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Evidence between air pollution and COPD admissions is inconsistent and limited in China.,In this study, we aimed to explore the effects of air pollutants on COPD admissions in Beijing, China.,Daily COPD hospital admission visits derived from tertiary and secondary hospitals in Beijing were retrieved from January 2013 to February 2017.,Air pollutant levels and meteorological data over the same periods were also achieved.,Generalized additive model was applied to estimate the percentage changes with 95% CIs in daily admissions corresponding to 10 µg/m3 increases in pollutants levels [1 mg/m3 in carbon monoxide (CO)], stratified by age, gender, and season.,Seventy-three thousand seventy-six COPD hospital admission visits were included with mean daily visits of 48 (21).,Cumulative lag effect with per 10 µg/m3 increase in air pollutant levels was largest for nitrogen dioxide (NO2) with 3.03% (95% CI: 1.82%-4.26%) at lag 06, for sulfur dioxide (SO2) with 2.07% (95% CI: 1.00%-3.15%) at lag 01, for particulate matter ≤10 µm in aerodynamic diameter (PM10) with 0.92% (95% CI: 0.55%-1.30%) at lag 07, and for particulate matter ≤2.5 µm in aerodynamic diameter (PM2.5) with 0.82% (95% CI: 0.38%-1.26%) at lag 06, respectively.,Percentage increase for each 1 mg/m3 increase in CO was 5.99% (95% CI: 2.74%-9.34%) at lag 06.,Further, stronger effects on COPD admissions were found in warm seasons than in cold seasons.,Short-term exposures to PM2.5, PM10, NO2, SO2, and CO had adverse effects on COPD hospitalizations in Beijing with different magnitudes and lag days. | We undertook this study to investigate whether there is an association between atmospheric fine particles (PM2.5) levels and inpatient admissions for chronic obstructive pulmonary disease (COPD) in Taipei, Taiwan.,Data on inpatient admissions for COPD and ambient on air pollution levels in Taipei were obtained for years 2006 to 2010.,We estimated the relative risk of inpatient admissions for COPD using a case-crossover design with the following control variables: weather measures, day of the week, seasonality, and long-term time trends.,For the single-pollutant model (not controlling for other atmospheric pollutants), COPD admissions were significantly and positively associated with higher PM2.5 levels during both warm days (>23 °C) and cool days (<23 °C), with an interquartile range increase of 12% (95% CI = 8-16%) and 3% (95% CI = 0-7%) in COPD admissions, respectively.,In the two-pollutant models, PM2.5 remained significant even controlling for SO2 or O3 on both warm and cool days.,Taken as a whole, our study demonstrates that higher levels of PM2.5 may increase the risk of inpatient admissions for COPD. | 1 |
Respiratory viruses frequently are recovered in the upper-respiratory tract during acute exacerbations of COPD (AECOPD), but their role as contributing pathogens remains unclear.,The usefulness of procalcitonin and C-reactive protein as indicators of the presence or absence of viral infection in this setting also needs to be evaluated.,The study was of a prospective cohort of patients with COPD admitted to the ED for AECOPD.,Reverse transcriptase-polymerase chain reaction (RT-PCR) for 14 respiratory viruses was performed on nasopharyngeal swabs collected at admission and after recovery in stable condition.,Eighty-six patients (mean age, 72 years; male, 64%) were included.,During AECOPD, upper-respiratory viral infections were detected in 44 (51%) patients: picornavirus in 22, metapneumovirus in seven, coronavirus in eight, influenza A/B in two, parainfluenza in two, and respiratory syncytial virus in three.,A dual infection was present in three patients.,After recovery, viruses were detected in only eight (11%) of 71 patients (P < .001 compared with AECOPD phase).,In five of these patients, no virus had been identified during the initial exacerbation, thus suggesting a new viral infection acquired during follow-up.,During AECOPD, procalcitonin and C-reactive protein levels did not differ significantly between patients with or without a proven viral infection.,Prevalence of upper-respiratory viral infection, as detected from nasopharyngeal swab by RT-PCR, is high in AECOPD and low after clinical recovery, suggesting that AECOPD frequently are triggered by viral infections initiated in the upper-respiratory tract.,In our study, serum procalcitonin and C-reactive protein did not discriminate virus-associated exacerbations from others.,clinicaltrials.gov; Identifier: NCT00448604. | Antibiotic overuse in respiratory illness is common and is associated with drug resistance and hospital-acquired infection.,Biomarkers that can identify bacterial infections may reduce antibiotic prescription.,We aimed to compare the usefulness of the biomarkers procalcitonin and C-reactive protein (CRP) in patients with pneumonia or exacerbations of asthma or COPD.,Patients with a diagnosis of community-acquired pneumonia or exacerbation of asthma or COPD were recruited during the winter months of 2006 to 2008.,Demographics, clinical data, and blood samples were collected.,Procalcitonin and CRP concentrations were measured from available sera.,Sixty-two patients with pneumonia, 96 with asthma, and 161 with COPD were studied.,Serum procalcitonin and CRP concentrations were strongly correlated (Spearman rank correlation coefficient [rs] = 0.56, P < .001).,Patients with pneumonia had increased procalcitonin and CRP levels (median [interquartile range] 1.27 ng/mL [2.36], 191 mg/L [159]) compared with those with asthma (0.03 ng/mL [0.04], 9 mg/L [21]) and COPD (0.05 ng/mL [0.06], 16 mg/L [34]).,The area under the receiver operating characteristic curve (95% CI) for distinguishing between patients with pneumonia (antibiotics required) and exacerbations of asthma (antibiotics not required), for procalcitonin and CRP was 0.93 (0.88-0.98) and 0.96 (0.93-1.00).,A CRP value > 48 mg/L had a sensitivity of 91% (95% CI, 80%-97%) and specificity of 93% (95% CI, 86%-98%) for identifying patients with pneumonia.,Procalcitonin and CRP levels can both independently distinguish pneumonia from exacerbations of asthma.,CRP levels could be used to guide antibiotic therapy and reduce antibiotic overuse in hospitalized patients with acute respiratory illness. | 1 |
With the current wealth of new inhalers available and insurance policy driven inhaler switching, the need for insights in optimal education on inhaler use is more evident than ever.,We aimed to systematically review educational inhalation technique interventions, to assess their overall effectiveness, and identify main drivers of success.,Medline, Embase and CINAHL databases were searched for randomised controlled trials on educational inhalation technique interventions.,Inclusion eligibility, quality appraisal (Cochrane’s risk of bias tool) and data extraction were performed by two independent reviewers.,Regression analyses were performed to identify characteristics contributing to inhaler technique improvement.,Thirty-seven of the 39 interventions included (95%) indicated statistically significant improvement of inhaler technique.,However, average follow-up time was relatively short (5 months), 28% lacked clinical relevant endpoints and all lacked cost-effectiveness estimates.,Poor initial technique, number of inhalation procedure steps, setting (outpatient clinics performing best), and time elapsed since intervention (all, p < 0.05), were shown to have an impact on effectiveness of the intervention, explaining up to 91% of the effectiveness variation.,Other factors, such as disease (asthma vs. chronic obstructive pulmonary disease), education group size (individual vs. group training) and inhaler type (dry powder inhalers vs. pressurised metered dose inhalers) did not play a significant role.,Notably, there was a trend (p = 0.06) towards interventions in adults being more effective than those in children and the intervention effect seemed to wane over time.,In conclusion, educational interventions to improve inhaler technique are effective on the short-term.,Periodical intervention reinforcement and longer follow-up studies, including clinical relevant endpoints and cost-effectiveness, are recommended. | The study aims at investigating the influence of several factors on the probability of receiving one of the two tiotropium formulations (Respimat or Handihaler).,Drug utilisation study.,All residents in the Region Umbria, Italy, aged ≥45 years, who received prescriptions of tiotropium during 2011-2012.,Two groups of patients were studied: (1) incident users of the two tiotropium formulations (ie, without tiotropium prescriptions in the previous 6 months); (2) switchers from Handihaler to Respimat.,Users of the two formulations were compared with regard to baseline characteristics and medical history.,The adjusted OR of receiving Respimat was estimated for several factors.,Incident users of the two formulations (4390 participants) had similar characteristics.,They were older and with more comorbidities than patients included in randomised control trials (RCTs).,Among prevalent users of Handihaler, the probability of switching to Respimat was greater in patients with severe respiratory disease (users of ≥4 respiratory drugs: adjusted OR=4.62; 95% CI 2.46 to 8.69) and among β-blocker users (adjusted OR=1.76; 95% CI 1.13 to 2.75).,Age above 75 years and lipid-lowering drug use reduced the probability of switching.,A positive association was also found between neurological conditions and the use of Respimat.,When starting tiotropium treatment, the choice between the two formulations is weakly affected by comorbidities and chronic obstructive pulmonary disease severity.,Instead, these characteristics influence the likelihood of switching from Handihaler to Respimat.,Since tiotropium users in clinical practice are more severe than those included in RCTs, further aetiological studies are needed to compare the safety profile of the two formulations in routine care. | 1 |
We aimed to assess the effects of comorbidities on COPD costs and to investigate the relationship between comorbidities and clinical variables.,All patients hospitalized with a diagnosis of COPD exacerbation between January 1, 2014, and December 31, 2014, at all state hospitals of Aydın province, a city located in the western part of Turkey, were included in this study.,The costs examined in the study pertained to medications, laboratory tests, hospital stays, and other treatment-related factors, such as consumption of materials, doctor visits, and consultation fees.,A total of 3,095 patients with 5,237 exacerbations (mean age, 71.9±10.5 years; 2,434 males and 661 females) were evaluated.,For 880 of the patients (28.9%), or 3,852 of the exacerbations (73.1%), at least one comorbid disease was recorded.,The mean cost of each exacerbation was $808.5±1,586, including $325.1±879.9 (40.7%) for hospital stays, $223.1±1,300.9 (27.6%) for medications, $46.3±49.6 (0.9%) for laboratory expenditures, and $214±1,068 (26.5%) for other treatment-related factors, such as consumption of materials, doctor visits, and consultation fees.,The cost of each exacerbation was $1,014.9 in patients with at least one comorbidity, whereas it was $233.6 in patients without comorbidity (P<0.001).,Age >65 years, female gender, hospitalization in an intensive care unit, invasive or noninvasive mechanical ventilation, and a long duration of hospitalization were all found to be significant factors in increasing total costs during the exacerbations requiring hospitalization (P<0.05 for all).,Comorbidities have an important role in the total costs of acute exacerbations of COPD.,Strategies for the prevention, diagnosis, and effective management of comorbidities would decrease the overall financial burden associated with acute exacerbations of COPD. | To study patients’ levels of exercise activity and the clinical characteristics that relate to physical activity and inactivity among patients with chronic obstructive pulmonary disease (COPD).,A postal questionnaire was administered to 719 patients with COPD in 2010; patients were recruited from the Helsinki and Turku University Central Hospitals in Finland and have been followed since 2005.,The questionnaire asked participants about their exercise routines and other daily activities, potential restrictions to exercise, health-related quality of life, and subjective sensations of dyspnea upon exertion.,A total of 50% of the participants reported exercising > 2 times a week throughout the year.,The proportion of the exercise inactive patients increased in parallel with disease progression, but the participants exhibited great variation in the degree of activity as well as in sport choices.,Year-round activity was better maintained among patients who exercised both indoors and outdoors.,Training activity was significantly correlated with patients’ reported subjective dyspnea (r = 0.32, P < 0.001), health-related quality of life (r = 0.25, P < 0.001), mobility score (r = 0.37, P < 0.001), and bronchial obstruction (r = 0.18, P < 0.001).,Active patients did not differ from inactive patients in terms of sex, age, smoking status, somatic comorbidities, or body mass index.,Irrespective of the level of severity of patients’ COPD, the most significant barrier to exercising was the subjective sensation of dyspnea.,When a patient with COPD suffers from dyspnea and does not have regular exercise routines, the patient will most likely benefit from an exercise program tailored to his or her physical capabilities. | 1 |
We sought to determine whether circulating inflammatory biomarkers were associated with the frequent exacerbator phenotype in stable COPD patients ie, those with two or more exacerbations in the previous year.,Eighty-eight stable, severe, COPD patients (4 females) were assessed for exacerbation frequency, pulmonary function, fraction of expired nitric oxide (FENO); inflammatory variables were measured in venous blood.,Logistic regression assessed associations between the frequent exacerbator phenotype and systemic inflammation.,Compared with infrequent exacerbators, frequent exacerbators (n=10; 11.4%) had greater serum concentration (median (25th-75th quartile)) of serum amyloid A (SAA; 134 (84-178) vs 71 (38-116) ng/mL; P=0.024), surfactant protein D (SP-D; 15.6 (9.0-19.3) vs 8.5 (3.6-14.9) ng/mL; P=0.049) and interleukin-4 (IL-4; 0.12 (0.08-1.44) vs 0.03 (0.01-0.10) pg/mL; P=0.001).,SAA, SP-D and IL-4 were not significantly correlated with FEV1%predicted or FVC %predicted.,After adjusting for sex, age, BMI, FEV1/FVC and smoking pack-years, only SAA remained independently associated with the frequent exacerbator phenotype (OR 1.49[1.09-2.04]; P=0.012).,The odds of being a frequent exacerbator was 18-times greater in the highest SAA quartile (≥124.1 ng/mL) than the lowest SAA quartile (≤44.1 ng/mL) (OR 18.34[1.30-258.81]; P=0.031), and there was a significant positive trend of increasing OR with increasing SAA quartile (P=0.008).,For SAA, the area under the receiver operating characteristic curve was 0.721 for identification of frequent exacerbators; an SAA cut-off of 87.0 ng/mL yielded an 80% sensitivity and 61.5% specificity.,In stable COPD patients, SAA was independently associated with the frequent exacerbator phenotype, suggesting that SAA may be a useful serum biomarker to inform progression or management in COPD. | Coronavirus disease 2019 (COVID-19) is an evolving infectious disease that dramatically spread all over the world in the early part of 2020.,No studies have yet summarized the potential severity and mortality risks caused by COVID-19 in patients with chronic obstructive pulmonary disease (COPD), and we update information in smokers.,We systematically searched electronic databases from inception to March 24, 2020.,Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.,Study quality was assessed using a modified version of the Newcastle-Ottawa Scale.,We synthesized a narrative from eligible studies and conducted a meta-analysis using a random-effects model to calculate pooled prevalence rates and 95% confidence intervals (95%CI).,In total, 123 abstracts were screened and 61 full-text manuscripts were reviewed.,A total of 15 studies met the inclusion criteria, which included a total of 2473 confirmed COVID-19 patients.,All studies were included in the meta-analysis.,The crude case fatality rate of COVID-19 was 7.4%.,The pooled prevalence rates of COPD patients and smokers in COVID-19 cases were 2% (95% CI, 1%-3%) and 9% (95% CI, 4%-14%) respectively.,COPD patients were at a higher risk of more severe disease (risk of severity = 63%, (22/35) compared to patients without COPD 33.4% (409/1224) [calculated RR, 1.88 (95% CI, 1.4-2.4)].,This was associated with higher mortality (60%).,Our results showed that 22% (31/139) of current smokers and 46% (13/28) of ex-smokers had severe complications.,The calculated RR showed that current smokers were 1.45 times more likely [95% CI: 1.03-2.04] to have severe complications compared to former and never smokers.,Current smokers also had a higher mortality rate of 38.5%.,Although COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD.,Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate.,Effective preventive measures are required to reduce COVID-19 risk in COPD patients and current smokers. | 1 |
The minimal clinically important difference (MCID) defines to what extent change on a health status instrument is clinically relevant, which aids scientists and physicians in measuring therapy effects.,This is the first study that aimed to establish the MCID of the Clinical chronic obstructive pulmonary disease (COPD) Questionnaire (CCQ), the COPD Assessment Test (CAT) and the St George’s Respiratory Questionnaire (SGRQ) in the same pulmonary rehabilitation population using multiple approaches.,In total, 451 COPD patients participated in a 3-week Pulmonary Rehabilitation (PR) programme (58 years, 65% male, 43 pack-years, GOLD stage II/III/IV 50/39/11%).,Techniques used to assess the MCID were anchor-based approaches, including patient-referencing, criterion-referencing and questionnaire-referencing, and the distribution-based methods standard error of measurement (SEM), 1.96SEM and half standard deviation (0.5s.d.).,Patient- and criterion-referencing led to MCID estimates of 0.56 and 0.62 (CCQ); 3.12 and 2.96 (CAT); and 8.40 and 9.28 (SGRQ).,Questionnaire-referencing suggested MCID ranges of 0.28-0.61 (CCQ), 1.46-3.08 (CAT) and 6.86-9.47 (SGRQ).,The SEM, 1.96SEM and 0.5s.d. were 0.29, 0.56 and 0.46 (CCQ); 3.28, 6.43 and 2.80 (CAT); 5.20, 10.19 and 6.06 (SGRQ).,Pooled estimates were 0.52 (CCQ), 3.29 (CAT) and 7.91 (SGRQ) for improvement.,MCID estimates differed depending on the method used.,Pooled estimates suggest clinically relevant improvements needing to exceed 0.40 on the CCQ, 3.00 on the CAT and 7.00 on the SGRQ for moderate to very severe COPD patients.,The MCIDs of the CAT and SGRQ in the literature might be too low, leading to overestimation of treatment effects for patients with COPD. | Objective To investigate the long term effectiveness of integrated disease management delivered in primary care on quality of life in patients with chronic obstructive pulmonary disease (COPD) compared with usual care.,Design 24 month, multicentre, pragmatic cluster randomised controlled trial,Setting 40 general practices in the western part of the Netherlands,Participants Patients with COPD according to GOLD (Global Initiative for COPD) criteria.,Exclusion criteria were terminal illness, cognitive impairment, alcohol or drug misuse, and inability to fill in Dutch questionnaires.,Practices were included if they were willing to create a multidisciplinary COPD team.,Intervention General practitioners, practice nurses, and specialised physiotherapists in the intervention group received a two day training course on incorporating integrated disease management in practice, including early recognition of exacerbations and self management, smoking cessation, physiotherapeutic reactivation, optimal diagnosis, and drug adherence.,Additionally, the course served as a network platform and collaborating healthcare providers designed an individual practice plan to integrate integrated disease management into daily practice.,The control group continued usual care (based on international guidelines).,Main outcome measures The primary outcome was difference in health status at 12 months, measured by the Clinical COPD Questionnaire (CCQ); quality of life, Medical Research Council dyspnoea, exacerbation related outcomes, self management, physical activity, and level of integrated care (PACIC) were also assessed as secondary outcomes.,Results Of a total of 1086 patients from 40 clusters, 20 practices (554 patients) were randomly assigned to the intervention group and 20 clusters (532 patients) to the usual care group.,No difference was seen between groups in the CCQ at 12 months (mean difference -0.01, 95% confidence interval -0.10 to 0.08; P=0.8).,After 12 months, no differences were seen in secondary outcomes between groups, except for the PACIC domain “follow-up/coordination” (indicating improved integration of care) and proportion of physically active patients.,Exacerbation rates as well as number of days in hospital did not differ between groups.,After 24 months, no differences were seen in outcomes, except for the PACIC follow-up/coordination domain.,Conclusion In this pragmatic study, an integrated disease management approach delivered in primary care showed no additional benefit compared with usual care, except improved level of integrated care and a self reported higher degree of daily activities.,The contradictory findings to earlier positive studies could be explained by differences between interventions (provider versus patient targeted), selective reporting of positive trials, or little room for improvement in the already well developed Dutch healthcare system.,Trial registration Netherlands Trial Register NTR2268. | 1 |
The Spanish COPD guideline (GesEPOC) classifies COPD into four clinical phenotypes based on the exacerbation frequency and dominant clinical manifestations.,In this study, we compared the disease-specific health-related quality of life (HRQoL) of patients with different clinical phenotypes.,This was a cross-sectional study of patients with COPD attending the respiratory medicine clinic of University of Malaya Medical Centre from 1 June 2017 to 31 May 2018.,Disease-specific HRQoL was assessed by using the COPD Assessment Test (CAT) and St George’s Respiratory Questionnaire for COPD (SGRQ-c).,Of 189 patients, 28.6% were of non-exacerbator phenotype (NON-AE), 18.5% were of exacerbator with emphysema phenotype (AE NON-CB), 39.7% were of exacerbator with chronic bronchitis phenotype (AE CB), and 13.2% had asthma-COPD overlap syndrome phenotype (ACOS).,The total CAT and SGRQ-c scores were significantly different between the clinical phenotypes (P<0.001).,Patients who were AE CB had significantly higher total CAT score than those with ACOS (P=0.033), AE NON-CB (P=0.001), and NON-AE (P<0.001).,Concerning SGRQ-c, patients who were AE CB also had a significantly higher total score than those with AE NON-CB (P=0.001) and NON-AE (P<0.001).,However, the total SGRQ-c score of AE CB patients was only marginally higher than those who had ACOS (P=0.187).,There was a significant difference in the score of each CAT item (except CAT 7) and SGRQ-c components between clinical phenotypes, with AE CB patients recording the highest score in each of them.,Patients who were AE CB had significantly poorer HRQoL than other clinical phenotypes and recorded the worst score in each of the CAT items and SGRQ-c components.,Therefore, AE CB patients may warrant a different treatment approach that focuses on the exacerbation and chronic bronchitis components. | The Korea Chronic Obstructive Pulmonary Disorders Subgroup Study Team (Korea COPD Subgroup Study team, KOCOSS) is a multicenter observational study that includes 956 patients (mean age 69.9 ± 7.8 years) who were enrolled from 45 tertiary and university-affiliated hospitals from December 2011 to October 2014.,The initial evaluation for all patients included pulmonary function tests (PFT), 6-minute walk distance (6MWD), COPD Assessment Test (CAT), modified Medical Research Council (mMRC) dyspnea scale, and the COPD-specific version of St.,George’s Respiratory Questionnaire (SGRQ-C).,Here, we report the comparison of baseline characteristics between patients with early- (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage I and II/groups A and B) and late-stage COPD (GOLD stage III and IV/groups C and D).,Among all patients, the mean post-bronchodilator FEV1 was 55.8% ± 16.7% of the predicted value, and most of the patients were in GOLD stage II (520, 56.9%) and group B (399, 42.0%).,The number of exacerbations during one year prior to the first visit was significantly lower in patients with early COPD (0.4 vs.,0.9/0.1 vs.,1.2), as were the CAT score (13.9 vs.,18.3/13.5 vs.,18.1), mMRC (1.4 vs.,2.0/1.3 vs.1.9), and SGRQ-C total score (30.4 vs.,42.9/29.1 vs.,42.6) compared to late-stage COPD (all P < 0.001).,Common comorbidities among all patients were hypertension (323, 37.7%), diabetes mellitus (139, 14.8%), and depression (207, 23.6%).,The data from patients with early COPD will provide important information towards early detection, proper initial management, and design of future studies. | 1 |
In most countries, nearly 6% of the adults are suffering from chronic obstructive pulmonary disease (COPD), which puts a huge economic burden on the society.,Moreover, COPD has been considered as an independent risk factor for pulmonary embolism (PE).,In this review, we summarized the existing evidence that demonstrates the associations between COPD exacerbation and PE from various aspects, including epidemiology, pathophysiological changes, risk factors, clinical features, management, and prognosis.,We searched the terms “chronic obstructive pulmonary disease,” “pulmonary embolism,” “exacerbations,” and “thromboembolic” in PubMed database and collected the results up to April 2018.,The language was limited to English.,We thoroughly examined the titles and abstracts of all studies that met our search strategy.,The data from prospective studies, meta-analyses, retrospective studies, and recent reviews were selected for preparing this review.,The prevalence of PE in patients with COPD exacerbation varied a lot among different studies, mainly due to the variations in race, sample size, study design, research setting, and enrollment criteria.,Overall, whites and African Americans showed significantly higher prevalence of PE than Asian people, and the hospitalized patients showed higher prevalence of PE compared to those who were evaluated in emergency department.,PE is easily overlooked in patients with COPD exacerbation due to the similar clinical symptoms.,However, several factors have been identified to contribute to the increased risk of PE during COPD exacerbation.,Obesity and lower limb asymmetry were described as independent predictors for PE.,Moreover, due to the high risk of PE, thromboprophylaxis has been used as an important treatment for hospitalized patients with COPD exacerbation.,According to the previous studies, COPD patients with PE experienced an increased risk of death and prolonged length of hospital stay.,Therefore, the thromboembolic risk in patients with acute exacerbation of COPD, especially in the hospitalized patients, should carefully be evaluated. | Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities.,COPD exacerbations and comorbidities contribute to the overall severity in individual patients.,Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age.,Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations.,However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide.,This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale.,Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases.,All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases.,In this review, we focus on the major comorbidities that affect COPD patients.,We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs.,We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity. | 1 |
