the involvement of PINK1 and PARK2 in mitophagy, knockdown and overexpression experiments were performed.,PINK1 and PARK2 protein levels in lungs from patients were evaluated by means of lung homogenate and immunohistochemistry.,We demonstrated that CSE-induced mitochondrial damage was accompanied by increased ROS production and HBEC senescence.,CSE-induced mitophagy was inhibited by PINK1 and PARK2 knockdown, resulting in enhanced mitochondrial ROS production and cellular senescence in HBEC.,Evaluation of protein levels demonstrated decreased PARK2 in COPD lungs compared with non-COPD lungs.,These results suggest that PINK1-PARK2 pathway-mediated mitophagy plays a key regulatory role in CSE-induced mitochondrial ROS production and cellular senescence in HBEC.,Reduced PARK2 expression levels in COPD lung suggest that insufficient mitophagy is a part of the pathogenic sequence of COPD. | Asthma and chronic obstructive pulmonary disease (COPD) are characterized by different patterns of airway remodeling, which all include an increased mass of bronchial smooth muscle (BSM).,A remaining major question concerns the mechanisms underlying such a remodeling of BSM.,Because mitochondria play a major role in both cell proliferation and apoptosis, we hypothesized that mitochondrial activation in BSM could play a role in this remodeling.,We describe that both the mitochondrial mass and oxygen consumption were higher in the BSM from asthmatic subjects than in that from both COPD and controls.,This feature, which is specific to asthma, was related to an enhanced mitochondrial biogenesis through up-regulation of peroxisome proliferator-activated receptor γ coactivator (PGC)-1α, nuclear respiratory factor-1, and mitochondrial transcription factor A.,The priming event of such activation was an alteration in BSM calcium homeostasis.,BSM cell apoptosis was not different in the three groups of subjects.,Asthmatic BSM was, however, characterized by increased cell growth and proliferation.,Both characteristics were completely abrogated in mitochondria-deficient asthmatic BSM cells.,Conversely, in both COPD and control BSM cells, induction of mitochondrial biogenesis reproduced these characteristics.,Thus, BSM in asthmatic patients is characterized by an altered calcium homeostasis that increases mitochondrial biogenesis, which, in turn, enhances cell proliferation, leading to airway remodeling. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) repeat acute exacerbations (AE).,Global Initiative for Chronic Obstructive Lung Disease (GOLD) is only available for patients in stable phase.,Currently, there is a lack of assessment and prediction methods for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients during hospitalization.,To enhance the monitoring and treatment of AECOPD patients, we develop a novel C5.0 decision tree classifier to predict the prognosis of AECOPD hospitalized patients with objective clinical indicators.,The medical records of 410 hospitalized AECOPD patients are collected and 28 features including vital signs, medical history, comorbidities and various inflammatory indicators are selected.,The overall accuracy of the proposed C5.0 decision tree classifier is 80.3% (65 out of 81 participants) with 95% Confidence Interval (CI):(0.6991, 0.8827) and Kappa 0.6054.,In addition, the performance of the model constructed by C5.0 exceeds the C4.5, classification and regression tree (CART) model and the iterative dichotomiser 3 (ID3) model.,The C5.0 decision tree classifier helps respiratory physicians to assess the severity of the patient early, thereby guiding the treatment strategy and improving the prognosis of patients. | A hallmark of the diagnosis of chronic obstructive pulmonary disease (COPD) is the measurement of post-bronchodilator (post-BD) airflow obstruction (AO) by spirometry, but spirometry is not enough for the provision of a clinical diagnosis.,In the majority of previous epidemiological studies, COPD diagnosis has been based on spirometry and a few clinical characteristics.,The aim of our study was to identify outcomes in patients newly diagnosed with airflow obstruction (AO) based on a diagnostic work-up conducted as part of a population-based cross-sectional study in North-Western Russia.,Spirometry was performed before (pre-BD) and after BD administration, and AO was defined using the FEV1/FVC <0.70 and FEV1/FVC <lower limit of normal cut-off values.,Relevant symptoms were recorded.,Participants with AO identified at baseline were then examined by a pulmonologist, including a clinical examination and second spirometry with BD test.,Of the 102 participants with post-BD AO in the initial assessment, only 60.8% still had AO identified at the second examination; among these patients, the following final diagnoses were reported: COPD (n = 41), asthma (n = 5), asthma-COPD overlap syndrome (ACOS) (n = 4) and likely ACOS (n = 5).,Of the 65 participants with pre-BD AO, 23.1% had post-BD AO at the second assessment, and these patients had been diagnosed with COPD (n = 12), asthma (n = 1), ACOS (n = 1), likely ACOS (n = 1).,Serial spirometric assessments complemented by a comprehensive clinical evaluation are recommended in new epidemiological studies.,A single lung function test is insufficient to accurately diagnose chronic obstructive pulmonary disease (COPD).,A team led by Jean-Marie Degryse from the Université Catholique de Louvain, Belgium, studied patients in Northwestern Russia who showed signs of airflow obstruction, as measured by a spirometer, a medical device that records the amount of air inhaled and exhaled and the speed of breath.,Among those who initially showed signs of limited lung function, even after treatment with a bronchodilator, a large proportion did not exhibit airflow obstruction on a second spirometry test months later.,Moreover, not everyone who had confirmed airflow obstruction were diagnosed with COPD when examined by a pulmonologist.,Some had asthma or asthma-COPD overlap syndrome.,The findings point to the need for clinical assessments and follow-up spirometry tests to accurately diagnose and manage COPD. | 1 |
There is limited information about the initiation of triple therapy (TT) in patients with chronic obstructive pulmonary disease (COPD) in primary care.,This was an observational, population-based study in patients identified from a primary care electronic medical records database in Catalonia from 2011 to 2015 aimed to identify the use of TT in patients with newly diagnosed COPD.,A total of 69,668 newly diagnosed patients were identified of whom 11,524 (16.5%) initiated TT, of whom 8626 initiated TT at or immediately after COPD diagnosis.,Among them, 72.3% were GOLD A/B, 14.6% were frequent exacerbators, and 7.1% had asthma-COPD overlap (ACO).,Variables associated with TT initiation were: male sex, older age, previous exacerbations, ACO, a previous treatment regimen containing an inhaled corticosteroid, previous pneumonia, and history of lung cancer.,A significant number of COPD patients in Primary Care initiated TT shortly after or even before an established COPD diagnosis. | 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. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by varying trajectories of decline.,Information regarding the prognostic value of preventing short-term clinically important deterioration (CID) in lung function, health status, or first moderate/severe exacerbation as a composite endpoint of worsening is needed.,We evaluated post hoc the link between early CID and long-term adverse outcomes.,CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV1), ≥4-unit increase in St George’s Respiratory Questionnaire (SGRQ) score from baseline, and/or a moderate/severe exacerbation during enrollment in two 3-year studies.,Presence of CID was assessed at 6 months for the principal analysis (TORCH) and 12 months for the confirmatory analysis (ECLIPSE).,Association between presence (+) or absence (-) of CID and long-term deterioration in FEV1, SGRQ, future risk of exacerbations, and all-cause mortality was assessed.,In total, 2870 (54%; TORCH) and 1442 (73%; ECLIPSE) patients were CID+.,At 36 months, in TORCH, CID+ patients (vs CID-) had sustained clinically significant worsening of FEV1 (- 117 mL; 95% confidence interval [CI]: - 134, - 100 mL; P < 0.001) and SGRQ score (+ 6.42 units; 95% CI: 5.40, 7.45; P < 0.001), and had higher risk of exacerbations (hazard ratio [HR]: 1.61 [95% CI: 1.50, 1.72]; P < 0.001) and all-cause mortality (HR: 1.41 [95% CI: 1.15, 1.72]; P < 0.001).,Similar risks post-CID were observed in ECLIPSE.,A CID within 6-12 months of follow-up was consistently associated with increased long-term risk of exacerbations and all-cause mortality, and predicted sustained meaningful loss in FEV1 and health status amongst survivors.,NCT00268216; NCT00292552.,The online version of this article (10.1186/s12931-018-0928-3) contains supplementary material, which is available to authorized users. | During most COPD exacerbations, patients continue to live in the community but there is little information on changes in activity during exacerbations due to the difficulties of obtaining recent, prospective baseline data.,Patients recorded on daily diary cards any worsening in respiratory symptoms, peak expiratory flow (PEF) and the number of steps taken per day measured with a Yamax Digi-walker pedometer.,Exacerbations were defined by increased respiratory symptoms and the number of exacerbations experienced in the 12 months preceding the recording of daily step count used to divide patients into frequent (> = 2/year) or infrequent exacerbators.,The 73 COPD patients (88% male) had a mean (±SD) age 71(±8) years and FEV1 53(±16)% predicted.,They recorded pedometer data on a median 198 days (IQR 134-353).,At exacerbation onset, symptom count rose by 1.9(±1.3) and PEF fell by 7(±13) l/min.,Mean daily step count fell from 4154(±2586) steps/day during a preceding baseline week to 3673(±2258) step/day during the initial 7 days of exacerbation (p = 0.045).,Patients with larger falls in activity at exacerbation took longer to recover to stable level (rho = −0.56; p < 0.001).,Recovery in daily step count was faster (median 3.5 days) than for exacerbation symptoms (median 11 days; p < 0.001).,Recovery in step count was also faster in untreated compared to treated exacerbation (p = 0.030).,Daily step count fell faster over time in the 40 frequent exacerbators, by 708 steps/year, compared to 338 steps/year in 33 infrequent exacerbators (p = 0.002).,COPD exacerbations reduced physical activity and frequent exacerbations accelerate decline in activity over time. | 1 |
Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV1), and its ratio to forced vital capacity (FEV1/FVC).,Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV1 and FEV1/FVC across 19 studies (total N = 50,047).,We identified three novel loci not previously associated with pulmonary function.,SNPs in or near DNER (smallest P JMA = 5.00×10−11), HLA-DQB1 and HLA-DQA2 (smallest P JMA = 4.35×10−9), and KCNJ2 and SOX9 (smallest P JMA = 1.28×10−8) were associated with FEV1/FVC or FEV1 in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction.,The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated.,We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue.,DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers.,Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects. | Pulmonary function measures reflect respiratory health and predict mortality, and are used in the diagnosis of chronic obstructive pulmonary disease (COPD).,We tested genome-wide association with the forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in 48,201 individuals of European ancestry, with follow-up of top associations in up to an additional 46,411 individuals.,We identified new regions showing association (combined P<5×10−8) with pulmonary function, in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1, and KCNE2.,Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function. | 1 |
In order to review the epidemiologic evidence concerning previous lung diseases as risk factors for lung cancer, a meta-analysis and systematic review was conducted.,Relevant studies were identified through MEDLINE searches.,Using random effects models, summary effects of specific previous conditions were evaluated separately and combined.,Stratified analyses were conducted based on smoking status, gender, control sources and continent.,A previous history of COPD, chronic bronchitis or emphysema conferred relative risks (RR) of 2.22 (95% confidence interval (CI): 1.66, 2.97) (from 16 studies), 1.52 (95% CI: 1.25, 1.84) (from 23 studies) and 2.04 (95% CI: 1.72, 2.41) (from 20 studies), respectively, and for all these diseases combined 1.80 (95% CI: 1.60, 2.11) (from 39 studies).,The RR of lung cancer for subjects with a previous history of pneumonia was 1.43 (95% CI: 1.22-1.68) (from 22 studies) and for subjects with a previous history of tuberculosis was 1.76 (95% CI = 1.49, 2.08), (from 30 studies).,Effects were attenuated when restricting analysis to never smokers only for COPD/emphysema/chronic bronchitis (RR = 1.22, 0.97-1.53), however remained significant for pneumonia 1.36 (95% CI: 1.10, 1.69) (from 8 studies) and tuberculosis 1.90 (95% CI: 1.45, 2.50) (from 11 studies).,Previous lung diseases are associated with an increased risk of lung cancer with the evidence among never smokers supporting a direct relationship between previous lung diseases and lung cancer. | Indacaterol is a novel, once-daily (o.d.) inhaled, long-acting β2-agonist in development for chronic obstructive pulmonary disease (COPD).,This 12-week, double-blind study compared the efficacy, safety, and tolerability of indacaterol to that of placebo in patients with moderate-to-severe COPD.,Efficacy variables included 24-h trough FEV1 (mean of 23 h 10 min and 23 h 45 min post-dose) at Week 12 (primary endpoint) and after Day 1, and the percentage of COPD days with poor control (i.e., worsening symptoms).,Safety was assessed by adverse events (AEs), mean serum potassium and blood glucose, QTc (Fridericia), and vital signs.,Patients were randomised (n = 416, mean age 63 years) to receive either indacaterol 150 μg o.d. (n = 211) or placebo (n = 205) via a single-dose dry-powder inhaler; 87.5% completed the study.,Trough FEV1 (LSM ± SEM) at Week 12 was 1.48 ± 0.018 L for indacaterol and 1.35 ± 0.019 L for placebo, a clinically relevant difference of 130 ± 24 mL (p < 0.001).,Trough FEV1 after one dose was significantly higher with indacaterol than placebo (p < 0.001).,Indacaterol demonstrated significantly higher peak FEV1 than placebo, both on Day 1 and at Week 12, with indacaterol-placebo differences (LSM ± SEM) of 190 ± 28 (p < 0.001) and 160 ± 28 mL (p < 0.001), respectively.,Standardised AUC measurements for FEV1 (between 5 min and 4 h, 5 min and 1 h, and 1 and 4 h post-dose) at Week 12 were all significantly greater with indacaterol than placebo (p < 0.001), with LSM (± SEM) differences of 170 ± 24, 180 ± 24, and 170 ± 24 mL, respectively.,Indacaterol significantly reduced the percentage of days of poor control versus placebo by 22.5% (p < 0.001) and was also associated with significantly reduced use of rescue medication (p < 0.001).,The overall rates of AEs were comparable between the groups (indacaterol 49.3%, placebo 46.8%), with the most common AEs being COPD worsening (indacaterol 8.5%, placebo 12.2%) and cough (indacaterol 6.2%, placebo 7.3%).,One patient died in the placebo group.,Serum potassium and blood glucose levels did not differ significantly between the two groups, and no patient had QTc >500 ms.,Indacaterol 150 μg o.d. provided clinically significant and sustained bronchodilation, reduced rescue medication use, and had a safety and tolerability profile similar to placebo.,NCT00624286 | 1 |
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. | Exercise intolerance, exertional dyspnea, reduced health-related quality of life, and acute exacerbations are features characteristic of chronic obstructive pulmonary disease (COPD).,Patients with a primary diagnosis of COPD often report comorbidities and other secondary manifestations, which diversifies the clinical presentation.,Pulmonary rehabilitation that includes whole body exercise training is a critical part of management, and core programs involve endurance and resistance training for the upper and lower limbs.,Improvement in maximal and submaximal exercise capacity, dyspnea, fatigue, health-related quality of life, and psychological symptoms are outcomes associated with exercise training in pulmonary rehabilitation, irrespective of the clinical state in which it is commenced.,There may be benefits for the health care system as well as the individual patient, with fewer exacerbations and subsequent hospitalization reported with exercise training.,The varying clinical profile of COPD may direct the need for modification to traditional training strategies for some patients.,Interval training, one-legged cycling (partitioning) and non-linear periodized training appear to be equally or more effective than continuous training.,Inspiratory muscle training may have a role as an adjunct to whole body training in selected patients.,The benefits of balance training are also emerging.,Strategies to ensure that health enhancing behaviors are adopted and maintained are essential.,These may include training for an extended duration, alternative environments to undertake the initial program, maintenance programs following initial exercise training, program repetition, and incorporation of approaches to address behavioral change.,This may be complemented by methods designed to maximize uptake and completion of a pulmonary rehabilitation program. | 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. | Observational studies using case-control designs have showed an increased risk of pneumonia associated with inhaled corticosteroid (ICS)-containing medications in patients with chronic obstructive pulmonary disease (COPD).,New-user observational cohort designs may minimize biases associated with previous case-control designs.,To estimate the association between ICS and pneumonia among new users of ICS relative to inhaled long-acting bronchodilator (LABD) monotherapy.,Pneumonia events in COPD patients ≥45 years old were compared among new users of ICS medications (n = 11,555; ICS, ICS/long-acting β2-agonist [LABA] combination) and inhaled LABD monotherapies (n = 6,492; LABA, long-acting muscarinic antagonists) using Cox proportional hazards models, with propensity scores to adjust for confounding.,Setting: United Kingdom electronic medical records with linked hospitalization and mortality data (2002-2010).,New users were censored at earliest of: pneumonia event, death, changing/discontinuing treatment, or end of follow-up.,Outcomes: severe pneumonia (primary) and any pneumonia (secondary).,Following adjustment, new use of ICS-containing medications was associated with an increased risk of pneumonia hospitalization (n = 322 events; HR = 1.55, 95% CI: 1.14, 2.10) and any pneumonia (n = 702 events; HR = 1.49, 95% CI: 1.22, 1.83).,Crude incidence rates of any pneumonia were 48.7 and 30.9 per 1000 person years among the ICS-containing and LABD cohorts, respectively.,Excess risk of pneumonia with ICS was reduced when requiring ≥1 month or ≥ 6 months of new use.,There was an apparent dose-related effect, with greater risk at higher daily doses of ICS.,There was evidence of channeling bias, with more severe patients prescribed ICS, for which the analysis may not have completely adjusted.,The results of this new-user cohort study are consistent with published findings; ICS were associated with a 20-50% increased risk of pneumonia in COPD, which reduced with exposure time.,This risk must be weighed against the benefits when prescribing ICS to patients with COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is a major public health problem, associated with considerable morbidity and health care costs.,The global burden of COPD morbidity is predicted to rise substantially in the coming decade, but could be moderated by better use of existing management strategies.,Smoking cessation, medication therapy, and pulmonary rehabilitation have all been shown to diminish morbidity and improve patient outcomes.,But each of these strategies requires adherence.,Adherence is crucial for optimizing clinical outcomes in COPD, with nonadherence resulting in a significant health and economic burden.,Suboptimal medication adherence is common among COPD patients, due to a number of factors that involve the medication, the delivery device, the patient, and the health professionals caring for the patient.,Lack of medication adherence needs to be identified and addressed by using simplified treatment regimens, increasing patient knowledge about self-management, and enhancing provider skills in patient education, communication, and adherence counseling.,This article reports some of the challenges of medication nonadherence faced by the clinician in the management of COPD, and suggests ways to evaluate and improve adherence effectively in primary care. | 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 | 1 |
The PHARMACOP-intervention significantly improved medication adherence and inhalation technique for patients with COPD compared with usual care.,This study aimed to evaluate its cost-effectiveness.,An economic analysis was performed from the Belgian healthcare payer’s perspective.,A Markov model was constructed in which a representative group of patients with COPD (mean age of 70 years, 66% male, 43% current smokers and mean Forced Expiratory Volume in 1 second of % predicted of 50), was followed for either receiving the 3-month PHARMACOP-intervention or usual care.,Three types of costs were calculated: intervention costs, medication costs and exacerbation costs.,Outcome measures included the number of hospital-treated exacerbations, cost per prevented hospital-treated exacerbation and cost per Quality Adjusted Life-Year.,Follow-up was 1 year in the basecase analysis.,Sensitivity and scenario analyses (including long-term follow-up) were performed to assess uncertainty.,In the basecase analysis, the average overall costs per patient for the PHARMACOP-intervention and usual care were €2,221 and €2,448, respectively within the 1-year time horizon.,This reflects cost savings of €227 for the PHARMACOP-intervention.,The PHARMACOP-intervention resulted in the prevention of 0.07 hospital-treated exacerbations per patient (0.177 for PHARMACOP versus 0.244 for usual care).,Results showed robust cost-savings in various sensitivity analyses.,Optimization of current pharmacotherapy (e.g. close monitoring of inhalation technique and medication adherence) has been shown to be cost-saving and should be considered before adding new therapies. | Adherence to medication among individuals with chronic obstructive pulmonary disease (COPD) is suboptimal and has negative impacts on survival and health care costs.,No systematic review has examined the effectiveness of interventions designed to improve medication adherence.,Electronic databases Medline and Cochrane were searched using a combination of MeSH and keywords.,Eligible studies were interventions with a primary or secondary aim to improve medication adherence among individuals with COPD published in English.,Included studies were assessed for methodological quality using the Effective Practice and Organisation of Care (EPOC) criteria.,Of the 1,186 papers identified, seven studies met inclusion criteria.,Methodological quality of the studies was variable.,Five studies identified effective interventions.,Strategies included: brief counselling; monitoring and feedback about inhaler use through electronic medication delivery devices; and multi-component interventions consisting of self-management and care co-ordination delivered by pharmacists and primary care teams.,Further research is needed to establish the most effective and cost effective interventions.,Special attention should be given to increasing patient sample size and using a common measure of adherence to overcome methodological limitations.,Interventions that involve caregivers and target the healthcare provider as well as the patient should be further explored. | 1 |
Reduced physical activity is an important feature of Chronic Obstructive Pulmonary Disease (COPD).,Various activity monitors are available but their validity is poorly established.,The aim was to evaluate the validity of six monitors in patients with COPD.,We hypothesized triaxial monitors to be more valid compared to uniaxial monitors.,Thirty-nine patients (age 68±7years, FEV1 54±18%predicted) performed a one-hour standardized activity protocol.,Patients wore 6 monitors (Kenz Lifecorder (Kenz), Actiwatch, RT3, Actigraph GT3X (Actigraph), Dynaport MiniMod (MiniMod), and SenseWear Armband (SenseWear)) as well as a portable metabolic system (Oxycon Mobile).,Validity was evaluated by correlation analysis between indirect calorimetry (VO2) and the monitor outputs: Metabolic Equivalent of Task [METs] (SenseWear, MiniMod), activity counts (Actiwatch), vector magnitude units (Actigraph, RT3) and arbitrary units (Kenz) over the whole protocol and slow versus fast walking.,Minute-by-minute correlations were highest for the MiniMod (r = 0.82), Actigraph (r = 0.79), SenseWear (r = 0.73) and RT3 (r = 0.73).,Over the whole protocol, the mean correlations were best for the SenseWear (r = 0.76), Kenz (r = 0.52), Actigraph (r = 0.49) and MiniMod (r = 0.45).,The MiniMod (r = 0.94) and Actigraph (r = 0.88) performed better in detecting different walking speeds.,The Dynaport MiniMod, Actigraph GT3X and SenseWear Armband (all triaxial monitors) are the most valid monitors during standardized physical activities.,The Dynaport MiniMod and Actigraph GT3X discriminate best between different walking speeds. | Persons with Chronic Obstructive Pulmonary Disease (COPD), performing some level of regular physical activity, have a lower risk of both COPD-related hospital admissions and mortality.,COPD patients of all stages seem to benefit from exercise training programs, thereby improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue.,Physical inactivity, which becomes more severe with increasing age, is a point of concern in healthy older adults.,COPD might worsen this scenario, but it is unclear to what degree.,This literature review aims to present the extent of the impact of COPD on objectively-measured daily physical activity (DPA).,The focus is on the extent of the impact that COPD has on duration, intensity, and counts of DPA, as well as whether the severity of the disease has an additional influence on DPA.,A literature review was performed in the databases PubMed [MEDLINE], Picarta, PEDRO, ISI Web of Knowledge and Google scholar.,After screening, 11 studies were identified as being relevant for comparison between COPD patients and healthy controls with respect to duration, intensity, and counts of DPA.,Four more studies were found to be relevant to address the subject of the influence the severity of the disease may have on DPA.,The average percentage of DPA of COPD patients vs. healthy control subjects for duration was 57%, for intensity 75%, and for activity counts 56%.,Correlations of DPA and severity of the disease were low and/or not significant.,From the results of this review, it appears that patients with COPD have a significantly reduced duration, intensity, and counts of DPA when compared to healthy control subjects.,The intensity of DPA seems to be less affected by COPD than duration and counts.,Judging from the results, it seems that severity of COPD is not strongly correlated with level of DPA.,Future research should focus in more detail on the relation between COPD and duration, intensity, and counts of DPA, as well as the effect of disease severity on DPA, so that these relations become more understandable. | 1 |
COPD is characterized by persistent respiratory symptoms and airflow limitation, caused by a mixture of small airway disease and pulmonary emphysema.,Programmed cell death has drawn the attention of COPD researchers because emphysema is thought to result from epithelial cell death caused by smoking.,Although apoptosis has long been thought to be the sole form of programmed cell death, recent studies have reported the existence of a genetically programmed and regulated form of necrosis called necroptosis.,Autophagy was also previously considered a form of programmed cell death, but this has been reconsidered.,However, recent studies have revealed that autophagy can regulate programmed cell death, including apoptosis and necroptosis.,It is also becoming clear that autophagy can selectively degrade specific proteins, organelles, and invading bacteria by a process termed “selective autophagy” and that this process is related to the pathogenesis of human diseases.,In this review, we outline the most recent studies implicating autophagy, selective autophagy, and necroptosis in COPD.,Strategies targeting these pathways may yield novel therapies for COPD. | This study compared reticular basement membrane (Rbm) and vascular remodelling within the bronchial mucosa of subjects with chronic obstructive pulmonary disease (COPD) with those from patients with asthma, to test the ‘Dutch hypothesis’ of whether these are essentially the same or different pathological conditions.,Bronchoscopic biopsies were stained with anti-collagen IV antibody; 18 current smoking COPD, 10 symptomatic asthmatics and 13 healthy non-smoking controls were studied.,The Rbm in COPD was fragmented, non-homogeneous, variable in thickness and hypervascular, whereas in asthma the Rbm was compact and homogeneous with no evidence of increased vascularity compared to controls.,Length of Rbm splitting presented as percentage of Rbm length was used to measure fragmentation; it was greater in COPD than in controls and asthmatics [median (range) 20.7% (0.4-68.5) versus 5.3% (0.0-21.7) versus 1.5% (0.0-15.1), P < 0.001].,The number of Rbm vessels/mm Rbm [median (range) 10.1 (1.6-23.0) versus 4.5 (0.0-26.4) versus 4.4 (0.4-8.1), P < 0.01] and area of Rbm vessels, μm2/mm Rbm [median (range) 953 (115-2456) versus 462 (0-3263) versus 426 (32-2216), P < 0.05] was also increased in COPD compared to normal subjects and asthmatics.,The characteristics of Rbm remodelling are quite different in asthma and COPD. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) are at higher risk of stroke than those without COPD.,This study aims to explore the impact of inhaled pharmacotherapy on stroke risk in COPD patients during a three-year follow-up, using a nationwide, population-based study and a matched cohort design.,The study cohort comprised 10,413 patients who had received COPD treatment between 2004 and 2006; 41,652 randomly selected subjects comprised the comparison cohort.,Cox proportional hazard regressions and two-stage propensity score calibration were performed to determine the impact of various inhaled therapies including short-acting muscarinic antagonists, long-acting muscarinic antagonists, short-acting β-agonists (SABAs), long-acting β-agonists (LABAs), and LABA plus inhaled corticosteroid (ICS), on the risk after adjustment for patient demographic characteristics and comorbid disorders.,Of the 52,065 sampled patients, 2,689 (5.2%) developed stroke during follow-up, including 727 (7.0%) from the COPD cohort and 1,962 (4.7%) from the comparison cohort (p < 0.001).,Treatment with SABA was associated with 1.67-fold (95% CI 1.45-1.91; p < 0.001) increased risk of stroke in COPD patients.,By contrast, the cumulative incidence of stroke was significantly lower in those treated with LABA plus ICS than those treated without (adjusted hazard ratio 0.75, 95% CI 0.60-0.94, p = 0.014).,Among COPD patients, the use of inhaled SABA is associated with an increased risk of stroke, and combination treatment with inhaled LABA and ICS relates to a risk reduction.,Further prospective research is needed to verify whether LABA plus ICS confers protection against stroke in patients with COPD. | To estimate the incidence of pneumonia by COPD status and the excess cost of inpatient primary pneumonia in elders with COPD.,A retrospective, longitudinal study using claims linked to eligibility/demographic data for a 5% sample of fee-for-service Medicare beneficiaries from 2005 through 2007.,Incidence rates of pneumonia were calculated for elders with and without COPD and for elders with COPD and coexistent congestive heart failure (CHF).,Propensity-score matching with multivariate generalized linear regression was used to estimate the excess direct medical cost of inpatient primary pneumonia in elders with COPD as compared with elders with COPD but without a pneumonia hospitalization.,Elders with COPD had nearly six-times the incidence of pneumonia compared with elders without COPD (167.6/1000 person-years versus 29.5/1000 person-years; RR=5.7, p <0 .01); RR increased to 8.1 for elders with COPD and CHF compared with elders without COPD.,The incidence of inpatient primary pneumonia among elders with COPD was 54.2/1000 person-years compared with 7/1000 person-years for elders without COPD; RR=7.7, p<0.01); RR increased to 11.0 for elders with COPD and CHF compared with elders without COPD.,The one-year excess direct medical cost of inpatient pneumonia in COPD patients was $ 22,697 ($45,456 in cases vs. $ 22,759 in controls (p <0.01)); 70.2% of this cost was accrued during the quarter of the index hospitalization.,During months 13 through 24 following the index hospitalization, the excess direct medical cost was $ 5,941 ($23,215 in cases vs. $ 17,274 in controls, p<0.01).,Pneumonia occurs more frequently in elders with COPD than without COPD.,The excess direct medical cost in elders with inpatient pneumonia extends up to 24 months following the index hospitalization and represents $28,638 in 2010 dollars. | 1 |
Quality of life (QoL) has a weak relationship with lung function (LF) impairment in COPD; some cope well despite poor LF, whereas others suffer disproportionate QoL impairment despite well-preserved LF.,Adjuvant non-pharmacological interventions such as rehabilitation and psychological/behavioural support may help if acceptable and targeted appropriately, but they are under-used and sometimes declined by patients.,This study aimed to explore and understand variations in experiences and coping strategies in patients with different severities of disease and disease-specific QoL.,Thirty-four participants were purposively sampled across a spectrum of LF and QoL impairment, to cover a grid of sub-groups (‘very severe LF, good QoL’, moderate LF, poor QoL’ and so on).,Semi-structured interviews, digitally recorded, were analysed by thematic analysis.,Data saturation was achieved.,Four themes emerged: symptom impact, coping strategies, coping challenges and support needs.,Most of them described using multiple coping strategies, yet over half reported significant challenges coping with COPD, including psychological impact, non-acceptance of diagnosis and/or disease progression, effects of co-morbidities and inadequate self-management skills.,Approximately half of the participants wanted further help, ideally non-pharmacological, across all LF impairment groups but mainly with lower QoL.,Those with lower QoL additionally reported greater psychological distress and greater use of non-pharmacological support strategies where accessible.,Patients who develop effective coping strategies have a better QoL independent of objective LF, whereas others cope poorly, are aware of this and report more use of non-pharmacological approaches.,This study suggests that severely impaired QoL, irrelevant of lung function, is a powerful patient-centred indication to explore the positive benefits of psychological and behavioural support for distressed COPD patients. | Nighttime symptoms can negatively impact the quality of life of patients with chronic obstructive pulmonary disease (COPD).,The Nighttime Symptoms of COPD Instrument (NiSCI) was designed to measure the occurrence and severity of nighttime symptoms in patients with COPD, the impact of symptoms on nighttime awakenings, and rescue medication use.,The objective of this study was to explore item reduction, inform scoring recommendations, and evaluate the psychometric properties of the NiSCI.,COPD patients participating in a Phase III clinical trial completed the NiSCI daily.,Item analyses were conducted using weekly mean and single day scores.,Descriptive statistics (including percentage of respondents at floor/ceiling and inter-item correlations), factor analyses, and Rasch model analyses were conducted to examine item performance and scoring.,Test-retest reliability was assessed for the final instrument using the intraclass correlation coefficient (ICC).,Correlations with assessments conducted during study visits were used to evaluate convergent and known-groups validity.,Data from 1,663 COPD patients aged 40-93 years were analyzed.,Item analyses supported the generation of four scores.,A one-factor structure was confirmed with factor analysis and Rasch analysis for the symptom severity score.,Test-retest reliability was confirmed for the six-item symptom severity (ICC, 0.85), number of nighttime awakenings (ICC, 0.82), and rescue medication (ICC, 0.68) scores.,Convergent validity was supported by significant correlations between the NiSCI, St George’s Respiratory Questionnaire, and Exacerbations of Chronic Obstructive Pulmonary Disease Tool-Respiratory Symptoms scores.,The results suggest that the NiSCI can be used to determine the severity of nighttime COPD symptoms, the number of nighttime awakenings due to COPD symptoms, and the nighttime use of rescue medication.,The NiSCI is a reliable and valid instrument to evaluate these concepts in COPD patients in clinical trials and clinical practice.,Scoring recommendations and steps for further research are discussed. | 1 |
Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation. | The successful management of asthma and chronic obstructive pulmonary disease (COPD) mostly depends on adherence to inhalation drug therapy, the usage of which is commonly associated with many difficulties in real life.,Improvement of patients’ adherence to inhalation technique could lead to a better outcome in the treatment of asthma and COPD.,The aim of this study was to assess the utility of inhalation technique in clinical and functional control of asthma and COPD during a 3-month follow-up.,A total of 312 patients with asthma or COPD who used dry powder Turbuhaler were enrolled in this observational study.,During three visits (once a month), training in seven-step inhalation technique was given and it was practically demonstrated.,Correctness of patients’ usage of inhaler was assessed in three visits by scoring each of the seven steps during administration of inhaler dose.,Assessment of disease control was done at each visit and evaluated as: fully controlled, partially controlled, or uncontrolled.,Patients’ subjective perception of the simplicity of inhalation technique, disease control, and quality of life were assessed by using specially designed questionnaires.,Significant improvement in inhalation technique was achieved after the third visit compared to the first one, as measured by the seven-step inhaler usage score (5.94 and 6.82, respectively; P<0.001).,Improvement of disease control significantly increased from visit 1 to visit 2 (53.9% and 74.5%, respectively; P<0.001) and from visit 2 to visit 3 (74.5% and 77%, respectively; P<0.001).,Patients’ subjective assessment of symptoms and quality of life significantly improved from visit 1 to visit 3 (P<0.001).,Adherence to inhalation therapy is one of the key factors of successful respiratory disease treatment.,Therefore, health care professionals should insist on educational programs aimed at improving patients’ inhalation technique with different devices, resulting in better long-term disease control and improved quality of life. | 1 |
Purpose: To determine to what extent chronic obstructive pulmonary disease (COPD) affects mortality and morbidity rates in patients treated with off-pump coronary artery bypass graft (CABG).,Methods: A total of 321 patients treated with off-pump CABG were included in the present study.,Of the 321 patients, 46 patients had COPD and they were designated as Group 1 and the remaining 275 patients did not have COPD and they were considered as Group 2.,We compared the data obtained from the patients in both groups.,Results: While preoperative spirometry values and arterial blood gas oxygen saturation levels were significantly lower, the partial values of carbon dioxide were higher in Group 1.,Likewise, extubation time, the amount of drainage and blood transfusion, inotropic support, prolonged intubation, pulmonary complications, the use of bronchodilators, and steroids were statistically higher in Group 1 when compared with Group 2.,Overall, there was no marked difference between the two groups in terms of mortality incidence.,Conclusion: We found similar morbidity and mortality rates among the patients with COPD and without COPD when they were treated with off-pump CABG.,Therefore, the present results indicate that the presence of COPD is not associated with in-hospital mortality or severe morbidity post-CABG by off-pump approach. | Little is known about the effect of long-term aspirin use on acute severity of COPD.,We hypothesized that, in patients hospitalized for acute exacerbation of COPD (AECOPD), long-term aspirin use is associated with lower risks of disease severity (in-hospital death, mechanical ventilation use, and hospital length-of-stay).,We conducted a retrospective cohort study using large population-based data from 2012 through 2013.,Among 206,686 patients (aged ≥40 years) hospitalized for AECOPD, aspirin users had lower in-hospital mortality (1.0 vs.,1.4%; OR 0.60 [95% CI 0.50-0.72]; P < 0.001) and lower risk of invasive mechanical ventilation use (1.7 vs.,2.6%; OR 0.64 [95% CI 0.55-0.73]; P < 0.001) compared to non-users, while there was no significant difference in risks of non-invasive positive pressure ventilation use.,Length-of-stay was shorter in aspirin users compared to non-users (P < 0.001).,In sum, in patients with AECOPD, aspirin use was associated with lower rates of in-hospital mortality and invasive mechanical ventilation use, and shorter length-of-stay. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by irreversible, progressive obstruction of lung airflow.,Dyspnea (shortness of breath [SOB]) is the COPD symptom which most negatively impacts patients’ daily activities.,To assess how SOB affects daily activities, 37 items were drafted through focus group discussions and cognitive interviews with COPD patients to develop a patient-reported outcome instrument: the Shortness of Breath with Daily Activities questionnaire (SOBDA).,Psychometric analysis was conducted to reduce the number of items and evaluate the measurement properties of the final SOBDA.,Prospective, observational study of 334 COPD patients, recruited from 24 pulmonology and internal medicine clinics in the United States.,The 37-item SOBDA was administered to patients each evening for 28 days using an electronic diary.,Patients answered every item and rated their level of SOB experienced that day during specific activities.,Item selection was conducted by examining item characteristics, dimensionality, and Rasch model analysis results.,The decision to delete an item was based on psychometric evidence, content validity, and expert clinical input.,The final SOBDA instrument was evaluated for internal consistency, reproducibility, convergent validity, known-groups validity, and responsiveness.,Twenty-four items from the 37-item pool were removed following the item selection process: nine items were removed due to high item-to-item correlations; five due to floor effects; three due to infrequent activity; one due to gender bias; two due to low factor loadings; three due to unordered response options; and one due to expert’s discretion.,Internal consistency and reproducibility of the final SOBDA were demonstrated by Cronbach Alpha = 0.87, and intra-class correlation coefficient = 0.91.,Convergent validity was demonstrated by high correlation with the CRQ-SAS (0.60) and SGRQ-C (0.61).,Known groups validity was demonstrated by significant difference between ratings of the mMRC and clinical global rating of severity.,Evaluation of the ability to detect change was not performed owing to too few responders at the end of the study.,Through the empirical item reduction process, 13 items were selected from the 37-item pool generated during qualitative development.,The final 13-item SOBDA is a reliable and valid instrument for use in clinical trials. | Chronic obstructive pulmonary disease (COPD) patients may suffer from poor sleep and health-related quality of life.,We hypothesized that disturbed sleep in COPD is correlated with quality of life.,In 180 patients with COPD (forced expired volume in 1 second [FEV1] 47.6 ± 15.2% predicted, 77.8% male, aged 65.9 ± 11.7 years), we administered general (Health Utilities Index 3) and disease-specific (St George’s Respiratory) questionnaires and an index of disturbed sleep (Pittsburgh Sleep Quality Index).,Overall scores indicated poor general (Health Utilities Index 3: 0.52 ± 0.38), disease- specific (St George’s: 57.0 ± 21.3) quality of life and poor sleep quality (Pittsburgh 11.0 ± 5.4).,Sleep time correlated with the number of respiratory and anxiety symptoms reported at night.,Seventy-seven percent of the patients had Pittsburg scores >5, and the median Pittsburgh score was 12.,On multivariate regression, the Pittsburgh Sleep Quality Index was an independent predictor of both the Health Utilities Index 3 and the St George’s scores, accounting for 3% and 5%, respectively, of the scores.,Only approximately 25% of the patients demonstrated excessive sleepiness (Epworth Sleepiness Scale >9).,Most patients with COPD suffer disturbed sleep.,Sleep quality was correlated with general and disease-specific quality of life.,Only a minority of COPD patients complain of being sleepy. | 1 |
Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) was proposed by the science committees of both Global Initiative for Asthma (GINA) and Global Initiative for Chronic Obstructive Lung Disease (GOLD).,However, the definition of ACOS has remained unclear all over the world, and the prevalence rate of ACOS is basically dependent on the patient’s symptoms or the physician’s opinion, based on questionnaire testing.,In the current case report, we investigated the prevalence rate of COPD patients with high levels of fractional exhaled nitric oxide (FENO) or immunoglobulin E (IgE) as candidate markers of ACOS in COPD, as a multicenter, cross-sectional study.,Outpatients with COPD were enrolled from Tohoku University Hospital, Sendai, Japan, and five hospitals (Tohoku University Hospital, Sendai, Japan; NTT East Tohoku Hospital, Sendai, Japan; Wakayama Medical University Hospital, Kimiidera, Japan; Hiraka General Hospital, Yokote, Japan; Iwate Prefectural Isawa Hospital, Oshu, Japan) with pulmonary physicians from March 1, 2013 to February 28, 2014.,When they were estimated using 35 ppb as the cutoff value of FENO, the prevalence rate of ACOS was 16.3% in COPD.,When estimated by both FENO and IgE, the high-FENO/high-IgE group was 7.8% in COPD.,To the best of our knowledge, this study is the first to detect the prevalence rate of ACOS in COPD populations by using objective biomarkers.,The results from the current study should be useful to identify the subgroup requiring early intervention by inhaled corticosteroids/long-acting beta agonist combination in COPD in order to improve the long-term management for ACOS. | 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 |
Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and loss of lung tissue mainly consisting of extracellular matrix (ECM).,Three of the main ECM components are type I collagen, the main constituent in the interstitial matrix, type VI collagen, and elastin, the signature protein of the lungs.,During pathological remodeling driven by inflammatory cells and proteases, fragments of these proteins are released into the bloodstream, where they may serve as biomarkers for disease phenotypes.,The aim of this study was to investigate the lung ECM remodeling in healthy controls and COPD patients in the COPDGene study.,The COPDGene study recruited 10,300 COPD patients in 21 centers.,A subset of 89 patients from one site (National Jewish Health), including 52 COPD patients, 12 never-smoker controls and 25 smokers without COPD controls, were studied for serum ECM biomarkers reflecting inflammation-driven type I and VI collagen breakdown (C1M and C6M, respectively), type VI collagen formation (Pro-C6), as well as elastin breakdown mediated by neutrophil elastase (EL-NE).,Correlation of biomarkers with lung function, the SF-36 quality of life questionnaire, and other clinical characteristics was also performed.,The circulating concentrations of biomarkers C6M, Pro-C6, and EL-NE were significantly elevated in COPD patients compared to never-smoking control patients (all p < 0.05).,EL-NE was significantly elevated in emphysema patients compared to smoking controls (p < 0.05) and never-smoking controls (p < 0.005), by more than 250%.,C1M was inversely associated with forced expiratory volume in 1 s (FEV1) (r = −0.344, p = 0.001), as was EL-NE (r = −0.302, p = 0.004) and Pro-C6 (r = −0.259, p = 0.015).,In the patients with COPD, Pro-C6 was correlated with percent predicted Forced Vital Capacity (FVC) (r = 0.281, p = 0.046) and quality of life using SF-36.,C6M and Pro-C6, were positively correlated with blood eosinophil numbers in COPD patients (r = 0.382, p = 0.006 and r = 0.351, p = 0.012, respectively).,These data suggest that type VI collagen turnover and elastin degradation by neutrophil elastase are associated with COPD-induced inflammation (eosinophil-bronchitis) and emphysema.,Serological assessment of type VI collagen and elastin turnover may assist in identification of phenotypes likely to be associated with progression and amenable to precision medicine for clinical trials. | Cigarette smoke (CS)-induced mitochondrial damage with increased reactive oxygen species (ROS) production has been implicated in COPD pathogenesis by accelerating senescence.,Mitophagy may play a pivotal role for removal of CS-induced damaged mitochondria, and the PINK1 (PTEN-induced putative kinase 1)-PARK2 pathway has been proposed as a crucial mechanism for mitophagic degradation.,Therefore, we sought to investigate to determine if PINK1-PARK2-mediated mitophagy is involved in the regulation of CS extract (CSE)-induced cell senescence and in COPD pathogenesis.,Mitochondrial damage, ROS production, and cell senescence were evaluated in primary human bronchial epithelial cells (HBEC).,Mitophagy was assessed in BEAS-2B cells stably expressing EGFP-LC3B, using confocal microscopy to measure colocalization between TOMM20-stained mitochondria and EGFP-LC3B dots as a representation of autophagosome formation.,To elucidate the involvement of PINK1 and PARK2 in mitophagy, knockdown and overexpression experiments were performed.,PINK1 and PARK2 protein levels in lungs from patients were evaluated by means of lung homogenate and immunohistochemistry.,We demonstrated that CSE-induced mitochondrial damage was accompanied by increased ROS production and HBEC senescence.,CSE-induced mitophagy was inhibited by PINK1 and PARK2 knockdown, resulting in enhanced mitochondrial ROS production and cellular senescence in HBEC.,Evaluation of protein levels demonstrated decreased PARK2 in COPD lungs compared with non-COPD lungs.,These results suggest that PINK1-PARK2 pathway-mediated mitophagy plays a key regulatory role in CSE-induced mitochondrial ROS production and cellular senescence in HBEC.,Reduced PARK2 expression levels in COPD lung suggest that insufficient mitophagy is a part of the pathogenic sequence of COPD. | 1 |
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 | Exercise training improves exercise tolerance in chronic obstructive pulmonary disease (COPD).,Tiotropium 18 μg once daily induces sustained bronchodilation throughout the day and reduces hyperinflation, one of the pathophysiological factors contributing to exertional dyspnea in COPD patients.,To determine whether tiotropium enhances the effects of exercise training in patients with COPD.,Multicenter, 25 week randomized, double-blind, placebo-controlled, parallel-group study.,Twelve Italian Pulmonary Units practicing pulmonary rehabilitation.,Two hundred thirty four COPD patients (196 males; mean age: 67.4 ± 7.6; forced expiratory volume at 1 second (FEV1): 41.4 ± 13.0% predicted) were randomised to tiotropium 18 μg or placebo inhalation capsules taken once daily.,Both groups underwent a 8 week pulmonary rehabilitation program (PR) consisting of 3 exercise training session per week.,Baseline, at the end of PR and after 12 weeks, patients completed pulmonary function testing, six minute walking test (6MWT), the Baseline and Transition Dyspnea Index (BDI and TDI), and the St.,George’s Respiratory Questionnaire (SGRQ).,Relative to placebo, tiotropium had larger trough and post-study drug FEV1 responses on all test days.,At the end of and 12 weeks following PR, patients on tiotropium showed no statistically significant differences in 6MWT compared to patients on placebo.,Compared to the period immediately prior to PR, the mean improvement in 6MWT was only 29.7 meters (7.1%) for the combined cohort.,Mean TDI focal scores at the end of PR were 3.60 for tiotropium and 2.25 for placebo (p < 0.01).,At 12 weeks after PR, TDI focal scores were 2.71 for tiotropium and 2.11 for placebo (p = 0.16).,Reduction in all four SGRQ component scores, indicating an improvement in health-related quality of life, was observed for the tiotropium group over the duration of the study compared to placebo but the differences were not statistically significant.,During the study period, there were fewer exacerbations and exacerbation days in the tiotropium group.,Although significant improvements were observed with perceived dyspnea, compared to placebo, the addition of tiotropium to pulmonary rehabilitation did not improve the 6MWT. | 1 |
Cigarette smoking is the main risk factor for the development of chronic obstructive pulmonary disease (COPD), a major cause of morbidity and mortality worldwide.,Despite this, the cellular and molecular mechanisms that contribute to COPD pathogenesis are still poorly understood.,The objective of this study was to assess IL-1 α and β expression in COPD patients and to investigate their respective roles in perpetuating cigarette smoke-induced inflammation.,Functional studies were pursued in smoke-exposed mice using gene-deficient animals, as well as blocking antibodies for IL-1α and β.,Here, we demonstrate an underappreciated role for IL-1α expression in COPD.,While a strong correlation existed between IL-1α and β levels in patients during stable disease and periods of exacerbation, neutrophilic inflammation was shown to be IL-1α-dependent, and IL-1β- and caspase-1-independent in a murine model of cigarette smoke exposure.,As IL-1α was predominantly expressed by hematopoietic cells in COPD patients and in mice exposed to cigarette smoke, studies pursued in bone marrow chimeric mice demonstrated that the crosstalk between IL-1α+ hematopoietic cells and the IL-1R1+ epithelial cells regulates smoke-induced inflammation.,IL-1α/IL-1R1-dependent activation of the airway epithelium also led to exacerbated inflammatory responses in H1N1 influenza virus infected smoke-exposed mice, a previously reported model of COPD exacerbation.,This study provides compelling evidence that IL-1α is central to the initiation of smoke-induced neutrophilic inflammation and suggests that IL-1α/IL-1R1 targeted therapies may be relevant for limiting inflammation and exacerbations in COPD. | Chronic obstructive pulmonary disease is a progressive lung disease that is punctuated by periods of exacerbations (worsening of symptoms) that are attributable to viral infections.,While rhinoviruses are most commonly isolated viruses during episodes of exacerbation, influenza viruses have the potential to become even more problematic with the increased likelihood of an epidemic.,This study examined the impact of current and potential pharmacological targets namely the systemic corticosteroid dexamethasone and the peroxisome proliferator-activated receptor- gamma agonist pioglitazone on the outcome of infection in smoke-exposed mice.,C57BL/6 mice were exposed to room air or cigarette smoke for 4 days and subsequently inoculated with an H1N1 influenza A virus.,Interventions were delivered daily during the course of infection.,We show that smoke-exposed mice have an exacerbated inflammatory response following infection.,While smoke exposure did not compromise viral clearance, precision cut lung slices from smoke-exposed mice showed greater expression of CC (MCP-1, -3), and CXC (KC, MIP-2, GCP-2) chemokines compared to controls when stimulated with a viral mimic or influenza A virus.,While dexamethasone treatment partially attenuated the inflammatory response in the broncho-alveolar lavage of smoke-exposed, virally-infected animals, viral-induced neutrophilia was steroid insensitive.,In contrast to controls, dexamethasone-treated smoke-exposed influenza-infected mice had a worsened health status.,Pioglitazone treatment of virally-infected smoke-exposed mice proved more efficacious than the steroid intervention.,Further mechanistic evaluation revealed that a deficiency in CCR2 did not improve the inflammatory outcome in smoke-exposed, virally-infected animals.,This animal model of cigarette smoke and H1N1 influenza infection demonstrates that smoke-exposed animals are differentially primed to respond to viral insult.,While providing a platform to test pharmacological interventions, this model demonstrates that treating viral exacerbations with alternative anti-inflammatory drugs, such as PPAR-gamma agonists should be further explored since they showed greater efficacy than systemic corticosteroids. | 1 |
The fixed-dose dual bronchodilator combination (FDC) of tiotropium and olodaterol showed increased effectiveness regarding lung function and health-related quality of life in patients with chronic obstructive pulmonary disease (COPD) compared with the use of its mono-components.,Yet, while effectiveness and safety have been shown, the health economic implication of this treatment is still unknown.,The aim of this study was to assess the cost-utility and budget impact of tiotropium-olodaterol FDC in patients with moderate to very severe COPD in the Netherlands.,A cost-utility study was performed, using an individual-level Markov model.,To populate the model, individual patient-level data (age, height, sex, COPD duration, baseline forced expiratory volume in 1 second) were obtained from the tiotropium-olodaterol TOnado trial.,In the model, forced expiratory volume in 1 second and patient-level data were extrapolated to utility and survival, and treatment with tiotropium-olodaterol FDC was compared with tiotropium.,Cost-utility analysis was performed from the Dutch health care payer’s perspective using a 15-year time horizon in the base-case analysis.,The standard Dutch discount rates were applied (costs: 4.0%; effects: 1.5%).,Both univariate and probabilistic sensitivity analyses were performed.,Budget impact was annually assessed over a 5-year time horizon, taking into account different levels of medication adherence.,As a result of cost increases, combined with quality-adjusted life-year (QALY) gains, results showed that tiotropium-olodaterol FDC had an incremental cost-effectiveness ratio of €7,004/QALY.,Without discounting, the incremental cost-effectiveness ratio was €5,981/QALY.,Results were robust in univariate and probabilistic sensitivity analyses.,Budget impact was estimated at €4.3 million over 5 years assuming 100% medication adherence.,Scenarios with 40%, 60%, and 80% adherence resulted in lower 5-year incremental cost increases of €1.7, €2.6, and €3.4 million, respectively.,Tiotropium-olodaterol FDC can be considered a cost-effective treatment under current Dutch cost-effectiveness thresholds. | Inhaled corticosteroid/long-acting β2-agonist combinations (ICS/LABA) have emerged as first line therapies for chronic obstructive pulmonary disease (COPD) patients with exacerbation history.,No randomized clinical trial has compared exacerbation rates among COPD patients receiving budesonide/formoterol combination (BFC) and fluticasone/salmeterol combination (FSC) to date, and only limited comparative data are available.,This study compared the real-world effectiveness of approved BFC and FSC treatments among matched cohorts of COPD patients in a large US managed care setting.,COPD patients (≥40 years) naive to ICS/LABA who initiated BFC or FSC treatments between 03/01/2009-03/31/2012 were identified in a geographically diverse US managed care database and followed for 12 months; index date was defined as first prescription fill date.,Patients with a cancer diagnosis or chronic (≥180 days) oral corticosteroid (OCS) use within 12 months prior to index were excluded.,Patients were matched 1-to-1 on demographic and pre-initiation clinical characteristics using propensity scores from a random forest model.,The primary efficacy outcome was COPD exacerbation rate, and secondary efficacy outcomes included exacerbation rates by event type and healthcare resource utilization.,Pneumonia objectives included rates of any diagnosis of pneumonia and pneumonia-related healthcare resource utilization.,Matching of the identified 3,788 BFC and 6,439 FSC patients resulted in 3,697 patients in each group.,Matched patients were well balanced on age (mean = 64 years), gender (BFC: 52% female; FSC: 54%), prior COPD-related medication use, healthcare utilization, and comorbid conditions.,During follow-up, no significant difference was seen between BFC and FSC patients for number of COPD-related exacerbations overall (rate ratio [RR] = 1.02, 95% CI = [0.96,1.09], p = 0.56) or by event type: COPD-related hospitalizations (RR = 0.96), COPD-related ED visits (RR = 1.11), and COPD-related office/outpatient visits with OCS and/or antibiotic use (RR = 1.01).,The proportion of patients diagnosed with pneumonia during the post-index period was similar for patients in each group (BFC = 17.3%, FSC = 19.0%, odds ratio = 0.92 [0.81,1.04], p = 0.19), and no difference was detected for pneumonia-related healthcare utilization by place of service.,This study demonstrated no difference in COPD-related exacerbations or pneumonia events between BFC and FSC treatment groups for patients new to ICS/LABA treatment in a real-world setting.,ClinicalTrials.gov identifier NCT01921127. | 1 |
The soluble cleaved urokinase plasminogen activator receptor (scuPAR) is a circulating protein detected in multiple diseases, including various cancers, cardiovascular disease, and kidney disease, where elevated levels of scuPAR have been associated with worsening prognosis and increased disease aggressiveness.,We aimed to identify novel genetic and biomolecular mechanisms regulating scuPAR levels.,Elevated serum scuPAR levels were identified in asthma (n=514) and chronic obstructive pulmonary disease (COPD; n=219) cohorts when compared to controls (n=96).,In these cohorts, a genome-wide association study of serum scuPAR levels identified a human plasma kallikrein gene (KLKB1) promoter polymorphism (rs4253238) associated with serum scuPAR levels in a control/asthma population (P=1.17×10−7), which was also observed in a COPD population (combined P=5.04×10−12).,Using a fluorescent assay, we demonstrated that serum KLKB1 enzymatic activity was driven by rs4253238 and is inverse to scuPAR levels.,Biochemical analysis identified that KLKB1 cleaves scuPAR and negates scuPAR's effects on primary human bronchial epithelial cells (HBECs) in vitro.,Chymotrypsin was used as a proproteolytic control, while basal HBECs were used as a control to define scuPAR-driven effects.,In summary, we reveal a novel post-translational regulatory mechanism for scuPAR using a hypothesis-free approach with implications for multiple human diseases.-Portelli, M.,A., Siedlinski, M., Stewart, C.,E., Postma, D.,S., Nieuwenhuis, M.,A., Vonk, J.,M., Nurnberg, P., Altmuller, J., Moffatt, M.,F., Wardlaw, A.,J., Parker, S.,G., Connolly, M.,J., Koppelman, G.,H., Sayers, I.,Genome-wide protein QTL mapping identifies human plasma kallikrein as a post-translational regulator of serum uPAR levels. | 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 |
Exacerbations of COPD are clinically relevant events with therapeutic and prognostic implications.,Yet, significant heterogeneity of clinical presentation and disease progression exists within acute exacerbations of COPD (AECOPD).,Currently, different phenotypes have been widely used to describe the characteristics among patients with AECOPD.,This has proved to be significant in the treatment and prediction of the outcomes of the disease.,In this review of published literature, the phenotypes of AECOPD were classified according to etiology, inflammatory biomarkers, clinical manifestation, comorbidity, the frequency of exacerbations, and so on.,This review concentrates on advancements in the use of phenotypes of AECOPD. | Objective To investigate whether an early rehabilitation intervention initiated during acute admission for exacerbations of chronic respiratory disease reduces the risk of readmission over 12 months and ameliorates the negative effects of the episode on physical performance and health status.,Design Prospective, randomised controlled trial.,Setting An acute cardiorespiratory unit in a teaching hospital and an acute medical unit in an affiliated teaching district general hospital, United Kingdom.,Participants 389 patients aged between 45 and 93 who within 48 hours of admission to hospital with an exacerbation of chronic respiratory disease were randomised to an early rehabilitation intervention (n=196) or to usual care (n=193).,Main outcome measures The primary outcome was readmission rate at 12 months.,Secondary outcomes included number of hospital days, mortality, physical performance, and health status.,The primary analysis was by intention to treat, with prespecified per protocol analysis as a secondary outcome.,Interventions Participants in the early rehabilitation group received a six week intervention, started within 48 hours of admission.,The intervention comprised prescribed, progressive aerobic, resistance, and neuromuscular electrical stimulation training.,Patients also received a self management and education package.,Results Of the 389 participants, 320 (82%) had a primary diagnosis of chronic obstructive pulmonary disease. 233 (60%) were readmitted at least once in the following year (62% in the intervention group and 58% in the control group).,No significant difference between groups was found (hazard ratio 1.1, 95% confidence interval 0.86 to 1.43, P=0.4).,An increase in mortality was seen in the intervention group at one year (odds ratio 1.74, 95% confidence interval 1.05 to 2.88, P=0.03).,Significant recovery in physical performance and health status was seen after discharge in both groups, with no significant difference between groups at one year.,Conclusion Early rehabilitation during hospital admission for chronic respiratory disease did not reduce the risk of subsequent readmission or enhance recovery of physical function following the event over 12 months.,Mortality at 12 months was higher in the intervention group.,The results suggest that beyond current standard physiotherapy practice, progressive exercise rehabilitation should not be started during the early stages of the acute illness.,Trial registration Current Controlled Trials ISRCTN05557928. | 1 |