The aetiology of acute exacerbations of COPD (AECOPD) is incompletely understood.,Understanding the relationship between chronic bacterial airway infection and viral exposure may explain the incidence and seasonality of these events.,In this prospective, observational cohort study (NCT01360398), patients with COPD aged 40-85 years underwent sputum sampling monthly and at exacerbation for detection of bacteria and viruses.,Results are presented for subjects in the full cohort, followed for 1 year.,Interactions between exacerbation occurrence and pathogens were investigated by generalised estimating equation and stratified conditional logistic regression analyses.,The mean exacerbation rate per patient-year was 3.04 (95% CI 2.63 to 3.50).,At AECOPD, the most common bacterial species were non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis, and the most common virus was rhinovirus.,Logistic regression analyses (culture bacterial detection) showed significant OR for AECOPD occurrence when M. catarrhalis was detected regardless of season (5.09 (95% CI 2.76 to 9.41)).,When NTHi was detected, the increased risk of exacerbation was greater in high season (October-March, OR 3.04 (1.80 to 5.13)) than low season (OR 1.22 (0.68 to 2.22)).,Bacterial and viral coinfection was more frequent at exacerbation (24.9%) than stable state (8.6%).,A significant interaction was detected between NTHi and rhinovirus presence and AECOPD risk (OR 5.18 (1.92 to 13.99); p=0.031).,AECOPD aetiology varies with season.,Rises in incidence in winter may be driven by increased pathogen presence as well as an interaction between NTHi airway infection and effects of viral infection.,Results, NCT01360398. | This study aimed to evaluate the effects of vitamin D intake on COPD exacerbation and FEV1 in the patients with severe and very severe COPD.,This double blind placebo control randomized clinical trial study was done in the Ashayer university hospital in Khorramabad in 2012.,Eighty eight patients with severe and very severe COPD were randomly selected from those who recoursed to the internal medicine clinic of Ashayer hospital.,They were randomly allocated to case and placebo group.,The patients received routine treatment for COPD.,Along with the routine treatment, placebo group received 100,000 IU of oral vitamin D per month, for 6 months.,Data was analyzed using SPSS computer software, paired t-test, independent t-test, non parametric t-test and Pearson correlation coefficients.,In each group, there were 44 patients.,After the intervention, there were significant differences in FEV1 and the number of COPD exacerbation between the case and control group patients.,Also, after the study, in the case group, FEV1 was increased and the number of COPD exacerbation was decreased significantly.,Vitamin D intake decreased COPD exacerbation and improved FEV1 in the patients with severe and very severe COPD.,It is suggested that baseline serum vitamin D levels will recorded in similar studies and the effect of vitamin D intake will evaluated regarding the baseline serum vitamin D levels. | 1 |
As lung function declines rapidly in the early stages of chronic obstructive pulmonary disease (COPD), the effects of bronchodilators in patients with moderate disease and those who have not previously received maintenance therapy are of interest.,OTEMTO® 1 and 2 were two replicate, 12-week, Phase III studies investigating the benefit of tiotropium + olodaterol on lung function and quality of life in patients with moderate to severe disease.,Post hoc analyses were performed to assess the benefits for patients according to disease severity and treatment history.,Four subgroup analyses were performed: Global initiative for chronic Obstructive Lung Disease (GOLD) 2/3, GOLD A/B/C/D, treatment naive/not treatment naive and receiving inhaled corticosteroids (ICS) at baseline/not receiving ICS at baseline.,Primary end points were change in forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h response, change in trough FEV1 and St George’s Respiratory Questionnaire (SGRQ) total score.,Transition Dyspnoea Index (TDI) focal score was a secondary end point, and SGRQ and TDI responder analyses were further end points; all were assessed at 12 weeks.,In all subgroups, patients receiving tiotropium + olodaterol responded better overall than those receiving tiotropium monotherapy.,Improvements with tiotropium + olodaterol over placebo or tiotropium monotherapy were noted across GOLD 2/3 and GOLD A/B/C/D; however, improvements in SGRQ total score were most evident in the GOLD B subgroup.,Moreover, lung-function outcomes were generally greater in those patients who had been receiving previous long-acting bronchodilator and/or ICS maintenance treatment.,These data suggest that tiotropium + olodaterol should be considered as a treatment option in patients with moderate COPD who are initiating maintenance therapy, as well as those with more severe disease.,ClinicalTrials.gov: NCT01964352 and NCT02006732.,The online version of this article (doi:10.1186/s12931-016-0387-7) contains supplementary material, which is available to authorized users. | 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 |
COPD is the third leading cause of death in the world.,Utilizing care bundles during acute COPD exacerbations results in fewer complications and lower costs.,Our aim was to construct a COPD exacerbation care bundle and evaluate the effects on patient care.,We conducted a prospective analysis of 44 patients admitted with a COPD exacerbation to a single tertiary care facility.,Primary outcomes included length of stay, readmission rates, and hospital costs.,Secondary outcomes included patient education, pulmonologist follow-up, and timeliness of medication administration.,Two cohorts were analyzed: those treated with an electronic COPD care bundle (cases; N=22) versus those treated without the care bundle (controls; N=22).,Mean length of stay (51.2 vs 101.1 hours in controls; P-value =0.001), 30-day readmission rates (9.1% vs 54.4% in controls; P-value =0.001), and 60-day readmission rates (22.7% vs 77% in controls; P-value =0.0003) decreased in the care bundle group.,Ninety-day hospital costs had a significant difference in the care bundle group (US$7,652 vs US$19,954 in controls; P-value =0.044).,Secondary outcomes included a 100% rate of COPD inhaler teaching (vs 27.3% in controls; P-value <0.001), 59.1% rate of pulmonologist follow-up after discharge (vs 18.2% in controls; P-value =0.005), and a mean reduction in time to steroid administration (7.0 hours; P-value =0.015) seen in the care bundle cases.,Our significant findings coupled with the recent success of standardized algorithms in managing COPD exacerbations stress the importance of enforcing clinical guidelines that can enhance patient care.,We demonstrated improved care for COPD exacerbation patients during hospitalizations, thereby decreasing morbidity and the financial burden hospitals face in regard to this increasingly prevalent disease. | 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. | 1 |
Dietary beetroot juice (BR) supplementation has been shown to reduce the oxygen (O2) consumption of standardized exercise and reduce resting blood pressure (BP) in healthy individuals.,However, the physiological response of BR in chronic obstructive pulmonary disease (COPD) remains controversial.,The objective was to test exercise performance in COPD, supplementing with higher doses of BR for a longer duration compared to previous trials in this patient group.,Fifteen COPD patients consumed concentrated BR (2×70 mL twice daily, each containing 300 mg nitrate) or placebo (PL) (2×70 mL twice daily, nitrate-negligible) in a randomized order for 6 consecutive days.,On day 7, participants consumed either BR or PL 150 min before testing.,BP was measured before completing 6-minute walk test (6MWT) and two trials of submaximal cycling.,The protocol was repeated after a minimum washout of 7 days.,Plasma nitrite concentration was higher in the BR condition compared to PL (P<0.01).,There was no difference between the BR and PL conditions regarding the covered distance during the 6MWT (mean ± standard error of the mean: 515±35 m (BR) vs 520±38 m (PL), P=0.46), O2 consumption of submaximal exercise (trial 1 P=0.31 vs trial 2 P=0.20), physical activity level (P>0.05), or systolic BP (P=0.80).,However, diastolic BP (DBP) was reduced after BR ingestion compared to baseline (mean difference: 4.6, 95% CI: 0.1-9.1, P<0.05).,Seven days of BR ingestion increased plasma nitrite concentrations and lowered DBP in COPD patients.,However, BR did not increase functional walking capacity, O2 consumption during submaximal cycling, or physical activity level during the intervention period. | Diet and nutrition may be important modifiable risk factors for the development, progression and management of obstructive lung diseases such as asthma and chronic obstructive pulmonary disease (COPD).,This review examines the relationship between dietary patterns, nutrient intake and weight status in obstructive lung diseases, at different life stages, from in-utero influences through childhood and into adulthood.,In vitro and animal studies suggest important roles for various nutrients, some of which are supported by epidemiological studies.,However, few well-designed human intervention trials are available to definitively assess the efficacy of different approaches to nutritional management of respiratory diseases.,Evidence for the impact of higher intakes of fruit and vegetables is amongst the strongest, yet other dietary nutrients and dietary patterns require evidence from human clinical studies before conclusions can be made about their effectiveness. | 1 |
Conduct a cost-effectiveness analysis of FreeO2 technology versus manual oxygen-titration technology for patients with chronic obstructive pulmonary disease (COPD) hospitalised for acute exacerbations.,Tertiary acute care hospital in Quebec, Canada.,47 patients with COPD hospitalised for acute exacerbations.,An automated oxygen-titration and oxygen-weaning technology.,The costs for hospitalisation and follow-up for 180 days were calculated using a microcosting approach and included the cost of FreeO2 technology.,Incremental cost-effectiveness ratios (ICERs) were calculated using bootstrap resampling with 5000 replications.,The main effect variable was the percentage of time spent at the target oxygen saturation (SpO2).,The other two effect variables were the time spent in hyperoxia (target SpO2+5%) and in severe hypoxaemia (SpO2 <85%).,The resamplings were based on data from a randomised controlled trial with 47 patients with COPD hospitalised for acute exacerbations.,FreeO2 generated savings of 20.7% of the per-patient costs at 180 days (ie, −$C2959.71).,This decrease is nevertheless not significant at the 95% threshold (P=0.13), but the effect variables all improved (P<0.001).,The improvement in the time spent at the target SpO2 was 56.3%.,The ICERs indicate that FreeO2 technology is more cost-effective than manual oxygen titration with a savings of −$C96.91 per percentage point of time spent at the target SpO2 (95% CI −301.26 to 116.96).,FreeO2 technology could significantly enhance the efficiency of the health system by reducing per-patient costs at 180 days.,A study with a larger patient sample needs to be carried out to confirm these preliminary results.,NCT01393015; Post-results. | Natural history of chronic obstructive pulmonary disease (COPD) is punctuated by exacerbations; however, little is known about prognosis of the first-ever COPD exacerbation and variables predicting its outcomes.,A population-based cohort study among COPD patients with their first-ever exacerbations requiring hospitalizations was conducted.,Main outcomes were in-hospital mortality and one-year mortality after discharge.,Demographics, comorbidities, medications and in-hospital events were obtained to explore outcome predictors.,The cohort comprised 4204 hospitalized COPD patients, of whom 175 (4%) died during the hospitalization.,In-hospital mortality was related to higher age (odds ratio [OR]: 1.05 per year; 95% confidence interval [CI]: 1.03-1.06) and Charlson comorbidity index score (OR: 1.08 per point; 95% CI: 1.01-1.15); angiotensin II receptor blockers (OR: 0.61; 95% CI: 0.38-0.98) and β blockers (OR: 0.63; 95% CI: 0.41-0.95) conferred a survival benefit.,At one year after discharge, 22% (871/4029) of hospital survivors were dead.,On multivariate Cox regression analysis, age and Charlson comorbidity index remained independent predictors of one-year mortality.,Longer hospital stay (hazard ratio [HR] 1.01 per day; 95% CI: 1.01-1.01) and ICU admission (HR: 1.33; 95% CI: 1.03-1.73) during the hospitalization were associated with higher mortality risks.,Prescription of β blockers (HR: 0.79; 95% CI: 0.67-0.93) and statins (HR: 0.66; 95% CI: 0.47-0.91) on hospital discharge were protective against one-year mortality.,Even the first-ever severe COPD exacerbation signifies poor prognosis in COPD patients.,Comorbidities play a crucial role in determining outcomes and should be carefully assessed.,Angiotensin II receptor blockers, β blockers and statins may, in theory, have dual cardiopulmonary protective properties and probably alter prognosis of COPD patients.,Nevertheless, the limitations inherent to a claims database study, such as the diagnostic accuracy of COPD and its exacerbation, should be born in mind. | 1 |
Psoriasis is considered a systemic inflammatory disorder.,Previous studies have reported conflicting positive or negative correlations between psoriasis and chronic obstructive pulmonary disease.,We performed a meta-analysis to determine whether there is an associated risk between psoriasis and chronic obstructive pulmonary disease.,We performed a complete 30-year literature search of MEDLINE, Embase, and Cochrane Central Register databases on this topic.,Four observational studies with a total of 13,418 subjects were identified.,The odds ratios of chronic obstructive pulmonary disease in subjects with psoriasis/mild-to-moderate psoriasis were analyzed using the random-effects model, while the odds ratios of chronic obstructive pulmonary disease in subjects with severe psoriasis and current smoking in subjects with psoriasis were analyzed using the fixed-effect model.,We found that psoriasis patients were at a greater risk of developing chronic obstructive pulmonary disease than the general population (odds ratio, 1.90; 95% confidence interval, 1.36-2.65) and that the association between of psoriasis and with chronic obstructive pulmonary disease was stronger among patients with severe psoriasis (odds ratio, 2.15; 95% confidence interval, 1.26-3.67).,Psoriasis patients should be advised to cease smoking to reduce their risk of COPD.,Moreover, identification of this potential risk may enable earlier implementation of preventive measures for reduction comorbidity and mortality rates. | Several studies have reported an association between chronic obstructive pulmonary disease (COPD) and periodontal diseases.,However, a large-scale population-based cohort study was previously absent from the literature.,Therefore, we evaluated the risk of periodontal diseases in patients with COPD in a nationwide population.,From the National Health Insurance claims data of Taiwan, we identified 22,332 patients with COPD who were newly diagnosed during 2000 to 2010.,For each case, two individuals without COPD were randomly selected and frequency matched by age, sex, and diagnosis year.,Both groups were followed up till the end of 2011.,The overall incidence of periodontal diseases was 1.19-fold greater in the COPD group than in the comparison group (32.2 vs 26.4 per 1000 person-years; 95% confidence interval [CI] 1.15-1.24).,Compared with non-COPD patients, the adjusted hazard ratios of patients with COPD increased with the number of emergency room visits (from 1.14 [95% CI 1.10-1.19] to 5.09 [95% CI 4.53-5.72]) and admissions (from 1.15 [95% CI 1.10-1.20] to 3.17 [95% CI 2.81-3.57]).,In addition, the adjusted hazard ratios of patients with COPD treated with inhaled corticosteroids (1.22, 95% CI 1.11-1.34) and systemic corticosteroids (1.15, 95% CI 1.07-1.23) were significantly higher than those of patients not treated with corticosteroids.,Patient with COPD are at a higher risk of developing periodontal diseases than the general population.,Our results also support that the risk of periodontal diseases is proportional to COPD control.,In addition, patients who receive corticosteroid treatment are at a higher risk of developing periodontal diseases. | 1 |
Information about daily physical activity levels (PAL) in subjects with undiagnosed chronic obstructive pulmonary disease (COPD) is scarce.,This study aims to assess PA and to investigate the associations between PA and clinical characteristics in subjects with newly diagnosed COPD.,Fifty-nine subjects with a new spirometry-based diagnosis of mild (n=38) and moderate (n=21) COPD (63±6 years, 68% male) were matched with 65 smoking controls (62±7 years, 75% male).,PA (daily steps, time spent in moderate-to-vigorous intense physical activities (MVPA) and PAL) was measured by accelerometry.,Dyspnoea, complete pulmonary function tests, peripheral muscle strength and exercise capacity served as clinical characteristics.,PA was significantly lower in COPD versus smoking controls (7986±2648 vs 9765±3078 steps, 64 (27-120) vs 110 (55-164) min of MVPA, 1.49±0.21 vs 1.62±0.24 PAL respectively, all p<0.05).,Subjects with COPD with either mild symptoms of dyspnoea (mMRC 1), those with lower diffusion capacity (TL,co), low 6 min walking distance (6MWD) or low maximal oxygen uptake (VO2 peak) had significantly lower PA.,Multiple regression analysis identified 6 MWD and TL,co as independent predictors of PA in COPD.,The reduction in PA starts early in the disease, even when subjects are not yet diagnosed with COPD.,Inactivity is more pronounced in subjects with mild symptoms of dyspnoea, lower levels of diffusion capacity and exercise capacity. | The efficacy of inhaled salmeterol plus fluticasone propionate (SFC) in patients with severe or very severe COPD is well documented.,However, there are only limited data about the influence of GOLD severity staging on the effectiveness of SFC, particularly in patients with milder disease.,TORCH was a 3-year, double-blind, placebo-controlled trial of 6112 patients with moderate/severe COPD with pre-bronchodilator FEV1 < 60% predicted (mean age 65 years, 76% male, mean 44% predicted FEV1, 43% current smokers).,To understand the relative efficacy of SFC and its components by GOLD stages, we conducted a post-hoc analysis of the TORCH dataset using baseline post-bronchodilator FEV1 to segment patients into three groups: moderate COPD (GOLD stage II and above: ≥ 50%; n = 2156), severe COPD (GOLD stage III: 30% to < 50%; n = 3019) and very severe COPD (GOLD stage IV: < 30%; n = 937).,Compared with placebo, SFC improved post-bronchodilator FEV1: 101 ml (95% confidence interval [CI]: 71, 132) in GOLD stage II, 82 ml (95% CI: 60, 104) in GOLD stage III and 96 ml (95% CI: 54, 138) in GOLD stage IV patients, and reduced the rate of exacerbations: 31% (95% CI: 19, 40) in GOLD stage II, 26% (95% CI: 17, 34) in GOLD stage III and 14% (95% CI: -4, 29) in GOLD stage IV.,SFC improved health status to a greater extent than other treatments regardless of baseline GOLD stage.,Similarly, SFC reduced the risk of death by 33% (hazard ratio [HR] 0.67; 95% CI: 0.45, 0.98) for GOLD stage II, 5% (HR 0.95; 95% CI: 0.73, 1.24) for GOLD stage III, and 30% (HR 0.70; 95% CI: 0.47, 1.05) for GOLD stage IV.,The rates of adverse events were similar across treatment arms and increased with disease severity.,Overall, there was a higher incidence of pneumonia in the fluticasone propionate and SFC arms, compared with other treatments in all GOLD stages.,In the TORCH study, SFC reduced moderate-to-severe exacerbations and improved health status and FEV1 across GOLD stages.,Treatment with SFC may be associated with reduced mortality compared with placebo in patients with GOLD stage II disease.,The effects were similar to those reported for the study as a whole.,Thus, SFC is an effective treatment option for patients with GOLD stage II COPD.,Clinicaltrial.gov registration NCT00268216; Study number: SCO30003 | 1 |
The FLAME study demonstrated that indacaterol/glycopyrronium (IND/GLY), the fixed-dose combination of a long-acting β2-agonist (LABA, IND) and a long-acting muscarinic antagonist (LAMA, GLY), was superior to salmeterol/fluticasone combination (SFC) in preventing exacerbations in COPD patients with a high risk of exacerbations.,In this study, we report a prespecified analysis of the efficacy and safety of IND/GLY versus SFC in Asian patients from the FLAME study.,Patients from Asian centers with moderate-to-very severe COPD and ≥1 exacerbation in the previous year from the 52-week, randomized FLAME study were included.,IND/GLY was compared versus SFC for effects on exacerbations, lung function (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC]), health status (St George’s Respiratory Questionnaire [SGRQ]), rescue medication use, and safety.,A total of 510 Asian patients (IND/GLY, n=250 or SFC, n=260) were included.,Compared to the overall FLAME population, the Asian cohort had more males, a shorter duration of COPD, fewer patients using inhaled corticosteroid (ICS) at screening, fewer current smokers, and more patients with very severe COPD.,IND/GLY significantly reduced the rate of moderate/severe exacerbations (rate ratio: 0.75; 95% confidence interval: 0.58-0.97; P=0.027) and prolonged time to first moderate/severe exacerbation versus SFC (hazard ratio: 0.77; 95% confidence interval: 0.59-1.01; P=0.055).,Predose trough FEV1 and FVC significantly improved in Asian patients (P<0.001).,IND/GLY improved SGRQ for COPD (SGRQ-C score; P=0.006) and reduced rescue medication use (P=0.058) at week 52.,Pneumonia incidence was 3.6% with IND/GLY and 7.7% with SFC (P=0.046).,In exacerbating Asian COPD patients, IND/GLY was more effective than SFC. | Two 1-year studies evaluated the long-term efficacy and safety of tiotropium 5 or 10 μg versus placebo, inhaled via the Respimat® Soft Mist™ Inhaler (SMI).,The two studies were combined and had 4 co-primary endpoints (trough FEV1 response, Mahler Transition Dyspnea Index [TDI] and St George’s Respiratory Questionnaire scores all at week 48, and COPD exacerbations per patient-year).,A total of 1990 patients with COPD participated (mean FEV1: 1.09 L).,The mean trough FEV1 response of tiotropium 5 or 10 μg relative to placebo was 127 or 150 mL, respectively (both P < 0.0001).,The COPD exacerbation rate was significantly lower with tiotropium 5 μg (RR = 0.78; P = 0.002) and tiotropium 10 μg (RR = 0.73; P = 0.0008); the health-related quality of life and Mahler TDI co-primary endpoints were significantly improved with both doses (both P < 0.0001).,Adverse events were generally balanced except anticholinergic class effects, which were more frequent with active treatment.,Fatal events occurred in 2.4% (5 μg), 2.7% (10 μg), and 1.6% (placebo) of patients; these differences were not significant.,Tiotropium Respimat® SMI 5 μg demonstrated sustained improvements in patients with COPD relative to placebo and similar to the 10 μg dose but with a lower frequency of anticholinergic adverse events. | 1 |
The Finnish Medical Society Duodecim initiated and managed the update of the Finnish national guideline for chronic obstructive pulmonary disease (COPD).,The Finnish COPD guideline was revised to acknowledge the progress in diagnosis and management of COPD.,This Finnish COPD guideline in English language is a part of the original guideline and focuses on the diagnosis, assessment and pharmacotherapy of stable COPD.,It is intended to be used mainly in primary health care but not forgetting respiratory specialists and other healthcare workers.,The new recommendations and statements are based on the best evidence available from the medical literature, other published national guidelines and the GOLD (Global Initiative for Chronic Obstructive Lung Disease) report.,This guideline introduces the diagnostic approach, differential diagnostics towards asthma, assessment and treatment strategy to control symptoms and to prevent exacerbations.,The pharmacotherapy is based on the symptoms and a clinical phenotype of the individual patient.,The guideline defines three clinically relevant phenotypes including the low and high exacerbation risk phenotypes and the neglected asthma-COPD overlap syndrome (ACOS).,These clinical phenotypes can help clinicians to identify patients that respond to specific pharmacological interventions.,For the low exacerbation risk phenotype, pharmacotherapy with short-acting β2-agonists (salbutamol, terbutaline) or anticholinergics (ipratropium) or their combination (fenoterol-ipratropium) is recommended in patients with less symptoms.,If short-acting bronchodilators are not enough to control symptoms, a long-acting β2-agonist (formoterol, indacaterol, olodaterol or salmeterol) or a long-acting anticholinergic (muscarinic receptor antagonists; aclidinium, glycopyrronium, tiotropium, umeclidinium) or their combination is recommended.,For the high exacerbation risk phenotype, pharmacotherapy with a long-acting anticholinergic or a fixed combination of an inhaled glucocorticoid and a long-acting β2-agonist (budesonide-formoterol, beclomethasone dipropionate-formoterol, fluticasone propionate-salmeterol or fluticasone furoate-vilanterol) is recommended as a first choice.,Other treatment options for this phenotype include combination of long-acting bronchodilators given from separate inhalers or as a fixed combination (glycopyrronium-indacaterol or umeclidinium-vilanterol) or a triple combination of an inhaled glucocorticoid, a long-acting β2-agonist and a long-acting anticholinergic.,If the patient has severe-to-very severe COPD (FEV1 < 50% predicted), chronic bronchitis and frequent exacerbations despite long-acting bronchodilators, the pharmacotherapy may include also roflumilast.,ACOS is a phenotype of COPD in which there are features that comply with both asthma and COPD.,Patients belonging to this phenotype have usually been excluded from studies evaluating the effects of drugs both in asthma and in COPD.,Thus, evidence-based recommendation of treatment cannot be given.,The treatment should cover both diseases.,Generally, the therapy should include at least inhaled glucocorticoids (beclomethasone dipropionate, budesonide, ciclesonide, fluticasone furoate, fluticasone propionate or mometasone) combined with a long-acting bronchodilator (β2-agonist or anticholinergic or both). | 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 |