The aim of the study was to examine the longitudinal change in quality of life components of patients with chronic obstructive pulmonary disease (COPD).,In the Hokkaido COPD Cohort Study, 261 subjects were appropriately treated and followed over 5 years with a 74% follow-up rate at the end.,The longitudinal changes in St George’s Respiratory Questionnaire (SGRQ) scores were annually evaluated with forced expiratory volume in 1 second (FEV1).,The subjects were classified into the rapid decliners, slow decliners, and sustainers based on ΔFEV1/year.,The activity component of SGRQ generally deteriorated over time, and its annual decline was the greatest in the rapid decliners (<25th percentile).,In contrast, the symptom component improved significantly year by year in the sustainers (>75 percentile), and it did not deteriorate even in the rapid decliners.,Of the baseline data, predictors for worsening of the activity component were older age and lower body mass index.,Larger reversibility was related to symptom component improvement.,Of the follow-up data, ΔFEV1/year was the best predictor for worsening of the components of SGRQ.,Continuous smoking was another factor for worsening of the activity component.,For the symptom component, a history of exacerbation by admission definition was the determinant of its deterioration, whereas use of beta agonists was related to improvement.,The longitudinal changes of quality of life and their determinants are markedly different and independent between its components.,The activity component of SGRQ generally deteriorated over years, while the symptom component rather improved in some patients with COPD under appropriate treatment. | 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. | 1 |
Special attention has emerged towards biomass smoke-induced chronic obstructive pulmonary disease (COPD), providing new knowledge for prevention and therapeutic approach of non-smoker COPD patients.,However, the understanding of biomass smoke COPD is still limited and somewhat controversial.,The aim of the present study was to compare COPD exclusively caused by tobacco smoking with COPD exclusively caused by environmental or occupational exposures.,For this cross-sectional study, COPD patients were recruited from outpatient clinics and formed two groups: non-smoker COPD group (n=16) with exposure to biomass smoke who did not smoke cigarette and tobacco smoker COPD group (n=15) with people who did not report biomass smoke exposure.,Subjects underwent pulmonary function tests, thoracic high-resolution computed tomography, 6-min walk test, and sputum induction.,The non-smoker COPD group had biomass smoke exposure of 133.3±86 hour-years.,The tobacco COPD group smoked 48.5±27.4 pack-years.,Women were 62.5 and 66.7%, respectively, of non-smokers and smokers.,The non-smoker COPD group showed higher prevalence of dyspnea, lower arterial oxygen tension (PaO2), and lower arterial oxygen saturation (SaO2%) with similar spirometry results, lung volumes, and diffusion capacity.,Regarding inflammatory biomarkers, differences were detected in sputum number of lymphomononuclear cells and in sputum concentrations of interleukin (IL)-6 and IL-8 with higher values in the smoker group.,Emphysema was more prevalent in the tobacco smoker group, which also showed higher relative bronchial wall thickness and lower lung density by quantitative analysis.,Biomass smoke induced more hypoxemia compared to tobacco in COPD patients with similar severity. | Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD); however, the similarities and differences in clinical presentation between smokers and nonsmokers are not fully described in patients with COPD.,This study was designed to address this issue in a general teaching hospital in the People’s Republic of China.,The medical records of patients hospitalized with a lung mass for further evaluation at Zhongshan Hospital, Fudan University, from January 2006 to December 2010 were reviewed and the data of interest were collected.,The definition of COPD was according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric criteria.,Participants who had a previous exacerbation within 4 weeks of admission, airflow limitation due to abnormalities in the large airways, or with other pulmonary diseases were excluded.,Included subjects were divided into nonsmokers with COPD and smokers with COPD by a cutoff of a 5 pack-year smoking history.,A total of 605 subjects were included in the final analysis.,The average age was 64.8±8.5 years and 62.0% (375/605) were smokers.,Eighty percent of the patients had mild to moderate disease (GOLD grade 1-2).,Age and years with COPD were comparable between the two groups.,Compared with smokers with COPD, nonsmokers with COPD were more likely to be female, reported less chronic cough and sputum, have less emphysema on radiologic examination, and higher measures of forced expiratory volume in the first second percent predicted (FEV1), forced expiratory volume in one second/forced vital capacity (FEV1/FVC%) percent predicted, maximal voluntary ventilation percent predicted, diffusing capacity of lung (DLCO) percent predicted, and DLCO/alveolar volume percent predicted, with lower levels of residual volume percent predicted and residual volume/total lung capacity percent predicted.,There were no significant differences between the two groups with regard to distribution of disease severity, vital capacity percent predicted, total lung capacity percent predicted, PaO2, PaCO2, modified Medical Research Council dyspnea score, wheezing, airway reversibility, and comorbidities.,Smoking amount (pack-years) was correlated negatively with FEV1 percent predicted, FEV1/FVC% percent predicted, inspiratory capacity percent predicted, inspiratory capacity/total lung capacity percent predicted, and DLCO percent predicted, and correlated positively with GOLD grade and symptoms.,Non-smokers with COPD had less impairment in airflow limitation and gas exchange, and a lower prevalence of emphysema, chronic cough, and sputum compared with their smoking counterparts.,Tobacco cessation is warranted in smokers with COPD. | 1 |
The burden of asthma and COPD among patients is high and people affected are frequently hospitalized due to exacerbations.,There are numerous reasons for the lack of disease control in asthma and COPD patients.,It is associated with non-adherence to guidelines on the part of the health care provider and with poor inhalation technique and/or non-adherence to the prescribed treatment plan by the patient.,This study aims to present data on inhaler technique and its impact on quality of life (QoL) and symptom control in a typical population of patients with chronic lung disease from a randomized controlled trial on medication adherence.,For this cross-sectional analysis, 165 asthma and COPD patients were analyzed.,Correct application of inhaler devices was tested using pre-defined checklists for each inhaler type.,QoL and symptom control were investigated using COPD Assessment Test (CAT) and Asthma Control Test (ACT).,Spirometry was used to measure forced vital capacity (FVC) and forced expiratory volume in one second (FEV1).,Overall, incorrect inhalation technique ranged from 0 to 53% depending on the type of inhaler.,COPD patients with incorrect device application had a higher CAT sum score compared to those with a correct device application (P = .02).,Moreover, COPD patients with incorrect device application were more likely to suffer from cough (P = .03) and were more breathless while walking uphill or a flight of stairs (P = .02).,While there was no significance found in asthma patients, COPD patients who used their devices correctly had a significantly better mean FEV1% predicted at baseline compared to those who applied their devices incorrectly (P = .04).,Correct inhalation of prescribed medication is associated with improved health status and lung function.,These findings should encourage health professionals to provide instructions on correct inhalation technique and to regularly re-evaluate the patients’ inhalation technique.,ClinicalTrials.gov: NCT0238672, Registered 14 February 2014. | Physicians consider ease of use, satisfaction, and preferences when prescribing an inhaler device.,These factors may impact appropriate usage and compliance.,The objectives were to quantify the relative importance of inhaler attributes in patients currently using Combivent Respimat by eliciting preferences for performance and convenience attributes assessed by items in the Patient Satisfaction and Preference Questionnaire (PASAPQ).,Using a pharmacy database, 19,964 adults in the United States who filled ≥2 Combivent Respimat prescriptions were identified.,Of those, 8150 patients were randomly selected to receive invitation letters.,The online cross-sectional survey included the PASAPQ and best-worst scaling (BWS) questions.,The PASAPQ measures satisfaction with medication attributes across two domains: performance and convenience.,BWS questions asked participants to select the most and least important device attributes.,A descriptive statistics analysis of the PASAPQ and a random-parameters logit model of BWS responses were conducted.,The survey was completed by 503 participants.,Most were female (57.3%), white (88.5%), and 51-70 years old (67.6%).,Approximately 47% reported a chronic obstructive pulmonary disease diagnosis, 21.9% asthma, 8.2% other lung disease, and 23.1% more than one lung disease.,PASAPQ scores indicated that the majority were satisfied or very satisfied; up to 20% reported being dissatisfied with Combivent Respimat.,The three most important inhaler attributes were Feeling that your medicine gets into your lungs, Inhaler works reliably, and Inhaler makes inhaling your medicine easy.,The most important attributes corresponded to six of seven items in the PASAPQ performance domain.,Most participants reported satisfaction with Combivent Respimat.,Performance attributes were more important than convenience attributes. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is associated with subclinical systemic atherosclerosis and pulmonary vascular remodelling characterized by intimal hyperplasia and luminal narrowing.,We aimed to determine differences in the intimal thickening of systemic and pulmonary arteries in COPD subjects and smokers.,Secondary aims include comparisons with a non-smokers group; determining the clinical variables associated with systemic and pulmonary intimal thickening, and the correlations between systemic and pulmonary remodelling changes.,All consecutive subjects undergoing lung resection were included and divided into 3 groups: 1) COPD, 2) smokers, and 3) non-smokers.,Sections of the 5th intercostal artery and muscular pulmonary arteries were measured by histo-morphometry.,Four parameters of intimal thickening were evaluated: 1) percentage of intimal area (%IA), 2) percentage of luminal narrowing, 3) intimal thickness index, and 4) intima-to-media ratio.,In the adjusted analysis, the systemic arteries of COPD subjects showed greater intimal thickening (%IA) than those of smokers (15.6±1.5% vs.,14.2±1.6%, p = 0.038).,In the pulmonary arteries, significant differences were observed for %IA between the 2 groups (37.3±2.2% vs.,29.3±2.3%, p = 0.016).,Among clinical factors, metabolic syndrome, gender and COPD status were associated with the systemic intimal thickening, while only COPD status was associated with pulmonary intimal thickening.,A correlation between the %IA of the systemic and pulmonary arteries was observed (Spearman’s rho = 0.46, p = 0.008).,Greater intimal thickening in systemic and pulmonary arteries is observed in COPD patients than in smokers.,There is a correlation between systemic and pulmonary vascular remodelling in the overall population. | To investigate patient characteristics of an unselected primary care population associated with risk of first hospital admission and readmission for acute exacerbation of chronic obstructive pulmonary disease (AECOPD).,Retrospective open cohort using pseudonymised electronic primary care data linked to secondary care data.,Primary care; Lothian (population approximately 800 000), Scotland.,Data from 7002 patients from 72 general practices with a COPD diagnosis date between 2000 and 2008 recorded in their primary care record.,Patients were followed up until 2010, death or they left a participating practice.,First and subsequent admissions for AECOPD (International Classification of Diseases (ICD) 10 codes J44.0, J44.1 in any diagnostic position) after COPD diagnosis in primary care.,1756 (25%) patients had at least 1 AECOPD admission; 794 (11%) had at least 1 readmission and the risk of readmission increased with each admission.,Older age at diagnosis, more severe COPD, low body mass index (BMI), current smoking, increasing deprivation, COPD admissions and interventions for COPD prior to diagnosis in primary care, and comorbidities were associated with higher risk of first AECOPD admission in an adjusted Cox proportional hazards regression model.,More severe COPD and COPD admission prior to primary care diagnosis were associated with increased risk of AECOPD readmission in an adjusted Prentice-Williams-Peterson model.,High BMI was associated with a lower risk of first AECOPD admission and readmission.,Several patient characteristics were associated with first AECOPD admission in a primary care cohort of people with COPD but fewer were associated with readmission.,Prompt diagnosis in primary care may reduce the risk of AECOPD admission and readmission.,The study highlights the important role of primary care in preventing or delaying a first AECOPD admission. | 1 |
The objective of this study was to compare the cost-effectiveness of the fixed-dose combination (FDC) of tiotropium + olodaterol Respimat® FDC with tiotropium alone for patients with chronic obstructive pulmonary disease (COPD) in the Italian health care setting using a newly developed patient-level Markov model that reflects the current understanding of the disease.,While previously published models have largely been based around a cohort approach using a Markov structure and GOLD stage stratification, an individual-level Markov approach was selected for the new model.,Using patient-level data from the twin TOnado trials assessing Tiotropium + olodaterol Respimat® FDC versus tiotropium, outcomes were modelled based on the trough forced expiratory volume (tFEV1) of over 1000 patients in each treatment arm, tracked individually at trial visits through the 52-week trial period, and after the trial period it was assumed to decline at a constant rate based on disease stage.,Exacerbation risk was estimated based on a random-effects logistic regression analysis of exacerbations in UPLIFT.,Mortality by age and disease stage was estimated from an analysis of TIOSPIR trial data.,Cost of bronchodilators and other medications, routine management, and costs of treatment for moderate and severe exacerbations for the Italian setting were included.,A cost-effectiveness analysis was conducted over a 15-year time horizon from the perspective of the Italian National Health Service.,Aggregating total costs and quality-adjusted life years (QALYs) for each treatment cohort over 15 years and comparing tiotropium + olodaterol Respimat® FDC with tiotropium alone, resulted in mean incremental costs per patient of €1167 and an incremental cost-effectiveness ratio (ICER) of €7518 per additional QALY with tiotropium + olodaterol Respimat® FDC.,The lung function outcomes observed for tiotropium + olodaterol Respimat® FDC in TOnado drove the results in terms of slightly higher mean life-years (12.24 versus 12.07) exacerbation-free months (11.36 versus 11.32) per patient and slightly fewer moderate and severe exacerbations per patient-year (0.411 versus 0.415; 0.21 versus 0.24) versus tiotropium.,Probabilistic sensitivity analyses showed tiotropium + olodaterol Respimat® FDC to be the more cost-effective treatment in 95.2% and 98.4% of 500 simulations at thresholds of €20,000 and €30,000 per QALY respectively.,Tiotropium + olodaterol Respimat® FDC is a cost-effective bronchodilator in the maintenance treatment of COPD for the Italian health care system. | The once-daily long-acting muscarinic antagonist (LAMA) tiotropium and once-daily long-acting β2-agonist (LABA) olodaterol have been studied as a once-daily fixed-dose combination (FDC) in patients with chronic obstructive pulmonary disease (COPD).,Two large, 52-week, double-blind, parallel-group studies in patients with moderate-very severe COPD demonstrated that tiotropium + olodaterol significantly improved lung function and symptoms versus the monocomponents.,This post hoc analysis determined effects on lung function by prior LAMA or LABA maintenance treatment and initial disease severity.,5162 patients were randomized and treated with olodaterol 5 µg, tiotropium 2.5 µg, tiotropium 5 µg, tiotropium + olodaterol 2.5/5 µg, or tiotropium + olodaterol 5/5 µg (all once daily via Respimat® inhaler).,Primary efficacy (lung-function) end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) and trough FEV1 responses (i.e., change from baseline).,Pooled data are presented for the following subgroups: prior maintenance treatment with LAMA or LABA, Global initiative for chronic Obstructive Lung Disease (GOLD) 2 (predicted FEV1 50% to <80%) and 3 (30% to <50%)/4 (<30%), sex, age, and prior use of inhaled corticosteroids.,Tiotropium + olodaterol FDC improved lung function over the monocomponents in patients with GOLD 2 and 3-4 disease, irrespective of prior LAMA or LABA maintenance therapy; most comparisons between FDCs and their respective monocomponents were statistically significant (P < 0.05).,FEV1 AUC0-3 and trough FEV1 responses for the individual treatments were generally greater in patients with less severe COPD at baseline.,Tiotropium + olodaterol 5/5 µg significantly improved FEV1 AUC0-3 and trough FEV1 in all GOLD severity groups compared to olodaterol 5 µg and tiotropium 5 µg alone, irrespective of whether patients had received prior LAMA or LABA maintenance treatment.,Improvements from baseline in lung function were generally greater in patients with less severe disease.,Boehringer Ingelheim.,Trial registration: ClinicalTrials.gov numbers, NCT01431274 and NCT01431287.,The online version of this article (doi:10.1007/s12325-015-0218-0) contains supplementary material, which is available to authorized users. | 1 |
Electronic cigarettes (ECs) are battery-operated devices designed to vaporise nicotine, which may help smokers quitting or reducing their tobacco consumption.,There is a lack of data on the health effects of EC use among smokers with COPD and whether regular use results in improvement in subjective and objective COPD outcomes.,We investigated long-term changes in objective and subjective respiratory outcomes in smokers with a diagnosis of COPD who quit or reduced substantially their tobacco consumption by supplementing with or converting only to ECs use.,We conducted a retrospective chart review of patients with COPD to identify those reporting regular daily use of ECs on at least two follow-up visits at 12- (F/up1) and 24-months (F/up2).,Regularly smoking COPD patients were included as a reference group.,A marked reduction in cigarette consumption was observed in ECs users.,A significant reduction in COPD exacerbations was reported in the COPD EC user group, their mean (±SD) decreasing from 2.3 (±1) at baseline to 1.8 (±1; p = 0.002) and 1.4 (±0.9; p < 0.001) at F/up1 and F/up2 respectively.,A significant reduction in COPD exacerbations was also observed in ECs users who also smoked conventional cigarettes (i.e. ‘dual users’).,COPD symptoms and ability to perform physical activities improved statistically in the EC group at both visits, with no change in the control group.,These findings suggest that ECs use may aid smokers with COPD reduce their cigarette consumption or remain abstinent, which results in marked improvements in annual exacerbation rate as well as subjective and objective COPD outcomes. | Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory condition in adults and is characterized by progressive airflow limitation that is not fully reversible.,The main etiological agents linked with COPD are cigarette smoking and biomass exposure but respiratory infection is believed to play a major role in the pathogenesis of both stable COPD and in acute exacerbations.,Acute exacerbations are associated with more rapid decline in lung function and impaired quality of life and are the major causes of morbidity and mortality in COPD.,Preventing exacerbations is a major therapeutic goal but currently available treatments for exacerbations are not very effective.,Historically, bacteria were considered the main infective cause of exacerbations but with the development of new diagnostic techniques, respiratory viruses are also frequently detected in COPD exacerbations.,This article aims to provide a state-of-the art review of current knowledge regarding the role of infection in COPD, highlight the areas of ongoing debate and controversy, and outline emerging technologies and therapies that will influence future diagnostic and therapeutic pathways in COPD. | 1 |
Exacerbations of COPD are frequent and commonly triggered by respiratory tract infections.,The purpose of our study was to investigate innate immunity in stable COPD patients.,Induced sputum was collected from 51 stable consecutive COPD patients recruited from the COPD Clinic of CHU Liege and 35 healthy subjects.,Expression of interferons beta (IFN-β) and lambda1 (IL-29), IFN-stimulated genes (ISGs) MxA, OAS, and viperin were measured in total sputum cells by reverse transcription quantitative polymerase chain reaction (RT-qPCR).,The presence of Picornaviruses was assessed by RT-PCR, while potential pathogenic microorganisms (PPM) were identified by sputum bacteriology.,Expression of IL-29 was found in 16 of 51 COPD patients (31%) and in nine of 35 healthy subjects (26%), while IFN-β was detected in six of 51 COPD patients (12%) and in two of 35 healthy subjects (6%).,ISGs were easily detectable in both groups.,In the whole group of COPD patients, OAS expression was decreased (P<0.05), while that of viperin was increased (P<0.01) compared to healthy subjects.,No difference was found with respect to MxA.,COPD patients from group D of Global Initiative for Chronic Obstructive Lung Disease (GOLD) had reduced expression of all three ISGs (P<0.01 for MxA, P<0.05 for OAS, and P<0.01 for viperin) as compared to those of group B patients.,Picornaviruses were detected in eight of 51 (16%) COPD patients vs four of 33 (12%) healthy subjects, while PPM were detected in seven of 39 (18%) COPD patients and associated with raised sputum neutrophil counts.,IFN-β expression was raised when either picornavirus or PPM were detected (P=0.06), but no difference was seen regarding IL-29 or ISGs.,ISGs expression was reduced in severe COPD that may favor exacerbation and contribute to disease progress by altering response to infection. | Eosinophilic airway inflammation is observed in 10-30% of COPD subjects.,Whether increased eosinophils or impairment in their clearance by macrophages is associated with the severity and frequency of exacerbations is unknown.,We categorised 103 COPD subjects into 4 groups determined by the upper limit of normal for their cytoplasmic macrophage red hue (<6%), an indirect measure of macrophage efferocytosis of eosinophils, and area under the curve sputum eosinophil count (≥3%/year).,Eosinophil efferocytosis by monocyte-derived macrophages was studied in 17 COPD subjects and 8 normal controls.,There were no differences in baseline lung function, health status or exacerbation frequency between the groups: A-low red hue, high sputum eosinophils (n = 10), B-high red hue, high sputum eosinophils (n = 16), C-low red hue, low sputum eosinophils (n = 19) and D- high red hue, low sputum eosinophils (n = 58).,Positive bacterial culture was lower in groups A (10%) and B (6%) compared to C (44%) and D (21%) (p = 0.01).,The fall in FEV1 from stable to exacerbation was greatest in group A (ΔFEV1 [95 % CI] -0.41 L [-0.65 to -0.17]) versus group B (-0.16 L [-0.32 to -0.011]), C (-0.11 L [-0.23 to -0.002]) and D (-0.16 L [-0.22 to -0.10]; p = 0.02).,Macrophage efferocytosis of eosinophils was impaired in COPD versus controls (86 [75 to 92]% versus 93 [88 to 96]%; p = 0.028); was most marked in group A (71 [70 to 84]%; p = 0.0295) and was inversely correlated with exacerbation frequency (r = -0.63; p = 0.006).,Macrophage efferocytosis of eosinophils is impaired in COPD and is related to the severity and frequency of COPD exacerbations. | 1 |
Pulmonary inflammation, oxidants-antioxidants imbalance, as well as innate and adaptive immunity have been proposed as playing a key role in the development of COPD.,The role of vitamins, as assessed either by food frequency questionnaires or measured in serum levels, have been reported to improve pulmonary function, reduce exacerbations and improve symptoms.,Vitamin supplements have therefore been proposed to be a potentially useful additive to COPD therapy.,A systematic literature review was performed on the association of vitamins and COPD.,The role of vitamin supplements in COPD was then evaluated.,The results of this review showed that various vitamins (vitamin C, D, E, A, beta and alpha carotene) are associated with improvement in features of COPD such as symptoms, exacerbations and pulmonary function.,High vitamin intake would probably reduce the annual decline of FEV1.,There were no studies that showed benefit from vitamin supplementation in improved symptoms, decreased hospitalization or pulmonary function. | There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD).,The only known genetic risk factor is severe deficiency of α1-antitrypsin, which is present in 1-2% of individuals with COPD.,We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study.,The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population.,Logistic regression models with adjustments of covariates were used to analyze the case-control populations.,Family-based association analyses were conducted for a diagnosis of COPD and lung function in the family populations.,Two SNPs at the α-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study.,They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48×10−10, (rs8034191) and 5.74×10−10 (rs1051730).,Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations.,The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%.,The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels.,Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; doi:10.1371/journal.pgen.1000429).,The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD.,CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer. | 1 |
Two once-daily long-acting muscarinic antagonists (LAMAs) are currently available for the treatment of chronic obstructive pulmonary disease (COPD) - tiotropium and glycopyrronium.,Previous studies have compared glycopyrronium with open-label tiotropium.,In the GLOW5 study, we compare glycopyrronium with blinded tiotropium.,In this blinded, double-dummy, parallel group, 12-week study, patients with moderate-to-severe COPD were randomized 1:1 to glycopyrronium 50 μg once daily or tiotropium 18 μg once daily.,The primary objective was to demonstrate the non-inferiority of glycopyrronium versus blinded tiotropium with respect to trough forced expiratory volume in 1 second (FEV1) following 12 weeks of treatment (non-inferiority margin: -50 mL).,Secondary objectives were to evaluate glycopyrronium versus tiotropium for other spirometric outcomes, breathlessness (Transition Dyspnea Index; TDI), health status (St George’s Respiratory Questionnaire; SGRQ), daily rescue medication use, COPD exacerbations and COPD symptoms over 12 weeks of treatment.,657 patients were randomized (glycopyrronium: 327; tiotropium: 330); 96% (630 patients) completed the study.,Least squares mean trough FEV1 for both glycopyrronium and tiotropium was 1.405 L at Week 12, meeting the criterion for non-inferiority (mean treatment difference: 0 mL, 95% CI: -32, 31 mL).,Glycopyrronium demonstrated rapid bronchodilation following first dose on Day 1, with significantly higher FEV1 at all time points from 0-4 h post-dose versus tiotropium (all p < 0.001).,FEV1 area under the curve from 0-4 h (AUC0-4h) post-dose with glycopyrronium was significantly superior to tiotropium on Day 1 (p < 0.001) and was comparable to tiotropium at Week 12.,Glycopyrronium demonstrated comparable improvements to tiotropium in TDI focal score, SGRQ total score, rescue medication use and the rate of COPD exacerbations (all p = not significant).,Patients on glycopyrronium also had a significantly lower total COPD symptom score versus patients on tiotropium after 12 weeks (p = 0.035).,Adverse events were reported by a similar percentage of patients receiving glycopyrronium (40.4%) and tiotropium (40.6%).,In patients with moderate-to-severe COPD, 12-week blinded treatment with once-daily glycopyrronium 50 μg or tiotropium 18 μg, provided similar efficacy and safety, with glycopyrronium having a faster onset of action on Day 1 versus tiotropium.,ClinicalTrial.gov, NCT01613326 | 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 | 1 |
‘Clinically important deterioration’ (CID) is a composite endpoint measuring worsening of the key clinical features of chronic obstructive pulmonary disease (COPD), namely lung function, patient-reported outcomes, and exacerbations.,ACLIFORM and AUGMENT were two 24-week, randomized, double-blind, phase III studies assessing twice-daily (BID) aclidinium bromide (AB) 400 μg/formoterol fumarate (FF) 12 μg.,This pooled post-hoc analysis assessed the effects of AB/FF 400/12 μg on both first and sustained CID events versus placebo and monotherapies in patients with moderate to severe COPD.,A first CID event was defined as the occurrence of a moderate/severe exacerbation or the worsening from baseline in ≥1 of the following: trough forced expiratory volume in 1 second (FEV1; ≥100 mL), Transition Dyspnea Index (TDI) focal score (≥1 unit), or St George’s Respiratory Questionnaire (SGRQ) total score (≥4 units).,A ‘sustained’ CID was defined as a worsening maintained at all subsequent visits from appearance to week 24 or a moderate/severe exacerbation at any time.,CID events were assessed at three visits (weeks 4, 12, and 24); trough FEV1 was also measured at weeks 1 and 18.,AB/FF 400/12 μg reduced the risk of a first CID event by 45% versus placebo (hazard ratio [HR] 0.55, p < 0.001), 18% versus FF 12 μg (HR 0.82, p < 0.01), and 15% versus AB 400 μg (HR 0.85, p < 0.05).,Similarly, AB/FF 400/12 μg reduced the risk of a sustained CID event by 48% versus placebo (HR 0.52, p < 0.001) and 22% versus FF 12 μg (HR 0.78, p < 0.01).,AB/FF 400/12 μg reduced the risk of a first or sustained CID event for all four components versus placebo (trough FEV1 and TDI, first and sustained CID, all p < 0.001; SGRQ first CID p < 0.001; SGRQ sustained CID, p < 0.01; exacerbations first and sustained CID, both p < 0.05) and TDI and SGRQ versus FF 12 μg (TDI, first and sustained CID both p < 0.05; SGRQ first CID p < 0.01), and SGRQ versus AB 400 μg (first CID, p < 0.05).,AB/FF 400/12 μg BID may provide greater airway stability and fewer exacerbations or deteriorations in lung function, health status, or dyspnea compared with placebo or monotherapies.,Clinicaltrials.gov NCT01462942 (ACLIFORM); registered 26 October 2011.,Clinicaltrials.gov NCT01437397 (AUGMENT); registered 19 September 2011.,The online version of this article (doi:10.1186/s12931-017-0583-0) contains supplementary material, which is available to authorized users. | Endpoints that evaluate deterioration rather than improvement of disease may have clinical utility in COPD.,In this analysis, we compared the effects of different maintenance treatments on the prevention of clinically important deterioration (CID) in moderate-to-severe COPD patients.,Data were analyzed from three 26-week studies comparing indacaterol/glycopyrronium (IND/GLY) with tiotropium (TIO) or salmeterol/fluticasone (SFC).,Two definitions of CID were used; each was a composite of three outcome measures typically associated with COPD.,Definition 1 (D1) comprised a ≥100 mL decrease in forced expiratory volume in 1 second (FEV1), a ≥4-unit increase in St George’s Respiratory Questionnaire, and a moderate-to-severe COPD exacerbation.,In Definition 2 (D2), a ≥1-unit decrease in transition dyspnea index replaced FEV1.,Using D1, IND/GLY significantly reduced the risk of first or sustained CID versus either TIO (hazard ratio 0.72 [0.61, 0.86], P=0.0003 and 0.73 [0.61, 0.89], P=0.001) or SFC (0.67 [0.57, 0.80] and 0.63 [0.52, 0.77], both P<0.0001).,With D2, IND/GLY significantly reduced the risk of first, but not sustained, CID versus TIO (0.80 [0.64 to 0.99], P=0.0359 and 0.85 [0.66, 1.10], P=0.2208) and both first and sustained CID versus SFC (0.73 [0.61, 0.88], P=0.001 and 0.72 [0.58, 0.90], P=0.0036).,These data confirm the utility of the CID endpoint as a means of monitoring COPD worsening in patients with moderate-to-severe COPD.,Using the CID measure, we demonstrated that dual bronchodilation with IND/GLY significantly reduced the risk of CID versus either long-acting muscarinic antagonist or long-acting β2-agonist/inhaled corticosteroid treatment, providing further evidence for the benefit of dual bronchodilation in this patient population. | 1 |