The optimal use of various therapeutic combinations for moderate/severe chronic obstructive pulmonary disease (COPD) is unclear.,The GLISTEN trial compared the efficacy of two long-acting anti-muscarinic antagonists (LAMA), when combined with an inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA).,This randomised, blinded, placebo-controlled trial in moderate/severe COPD patients compared once-daily glycopyrronium (GLY) 50 µg, once-daily tiotropium (TIO) 18 µg or placebo (PLA), when combined with salmeterol/fluticasone propionate (SAL/FP) 50/500 µg twice daily.,The primary objective was to determine the non-inferiority of GLY+SAL/FP versus TIO+SAL/FP on trough FEV1 after 12 weeks.,An important secondary objective was whether addition of GLY to SAL/FP was better than SAL/FP alone.,773 patients (mean FEV1 57.2% predicted) were randomised; 84.9% completed the trial.,At week 12, GLY+SAL/FP demonstrated non-inferiority to TIO+SAL/FP for trough FEV1: least square mean treatment difference (LSMdiff) −7 mL (SE 17.4) with a lower limit for non-inferiority of −60 mL.,There was significant increase in week 12 trough FEV1 with GLY+SAL/FP versus PLA+SAL/FP (LSMdiff 101 mL, p<0.001).,At 12 weeks, GLY+SAL/FP produced significant improvement in St George's Respiratory Questionnaire total score versus PLA+SAL/FP (LSMdiff −2.154, p=0.02).,GLY+SAL/FP demonstrated significant rescue medication reduction versus PLA+SAL/FP (LSMdiff −0.72 puffs/day, p<0.001).,Serious adverse events were similar for GLY+SAL/FP, TIO+SAL/FP and PLA+SAL/FP with an incidence of 5.8%, 8.5% and 5.8%, respectively.,GLY+SAL/FP showed comparable improvements in lung function, health status and rescue medication to TIO+SAL/FP.,Importantly, addition of GLY to SAL/FP demonstrated significant improvements in lung function, health status and rescue medication compared to SAL/FP.,NCT01513460. | Little is known about the role of guidelines for the practical management of chronic obstructive pulmonary disease (COPD) by office-based pulmonary specialists.,The aim of this study was to assess their outpatient management in relation to current guideline recommendations for COPD.,A nationwide prospective cross-sectional COPD questionnaire survey in the form of a multiple-choice questionnaire was sent to 1000 office-based respiratory specialists in Germany.,The product-neutral questions focused on routine COPD management and were based on current national and international COPD guideline recommendations being consistent in severity classification and treatment recommendations.,A total of 590 pulmonary specialists (59%) participated in the survey.,Body plethysmography was considered the standard for diagnosis (65.9%), followed by spirometry (32%).,Most respondents were able to cite the correct spirometric criteria for classifying moderate (87%) to very severe COPD (77%).,A quarter of the respondents equated the World Health Organization (WHO) definition of chronic bronchitis with COPD.,Notably, most participants preferred the updated national COPD guidelines (51.4%) to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines (40.2%).,Improvement of functional exercise capacity and quality of life were considered the two most relevant treatment goals; whereas impact on mortality was secondary.,Treatment of COPD largely complied with the guidelines.,However, a significant percentage of the pulmonary specialists differed in their assessment of the benefits of various therapeutic measures from evidence-based results.,Referral for pulmonary rehabilitation was uncommon, regardless of the severity of COPD.,The findings of this large national survey suggest that most pulmonary specialists adhere to the current COPD guideline recommendations in daily practice.,However, physicians’ knowledge of guidelines is not sufficient as the sole benchmark when assessing their implementation in day-to-day practice.,Necessary changes in the health care system must include more effective ways to transfer knowledge to clinical practice and to give access to interventions of proven clinical benefit. | 1 |
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. | To explore the acute systemic inflammatory and anabolic effects of cycling in hospital admitted patients with chronic obstructive pulmonary disease (COPD) and in patients with clinically stable disease.,Cross-sectional comparative study.,University Hospital Gasthuisberg, a tertiary care setting.,16 patients with clinically stable COPD (no acute exacerbation in the past 12 weeks; median age: 73 years (IQR: 60 to 75); median forced expiratory volume in the first second (FEV1): 45% predicted (IQR: 33 to 58)) and 14 patients who were admitted to a hospital due an acute exacerbation of COPD (median age: 65 years (IQR: 59 to 74); median FEV1 to on day 8 of hospital stay: 41% predicted (IQR: 33 to 54)).,None.,Circulating levels of C reactive protein, interleukin 6, interleukin 8 and insulin-like growth factor I were determined before, at the end and 2 and 30 minutes after a symptom-limited peak cycling test and before, at the end and 2 and 30 minutes after a symptom-limited constant-work-rate cycling test at 70% of the peak load.,Non-significant changes in the circulating markers of inflammation and anabolism were found during or up to 30 minutes after ceasing the peak or constant-work-rate cycling exercise tests.,The systemic responses of the hospitalized patients with COPD did not differ from those with clinically stable disease.,High-intensity cycling exercises did not increase the circulating levels of inflammatory markers in patients with chronic obstructive pulmonary disease, irrespective of their clinical stability. | 1 |
This study was performed to evaluate the effect of sex on bronchial parameters and the predicted forced expiratory volume in 1 s expressed as a percentage of the forced vital capacity (FEV1% pred) on pulmonary function testing.,The data of 359 patients with chronic obstructive pulmonary disease (COPD) with available FEV1% pred and computed tomography (CT) images were retrospectively reviewed.,FACT-Digital lung TM software (DeXin, Xi’an, China) was used to perform fully automated three-dimensional CT quantitative measurements of the bronchi.,Generation 5 to 7 bronchi were measured, and the parameters analyzed were the lumen diameter (LD), wall thickness (WT), lumen area (LA), and WA% [WA / (WA + LA) × 100%].,In the smoking, smoking cessation, and nonsmoking groups, women had a significantly larger WA% and smaller LD, WT, and LA than men.,The FEV1% pred was significantly lower in women than men in the smoking and smoking cessation groups.,The FEV1% pred was significantly higher in women than men in the nonsmoking group.,Sex-related differences may partially explain why smoking women experience more severe pulmonary function impairment than men among patients with COPD. | Never smokers comprise a substantial proportion of patients with COPD.,Their characteristics and possible risk factors in this population are not yet well defined.,We analyzed data from 14 countries that participated in the international, population-based Burden of Obstructive Lung Disease (BOLD) study.,Participants were aged ≥ 40 years and completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors.,A diagnosis of COPD was based on the postbronchodilator FEV1/FVC ratio, according to current GOLD (Global Initiative for Obstructive Lung Disease) guidelines.,In addition to this, the lower limit of normal (LLN) was evaluated as an alternative threshold for the FEV1/FVC ratio.,Among 4,291 never smokers, 6.6% met criteria for mild (GOLD stage I) COPD, and 5.6% met criteria for moderate to very severe (GOLD stage II+) COPD.,Although never smokers were less likely to have COPD and had less severe COPD than ever smokers, never smokers nonetheless comprised 23.3% (240/1,031) of those classified with GOLD stage II+ COPD.,This proportion was similar, 20.5% (171/832), even when the LLN was used as a threshold for the FEV1/FVC ratio.,Predictors of COPD in never smokers include age, education, occupational exposure, childhood respiratory diseases, and BMI alterations.,This multicenter international study confirms previous evidence that never smokers comprise a substantial proportion of individuals with COPD.,Our data suggest that, in addition to increased age, a prior diagnosis of asthma and, among women, lower education levels are associated with an increased risk for COPD among never smokers. | 1 |
The study evaluated the efficacy of beclomethasone dipropionate/formoterol fumarate (BDP/FF) extrafine combination versus fluticasone propionate/salmeterol (FP/S) combination in COPD patients.,The trial was a 12-week multicentre, randomised, double-blind, double dummy study; 419 patients with moderate/severe COPD were randomised to BDP/FF 200/12 μg or FP/S 500/50 μg twice daily.,The primary objective was to demonstrate the equivalence between treatments in terms of Transition Dyspnoea Index (TDI) score and the superiority of BDP/FF in terms of change from pre-dose in the first 30 minutes in forced expiratory volume in the first second (FEV1).,Secondary endpoints included lung function, symptom scores, symptom-free days and use of rescue medication, St.,George’s Respiratory Questionnaire, six minute walking test and COPD exacerbations.,BDP/FF was equivalent to FP/S in terms of TDI score and superior in terms of FEV1 change from pre-dose (p < 0.001).,There were no significant differences between treatments in secondary outcome measures, confirming overall comparability in terms of efficacy and tolerability.,Moreover, a clinically relevant improvement (>4 units) in SGRQ was detected in the BDP/FF group only.,BDP/FF extrafine combination provides COPD patients with an equivalent improvement of dyspnoea and a faster bronchodilation in comparison to FP/S.,ClinicalTrials.gov: NCT01245569 | Tiotropium is reimbursed since March 2004 in Belgium for the treatment of Chronic Obstructive Pulmonary Disease (COPD).,Questions however remain on this product's value for money.,The purpose of this study is to calculate tiotropium's cost-effectiveness under real-world conditions.,Strengths of both observational and RCT data were combined in a model.,A large longitudinal (2002-2006) observational dataset of regular tiotropium users (56 321 patients) was analysed to retrieve the baseline risk for exacerbations and exacerbation-related hospitalisations the year before the first delivery of tiotropium.,The relative treatment effect from the UPLIFT (Understanding Potential Long-term Impacts on Function with Tiotropium) trial was then applied to this baseline risk to reflect the effect of tiotropium treatment and calculate the intervention's incremental cost-effectiveness ratio (ICER).,After 1000 Latin Hypercube simulations, the incremental benefit expressed as quality-adjusted life years (QALY) gained is on average 0.00048 (95% confidence interval (CI) 0.00009 - 0.00092).,In combination with a substantial mean incremental cost of €373 per patient (95% CI 279 - 475), this results in an unfavourable average ICER of €1 244 023 (95% CI 328 571 - 4 712 704) per QALY gained.,Results were most sensitive to the treatment effect on hospitalisations.,Based on our large observational database, up to 89% of the patients were not hospitalised for COPD in the year before the first tiotropium delivery.,The main cause for tiotropium's unfavourable cost-effectiveness ratio is a combination of a relative high price for tiotropium, a low number of hospitalisations without tiotropium treatment (on average 0.14/year) and a non-significant treatment effect (on average 0.94) with respect to avoiding exacerbation-related hospitalisations.,From an economic point of view, a revision of reimbursement modalities (e.g. with a lower price) would be justified and would entail a more efficient use of resources. | 1 |
High blood eosinophil count is a predictive biomarker for response to inhaled corticosteroids in prevention of acute exacerbation of COPD, and low blood eosinophil count is associated with pneumonia risk in COPD patients taking inhaled corticosteroids.,However, the prognostic role of blood eosinophil count remains underexplored.,Therefore, we investigated the associated factors and mortality based on blood eosinophil count in COPD.,Patients with COPD were recruited from 16 hospitals of the Korean Obstructive Lung Disease cohort (n=395) and COPD in Dusty Area cohort (n=234) of Kangwon University Hospital.,The two merged cohorts were divided based on blood eosinophil count into three groups: high (≥5%), middle (2%-5%), and low (<2%).,The high group had longer six-minute walk distance (high =445.8±81.4, middle =428.5±88.0, and low =414.7±86.3 m), higher body mass index (23.3±3.1, 23.1±3.1, and 22.5±3.2 kg/m2), lower emphysema index (18.5±14.1, 22.2±15.3, and 23.7±16.3), and higher inspiratory capacity/total lung capacity ratio (32.6±7.4, 32.4±9.2, and 29.9% ± 8.9%) (P<0.05).,The survival period increased with increasing blood eosinophil count (high =9.52±0.23, middle =8.47±1.94, and low =7.42±0.27 years, P<0.05).,Multivariate linear regression analysis revealed that the emphysema index was independently and negatively correlated with blood eosinophil count (P<0.05).,In COPD, the severity of emphysema was independently linked with low blood eosinophil count and the longer survival period was associated with increased blood eosinophil count, though it was not proven in the multivariate analysis. | Sputum eosinophilia occurs in approximately one-third of stable chronic obstructive pulmonary disease (COPD) patients and can predict exacerbation risk and response to corticosteroid treatments.,Sputum induction, however, requires expertise, may not always be successful, and does not provide point-of-care results.,Easily applicable diagnostic markers that can predict sputum eosinophilia in stable COPD patients have the potential to progress COPD management.,This study investigated the correlation and predictive relationship between peripheral blood and sputum eosinophils.,It also examined the repeatability of blood eosinophil counts.,Stable COPD patients (n=141) were classified as eosinophilic or noneosinophilic based on their sputum cell counts (≥3%), and a cross-sectional analysis was conducted comparing their demographics, clinical characteristics, and blood cell counts.,Receiver operating characteristic curve analysis was used to assess the predictive ability of blood eosinophils for sputum eosinophilia.,Intraclass correlation coefficient was used to examine the repeatability of blood eosinophil counts.,Blood eosinophil counts were significantly higher in patients with sputum eosinophilia (n=45) compared to those without (0.3×109/L vs 0.15×109/L; P<0.0001).,Blood eosinophils correlated with both the percentage (ρ=0.535; P<0.0001) and number of sputum eosinophils (ρ=0.473; P<0.0001).,Absolute blood eosinophil count was predictive of sputum eosinophilia (area under the curve =0.76, 95% confidence interval [CI] =0.67-0.84; P<0.0001).,At a threshold of ≥0.3×109/L (specificity =76%, sensitivity =60%, and positive likelihood ratio =2.5), peripheral blood eosinophil counts enabled identification of the presence or absence of sputum eosinophilia in 71% of the cases.,A threshold of ≥0.4×109/L had similar classifying ability but better specificity (91.7%) and higher positive likelihood ratio (3.7).,In contrast, ≥0.2×109/L offered a better sensitivity (91.1%) for ruling out sputum eosinophilia.,There was a good agreement between two measurements of blood eosinophil count over a median of 28 days (intraclass correlation coefficient =0.8; 95% CI =0.66-0.88; P<0.0001).,Peripheral blood eosinophil counts can help identify the presence or absence of sputum eosinophilia in stable COPD patients with a reasonable degree of accuracy. | 1 |
Previous clinical audits of COPD have provided relevant information about medical intervention in exacerbation admissions.,The present study aims to evaluate adherence to current guidelines in COPD through a clinical audit.,This is a pilot clinical audit performed in hospital outpatient respiratory clinics in Andalusia, Spain (eight provinces with more than 8 million inhabitants), including 9 centers (20% of the public centers in the area) between 2013 and 2014.,Cases with an established diagnosis of COPD based on risk factors, clinical symptoms, and a post-bronchodilator FEV1/FVC ratio of less than 0.70 were deemed eligible.,The performance of the outpatient clinics was benchmarked against three guidance documents available at the time of the audit.,The appropriateness of the performance was categorized as excellent (>80%), good (60−80%), adequate (40−59%), inadequate (20−39%), and highly inadequate (<20%).,During the audit, 621 clinical records were audited.,Adherence to the different guidelines presented a considerable variability among the different participating hospitals, with an excellent or good adherence for symptom recording, MRC or CAT use, smoking status evaluation, spirometry, or bronchodilation therapy.,The most outstanding areas for improvement were the use of the BODE index, the monitoring of treatments, the determination of alpha1-antitrypsin, the performance of exercise testing, and vaccination recommendations.,The present study reflects the situation of clinical care for COPD patients in specialized secondary care outpatient clinics.,Adherence to clinical guidelines shows considerable variability in outpatient clinics managing COPD patients, and some aspects of the clinical care can clearly be improved. | A combination of inhaled corticosteroid and long-acting beta2 agonist (ICS/LABA) is used frequently to treat chronic obstructive pulmonary disease (COPD) patients.,The aim of the study was to determine whether prescribing ICS/LABA to COPD patients in primary care in 2009/10 was within the GOLD guidelines and whether and to what degree patient characteristics were associated with prescription of these drugs by GPs.,This was a cross-sectional study in seven Norwegian GP practices.,Patients registered with a diagnosis of asthma or COPD in the previous five years were included.,Among the 376 patients included in the analysis, 149 patients had COPD, defined as a post-bronchodilator FEV1/FVC <0.7 and 55.6% of these patients were treated with ICS/LABA.,The rate of prescribing was significantly higher in the COPD patients also diagnosed with asthma than in those with COPD as the only diagnosis, 66.7%, and 39.0%, respectively (P = 0.001).,The prescribing rate in the latter subgroup would have been 18.6% if the 2007 GOLD guidelines had been followed.,One or more exacerbations in the previous year was the strongest predictor of ICS/LABA prescribing in the COPD patients who were not registered with a concomitant diagnosis of asthma (OR 3.2, 95% CI 1.0-10.0) but this association was limited to the patients with severe disease (FEV1% predicted <50) (OR 13.5, 95% CI 1.8-101.1).,Cardiovascular disease was associated with decreased ICS/LABA prescribing (OR 0.4, 95% CI 0.2-0.8) in the COPD group.,A Kappa coefficient of 0.32 was found between the actual prescribing rate and that recommended in the 2007 GOLD guidelines.,Overprescribing of ICS/LABA for the COPD patients was shown.,Previous exacerbation was a strong predictor of ICS/LABA prescribing only in patients with severe COPD.,Because of the low emphasis on previous exacerbation when prescribing for COPD patients with mild to moderate disease, the actual prescribing rate agreed more closely with the GOLD guidelines from 2007 than with those published in 2011.,Cardiovascular disease was associated with decreased prescribing, indicating that GPs adjust the treatment in cases with multimorbidity. | 1 |
Purpose: Global evidence-based treatment strategies for chronic obstructive pulmonary disease (COPD) recommend using long-acting bronchodilators (LABDs) as maintenance therapy.,However, COPD patients are often undertreated.,We examined COPD treatment patterns among Medicare beneficiaries who initiated arformoterol tartrate, a nebulized long-acting beta2 agonist (LABA), and identified the predictors of initiation.,Methods: Using a 100% sample of Medicare administrative data, we identified beneficiaries with a COPD diagnosis (ICD-9 490-492.xx, 494.xx, 496.xx) between 2010 and 2014 who had ≥1 year of continuous enrollment in Parts A, B, and D, and ≥2 COPD-related outpatient visits within 30 days or ≥1 hospitalization(s).,After applying inclusion/exclusion criteria, three cohorts were identified: (1) study group beneficiaries who received nebulized arformoterol (n=11,886), (2) a subset of the study group with no LABD use 90 days prior to initiating arformoterol (n=5,542), and (3) control group beneficiaries with no nebulized LABA use (n=220,429).,Logistic regression was used to evaluate predictors of arformoterol initiation.,Odds ratios (ORs), 95% confidence intervals (CIs), and p values were computed.,Results: Among arformoterol users, 47% (n=5,542) had received no LABDs 90 days prior to initiating arformoterol.,These beneficiaries were being treated with a nebulized (50%) or inhaled (37%) short-acting bronchodilator or a systemic corticosteroid (46%), and many received antibiotics (37%).,Compared to controls, beneficiaries who initiated arformoterol were significantly more likely to have had an exacerbation, a COPD-related hospitalization, and a pulmonologist or respiratory therapist visit prior to initiation (all p<0.05).,Beneficiaries with moderate/severe psychiatric comorbidity or dual-eligible status were significantly less likely to initiate arformoterol, as compared to controls (all p<0.05).,Conclusion: Medicare beneficiaries who initiated nebulized arformoterol therapy had more exacerbations and hospitalizations than controls 90 days prior to initiation.,Findings revealed inadequate use of maintenance medications, suggesting a lack of compliance with evidence-based treatment guidelines. | 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) outpatients account for a large burden of usual care by respirologists.,EPOCONSUL is the first national clinical audit conducted in Spain on the medical care for COPD patients delivered in outpatient respiratory clinics.,We aimed to evaluate the clinical interventions and the degree of adherence to recommendations in outpatients of current COPD clinical practice guidelines.,This is an observational study with prospective recruitment (May 2014-May 2015) of patients with a COPD diagnosis as seen in outpatient respiratory clinics.,The information collected was historical in nature as for the clinical data of the last and previous consultations, and the information concerning hospital resources was concurrent.,A total of 17,893 clinical records of COPD patients in outpatient respiratory clinics from 59 Spanish hospitals were evaluated.,Of the 5,726 patients selected, 4,508 (78.7%) were eligible.,Overall, 12.1% of COPD patients did not fulfill a diagnostic spirometry criteria.,Considerable variability existed in the available resources and work organization of the hospitals, although the majority were university hospitals with respiratory inpatient units.,There was insufficient implementation of clinical guidelines in preventive and educational matters.,In contrast, quantitative evaluation of dyspnea grade (81.9%) and exacerbation history (70.9%) were more frequently performed.,Only 12.4% had COPD severity calculated according to the Body mass index, airflow Obstruction, Dyspnoea and Exercise capacity (BODE) index.,Phenotype characteristics according to Spanish National Guideline for COPD were determined in 46.3% of the audited patients, and the risk evaluation according to Global initiative for chronic Obstructive Lung Disease was estimated only in 21.9%.,The EPOCONSUL study reports the current situation of medical care for COPD patients in outpatient clinics in Spain, revealing its variability, strengths, and weaknesses.,This information has to be accounted for by health managers to define corrective strategies and maximize good clinical practice. | 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 |
Studies of patients admitted to hospital with COVID-19 have found varying mortality outcomes associated with underlying respiratory conditions and inhaled corticosteroid use.,Using data from a national, multicentre, prospective cohort, we aimed to characterise people with COVID-19 admitted to hospital with underlying respiratory disease, assess the level of care received, measure in-hospital mortality, and examine the effect of inhaled corticosteroid use.,We analysed data from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study.,All patients admitted to hospital with COVID-19 across England, Scotland, and Wales between Jan 17 and Aug 3, 2020, were eligible for inclusion in this analysis.,Patients with asthma, chronic pulmonary disease, or both, were identified and stratified by age (<16 years, 16-49 years, and ≥50 years).,In-hospital mortality was measured by use of multilevel Cox proportional hazards, adjusting for demographics, comorbidities, and medications (inhaled corticosteroids, short-acting β-agonists [SABAs], and long-acting β-agonists [LABAs]).,Patients with asthma who were taking an inhaled corticosteroid plus LABA plus another maintenance asthma medication were considered to have severe asthma.,75 463 patients from 258 participating health-care facilities were included in this analysis: 860 patients younger than 16 years (74 [8·6%] with asthma), 8950 patients aged 16-49 years (1867 [20·9%] with asthma), and 65 653 patients aged 50 years and older (5918 [9·0%] with asthma, 10 266 [15·6%] with chronic pulmonary disease, and 2071 [3·2%] with both asthma and chronic pulmonary disease).,Patients with asthma were significantly more likely than those without asthma to receive critical care (patients aged 16-49 years: adjusted odds ratio [OR] 1·20 [95% CI 1·05-1·37]; p=0·0080; patients aged ≥50 years: adjusted OR 1·17 [1·08-1·27]; p<0·0001), and patients aged 50 years and older with chronic pulmonary disease (with or without asthma) were significantly less likely than those without a respiratory condition to receive critical care (adjusted OR 0·66 [0·60-0·72] for those without asthma and 0·74 [0·62-0·87] for those with asthma; p<0·0001 for both).,In patients aged 16-49 years, only those with severe asthma had a significant increase in mortality compared to those with no asthma (adjusted hazard ratio [HR] 1·17 [95% CI 0·73-1·86] for those on no asthma therapy, 0·99 [0·61-1·58] for those on SABAs only, 0·94 [0·62-1·43] for those on inhaled corticosteroids only, 1·02 [0·67-1·54] for those on inhaled corticosteroids plus LABAs, and 1·96 [1·25-3·08] for those with severe asthma).,Among patients aged 50 years and older, those with chronic pulmonary disease had a significantly increased mortality risk, regardless of inhaled corticosteroid use, compared to patients without an underlying respiratory condition (adjusted HR 1·16 [95% CI 1·12-1·22] for those not on inhaled corticosteroids, and 1·10 [1·04-1·16] for those on inhaled corticosteroids; p<0·0001).,Patients aged 50 years and older with severe asthma also had an increased mortality risk compared to those not on asthma therapy (adjusted HR 1·24 [95% CI 1·04-1·49]).,In patients aged 50 years and older, inhaled corticosteroid use within 2 weeks of hospital admission was associated with decreased mortality in those with asthma, compared to those without an underlying respiratory condition (adjusted HR 0·86 [95% CI 0·80−0·92]).,Underlying respiratory conditions are common in patients admitted to hospital with COVID-19.,Regardless of the severity of symptoms at admission and comorbidities, patients with asthma were more likely, and those with chronic pulmonary disease less likely, to receive critical care than patients without an underlying respiratory condition.,In patients aged 16 years and older, severe asthma was associated with increased mortality compared to non-severe asthma.,In patients aged 50 years and older, inhaled corticosteroid use in those with asthma was associated with lower mortality than in patients without an underlying respiratory condition; patients with chronic pulmonary disease had significantly increased mortality compared to those with no underlying respiratory condition, regardless of inhaled corticosteroid use.,Our results suggest that the use of inhaled corticosteroids, within 2 weeks of admission, improves survival for patients aged 50 years and older with asthma, but not for those with chronic pulmonary disease.,National Institute for Health Research, Medical Research Council, NIHR Health Protection Research Units in Emerging and Zoonotic Infections at the University of Liverpool and in Respiratory Infections at Imperial College London in partnership with Public Health England. | The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) a pandemic [1].,COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,COVID-19 displays symptoms ranging from mild to severe (pneumonia) that can lead to death in some individuals [2-4].,As of 18 April 2020, there have been 2 280 945 cases of COVID-19 worldwide and 156 354 deaths [5].,SARS-CoV-2 uses the angiotensin-converting enzyme II (ACE-2) as the cellular entry receptor [6].,While the virus can infect individuals of any age, to date, most of the severe cases have been described in those >55 years of age and with significant comorbidities, such as COPD [7].,Here, we determined whether patients with COPD have increased expression of ACE-2 in bronchial epithelial cells in the lower respiratory tract.,Smokers and those with COPD have increased airway expression of ACE-2, which is the entry receptor for the COVID-19 virus.,This may explain the increased risk of severe COVID-19 in these subpopulations and highlight the importance of smoking cessation.https://bit.ly/3bC29es | 1 |
Readmission rates following hospitalisation for COPD exacerbations are unacceptably high, and the contributing factors are poorly understood.,Our objective was to summarise and evaluate the factors associated with 30- and 90-day all-cause readmission following hospitalisation for an exacerbation of COPD.,We systematically searched electronic databases from inception to 5 November 2019.,Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.,Study quality was assessed using a modified version of the Newcastle-Ottawa Scale.,We synthesised a narrative from eligible studies and conducted a meta-analysis where this was possible using a random-effects model.,In total, 3533 abstracts were screened and 208 full-text manuscripts were reviewed.,A total of 32 papers met the inclusion criteria, and 14 studies were included in the meta-analysis.,The readmission rate ranged from 8.8-26.0% at 30 days and from 17.5-39.0% at 90 days.,Our narrative synthesis showed that comorbidities, previous exacerbations and hospitalisations, and increased length of initial hospital stay were the major risk factors for readmission at 30 and 90 days.,Pooled adjusted odds ratios (95% confidence intervals) revealed that heart failure (1.29 (1.22-1.37)), renal failure (1.26 (1.19-1.33)), depression (1.19 (1.05-1.34)) and alcohol use (1.11 (1.07-1.16)) were all associated with an increased risk of 30-day all-cause readmission, whereas being female was a protective factor (0.91 (0.88-0.94)).,Comorbidities, previous exacerbations and hospitalisation, and increased length of stay were significant risk factors for 30- and 90-day all-cause readmission after an index hospitalisation with an exacerbation of COPD.,Clinicians need to take a holistic approach including attention to comorbidities in the pre-discharge care of patients with COPD exacerbations to reduce the potential risk of readmission.http://bit.ly/2sucXKV | Pulmonary rehabilitation (PR) is recommended in the management of people with chronic obstructive pulmonary disease (COPD), but referral to this service is low.,To identify barriers to, and facilitators for, referral to PR programmes from the perspective of Australian general practitioners.,Semi-structured interviews were conducted with general practitioners involved in the care of people with COPD.,Interview questions were informed by a validated behavioural framework and asked about participants’ experience of referring people with COPD for PR, and barriers to, or facilitators of, this behaviour.,Interviews were audiotaped, transcribed verbatim, and analysed using content analysis.,Twelve general practitioners participated in this study, 10 of whom had never referred a patient to a PR programme.,Four major categories relating to barriers to referral were identified: low knowledge of PR for COPD; low knowledge of how to refer; actual or anticipated access difficulties for patients; and questioning the need to do more to promote exercise behaviour change.,Awareness of benefit was the only current facilitator.,Three major categories of potential facilitators were identified: making PR part of standard COPD care through financial incentive; improving information flow with regard to referrals and services; and informing patients and public.,Significant barriers to referral exist, but opportunities to change the organisation of practice and information management were identified.,Behaviour change strategies which directly target these barriers and incorporate facilitators should make up the key components of interventions to improve referral to PR by general practitioners who care for people with COPD. | 1 |
Both chronic Obstruction Pulmonary Disease (COPD) and lung cancer are leading causes of death globally.,Although COPD and lung cancer coexist frequently, it is unknown whether lung cancer patients with COPD harbor distinct genomic characteristics compared to those without COPD.,In this study, we retrospectively analyzed genomic sequencing data from 272 patients with lung adenocarcinoma (LUAD) and compared the genetic alterations in LUAD patients with and without COPD.,Integrative analysis of whole-genome and exome sequencing data revealed that COPD and non-COPD groups showed high concordance in mutational burden and spectra.,Notably, we also found that EGFR mutations were more prevalent in LUAD patients without COPD, whereas mutated LRP1B was more frequently observed in LUAD patients with COPD.,In addition, multi-variable analysis with logistic regression demonstrated that mutation of LRP1B was a predictive marker for the presence of COPD in the patients with LUAD.,Our analysis demonstrated for the first time the high concordance in genomic alterations between the tumors from LUAD patients with and without COPD.,We also identified higher prevalence of LRP1B among the LUAD patients with COPD, which might help understand the underlying mechanisms which link COPD and lung cancer. | Cellular senescence has been associated with the structural and functional decline observed during physiological lung aging and in chronic obstructive pulmonary disease (COPD).,Airway epithelial cells are the first line of defense in the lungs and are important to COPD pathogenesis.,However, the mechanisms underlying airway epithelial cell senescence, and particularly the role of telomere dysfunction in this process, are poorly understood.,We aimed to investigate telomere dysfunction in airway epithelial cells from patients with COPD, in the aging murine lung and following cigarette smoke exposure.,We evaluated colocalization of γ-histone protein 2A.X and telomeres and telomere length in small airway epithelial cells from patients with COPD, during murine lung aging, and following cigarette smoke exposure in vivo and in vitro.,We found that telomere-associated DNA damage foci increase in small airway epithelial cells from patients with COPD, without significant telomere shortening detected.,With age, telomere-associated foci increase in small airway epithelial cells of the murine lung, which is accelerated by cigarette smoke exposure.,Moreover, telomere-associated foci predict age-dependent emphysema, and late-generation Terc null mice, which harbor dysfunctional telomeres, show early-onset emphysema.,We found that cigarette smoke accelerates telomere dysfunction via reactive oxygen species in vitro and may be associated with ataxia telangiectasia mutated-dependent secretion of inflammatory cytokines interleukin-6 and -8.,We propose that telomeres are highly sensitive to cigarette smoke-induced damage, and telomere dysfunction may underlie decline of lung function observed during aging and in COPD. | 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. | Umeclidinium (UMEC; long-acting muscarinic antagonist) plus vilanterol (VI; long-acting beta2 agonist [LABA]) and the LABA/inhaled corticosteroid fluticasone propionate/salmeterol (FP/SAL) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD).,This 12-week, multicentre, double-blind, parallel-group, double-dummy study compared the efficacy and safety of these treatments in symptomatic patients with moderate-to-severe COPD with no exacerbations in the year prior to enrolment.,Patients (n = 717) were randomised 1:1 to once-daily UMEC/VI 62.5/25 mcg or twice-daily FP/SAL 500/50 mcg.,Endpoints included 0-24 h weighted mean (wm) forced expiratory volume in 1 s (FEV1) (Day 84; primary), trough FEV1 (Day 85; secondary), other lung function endpoints, symptoms, quality of life (QoL) and safety.,Improvements with UMEC/VI versus FP/SAL were 0.080 L (95 % confidence interval: 0.046-0.113; wmFEV1) and 0.090 L (0.055-0.125; trough FEV1) (both p < 0.001).,UMEC/VI statistically significantly improved all other lung function measures versus FP/SAL.,Both treatments demonstrated a clinically meaningful improvement in symptoms (Transition Dyspnoea Index ≥1 unit) and QoL (St George’s Respiratory Questionnaire Total score ≥4 unit decrease from baseline) over 12 weeks.,The incidence of adverse events was 28 % (UMEC/VI) and 29 % (FP/SAL); nasopharyngitis and headache were most common.,Once-daily UMEC/VI 62.5/25 mcg over 12 weeks resulted in significant and sustained improvements in lung function versus twice-daily FP/SAL 500/50 mcg in patients with moderate-to-severe COPD and with no exacerbations in the year prior to enrolment.,NCT01822899 Registration date: March 28, 2013,The online version of this article (doi:10.1186/s12890-015-0092-1) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) patients are at increased risk of poor outcome from Coronavirus disease (COVID-19).,Early data suggest elevated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) receptor angiotensin converting enzyme 2 (ACE2) expression, but relationships to disease phenotype and downstream regulators of inflammation in the Renin-Angiotensin system (RAS) are unknown.,We aimed to determine the relationship between RAS gene expression relevant to SARS-CoV-2 infection in the lung with disease characteristics in COPD, and the regulation of newly identified SARS-CoV-2 receptors and spike-cleaving proteases, important for SARS-CoV-2 infection.,We quantified gene expression using RNA sequencing of epithelial brushings and bronchial biopsies from 31 COPD and 37 control subjects.,ACE2 gene expression (log2-fold change (FC)) was increased in COPD compared to ex-smoking (HV-ES) controls in epithelial brushings (0.25, p = 0.042) and bronchial biopsies (0.23, p = 0.050), and correlated with worse lung function (r = − 0.28, p = 0.0090).,ACE2 was further increased in frequent exacerbators compared to infrequent exacerbators (0.51, p = 0.00045) and associated with use of ACE inhibitors (ACEi) (0.50, p = 0.0034), having cardiovascular disease (0.23, p = 0.048) or hypertension (0.34, p = 0.0089), and inhaled corticosteroid use in COPD subjects in bronchial biopsies (0.33, p = 0.049).,Angiotensin II receptor type (AGTR)1 and 2 expression was decreased in COPD bronchial biopsies compared to HV-ES controls with log2FC of -0.26 (p = 0.033) and − 0.40, (p = 0.0010), respectively.,However, the AGTR1:2 ratio was increased in COPD subjects compared with HV-ES controls, log2FC of 0.57 (p = 0.0051).,Basigin, a newly identified potential SARS-CoV-2 receptor was also upregulated in both brushes, log2FC of 0.17 (p = 0.0040), and bronchial biopsies, (log2FC of 0.18 (p = 0.017), in COPD vs HV-ES.,Transmembrane protease, serine (TMPRSS)2 was not differentially regulated between control and COPD.,However, various other spike-cleaving proteases were, including TMPRSS4 and Cathepsin B, in both epithelial brushes (log2FC of 0.25 (p = 0.0012) and log2FC of 0.56 (p = 5.49E−06), respectively) and bronchial biopsies (log2FC of 0.49 (p = 0.00021) and log2FC of 0.246 (p = 0.028), respectively).,This study identifies key differences in expression of genes related to susceptibility and aetiology of COVID-19 within the COPD lung.,Further studies to understand the impact on clinical course of disease are now required.,The online version contains supplementary material available at 10.1186/s12931-021-01755-3. | Currently, chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide.,The determination of immune mechanisms of inflammation in the disease presents an important challenge for fundamental medical research.,According to modern views, Toll-like receptors (TLRs), among which TLR2 and TLR4 play a key role, are one of the essential components of inflammatory process in COPD.,This review focuses on following aspects: the role of TLR2 and TLR4 in the initiation of inflammatory process in COPD; the mechanisms of influence of various exogenous factors (cigarette smoke, suspended particulate matter, and bacteria) on the expression of TLR2 and TLR4; the contribution of these TLRs to the T-helper (Th) immune response development in COPD, in particular to the Th17 immune response, which contributes to the progression of the disease and therapeutic implications of TLR2 and TLR4 in COPD. | 1 |
The establishment of high-intensity (HI) noninvasive ventilation (NIV) that targets elevated PaCO2 has led to an increase in the use of long-term NIV to treat patients with chronic hypercapnic COPD.,However, the role of the ventilation interface, especially in more aggressive ventilation strategies, has not been systematically assessed.,Ventilator settings and NIV compliance were assessed in this prospective cross-sectional monocentric cohort study of COPD patients with pre-existing NIV.,Daytime arterialized blood gas analyses and lung function testing were also performed.,The primary end point was the distribution among study patients of interfaces (full-face masks [FFMs] vs nasal masks [NMs]) in a real-life setting.,The majority of the 123 patients studied used an FFM (77%), while 23% used an NM.,Ventilation settings were as follows: mean ± standard deviation (SD) inspiratory positive airway pressure (IPAP) was 23.2±4.6 mbar and mean ± SD breathing rate was 16.7±2.4/minute.,Pressure support ventilation (PSV) mode was used in 52.8% of patients, while assisted pressure-controlled ventilation (aPCV) was used in 47.2% of patients.,Higher IPAP levels were associated with an increased use of FFMs (IPAP <21 mbar: 73% vs IPAP >25 mbar: 84%).,Mean compliance was 6.5 hours/day, with no differences between FFM (6.4 hours/day) and NM (6.7 hours/day) users.,PaCO2 assessment of ventilation quality revealed comparable results among patients with FFMs or NMs.,This real-life trial identified the FFM as the predominantly used interface in COPD patients undergoing long-term NIV.,The increased application of FFMs is, therefore, likely to be influenced by higher IPAP levels, which form part of the basis for successful application of HI-NIV in clinical practice. | Background: The objective of the present analysis is to describe the outcomes of high-intensity non-invasive positive pressure ventilation (NPPV) aimed at maximally decreasing PaCO2 as an alternative to conventional NPPV with lower ventilator settings in stable hypercapnic COPD patients.,Methods: Physiological parameters, exacerbation rates and long-term survival were assessed in 73 COPD patients (mean FEV1 30±12 %predicted) who were established on high-intensity NPPV due to chronic hypercapnic respiratory failure between March 1997 and May 2006.,Results: Controlled NPPV with breathing frequencies of 21±3 breath/min and mean inspiratory/expiratory positive airway pressures of 28±5/5±1 cmH2O led to significant improvements in blood gases, lung function and hematocrit after two months.,Only sixteen patients (22%) required hospitalisation due to exacerbation during the first year, with anaemia increasing the risk for exacerbation.,Two- and five-year survival rates of all patients were 82% and 58%, respectively.,The five year survival rate was 32% and 83% in patients with low (≤39%) and high (≥55%) hematocrit, respectively.,Conclusion: High-intensity NPPV improves blood gases, lung function and hematocrit, and is also associated with low exacerbation rates and a favourable long-term outcome.,The current report strongly emphasises the need for randomised controlled trials evaluating the role of high-intensity NPPV in stable hypercapnic COPD patients. | 1 |
COPD is a highly heterogeneous disease.,Potential biomarkers to identify patients with COPD who will derive the greatest benefit from inhaled corticosteroid (ICS) treatment are needed.,Blood eosinophil count can serve as a predictive biomarker for the efficacy of ICS treatment.,The aim of this systematic review and meta-analysis was to assess whether a blood eosinophil count of ≥2% in patients undergoing ICS therapy was associated with a greater reduction in COPD exacerbation rate and pneumonia incidence.,An electronic search was performed using the keywords “COPD”, “eosinophil”, and “clinical trial” in the PubMed and EMBASE databases to retrieve articles, up to 2017, relevant to our focus.,Data were extracted, and a meta-analysis was conducted using RevMan 5 (version 5.3.5).,Five studies comprising 12,496 patients with moderate-to-very severe COPD were included.,At baseline, 60% of the patients had ≥2% blood eosinophils.,Our meta-analysis showed a 17% reduction in exacerbation of moderate/severe COPD in patients with ≥2% blood eosinophils undergoing ICS therapy compared to the non-ICS/ICS withdrawal/placebo group.,The difference between the two types of treatment was significant (risk ratio [RR], 0.816; 95% CI, 0.67-0.99; P=0.03).,Furthermore, the risk of pneumonia-related events was significantly increased in the subgroup with eosinophil count ≥2% undergoing ICS-containing treatments (RR, 1.969; 95% CI, 1.369-2.833; P<0.001).,There was no significant difference in the subgroup with eosinophil count <2% (RR, 1.29; 95% CI, 0.888-1.879; P<0.181).,The results of our meta-analysis suggest that the 2% threshold for blood eosinophils could accurately predict ICS treatment response in patients with COPD, but increased the risk of pneumonia. | Recent studies that assessed the relevance of the blood eosinophil count as a biomarker in patients with COPD may have overestimated it because they included patients with asthma-COPD overlap syndrome (ACOS).,We investigated the clinical implications of the blood eosinophil count in patients with non-ACOS COPD.,From a Korean COPD Subtype Study (KOCOSS) cohort, we selected patients with non-ACOS COPD after excluding ACOS patients according to Spanish criteria.,Clinical characteristics and the incidence of moderate-to-severe exacerbation were compared among the four groups stratified according to the quartiles of blood eosinophil percent and count.,Of the KOCOSS cohort of 1,132 patients with COPD, 467 non-ACOS COPD patients (41.2%) with data of blood eosinophil count remained after excluding those with ACOS based on the Spanish definition.,There was no difference in clinical characteristics among groups classified according to the quartiles of eosinophil percent and count.,On multivariate logistic regression, eosinophil quartiles in percent and absolute count were not associated with the incidence of moderate-to-severe acute exacerbations of COPD (AECOPD).,The eosinophil count did not affect the risk of AECOPD or forced expiratory volume in 1 second (FEV1) changes according to exposure to inhaled corticosteroid (ICS).,However, by increasing the cutoff value for the eosinophil count from 200/μL to 600/μL, the odds ratio for risk of exacerbation increased serially from 0.82 to 2.96 on trend analysis.,In patients with non-ACOS COPD, the blood eosinophil count and percent were not associated with FEV1 changes, quality of life (QoL), AECOPD frequency, or response to ICS.,The clinical implication of the blood eosinophil count should not be overestimated in patients with non-ACOS COPD. | 1 |
The aims of this systematic review were to determine which blood-based molecules have been evaluated as possible biomarkers to diagnose chronic obstructive pulmonary disease (COPD) exacerbations (AECOPD) and to ascertain the quality of these biomarker publications.,Patients of interest were those that have been diagnosed with COPD.,MEDLINE, EMBASE, and CINAHL databases were searched systematically through February 2015 for publications relating to AECOPD diagnostic biomarkers.,We used a modified guideline for the REporting of tumor MARKer Studies (mREMARK) to assess study quality.,Additional components of quality included the reporting of findings in a replication cohort and the use of receiver-operating characteristics area-under-the curve statistics in evaluating performance. 59 studies were included, in which the most studied biomarkers were C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α).,CRP showed consistent elevations in AECOPD compared to control subjects, while IL-6 and TNF-α had variable statistical significance and results. mREMARK scores ranged from 6 to 18 (median score of 13). 12 articles reported ROC analyses and only one study employed a replication cohort to confirm biomarker performance.,Studies of AECOPD diagnostic biomarkers remain inconsistent in their reporting, with few studies employing ROC analyses and even fewer demonstrating replication in independent cohorts. | The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally. | 1 |
We tested the role of endothelial dysfunction in the development of COPD/emphysema.,We found that restoration of lung endothelial cells and blockade of endothelial-derived leucine-rich α-2-glycoprotein perturbs the pathogenesis of COPD/emphysema.,Chronic obstructive pulmonary disease (COPD) is marked by airway inflammation and airspace enlargement (emphysema) leading to airflow obstruction and eventual respiratory failure.,Microvasculature dysfunction is associated with COPD/emphysema.,However, it is not known if abnormal endothelium drives COPD/emphysema pathology and/or if correcting endothelial dysfunction has therapeutic potential.,Here, we show the centrality of endothelial cells to the pathogenesis of COPD/emphysema in human tissue and using an elastase-induced murine model of emphysema.,Airspace disease showed significant endothelial cell loss, and transcriptional profiling suggested an apoptotic, angiogenic, and inflammatory state.,This alveolar destruction was rescued by intravenous delivery of healthy lung endothelial cells.,Leucine-rich α-2-glycoprotein-1 (LRG1) was a driver of emphysema, and deletion of Lrg1 from endothelial cells rescued vascular rarefaction and alveolar regression.,Hence, targeting endothelial cell biology through regenerative methods and/or inhibition of the LRG1 pathway may represent strategies of immense potential for the treatment of COPD/emphysema. | Sirtuin-1 (SIRT1) and SIRT6, NAD+-dependent Class III protein deacetylases, are putative anti-aging enzymes, down-regulated in patients with chronic obstructive pulmonary disease (COPD), which is characterized by the accelerated ageing of the lung and associated with increased oxidative stress.,Here, we show that oxidative stress (hydrogen peroxide) selectively elevates microRNA-34a (miR-34a) but not the related miR-34b/c, with concomitant reduction of SIRT1/-6 in bronchial epithelial cells (BEAS2B), which was also observed in peripheral lung samples from patients with COPD.,Over-expression of a miR-34a mimic caused a significant reduction in both mRNA and protein of SIRT1/-6, whereas inhibition of miR-34a (antagomir) increased these sirtuins.,Induction of miR-34a expression with H2O2 was phosphoinositide-3-kinase (PI3K) dependent as it was associated with PI3Kα activation as well as phosphatase and tensin homolog (PTEN) reduction.,Importantly, miR-34a antagomirs increased SIRT1/-6 mRNA levels, whilst decreasing markers of cellular senescence in airway epithelial cells from COPD patients, suggesting that this process is reversible.,Other sirtuin isoforms were not affected by miR-34a.,Our data indicate that miR-34a is induced by oxidative stress via PI3K signaling, and orchestrates ageing responses under oxidative stress, therefore highlighting miR-34a as a new therapeutic target and biomarker in COPD and other oxidative stress-driven aging diseases. | 1 |