Noninvasive ventilation (NIV) reduces the rate of endotracheal intubation (ETI) and overall mortality in severe acute exacerbation of COPD (AECOPD) with acute respiratory failure and is increasingly applied in respiratory intermediate care units.,However, inadequate patient selection and incorrect management of NIV increase mortality.,We aimed to identify factors that predict the outcome of NIV in AECOPD.,Also, we looked for factors that influence ventilator settings and duration.,A prospective cohort study was undertaken in a respiratory intermediate care unit in an academic medical center between 2016 and 2017.,Age, BMI, lung function, arterial pH and pCO2 at admission (t0), at 1-2 h (t1) and 4-6 h (t2) after admission, creatinine clearance, echocardiographic data (that defined left heart dysfunction), mean inspiratory pressure during the first 72 h (mIPAP-72 h) and hours of NIV during the first 72 h (dNIV-72 h) were recorded.,Main outcome was NIV failure (i.e., ETI or in-hospital death).,Secondary outcomes were in-hospital mortality, length of stay (LOS), duration of NIV (days), mIPAP-72 h, and dNIV-72 h.,We included 89 patients (45 male, mean age 67.6 years) with AECOPD that required NIV.,NIV failure was 12.4%, and in-hospital mortality was 11.2%.,NIV failure was correlated with days of NIV, LOS, in-hospital mortality (p < 0.01), and kidney dysfunction (p < 0.05).,In-hospital mortality was strongly associated with days of NIV (OR 1.27, 95%CI: 1.07-1.5, p < 0.01) and with FEV1 (p < 0.05).,All other investigated parameters (including left heart dysfunction, dNIV-72 h, mIPAP-72 h, pH, etc.) did not influence NIV failure or mortality. dNIV-72 h and days of NIV were independent predictors of LOS (p < 0.01).,Regarding the secondary outcomes, left heart dysfunction and pH at 1-2 h independently predicted NIV duration (dNIV-72 h, p < 0.01), while BMI and baseline pCO2 predicted NIV settings (mIPAP-72 h, p < 0.01).,In-hospital mortality and NIV failure were not influenced by BMI, left heart dysfunction, age, nor by arterial blood gas values in the first 6 h of NIV.,Patients with severe acidosis and left heart dysfunction required prolonged use of NIV.,BMI and pCO2 levels influence the NIV settings in AECOPD regardless of lung function. | COPD is a significant cause of morbidity and mortality.,In some patients with COPD, eosinophils contribute to inflammation that promotes airway obstruction; approximately a third of stable COPD patients have evidence of eosinophilic inflammation.,Although the eosinophil threshold associated with clinical relevance in patients with COPD is currently subject to debate, eosinophil counts hold potential as biomarkers to guide therapy.,In particular, eosinophil counts may be useful in assessing which patients may benefit from inhaled corticosteroid therapy, particularly regarding exacerbation prevention.,In addition, several therapies targeting eosinophilic inflammation are available or in development, including monoclonal antibodies targeting the IL5 ligand, the IL5 receptor, IL4, and IL13.,The goal of this review was to describe the biologic characteristics of eosinophils, their role in COPD during exacerbations and stable disease, and their use as biomarkers to aid treatment decisions.,We also propose an algorithm for inhaled corticosteroid use, taking into consideration eosinophil counts and pneumonia history, and emerging eosinophil-targeted therapies in COPD. | 1 |
Chronic respiratory diseases (CRDs) are leading causes of morbidity worldwide.,However, the spatial and temporal trends in prevalence and incidence of CRDs have not been estimated.,Based on data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017, we analyzed the prevalence and incidence trends of CRDs from 1990 to 2017 according to age, sex, region and disease pattern.,Furthermore, the correlations between the incidence and the World Bank income levels, sociodemographic index (SDI), and human development index (HDI) levels were analyzed to assess the factors affecting incidence.,The total number of CRD cases increased by 39.5% from 1990 to 2017, nevertheless, the age-standardized prevalence rate (ASPR) and age-standardized incidence rate (ASIR) showed decreasing trends.,The ASIRs of CRD, chronic obstructive pulmonary disease (COPD), pneumoconiosis, and asthma decreased, whereas the ASIR of interstitial lung disease and pulmonary sarcoidosis increased during the past 27 years.,Significant differences between males and females in the incidence rates of pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis were observed.,Elderly people especially suffered from CRDs, except for asthma.,For COPD, the ASIR decreased from low-SDI regions to high-SDI regions.,The ASIR of interstitial lung disease and pulmonary sarcoidosis in the high-SDI region was highest and have increased mostly.,The ASIRs for pneumoconiosis and asthma were inversely related to the HDI.,In 2017, CRDs were still the leading causes of morbidity worldwide.,A large proportion of the disease burden was attributed to asthma and COPD.,The incidence rates of all four types of CRDs varied greatly across the world.,Statistically significant correlation was found between the ASIR and SDI/HDI. | Histone acetyltransferases (HAT) and histone deacetylases (HDAC) are enzymes that upregulate and down-regulate pro-inflammatory gene transcription respectively.,HDAC2 is required by corticosteroids to switch off activated inflammatory genes and is reduced in lung macrophages in COPD.,We have shown that COPD patients have increased steroid resistant CD28null (senescent) pro-inflammatory T and NKT-like peripheral blood cells (particularly CD8+ subsets) and we hypothesized that these changes would be associated with a loss of HDAC2 from these senescent pro-inflammatory lymphocytes.,Blood was collected from 10 COPD and 10 aged-matched controls.,Intracellular pro-inflammatory cytokines, IFNγ and TNFα, and expression of CD28, HDAC2 and HAT, were determined in lymphocyte subsets in the presence of ± 5 mg/ml theophylline (HDAC2 activator), 10 μM prednisolone and 2.5 ng/ml cyclosporine A (immunosuppressant), using flow cytometry.,There was a loss of HDAC2 from CD28null CD8+ T and NKT-like cells in COPD.,There was a significant negative correlation between HDAC2 expression and the percentage of CD28null CD8+ T and NKT-like cells producing IFNγ or TNFα in all subjects (eg, COPD: R = −.763, p < 0.001 for T-cell IFNγ).,There was a synergistic upregulation of HDAC2 and associated decrease in pro-inflammatory cytokine production in CD28nullCD8+ T and NKT-like cells in the presence of 5 mg/L theophylline + 10−6 M prednisolone or 2.5 ng/mL cyclosporine A (CsA).,Lymphocyte senescence in COPD is associated with loss of HDAC2 in CD28nullCD8+ T and NKT-like cells.,Alternative treatment options such as combined theophylline with low-dose CsA, that inhibit these pro-inflammatory cells, may reduce systemic inflammation in COPD. | 1 |
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. | Choosing the appropriate time to switch to noninvasive positive-pressure ventilation (NPPV) plays a crucial role in promoting successful weaning.,However, optimal timing for transitioning and weaning patients from mechanical ventilation (MV) to NPPV has not been clearly established.,In China, the pulmonary infection control (PIC) window as a switching point for weaning from MV has been performed for many years, without definitive evidence of clinical benefit.,This study aimed to summarize the evidence for NPPV at the PIC window for patients with respiratory failure from COPD.,A comprehensive search for randomized controlled trials (RCTs) was performed.,The trials were all parallel studies comparing the PIC window weaning strategy versus conventional weaning strategy in treatment of patients with respiratory failure due to COPD.,Sixteen studies of 647 participants were eligible.,When compared with conventional weaning strategy, early extubation followed by NPPV at the point of PIC window significantly reduced the mortality rate (risk ratios [RRs] 0.36, 95% confidence interval [CI] 0.23 to 0.57) and ventilator-associated pneumonia (VAP) (RR 0.28, 95% CI 0.19 to 0.41); it also decreased the duration of invasive ventilation (weighted mean difference [WMD] −7.68 days, 95% CI −9.43 to −5.93) and total duration of ventilation (WMD −5.93 days, 95% CI −7.29 to −4.58), which also shortened the lengths of stay in an intensive care unit (WMD −8.51 days, 95% CI −10.23 to −6.79), as well as length of stay in hospital (WMD −8.47 days, 95% CI −8.61 to −7.33).,The results showed that the PIC window as a switching point for sequential ventilation in treatment of respiratory failure in COPD patients may be beneficial.,It might yield not only relevant information for caregivers in China but also new insights for considering the PIC window by physicians in other countries. | 1 |
Asthma and chronic obstructive pulmonary disease (COPD) are both highly prevalent conditions that can coexist in the same individual: the so-called ‘asthma -COPD overlap’ (ACO).,Its prevalence and prognosis vary widely depending on how ACO is defined in each publication, the severity of bronchial obstruction of patients included and the treatment they are receiving.,Although there is a lack of evidence about the biology of ACO, the overlap of both diseases should express a mixture of a Th1 inflammatory pattern (characteristic of COPD) and a Th2 signature (characteristic of asthma).,In this review we support a novel algorithm for ACO diagnosis proposed by the Spanish Respiratory Society (SEPAR), based on a sequential evaluation that considers: (a) the presence of chronic airflow limitation in a smoker or ex-smoker patient ⩾35 years old; (b) a current diagnosis of asthma; and (c) the existence of a very positive bronchodilator test (PBT; ⩾15% and ⩾400 ml) or the presence of eosinophilia in blood (⩾300 eosinophils/μl).,This algorithm can identify those patients who may benefit from a treatment with inhaled corticosteroids (ICSs) and maybe from biological drugs in a near future.,In addition, it is easily applicable in clinical practice.,The major disadvantage is that it groups patients with very different characteristics under the ACO’s umbrella.,In view of this heterogeneity, we recommend a strategy of defining specific and measurable therapeutic objectives for every single patient and identifying the traits that can be treated to achieve those objectives. | There are very few studies that have investigated the muscle strength and endurance of upper limbs (UL) in chronic obstructive pulmonary disease (COPD).,We undertook this study to measure and compare the skeletal muscle strength and endurance of UL in COPD patients and age matched healthy controls and to study the association between lung function parameters and UL muscle strength and endurance.,Forty one COPD patients and 45 height and weight matched healthy subjects of the same age group were studied.,UL skeletal muscle strength and endurance were measured using the hand grip dynamometer test.,Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), forced expiratory flow during 25-75% FVC (FEF25-75%) and peak expiratory flow rate (PEFR) were measured.,The handgrip muscle strength and endurance between the two groups were compared and correlations between FVC and FEV1 with muscle strength and endurance were analyzed.,The mean handgrip strength and mean muscle endurance in COPD patients were significantly lesser than the normal subjects in both males and females (P<0.001).,There was significant positive correlation between muscle strength and FVC in males (r2=0.32, P<0.05); and between muscle strength and FEV1 in females (r2=0.20, P<0.05).,The study showed that the handgrip muscle strength decreases as the FVC and FEV1 decrease in patients with COPD.,Identifying those patients who have reduced strength and endurance will allow early interventions targeted at improving the quality of life of the patient. | 1 |
The impact of rehabilitation-induced changes in 6-minute walk distance (6MWD) on the survival of patients with chronic obstructive pulmonary disease (COPD) has not been fully elucidated.,This study sought to determine the association of baseline 6MWD and its changes after pulmonary rehabilitation (PR) with 5-year survival in patients with COPD.,Patients who were referred to a 12-week outpatient PR program were followed up for 5 years postcompletion, and survival status was verified.,Survival was analyzed according to four groups based upon initial 6MWD (6MWDi) and its changes (Δ6MWD) after PR (Group 1: 6MWDi ≥350 m and Δ6MWD ≥30 m; Group 2: 6MWDi ≥350 m and Δ6MWD <30 m; Group 3: 6MWDi <350 m and Δ6MWD ≥30 m; and Group 4: 6MWDi <350 m and Δ6MWD <30 m) via Kaplan-Meier analysis and log rank test.,Cox regression was performed to identify possible confounders of mortality estimates.,In total, 423 patients (with mean ± standard deviation of forced expiratory volume in the first second [FEV1] 43±16% predicted, age 65±8 years, and 6WMDi 381±134 m) underwent PR between 1999 and 2010.,Survival rates decreased progressively from Group 1 to Group 4 (Group 1, 81%; Group 2, 69%; Group 3, 47%; Group 4, 27%; log rank test, P<0.05).,6MWDi ≥350 m (hazard ratio [HR] 0.39 [95% confidence interval {CI} 0.30-0.50]) and Δ6MWD ≥30 m (HR 0.66 [95% CI 0.51-0.85]) were strongly and independently associated with survival.,Compared with Group 1, mortality risks progressively increased in Group 2 (HR 1.36 [95% CI 0.92-2.00]; not significant), Group 3 (HR 1.90 [95% CI 1.28-2.84]; P=0.001), and Group 4 (HR 3.28 [95% CI 2.02-5.33]; P<0.0001).,Both poor 6MWD and lack of improvement >30 m after PR are associated with worse 5-year survival in patients with COPD. | Physical inactivity is a cardinal feature of chronic obstructive pulmonary disease (COPD), and is associated with increased morbidity and mortality.,Pedometers, which have been used in healthy populations, might also increase physical activity in patients with COPD.,COPD patients taking part in a 3-month individualised programme to promote an increase in their daily physical activity were randomised to either a standard programme of physical activity encouragement alone, or a pedometer-based programme.,Assessments were performed by investigators blinded to treatment allocation.,Change in average 1-week daily step count, 6-min walking distance (6MWD), modified Medical Research Council scale, St George’s respiratory questionnaire (SGRQ) and COPD assessment test (CAT) were compared between groups.,102 patients were recruited, of whom 97 completed the programme (pedometer group: n=50; control group: n=47); 60.8% were male with a mean±sd age of 68.7±8.5 years, and forced expiratory volume in 1 s (FEV1) 66.1±19.4% and FEV1/forced vital capacity 55.2±9.5%.,Both groups had comparable characteristics at baseline.,The pedometer group had significantly greater improvements in: physical activity 3080±3254 steps·day−1versus 138.3±1950 steps·day−1 (p<0.001); SGRQ −8.8±12.2 versus −3.8±10.9 (p=0.01); CAT score −3.5±5.5 versus −0.6±6.6 (p=0.001); and 6MWD 12.4±34.6 versus −0.7±24.4 m (p=0.02) than patients receiving activity encouragement only.,A simple physical activity enhancement programme using pedometers can effectively improve physical activity level and quality of life in COPD patients.,Pedometer-based programme produced clinically important improvements in physical activity and health status in COPDhttp://ow.ly/AmcCO | 1 |
Chronic obstructive pulmonary disease is associated with a high healthcare resource and cost burden.,Healthcare resource utilization was analyzed in patients with symptomatic chronic obstructive pulmonary disease at risk of exacerbations in the FULFIL study.,Patients received either once-daily, single inhaler triple therapy (fluticasone furoate/umeclidinium/vilanterol) 100 µg/62.5 µg/25 µg or twice-daily dual inhaled corticosteroid/long-acting beta agonist therapy (budesonide/formoterol) 400 µg/12 µg.,FULFIL was a phase III, randomized, double-blind, double-dummy, multicenter study.,Unscheduled contacts with healthcare providers were recorded by patients in a daily electronic diary; the costs of healthcare resource utilization were calculated post hoc using UK reference costs.,Over 24 weeks, slightly fewer patients who received fluticasone furoate/umeclidinium/vilanterol (169/911; 18.6%) required contacts with healthcare providers compared with budesonide/formoterol (180/899; 20.0%).,Over 52 weeks in an extension population, fewer patients who received fluticasone furoate/umeclidinium/vilanterol required unscheduled contacts with healthcare providers compared with budesonide/formoterol (25.2% vs.,32.7%).,Non-drug costs per treated patient per year were lower in the fluticasone furoate/umeclidinium/vilanterol group than the budesonide/formoterol group over 24 and 52 weeks (£653.80 vs.,£763.32 and £749.22 vs.,£988.03, respectively), with the total annualized cost over 24 weeks being slightly greater for fluticasone furoate/umeclidinium/vilanterol than budesonide/formoterol (£1,289.35 vs.,£1,267.45).,This healthcare resource utilization evidence suggests that, in a clinical trial setting over a 24- or 52-week timeframe, non-drug costs associated with management of a single inhaler fluticasone furoate/umeclidinium/vilanterol are lower compared with twice-daily budesonide/formoterol.,ClinicalTrials.gov number: NCT02345161.,GSK,The online version of this article (doi:10.1007/s12325-017-0604-x) contains supplementary material, which is available to authorized users. | Several composite markers have been proposed for risk assessment in chronic obstructive pulmonary disease (COPD).,However, choice of parameters and score complexity restrict clinical applicability.,Our aim was to provide and validate a simplified COPD risk index independent of lung function.,The PROMISE study (n=530) was used to develop a novel prognostic index.,Index performance was assessed regarding 2-year COPD-related mortality and all-cause mortality.,External validity was tested in stable and exacerbated COPD patients in the ProCOLD, COCOMICS and COMIC cohorts (total n=2988).,Using a mixed clinical and statistical approach, body mass index (B), severe acute exacerbations of COPD frequency (AE), modified Medical Research Council dyspnoea severity (D) and copeptin (C) were identified as the most suitable simplified marker combination. 0, 1 or 2 points were assigned to each parameter and totalled to B-AE-D or B-AE-D-C.,It was observed that B-AE-D and B-AE-D-C were at least as good as BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity), ADO (age, dyspnoea, airflow obstruction) and DOSE (dyspnoea, obstruction, smoking, exacerbation) indices for predicting 2-year all-cause mortality (c-statistic: 0.74, 0.77, 0.69, 0.72 and 0.63, respectively; Hosmer-Lemeshow test all p>0.05).,Both indices were COPD specific (c-statistic for predicting COPD-related 2-year mortality: 0.87 and 0.89, respectively).,External validation of B-AE-D was performed in COCOMICS and COMIC (c-statistic for 1-year all-cause mortality: 0.68 and 0.74; c-statistic for 2-year all-cause mortality: 0.65 and 0.67; Hosmer-Lemeshow test all p>0.05).,The B-AE-D index, plus copeptin if available, allows a simple and accurate assessment of COPD-related risk.,The B-AE-D indices allow a simple and accurate assessment of COPD-related risk in the absence of lung functionhttp://ow.ly/XFBox | 1 |
Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation. | Non-typeable Haemophilus influenza (NTHi) infection is common in COPD.,Corticosteroids can have limited therapeutic effects in COPD patients.,NTHi causes corticosteroid insensitive cytokine production from COPD alveolar macrophages.,We investigated the mechanisms by which NTHi causes corticosteroid insensitive inflammatory responses, and the effects of NTHi exposure on COPD macrophage polarisation.,Alveolar macrophages from COPD patients and controls were exposed to NTHi in conjunction with the corticosteroid dexamethasone and/or the p38 MAPK inhibitor BIRB-796.,Cytokine release, GR phosphorylation and modulation and macrophage phenotype were analysed.,Dexamethasone significantly inhibited NTHi induced TNF-α, IL-6 and IL-10 from COPD macrophages but, CXCL8 was not suppressed.,BIRB-796 combined with dexamethasone caused significantly greater inhibition of all cytokines than either drug alone (p < 0.05 all comparisons).,NTHi caused phosphorylation of GR S226 reducing GR nuclear localisation, an effect regulated by p38 MAPK.,NTHi altered macrophage polarisation by increasing IL-10 and decreasing CD36, CD206, CD163 and HLA-DR.,NTHi exposure causes p38 MAPK dependent GR phosphorylation associated with decreased GR function in COPD alveolar macrophages.,Combining a p38 MAPK inhibitor with corticosteroids can enhance anti-inflammatory effects during NTHi exposure of COPD alveolar macrophages.,NTHi causes macrophage polarisation that favours bacterial persistence.,The online version of this article (doi:10.1186/s12931-017-0539-4) contains supplementary material, which is available to authorized users. | 1 |
Adherence to chronic obstructive pulmonary disease (COPD) maintenance medication is important for managing symptoms and exacerbation risk, and is associated with reduced mortality, hospitalizations, and costs.,This study compared on-treatment exacerbations, medical costs, and medication adherence in patients with COPD initiating treatment with umeclidinium/vilanterol (UMEC/VI) or tiotropium (TIO).,This retrospective matched cohort study selected patients from Optum’s de-identified Clinformatics Data Mart database who initiated maintenance treatment with UMEC/VI or TIO between 01/01/2014 and 12/31/2017 (index date defined as the first dispensing).,Eligible patients were ≥ 40 years of age and had ≥ 12 months continuous health plan coverage pre- and post-index; ≥ 1 medical claim for COPD pre-index or on the index date; no moderate/severe COPD-related exacerbations on the index date; no asthma diagnosis pre- or post-index; no maintenance medication fills containing inhaled corticosteroids, long-acting β2-agonists, or long-acting muscarinic antagonists pre-index or on the index date; and no fills for both UMEC/VI and TIO on the index date.,Outcomes included time-to-first (Kaplan-Meier analysis) and rates of on-treatment COPD-related moderate/severe exacerbations, medication adherence (proportion of days covered [PDC] and proportion of adherent patients [PDC ≥ 0.8]), and COPD-related medical costs per patient per month (PPPM).,Propensity score matching was used to adjust for potential confounders.,Each cohort included 3929 matched patients.,Kaplan-Meier rates of on-treatment COPD-related exacerbations were similar between cohorts (hazard ratio at 12 months; overall: 0.93, moderate: 0.92, severe: 1.07; all p > 0.05).,UMEC/VI versus TIO initiators had significantly higher adherence (mean PDC: 0.44 vs 0.37; p < 0.001; proportion with PDC ≥ 0.8: 22.0% vs 16.4%; p< 0.001) and significantly lower mean on-treatment COPD-related total medical costs ($867 vs $1095 PPPM; p = 0.028), driven by lower outpatient visit costs.,These findings provide valuable information for physicians considering UMEC/VI or TIO as initial maintenance therapy options for patients with COPD.,The online version contains supplementary material available at 10.1186/s12890-021-01612-5. | Poor adherence to inhaled therapy is common in patients with asthma and COPD.,An inhaler selection based on patients’ preference could be beneficial to adherence and treatment effectiveness.,Properly designed questionnaires can assess patients’ satisfaction with their medication devices.,The aim of this study was to estimate, using the Feeling of Satisfaction with Inhaler (FSI-10) questionnaire, the ease of use and satisfaction of patients regarding three different marketed dry powder inhalers (DPIs): Diskus® (DK), Elpenhaler® (EH), and Turbuhaler® (TH).,The FSI-10 is a self-completed questionnaire to assess patients’ opinions regarding ease of use, portability, and usability of devices, irrespective of the drug used.,We performed a 4-week, open, noninterventional, multicenter, parallel clinical study in 560 asthmatic and 561 COPD patients.,During the first visit, patients were classified into three groups according to the DPI they were already using.,Patients were regularly receiving their treatments (Seretide DK, Rolenium EH, and Symbicort TH) and agreed to complete the FSI-10 questionnaire in the second visit.,A total of 517 COPD and 523 asthma patients completed the study.,All DPIs tested received satisfactory results, while the EH obtained consistently higher scores in the FSI-10 in both COPD and asthma patients (44.7 and 44.1 vs 41.5 and 43 for TH, 40.8 and 41.4 for DK, P<0.001 and P<0.01, respectively).,TH was rated better than DK by asthma patients.,Patients suffering with severe COPD tended to express higher feeling of satisfaction than those with moderate or mild disease, irrespective of the device used.,All DPIs tested were highly acceptable by asthma and COPD patients of different ages; nevertheless, EH received significantly higher ratings in most of the questionnaire domains.,COPD patients in advanced stages of the disease generally expressed higher level of satisfaction with their devices. | 1 |
Most studies have focused on the prevalence of deep vein thrombosis (DVT) and pulmonary embolism in patients with chronic obstructive pulmonary disease (COPD) and acute exacerbation in Caucasian populations.,DVT is supposedly less likely to occur among Asians than Caucasians, and the primary purpose of this study was to determine the actual incidence of DVT in patients with COPD in Asian populations.,We enrolled patients over the age of 40 with a diagnosis of COPD (International Classification of Diseases, Ninth Revision [ICD-9]: 490-492, 496; A-code: A323 and A325) between 1998 and 2008.,The index date was the date of first-time COPD diagnosis.,We excluded the patients who had been diagnosed with COPD and DVT (The International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]: 453.8) before index date.,The control group was frequency-matched according to age (3-year stratum), sex, and the year of admission, at a 2:1 ratio.,Patients were followed from index date to when either a diagnosis of DVT was made, death occurred, December 31, 2009 was reached, or when the patients withdrew from the National Health Insurance program.,The overall incidence rate of DVT was 18.78 per 10,000 person-years in patients with COPD, and the adjusted hazard ration of DVT in patients with COPD was 1.38 (95% confidence interval 1.06-1.80), which was greater than patients without COPD after adjusting for age, sex, atrial fibrillation, hypertension, diabetes, hyperlipidemia, cerebrovascular accident, congestive heart failure, lower leg fracture or surgery, and cancer.,Asian patients with COPD had a higher incidence of DVT than non-COPD patients. | Patients with chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD) share common risk factors.,However, there is limited information about COPD and CKD.,This is case-cohort study was carried out using the Taiwanese National Health Insurance Research Database to evaluate the correlation between COPD and CKD.,We identified cases aged older than 40 years who had an inpatient hospitalization with a first-time COPD diagnosis between 1998 and 2008.,Control were selected from hospitalized patients without COPD or CKD and were matched according to age, gender, and year of admission at a 2:1 ratio.,Cox proportional hazards model was used to assess the association of CKD and COPD.,The overall incidence of CKD was higher in the COPD group (470.9 per 104 person-years) than in the non-COPD group (287.52 per 104 person-years).,The adjusted hazard ratio of case was 1.61 (P < 0.0001) times that of control.,COPD was found to be associated with kidney disease from our follow-up.,To detect CKD early, early diagnosis of CKD in patients with COPD and prompt initiation of monitoring and treatment are imperative. | 1 |
In the 2014 Global initiative for chronic Obstructive Lung Disease guidelines, bronchiectasis was for the first time defined as a comorbidity of chronic obstructive pulmonary disease (COPD), and this change has been retained in the 2015 update, which emphasizes the influence of bronchiectasis in the natural history of COPD.,The present meta-analysis was aimed at summarizing the impact of bronchiectasis on patients with COPD.,Databases including Embase, PubMed, and the Cochrane Central Register of Controlled Trials were searched comprehensively to identify all relevant human clinical studies published until August 2014.,Bronchiectasis was confirmed either by computed tomography or high-resolution computed tomography.,One or more clinicopathological or demographical characteristics, including age, sex, smoking history, daily sputum production, exacerbations, inflammatory biomarkers, lung function, and colonization by potentially pathogenic microorganisms (PPMs), were compared between COPD patients with and without bronchiectasis.,Six observational studies with 881 patients were included in the meta-analysis.,The mean prevalence of bronchiectasis in patients with COPD was 54.3%, ranging from 25.6% to 69%.,Coexistence of bronchiectasis and COPD occurred more often in male patients with longer smoking history.,Patients with COPD and comorbid bronchiectasis had greater daily sputum production, more frequent exacerbation, poorer lung function, higher level of inflammatory biomarkers, more chronic colonization by PPMs, and higher rate of Pseudomonas aeruginosa isolation.,In spite of the heterogeneity between included studies and detectable publication bias, this meta-analysis demonstrated the impact of bronchiectasis in patients with COPD in all directions, indicating that coexistence of bronchiectasis should be considered a pathological phenotype of COPD, which may have a predictive value. | COPD is a heterogeneous disease characterized by airflow obstruction and diagnosed by lung function.,CT imaging is emerging as an important, noninvasive tool in phenotyping COPD.,However, the use of CT imaging in defining the disease heterogeneity above lung function is not fully known.,Seventy-five patients with COPD (58 men, 17 women) were studied with CT imaging and with measures of airway inflammation.,Airway physiology and health status were also determined.,The presence of emphysema (EM), bronchiectasis (BE), and bronchial wall thickening (BWT) was found in 67%, 27%, and 27% of subjects, respectively.,The presence of EM was associated with lower lung function (mean difference % FEV1, −20%; 95% CI, −28 to −11; P < .001).,There was no difference in airway inflammation, exacerbation frequency, or bacterial load in patients with EM alone or with BE and/or BWT ± EM.,The diffusing capacity of the lung for carbon monoxide/alveolar volume ratio was the most sensitive and specific parameter in identifying EM (area under the receiver operator characteristic curve, 0.87; 95% CI, 0.79-0.96).,Physiologic cluster analysis identified three clusters, two of which were EM predominant and the third characterized by a heterogeneous combination of EM and BE.,The application of CT imaging can be useful as a tool in the multidimensional approach to phenotyping patients with COPD. | 1 |