This study aimed to inform understanding of how to optimise patient-perceived benefits from a breathlessness service designed for patients with moderate to very severe chronic obstructive pulmonary disease (COPD).,The Westmead Breathlessness Service (WBS) trains patients to self-manage over an 8-week programme, with multidisciplinary input and home visits.,A qualitative approach was taken, using semi-structured telephone interviews.,Each transcript was globally rated as suggesting ‘significant’, ‘some’ or ‘no’ impact from WBS, and thematic analysis used an integrative approach.,Forty-one consecutive participants were interviewed to reach ‘information power’.,Eighteen (44%) participants reported ‘significant’ impact, 17 (41%) ‘some’ impact, and two (5%) ‘no’ impact.,Improvements to breathlessness were usually in the affective and impact dimensions but, more uncommonly, also sensory-perceptual.,Participants who benefited in self-esteem, confidence and motivation attributed this to one-to-one multidisciplinary coaching and home visits.,Further research should test whether including/excluding more intensive programme elements based on individual need might improve cost-effectiveness. | Breathlessness is the most common and intrusive symptom of advanced non-malignant respiratory and cardiac conditions.,The Breathlessness Intervention Service (BIS) is a multi-disciplinary complex intervention, theoretically underpinned by a palliative care approach, utilising evidence-based non-pharmacological and pharmacological interventions to support patients with advanced disease in managing their breathlessness.,Having published the effectiveness and cost effectiveness of BIS for patients with advanced cancer and their carers, we sought to establish its effectiveness, and cost effectiveness, in advanced non-malignant conditions.,This was a single-centre Phase III fast-track single-blind mixed method RCT of BIS versus standard care for breathless patients with non-malignant conditions and their carers.,Randomisation was to one of two groups (randomly permuted blocks).,Eighty-seven patients referred to BIS were randomised (intervention arm n = 44; control arm n = 43 received BIS after four-week wait); 79 (91 %) completed to key outcome measurement.,The primary outcome measure was 0-10 numeric rating scale for patient distress due to breathlessness at four weeks.,Secondary outcome measures were Chronic Respiratory Questionnaire, Hospital Anxiety and Depression Scale, Client Service Receipt Inventory, EQ-5D and topic-guided interviews.,Qualitative analyses showed the positive impact of BIS on patients with non-malignant conditions and their carers; quantitative analyses showed a non-significant greater reduction in the primary outcome (‘distress due to breathlessness’), when compared to standard care, of -0.24 (95 % CI: -1.30, 0.82).,BIS resulted in extra mean costs of £799, reducing to £100 when outliers were excluded; neither difference was statistically significant.,The quantitative findings contrasted with those previously reported for patients with cancer and their carers, which showed BIS to be both clinically and cost effective.,For patients with non-malignant conditions there was a notable trend of improvement over both trial arms to the key measurement point; participants may have experienced a therapeutic effect from the research interviews, diluting the intervention’s impact.,BIS had a statistically non-significant effect for patients with non-malignant conditions, and slightly increased service costs, but had a qualitatively positive impact consistent with findings for advanced cancer.,Trials of palliative care interventions should consider multiple, mixed method, primary outcomes and ensure that protocols limit potential contaminating therapeutic effects in study designs.,Current Controlled Trials ISRCTN04119516 (December 2008); ClinicalTrials.gov NCT00678405 (May 2008),The online version of this article (doi:10.1186/s13063-016-1304-6) contains supplementary material, which is available to authorized users. | 1 |
Vertebral compression fractures (VCF) are common in COPD patients, with osteoporosis being the main cause.,The clinical impact of VCF derives mostly from both pain and chest deformity, which may lead to ventilatory and physical activity limitations.,Surprisingly, the consequences of VCF on the quality outcomes of hospital care are poorly known.,To assess these indicators in patients hospitalized due to a COPD exacerbation (ECOPD) who also have VCF.,Clinical characteristics and quality care indicators were assessed in two one-year periods, one retrospective (exploratory) and one prospective (validation), in all consecutive patients hospitalized for ECOPD.,Diagnosis of VCF was based on the reduction of >20% height of the vertebral body evaluated in standard lateral chest X-ray (three independent observers).,From the 248 patients admitted during the exploratory phase, a third had at least one VCF.,Underdiagnosis rate was 97.6%, and patients with VCF had more admissions (normalized for survival), longer hospital stays, and higher mortality than patients without (4 [25th-75th percentiles, 2-8] vs 3 [1-6] admissions, P<0.01; 12 [6-30] vs 9 [6-18] days, P<0.05; and 50 vs 32.1% deaths, P<0.01, respectively).,The risk of dying in the two following years was also higher in VCF patients (odds ratio: 2.11 [1.2-3.6], P<0.01).,The validation cohort consisted of 250 patients who showed very similar results.,The logistic regression analysis indicated that both VCF and age were factors independently associated with mortality.,Although VCF is frequently underdiagnosed in patients hospitalized for ECOPD, it is strongly associated with a worse prognosis and quality care outcomes. | Early palliative care is not a common practice for patients with COPD.,Important barriers are the identification of patients for palliative care and the organization of such care in this patient group.,Pulmonologists have a central role in providing good quality palliative care for patients with COPD.,To guide future research and develop services, their view on palliative care for these patients was explored.,A survey study was performed by the members of the Netherlands Association of Physicians for Lung Diseases and Tuberculosis.,The 256 respondents (31.8%) covered 85.9% of the hospital organizations in the Netherlands.,Most pulmonologists (92.2%) indicated to distinguish a palliative phase in the COPD trajectory, but there was no consensus about the different criteria used for its identification.,Aspects of palliative care in COPD considered important were advance care planning conversation (82%), communication between pulmonologist and general practitioner (77%), and identification of the palliative phase (75.8%), while the latter was considered the most important aspect for improvement (67.6%).,Pulmonologists indicated to prefer organizing palliative care for hospitalized patients with COPD themselves (55.5%), while 30.9% indicated to prefer cooperation with a specialized palliative care team (SPCT).,In the ambulatory setting, a multidisciplinary cooperation between pulmonologist, general practitioner, and a respiratory nurse specialist was preferred (71.1%).,To encourage pulmonologists to timely initiate palliative care in COPD, we recommend to conduct further research into more specific identification criteria.,Furthermore, pulmonologists should improve their skills of palliative care, and the members of the SPCT should be better informed about the management of COPD to improve care during hospitalization.,Communication between pulmonologist and general practitioner should be emphasized in training to improve palliative care in the ambulatory setting. | 1 |
The response to treatment and progression of Chronic Obstructive Pulmonary Disease (COPD) varies significantly.,Small airways disease (SAD) is being increasingly recognized as a key pathological feature of COPD.,Studies have brought forward pathological evidence of small airway damage preceding the development of emphysema and the detection of obstruction using traditional spirometry.,In recent years, there has been a renewed interest in the early detection of SAD and this has brought along an increased demand for physiological tests able to identify and quantify SAD.,Early detection of SAD allows early targeted therapy and this suggests the potential for altering the course of disease.,The aim of this article is to review the evidence available on the physiological testing of small airways.,The first half will focus on the role of lung function tests such as maximum mid-expiratory flow, impulse oscillometry and lung clearance index in detecting and quantifying SAD.,The role of Computed Tomography (CT) as a radiological biomarker will be discussed as well as the potential of recent CT analysis software to differentiate normal aging of the lungs to pathology.,The evidence behind SAD biomarkers sourced from blood as well as biomarkers sourced from sputum and broncho-alveolar lavage (BAL) will be reviewed.,This paper focuses on CC-16, sRAGE, PAI-1, MMP-9 and MMP-12. | COPD is a progressive inflammatory airway disease characterized by increased numbers of alveolar macrophages in the lungs.,Bacterial colonization of the lungs is a common feature in COPD and can promote inflammation through continual and repeated Toll-like receptor (TLR) stimulation.,We have studied the response of COPD alveolar macrophages to repetitive stimulation with TLR2 and TLR4 ligands.,We investigated the effect of sequential stimulation with different ligands to determine whether this results in tolerance or amplification of the immune response.,We stimulated alveolar macrophages from COPD patients (n=9) and smokers (n=8) with the TLR4 agonist lipopolysaccharide (LPS) or the TLR2 agonist Pam3CSK4 for 24 hours before restimulating again for 24 hours.,Cytokine protein release and gene expression were investigated.,Repetitive stimulation of COPD and smokers macrophages with LPS for both 24-hour periods caused a reduction in tumor necrosis factor α, CCL5, and IL-10 production compared to cells that were not exposed initially to LPS.,IL-6 and CXCL8 production were not significantly altered following repetitive LPS stimulation.,The same pattern was observed for repeated stimulation with Pam3CSK4.,Using COPD macrophages, LPS followed by Pam3CSK4 stimulation increased the levels of all cytokines compared to media followed by Pam3CSK4.,TLR tolerance in COPD alveolar macrophages occurs after repetitive stimulation with the same TLR ligand, but this only occurs for selected cytokines.,CXCL8 production is not reduced after repetitive TLR stimulation with the same ligand; this may be an important mechanism for the increased CXCL8 levels that have been observed in COPD.,We showed that TLR4 stimulation followed by TLR2 stimulation does not cause tolerance, but enhances cytokine production.,This may be a relevant mechanism by which bacteria cause excessive inflammation in COPD patients. | 1 |
Inhaled corticosteroids (ICSs) are a mainstay of COPD treatment for patients with a history of exacerbations.,Initial studies evaluating their use as monotherapy failed to show an effect on rate of pulmonary function decline in COPD, despite improvements in symptoms and reductions in exacerbations.,Subsequently, ICS use in combination with long-acting β2-agonists (LABAs) was shown to provide improved reductions in exacerbations, lung function, and health status.,ICS-LABA combination therapy is currently recommended for patients with a history of exacerbations despite treatment with long-acting bronchodilators alone.,The presence of eosinophilic bronchial inflammation, detected by high blood eosinophil levels or a history of asthma or asthma-COPD overlap, may define a population of patients in whom ICSs may be of particular benefit.,Prospective clinical studies to determine an appropriate threshold of eosinophil levels for predicting the beneficial effects of ICSs are needed.,Further study is also required in COPD patients who continue to smoke to assess the impact of cell- and tissue-specific changes on ICS responsiveness.,The safety profile of ICSs in COPD patients is confounded by comorbidities, age, and prior use of systemic corticosteroids.,The risk of pneumonia in patients with COPD is increased, particularly with more advanced age and worse disease severity.,ICS-containing therapy also has been shown to increase pneumonia risk; however, differences in study design and the definition of pneumonia events have led to substantial variability in risk estimates, and some data indicate that pneumonia risk may differ by the specific ICS used.,In summary, treatment with ICSs has a role in dual and triple therapy for COPD to reduce exacerbations and improve symptoms.,Careful assessment of COPD phenotypes related to risk factors, triggers, and comorbidities may assist in individualizing treatment while maximizing the benefit-to-risk ratio of ICS-containing COPD treatment. | The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends triple therapy (long-acting muscarinic receptor antagonists, long-acting beta-2 agonists, and inhaled corticosteroids) for patients with only the most severe COPD.,Data on the proportion of COPD patients on triple therapy and their characteristics are sparse and dated.,Objective 1 of this study was to estimate the proportion of all, and all treated, COPD patients receiving triple therapy.,Objective 2 was to characterize those on triple therapy and assess the concordance of triple therapy use with GOLD guidelines.,This retrospective study used claims from the IMS PharMetrics Plus database from 2009 to 2013.,Cohort 1 was selected to assess Objective 1 only; descriptive analyses were conducted in Cohort 2 to answer Objective 2.,A validated claims-based algorithm and severity and frequency of exacerbations were used as proxies for COPD severity.,Of all 199,678 patients with COPD in Cohort 1, 7.5% received triple therapy after diagnosis, and 25.5% of all treated patients received triple therapy.,In Cohort 2, 30,493 COPD patients (mean age =64.7 years) who initiated triple therapy were identified.,Using the claims-based algorithm, 34.5% of Cohort 2 patients were classified as having mild disease (GOLD 1), 40.8% moderate (GOLD 2), 22.5% severe (GOLD 3), and 2.3% very severe (GOLD 4).,Using exacerbation severity and frequency, 60.6% of patients were classified as GOLD 1/2 and 39.4% as GOLD 3/4.,In this large US claims database study, one-quarter of all treated COPD patients received triple therapy.,Although triple therapy is recommended for the most severe COPD patients, spirometry is infrequently assessed, and a majority of the patients who receive triple therapy may have only mild/moderate disease.,Any potential overprescribing of triple therapy may lead to unnecessary costs to the patient and health care system. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms and pathological consequences.,Although primarily viewed as a respiratory disease, COPD has both pulmonary and extrapulmonary effects, which have an impact on many aspects of physical, emotional, and mental well-being.,Traditional assessment of COPD relies heavily on measuring lung function, specifically forced expiratory volume in 1 second (FEV1).,However, the evidence suggests that FEV1 is a relatively poor correlate of symptoms such as breathlessness and the impact of COPD on daily life.,Furthermore, many consequences of the disease, including anxiety and depression and the ability to perform daily activities, can only be described and reported reliably by the patient.,Thus, in order to provide a comprehensive view of the effects of interventions in clinical trials, it is essential that spirometry is accompanied by assessments using patient-reported outcome (PRO) instruments.,We provide an overview of patient-reported outcome concepts in COPD, such as breathlessness, physical functioning, and health status, and evaluate the tools used for measuring these concepts.,Particular attention is given to the newly developed instruments emerging in response to recent regulatory guidelines for the development and use of PROs in clinical trials.,We conclude that although data from the development and validation of these new PRO instruments are emerging, to build the body of evidence that supports the use of a new instrument takes many years.,Furthermore, new instruments do not necessarily have better discriminative or evaluative properties than older instruments.,The development of new PRO tools, however, is crucial, not only to ensure that key COPD concepts are being reliably measured but also that the relevant treatment effects are being captured in clinical trials.,In turn, this will help us to understand better the patient’s experience of the disease. | Chronic obstructive pulmonary disease (COPD) is a complex disease with multifactorial background, based on the interaction of environmental and genetic factors.,Environmental factors are clearly related to the development of the disease.,However, family and twin studies suggested genetics factors to be one of the important determinants for the development of COPD.,Different approaches have been used to identify genes of interest.,Genomewide linkage analysis found areas of interest on different chromosomes, with some genes located in this regions being identified and replicated as susceptibility genes.,Numerous of candidate genes that could be linked to disease pathogenesis have been implicated in COPD genetics.,However, the candidate gene approach is often limited by inconsistent results in other study populations.,Recently, a combination of different methods is used giving more evidence for some candidate genes, including TGFß-1, Surfactant, SERPINE2 and microsomal epoxide hydrolase.,In the future ongoing exact phenotype definition, combination of several approaches, genome-wide association studies and animal model genetics will lead to new insights into the genetics of COPD, with epigenetic factors needs to be further investigated and considered in concert with genetic findings. | 1 |
Chronic obstructive pulmonary disease (COPD) outpatients account for a large burden of usual care by respirologists.,EPOCONSUL is the first national clinical audit conducted in Spain on the medical care for COPD patients delivered in outpatient respiratory clinics.,We aimed to evaluate the clinical interventions and the degree of adherence to recommendations in outpatients of current COPD clinical practice guidelines.,This is an observational study with prospective recruitment (May 2014-May 2015) of patients with a COPD diagnosis as seen in outpatient respiratory clinics.,The information collected was historical in nature as for the clinical data of the last and previous consultations, and the information concerning hospital resources was concurrent.,A total of 17,893 clinical records of COPD patients in outpatient respiratory clinics from 59 Spanish hospitals were evaluated.,Of the 5,726 patients selected, 4,508 (78.7%) were eligible.,Overall, 12.1% of COPD patients did not fulfill a diagnostic spirometry criteria.,Considerable variability existed in the available resources and work organization of the hospitals, although the majority were university hospitals with respiratory inpatient units.,There was insufficient implementation of clinical guidelines in preventive and educational matters.,In contrast, quantitative evaluation of dyspnea grade (81.9%) and exacerbation history (70.9%) were more frequently performed.,Only 12.4% had COPD severity calculated according to the Body mass index, airflow Obstruction, Dyspnoea and Exercise capacity (BODE) index.,Phenotype characteristics according to Spanish National Guideline for COPD were determined in 46.3% of the audited patients, and the risk evaluation according to Global initiative for chronic Obstructive Lung Disease was estimated only in 21.9%.,The EPOCONSUL study reports the current situation of medical care for COPD patients in outpatient clinics in Spain, revealing its variability, strengths, and weaknesses.,This information has to be accounted for by health managers to define corrective strategies and maximize good clinical practice. | FEV1 is universally used as a measure of severity in COPD.,Current thresholds are based on expert opinion and not on evidence.,We aimed to identify the best FEV1 (% predicted) and dyspnea (mMRC) thresholds to predict 5-yr survival in COPD patients.,We conducted a patient-based pooled analysis of eleven COPD Spanish cohorts (COCOMICS).,Survival analysis, ROC curves, and C-statistics were used to identify and compare the best FEV1 (%) and mMRC scale thresholds that predict 5-yr survival.,A total of 3,633 patients (93% men), totaling 15,878 person-yrs. were included, with a mean age 66.4±9.7, and predicted FEV1 of 53.8% (±19.4%).,Overall 975 (28.1%) patients died at 5 years.,The best thresholds that spirometrically split the COPD population were: mild ≥70%, moderate 56-69%, severe 36-55%, and very severe ≤35%.,Survival at 5 years was 0.89 for patients with FEV1≥70 vs.,0.46 in patients with FEV1 ≤35% (H.R: 6; 95% C.I.: 4.69-7.74).,The new classification predicts mortality significantly better than dyspnea (mMRC) or FEV1 GOLD and BODE cutoffs (all p<0.001).,Prognostic reliability is maintained at 1, 3, 5, and 10 years.,In younger patients, survival was similar for FEV1 (%) values between 70% and 100%, whereas in the elderly the relationship between FEV1 (%) and mortality was inversely linear.,The best thresholds for 5-yr survival were obtained stratifying FEV1 (%) by ≥70%, 56-69%, 36-55%, and ≤35%.,These cutoffs significantly better predict mortality than mMRC or FEV1 (%) GOLD and BODE cutoffs. | 1 |
Background.,An increase of chronic obstructive pulmonary disease (COPD) prevalence was reported in Canada despite the decline of the main risk factor.,Objectives.,To estimate incidence, prevalence, and mortality of COPD from 2001 to 2011 and establish the COPD burden by the evaluation of the age-period-cohort effects on incidence trends and the comorbidities prevalence estimations.,Methods.,A retrospective population-based cohort was built using Quebec health administrative data.,Change in trends was measured by relative percentage of changes and by joinpoint regression.,After a descriptive analysis of the trends, an age-period-cohort analysis was performed on incidence rates.,Results.,Overall increase in prevalence along with a decrease of incidence and all-cause mortality was observed.,Over time, all age-standardized trends were higher in men than women.,Despite higher rates, the number of incident and prevalent cases in women exceeds men since 2004.,The curve analysis by age groups showed over time a downshift for both sexes in incidence and all-cause mortality.,Further analysis showed the presence of a cohort effect in women.,Conclusion.,The burden of COPD has risen over time.,Women younger than 65 years old have been identified as at-risk group for healthcare planning. | Comorbidities are frequent in chronic obstructive pulmonary disease (COPD) and significantly impact on patients’ quality of life, exacerbation frequency, and survival.,There is increasing evidence that certain diseases occur in greater frequency amongst patients with COPD than in the general population, and that these comorbidities significantly impact on patient outcomes.,Although the mechanisms are yet to be defined, many comorbidities likely result from the chronic inflammatory state that is present in COPD.,Common problems in the clinical management of COPD include recognizing new comorbidities, determining the impact of comorbidities on patient symptoms, the concurrent treatment of COPD and comorbidities, and accurate prognostication.,The majority of comorbidities in COPD should be treated according to usual practice, and specific COPD management is infrequently altered by the presence of comorbidities.,Unfortunately, comorbidities are often under-recognized and under-treated.,This review focuses on the epidemiology of ten major comorbidities in patients with COPD.,Further, we emphasize the clinical impact upon prognosis and management considerations.,This review will highlight the importance of comorbidity identification and management in the practice of caring for patients with COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is an age-related disease, and its incidence rate is increasing every year.,MicroRNAs (miRNAs) play critical roles in the COPD process and function as key biomarkers or potential therapeutic targets for patients with COPD.,However, the potential roles and functional effects of miR-218 in COPD remain undefined.,The expression levels of miR-218 and bromodomain protein 4 (BRD4) were assessed by real-time quantitative polymerase chain reaction (RT-qPCR) or Western blot, respectively.,In addition, a COPD cell model was established using cigarette smoke extract (CSE) in bronchial epithelial cell line (BEAS-2B).,Enzyme-linked immunosorbent assay (ELISA) kit was applied to measure the concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) in cell supernatants of BEAS-2B cells.,Moreover, cell apoptosis was examined by flow cytometry assay.,The association relationship between miR-218 and BRD4 was confirmed by dual-luciferase reporter and RNA immunoprecipitation assay.,MiR-218 was downregulated in COPD and CSE-induced BEAS-2B cells, and it was positively correlated with forced expiratory volume in 1 second (FEV1) % in COPD patients.,Mechanically, overexpression of miR-218 or knockdown of BRD4 mitigated apoptosis and inflammation in BEAS-2B cells induced by CSE.,Additionally, overexpression of BRD4 weakened the miR-218-mediated effects on CSE-induced BEAS-2B cells.,Overexpression of miR-218 inhibited CSE-induced apoptosis and inflammation in BEAS-2B cells by targeting BRD4 expression. | Mitochondrial damage in airway epithelial cells plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD).,Sirtuin 3 (Sirt3) is a mitochondrial deacetylase regulating mitochondrial function, but its role in the pathogenesis of COPD is still unknown.,The aim of the present study was to investigate the effect of Sirt3 on airway epithelial mitochondria in cigarette smoke-induced COPD.,Our present study has shown serious airway inflammation, alveolar space enlargement, and mitochondrial damage of the airway epithelium in COPD rats.,Compared to the control rats, Sirt3 protein expression was significantly decreased in the airway epithelium and lung tissue homogenate from COPD rats.,In airway epithelial cells (BEAS-2B), cigarette smoke extract (CSE) treatment significantly decreased mRNA and protein expression of Sirt3 and manganese superoxide dismutase (MnSOD), as well as MnSOD activity in a concentration and time-dependent manner.,Sirt3 siRNA further significantly intensified the decreases in MnSOD expression and activity and aggravated mitochondrial oxidative stress and cell injury when airway epithelial cells were treated with 7.5% CSE.,In contrast, Sirt3 overexpression significantly prevented the decrease of MnSOD expression and activity and improved mitochondrial oxidative stress and cell injury in CSE-treated airway epithelial cells.,These data suggest that Sirt3 inhibits airway epithelial mitochondrial oxidative stress possibly through the regulation of MnSOD, thereby contributing to the pathogenesis of COPD. | 1 |
Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease.,For each patient, four of five treatments were administered once daily for 6 weeks, with a 21-day washout between treatments: tiotropium/olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg, olodaterol 5 µg or placebo, all via the Respimat inhaler.,Primary outcomes were inspiratory capacity prior to exercise and exercise endurance time during constant work-rate cycle ergometry to symptom limitation at 75% of peak incremental work rate after 6 weeks (2 h post-dose).,295 and 291 patients were treated in MORACTO 1 and 2, respectively.,Tiotropium/olodaterol 2.5/5 and 5/5 µg provided significant improvements in inspiratory capacity versus placebo and monotherapies (p<0.0001), and significant improvements in exercise endurance time versus placebo (p<0.0001).,Intensity of breathing discomfort was reduced following both doses of tiotropium/olodaterol versus placebo (p<0.0001).,Once-daily tiotropium/olodaterol yielded improvements in lung hyperinflation versus placebo and statistically significant improvements versus monotherapies.,Tiotropium/olodaterol also showed improvements in dyspnoea and exercise tolerance versus placebo but not consistently versus monotherapies.,T/O reduces lung hyperinflation in COPD versus T, O or placebo and increases exercise endurance versus placebohttp://ow.ly/ml3G307XW6a | Reduced physical activity (PA) in patients with COPD is associated with a poor prognosis.,Increasing PA is a key therapeutic target, but thus far few strategies have been found effective in this patient group.,To investigate the effectiveness of a 12-week semiautomated telecoaching intervention on PA in patients with COPD in a multicentre European randomised controlled trial.,343 patients from six centres, encompassing a wide spectrum of disease severity, were randomly allocated to either a usual care group (UCG) or a telecoaching intervention group (IG) between June and December 2014.,This 12-week intervention included an exercise booklet and a step counter providing feedback both directly and via a dedicated smartphone application.,The latter provided an individualised daily activity goal (steps) revised weekly and text messages as well as allowing occasional telephone contacts with investigators.,PA was measured using accelerometry during 1 week preceding randomisation and during week 12.,Secondary outcomes included exercise capacity and health status.,Analyses were based on modified intention to treat.,Both groups were comparable at baseline in terms of factors influencing PA.,At 12 weeks, the intervention yielded a between-group difference of mean, 95% CI (lower limit - upper limit; ll-ul) +1469, 95% CI (971 to 1965) steps/day and +10.4, 95% CI (6.1 to 14.7) min/day moderate PA; favouring the IG (all p≤0.001).,The change in 6-min walk distance was significantly different (13.4, 95% CI (3.40 to 23.5) m, p<0.01), favouring the IG.,In IG patients, an improvement could be observed in the functional state domain of the clinical COPD questionnaire (p=0.03) compared with UCG.,Other health status outcomes did not differ.,The amount and intensity of PA can be significantly increased in patients with COPD using a 12-week semiautomated telecoaching intervention including a step counter and an application installed on a smartphone.,NCT02158065. | 1 |
The cluster randomized controlled trial on (cost-)effectiveness of integrated chronic obstructive pulmonary disease (COPD) management in primary care (RECODE) showed that integrated disease management (IDM) in primary care had no effect on quality of life (QOL) in COPD patients compared with usual care (guideline-supported non-programmatic care).,It is possible that only a subset of COPD patients in primary care benefit from IDM.,We therefore examined which patients benefit from IDM, and whether patient characteristics predict clinical improvement over time.,Post-hoc analyses of the RECODE trial among 1086 COPD patients.,Logistic regression analyses were performed with baseline characteristics as predictors to examine determinants of improvement in QOL, defined as a minimal decline in Clinical COPD Questionnaire (CCQ) of 0.4 points after 12 and 24 months of IDM.,We also performed moderation analyses to examine whether predictors of clinical improvement differed between IDM and usual care.,Regardless of treatment type, more severe dyspnea (MRC) was the most important predictor of clinically improved QOL at 12 and 24 months, suggesting that these patients have most room for improvement.,Clinical improvement with IDM was associated with female gender (12-months) and being younger (24-months), and improvement with usual care was associated with having a depression (24-months).,More severe dyspnea is a key predictor of improved QOL in COPD patients over time.,More research is needed to replicate patient characteristics associated with clinical improvement with IDM, such that IDM programs can be offered to patients that benefit the most, and can potentially be adjusted to meet the needs of other patient groups as well.,Netherlands Trial Register, NTR2268.,Registered 31 March 2010. | Enhancing quality of life for people with long-term conditions by monitoring patient-reported outcome measure scores is a key domain of health care policy.,This study investigated the responsiveness of patient-reported outcome measures for long-term conditions.,A cohort survey was conducted in 33 primary care practices and 4485 patients (1334 asthma, 567 chronic obstructive pulmonary disease, 1121 diabetes, 525 epilepsy, 520 heart failure and 418 stroke) were sent a baseline survey containing a generic (EQ-5D) and a disease-specific measure.,Baseline respondents were sent a follow-up after 1 year.,Differences in scores for each long-term condition were assessed by paired t-tests.,The relationship between scores and self-reported ‘change in health’ was assessed by analysis of variance.,The baseline achieved a 38.4% response rate and the follow-up 71.5%.,The only significant difference for the EQ-5D was found for the Visual Analogue Scale in heart failure between baseline and follow-up, and for change in health.,Significant differences between baseline and follow-up scores were found on the disease-specific measures for 1 asthma dimension and 1 stroke dimension.,No significant differences were found for other conditions.,Significant differences between self-reported change in health and the disease-specific measures were found for 4 asthma dimensions and 2 stroke dimensions.,Few significant differences were found between the baseline and follow up or between ‘change in health’ and PROMs scores.,This could be explained by the time frame of one year being too short for change to occur or by the PROMs not being responsive enough to change in a primary care sample.,The latter is unlikely as the PROMs were in part chosen for their responsiveness to change.,The baseline response rates may mean that the sample is not representative, and stable patients may have been more likely to participate.,If PROMs are to be used routinely to monitor outcomes in LTCs, further research is needed to maximize response rates, to ensure that the PROMs used are reliable, valid and sensitive enough to detect change and that the time frame for data collection is appropriate.,The online version of this article (doi:10.1186/s12955-014-0123-2) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by the destruction of alveolar walls, chronic inflammation and persistent respiratory symptoms.,There is no curative clinical treatment for COPD.,In this context, cell-based therapy is a promising therapeutic alternative for COPD.,Thus, in this open, controlled and randomized Phase I Clinical Trial, we aimed to assess the safety of the infusion of autologous bone marrow mononuclear cells (BMMC), adipose-derived mesenchymal stromal cells (ADSC) and, especially, the safety of concomitant infusion (co-infusion) of BMMC and ADSC as a new therapeutic alternative for COPD.,The rationale for co-infusion of BMMC and ADSC is based on the hypothesis of an additive or synergistic therapeutic effect resulting from this association.,To achieve the proposed objectives, twenty patients with moderate-to-severe COPD were randomly divided into four groups: control group - patients receiving conventional treatment; BMMC group - patients receiving only BMMC; ADSC group - patients receiving only ADSC, and co-infusion group - patients receiving the concomitant infusion of BMMC and ADSC.,Patients were assessed for pulmonary function, biochemical profile, and quality of life over a 12 months follow-up.,No adverse events were detected immediately after the infusion of BMMC, ADSC or co-infusion.,In the 12-month follow-up, no causal relationship was established between adverse events and cell therapy procedures.,Regarding the efficacy, the BMMC group showed an increase in forced expiratory volume (FEV1) and diffusing capacity for carbon monoxide (DLCO).,Co-infusion group showed a DLCO, and gas exchange improvement and a better quality of life.,The results obtained allow us to conclude that cell-based therapy with co-infusion of BMMC and ADSC is a safe procedure and a promising therapeutic for COPD.,However, additional studies with a greater number of patients are needed before randomized and controlled Phase III clinical trials can be implemented. | The aim of this study was to characterize the evolution of lung function and -structure in elastase-induced emphysema in adult mice and the effect of mesenchymal stromal cell (MSC) administration on these parameters.,Adult mice were treated with intratracheal (4.8 units/100 g bodyweight) elastase to induce emphysema.,MSCs were administered intratracheally or intravenously, before or after elastase injection.,Lung function measurements, histological and morphometric analysis of lung tissue were performed at 3 weeks, 5 and 10 months after elastase and at 19, 20 and 21 days following MSC administration.,Elastase-treated mice showed increased dynamic compliance and total lung capacity, and reduced tissue-specific elastance and forced expiratory flows at 3 weeks after elastase, which persisted during 10 months follow-up.,Histology showed heterogeneous alveolar destruction which also persisted during long-term follow-up.,Jugular vein injection of MSCs before elastase inhibited deterioration of lung function but had no effects on histology.,Intratracheal MSC treatment did not modify lung function or histology.,In conclusion, elastase-treated mice displayed persistent characteristics of pulmonary emphysema.,Jugular vein injection of MSCs prior to elastase reduced deterioration of lung function.,Intratracheal MSC treatment had no effect on lung function or histology. | 1 |
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. | Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD).,The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.,In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.,At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints).,Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint).,All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.,Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk.,Aclidinium/formoterol may be an effective treatment for patients with COPD.,ClinicalTrials.gov: NCT01462942.,The online version of this article (doi:10.1186/1471-2466-14-178) contains supplementary material, which is available to authorized users. | 1 |
COPD is a complex, heterogeneous disease characterised by progressive development of airflow limitation.,Spirometry provides little information about key aspects of pathology and is poorly related to clinical outcome, so other tools are required to investigate the disease.,We sought to explore the relationships between quantitative CT analysis with functional, inflammatory and infective assessments of disease to identify the utility of imaging to stratify disease to better predict outcomes and disease response.,Patients from the AERIS study with moderate-very severe COPD underwent HRCT, with image analysis determining the quantity of emphysema (%LAA<− 950), small airways disease (E/I MLD) and bronchial wall thickening (Pi10).,At enrolment subjects underwent lung function testing, six-minute walk testing (6MWT), blood sampling for inflammatory markers and sputum sampling for white cell differential and microbiological culture and PCR.,122 subjects were included in this analysis.,Emphysema and small airways disease had independent associations with airflow obstruction (β = − 0.34, p < 0.001 and β = − 0.56, p < 0.001).,%LAA<− 950 had independent associations with gas transfer (β = − 0.37, p < 0.001) and E/I MLD with RV/TLC (β = 0.30, p =0.003).,The distance walked during the 6MWT was not associated with CT parameters, but exertional desaturation was independently associated with emphysema (β = 0.73, p < 0.001).,Pi10 did not show any independent associations with lung function or functional parameters.,No CT parameters had any associations with sputum inflammatory cells.,Greater emphysema was associated with lower levels of systemic inflammation (CRP β = − 0.34, p < 0.001 and fibrinogen β = − 0.28, p =0.003).,There was no significant difference in any of the CT parameters between subjects where potentially pathogenic bacteria were detected in sputum and those where it was not.,This study provides further validation for the use of quantitative CT measures of emphysema and small airways disease in COPD as they showed strong associations with pulmonary physiology and functional status.,In contrast to this quantitative CT measures showed few convincing associations with biological measures of disease, suggesting it is not an effective tool at measuring disease activity.,The online version of this article (10.1186/s12931-018-0734-y) contains supplementary material, which is available to authorized users. | Parametric response mapping (PRM) of paired CT lung images has been shown to improve the phenotyping of COPD by allowing for the visualization and quantification of non-emphysematous air trapping component, referred to as functional small airways disease (fSAD).,Although promising, large variability in the standard method for analyzing PRMfSAD has been observed.,We postulate that representing the 3D PRMfSAD data as a single scalar quantity (relative volume of PRMfSAD) oversimplifies the original 3D data, limiting its potential to detect the subtle progression of COPD as well as varying subtypes.,In this study, we propose a new approach to analyze PRM.,Based on topological techniques, we generate 3D maps of local topological features from 3D PRMfSAD classification maps.,We found that the surface area of fSAD (SfSAD) was the most robust and significant independent indicator of clinically meaningful measures of COPD.,We also confirmed by micro-CT of human lung specimens that structural differences are associated with unique SfSAD patterns, and demonstrated longitudinal feature alterations occurred with worsening pulmonary function independent of an increase in disease extent.,These findings suggest that our technique captures additional COPD characteristics, which may provide important opportunities for improved diagnosis of COPD patients. | 1 |
To identify factors that hinder discussions regarding chronic obstructive pulmonary disease (COPD) between primary care physicians (PCPs) and their patients in Sweden.,Primary health care centres (PHCCs) in Stockholm, Sweden.,A total of 59 PCPs.,Semi-structured individual and focus-group interviews between 2012 and 2014.,Data were analysed inspired by grounded theory methods (GTM).,Time-pressured patient-doctor consultations lead to deprioritization of COPD.,During unscheduled visits, deprioritization resulted from focusing only on acute health concerns, while during routine care visits, COPD was deprioritized in multi-morbid patients.,The reasons PCPs gave for deprioritizing COPD are: “Not becoming aware of COPD”, “Not becoming concerned due to clinical features”, “Insufficient local routines for COPD care”, “Negative personal attitudes and views about COPD”, “Managing diagnoses one at a time”, and “Perceiving a patient’s motivation as low’’.,De-prioritization of COPD was discovered during PCP consultations and several factors were identified associated with time constraints and multi-morbidity.,A holistic consultation approach is suggested, plus extended consultation time for multi-morbid patients, and better documentation and local routines.,Key pointsUnder-diagnosis and insufficient management of chronic obstructive pulmonary disease (COPD) are common in primary health care.,A patient-doctor consultation offers a key opportunity to identify and provide COPD care.,Time pressure, due to either high number of patients or multi-morbidity, leads to omission or deprioritization of COPD during consultation.Deprioritization occurs due to lack of awareness, concern, and local routines, negative personal views, non-holistic consultation approach, and low patient motivation.Better local routines, extended consultation time, and a holistic approach are needed when managing multi-morbid patients with COPD.,Under-diagnosis and insufficient management of chronic obstructive pulmonary disease (COPD) are common in primary health care.,A patient-doctor consultation offers a key opportunity to identify and provide COPD care.,Time pressure, due to either high number of patients or multi-morbidity, leads to omission or deprioritization of COPD during consultation.Deprioritization occurs due to lack of awareness, concern, and local routines, negative personal views, non-holistic consultation approach, and low patient motivation.Better local routines, extended consultation time, and a holistic approach are needed when managing multi-morbid patients with COPD.,Time pressure, due to either high number of patients or multi-morbidity, leads to omission or deprioritization of COPD during consultation.,Deprioritization occurs due to lack of awareness, concern, and local routines, negative personal views, non-holistic consultation approach, and low patient motivation.,Better local routines, extended consultation time, and a holistic approach are needed when managing multi-morbid patients with COPD. | Chronic obstructive pulmonary disease (COPD) is an underdiagnosed cause of morbidity and mortality worldwide.,Prevalence of COPD has been shown to be highly associated with positive smoking history and increasing age.,Spirometry is the method used for diagnosing COPD.,However, identifying patients at risk of COPD to undergo spirometry tests has been challenging.,Therefore, there is a need for new cost-effective and feasible diagnostic screening procedures for use in primary care centers.,Our aim was to describe the prevalence and severity of undiagnosed COPD in a group of patients with respiratory infections attending urgent primary care, and to identify those variables in patients' history that could be used to detect the disease.,Patients of 40-75 years (n = 138) attending urgent primary care center with acute respiratory tract infection, positive smoking history and no previously known pulmonary disease underwent pre- and post bronchodilator spirometry testing four to five weeks after the acute infection.,Prevalence and severity of COPD were estimated following the Global Initiative for COPD (GOLD) criteria.,Variables such as sex, age, current smoking status, smoking intensity (pack years) and type of infection diagnosis were assessed for possible associations with COPD.,The prevalence of previously undiagnosed COPD in our study group was 27%, of which 45% were in stage 1 (FEV1 ≥ 80% of predicted), 53% in stage 2 (50 ≤ FEV1 < 80% of predicted), 3% in stage 3 (30 ≤ FEV1 < 50% of predicted) and 0% in stage 4 (FEV1 < 30% of predicted).,We found a significant association between COPD and age ≥ 55 (OR = 10.9 [95% CI 3.8-30.1]) and between COPD and smoking intensity (pack years > 20) (OR = 3.2 [95% CI 1.2-8.5]).,Sex, current smoking status and type of infection diagnosis were not shown to be significantly associated with COPD.,A middle-aged or older patient with any type of common respiratory tract infection, positive smoking history and no previously known pulmonary disease has an increased likelihood of having underlying COPD.,These patients should be offered spirometry testing for diagnosis of COPD. | 1 |
The economic burden of COPD has not been well studied in China.,This study investigated the total costs caused by COPD and the influencing factors for the high economic burden in urban areas of China.,A cross-sectional study was carried out among 678 COPD patients in four cities in China in 2011.,The average annual direct medical costs (DMCs), direct nonmedical costs (DNMCs), and indirect costs (ICs) on COPD were measured by median and mean (± standard deviation).,Logistic regression model was used to explore factors related to high total costs on COPD.,The median annual DMCs, DNMCs, and ICs per COPD patient were RMB 5565 Yuan (US$ 862), 0 Yuan (US$ 0), and 0 Yuan (US$ 0), respectively, and the mean annual DMCs, DNMCs, and ICs per COPD patient were RMB 11968 (±22422) Yuan [US$ 1853 (±3472)], 539 (±2092) Yuan [US$ 83 (±324)], and 2087 (±8110) Yuan [US$ 323 (±1256)], respectively.,The annual DMCs, DNMCs, and ICs for diagnosed COPD patients were RMB 195.70 billion Yuan (US$ 30.30 billion), 8.78 billion Yuan (US$ 1.36 billion), and 34.10 billion Yuan (US$ 5.28 billion), respectively, in China.,Hospitalization accounted for 56.7% of the total costs.,High economic burden was significantly related to age, acute exacerbations, and disease severity in COPD patients.,COPD posed a heavy economic burden in China.,Measures to delay the disease progression and to reduce the risks of acute exacerbation and hospitalization will help substantially lower the costs for COPD care. | Chronic obstructive pulmonary disease (COPD) patients often have dysphagia through age and several co-morbidities, leading to aspiration pneumonia (AsP).,COPD patients also have increased risk of developing community-acquired pneumonia (CAP).,Using a national inpatient database in Japan, we aimed to compare clinical characteristics and outcomes between AsP and CAP in COPD patients and to verify the factors that affect in-hospital morality.,We retrospectively collected data on COPD patients (age ≥40 years) who were admitted for AsP or CAP in 1,165 hospitals across Japan between July 2010 and May 2013.,We performed multivariable logistic regression analyses to examine the association of various factors with all-cause in-hospital mortality for AsP and CAP.,Of 87,330 eligible patients, AsP patients were more likely to be older, male and have poorer general condition and more severe pneumonia than those with CAP.,In-hospital mortality in the AsP group was 22.7 % and 12.2 % in the CAP group.,After adjustment for patient background, AsP patients had significantly higher mortality than CAP patients (adjusted odds ratio, 1.19; 95 % confidence interval, 1.08-1.32).,Subgroup analyses showed higher mortality to be associated with male gender, underweight, dyspnea, physical disability, pneumonia severity, and several co-morbidities.,Further, older age and worse level of consciousness were associated with higher mortality in the CAP group, whereas those were not associated in the AsP group.,Clinical characteristics differed significantly between AsP and CAP in COPD patients.,AsP patients had significantly higher mortality than those with CAP.,The online version of this article (doi:10.1186/s12890-015-0064-5) contains supplementary material, which is available to authorized users. | 1 |
Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease.,For each patient, four of five treatments were administered once daily for 6 weeks, with a 21-day washout between treatments: tiotropium/olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg, olodaterol 5 µg or placebo, all via the Respimat inhaler.,Primary outcomes were inspiratory capacity prior to exercise and exercise endurance time during constant work-rate cycle ergometry to symptom limitation at 75% of peak incremental work rate after 6 weeks (2 h post-dose).,295 and 291 patients were treated in MORACTO 1 and 2, respectively.,Tiotropium/olodaterol 2.5/5 and 5/5 µg provided significant improvements in inspiratory capacity versus placebo and monotherapies (p<0.0001), and significant improvements in exercise endurance time versus placebo (p<0.0001).,Intensity of breathing discomfort was reduced following both doses of tiotropium/olodaterol versus placebo (p<0.0001).,Once-daily tiotropium/olodaterol yielded improvements in lung hyperinflation versus placebo and statistically significant improvements versus monotherapies.,Tiotropium/olodaterol also showed improvements in dyspnoea and exercise tolerance versus placebo but not consistently versus monotherapies.,T/O reduces lung hyperinflation in COPD versus T, O or placebo and increases exercise endurance versus placebohttp://ow.ly/ml3G307XW6a | 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 |
Patients with chronic obstructive pulmonary disease (COPD) have a modified clinical presentation of venous thromboembolism (VTE) but also a worse prognosis than non-COPD patients with VTE.,As it may induce therapeutic modifications, we evaluated the influence of the initial VTE presentation on the 3-month outcomes in COPD patients.,COPD patients included in the on-going world-wide RIETE Registry were studied.,The rate of pulmonary embolism (PE), major bleeding and death during the first 3 months in COPD patients were compared according to their initial clinical presentation (acute PE or deep vein thrombosis (DVT)).,Of the 4036 COPD patients included, 2452 (61%; 95% CI: 59.2-62.3) initially presented with PE.,PE as the first VTE recurrence occurred in 116 patients, major bleeding in 101 patients and mortality in 443 patients (Fatal PE: first cause of death).,Multivariate analysis confirmed that presenting with PE was associated with higher risk of VTE recurrence as PE (OR, 2.04; 95% CI: 1.11-3.72) and higher risk of fatal PE (OR, 7.77; 95% CI: 2.92-15.7).,COPD patients presenting with PE have an increased risk for PE recurrences and fatal PE compared with those presenting with DVT alone.,More efficient therapy is needed in this subtype of patients. | Depression and anxiety are very common in people with chronic obstructive pulmonary disease (COPD) and are associated with excess morbidity and mortality.,Patients prefer non-drug treatments and clinical guidelines promote non-pharmacological interventions as first line therapy for depression and anxiety in people with long term conditions.,However the comparative effectiveness of psychological and lifestyle interventions among COPD patients is not known.,We assessed whether complex psychological and/or lifestyle interventions are effective in reducing symptoms of anxiety and depression in patients with COPD.,We then determined what types of psychological and lifestyle interventions are most effective.,Systematic review of randomised controlled trials of psychological and/or lifestyle interventions for adults with COPD that measured symptoms of depression and/or anxiety.,CENTRAL, Medline, Embase, PsychINFO, CINAHL, ISI Web of Science and Scopus were searched up to April 2012.,Meta-analyses using random effects models were undertaken to estimate the average effect of interventions on depression and anxiety.,Thirty independent comparisons from 29 randomised controlled trials (n = 2063) were included in the meta-analysis.,Overall, psychological and/or lifestyle interventions were associated with small reductions in symptoms of depression (standardised mean difference −0.28, 95% confidence interval −0.41 to −0.14) and anxiety (standardised mean difference −0.23, 95% confidence interval −0.38 to −0.09).,Multi-component exercise training was the only intervention subgroup associated with significant treatment effects for depression (standardised mean difference −0.47, 95% confidence interval −0.66 to −0.28), and for anxiety (standardised mean difference −0.45, 95% confidence interval −0.71 to −0.18).,Complex psychological and/or lifestyle interventions that include an exercise component significantly improve symptoms of depression and anxiety in people with COPD.,Furthermore, multi-component exercise training effectively reduces symptoms of anxiety and depression in all people with COPD regardless of severity of depression or anxiety, highlighting the importance of promoting physical activity in this population. | 1 |