In the last two decades, mesenchymal stem cells (MSCs) have been pre-clinically utilized in the treatment of a variety of kinds of diseases including chronic obstructive pulmonary disease (COPD).,The aim of the current study was to systematically review and conduct a meta-analysis on the published pre-clinical studies of MSC administration in the treatment of COPD in animal models.,A systematic search of electronic databases was performed.,Statistical analysis was performed using the Comprehensive Meta-Analysis software (Version 3).,The pooled Hedges’s g with 95% confidence intervals (95% CIs) was adopted to assess the effect size.,Random effect model was used due to the heterogeneity between the studies.,A total of 20 eligible studies were included in the current systematic review.,The overall meta-analysis showed that MSC administration was significantly in favor of attenuating acute lung injury (Hedges’s g = -2.325 ± 0.145 with 95% CI: -2.609 ~ -2.040, P < 0.001 for mean linear intercept, MLI; Hedges’s g = -3.488 ± 0.504 with 95% CI: -4.476 ~ -2.501, P < 0.001 for TUNEL staining), stimulating lung tissue repair (Hedges’s g = 3.249 ± 0.586 with 95% CI: 2.103~ 4.394, P < 0.001) and improving lung function (Hedges’s g = 2.053 ± 0.408 with 95% CI: 1.253 ~ 2.854, P< 0.001).,The mechanism of MSC therapy in COPD is through ameliorating airway inflammation (Hedges’s g = -2.956 ± 0.371 with 95% CI: -3.683 ~ -2.229, P< 0.001) and stimulating cytokine synthesis that involves lung tissue repair (Hedges’s g = 3.103 ± 0.734 with 95% CI: 1.664 ~ 4.541, P< 0.001).,This systematic review and meta-analysis suggest a promising role for MSCs in COPD treatment.,Although the COPD models may not truly mimic COPD patients, these pre-clinical studies demonstrate that MSC hold promise in the treatment of chronic lung diseases including COPD.,The mechanisms of MSCs role in preclinical COPD treatment may be associated with attenuating airway inflammation as well as stimulating lung tissue repair. | Stem cell transplantation is a promising method for the treatment of chronic obstructive pulmonary disease (COPD), and mesenchymal stem cells (MSCs) have clinical potential for lung repair/regeneration.,However, the rates of engraftment and differentiation are generally low following MSC therapy for lung injury.,In previous studies, we constructed a pulmonary surfactant-associated protein A (SPA) suicide gene system, rAAV-SPA-TK, which induced apoptosis in alveolar epithelial type II (AT II) cells and vacated the AT II cell niche.,We hypothesized that this system would increase the rates of MSC engraftment and repair in COPD rats.,The MSC engraftment rate and morphometric changes in lung tissue in vivo were investigated by in situ hybridization, hematoxylin and eosin staining, Masson’s trichrome staining, immunohistochemistry, and real-time PCR.,The expression of hypoxia inducible factor (HIF-1α) and stromal cell-derived factor-1 (SDF-1), and relationship between HIF-1α and SDF-1 in a hypoxic cell model were analyzed by real-time PCR, western blotting, and enzyme-linked immunosorbent assay.,rAAV-SPA-TK transfection increased the recruitment of MSCs but induced pulmonary fibrosis in COPD rats.,HIF-1α and SDF-1 expression were enhanced after rAAV-SPA-TK transfection.,Hypoxia increased the expression of HIF-1α and SDF-1 in the hypoxic cell model, and SDF-1 expression was augmented by HIF-1α under hypoxic conditions.,Vacant AT II cell niches increase the homing and recruitment of MSCs to the lung in COPD rats.,MSCs play an important role in lung repair and promote collagen fiber deposition after induction of secondary damage in AT II cells by rAAV-SPA-TK, which involves HIF-1α and SDF-1 signaling. | 1 |
Epithelial-mesenchymal transition (EMT) plays a crucial role in small airway fibrosis of patients with chronic obstructive pulmonary disease (COPD).,Increasing evidence suggests that the urokinase plasminogen activator receptor (uPAR) is involved in the pathogenesis of COPD.,Increased uPAR expression has been implicated in the promotion of EMT in numerous cancers; however the role of uPAR in EMT in small airway epithelial cells of patients with COPD remains unclear.,In this study, we investigated the degree of EMT and uPAR expression in lung epithelium of COPD patients, and verified the effect of uPAR on cigarette smoke extract (CSE)-induced EMT in vitro.,The expression of EMT biomarkers and uPAR was assessed in lung epithelium specimens from non-smokers (n = 25), smokers (n = 25) and non-smokers with COPD (n = 10) and smokers with COPD (n = 18).,The role of uPAR on CSE-induced EMT in human small airway epithelial cells (HSAEpiCs) was assessed by silencing uPAR expression in vitro.,Markers of active EMT and uPAR expression were significantly increased in the small airway epithelium of patients with COPD compared with controls.,We also observed a significant correlation between uPAR and vimentin expression in the small airway epithelium.,In vitro, CSE-induced EMT in HSAEpiCs was associated with high expression of uPAR, and targeted silencing of uPAR using shRNA inhibited CSE-induced EMT.,Finally, we demonstrate that the PI3K/Akt signaling pathway is required for uPAR-mediated EMT in HSAEpiCs.,A uPAR-dependent signaling pathway is required for CSE-induced EMT, which contributes to small airway fibrosis in COPD.,We propose that increased uPAR expression in the small airway epithelium of patients with COPD participates in an active EMT process. | Despite a number of important differences in the pathogenesis, course and prognosis of asthma and chronic obstructive pulmonary disease (COPD), these two entities also have common features with airway inflammation being one of them.,Airway remodeling is a characteristic feature of asthma, but data on the bronchial wall thickening in COPD patients are still scarce.,To assess the relation between the inflammatory cell count in the bronchoalveolar lavage fluid (BALF) and thickness of bronchial walls assessed by high resolution computed tomography (HRCT) in asthma and COPD patients.,The study was conducted in 9 patients with mild-to-moderate asthma (M/F 4/5, mean age 35 ± 10 years) and 11 patients with mild-to-moderate COPD (M/F 7/4, mean age 57 ± 9 years).,In all subjects lung function tests and HRCT scanning of the chest were performed.,External (D) and internal (L) diameters of the airways were assessed at five selected lung levels.,The lumen area (AL), wall area (WA), wall thickness (WT) and bronchial wall thickness (WT/D ratio) were calculated.,Eight patients with asthma and 8 patients with COPD underwent fiberoptic bronchoscopy and bronchoalveolar lavage (BAL).,Total and differential cell counts were assessed in the BAL fluid.,Mean FEV1% pred was 80 ± 19%, and 73 ± 20% in asthma and COPD patients, respectively (NS).,No significant differences in the total and differential cell counts in BALF were found in patients with asthma and COPD.,There were no significant differences in the airway diameter or airway wall thickness.,The mean inner airway diameter was 1.4 ± 0.3 and 1.2 ± 0.3 mm and the mean lumen area was 1.8 ± 0.7 and 1.6 ± 0.7 mm2 in asthma and COPD, respectively (NS).,Negative correlations between the eosinophil count in BALF and inner airway diameter (r = -0.7, P < 0.05) and lumen area (r = -0.7, P < 0.05) were found in asthmatics.,There was no significant relationship between the BALF cell count and airway wall thickness in COPD patients.,In mild-to-moderate asthma and COPD the airway diameter and thickness are similar.,In asthmatics, the airway diameter might be associated with eosinophil count in BAL fluid. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with increased risk of severe COVID-19, but the mechanisms are unclear.,Besides, patients with severe COVID-19 have been reported to have increased levels of several immune mediators.,Ninety-two proteins were quantified in 315 plasma samples from 118 asthmatics, 99 COPD patients and 98 healthy controls (age 40-90 years), who were recruited in Colombia before the COVID-19 pandemic.,Protein levels were compared between each disease group and healthy controls.,Significant proteins were compared to the gene signatures of SARS-CoV-2 infection reported in the “COVID-19 Drug and Gene Set Library” and with experimentally tested protein biomarkers of severe COVID-19.,Forty-one plasma proteins showed differences between patients and controls.,Asthmatic patients have increased levels in IL-6 while COPD patients have a broader systemic inflammatory dysregulation driven by HGF, OPG, and several chemokines (CXCL9, CXCL10, CXCL11, CX3CL1, CXCL1, MCP-3, MCP-4, CCL3, CCL4 and CCL11).,These proteins are involved in chemokine signaling pathways related with response to viral infections and some, were found up-regulated upon SARS-CoV-2 experimental infection of Calu-3 cells as reported in the COVID-19 Related Gene Sets database.,An increase of HPG, CXCL9, CXCL10, IL-6, MCP-3, TNF and EN-RAGE has also been experimentally detected in patients with severe COVID-19.,COPD patients have altered levels of plasma proteins that have been reported increased in patients with severe COVID-19.,Our study suggests that COPD patients have a systemic dysregulation in chemokine networks (including HGF and CXCL9) that could make them more susceptible to severe COVID-19.,Also, that IL-6 levels are increased in some asthmatic patients (especially in females) and this may influence their response to COVID-19.,The findings in this study depict a novel panel of inflammatory plasma proteins in COPD patients that may potentially associate with increased susceptibility to severe COVID-19 and might be useful as a biomarker signature after future experimental validation. | Chronic obstructive pulmonary disease (COPD) causes significant morbidity and mortality worldwide.,Estimation of incidence, prevalence and disease burden through routine insurance data is challenging because of under-diagnosis and under-treatment, particularly for early stage disease in health care systems where outpatient International Classification of Diseases (ICD) diagnoses are not collected.,This poses the question of which criteria are commonly applied to identify COPD patients in claims datasets in the absence of ICD diagnoses, and which information can be used as a substitute.,The aim of this systematic review is to summarize previously reported methodological approaches for the identification of COPD patients through routine data and to compile potential criteria for the identification of COPD patients if ICD codes are not available.,A systematic literature review was performed in Medline via PubMed and Google Scholar from January 2000 through October 2018, followed by a manual review of the included studies by at least two independent raters.,Study characteristics and all identifying criteria used in the studies were systematically extracted from the publications, categorized, and compiled in evidence tables.,In total, the systematic search yielded 151 publications.,After title and abstract screening, 38 publications were included into the systematic assessment.,In these studies, the most frequently used (22/38) criteria set to identify COPD patients included ICD codes, hospitalization, and ambulatory visits.,Only four out of 38 studies used methods other than ICD coding.,In a significant proportion of studies, the age range of the target population (33/38) and hospitalization (30/38) were provided.,Ambulatory data were included in 24, physician claims in 22, and pharmaceutical data in 18 studies.,Only five studies used spirometry, two used surgery and one used oxygen therapy.,A variety of different criteria is used for the identification of COPD from routine data.,The most promising criteria set in data environments where ambulatory diagnosis codes are lacking is the consideration of additional illness-related information with special attention to pharmacotherapy data.,Further health services research should focus on the application of more systematic internal and/or external validation approaches. | 1 |
Airway epithelium integrity is essential to maintain its role of mechanical and functional barrier.,Recurrent epithelial injuries require a complex mechanism of repair to restore its integrity.,In chronic obstructive pulmonary disease (COPD), an abnormal airway epithelial repair may participate in airway remodeling.,The objective was to determine if airway epithelial wound repair of airway epithelium is abnormal in COPD.,Patients scheduled for lung resection were prospectively recruited.,Demographic, clinical data and pulmonary function tests results were recorded.,Emphysema was visually scored and histological remodeling features were noted.,Primary bronchial epithelial cells (BEC) were extracted and cultured for wound closure assay.,We determined the mean speed of wound closure (MSWC) and cell proliferation index, matrix metalloprotease (MMP)-2, MMP-9 and cytokines levels in supernatants of BEC 18 hours after cell wounding.,In a subset of patients, bronchiolar epithelial cells were also cultured for wound closure assay for MSWC analyze.,13 COPD and 7 non COPD patients were included.,The severity of airflow obstruction and the severity of emphysema were associated with a lower MSWC in BEC (p = 0.01, 95% CI [0.15-0.80]; p = 0.04, 95% CI [−0.77;-0.03] respectively).,Cell proliferation index was decreased in COPD patients (19 ± 6% in COPD vs 27 ± 3% in non COPD, p = 0.04).,The severity of COPD was associated with a lower level of MMP-2 (7.8 ± 2 105 AU in COPD GOLD D vs 12.8 ± 0.13 105 AU in COPD GOLD A, p = 0.04) and a lower level of IL-4 (p = 0.03, 95% CI [0.09;0.87]).,Moreover, higher levels of IL-4 and IL-2 were associated with a higher MSWC (p = 0.01, 95% CI [0.17;0.89] and p = 0.02, 95% CI [0.09;0.87] respectively).,Clinical characteristics and smoking history were not associated with MSWC, cell proliferation index or MMP and cytokines levels.,Finally, we showed an association of the MSWC of bronchial and corresponding bronchiolar epithelial cells obtained from the same patients (p = 0.02, 95% CI [0.12;0.89]).,Our results showed an abnormal bronchial epithelial wound closure process in severe COPD.,Further studies are needed to elucidate the contribution and the regulation of this mechanism in the complex pathophysiology of COPD.,The online version of this article (doi:10.1186/s12931-014-0151-9) contains supplementary material, which is available to authorized users. | Eosinophilic airway inflammation is observed in 10-30% of COPD subjects.,Whether increased eosinophils or impairment in their clearance by macrophages is associated with the severity and frequency of exacerbations is unknown.,We categorised 103 COPD subjects into 4 groups determined by the upper limit of normal for their cytoplasmic macrophage red hue (<6%), an indirect measure of macrophage efferocytosis of eosinophils, and area under the curve sputum eosinophil count (≥3%/year).,Eosinophil efferocytosis by monocyte-derived macrophages was studied in 17 COPD subjects and 8 normal controls.,There were no differences in baseline lung function, health status or exacerbation frequency between the groups: A-low red hue, high sputum eosinophils (n = 10), B-high red hue, high sputum eosinophils (n = 16), C-low red hue, low sputum eosinophils (n = 19) and D- high red hue, low sputum eosinophils (n = 58).,Positive bacterial culture was lower in groups A (10%) and B (6%) compared to C (44%) and D (21%) (p = 0.01).,The fall in FEV1 from stable to exacerbation was greatest in group A (ΔFEV1 [95 % CI] -0.41 L [-0.65 to -0.17]) versus group B (-0.16 L [-0.32 to -0.011]), C (-0.11 L [-0.23 to -0.002]) and D (-0.16 L [-0.22 to -0.10]; p = 0.02).,Macrophage efferocytosis of eosinophils was impaired in COPD versus controls (86 [75 to 92]% versus 93 [88 to 96]%; p = 0.028); was most marked in group A (71 [70 to 84]%; p = 0.0295) and was inversely correlated with exacerbation frequency (r = -0.63; p = 0.006).,Macrophage efferocytosis of eosinophils is impaired in COPD and is related to the severity and frequency of COPD exacerbations. | 1 |
Chronic obstructive pulmonary disease (COPD) exacerbations are associated with systemic consequences.,Data from a 4-year trial (Understanding Potential Long-term Impacts on Function with Tiotropium [UPLIFT®], n = 5,992) were used to determine risk for nonlower respiratory serious adverse events (NRSAEs) following an exacerbation.,Patients with ≥1 exacerbation were analyzed.,NRSAE incidence rates (incidence rate [IR], per 100 patient-years) were calculated for the 30 and 180 days before and after the first exacerbation.,NRSAEs were classified by diagnostic terms and organ classes.,Maentel-Haenszel rate ratios (RR) (pre- and postexacerbation onset) along with 95% confidence intervals (CI) were computed.,A total of 3,960 patients had an exacerbation.,The mean age was 65 years, forced expiratory volume in 1 s (FEV1) was 38% predicted, and 74% were men.,For all NRSAEs, the IRs 30 days before and after an exacerbation were 20.2 and 65.2 with RR (95% CI) = 3.22 (2.40-4.33).,The IRs for the 180-day periods were 13.2 and 31.0 with RR (95% CI) = 2.36 (1.93-2.87).,The most common NRSAEs by organ class for both time periods were cardiac, respiratory system (other), and gastrointestinal.,All NRSAEs as well as cardiac events were more common after the first exacerbation, irrespective of whether the patient had cardiac disease at baseline.,The findings confirm that, after exacerbations, serious adverse events in other organ systems are more frequent, particularly those that are cardiac in nature. | The mortality and incidence of chronic obstructive pulmonary disease (COPD) and coronary heart disease increase with age.,Despite the clear evidence of beta blockers (BBs) effectiveness, there is a general reluctance to use them in patients with COPD due to a perceived contraindication and fear of inducing adverse reactions and bronchspasm.,BBs are well tolerated in patients with cardiac disease and concomitant COPD with no evidence of worsening of respiratory symptoms or FEV1, and the safety of BBs in patients with COPD has been demonstrated, but their use in this group of patients remains low.,The cumulative evidence from trials and meta-analysis indicates that cardioselective BBs should not be withheld in patients with reactive airway disease or COPD.,Patients with COPD have a high incidence of cardiac events necessitating careful consideration of prophylactic treatment.,The benefits of beta blockade in this group appear to outweigh any potential risk of side effects according to the available evidence.,In this article, we will discuss the use of BBs in patients with COPD and review the evidence for their use and safety in this group of patients. | 1 |
Prediction models for exacerbations in patients with chronic obstructive pulmonary disease (COPD) are scarce.,Our aim was to develop and validate a new model to predict exacerbations in patients with COPD.,The derivation cohort consisted of patients aged 65 years or over, with a COPD diagnosis, who were followed up over 24 months.,The external validation cohort consisted of another cohort of COPD patients, aged 50 years or over.,Exacerbations of COPD were defined as symptomatic deterioration requiring pulsed oral steroid use or hospitalization.,Logistic regression analysis including backward selection and shrinkage were used to develop the final model and to adjust for overfitting.,The adjusted regression coefficients were applied in the validation cohort to assess calibration of the predictions and calculate changes in discrimination applying C-statistics.,The derivation and validation cohort consisted of 240 and 793 patients with COPD, of whom 29% and 28%, respectively, experienced an exacerbation during follow-up.,The final model included four easily assessable variables: exacerbations in the previous year, pack years of smoking, level of obstruction, and history of vascular disease, with a C-statistic of 0.75 (95% confidence interval [CI]: 0.69-0.82).,Predictions were well calibrated in the validation cohort, with a small loss in discrimination potential (C-statistic 0.66 [95% CI 0.61-0.71]).,Our newly developed prediction model can help clinicians to predict the risk of future exacerbations in individual patients with COPD, including those with mild disease. | 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. | 1 |
Clinical manifestations of chronic obstructive pulmonary disease (COPD), including airflow limitation, dyspnea, and activity limitation, ultimately lead to impaired health-related quality of life (HRQoL).,This 9-month, randomized, double-blind, multicenter study compared the effect of once-daily tiotropium 18 μg and placebo on HRQoL, spirometric parameters, and exacerbations in 554 patients with moderate-to-severe COPD.,HRQoL was assessed using the St.,George’s Respiratory Questionnaire (SGRQ) and the new 8-item Visual Simplified Respiratory Questionnaire (VSRQ), which is currently being validated.,The primary efficacy endpoint was the proportion of patients achieving a reduction of at least 4 units in the SGRQ total score at study end (Month 9).,Mean ± SD baseline SGRQ total score was 47.4 ± 18.1.,Significantly more tiotropium-treated patients achieved a reduction of at least 4 units in the SGRQ score vs placebo at study end (59.1% vs 48.2%, respectively; p = 0.029).,Tiotropium significantly improved spirometric parameters (forced expiratory volume in 1 second [FEV1]: 0.11 ± 0.02 L vs 0.01 ± 0.02 L; between-group difference: 0.10 ± 0.03 L, p = 0.0001) and reduced exacerbations vs placebo.,Maintenance treatment with tiotropium provided significant and clinically relevant improvements in HRQoL, as measured by the SGRQ. | Clinical trials of tiotropium have principally recruited patients from secondary care with more severe chronic obstructive pulmonary disease (COPD), and typically had included limitation of concomitant medication.,In primary care, which is the most common setting for COPD management, many patients may have milder disease, and also may take a broad range of concomitant medication.,This randomised, placebo-controlled, parallel-group, 12-week, 44-centre study investigated the efficacy (trough forced expiratory volume in 1 second [FEV1] response) and safety of additional treatment with once-daily tiotropium 18 μg via the HandiHaler® in a primary care COPD population (tiotropium: N = 191, FEV1 = 1.25 L [47.91% predicted]; placebo: N = 183, FEV1 = 1.32 L [49.86% predicted]).,Secondary endpoints included: trough forced vital capacity (FVC) response, weekly use of rescue short-acting β-agonist, and exacerbation of COPD (complex of respiratory symptoms/events of >3 days in duration requiring a change in treatment).,Treatment effects were determined using non-parametric analysis.,At Week 12, median improvement in trough FEV1 response with tiotropium versus placebo was 0.06 L (p = 0.0102).,The improvement was consistent across baseline treatment and COPD severity.,Median improvement in FVC at 2, 6 and 12 weeks was 0.12 L (p < 0.001).,The percentage of patients with ≥1 exacerbation was reduced (tiotropium 9.5%; placebo 17.9%; p = 0.0147), independent of disease severity.,Rescue medication usage was significantly reduced in the tiotropium group compared with placebo.,Adverse event profile was consistent with previous studies.,Tiotropium provides additional benefits to usual primary care management in a representative COPD population.,The identifier is: NCT00274079. | 1 |
Chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity and mortality in the United States.,Exacerbations- acute worsening of COPD symptoms-can be mild to severe in nature.,Increased healthcare resource use is common among patients with frequent exacerbations, and exacerbations are a major cause of the high 30-day hospital readmission rates associated with COPD.,This review provides a concise overview of the literature regarding the impact of COPD exacerbations on both the patient and the healthcare system, the recommendations for pharmacologic management of COPD, and the strategies employed to improve patient care and reduce hospitalizations and readmissions.,COPD exacerbations significantly impact patients’ health-related quality of life and disease progression; healthcare costs associated with severe exacerbation-related hospitalization range from $7,000 to $39,200.,Timely and appropriate maintenance pharmacotherapy, particularly dual bronchodilators for maximizing bronchodilation, can significantly reduce exacerbations in patients with COPD.,Additionally, multidisciplinary disease-management programs include pulmonary rehabilitation, follow-up appointments, aftercare, inhaler training, and patient education that can reduce hospitalizations and readmissions for patients with COPD.,Maximizing bronchodilation by the appropriate use of maintenance therapy, together with multidisciplinary disease-management and patient education programs, offers opportunities to reduce exacerbations, hospitalizations, and readmissions for patients with COPD. | Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation. | 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. | It is extremely important to objectively take a view of population health to provide useful information to decision makers, health-sector leaders, researchers, and informed citizens.,This study aims to examine the burden of disease in Korea as of 2015, and to study how the burden of disease changes with the passage of time.,We used results from the Korean National Burden of Disease and Injuries Study 2015 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive disability-adjusted life years (DALYs) by gender and age groups from 2007 to 2015.,DALYs were calculated as the sum of the years of life lost (YLLs) and the years lived with disability (YLDs).,In 2015, the burden of disease for Korean people was calculated at 29,476 DALYs per 100,000 population.,DALYs caused by low back pain were the highest, followed by diabetes mellitus and chronic obstructive pulmonary disease.,The burden of disease showed a consistently increasing trend from 2007 to 2015.,Although YLLs have been on the decrease since 2011, the increase in YLDs has contributed to the overall rise in DALYs.,The DALYs per 100,000 population in 2015 increased by 28.1% compared to 2007.,As for the diseases for which the burden of disease is substantially increasing, it is needed to establish appropriate policies in a timely manner.,The results of this study are expected to be the basis for prioritizing public health and health care policies in Korea. | 1 |
The global increase in the prevalence and incidence of obesity has called serious attention to this issue as a major public health concern.,Obesity is associated with many chronic diseases, including cardiovascular disease and diabetes, and recently the role of overweight and obesity in lung disease has received new interest.,Independently of obesity, diet also plays a role as a risk factor for many chronic diseases, and evidence is accumulating to support a role for diet in the prevention and management of several lung diseases.,Chronic obstructive lung disease is the third-leading cause of death globally, and both obesity and diet appear to play roles in its pathophysiology.,Obesity has been associated with decreased lung-function measures in population-based studies, with increased prevalence of several lung diseases and with compromised pulmonary function.,In contrast, obesity has a protective effect against mortality in severe chronic obstructive pulmonary disease (COPD).,Nutrient intake and dietary patterns have also been associated with lung-function measures and the development and progression of COPD.,Taken together, this suggests that a focus on obesity and diet should be part of public health campaigns to reduce the burden of lung disease, and could have important implications for clinicians in the management of their patients.,Future research should also focus on elucidating these relationships in diverse populations and age-groups, and on understanding the complex interaction between behavior, environment, and genetics in the development and progression of COPD.,The goal of this article is to review current evidence regarding the role that obesity and diet play in the development of COPD, and in COPD-related outcomes. | Since the discovery of alpha-1 antitrypsin in the early 1960s, several new genes have been suggested to play a role in chronic obstructive pulmonary disease (COPD) pathogenesis.,Yet, in spite of those advances, much about the genetic basis of COPD still remains to be discovered.,Unbiased approaches, such as genome-wide association (GWA) studies, are critical to identify genes and pathways and to verify suggested genetic variants.,Indeed, most of our current understanding about COPD candidate genes originates from GWA studies.,Experiments in form of cross-study replications and advanced meta-analyses have propelled the field towards unravelling details about COPD's pathogenesis.,Here, we review the discovery of genetic variants in association with COPD phenotypes by discussing the available approaches and current findings.,Limitations of current studies are considered and future directions provided. | 1 |
After the development of the COPD Strategy of the National Health Service in Spain, all scientific societies, patient organisations, and central and regional governments formed a partnership to enhance care and research in COPD.,At the same time, the Spanish Society of Pneumology and Thoracic Surgery (SEPAR) took the initiative to convene the various scientific societies involved in the National COPD Strategy and invited them to participate in the development of the new Spanish guidelines for COPD (Guía Española de la EPOC; GesEPOC).,Probably the more innovative approach of GesEPOC is to base treatment of stable COPD on clinical phenotypes, a term which has become increasingly used in recent years to refer to the different clinical forms of COPD with different prognostic implications.,The proposed phenotypes are: (A) infrequent exacerbators with either chronic bronchitis or emphysema; (B) overlap COPD-asthma; (C) frequent exacerbators with emphysema predominant; and (D) frequent exacerbators with chronic bronchitis predominant.,The assessment of severity has also been updated with the incorporation of multidimensional indices.,The severity of the obstruction, as measured by forced expiratory volume in 1 second, is essential but not sufficient.,Multidimensional indices such as the BODE index have shown excellent prognostic value.,If the 6-minute walking test is not performed routinely, its substitution by the frequency of exacerbations (BODEx index) provides similar prognostic properties.,This proposal aims to achieve a more personalised management of COPD according to the clinical characteristics and multidimensional assessment of severity. | Current methods for assessing clinical outcomes in COPD mainly rely on physiological tests combined with the use of questionnaires.,The present review considers commonly used outcome measures such as lung function, health status, exercise capacity and physical activity, dyspnoea, exacerbations, the multi-dimensional BODE score, and mortality.,Based on current published data, we provide a concise overview of the principles, strengths and weaknesses, and discuss open questions related to each methodology.,Reviewed is the current set of markers for measuring clinically relevant outcomes with particular emphasis on their limitations and opportunities that should be recognized when assessing and interpreting their use in clinical trials of COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is the third cause of disease-related death and brings a heavy burden to human health.,Long non-coding RNA (lncRNA) was revealed to participate in COPD pathogenesis.,This study aims to establish the effects and regulatory mechanism of lncRNA long intergenic non-coding 00987 (LINC00987) in lipopolysaccharide (LPS)-induced apoptosis, oxidative stress, inflammation and autophagy in BEAS-2B cells.,The expression levels of LINC00987 and let-7b-5p were detected by real-time quantitativepolymerase chain reaction (RT-qPCR).,The expression of apoptosis-associated proteins, oxidative stress (ROS)-related proteins, autophagy-related proteins and sirtuin1 (SIRT1) protein was determined by Western blot.,Cell viability was illustrated by cell counting kit-8 (CCK-8) assay.,Cell apoptosis was investigated by caspase3 activity and apoptosis analysis assays.,ROS, inflammation and autophagy were demonstrated by detecting reactive ROS level and superoxide dismutase (SOD) activity, enzyme-linked immunosorbent assay (ELISA) and Western blot analysis, respectively.,The binding sites between let-7b-5p and LINC00987 or SIRT1 were predicted by lncBase or miRWalk online database, and identified by dual-luciferase reporter assay.,LINC00987 expression was strikingly downregulated and let-7b-5p expression was obviously upregulated in COPD tissues and LPS-induced BEAS-2B cells compared with control groups.,LINC00987 overexpression promoted BEAS-2B cells against LPS-mediated viability, apoptosis, oxidative stress, inflammation and autophagy, whereas these effects were attenuated by let-7b-5p mimic or SIRT1 knockdown.,Furthermore, LINC00987 sponged let-7b-5p and let-7b-5p bound to SIRT1.,LINC00987 ameliorated COPD through modulating LPS-induced cell apoptosis, oxidative stress, inflammation and autophagy via sponging let-7b-5p to associate with SIRT1.,This finding will provide a theoretical basis for the research of LncRNA-mediated treatment in COPD. | This study aimed to explore cytokine serum levels and the ratio of type 1 T helper (Th1)/Th2 cells in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).,A total 245 patients diagnosed with AECOPD and 193 patients who progressed to stable COPD after the initiation of treatment in hospital were selected, while a further 50 healthy individuals served as controls.,All patients with COPD were diagnosed using Global Initiative for Chronic Obstructive Lung Disease criteria.,Serum concentrations of interleukin (IL)-2, interferon (IFN)-γ, IL-4, IL-10, IL-17, and immunoglobulin (Ig)E were measured using enzyme-linked immunosorbent assays.,AECOPD patients had higher levels of IL-2, IFN-γ, IL-4, IL-10, IL-17, and IgE than those with stable COPD or controls.,Intriguingly, the ratios of Th1/Th2 and IL-17/IgE were lower in AECOPD patients compared with the other two groups.,These data suggest that AECOPD patients produce more IgE and have more differentiated Th2 cells than other groups.,Our findings suggest that an imbalance of circulating CD4+ T cell subsets correlates with AECOPD, and that a shift of Th1/Th2 and IL-17/IgE ratios may be caused by increased Th2 cell production. | 1 |
Oxidative stress is a major driving mechanism in the pathogenesis of COPD.,There is increased oxidative stress in the lungs of COPD patients due to exogenous oxidants in cigarette smoke and air pollution and due to endogenous generation of reactive oxygen species by inflammatory and structural cells in the lung.,Mitochondrial oxidative stress may be particularly important in COPD.,There is also a reduction in antioxidant defences, with inactivation of several antioxidant enzymes and the transcription factors Nrf2 and FOXO that regulate multiple antioxidant genes.,Increased systemic oxidative stress may exacerbate comorbidities and contribute to skeletal muscle weakness.,Oxidative stress amplifies chronic inflammation, stimulates fibrosis and emphysema, causes corticosteroid resistance, accelerates lung aging, causes DNA damage and stimulates formation of autoantibodies.,This suggests that treating oxidative stress by antioxidants or enhancing endogenous antioxidants should be an effective strategy to treat the underlying pathogenetic mechanisms of COPD.,Most clinical studies in COPD have been conducted using glutathione-generating antioxidants such as N-acetylcysteine, carbocysteine and erdosteine, which reduce exacerbations in COPD patients, but it is not certain whether this is due to their antioxidant or mucolytic properties.,Dietary antioxidants have so far not shown to be clinically effective in COPD.,There is a search for more effective antioxidants, which include superoxide dismutase mimetics, NADPH oxidase inhibitors, mitochondria-targeted antioxidants and Nrf2 activators. | Inflammation and oxidative stress play critical roles in patients with chronic obstructive pulmonary disease (COPD).,Mitochondrial oxidative stress might be involved in driving the oxidative stress-induced pathology.,We sought to determine the effects of oxidative stress on mitochondrial function in the pathophysiology of airway inflammation in ozone-exposed mice and human airway smooth muscle (ASM) cells.,Mice were exposed to ozone, and lung inflammation, airway hyperresponsiveness (AHR), and mitochondrial function were determined.,Human ASM cells were isolated from bronchial biopsy specimens from healthy subjects, smokers, and patients with COPD.,Inflammation and mitochondrial function in mice and human ASM cells were measured with and without the presence of the mitochondria-targeted antioxidant MitoQ.,Mice exposed to ozone, a source of oxidative stress, had lung inflammation and AHR associated with mitochondrial dysfunction and reflected by decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial oxidative stress, and reduced mitochondrial complex I, III, and V expression.,Reversal of mitochondrial dysfunction by the mitochondria-targeted antioxidant MitoQ reduced inflammation and AHR.,ASM cells from patients with COPD have reduced ΔΨm, adenosine triphosphate content, complex expression, basal and maximum respiration levels, and respiratory reserve capacity compared with those from healthy control subjects, whereas mitochondrial reactive oxygen species (ROS) levels were increased.,Healthy smokers were intermediate between healthy nonsmokers and patients with COPD.,Hydrogen peroxide induced mitochondrial dysfunction in ASM cells from healthy subjects.,MitoQ and Tiron inhibited TGF-β-induced ASM cell proliferation and CXCL8 release.,Mitochondrial dysfunction in patients with COPD is associated with excessive mitochondrial ROS levels, which contribute to enhanced inflammation and cell hyperproliferation.,Targeting mitochondrial ROS represents a promising therapeutic approach in patients with COPD. | 1 |
Pulmonary rehabilitation (PR) is a guideline-recommended multifaceted intervention that improves the physical and psychological well-being of people with chronic respiratory diseases (CRDs), though most of the evidence derives from trials in high-resource settings.,In low- and middle-income countries, PR services are under-provided.,We aimed to review the effectiveness, components and mode of delivery of PR in low-resource settings.,Following Cochrane methodology, we systematically searched (1990 to October 2018; pre-publication update March 2020) MEDLINE, EMBASE, CABI, AMED, PUBMED, and CENTRAL for controlled clinical trials of adults with CRD (including but not restricted to chronic obstructive pulmonary disease) comparing PR with usual care in low-resource settings.,After duplicate selection, we extracted data on exercise tolerance, health-related quality of life (HRQoL), breathlessness, included components, and mode of delivery.,We used Cochrane risk of bias (RoB) to assess study quality and synthesised data narratively.,From 8912 hits, we included 13 studies: 11 were at high RoB; 2 at moderate RoB.,PR improved functional exercise capacity in 10 studies, HRQoL in 12, and breathlessness in 9 studies.,One of the two studies at moderate RoB showed no benefit.,All programmes included exercise training; most provided education, chest physiotherapy, and breathing exercises.,Low cost services, adapted to the setting, used limited equipment and typically combined outpatient/centre delivery with a home/community-based service.,Multicomponent PR programmes can be delivered in low-resource settings, employing a range of modes of delivery.,There is a need for a high-quality trial to confirm the positive findings of these high/moderate RoB studies. | The aim of this study was to describe the impact of chronic obstructive pulmonary disease (COPD) on health status in the Burden of Obstructive Lung Disease (BOLD) populations.,We conducted a cross-sectional, general population-based survey in 11 985 subjects from 17 countries.,We measured spirometric lung function and assessed health status using the Short Form 12 questionnaire.,The physical and mental health component scores were calculated.,Subjects with COPD (post-bronchodilator forced expiratory volume in 1 s/forced vital capacity <0.70, n = 2269) had lower physical component scores (44±10 versus 48±10 units, p<0.0001) and mental health component scores (51±10 versus 52±10 units, p = 0.005) than subjects without COPD.,The effect of reported heart disease, hypertension and diabetes on physical health component scores (-3 to -4 units) was considerably less than the effect of COPD Global Initiative for Chronic Obstructive Lung Disease grade 3 (-8 units) or 4 (-11 units).,Dyspnoea was the most important determinant of a low physical and mental health component scores.,In addition, lower forced expiratory volume in 1 s, chronic cough, chronic phlegm and the presence of comorbidities were all associated with a lower physical health component score.,COPD is associated with poorer health status but the effect is stronger on the physical than the mental aspects of health status.,Severe COPD has a greater negative impact on health status than self-reported cardiovascular disease and diabetes.,COPD is related to worse health status: impairment is greater than in self-reported cardiovascular diseases or diabeteshttp://ow.ly/p1cIx | 1 |
Exacerbations are critical events in chronic pulmonary obstructive disease (COPD).,The frequency of COPD exacerbations is associated with the prognosis, including mortality, but no useful biomarker has been established.,The present retrospective study investigated 481 COPD patients.,Clinical features in the stable period were compared between patients who experienced severe exacerbation (n = 88, 18.3%) and those who never experienced severe exacerbation (n = 393, 81.7%).,In the patients who experienced exacerbations, clinical features were also compared between frequent exacerbators (exacerbation rate ≥ 2 times/year, n = 27, 30.7%) and infrequent exacerbators (1 time/year, n = 61, 69.3%).,Compared to COPD patients who never experienced exacerbations, body mass index (BMI), serum albumin, and pulmonary functions were significantly lower, and the cardiovascular disease comorbidity rate, COPD assessment test score, modified Medical Research Council dyspnea scale, and use of long-term oxygen therapy, long-acting β2 adrenergic agonist therapy, inhaled corticosteroid therapy, and macrolide therapy were significantly higher in COPD patients with exacerbations (all p < 0.01).,In patients who experienced exacerbations, frequent exacerbators had significantly lower % forced expiratory volume in 1.0 s and a higher risk of critical exacerbations, percentage of blood eosinophils, history of mechanical ventilation use, and use of long-term oxygen therapy and of macrolide therapy than infrequent exacerbators (all p < 0.01).,On multivariate analysis, the percentage of blood eosinophils was the parameter most correlated with exacerbation frequency (β value [95% confidence interval] 1.45 [1.12-1.88], p < 0.01).,Blood eosinophil in the stable period is the factor most correlated with the frequency of severe exacerbations.,Trial registration: The patients in this study was registered retrospectively | Blood eosinophil is a readily available biomarker to reflect the eosinophilic inflammation in chronic obstructive pulmonary disease (COPD) patients, yet its association with exacerbation is inconclusive.,It is uncertain which measurement, eosinophil percentage or absolute eosinophil count, should be used and what is the optimal cutoff for exacerbation prediction.,A total of 247 COPD patients were included in this retrospective cohort study.,Blood eosinophil during stable disease state, baseline demographics, and clinical characteristics in 12 months after the index complete blood count (CBC) were recorded.,Exacerbation frequencies were compared between patients with high and low blood eosinophil percentage using 2% as cut-off.,Logistic regression and receiver operating characteristics (ROC) curve analyses were conducted.,Patients with blood eosinophil ≥2% were associated with more frequent exacerbations than patients with eosinophil <2% in the 12 months after the index CBC (mean exacerbation 1.07 vs 0.34, p < 0.001).,Higher blood eosinophil percentage conferred a higher risk of exacerbation.,Adjusted odds ratio for exacerbation in 12 months after the index CBC for blood eosinophil ≥2% was 2.98 (95% confidence interval = 1.42-6.25).,The area under the ROC curve of eosinophil percentage was significantly higher than that of absolute eosinophil count (0.678 vs 0.640, p = 0.010).,The optimal cutoff of blood eosinophil percentage for exacerbation prediction was 2.8%.,Blood eosinophilia was associated with higher exacerbation risk in COPD patients.,Further studies are required to elucidate the mechanism of eosinophilic inflammation in COPD and determine the optimal treatment strategy to reduce exacerbations. | 1 |
Therapeutic adherence of patients with chronic obstructive pulmonary disease (COPD) is poor.,This study evaluated the effectiveness of a multifactorial intervention on improving the therapeutic adherence in chronic obstructive pulmonary disease (COPD) patients with scheduled inhalation therapy.,The study design consisted of a randomised controlled trial in a primary care setting. 146 patients diagnosed with COPD were randomly allocated into two groups using the block randomisation technique.,One-year follow-ups with three visits were performed.,The intervention consisted of motivational aspects related to adherence (beliefs and behaviour) in the form of group and individual interviews, cognitive aspects in the form of information about the illness and skills in the form of training in inhalation techniques.,Cognitive-emotional aspects and training in inhalation techniques were reinforced during all visits of the intervention group.,The main outcome measure was adherence to the medication regimen.,Therapeutic adherence was determined by the percentage of patients classified as good adherent as evaluated by dose or pill count.,Of the 146 participants (mean age 69.8 years, 91.8% males), 41.1% reported adherence (41.9% of the control group and 40.3% of the intervention group).,When multifactorial intervention was applied, the reported adherence was 32.4% for the control group and 48.6% for the intervention group, which showed a statistically significant difference (p = 0.046).,Number needed to treat is 6.37.,In the intervention group, cognitive aspects increased by 23.7% and skilled performance of inhalation techniques increased by 66.4%.,The factors related to adherence when multifactorial intervention was applied were the number of exacerbations (OR = 0.66), visits to health centre (OR = 0.93) and devices (OR = 2.4); illness severity (OR = 0.67), beta-2-adrenergic (OR = 0.16) and xantine (OR = 0.19) treatment; activity (OR = 1.03) and impact (OR = 1.03) scales of the Saint George Respiratory Questionnaire.,Application of the multifactorial intervention designed for this study (COPD information, dose reminders, audio-visual material, motivational aspects and training in inhalation techniques) resulted in an improvement in therapeutic adherence in COPD patients with scheduled inhalation therapy.,Current Controlled Trials ISRCTN18841601. | Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of disability, hospitalization, and premature mortality.,General practice is well placed to diagnose and manage COPD, but there is a significant gap between evidence and current practice, with a low level of awareness and implementation of clinical practice guidelines.,Under-diagnosis of COPD is a world-wide problem, limiting the benefit that could potentially be achieved through early intervention strategies such as smoking cessation, dietary advice, and exercise.,General practice is moving towards more structured chronic disease management, and the increasing involvement of practice nurses in delivering chronic care.,A pragmatic cluster randomised trial will test the hypothesis that intervention by a practice nurse-general practitioner (GP) team leads to improved health-related quality of life and greater adherence with clinical practice guidelines for patients with newly-diagnosed COPD, compared with usual care.,Forty general practices in greater metropolitan Sydney Australia will be recruited to identify patients at risk of COPD and invite them to attend a case finding appointment.,Practices will be randomised to deliver either practice nurse-GP partnership care, or usual care, to patients newly-diagnosed with COPD.,The active intervention will involve the practice nurse and GP working in partnership with the patient in developing and implementing a care plan involving (as appropriate), smoking cessation, immunisation, pulmonary rehabilitation, medication review, assessment and correction of inhaler technique, nutritional advice, management of psycho-social issues, patient education, and management of co-morbidities.,The primary outcome measure is health-related quality of life, assessed with the St George’s Respiratory Questionnaire 12 months after diagnosis.,Secondary outcome measures include validated disease-specific and general health related quality of life measures, smoking and immunisation status, medications, inhaler technique, and lung function.,Outcomes will be assessed by project officers blinded to patients’ randomization groups.,This study will use proven case-finding methods to identify patients with undiagnosed COPD in general practice, where improved care has the potential for substantial benefit in health and healthcare utilization.,The study provides the capacity to trial a new model of team-based assessment and management of newly diagnosed COPD in Australian primary care.,ACTRN12610000592044\ | 1 |
The Global initiative for chronic Obstructive Lung Disease (GOLD) Committee has proposed a chronic obstructive pulmonary disease (COPD) assessment framework focused on symptoms and on exacerbation risk.,This study will evaluate a symptom and exacerbation risk-based treatment strategy based on GOLD in a real-world setting in Japan.,Optimal management of COPD will be determined by assessing symptoms using the COPD Assessment Test (CAT) and by assessing the frequency of exacerbations.,This study (ClinicalTrials.gov identifier: NCT01762800) is a 24-week, multicenter, randomized, double-blind, double-dummy, parallel-group study.,It aims to recruit 400 patients with moderate-to-severe COPD.,Patients will be randomized to receive treatment with either salmeterol/fluticasone propionate (SFC) 50/250 μg twice daily or with tiotropium bromide 18 μg once daily.,Optimal management of patients will be assessed at four-weekly intervals and, if patients remain symptomatic, as measured using the CAT, or experience an exacerbation, they have the option to step up to treatment with both drugs, ie, SFC twice daily and tiotropium once daily (TRIPLE therapy).,The primary endpoint of the study will be the proportion of patients who are able to remain on the randomized therapy.,No data are available.,This paper summarizes the methodology of the study in advance of the study starting.,The results of this study will help physicians to understand whether TRIPLE therapy is more effective than either treatment strategy alone in controlling symptoms and exacerbations in patients with moderate-to-severe COPD.,It will also help physicians to understand the GOLD recommendation work in Japan. | 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 |
Background: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD).,It represents a collaborative effort on the part of a panel of expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thoracic Society.,Methods: Comprehensive evidence syntheses were performed on all relevant studies that addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts.,The evidence was appraised, rated, and graded, and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.,Results: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations: 1) a strong recommendation for the use of long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance; 2) a conditional recommendation for the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year; 3) a conditional recommendation for ICS withdrawal for patients with COPD receiving triple therapy (ICS/LABA/LAMA) if the patient has had no exacerbations in the past year; 4) no recommendation for or against ICS as an additive therapy to long-acting bronchodilators in patients with COPD and blood eosinophilia, except for those patients with a history of one or more exacerbations in the past year requiring antibiotics or oral steroids or hospitalization, for whom ICS is conditionally recommended as an additive therapy; 5) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and 6) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy.,Conclusions: The task force made recommendations regarding the pharmacologic treatment of COPD based on currently available evidence.,Additional research in populations that are underrepresented in clinical trials is needed, including studies in patients with COPD 80 years of age and older, those with multiple chronic health conditions, and those with a codiagnosis of COPD and asthma. | Pulmonary Rehabilitation for moderate Chronic Obstructive Pulmonary Disease in primary care could improve patients’ quality of life.,This study aimed to assess the efficacy of a 3-month Pulmonary Rehabilitation (PR) program with a further 9 months of maintenance (RHBM group) compared with both PR for 3 months without further maintenance (RHB group) and usual care in improving the quality of life of patients with moderate COPD.,We conducted a parallel-group, randomized clinical trial in Majorca primary health care in which 97 patients with moderate COPD were assigned to the 3 groups.,Health outcomes were quality of life, exercise capacity, pulmonary function and exacerbations.,We found statistically and clinically significant differences in the three groups at 3 months in the emotion dimension (0.53; 95%CI0.06-1.01) in the usual care group, (0.72; 95%CI0.26-1.18) the RHB group (0.87; 95%CI 0.44-1.30) and the RHBM group as well as in fatigue (0.47; 95%CI 0.17-0.78) in the RHBM group.,After 1 year, these differences favored the long-term rehabilitation group in the domains of fatigue (0.56; 95%CI 0.22-0.91), mastery (0.79; 95%CI 0.03-1.55) and emotion (0.75; 95%CI 0.17-1.33).,Between-group analysis only showed statistically and clinically significant differences between the RHB group and control group in the dyspnea dimension (0.79 95%CI 0.05-1.52).,No differences were found for exacerbations, pulmonary function or exercise capacity.,We found that patients with moderate COPD and low level of impairment did not show meaningful changes in QoL, exercise tolerance, pulmonary function or exacerbation after a one-year, community based rehabilitation program.,However, long-term improvements in the emotional, fatigue and mastery dimensions (within intervention groups) were identified.,ISRCTN94514482 | 1 |
Previous studies have investigated the effects of air pollution on chronic obstructive pulmonary disease (COPD) patients using either fixed-site measurements or a limited number of personal measurements, usually for one pollutant and a short time period.,These limitations may introduce bias and distort the epidemiological associations as they do not account for all the potential sources or the temporal variability of pollution.,We used detailed information on individuals’ exposure to various pollutants measured at fine spatiotemporal scale to obtain more reliable effect estimates.,A panel of 115 patients was followed up for an average continuous period of 128 days carrying a personal monitor specifically designed for this project that measured temperature, nitrogen dioxide (NO2), ozone (O3), nitric oxide (NO), carbon monoxide (CO), and particulate matter with aerodynamic diameter <2.5 and <10 μm at 1-min time resolution.,Each patient recorded daily information on respiratory symptoms and measured peak expiratory flow (PEF).,A pulmonologist combined related data to define a binary variable denoting an “exacerbation”.,The exposure-response associations were assessed with mixed effects models.,We found that gaseous pollutants were associated with a deterioration in patients’ health.,We observed an increase of 16.4% (95% CI 8.6-24.6%), 9.4% (95% CI 5.4-13.6%) and 7.6% (95% CI 3.0-12.4%) in the odds of exacerbation for an interquartile range increase in NO2, NO and CO, respectively.,Similar results were obtained for cough and sputum.,O3 was found to have adverse associations with PEF and breathlessness.,No association was observed between particulate matter and any outcome.,Our findings suggest that, when considering total personal exposure to air pollutants, mainly the gaseous pollutants affect COPD patients’ health.,Significant adverse associations were found between the respiratory health of COPD patients and their personal exposure to gaseous pollutants measured using portable sensors over 6 months.,No significant associations were found for particulate pollutants.https://bit.ly/3aqMT6O | ICAM-1 is a major receptor for ~60% of human rhinoviruses, and non-typeable Haemophilus influenzae, two major pathogens in COPD.,Increased cell-surface expression of ICAM-1 in response to tobacco smoke exposure has been suggested.,We have investigated epithelial ICAM-1 expression in both the large and small airways, and lung parenchyma in smoking-related chronic airflow limitation (CAL) patients.,We evaluated epithelial ICAM-1 expression in resected lung tissue: 8 smokers with normal spirometry (NLFS); 29 CAL patients (10 small-airway disease; 9 COPD-smokers; 10 COPD ex-smokers); Controls (NC): 15 normal airway/lung tissues.,Immunostaining with anti-ICAM-1 monoclonal antibody was quantified with computerized image analysis.,The percent and type of cells expressing ICAM-1 in large and small airway epithelium and parenchyma were enumerated, plus percentage of epithelial goblet and submucosal glands positive for ICAM- 1.,A major increase in ICAM-1 expression in epithelial cells was found in both large (p < 0.006) and small airways (p < 0.004) of CAL subjects compared to NC, with NLFS being intermediate.,In the CAL group, both basal and luminal areas stained heavily for ICAM-1, so did goblet cells and sub-mucosal glands, however in either NC or NLFS subjects, only epithelial cell luminal surfaces stained.,ICAM-1 expression on alveolar pneumocytes (mainly type II) was slightly increased in CAL and NLFS (p < 0.01).,Pack-years of smoking correlated with ICAM-1 expression (r = 0.49; p < 0.03).,Airway ICAM-1 expression is markedly upregulated in CAL group, which could be crucial in rhinoviral and NTHi infections.,The parenchymal ICAM-1 is affected by smoking, with no further enhancement in CAL subjects.,The online version of this article (doi:10.1186/s12931-016-0483-8) contains supplementary material, which is available to authorized users. | 1 |
Cigarette smoking is the leading modifiable risk factor for disease and death worldwide.,Previous studies quantifying gene-level expression have documented the effect of smoking on mRNA levels.,Using RNA sequencing, it is possible to analyze the impact of smoking on complex regulatory phenomena (e.g. alternative splicing, differential isoform usage) leading to a more detailed understanding of the biology underlying smoking-related disease.,We used whole-blood RNA sequencing to describe gene and exon-level expression differences between 229 current and 286 former smokers in the COPDGene study.,We performed differential gene expression and differential exon usage analyses using the voom/limma and DEXseq R packages.,Samples from current and former smokers were compared while controlling for age, gender, race, lifetime smoke exposure, cell counts, and technical covariates.,At an adjusted p-value <0.05, 171 genes were differentially expressed between current and former smokers.,Differentially expressed genes included 7 long non-coding RNAs that have not been previously associated with smoking: LINC00599, LINC01362, LINC00824, LINC01624, RP11-563D10.1, RP11-98G13.1, AC004791.2.,Secondary analysis of acute smoking (having smoked within 2-h) revealed 5 of the 171 smoking genes demonstrated an acute response above the baseline effect of chronic smoking.,Exon-level analyses identified 9 exons from 8 genes with significant differential usage by smoking status, suggesting smoking-induced changes in isoform expression.,Transcriptomic changes at the gene and exon levels from whole blood can refine our understanding of the molecular mechanisms underlying the response to smoking.,The online version of this article (10.1186/s12920-017-0295-9) contains supplementary material, which is available to authorized users. | There is a need for more powerful methods to identify low-effect SNPs that contribute to hereditary COPD pathogenesis.,We hypothesized that SNPs contributing to COPD risk through cis-regulatory effects are enriched in genes comprised by bronchial epithelial cell (BEC) expression patterns associated with COPD.,To test this hypothesis, normal BEC specimens were obtained by bronchoscopy from 60 subjects: 30 subjects with COPD defined by spirometry (FEV1/FVC < 0.7, FEV1% < 80%), and 30 non-COPD controls.,Targeted next generation sequencing was used to measure total and allele-specific expression of 35 genes in genome maintenance (GM) genes pathways linked to COPD pathogenesis, including seven TP53 and CEBP transcription factor family members.,Shrinkage linear discriminant analysis (SLDA) was used to identify COPD-classification models.,COPD GWAS were queried for putative cis-regulatory SNPs in the targeted genes.,On a network basis, TP53 and CEBP transcription factor pathway gene pair network connections, including key DNA repair gene ERCC5, were significantly different in COPD subjects (e.g., Wilcoxon rank sum test for closeness, p-value = 5.0E-11).,ERCC5 SNP rs4150275 association with chronic bronchitis was identified in a set of Lung Health Study (LHS) COPD GWAS SNPs restricted to those in putative regulatory regions within the targeted genes, and this association was validated in the COPDgene non-hispanic white (NHW) GWAS.,ERCC5 SNP rs4150275 is linked (D’ = 1) to ERCC5 SNP rs17655 which displayed differential allelic expression (DAE) in BEC and is an expression quantitative trait locus (eQTL) in lung tissue (p = 3.2E-7).,SNPs in linkage (D’ = 1) with rs17655 were predicted to alter miRNA binding (rs873601).,A classifier model that comprised gene features CAT, CEBPG, GPX1, KEAP1, TP73, and XPA had pooled 10-fold cross-validation receiver operator characteristic area under the curve of 75.4% (95% CI: 66.3%-89.3%).,The prevalence of DAE was higher than expected (p = 0.0023) in the classifier genes.,GM genes comprised by COPD-associated BEC expression patterns were enriched for SNPs with cis-regulatory function, including a putative cis-rSNP in ERCC5 that was associated with COPD risk.,These findings support additional total and allele-specific expression analysis of gene pathways with high prior likelihood for involvement in COPD pathogenesis.,The online version of this article (10.1186/s12890-018-0603-y) contains supplementary material, which is available to authorized users. | 1 |
The benefits of pharmacotherapy with tiotropium HandiHaler 18 μg for patients with chronic obstructive pulmonary disease (COPD) have been previously demonstrated.,However, few data exist regarding the treatment of moderate disease (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II).,To determine whether tiotropium improves lung function/patient-reported outcomes in patients with GOLD stage II COPD naive to maintenance therapy.,A randomised 24-week double-blind placebo-controlled trial of tiotropium 18 μg once daily (via HandiHaler) was performed in maintenance therapy-naive patients with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7 and post-bronchodilator FEV1 ⩾50 and <80%.,A total of 457 patients were randomised (238 tiotropium, 219 placebo; mean age 62 years; FEV1 1.93 l (66% predicted)).,Tiotropium was superior to placebo in mean change from baseline in post-dose FEV1 area under the curve from 0 to 3 h (AUC0-3h) at week 24 (primary endpoint): 0.19 vs.,−0.03 l (least-squares mean difference 0.23 l, P<0.001).,FVC AUC0-3h, trough and peak FEV1 and FVC were significantly improved with tiotropium versus placebo (P<0.001).,Compared with placebo, tiotropium provided numerical improvements in physical activity (P=NS).,Physician’s Global Assessment (health status) improved (P=0.045) with less impairment on the Work Productivity and Activity Impairment questionnaire (P=0.043) at week 24.,The incidence of exacerbations, cough, bronchitis and dyspnoea was lower with tiotropium than placebo.,Tiotropium improved lung function and patient-reported outcomes in maintenance therapy-naive patients with GOLD stage II COPD, suggesting benefits in initiating maintenance therapy early. | Medications for respiratory disorders including asthma and chronic obstructive pulmonary disease (COPD) are typically delivered to the lung by means of a handheld inhaler.,Patient preference for and ability to use the inhaler may influence their adherence to maintenance therapy, and adherence may affect treatment outcomes.,In this study, patient experience of using a dry powder inhaler (DPI), the ELLIPTA™ DPI, in clinical trials of a new maintenance therapy for asthma and COPD was investigated.,The ELLIPTA DPI has been designed to contain two separate blister strips from which inhalation powder can be delivered, and to be simple to use with a large, easy-to-read dose counter.,Semi-structured, in-depth, qualitative interviews were carried out 2-4 weeks after patients had completed one of six phase IIIa clinical trials using the ELLIPTA DPI.,Interview participants were asked about their satisfaction with various attributes of the inhaler and their preference for the ELLIPTA DPI relative to currently-prescribed inhalers, and responses were explored using an inductive content analysis approach.,Participants also rated the performance of the inhaler on several criteria, using a subjective 1-10 scale.,Participants with asthma (n = 33) and COPD (n = 42) reported high levels of satisfaction with the ELLIPTA DPI.,It was frequently described as straightforward to operate and easy to use by interview participants.,Ergonomic design, mouthpiece fit, and dose counter visibility and ease of interpretation emerged as frequently cited drivers of preference for the ELLIPTA DPI compared with their current prescribed inhaler.,Of participants with asthma, 71% preferred the ELLIPTA DPI to DISKUS™ and 60% to metered dose inhalers.,Of participants with COPD, 86% preferred the ELLIPTA DPI to DISKUS, 95% to HandiHaler™, and 85% to metered dose inhalers.,Overall average performance scores were >9 (out of 10) in participants with asthma and COPD.,The ELLIPTA DPI was associated with high patient satisfaction and was preferred to other inhalers by interview participants with asthma and COPD.,The development of an inhaler that is regarded as easy and intuitive to use may have positive implications for adherence to therapy in asthma and COPD.,Asthma: NCT01165138, NCT01431950.,COPD: NCT01053988, NCT01054885, NCT01009463, NCT01017952. | 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. | Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation.,Autophagy is a degradative process involving lysosomal turnover of cellular components, though its role in human diseases remains unclear.,Increased autophagy was observed in lung tissue from COPD patients, as indicated by electron microscopic analysis, as well as by increased activation of autophagic proteins (microtubule-associated protein-1 light chain-3B, LC3B, Atg4, Atg5/12, Atg7).,Cigarette smoke extract (CSE) is an established model for studying the effects of cigarette smoke exposure in vitro.,In human pulmonary epithelial cells, exposure to CSE or histone deacetylase (HDAC) inhibitor rapidly induced autophagy.,CSE decreased HDAC activity, resulting in increased binding of early growth response-1 (Egr-1) and E2F factors to the autophagy gene LC3B promoter, and increased LC3B expression.,Knockdown of E2F-4 or Egr-1 inhibited CSE-induced LC3B expression.,Knockdown of Egr-1 also inhibited the expression of Atg4B, a critical factor for LC3B conversion.,Inhibition of autophagy by LC3B-knockdown protected epithelial cells from CSE-induced apoptosis.,Egr-1 −/− mice, which displayed basal airspace enlargement, resisted cigarette-smoke induced autophagy, apoptosis, and emphysema.,We demonstrate a critical role for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke exposure in vitro and in vivo.,The induction of autophagy at early stages of COPD progression suggests novel therapeutic targets for the treatment of cigarette smoke induced lung injury. | 1 |
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. | Objective To test the effectiveness of telemonitoring integrated into existing clinical services such that intervention and control groups have access to the same clinical care.,Design Researcher blind, multicentre, randomised controlled trial.,Setting UK primary care (Lothian, Scotland).,Participants Adults with at least one admission for chronic obstructive pulmonary disease (COPD) in the year before randomisation.,We excluded people who had other significant lung disease, who were unable to provide informed consent or complete the study, or who had other significant social or clinical problems.,Interventions Participants were recruited between 21 May 2009 and 28 March 2011, and centrally randomised to receive telemonitoring or conventional self monitoring.,Using a touch screen, telemonitoring participants recorded a daily questionnaire about symptoms and treatment use, and monitored oxygen saturation using linked instruments.,Algorithms, based on the symptom score, generated alerts if readings were omitted or breached thresholds.,Both groups received similar care from existing clinical services.,Main outcome measures The primary outcome was time to hospital admission due to COPD exacerbation up to one year after randomisation.,Other outcomes included number and duration of admissions, and validated questionnaire assessments of health related quality of life (using St George’s respiratory questionnaire (SGRQ)), anxiety or depression (or both), self efficacy, knowledge, and adherence to treatment.,Analysis was intention to treat.,Results Of 256 patients completing the study, 128 patients were randomised to telemonitoring and 128 to usual care; baseline characteristics of each group were similar.,The number of days to admission did not differ significantly between groups (adjusted hazard ratio 0.98, 95% confidence interval 0.66 to 1.44).,Over one year, the mean number of COPD admissions was similar in both groups (telemonitoring 1.2 admissions per person (standard deviation 1.9) v control 1.1 (1.6); P=0.59).,Mean duration of COPD admissions over one year was also similar between groups (9.5 days per person (standard deviation 19.1) v 8.8 days (15.9); P=0.88).,The intervention had no significant effect on SGRQ scores between groups (68.2 (standard deviation 16.3) v 67.3 (17.3); adjusted mean difference 1.39 (95% confidence interval −1.57 to 4.35)), or on other questionnaire outcomes.,Conclusions In participants with a history of admission for exacerbations of COPD, telemonitoring was not effective in postponing admissions and did not improve quality of life.,The positive effect of telemonitoring seen in previous trials could be due to enhancement of the underpinning clinical service rather than the telemonitoring communication.,Trial registration ISRCTN96634935.,Funding: The trial was funded by an NHS applied research programme grant from the Chief Scientist Office of the Scottish government (ARPG/07/03).,The funder had no role in study design and the collection, analysis, and interpretation of data and the writing of the article and the decision to submit it for publication.,NHS Lothian supported the telemonitoring service and the clinical services. | 1 |
Medications for respiratory disorders including asthma and chronic obstructive pulmonary disease (COPD) are typically delivered to the lung by means of a handheld inhaler.,Patient preference for and ability to use the inhaler may influence their adherence to maintenance therapy, and adherence may affect treatment outcomes.,In this study, patient experience of using a dry powder inhaler (DPI), the ELLIPTA™ DPI, in clinical trials of a new maintenance therapy for asthma and COPD was investigated.,The ELLIPTA DPI has been designed to contain two separate blister strips from which inhalation powder can be delivered, and to be simple to use with a large, easy-to-read dose counter.,Semi-structured, in-depth, qualitative interviews were carried out 2-4 weeks after patients had completed one of six phase IIIa clinical trials using the ELLIPTA DPI.,Interview participants were asked about their satisfaction with various attributes of the inhaler and their preference for the ELLIPTA DPI relative to currently-prescribed inhalers, and responses were explored using an inductive content analysis approach.,Participants also rated the performance of the inhaler on several criteria, using a subjective 1-10 scale.,Participants with asthma (n = 33) and COPD (n = 42) reported high levels of satisfaction with the ELLIPTA DPI.,It was frequently described as straightforward to operate and easy to use by interview participants.,Ergonomic design, mouthpiece fit, and dose counter visibility and ease of interpretation emerged as frequently cited drivers of preference for the ELLIPTA DPI compared with their current prescribed inhaler.,Of participants with asthma, 71% preferred the ELLIPTA DPI to DISKUS™ and 60% to metered dose inhalers.,Of participants with COPD, 86% preferred the ELLIPTA DPI to DISKUS, 95% to HandiHaler™, and 85% to metered dose inhalers.,Overall average performance scores were >9 (out of 10) in participants with asthma and COPD.,The ELLIPTA DPI was associated with high patient satisfaction and was preferred to other inhalers by interview participants with asthma and COPD.,The development of an inhaler that is regarded as easy and intuitive to use may have positive implications for adherence to therapy in asthma and COPD.,Asthma: NCT01165138, NCT01431950.,COPD: NCT01053988, NCT01054885, NCT01009463, NCT01017952. | The BEACON study evaluated the efficacy and safety of QVA149, a once-daily dual bronchodilator containing a fixed-dose combination of the long-acting β2-agonist (LABA) indacaterol and long-acting muscarinic antagonist (LAMA) glycopyrronium (NVA237), in development for the treatment of patients with chronic obstructive pulmonary disease (COPD), compared with the free-dose concurrent administration of indacaterol plus glycopyrronium (IND+GLY).,In this multicenter, double-blind, parallel group study, patients with stage II or stage III COPD (Global initiative for chronic Obstructive Lung Disease [GOLD] 2010) were randomized (1:1) to once-daily QVA149 (110 μg indacaterol/50 μg glycopyrronium) or concurrent administration of indacaterol (150 μg) and glycopyrronium (50 μg) via the Breezhaler® device (Novartis AG, Basel, Switzerland) for 4 weeks.,The primary endpoint was to evaluate the noninferiority of QVA149 as compared with concurrent administration of IND+GLY, for trough forced expiratory volume in 1 second (FEV1) after 4 weeks of treatment.,The other assessments included FEV1 area under the curve from 0 to 4 hours (AUC0-4 hours) at day 1 and week 4, symptom scores, rescue medication use, safety, and tolerability over the 4-week study period.,Of 193 patients randomized, 187 (96.9%) completed the study.,Trough FEV1 at week 4 for QVA149 and IND+GLY was 1.46 L ± 0.02 and 1.46 L ± 0.18, respectively.,The FEV1 AUC0-4 hours at day 1 and week 4 were similar between the two treatment groups.,Both treatment groups had a similar reduction in symptom scores and rescue medication use for the 4-week treatment period.,Overall, 25.6% of patients in QVA149 group and 25.2% in the IND+GLY group experienced an adverse event, with the majority being mild-to-moderate in severity.,No deaths were reported during the study or during the 30 days follow-up period.,The BEACON study demonstrated that once-daily QVA149 provides an efficacy and safety profile similar to the concurrent administration of its monocomponents indacaterol and glycopyrronium. | 1 |
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. | Abnormal apoptotic events in chronic obstructive pulmonary disease (COPD) subvert cellular homeostasis and may play a primary role in its pathogenesis.,However, studies in human subjects are limited.,p53 and bcl2 protein expression was measured by western blot on lung tissue specimens from 43 subjects (23 COPD smokers and 20 non-COPD smokers), using beta-actin as internal control.,Additionally, p53 and bcl2 expression patterns were evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded lung tissue sections from the same individuals.,Western blot analysis showed statistically significant increased p53 protein levels in COPD smokers in comparison with non-COPD smokers (p = 0.038), while bcl2 protein levels were not statistically different between the two groups.,Lung immunohistochemistry showed increased ratio of positive p53-stained type II pneumocytes/total type II pneumocytes in COPD smokers compared to non-COPD smokers (p = 0.01), whereas the p53 staining ratio in alveolar macrophages and in lymphocyte-like cells did not differ statistically between the two groups.,On the other hand, bcl2 expression did not differ between the two groups in all three cell types.,The increased expression of pro-apoptotic p53 in type II pneumocytes of COPD patients not counterbalanced by the anti-apoptotic bcl2 could reflect increased apoptosis in the alveolar epithelium of COPD patients.,Our results confirm previous experiments and support the hypothesis of a disturbance in the balance between the pro- and anti-apoptotic mediators in COPD. | 1 |
Identifying patients at risk of exacerbations and managing them appropriately to reduce this risk represents an important clinical challenge.,Numerous treatments have been assessed for the prevention of exacerbations and their efficacy may differ by patient phenotype.,Given their centrality in the treatment of COPD, there is strong rationale for maximizing bronchodilation as an initial strategy to reduce exacerbation risk irrespective of patient phenotype.,Therefore, in patients assessed as frequent exacerbators (>1 exacerbation/year) we propose initial bronchodilator treatment with a long-acting muscarinic antagonist (LAMA)/ long-acting β2-agonist (LABA).,For those patients who continue to experience >1 exacerbation/year despite maximal bronchodilation, we advocate treating according to patient phenotype.,Based on currently available data on adding inhaled corticosteroids (ICS) to a LABA, ICS might be added to a LABA/LAMA combination in exacerbating patients who have an asthma-COPD overlap syndrome or high blood eosinophil counts, while in exacerbators with chronic bronchitis, consideration should be given to treating with a phosphodiesterase (PDE)-4 inhibitor (roflumilast) or high-dose mucolytic agents.,For those patients who experience frequent bacterial exacerbations and/or bronchiectasis, addition of mucolytic agents or a macrolide antibiotic (e.g. azithromycin) should be considered.,In all patients at risk of exacerbations, pulmonary rehabilitation should be included as part of a comprehensive management plan.,The online version of this article (doi:10.1186/s12931-016-0425-5) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) is associated with exercise limitation and physical inactivity, which are believed to have significant long-term negative health consequences for patients.,While a number of COPD treatments and exercise training programmes increase exercise capacity, there is limited evidence for their effects on physical activity levels, with no clear association between exercise capacity and physical activity in clinical trials.,Physical activity depends on a number of behaviour, environmental and physiological factors.,We describe the design of the PHYSACTO trial, which is investigating the effects of bronchodilators, either alone or with exercise training, in combination with a standardised behaviour-change self-management programme, on exercise capacity and physical activity in patients with COPD.,It is hypothesised that bronchodilators in conjunction with a behaviour-change self-management programme will improve physical activity and that this effect will be amplified by the addition of exercise training.,Patients are being recruited from 34 sites in Australia, New Zealand, the USA, Canada and Europe.,Patients receiving a multicomponent intervention designed to support behaviour change related to physical activity are randomised to four treatment arms: placebo, tiotropium, tiotropium+olodaterol, and tiotropium+olodaterol+exercise training.,The primary outcome is improvement in exercise capacity after 8 weeks, measured by endurance time during a shuttle walk test.,The secondary outcome is improvement in physical activity, including objective accelerometer assessment and patient-reported functioning using the Functional Performance Inventory-Short Form and the novel hybrid PROactive instrument.,Additionally, the influence of moderating variables (ie, factors influencing a patient's choice to be physically active) on increases in physical activity is also explored.,The study has been approved by the relevant Institutional Review Boards, Independent Ethics Committee and Competent Authority according to national and international regulations.,The findings of the trial will be disseminated through relevant peer-reviewed journals and international conference presentations.,NCT02085161. | 1 |
Mesenchymal stem cells (MSCs), due to their potential for differentiation into alveolar epithelial cells and their immunosuppressive characteristics, are considered a new therapeutic agent in cell-based therapy of inflammatory lung disorders, including chronic obstructive pulmonary disease (COPD).,Since most of the MSC-mediated beneficent effects were the consequence of their paracrine action, herewith, we investigated the effects of a newly designed MSC-derived product “Exosome-derived Multiple Allogeneic Protein Paracrine Signaling (Exo-d-MAPPS)” in the attenuation of chronic airway inflammation by using an animal model of COPD (induced by chronic exposure to cigarette smoke (CS)) and clinical data obtained from Exo-d-MAPPS-treated COPD patients.,Exo-d-MAPPS contains a high concentration of immunomodulatory factors which are capable of attenuating chronic airway inflammation, including soluble TNF receptors I and II, IL-1 receptor antagonist, and soluble receptor for advanced glycation end products.,Accordingly, Exo-d-MAPPS significantly improved respiratory function, downregulated serum levels of inflammatory cytokines (TNF-α, IL-1β, IL-12, and IFN-γ), increased serum concentration of immunosuppressive IL-10, and attenuated chronic airway inflammation in CS-exposed mice.,The cellular makeup of the lungs revealed that Exo-d-MAPPS treatment attenuated the production of inflammatory cytokines in lung-infiltrated macrophages, neutrophils, and natural killer and natural killer T cells and alleviated the antigen-presenting properties of lung-infiltrated macrophages and dendritic cells (DCs).,Additionally, Exo-d-MAPPS promoted the expansion of immunosuppressive IL-10-producing alternatively activated macrophages, regulatory DCs, and CD4+FoxP3+T regulatory cells in inflamed lungs which resulted in the attenuation of chronic airway inflammation.,In a similar manner, as it was observed in an animal model, Exo-d-MAPPS treatment significantly improved the pulmonary status and quality of life of COPD patients.,Importantly, Exo-d-MAPPS was well tolerated since none of the 30 COPD patients reported any adverse effects after Exo-d-MAPPS administration.,In summing up, we believe that Exo-d-MAPPS could be considered a potentially new therapeutic agent in the treatment of chronic inflammatory lung diseases whose efficacy should be further explored in large clinical trials. | COPD is characterised by tissue destruction and inflammation.,Given the lack of curative treatments and the progressive nature of the disease, new treatments for COPD are highly relevant.,In vitro cell culture and animal studies have demonstrated that mesenchymal stromal cells (MSCs) have the capacity to modify immune responses and to enhance tissue repair.,These properties of MSCs provided a rationale to investigate their potential for treatment of a variety of diseases, including COPD.,Preclinical models support the hypothesis that MSCs may have clinical efficacy in COPD.,However, although clinical trials have demonstrated the safety of MSC treatment, thus far they have not provided evidence for MSC efficacy in the treatment of COPD.,In this review, we discuss the rationale for MSC-based cell therapy in COPD, the main findings from in vitro and in vivo preclinical COPD model studies, clinical trials in patients with COPD and directions for further research. | 1 |
To map and assess prognostic models for outcome prediction in patients with chronic obstructive pulmonary disease (COPD).,Systematic review.,PubMed until November 2018 and hand searched references from eligible articles.,Studies developing, validating, or updating a prediction model in COPD patients and focusing on any potential clinical outcome.,The systematic search yielded 228 eligible articles, describing the development of 408 prognostic models, the external validation of 38 models, and the validation of 20 prognostic models derived for diseases other than COPD.,The 408 prognostic models were developed in three clinical settings: outpatients (n=239; 59%), patients admitted to hospital (n=155; 38%), and patients attending the emergency department (n=14; 3%).,Among the 408 prognostic models, the most prevalent endpoints were mortality (n=209; 51%), risk for acute exacerbation of COPD (n=42; 10%), and risk for readmission after the index hospital admission (n=36; 9%).,Overall, the most commonly used predictors were age (n=166; 41%), forced expiratory volume in one second (n=85; 21%), sex (n=74; 18%), body mass index (n=66; 16%), and smoking (n=65; 16%).,Of the 408 prognostic models, 100 (25%) were internally validated and 91 (23%) examined the calibration of the developed model.,For 286 (70%) models a model presentation was not available, and only 56 (14%) models were presented through the full equation.,Model discrimination using the C statistic was available for 311 (76%) models. 38 models were externally validated, but in only 12 of these was the validation performed by a fully independent team.,Only seven prognostic models with an overall low risk of bias according to PROBAST were identified.,These models were ADO, B-AE-D, B-AE-D-C, extended ADO, updated ADO, updated BODE, and a model developed by Bertens et al.,A meta-analysis of C statistics was performed for 12 prognostic models, and the summary estimates ranged from 0.611 to 0.769.,This study constitutes a detailed mapping and assessment of the prognostic models for outcome prediction in COPD patients.,The findings indicate several methodological pitfalls in their development and a low rate of external validation.,Future research should focus on the improvement of existing models through update and external validation, as well as the assessment of the safety, clinical effectiveness, and cost effectiveness of the application of these prognostic models in clinical practice through impact studies.,PROSPERO CRD42017069247 | To assess whether spirometry done in hospital during an admission for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is clinically useful for long-term management.,Patients admitted to hospital with a clinical diagnosis of AECOPD had spirometry post-bronchodilator at discharge and approximately 4 weeks later.,Spirometry was achieved in less than half of those considered to have AECOPD.,Of 49 patients who had spirometry on both occasions, 41 met the GOLD criteria for COPD at discharge and 39 of these met the criteria at 1 month.,For the 41, spirometry was not statistically different between discharge and 1 month but often crossed arbitrary boundaries for classification of severity based on FEV1.,The eight who did not meet GOLD criteria at discharge were either misclassified due to comorbidities that reduce FVC, or they did not have COPD as a cause of their hospital admission.,Spirometry done in hospital at the time of AECOP is useful in patients with a high pre-test probability of moderate-to-severe COPD.,Small changes in spirometry at 1 month could place them up or down one grade of severity.,Spirometry at discharge may be useful to detect those who warrant further investigation. | 1 |
Telemonitoring (TM) of patients with COPD has gained much interest, but studies have produced conflicting results.,We aimed to investigate the effect of TM with the option of video consultations on quality of life (QoL) in patients with severe COPD.,COPD patients at high risk of exacerbations were eligible for the 6-month study and a total of 281 patients were equally randomized to either TM (n=141) or usual care (n=140).,TM comprised recording of symptoms, oxygen saturation, spirometry, and video consultations.,Algorithms generated alerts if readings breached thresholds.,Both groups filled in a health-related QoL questionnaire (15D©) and the COPD Assessment Test (CAT) at baseline and at 6 months.,Within-group differences were analyzed by paired t-test.,Most of the enrolled patients had severe COPD (86% with Global Initiative for Chronic Obstructive Lung Disease stage 3 or 4 and 45% with admission for COPD within the last year, respectively).,No difference in drop-out rate and mortality was found between the groups, and likewise there was no difference in 15D or CAT at baseline.,At 6 months, a significant improvement of 0.016 in 15D score (p=0.03; minimal clinically important difference 0.015) was observed in the TM group (compared to baseline), while there was no improvement in the control group −0.003 (p=0.68).,After stratifying 15D score at baseline to <0.75 or ≥0.75, respectively, there was a significant difference in the <0.75 TM group of 0.037 (p=0.001), which is a substantial improvement.,No statistically significant changes were found in CAT score.,Compared to the nonintervention group, TM as an add-on to usual care over a 6-month period improved QoL, as assessed by the 15D questionnaire, in patients with severe COPD, whereas no difference between groups was observed in CAT score. | 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 |
Transforming growth factor β (TGF-β), signaling induced by cigarette smoke (CS), plays an important role in the progression of airway diseases, like chronic bronchitis associated with chronic obstructive pulmonary disease (COPD), and in smokers.,Chronic bronchitis is characterized by reduced mucociliary clearance (MCC).,Cystic fibrosis transmembrane conductance regulator (CFTR) plays an important role in normal MCC.,TGF-β and CS (via TGF-β) promote acquired CFTR dysfunction by suppressing CFTR biogenesis and function.,Understanding the mechanism by which CS promotes CFTR dysfunction can identify therapeutic leads to reverse CFTR suppression and rescue MCC.,TGF-β alters the microRNAome of primary human bronchial epithelium.,TGF-β and CS upregulate miR-145-5p expression to suppress CFTR and the CFTR modifier, SLC26A9. miR-145-5p upregulation with a concomitant CFTR and SLC26A9 suppression was validated in CS-exposed mouse models.,While miR-145-5p antagonism rescued the effects of TGF-β in bronchial epithelial cells following transfection, an aptamer to block TGF-β signaling rescues CS- and TGF-β-mediated suppression of CFTR biogenesis and function in the absence of any transfection reagent.,These results demonstrate that miR-145-5p plays a significant role in acquired CFTR dysfunction by CS, and they validate a clinically feasible strategy for delivery by inhalation to locally modulate TGF-β signaling in the airway and rescue CFTR biogenesis and function.,The authors demonstrate that TGF-β and cigarette smoke upregulate miR-145-5p to suppress CFTR biogenesis.,This is also the first report of microRNA-mediated regulation of SLC26A9, an important CFTR-modifying gene, and the authors demonstrate that miR-145-5p is also involved in TGF-β- and cigarette smoke-mediated suppression of SLC26A9. | Chronic obstructive pulmonary disease (COPD) is an obstinate pulmonary disease, causing irreversible alveoli collapse and increasing the risk for cardiovascular disease.,Accumulating evidence has shown that the dysregulation of miRNAs is crucially involved in the pathogenesis and development of COPD.,However, the effects and role of microRNA-181c (miR-181c) have not been investigated in a murine model of COPD.,miR-181c expression was detected in human lung tissue samples of 34 patients, an in vivo murine model of CS exposure, and primary human bronchial epithelial cells (HBECs) by qRT-PCR.,Degeneration of lung tissue, necrosis, infiltration and neutrophil cells were assessed with H&E and flow cytometry.,Interleukin (IL)-6 and IL-8 levels were determined by an enzyme-linked immunosorbent assay and qRT-PCR.,Luciferase reporter assay and correlation analyses were used to confirm and measure the levels between miR-181c and its target CCN1.,We showed that miR-181c was significantly down-regulated in lung tissues from patients with COPD compared to individuals who had never smoked (p < 0.01).,We also observed a down-regulation of miR-181c in HBECs and a mouse model after cigarette smoke (CS) exposure.,Functional assays demonstrated that miR-181c over-expression decreased the inflammatory response, neutrophil infiltration, reactive oxygen species (ROS) generation, and inflammatory cytokines induced by CS, while its down-regulation produced the opposite effects.,Subsequent investigation found that CCN1 was a direct target of miR-181c.,CCN1 expression was increased in lung tissues of COPD patients, and was negatively correlated with miR-181c expression in human COPD samples (p < 0.01).,Taken together, our data suggest the critical roles of miR-181c and its target CCN1 in COPD development, and provide potential therapeutic targets for COPD treatment. | 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. | Eosinophilic airway inflammation is observed in 10-30% of COPD subjects.,Whether increased eosinophils or impairment in their clearance by macrophages is associated with the severity and frequency of exacerbations is unknown.,We categorised 103 COPD subjects into 4 groups determined by the upper limit of normal for their cytoplasmic macrophage red hue (<6%), an indirect measure of macrophage efferocytosis of eosinophils, and area under the curve sputum eosinophil count (≥3%/year).,Eosinophil efferocytosis by monocyte-derived macrophages was studied in 17 COPD subjects and 8 normal controls.,There were no differences in baseline lung function, health status or exacerbation frequency between the groups: A-low red hue, high sputum eosinophils (n = 10), B-high red hue, high sputum eosinophils (n = 16), C-low red hue, low sputum eosinophils (n = 19) and D- high red hue, low sputum eosinophils (n = 58).,Positive bacterial culture was lower in groups A (10%) and B (6%) compared to C (44%) and D (21%) (p = 0.01).,The fall in FEV1 from stable to exacerbation was greatest in group A (ΔFEV1 [95 % CI] -0.41 L [-0.65 to -0.17]) versus group B (-0.16 L [-0.32 to -0.011]), C (-0.11 L [-0.23 to -0.002]) and D (-0.16 L [-0.22 to -0.10]; p = 0.02).,Macrophage efferocytosis of eosinophils was impaired in COPD versus controls (86 [75 to 92]% versus 93 [88 to 96]%; p = 0.028); was most marked in group A (71 [70 to 84]%; p = 0.0295) and was inversely correlated with exacerbation frequency (r = -0.63; p = 0.006).,Macrophage efferocytosis of eosinophils is impaired in COPD and is related to the severity and frequency of COPD exacerbations. | 1 |
Acute COPD exacerbations account for much of the rising disability and costs associated with COPD, but data on predictive risk factors are limited.,The goal of the current study was to develop a robust, clinically based model to predict frequent exacerbation risk.,Patients identified from the Optimum Patient Care Research Database (OPCRD) with a diagnostic code for COPD and a forced expiratory volume in 1 second/forced vital capacity ratio <0.7 were included in this historical follow-up study if they were ≥40 years old and had data encompassing the year before (predictor year) and year after (outcome year) study index date.,The data set contained potential risk factors including demographic, clinical, and comorbid variables.,Following univariable analysis, predictors of two or more exacerbations were fed into a stepwise multivariable logistic regression.,Sensitivity analyses were conducted for subpopulations of patients without any asthma diagnosis ever and those with questionnaire data on symptoms and smoking pack-years.,The full predictive model was validated against 1 year of prospective OPCRD data.,The full data set contained 16,565 patients (53% male, median age 70 years), including 9,393 patients without any recorded asthma and 3,713 patients with questionnaire data.,The full model retained eleven variables that significantly predicted two or more exacerbations, of which the number of exacerbations in the preceding year had the strongest association; others included height, age, forced expiratory volume in 1 second, and several comorbid conditions.,Significant predictors not previously identified included eosinophilia and COPD Assessment Test score.,The predictive ability of the full model (C statistic 0.751) changed little when applied to the validation data set (n=2,713; C statistic 0.735).,Results of the sensitivity analyses supported the main findings.,Patients at risk of exacerbation can be identified from routinely available, computerized primary care data.,Further study is needed to validate the model in other patient populations. | To evaluate risk factors associated with exacerbation frequency in primary care.,Information on exacerbations of chronic obstructive pulmonary disease (COPD) has mainly been generated by secondary care-based clinical cohorts.,Retrospective observational cohort study.,Electronic medical records database (England and Wales).,58 589 patients with COPD aged ≥40 years with COPD diagnosis recorded between 1 April 2009 and 30 September 2012, and with at least 365 days of follow-up before and after the COPD diagnosis, were identified in the Clinical Practice Research Datalink.,Mean age: 69 years; 47% female; mean forced expiratory volume in 1s 60% predicted.,Data on moderate or severe exacerbation episodes defined by diagnosis and/or medication codes 12 months following cohort entry were retrieved, together with demographic and clinical characteristics.,Associations between patient characteristics and odds of having none versus one, none versus frequent (≥2) and one versus frequent exacerbations over 12 months follow-up were evaluated using multivariate logistic regression models.,During follow-up, 23% of patients had evidence of frequent moderate-to-severe COPD exacerbations (24% one; 53% none).,Independent predictors of increased odds of having exacerbations during the follow-up, either frequent episodes or one episode, included prior exacerbations, increasing dyspnoea score, increasing grade of airflow limitation, females and prior or current history of several comorbidities (eg, asthma, depression, anxiety, heart failure and cancer).,Primary care-managed patients with COPD at the highest risk of exacerbations can be identified by exploring medical history for the presence of prior exacerbations, greater COPD disease severity and co-occurrence of other medical conditions. | 1 |
COPD self-management reduces hospital admissions and improves health-related quality of life (HRQoL).,However, whilst most patients are managed in primary care, the majority of self-management trials have recruited participants with more severe disease from secondary care.,We report the findings of a systematic review of the effectiveness of community-based self-management interventions in primary care patients with COPD.,We systematically searched eleven electronic databases and identified 12 eligible randomised controlled trials with seven included in meta-analyses for HRQoL, anxiety and depression.,We report no difference in HRQoL at final follow-up (St George’s Respiratory Questionnaire total score −0.29; 95%CI −2.09, 1.51; I2 0%), nor any difference in anxiety or depression.,In conclusion, supported self-management interventions delivered in the community to patients from primary care do not appear to be effective.,Further research is recommended to identify effective self-management interventions suitable for primary care populations, particularly those with milder disease.,Further work is needed to ensure that self-management of chronic lung disease in primary care settings actively improves patients’ quality of life.,While self-management is beneficial to patients in secondary care with severe chronic obstructive pulmonary disease (COPD), few studies have examined self-management effectiveness in primary care patients with milder COPD.,Kate Jolly at the University of Birmingham, UK, and co-workers identified only 12 studies out of over 12,500 that specifically examined self-management in primary care.,Of these, seven were suitable for metanalysis.,The team found that community-based interventions to support self-management did not make a significant difference to patients’ perceived quality of life, or in reducing anxiety and depression.,They call for further research to identify specific support that will help patients with mild to moderate COPD cope and adapt to the progressive condition. | The prevalence of Non Communicable Diseases (NCDs) is still unknown in Nepal.,The Ministry of Health and Population, Government of Nepal has not yet formulated policy regarding NCDs in the absence of evidence based finding.,The study aims to find out the hospital based prevalence of NCDs in Nepal, thus directing the concerned authorities at policy level.,A cross sectional study was conducted to identify the hospital based prevalence of 4 NCDs (cancer, cardiovascular disease, diabetes mellitus and chronic obstructive pulmonary disease), wherein 400 indoor patients admitted during 2009 were randomly selected from each of the 31 selected health institutions which included all non-specialist tertiary level hospitals outside the Kathmandu valley (n = 25), all specialist tertiary level hospitals in the country (n = 3) and 3 non-specialist tertiary level hospitals inside the Kathmandu valley.,In case of Kathmandu valley, 3 non-specialist health institutions- one central hospital, one medical college and one private hospital were randomly selected.,The main analyses are based on the 28 non-specialist hospitals.,Univariate (frequency and percentage) and bivariate (cross-tabulation) analysis were used.,In non-specialist institutions, the hospital based NCD prevalence was 31%.,Chronic obstructive pulmonary disease (43%) was the most common NCD followed by cardiovascular disease (40%), diabetes mellitus (12%) and cancer (5%).,Ovarian (14%), stomach (14%) and lung cancer (10%) were the main cancers accounting for 38% of distribution.,Majority of CVD cases were hypertension (47%) followed by cerebrovascular accident (16%), congestive cardiac failure (11%), ischemic heart disease (7%), rheumatic heart disease (5%) and myocardial infarction (2%).,CVD was common in younger age groups while COPD in older age groups.,Majority among males (42%) and females (45%) were suffering from COPD.,The study was able to reveal that Nepal is also facing the surging burden of NCDs similar to other developing nations in South East Asia.,Furthermore, the study has provided a background data on NCDs in Nepal which should prove useful for the concerned organizations to focus and contribute towards the prevention, control and reduction of NCD burden and its risk factors. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) repeat acute exacerbations (AE).,Global Initiative for Chronic Obstructive Lung Disease (GOLD) is only available for patients in stable phase.,Currently, there is a lack of assessment and prediction methods for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients during hospitalization.,To enhance the monitoring and treatment of AECOPD patients, we develop a novel C5.0 decision tree classifier to predict the prognosis of AECOPD hospitalized patients with objective clinical indicators.,The medical records of 410 hospitalized AECOPD patients are collected and 28 features including vital signs, medical history, comorbidities and various inflammatory indicators are selected.,The overall accuracy of the proposed C5.0 decision tree classifier is 80.3% (65 out of 81 participants) with 95% Confidence Interval (CI):(0.6991, 0.8827) and Kappa 0.6054.,In addition, the performance of the model constructed by C5.0 exceeds the C4.5, classification and regression tree (CART) model and the iterative dichotomiser 3 (ID3) model.,The C5.0 decision tree classifier helps respiratory physicians to assess the severity of the patient early, thereby guiding the treatment strategy and improving the prognosis of patients. | The incidence of chronic obstructive pulmonary disease (COPD) is increasing worldwide.,In Japan and other countries, epidemiological studies have found that many patients with COPD are underdiagnosed and untreated, and thus, early detection and treatment of COPD has been emphasized.,Screening questionnaires may have utility in the initial detection of COPD.,This study aimed to validate and compare the COPD Population Screener (COPD-PS) and the International Primary Care Airway Group (IPAG) questionnaires in a general Japanese population.,Eligible subjects 40 years of age and older living in the town of Hisayama were solicited to participate in a health checkup in 2012.,All subjects 40-79 years of age without physician-diagnosed asthma or lung resection were recruited, and 2,336 subjects who fully completed both questionnaires and who had valid spirometry measurements were analyzed.,Persistent airflow obstruction (AO) was defined by a postbronchodilator forced expiratory volume in 1 second/forced vital capacity <0.70.,Receiver operating characteristic curves, net reclassification improvement, and integrated discrimination improvement were used to examine the ability of the COPD-PS and IPAG questionnaires to discriminate between subjects with and without AO.,The overall area under the receiver operating characteristic curve for the COPD-PS questionnaire was 0.747 (95% confidence interval [CI], 0.707-0.788) and for the IPAG was 0.775 (95% CI, 0.735-0.816), with no significant difference (P=0.09).,The net reclassification improvement and integrated discrimination improvement were −0.107 (95% CI, −0.273-0.058; P=0.203) and −0.014 (95% CI, −0.033-0.006; P=0.182), respectively.,The five-item COPD-PS questionnaire was comparable to the eight-item IPAG for discriminating between subjects with and without AO.,The COPD-PS is a simple and useful screening questionnaire for persistent AO. | 1 |
The fixed-dose dual bronchodilator combination (FDC) of tiotropium and olodaterol showed increased effectiveness regarding lung function and health-related quality of life in patients with chronic obstructive pulmonary disease (COPD) compared with the use of its mono-components.,Yet, while effectiveness and safety have been shown, the health economic implication of this treatment is still unknown.,The aim of this study was to assess the cost-utility and budget impact of tiotropium-olodaterol FDC in patients with moderate to very severe COPD in the Netherlands.,A cost-utility study was performed, using an individual-level Markov model.,To populate the model, individual patient-level data (age, height, sex, COPD duration, baseline forced expiratory volume in 1 second) were obtained from the tiotropium-olodaterol TOnado trial.,In the model, forced expiratory volume in 1 second and patient-level data were extrapolated to utility and survival, and treatment with tiotropium-olodaterol FDC was compared with tiotropium.,Cost-utility analysis was performed from the Dutch health care payer’s perspective using a 15-year time horizon in the base-case analysis.,The standard Dutch discount rates were applied (costs: 4.0%; effects: 1.5%).,Both univariate and probabilistic sensitivity analyses were performed.,Budget impact was annually assessed over a 5-year time horizon, taking into account different levels of medication adherence.,As a result of cost increases, combined with quality-adjusted life-year (QALY) gains, results showed that tiotropium-olodaterol FDC had an incremental cost-effectiveness ratio of €7,004/QALY.,Without discounting, the incremental cost-effectiveness ratio was €5,981/QALY.,Results were robust in univariate and probabilistic sensitivity analyses.,Budget impact was estimated at €4.3 million over 5 years assuming 100% medication adherence.,Scenarios with 40%, 60%, and 80% adherence resulted in lower 5-year incremental cost increases of €1.7, €2.6, and €3.4 million, respectively.,Tiotropium-olodaterol FDC can be considered a cost-effective treatment under current Dutch cost-effectiveness thresholds. | As lung function declines rapidly in the early stages of chronic obstructive pulmonary disease (COPD), the effects of bronchodilators in patients with moderate disease and those who have not previously received maintenance therapy are of interest.,OTEMTO® 1 and 2 were two replicate, 12-week, Phase III studies investigating the benefit of tiotropium + olodaterol on lung function and quality of life in patients with moderate to severe disease.,Post hoc analyses were performed to assess the benefits for patients according to disease severity and treatment history.,Four subgroup analyses were performed: Global initiative for chronic Obstructive Lung Disease (GOLD) 2/3, GOLD A/B/C/D, treatment naive/not treatment naive and receiving inhaled corticosteroids (ICS) at baseline/not receiving ICS at baseline.,Primary end points were change in forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h response, change in trough FEV1 and St George’s Respiratory Questionnaire (SGRQ) total score.,Transition Dyspnoea Index (TDI) focal score was a secondary end point, and SGRQ and TDI responder analyses were further end points; all were assessed at 12 weeks.,In all subgroups, patients receiving tiotropium + olodaterol responded better overall than those receiving tiotropium monotherapy.,Improvements with tiotropium + olodaterol over placebo or tiotropium monotherapy were noted across GOLD 2/3 and GOLD A/B/C/D; however, improvements in SGRQ total score were most evident in the GOLD B subgroup.,Moreover, lung-function outcomes were generally greater in those patients who had been receiving previous long-acting bronchodilator and/or ICS maintenance treatment.,These data suggest that tiotropium + olodaterol should be considered as a treatment option in patients with moderate COPD who are initiating maintenance therapy, as well as those with more severe disease.,ClinicalTrials.gov: NCT01964352 and NCT02006732.,The online version of this article (doi:10.1186/s12931-016-0387-7) contains supplementary material, which is available to authorized users. | 1 |
Female smokers have increased risk for chronic obstructive pulmonary disease (COPD) compared with male smokers who have a similar history of cigarette smoke exposure.,Tertiary lymphoid follicles are often found in the lungs of patients with severe COPD but sex-related differences have not been previously investigated.,We determined the impact of female sex hormones on chronic cigarette smoke-induced expression of lymphoid aggregates in mice with COPD-like pathologies.,Lymphoid aggregate counts, total aggregate cross-sectional area and foamy macrophage counts were determined morphometrically in male, female, and ovariectomized mice exposed to air or cigarette smoke for 6 months.,B-cell activating factor (BAFF) protein expression and markers of oxidative stress were evaluated in mouse lung tissues by immunofluorescence staining and gene expression analyses.,Quantitative histology was performed on lung tissue sections of human COPD lungs to evaluate follicle formation.,Lymphoid follicle and foamy macrophage counts as well as the total follicle cross-sectional area were differentially increased in lung tissues of female mice compared to male mice, and these differences were abolished by ovariectomy.,These lymphoid aggregates were positive for CD45, CD20, CD21 and BAFF expression.,Differential increases in Mmp12 and Cxcl2 gene expression correlated with an increase in foamy macrophages in parenchymal tissues of female but not male mice after smoke exposure.,Parenchymal tissues from female mice failed to induce antioxidant-related genes in response to smoke exposure, and this effect was restored by ovariectomy. 3-nitrotyrosine, a stable marker of oxidative stress, positively correlated with Mmp12 and Cxcl2 gene expression.,Hydrogen peroxide induced BAFF protein in mouse macrophage cell line.,In human lung tissues, female smokers with severe COPD demonstrated increased numbers of lymphoid follicles compared with males.,Chronic smoke exposure increases the risk of lymphoid aggregate formation in female mice compared with male mice, which is mediated female sex hormones and BAFF expression in an oxidative environment. | CD8 cells may contribute towards an autoimmune process in COPD.,Down regulation of T cell receptor (TCR) signalling molecules occurs in autoimmune diseases with consequent T cell dysfunction.,We hypothesise that TCR signalling is abnormal in COPD pulmonary CD8 cells.,Micro-array gene expression analysis of blood and pulmonary COPD CD8 samples was performed and compared to pulmonary CD8 cells from smoker controls (S).,We focused on the TCR signalling pathway, with validation of key findings using polymerase chain reaction and immunofluorescence.,TCR signalling molecules in COPD pulmonary CD8 cells were down regulated compared to blood CD8 cells (CD247: fold change (FC) −2.43, Q = 0.001; LCK: FC −2.25, Q = 0.01).,Micro-array analysis revealed no significant differences between COPD and S pulmonary CD8 cells.,However, PCR revealed significantly lower gene expression levels of CD247 (FC −1.79, p = 0.04) and LCK (FC −1.77, p = 0.01) in COPD compared to S pulmonary CD8 cells.,CD247 down regulation in COPD CD8 cells was confirmed by immunofluorescent staining of bronchoalveolar lavage cells: Significantly fewer COPD CD8 cells co-expressed CD247 compared to healthy non-smoker CD8 cells (mean 88.9 vs 75.2%, p<0.05) There is down regulation of TCR signalling molecules in COPD pulmonary CD8 cells.,This may cause T cell dysfunction. | 1 |
Co-morbidities are common in chronic obstructive pulmonary disease (COPD).,We assessed the contribution of common co-morbidities on health related quality of life (HRQoL) among COPD patients.,Using both generic (15D) and respiratory-specific (AQ20) instruments, HRQoL was assessed in a hospital based COPD population (N = 739, 64% males, mean age 64 years, SD 7 years) in this observational study with inferential analysis.,The prevalence of their co-morbidities was compared with those of 5000 population controls.,The patients represented all severity stages of COPD and the patterns of common concomitant disorders differed between patients.,Co-morbidities such as psychiatric conditions, alcohol abuse, cardiovascular diseases, and diabetes were more common among COPD patients than in age and gender matched controls.,Psychiatric conditions and alcohol abuse were the strongest determinants of HRQoL in COPD and could be detected by both 15D (Odds Ratio 4.7 and 2.3 respectively) and AQ20 (OR 2.0 and 3.0) instruments.,Compared to respiratory specific AQ20, generic 15D was more sensitive to the effects of comorbidities while AQ20 was slightly more sensitive for the low FEV1.,FEV1 was a strong determinant of HRQoL only at more severe stages of disease (FEV1 < 40% of predicted).,Poor HRQoL also predicted death during the next five years.,The results suggest that co-morbidities may impair HRQoL at an early stage of the disease, while bronchial obstruction becomes a significant determinant of HRQoL only in severe COPD. | Introduction.,Chronic obstructive pulmonary disease (COPD) is associated with comorbidities such as cardiovascular disease, metabolic disease, osteoporosis, and anxiety and/or depression.,Although pulmonary rehabilitation programs are proven to be beneficial in patients with COPD, it is unclear whether comorbidities influence pulmonary rehabilitation outcomes.,The aim of the present review was to investigate to what extent the presence of comorbidities can affect pulmonary rehabilitation outcomes.,Methods.,The systematic literature search (Pubmed, EMBASE, and PEDro) resulted in 4 articles meeting the inclusion criteria.,The odds ratios (95% confidence intervals) of the logistic regression analyses, with comorbidities as independent variables and pulmonary rehabilitation outcomes (dyspnea, functional exercise capacity, and quality of life) as dependent variables, were used for data extraction.,Results.,Patients with anxiety and/or depression less likely improve in dyspnea.,Osteoporosis is associated with less improvements in functional exercise capacity, while cardiovascular disease does not seem to negatively impact on this outcome.,Patients with cardiovascular comorbidity will experience less positive changes in quality of life.,Conclusion.,Evidence from literature suggests that comorbidities can have a negative influence on pulmonary rehabilitation outcomes.,Screening for comorbidities in pulmonary rehabilitation settings seems useful to readdress the right patients for individually tailored pulmonary rehabilitation. | 1 |
Health effects of electronic cigarette (EC) use in patients with chronic obstructive pulmonary disease (COPD) are largely unexplored.,We present findings from a long-term prospective assessment of respiratory parameters in a cohort of COPD patients who ceased or substantially reduced conventional cigarette use with ECs.,We prospectively re-evaluated COPD exacerbations, spirometric indices, subjective assessments (using the COPD Assessment Tool [CAT] scores), physical activity (measured by the 6-minute walk distance [6MWD]), and conventional cigarette use in EC users with COPD who were retrospectively assessed previously.,Baseline measurements prior to switching to EC use were compared to follow-up visits at 12, 24, and 36 months.,Age- and sex-matched regularly smoking COPD patients who were not using ECs were included as reference (control) group.,Complete data were available from 44 patients.,Compared to baseline in the EC-user group, there was a marked decline in the use of conventional cigarettes.,Although there was no change in lung function, significant improvements in COPD exacerbation rates, CAT scores, and 6MWD were observed consistently in the EC user group over the 3-year period (p<0.01).,Similar findings were noted in COPD EC users who also smoked conventional cigarettes (“dual users”).,The present study suggests that EC use may ameliorate objective and subjective COPD outcomes and that the benefits gained may persist long-term.,EC use may reverse some of the harm resulting from tobacco smoking in COPD patients. | During 2007-2010, the National Health and Nutrition Examination Survey (NHANES) conducted a spirometry component which obtained pre-bronchodilator pulmonary lung function data on a nationally representative sample of US adults aged 6-79 years and post-bronchodilator pulmonary lung function data for the subset of adults with airflow limitation.,The goals of this study were to 1) compute prevalence estimates of chronic obstructive pulmonary disease (COPD) using pre-bronchodilator and post-bronchodilator spirometry measurements and fixed ratio and lower limit of normal (LLN) diagnostic criteria and 2) examine the potential impact of nonresponse on the estimates.,This analysis was limited to those aged 40-79 years who were eligible for NHANES pre-bronchodilator spirometry (n=7,104).,Examinees with likely airflow limitation were further eligible for post-bronchodilator testing (n=1,110).,Persons were classified as having COPD based on FEV1/FVC < 70% (fixed ratio) or FEV1/FVC < lower limit of normal (LLN) based on person’s age, sex, height, and race/ethnicity.,Those without spirometry but self-reporting both daytime supplemental oxygen therapy plus emphysema and/or current chronic bronchitis were also classified as having COPD.,The final analytic samples for pre-bronchodilator and post-bronchodilator analyses were 77.1% (n=5,477) and 50.8% (n=564) of those eligible, respectively.,To account for non-response, NHANES examination weights were adjusted to the eligible pre-bronchodilator and post-bronchodilator subpopulations.,In 2007-2010, using the fixed ratio criterion and pre-bronchodilator test results, COPD prevalence was 20.9% (SE 1.1) among US adults aged 40-79 years.,Applying the same criterion to post-bronchodilator test results, prevalence was 14.0% (SE 1.0).,Using the LLN criterion and pre-bronchodilator test results, the COPD prevalence was 15.4% (SE 0.8), while applying the same criterion to post-bronchodilator test results, prevalence was 10.2% (SE 0.8).,The overall COPD prevalence among US adults aged 40-79 years varied from 10.2% to 20.9% based on whether pre- or post-bronchodilator values were used and which diagnostic criterion (fixed ratio or LLN) was applied.,The overall prevalence decreased by approximately 33% when airflow limitation was based on post-bronchodilator as compared to pre-bronchodilator spirometry, regardless of which diagnostic criterion was used. | 1 |
Rationale: In the IMPACT (Informing the Pathway of Chronic Obstructive Pulmonary Disease Treatment) trial, fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) significantly reduced exacerbations compared with FF/VI or UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease and a history of exacerbations.,Objectives: To understand whether inhaled corticosteroid (ICS) withdrawal affected IMPACT results, given direct transition from prior maintenance medication to study medication at randomization.,Methods: Exacerbations and change from baseline in trough FEV1 and St.,George’s Respiratory Questionnaire results were analyzed by prior ICS use.,Exacerbations were also analyzed while excluding data from the first 30 days.,Measurements and Main Results: FF/UMEC/VI significantly reduced the annual moderate/severe exacerbation rate compared with UMEC/VI in prior ICS users (29% reduction; P < 0.001), but only a numerical reduction was seen among prior ICS nonusers (12% reduction; P = 0.115).,To minimize impact from ICS withdrawal, in an analysis excluding the first 30 days, FF/UMEC/VI continued to significantly reduce the annual on-treatment moderate/severe exacerbation rate (19%; P < 0.001) compared with UMEC/VI.,The benefit of FF/UMEC/VI compared with UMEC/VI was seen for severe exacerbation rates, regardless of prior ICS use (prior ICS users, 35% reduction; P < 0.001; non-ICS users, 35% reduction; P = 0.018), and overall when excluding the first 30 days (29%; P < 0.001).,Improvements from baseline with FF/UMEC/VI compared with UMEC/VI were also maintained throughout the study for both trough FEV1 and St.,George’s Respiratory Questionnaire, regardless of prior ICS use.,Conclusions: These data support the important treatment effects of FF/UMEC/VI combination therapy on exacerbation reduction, lung function, and quality of life that do not appear to be related to abrupt ICS withdrawal.,Clinical trial registered with www.clinicaltrials.gov (NCT 02164513). | Dual bronchodilator therapy is reserved as a second-line treatment in patients with chronic obstructive pulmonary disease (COPD) and provides benefits in lung function and health status versus monotherapy.,The aim of this study was to determine whether early initiation of a dual bronchodilator versus monotherapy reduced the risk of deterioration in COPD.,This post hoc pooled analysis investigated the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 mcg/day compared with tiotropium (TIO) 18 mcg/day in a maintenance-naïve (MN) subgroup of patients relative to the intent-to-treat (ITT) population from three 6-month active comparator studies (n = 1747).,Other treatment arms (UMEC/VI 125/25, VI 25 and UMEC 125) comprised 850 patients in total but were not included in this analysis.,The primary endpoint was trough forced expiratory volume in 1 s (FEV1).,St George’s Respiratory Questionnaire (SGRQ) score, rescue medication use, and a novel composite endpoint of short-term clinically important deterioration (CID; ≥100 ml decrease in trough FEV1, ≥4-unit increase in SGRQ score, or a COPD exacerbation) were also assessed.,UMEC/VI improved trough FEV1 versus TIO at day 169 [least squares mean (95% confidence interval): MN: 146 ml (102-189) and ITT: 95 ml (71-118); both P < 0.001].,Both UMEC/VI and TIO improved SGRQ and rescue use in the two populations, with greater improvements in rescue use with UMEC/VI versus TIO.,UMEC/VI reduced the risk of short-term clinically important deterioration versus TIO [hazard ratio; 95% confidence interval: MN: 0.66 (0.51-0.85); ITT: 0.62 (0.54-0.71), both P ≤ 0.001].,Adverse events were similar across both populations and treatments.,Early use of dual-bronchodilator therapy has superior efficacy on lung function and may reduce the risk of short-term deterioration compared to monotherapy in symptomatic patients with COPD.,Clinical trial registration: GSK analysis 202066 (NCT01316900/DB2113360, NCT01316913/DB2113374, NCT01777334/ZEP117115).,Funding: This study was funded by GSK.,The online version of this article (doi:10.1007/s12325-016-0430-6) contains supplementary material, which is available to authorized users. | 1 |
Respiratory parameters are important predictors of prognosis in the COPD population.,Global Initiative for Obstructive Lung Disease (GOLD) 2017 Update resulted in a vertical shift of patients across COPD categories, with category B being the most populous and clinically heterogeneous.,The aim of our study was to investigate whether respiratory parameters might be associated with increased all-cause mortality within GOLD category B patients.,The data were extracted from the Czech Multicentre Research Database, a prospective, noninterventional multicenter study of COPD patients.,Kaplan-Meier survival analyses were performed at different levels of respiratory parameters (partial pressure of oxygen in arterial blood [PaO2], partial pressure of arterial carbon dioxide [PaCO2] and greatest decrease of basal peripheral capillary oxygen saturation during 6-minute walking test [6-MWT]).,Univariate analyses using the Cox proportional hazard model and multivariate analyses were used to identify risk factors for mortality in hypoxemic and hypercapnic individuals with COPD.,All-cause mortality in the cohort at 3 years of prospective follow-up reached 18.4%.,Chronic hypoxemia (PaO2 <7.3 kPa), hypercapnia (PaCO2 >7.0 kPa) and oxygen desaturation during the 6-MWT were predictors of long-term mortality in COPD patients with forced expiratory volume in 1 second ≤60% for the overall cohort and for GOLD B category patients.,Univariate analyses confirmed the association among decreased oxemia (<7.3 kPa), increased capnemia (>7.0 kPa), oxygen desaturation during 6-MWT and mortality in the studied groups of COPD subjects.,Multivariate analysis identified PaO2 <7.3 kPa as a strong independent risk factor for mortality.,Survival analyses showed significantly increased all-cause mortality in hypoxemic and hypercapnic GOLD B subjects.,More important, PaO2 <7.3 kPa was the strongest risk factor, especially in category B patients.,In contrast, the majority of the tested respiratory parameters did not show a difference in mortality in the GOLD category D cohort. | Patient-reported outcomes (PRO) questionnaires are being increasingly used in COPD clinical studies.,The challenge facing investigators is to determine what change is significant, ie what is the minimal clinically important difference (MCID).,This study aimed to identify the MCID for the clinical COPD questionnaire (CCQ) in terms of patient referencing, criterion referencing, and by the standard error of measurement (SEM).,Patients were ≥40 years of age, diagnosed with COPD, had a smoking history of >10 pack-years, and were participating in a randomized, controlled clinical trial comparing intravenous and oral prednisolone in patients admitted with an acute exacerbation of COPD.,The CCQ was completed on Days 1-7 and 42.,A Global Rating of Change (GRC) assessment was taken to establish the MCID by patient referencing.,For criterion referencing, health events during a period of 1 year after Day 42 were included in this analysis.,210 patients were recruited, 168 completed the CCQ questionnaire on Day42.,The MCID of the CCQ total score, as indicated by patient referencing in terms of the GRC, was 0.44.,The MCID of the CCQ in terms of criterion referencing for the major outcomes was 0.39, and calculation of the SEM resulted in a value of 0.21.,This investigation, which is the first to determine the MCID of a PRO questionnaire via more than one approach, indicates that the MCID of the CCQ total score is 0.4. | 1 |
Long-term oxygen therapy (LTOT) ≥ 15 h/day improves survival in hypoxemic chronic obstructive pulmonary disease (COPD).,LTOT 24 h/day is often recommended but may pose an unnecessary burden with no clear survival benefit compared with LTOT 15 h/day.,The aim was to test the hypothesis that LTOT 24 h/day decreases all-cause, respiratory, and cardiovascular mortality compared to LTOT 15 h/day in hypoxemic COPD.,This was a prospective, observational, population-based study of COPD patients starting LTOT between October 1, 2005 and June 30, 2009 in Sweden.,Overall and cause-specific mortality was analyzed using Cox and Fine-Gray regression, controlling for age, sex, prescribed oxygen dose, PaO2 (air), PaCO2 (air), Forced Expiratory Volume in one second (FEV1), WHO performance status, body mass index, comorbidity, and oral glucocorticoids.,A total of 2,249 included patients were included with a median follow-up of 1.1 years (interquartile range, 0.6-2.1). 1,129 (50%) patients died and no patient was lost to follow-up.,Higher LTOT duration analyzed as a continuous variable was not associated with any change in mortality rate (hazard ratio [HR] 1.00; (95% confidence interval [CI], 0.98 to 1.02) per 1 h/day increase above 15 h/day.,LTOT exactly 24 h/day was prescribed in 539 (24%) patients and LTOT 15-16 h/day in 1,231 (55%) patients.,Mortality was similar between the groups for all-cause, respiratory and cardiovascular mortality.,In hypoxemic COPD, LTOT 24 h/day was not associated with a survival benefit compared with treatment 15-16 h/day.,A design for a registry-based randomized trial (R-RCT) is proposed. | Fatigue is a disruptive symptom that inhibits normal functional performance of COPD patients in daily activities.,The availability of a short, simple, reliable and valid scale would improve assessment of the characteristics and influence of fatigue in COPD.,At baseline, 2107 COPD patients from the ECLIPSE cohort completed the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scale.,We used well-structured classic method, the principal components analysis (PCA) and Rasch analysis for structurally examining the 13-item FACIT-F.,Four items were less able to capture fatigue characteristics in COPD and were deleted.,PCA was applied to the remaining 9 items of the modified FACIT-F and resulted in three interpretable dimensions: i) general (5 items); ii) functional ability (2 items); and iii) psychosocial fatigue (2 items).,The modified FACIT-F had high internal consistency (Cronbach's α = 0.91) and it did not fit a uni-dimensional Rasch model, confirming the prior output from the PCA.,The correlations between total score and each dimension were ≥ 0.64 and within dimensions ≥0.43 (p < 0.001 for all).,The original and modified FACIT-F had significant convergent validity; its scores were associated with SGRQ total score (0.69 and 0.7) and mMRC dyspnoea scores (0.48 and 0.47), (p = <0.001 for all).,The scale had meaningful discriminating ability in identifying patients with poor exercise performance and more depressive symptoms.,The original and modified FACIT-F are valid and reliable scales in COPD.,The modified version is shorter and measures not only total fatigue but also its sub-components in COPD. | 1 |
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