The “can do, do do” concept aims at identifying subgroups among persons with chronic obstructive pulmonary disease (COPD).,Following a two-dimensional categorization, individuals are binarily classified with respect to their levels of physical capacity (“can’t do” or “can do”) and physical activity (“don’t do” or “do do”), resulting in four disjunct quadrants.,The approach has been debated recently and the latest articles have concluded that the quadrants should be specifically examined in terms of psychological aspects of physical activity.,Therefore, the goal of the present study was to explore the role of psychological variables in physical activity in the context of the “can do, do do” quadrant concept.,Within the scope of secondary data analyses of the “Stay Active After Rehabilitation” (STAR) randomized controlled trial, a total of 298 COPD rehabilitants of an inpatient pulmonary rehabilitation program were grouped into the suggested quadrants.,We set fixed cut-offs at 70% of relative 6-min walking test performances for healthy individuals (physical capacity dimension) and 5.000 steps per day (physical activity dimension).,Univariate and multivariate logistic regression analyses served to analyze whether depression scores, fear avoidance behaviors, disease-specific anxiety, self-concordance for physical activity, and five indicators of physical activity-related health competence (PAHCO) effectively discriminated between the “don’t do” and “do do” groups.,Among persons with lower relative physical capacity, depression scores, fear avoidance behaviors, and disease-specific anxiety (univariate case) significantly differentiated between the more and the less active.,Among persons with higher relative physical capacity, fear avoidance behaviors, disease-specific anxiety, as well as three PAHCO indicators (physical activity-specific self-efficacy, self-control, and affect regulation) significantly separated the more and the less active.,In multivariate analyses, only fear avoidance behaviors and affect regulation discriminated among individuals with better relative physical capacity.,The findings identified important psychological and competence-oriented variables that explain discrepancies in the quadrant concept.,Based on this, we discuss implications for physical activity promotion in individuals with COPD.,Respiratory research can benefit from future studies complementing the quadrant concept through further behavioral analyses.,Trial registration Clinicaltrials.gov, ID: NCT02966561.,Registered 17 November, 2016, https://clinicaltrials.gov/ct2/show/NCT02966561. | Pulmonary rehabilitation has short-term benefits on dyspnea, exercise capacity and quality of life in COPD, but evidence suggests these do not always translate to increased daily physical activity on a patient level.,This is attributed to a limited understanding of the determinants of physical activity maintenance following pulmonary rehabilitation.,This systematic review of qualitative research was conducted to understand COPD patients’ perceived facilitators and barriers to physical activity following pulmonary rehabilitation.,Electronic databases of published data, non-published data, and trial registers were searched to identify qualitative studies (interviews, focus groups) reporting the facilitators and barriers to physical activity following pulmonary rehabilitation for people with COPD.,Thematic synthesis of qualitative data was adopted involving line-by-line coding of the findings of the included studies, development of descriptive themes, and generation of analytical themes.,Fourteen studies including 167 COPD patients met the inclusion criteria.,Seven sub-themes were identified as influential to physical activity following pulmonary rehabilitation.,These included: intentions, self-efficacy, feedback of capabilities and improvements, relationship with health care professionals, peer interaction, opportunities following pulmonary rehabilitation and routine.,These encapsulated the facilitators and barriers to physical activity following pulmonary rehabilitation and were identified as sub-themes within the three analytical themes, which were beliefs, social support, and the environment.,The findings highlight the challenge of promoting physical activity following pulmonary rehabilitation in COPD and provide complementary evidence to aid evaluations of interventions already attempted in this area, but also adds insight into future development of interventions targeting physical activity maintenance in COPD. | 1 |
We examined the influence of overweight and obesity on pulmonary function, exercise tolerance, quality of life and response to pulmonary rehabilitation in COPD.,261 patients with COPD were divided into three groups: normal body mass index (BMI), overweight and obese.,Baseline and post rehabilitation pulmonary function, 6-min walking test (6MWT), endurance time during a constant workrate exercise test (CET) and St.,George's Respiratory Questionnaire (SGRQ) scores were compared between all three classes of BMI.,At baseline, obese and overweight patients had less severe airflow obstruction compared to normal BMI patients.,There was no baseline difference in CET performance or SGRQ scores across BMI classes and 6MWT was reduced in the presence of obesity (p < 0.01).,Compared to baseline, post-rehabilitation 6MWT, CET performance and SGRQ scores improved significantly in each group (p < 0.01), but 6MWT was still significantly lower in the presence of obesity.,Walking, but not cycling performance was worse in obese patients.,This difference was maintained post rehabilitation despite significant improvements.,Weight excess may counterbalance the effect of a better preserved respiratory function in the performance of daily activities such as walking.,However, obesity and overweight did not influence the magnitude of improvement after pulmonary rehabilitation. | 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 |
To describe symptoms and lung function in patients registered with asthma or chronic obstructive pulmonary disease (COPD) in primary care and to examine how spirometry findings fit with general practitioners’ (GPs) diagnoses.,Patients aged ≥40 years with a diagnosis of asthma or COPD registered in the electronic medical record during the previous 5 years were recruited at seven GP offices in Norway in 2009-2010.,Registered diagnosis, spirometry results, comorbidity, and reported symptoms were compared.,Among 376 patients, 62% were women.,Based on Global Initiative for Chronic Obstructive Lung Diseases criteria, a spirometry diagnosis of COPD could be made in 68.1% of the patients with a previous COPD diagnosis and in 17.1% of those diagnosed with asthma only (P < 0.001).,The κ agreement between last clinical diagnosis of COPD and COPD based on spirometry was 0.50.,A restrictive spirometry pattern was found in 19.4% and more frequently in patients diagnosed with both asthma and COPD (23.9%) than in patients diagnosed with COPD only (6.8%, P = 0.003).,The ability of GPs to differentiate between asthma and COPD seems to have considerably improved during the last decade, probably due to the dissemination of spirometry and guidelines for COPD diagnosis.,A diagnosis of COPD that cannot be confirmed by spirometry represents a challenge in clinical practice, in particular when a restrictive pattern on spirometry is found. | Major clinical gaps impede the evidence-based treatment of chronic obstructive pulmonary disease (COPD) in the primary care setting.,Studies are needed to measure the effectiveness of continuing medical education (CME) on improving physician competency and performance toward evidence-based COPD care.,Between September 26, 2009 and December 12, 2009, 769 primary care physicians participated in a series of 12 regional, live, interactive, case-based, multiformat, half-day CME programs on COPD.,A subgroup of randomly selected participants (n = 50) and demographically matched nonparticipants (n = 50) completed surveys that included case vignettes, a validated tool for measuring physician performance in clinical practice.,Cohen’s d was used to calculate the magnitude of difference between participants and nonparticipants in the delivery of evidence-based care.,Physicians who participated in CME programs were 50% more likely to provide evidence-based COPD care than physicians who did not participate.,Compared with nonparticipants, participating physicians were more likely to recognize COPD correctly in a patient presenting with dyspnea (74% versus 94%, P = 0.007), recognize that women may have a greater susceptibility than men to the toxic effects of smoking (54% versus 90%, P < 0.001), and identify the mechanisms of action of emerging therapies (33% versus 65%, P = 0.003).,Physicians who participated in a half-day regional CME program on COPD diagnosis, staging, and treatment were significantly more likely than nonparticipants to deliver evidence-based COPD care.,With multiformat, interactive, focused educational interventions, physicians can make diagnostic and therapeutic choices in the primary care setting that align more closely with current guidelines and clinical evidence in COPD management. | 1 |
chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and common in older adults.,The BODE Index is the most recognised mortality risk score in COPD but includes a 6-minute walk test (6MWT) that is seldom available in practise; the BODE Index may be better adopted if the 6MWT was replaced.,we investigated whether a modified BODE Index in which 6MWT was replaced by an alternative measure of physical capacity, specifically the short physical performance battery (SPPB) or components, retained its predictive ability for mortality in individuals with COPD.,we analysed 630 COPD patients from the ERICA cohort study for whom UK Office for National Statistics verified mortality data were available.,Variables tested at baseline included spirometry, 6MWT, SPPB and its components (4-m gait speed test [4MGS], chair stand and balance).,Predictive models were developed using stratified multivariable Cox regression, and assessed by C-indices and calibration plots with 10-fold cross-validation and replication.,during median 2 years of follow-up, 60 (10%) individuals died.,There was no significant difference between the discriminative ability of BODE6MWT (C-index 0.709, 95% confidence interval [CI], 0.680-0.737), BODESPPB (C-index 0.683, 95% CI, 0.647-0.712), BODE4MGS (C-index 0.676, 95% CI, 0.643-0.700) and BODEBALANCE (C-index 0.686, 95% CI, 0.651-0.713) for predicting mortality.,the SPPB, and its 4MGS and balance components, can potentially be used as an alternative to the 6MWT in the BODE Index without significant loss of predictive ability in all-cause mortality. | The Daily-PROactive and Clinical visit-PROactive Physical Activity (D-PPAC and C-PPAC) instruments in chronic obstructive pulmonary disease (COPD) combines questionnaire with activity monitor data to measure patients’ experience of physical activity.,Their amount, difficulty and total scores range from 0 (worst) to 100 (best) but require further psychometric evaluation.,To test reliability, validity and responsiveness, and to define minimal important difference (MID), of the D-PPAC and C-PPAC instruments, in a large population of patients with stable COPD from diverse severities, settings and countries.,We used data from seven randomised controlled trials to evaluate D-PPAC and C-PPAC internal consistency and construct validity by sex, age groups, COPD severity, country and language as well as responsiveness to interventions, ability to detect change and MID.,We included 1324 patients (mean (SD) age 66 (8) years, forced expiratory volume in 1 s 55 (17)% predicted).,Scores covered almost the full range from 0 to 100, showed strong internal consistency after stratification and correlated as a priori hypothesised with dyspnoea, health-related quality of life and exercise capacity.,Difficulty scores improved after pharmacological treatment and pulmonary rehabilitation, while amount scores improved after behavioural physical activity interventions.,All scores were responsive to changes in self-reported physical activity experience (both worsening and improvement) and to the occurrence of COPD exacerbations during follow-up.,The MID was estimated to 6 for amount and difficulty scores and 4 for total score.,The D-PPAC and C-PPAC instruments are reliable and valid across diverse COPD populations and responsive to pharmacological and non-pharmacological interventions and changes in clinically relevant variables. | 1 |
Asthma and chronic obstructive pulmonary disease (COPD) are characterized by airway obstruction and airflow limitation and pose a huge burden to society.,These obstructive lung diseases impact the lung physiology across multiple biological scales.,Environmental stimuli are introduced via inhalation at the organ scale, and consequently impact upon the tissue, cellular and sub-cellular scale by triggering signaling pathways.,These changes are propagated upwards to the organ level again and vice versa.,In order to understand the pathophysiology behind these diseases we need to integrate and understand changes occurring across these scales and this is the driving force for multiscale computational modeling.,There is an urgent need for improved diagnosis and assessment of obstructive lung diseases.,Standard clinical measures are based on global function tests which ignore the highly heterogeneous regional changes that are characteristic of obstructive lung disease pathophysiology.,Advances in scanning technology such as hyperpolarized gas MRI has led to new regional measurements of ventilation, perfusion and gas diffusion in the lungs, while new image processing techniques allow these measures to be combined with information from structural imaging such as Computed Tomography (CT).,However, it is not yet known how to derive clinical measures for obstructive diseases from this wealth of new data.,Computational modeling offers a powerful approach for investigating this relationship between imaging measurements and disease severity, and understanding the effects of different disease subtypes, which is key to developing improved diagnostic methods.,Gaining an understanding of a system as complex as the respiratory system is difficult if not impossible via experimental methods alone.,Computational models offer a complementary method to unravel the structure-function relationships occurring within a multiscale, multiphysics system such as this.,Here we review the current state-of-the-art in techniques developed for pulmonary image analysis, development of structural models of the respiratory system and predictions of function within these models.,We discuss application of modeling techniques to obstructive lung diseases, namely asthma and emphysema and the use of models to predict response to therapy.,Finally we introduce a large European project, AirPROM that is developing multiscale models to investigate structure-function relationships in asthma and COPD. | Chronic Obstructive Pulmonary Disease (COPD) patients are characterized by heterogeneous clinical manifestations and patterns of disease progression.,Two major factors that can be used to identify COPD subtypes are muscle dysfunction/wasting and co-morbidity patterns.,We hypothesized that COPD heterogeneity is in part the result of complex interactions between several genes and pathways.,We explored the possibility of using a Systems Medicine approach to identify such pathways, as well as to generate predictive computational models that may be used in clinic practice.,Our overarching goal is to generate clinically applicable predictive models that characterize COPD heterogeneity through a Systems Medicine approach.,To this end we have developed a general framework, consisting of three steps/objectives: (1) feature identification, (2) model generation and statistical validation, and (3) application and validation of the predictive models in the clinical scenario.,We used muscle dysfunction and co-morbidity as test cases for this framework.,In the study of muscle wasting we identified relevant features (genes) by a network analysis and generated predictive models that integrate mechanistic and probabilistic models.,This allowed us to characterize muscle wasting as a general de-regulation of pathway interactions.,In the co-morbidity analysis we identified relevant features (genes/pathways) by the integration of gene-disease and disease-disease associations.,We further present a detailed characterization of co-morbidities in COPD patients that was implemented into a predictive model.,In both use cases we were able to achieve predictive modeling but we also identified several key challenges, the most pressing being the validation and implementation into actual clinical practice.,The results confirm the potential of the Systems Medicine approach to study complex diseases and generate clinically relevant predictive models.,Our study also highlights important obstacles and bottlenecks for such approaches (e.g. data availability and normalization of frameworks among others) and suggests specific proposals to overcome them. | 1 |
Chronic Obstructive Pulmonary Disease is the third leading cause of death in the US, and is associated with periodic exacerbations, which account for the largest proportion of health care utilization, and lead to significant morbidity, mortality, and worsening lung function.,A subset of patients with COPD have frequent exacerbations, occurring 2 or more times per year.,Despite many interventions to reduce COPD exacerbations, there is a significant lack of knowledge in regards to their mechanisms and predisposing factors.,We describe here an important observation that defines antibody deficiency as a potential risk factor for frequent COPD exacerbations.,We report a case series of patients who have frequent COPD exacerbations, and who were found to have an underlying primary antibody deficiency syndrome.,We also report on the outcome of COPD exacerbations following treatment in a subset with of these patients with antibody deficiency.,We identified patients with COPD who had 2 or more moderate to severe exacerbations per year; immune evaluation including serum immunoglobulin levels and pneumococcal IgG titers was performed.,Patients diagnosed with an antibody deficiency syndrome were treated with either immunoglobulin replacement therapy or prophylactic antibiotics, and their COPD exacerbations were monitored over time.,A total of 42 patients were identified who had 2 or more moderate to severe COPD exacerbations per year.,Twenty-nine patients had an underlying antibody deficiency syndrome: common variable immunodeficiency (8), specific antibody deficiency (20), and selective IgA deficiency (1).,Twenty-two patients had a follow-up for at least 1 year after treatment of their antibody deficiency, which resulted in a significant reduction of COPD exacerbations, courses of oral corticosteroid use and cumulative annual dose of oral corticosteroid use, rescue antibiotic use, and hospitalizations for COPD exacerbations.,This case series identifies antibody deficiency as a potentially treatable risk factor for frequent COPD exacerbations; testing for antibody deficiency should be considered in difficult to manage frequently exacerbating COPD patients.,Further prospective studies are warranted to further test this hypothesis. | Acute exacerbations contribute to the morbidity and mortality associated with chronic obstructive pulmonary disease (COPD).,This proof-of-concept study evaluates whether intermittent pulsed moxifloxacin treatment could reduce the frequency of these exacerbations.,Stable patients with COPD were randomized in a double-blind, placebo-controlled trial to receive moxifloxacin 400 mg PO once daily (N = 573) or placebo (N = 584) once a day for 5 days.,Treatment was repeated every 8 weeks for a total of six courses.,Patients were repeatedly assessed clinically and microbiologically during the 48-week treatment period, and for a further 24 weeks' follow-up.,At 48 weeks the odds ratio (OR) for suffering an exacerbation favoured moxifloxacin: per-protocol (PP) population (N = 738, OR 0.75, 95% confidence interval (CI) 0.565-0.994, p = 0.046), intent-to-treat (ITT) population (N = 1149, OR 0.81, 95% CI 0.645-1.008, p = 0.059), and a post-hoc analysis of per-protocol (PP) patients with purulent/mucopurulent sputum production at baseline (N = 323, OR 0.55, 95% CI 0.36-0.84, p = 0.006).,There were no significant differences between moxifloxacin and placebo in any pre-specified efficacy subgroup analyses or in hospitalization rates, mortality rates, lung function or changes in St George's Respiratory Questionnaire (SGRQ) total scores.,There was, however, a significant difference in favour of moxifloxacin in the SGRQ symptom domain (ITT: -8.2 vs -3.8, p = 0.009; PP: -8.8 vs -4.4, p = 0.006).,Moxifloxacin treatment was not associated with consistent changes in moxifloxacin susceptibility.,There were more treatment-emergent, drug related adverse events with moxifloxacin vs placebo (p < 0.001) largely due to gastrointestinal events (4.7% vs 0.7%).,Intermittent pulsed therapy with moxifloxacin reduced the odds of exacerbation by 20% in the ITT population, by 25% among the PP population and by 45% in PP patients with purulent/mucopurulent sputum at baseline.,There were no unexpected adverse events and there was no evidence of resistance development.,ClinicalTrials.gov number, NCT00473460 (ClincalTrials.gov). | 1 |
Traditional Chinese medicine (TCM) has been used to treat chronic obstructive pulmonary disease (COPD) for many years.,This study aimed to evaluate the efficacy and safety of the comprehensive therapy based on the three common TCM patterns in stable COPD patients.,A four-center, open-label randomized controlled method was conducted.,A total of 352 patients were divided into the trial group (n = 176, treated with conventional Western medicine and Bu-Fei Jian-Pi granules, Bu-Fei Yi-Shen granules, and Yi-Qi Zi-Shen granules based on the TCM patterns respectively) and the control group (n = 176, treated with conventional Western medicine).,The frequency and duration of acute exacerbation, lung function, clinical symptoms, 6-minute walking distance (6MWD), dyspnea scale and quality of life were observed during a 6-month treatment period and at a further 12-month follow-up.,A total of 306 patients completed the study fully.,The full analysis set (FAS) population was 350 and the per-protocol analysis set (PPS) population was 306.,After the 6-month treatment and 12-month follow-up, there were significant differences between the trial and control group in the following: frequency of acute exacerbation (FAS: P = 0.000; PPS: P = 0.000); duration of acute exacerbation (FAS: P = 0.000; PPS: P = 0.001); FEV1 (FAS: P = 0.007; PPS: P = 0.008); symptoms (FAS: P = 0.001; PPS: P = 0.001); 6MWD (FAS: P = 0.045; PPS: P = 0.042); dyspnea scale (FAS: P = 0.002; PPS: P = 0.004); and physical domain (FAS: P = 0.000; PPS: P = 0.000), psychological domain (FAS: P = 0.008; PPS: P = 0.011), social domain (FAS: P = 0.001; PPS: P = 0.000) and environment domain (FAS: P = 0.015; PPS: P = 0.009) of the WHOQOL-BREF questionnaire.,There were no differences between the trial and control group in FVC, FEV1% and adverse events.,Based on the TCM patterns, Bu-Fei Jian-Pi granules, Bu-Fei Yi-Shen granules and Yi-Qi Zi-Shen granules have beneficial effects on measured outcomes in stable COPD patients over the 6-month treatment and 12-month follow-up, with no relevant between-group differences in adverse events.,This trial was registered at Chinese Clinical Trial Register Center, ChiCTR-TRC-11001406. | Asthma and chronic obstructive pulmonary disease (COPD) display features of overlap in airway physiology and airway inflammation.,Whether inflammatory phenotypes in airway disease describe similar mediator expression is unknown.,To explore the relationship of airway inflammation and cytokine and chemokine expression in asthma and COPD.,Subjects with asthma and COPD (n = 54 and n = 49) were studied.,Clinical characteristics and sputum were collected at entry into the study.,A 2-step sputum processing method was performed for supernatant and cytospin preparation.,Meso Scale Discovery and Luminex platforms were used to measure cytokines, chemokines and matrix metalloproteinase levels.,Analytes sensitive to dithiothreitol (DTT) that had increased recovery in the 2-step sputum process were IL-1β, 4, 5, 10, 13, IFN-γ, TNFRI, GM-CSF, CCL2, 3, 4, 5, 13 and 17.,There was a differential expression in IL-8, TNFRI and TNFRII between asthma and COPD [mean fold difference (95% CI): IL-8, 2.6 (1.3-5.4), p = 0.01; TNFRI, 2.1 (1.3-5.4), p = 0.03; TNFRII, 2.6 (1.2-5.6), p = 0.02].,In neutrophilic and eosinophilic airway inflammation, TNFα, TNFRI, TNFRII, IL-6, IL-8 and IL-5 could differentiate between these phenotypes.,However, these phenotypes were unrelated to the diagnosis of asthma or COPD.,Recovery of sputum mediators sensitive to DTT can be improved using the described sputum processing technique.,Within airway inflammatory sub-phenotypes there is a differential pattern of mediator expression that is independent of disease.,Whether these inflammatory phenotypes in asthma and COPD confer distinct pathogeneses, therapeutic responses and clinical phenotypes needs to be further evaluated. | 1 |
Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the most common reason for the hospitalization and death of pulmonary patients.,The use of antibiotics as adjuvant therapy for AECOPD, however, is still a matter of debate.,In this study, we searched the PubMed, EmBase, and Cochrane databases for randomized controlled trials published until September 2016 that evaluated the use of antibiotics for AECOPD treatment.,The major outcome variables were clinical cure rate and adverse effects.,The microbiological response rate, relapse of exacerbation, and mortality were also analysed.,A random-effect network was used to assess the effectiveness and tolerance of each antibiotic used for AECOPD treatment.,In this meta-analysis, we included 19 articles that assessed 17 types of antibiotics used in 5906 AECOPD patients.,The cluster ranking showed that dirithromycin had a high clinical cure rate with a low rate of adverse effects.,Ofloxacin, ciprofloxacin, and trimethoprim-sulfamethoxazole had high clinical cure rates with median rates of adverse effects.,In terms of the microbiological response rate, only doxycycline was significantly better than placebo (odds ratio (OR), 3.84; 95% confidence interval (CI), 1.96-7.54; p < 0.001).,There were no other significant results with respect to the frequency of recurrence or mortality.,Our study indicated that dirithromycin is adequate for improving the clinical cure rate of patients with AECOPD with few adverse effects.,Ofloxacin, ciprofloxacin, and trimethoprim-sulfamethoxazole are also recommended for disease treatment.,However, caution should still be exercised when using antibiotics to treat AECOPD.,Trial Registration Not applicable.,The online version of this article (doi: 10.1186/s12890-017-0541-0) contains supplementary material, which is available to authorized users. | The Asp358Ala variant in the interleukin-6 receptor (IL-6R) gene has been implicated in asthma, autoimmune and cardiovascular disorders, but its role in other respiratory conditions such as chronic obstructive pulmonary disease (COPD) has not been investigated.,The aims of this study were to evaluate whether there is an association between Asp358Ala and COPD or asthma risk, and to explore the role of the Asp358Ala variant in sIL-6R shedding from neutrophils and its pro-inflammatory effects in the lung.,We undertook logistic regression using data from the UK Biobank and the ECLIPSE COPD cohort.,Results were meta-analyzed with summary data from a further three COPD cohorts (7,519 total cases and 35,653 total controls), showing no association between Asp358Ala and COPD (OR = 1.02 [95% CI: 0.96, 1.07]).,Data from the UK Biobank showed a positive association between the Asp358Ala variant and atopic asthma (OR = 1.07 [1.01, 1.13]).,In a series of in vitro studies using blood samples from 37 participants, we found that shedding of sIL-6R from neutrophils was greater in carriers of the Asp358Ala minor allele than in non-carriers.,Human pulmonary artery endothelial cells cultured with serum from homozygous carriers showed an increase in MCP-1 release in carriers of the minor allele, with the difference eliminated upon addition of tocilizumab.,In conclusion, there is evidence that neutrophils may be an important source of sIL-6R in the lungs, and the Asp358Ala variant may have pro-inflammatory effects in lung cells.,However, we were unable to identify evidence for an association between Asp358Ala and COPD. | 1 |
Polymorphonuclear neutrophils have in recent years attracted new attention due to their ability to release neutrophil extracellular traps (NETs).,These web-like extracellular structures deriving from nuclear chromatin have been depicted in ambiguous roles between antimicrobial defence and host tissue damage.,NETs consist of DNA strands of varying thickness and are decorated with microbicidal and cytotoxic proteins.,Their principal structure has in recent years been characterised at molecular and ultrastructural levels but many features that are of direct relevance to cytotoxicity are still incompletely understood.,These include the extent of chromatin decondensation during NET formation and the relative amounts and spatial distribution of the microbicidal components within the NET.,In the present work, we analyse the structure of NETs found in induced sputum of patients with acutely exacerbated chronic obstructive pulmonary disease (COPD) using confocal laser microscopy and electron microscopy.,In vitro induced NETs from human neutrophils serve for purposes of comparison and extended analysis of NET structure.,Results demonstrate that COPD sputa are characterised by the pronounced presence of NETs and NETotic neutrophils.,We provide new evidence that chromatin decondensation during NETosis is most extensive and generates substantial amounts of double-helix DNA in ‘beads-on-a-string’ conformation.,New information is also presented on the abundance and location of neutrophil elastase (NE) and citrullinated histone H3 (citH3).,NE occurs in high densities in nearly all non-fibrous constituents of the NETs while citH3 is much less abundant.,We conclude from the results that (i) NETosis is an integral part of COPD pathology; this is relevant to all future research on the etiology and therapy of the disease; and that (ii) release of ‘beads-on-a-string’ DNA studded with non-citrullinated histones is a common feature of in vivo NETosis; this is of relevance to both the antimicrobial and the cytotoxic effects of NETs. | Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder for which new diagnostic and therapeutic approaches are required.,Hallmarks of COPD are matrix destruction and neutrophilic airway inflammation in the lung.,We have previously described two tri-peptides, N-α-PGP and PGP, which are collagen fragments and neutrophil chemoattractants.,In this study, we investigate if N-α-PGP and PGP are biomarkers and potential therapeutic targets for COPD.,Induced sputum samples from COPD patients, healthy controls and asthmatics were examined for levels of N-α-PGP and PGP using mass spectrometry and for the ability to generate PGP de novo from collagen.,Proteases important in PGP generation in the lung were identified by the use of specific inhibitors in the PGP generation assay and by instillation of proteases into mouse lungs.,Serum levels of PGP were compared between COPD patients and controls.,N-α-PGP was detected in most COPD sputum samples but in no asthmatics or controls.,PGP was detected in a few controls and in all COPD sputum samples, where it correlated with levels of myeloperoxidase.,COPD sputum samples had the ability to generate N-α-PGP and PGP de novo from collagen.,PGP generation by COPD sputum was blocked by inhibitors of matrix metalloproteases (MMP's) 1 and 9 and prolyl endopeptidase.,MMP's 1 and 9 and prolyl endopeptidase acted synergistically to generate PGP in vivo when instilled into mouse lungs.,Serum levels of PGP were also significantly higher in COPD patients than in controls,N-α-PGP and PGP may represent novel diagnostic tests and biomarkers for COPD.,Inhibition of this pathway may provide novel therapies for COPD directed at the chronic, neutrophilic, airway inflammation which underlies disease progression. | 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. | 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. | 1 |
To assess the effect of telehealthcare compared with usual practice in patients with chronic obstructive pulmonary disease (COPD).,A cluster-randomised trial with 26 municipal districts that were randomly assigned either to an intervention group whose members received telehealthcare in addition to usual practice or to a control group whose members received usual practice only (13 districts in each arm).,Twenty-six municipal districts in the North Denmark Region of Denmark.,Patients who fulfilled the Global Initiative for COPD guidelines and one of the following criteria: COPD Assessment Test score ≥10; or Medical Research Dyspnoea Council Scale ≥3; or Modified Medical Research Dyspnoea Council Scale ≥2; or ≥2 exacerbations during the past 12 months.,Health-related quality of life (HRQoL) assessed by the physical component summary (PCS) and mental component summary (MCS) scores of the Short Form 36-Item Health Survey, Version 2.,Data were collected at baseline and at 12 month follow-up and analysed according to the intention-to-treat principle with complete cases, n=574 (258 interventions; 316 controls) and imputed data, n=1225 (578 interventions, 647 controls) using multilevel modelling.,In the intention-to-treat analysis (n=1225), the raw mean difference in PCS from baseline to 12 month follow-up was −2.6 (SD 12.4) in the telehealthcare group and −2.8 (SD 11.9) in the usual practice group.,The raw mean difference in MCS scores in the same period was −4.7 (SD 16.5) and −5.3 (SD 15.5) for telehealthcare and usual practice, respectively.,The adjusted mean difference in PCS and MCS between groups at 12 months was 0.1 (95% CI −1.4 to 1.7) and 0.4 (95% CI −1.7 to 2.4), respectively.,The overall sample and all subgroups demonstrated no statistically significant differences in HRQoL between telehealthcare and usual practice.,NCT01984840; Results. | Pulmonary rehabilitation is a cornerstone of care for COPD but uptake of traditional centre-based programmes is poor.,We assessed whether home-based pulmonary rehabilitation, delivered using minimal resources, had equivalent outcomes to centre-based pulmonary rehabilitation.,A randomised controlled equivalence trial with 12 months follow-up.,Participants with stable COPD were randomly assigned to receive 8 weeks of pulmonary rehabilitation by either the standard outpatient centre-based model, or a new home-based model including one home visit and seven once-weekly telephone calls from a physiotherapist.,The primary outcome was change in 6 min walk distance (6MWD).,We enrolled 166 participants to receive centre-based rehabilitation (n=86) or home-based rehabilitation (n=80).,Intention-to-treat analysis confirmed non-inferiority of home-based rehabilitation for 6MWD at end-rehabilitation and the confidence interval (CI) did not rule out superiority (mean difference favouring home group 18.6 m, 95% CI −3.3 to 40.7).,At 12 months the CI did not exclude inferiority (−5.1 m, −29.2 to 18.9).,Between-group differences for dyspnoea-related quality of life did not rule out superiority of home-based rehabilitation at programme completion (1.6 points, −0.3 to 3.5) and groups were equivalent at 12 months (0.05 points, −2.0 to 2.1).,The per-protocol analysis showed the same pattern of findings.,Neither group maintained postrehabilitation gains at 12 months.,This home-based pulmonary rehabilitation model, delivered with minimal resources, produced short-term clinical outcomes that were equivalent to centre-based pulmonary rehabilitation.,Neither model was effective in maintaining gains at 12 months.,Home-based pulmonary rehabilitation could be considered for people with COPD who cannot access centre-based pulmonary rehabilitation.,NCT01423227, clinicaltrials.gov. | 1 |
Chronic obstructive pulmonary disease (COPD) was the fourth leading cause of death worldwide in 2015.,Current treatments for patients ease discomfort and help decrease disease progression; however, none improve lung function or change mortality.,COPD is heterogeneous in its molecular and clinical presentation, making it difficult to understand disease aetiology and define robust therapeutic strategies.,Given the complexity of the disease we propose a precision medicine approach to understanding and better treating COPD.,It is possible that multiOMICs can be used as a tool to integrate data from multiple fields.,Moreover, analysis of electronic medical records could aid in the treatment of patients and in the predictions of outcomes.,The Precision Medicine Initiative created in 2015 has made precision medicine approaches to treat disease a reality; one of these diseases being COPD. | Pulmonary rehabilitation is a cornerstone of care for COPD but uptake of traditional centre-based programmes is poor.,We assessed whether home-based pulmonary rehabilitation, delivered using minimal resources, had equivalent outcomes to centre-based pulmonary rehabilitation.,A randomised controlled equivalence trial with 12 months follow-up.,Participants with stable COPD were randomly assigned to receive 8 weeks of pulmonary rehabilitation by either the standard outpatient centre-based model, or a new home-based model including one home visit and seven once-weekly telephone calls from a physiotherapist.,The primary outcome was change in 6 min walk distance (6MWD).,We enrolled 166 participants to receive centre-based rehabilitation (n=86) or home-based rehabilitation (n=80).,Intention-to-treat analysis confirmed non-inferiority of home-based rehabilitation for 6MWD at end-rehabilitation and the confidence interval (CI) did not rule out superiority (mean difference favouring home group 18.6 m, 95% CI −3.3 to 40.7).,At 12 months the CI did not exclude inferiority (−5.1 m, −29.2 to 18.9).,Between-group differences for dyspnoea-related quality of life did not rule out superiority of home-based rehabilitation at programme completion (1.6 points, −0.3 to 3.5) and groups were equivalent at 12 months (0.05 points, −2.0 to 2.1).,The per-protocol analysis showed the same pattern of findings.,Neither group maintained postrehabilitation gains at 12 months.,This home-based pulmonary rehabilitation model, delivered with minimal resources, produced short-term clinical outcomes that were equivalent to centre-based pulmonary rehabilitation.,Neither model was effective in maintaining gains at 12 months.,Home-based pulmonary rehabilitation could be considered for people with COPD who cannot access centre-based pulmonary rehabilitation.,NCT01423227, clinicaltrials.gov. | 1 |
This study aimed to generate real-world evidence to assess the burden of comorbidities in COPD patients, to effectively manage these patients and optimize the associated healthcare resource allocation.,ARCTIC is a large, real-world, retrospective cohort study conducted in Swedish COPD patients using electronic medical record data collected between 2000 and 2014.,These patients were studied for prevalence of various comorbidities and for association of these comorbidities with exacerbations, mortality, and healthcare costs compared with an age-, sex-, and comorbidities-matched non-COPD reference population.,A total of 17,479 patients with COPD were compared with 84,514 non-COPD reference population.,A significantly higher prevalence of various comorbidities was observed in COPD patients 2 years post-diagnosis vs. reference population, with the highest percentage increase observed for cardiovascular diseases (81.8% vs.,30.7%).,Among the selected comorbidities, lung cancer was relatively more prevalent in COPD patients vs. reference population (relative risk, RR = 5.97, p < 0.0001).,Ischemic heart disease, hypertension, depression, anxiety, sleep disorders, osteoporosis, osteoarthritis, and asthma caused increased mortality rates in COPD patients.,Comorbidities that were observed to be significantly associated with increased number of severe exacerbations in COPD patients included heart failure, ischemic heart disease, depression/anxiety, sleep disorders, osteoporosis, lung cancer, and stroke.,The cumulative healthcare costs associated with comorbidities over 2 years after the index date were observed to be significantly higher in COPD patients (€27,692) vs. reference population (€5141) (p < 0.0001).,The data support the need for patient-centered treatment strategies and targeted healthcare resource allocation to reduce the humanistic and economic burden associated with COPD comorbidities.,Co-existing conditions should be taken into consideration when treating patients with chronic lung disease to ensure coherent and cost-effective disease management.,In a large-scale study of the Swedish population, Björn Ställberg at Uppsala University and co-workers analyzed electronic medical records spanning fourteen years for 17,479 patients with chronic obstructive pulmonary disease (COPD) and compared their health status with 84,514 age-, sex- and comorbidity-matched non-COPD members of the population.,Patients with COPD were significantly more likely to suffer from co-morbidities two years after initial diagnosis than their non-COPD counterparts, with cardiovascular diseases being the most common comorbidities.,Lung cancer, hypertension, depression and sleep disorders were among other comorbidities more prevalent in the COPD population.,These data support the need for fully integrated, targeted healthcare to reduce mortality and the economic burden associated with COPD. | The term multimorbidity is usually defined as the coexistence of two or more chronic conditions within an individual, whereas the term comorbidity traditionally describes patients with an index condition and one or more additional conditions.,Multimorbidity of chronic conditions markedly worsens outcomes in patients, increases treatment burden and increases health service costs.,Although patients with chronic respiratory disease often have physical comorbidities, they also commonly experience psychological problems such as depression and anxiety.,Multimorbidity is associated with increased health-care utilisation and specifically with an increased number of prescription drugs in individuals with multiple chronic conditions such as chronic obstructive pulmonary disease.,This npj Primary Care Respiratory Medicine Education Section case study involves a patient in a primary care consultation presenting several common diseases prevalent in people of this age.,The patient takes nine different drugs at this moment, one or more pills for each condition, which amounts to polypharmacy.,The problems related with polypharmacy recommend that a routine medication review by primary care physicians be performed to reduce the risk of adverse effects of polypharmacy among those with multiple chronic conditions.,The primary care physician has the challenging role of integrating all of the clinical problems affecting the patient and reviewing all medicaments (including over-the-counter medications) taken by the patient at any point in time, and has the has the key to prevent the unwanted consequences of polypharmacy.,Multimorbid chronic disease management can be achieved with the use of care planning, unified disease templates, use of information technology with appointment reminders and with the help of the wider primary care and community teams. | 1 |
The Phase IV, 8-week, randomized, double-blind, placebo-controlled ACTIVATE study (NCT02424344) evaluated the effect of aclidinium/formoterol (AB/FF) 400/12 μg twice daily on lung hyperinflation, exercise capacity, and physical activity in patients with moderate-to-severe COPD.,Patients received AB/FF (n=134) or placebo (n=133) (1:1) via the Genuair™/Pressair® dry powder inhaler for 8 weeks.,From Weeks 5 to 8, all patients participated in behavioral intervention (BI; daily messages providing step goals).,The primary end point was trough functional residual capacity (FRC) at Week 4.,Exercise endurance time and physical activity were assessed at Week 4 (pharmacotherapy only) and at Week 8 (8 weeks of pharmacotherapy plus 4 weeks of BI).,Other end points included post-dose FRC, residual volume, and inspiratory capacity (IC) at rest and during exercise.,After 4 weeks, trough FRC improved with AB/FF versus placebo but did not reach significance (125 mL; P=0.0690).,However, post-dose FRC, residual volume, and IC at rest improved significantly with AB/FF at Week 4 versus placebo (all P<0.0001).,AB/FF significantly improved exercise endurance time and IC at isotime versus placebo at Week 4 (P<0.01 and P<0.0001, respectively) and Week 8 (P<0.05 and P<0.0001, respectively).,AB/FF achieved higher step counts (P<0.01) with fewer inactive patients (P<0.0001) at Week 4 versus placebo.,Following BI, AB/FF maintained improvements in physical activity at Week 8 and nonsignificant improvements were observed with placebo.,AB/FF 400/12 μg demonstrated improvements in lung hyperinflation, exercise capacity, and physical activity versus placebo that were maintained following the addition of BI.,A 4-week period of BI might be too short to augment the improvements of physical activity observed with AB/FF. | Chest physiotherapy enhances sputum evacuation in COPD patients.,It can be applied as a single technique or as a combination of techniques including intrapulmonary percussive ventilation (IPV).,Recently developed assessment techniques may provide new insights into the effect of airway clearance techniques.,Five moderate to severe COPD patients (three females and two males; mean forced expiratory volume in 1 second of 39.49% predicted) who were admitted in the hospital for an acute exacerbation were included in this study.,A novel imaging technique was used, together with other conventional techniques, to visualize the short-term effects of a single IPV treatment in COPD patients.,No significant changes were noted in the lung function parameters or arterial blood gases measured within 1 hour after the end of the IPV session.,Computed tomography images detected changes in the airway patency after the IPV treatment compared with before treatment.,Local resistances, calculated for the three-dimensional models, showed local changes in airway resistance.,The effects of a single IPV session can be visualized by functional imaging.,This functional imaging allows a calculation of changes in local airway resistance and local changes in airway volume in COPD patients without affecting conventional lung function parameters. | 1 |
Understanding the genetic basis of airflow obstruction and smoking behaviour is key to determining the pathophysiology of chronic obstructive pulmonary disease (COPD).,We used UK Biobank data to study the genetic causes of smoking behaviour and lung health.,We sampled individuals of European ancestry from UK Biobank, from the middle and extremes of the forced expiratory volume in 1 s (FEV1) distribution among heavy smokers (mean 35 pack-years) and never smokers.,We developed a custom array for UK Biobank to provide optimum genome-wide coverage of common and low-frequency variants, dense coverage of genomic regions already implicated in lung health and disease, and to assay rare coding variants relevant to the UK population.,We investigated whether there were shared genetic causes between different phenotypes defined by extremes of FEV1.,We also looked for novel variants associated with extremes of FEV1 and smoking behaviour and assessed regions of the genome that had already shown evidence for a role in lung health and disease.,We set genome-wide significance at p<5 × 10−8.,UK Biobank participants were recruited from March 15, 2006, to July 7, 2010.,Sample selection for the UK BiLEVE study started on Nov 22, 2012, and was completed on Dec 20, 2012.,We selected 50 008 unique samples: 10 002 individuals with low FEV1, 10 000 with average FEV1, and 5002 with high FEV1 from each of the heavy smoker and never smoker groups.,We noted a substantial sharing of genetic causes of low FEV1 between heavy smokers and never smokers (p=2·29 × 10−16) and between individuals with and without doctor-diagnosed asthma (p=6·06 × 10−11).,We discovered six novel genome-wide significant signals of association with extremes of FEV1, including signals at four novel loci (KANSL1, TSEN54, TET2, and RBM19/TBX5) and independent signals at two previously reported loci (NPNT and HLA-DQB1/HLA-DQA2).,These variants also showed association with COPD, including in individuals with no history of smoking.,The number of copies of a 150 kb region containing the 5′ end of KANSL1, a gene that is important for epigenetic gene regulation, was associated with extremes of FEV1.,We also discovered five new genome-wide significant signals for smoking behaviour, including a variant in NCAM1 (chromosome 11) and a variant on chromosome 2 (between TEX41 and PABPC1P2) that has a trans effect on expression of NCAM1 in brain tissue.,By sampling from the extremes of the lung function distribution in UK Biobank, we identified novel genetic causes of lung function and smoking behaviour.,These results provide new insight into the specific mechanisms underlying airflow obstruction, COPD, and tobacco addiction, and show substantial shared genetic architecture underlying airflow obstruction across individuals, irrespective of smoking behaviour and other airway disease.,Medical Research Council. | Substantial evidence suggests that there is genetic susceptibility to chronic obstructive pulmonary disease (COPD).,To identify common genetic risk variants, we performed a genome-wide association study in 2940 cases and 1380 smoking controls with normal lung function.,We demonstrate a novel susceptibility locus at 4q22.1 in FAM13A (rs7671167, OR=0.76, P=8.6×10−8) and provide evidence of replication in one case-control and two family-based cohorts (for all studies, combined P=1.2×10−11). | 1 |
Transforming growth factor-beta1 (TGF-β1) is a multipotential cytokine with angiogenic activity.,There are only limited data about its role in airway remodeling in COPD.,We have previously shown that the reticular basement membrane (Rbm) is hypervascular in the airways of current smokers either with or without chronic obstructive pulmonary disease (COPD).,This study evaluated TGF-β1 immunostaining in the Rbm and its relationship to vascularity in smokers with or without COPD.,Bronchial biopsies from 15 smokers with normal lung function, 19 current and 14 ex-smokers with COPD were immunostained for TGF-β1 antibody and compared to 17 healthy controls.,The percentage area of tissue and also number and area of vessels staining positively for TGF-β1 were measured and compared between groups.,Some bronchial biopsies from current smoking COPD subjects were also stained for phosphorylated (active) Smad2/3.,Epithelial TGF- β1 staining was not different between COPD current smokers and normal controls.,TGF-β1 stained vessels in the Rbm were increased in smokers with normal lung function, current smoking COPD and ex-smokers with COPD compared to controls [median (range) for number of vessels/mm Rbm 2.5 (0.0-12.7), 3.4 (0.0-8.1) and 1.0 (0.0-6.3) vs.,0.0 (0.0-7.0), p<0.05].,Percentage of vessels stained was also increased in these clinical groups.,Preliminary data suggest that in current smoking COPD subjects endothelial cells and cells in the Rbm stain positively for phosphorylated Smad2/3 suggesting TGF-β1 is functionally active in this situation.,Vessel-associated TGF-β1 activity is increased in the bronchial Rbm in smokers and especially those with COPD. | 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 |
The role of anxiety and depression in the physical activity (PA) of patients with COPD is controversial.,We prospectively assessed the effect of symptoms of anxiety and depression on PA in COPD patients.,We evaluated anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), PA (Dynaport® accelerometer), and other relevant characteristics in 220 COPD patients from five European countries at baseline and at 6 and 12 months of follow-up.,HADS score was categorized as: no symptoms (score 0-7), suggested (8-10), and probable (>11) anxiety or depression.,We estimated the association between anxiety and depression at t (baseline and 6 months) and PA at t+1 (6 and 12 months) using regression models with a repeated measures approach.,Patients had a mean (standard deviation) age of 67 (8) years, forced expiratory volume in 1 second 57 (20)% predicted.,At baseline, the prevalence of probable anxiety and depression was 10% and 5%, respectively.,In multivariable models adjusted by confounders and previous PA, patients performed 81 fewer steps/day (95% confidence interval, −149 to −12, P=0.02) per extra point in HADS-depression score.,HADS-anxiety symptoms were not associated with PA.,In COPD patients, symptoms of depression are prospectively associated with a measurable reduction in PA 6 months later. | COPD patients may be at increased risk for vitamin D (25(OH)D) deficiency, but risk factors for deficiency among COPD patients have not been extensively reported.,Serum 25(OH)D levels were measured by liquid chromatography double mass spectrometry in subjects aged 40-76 years from Western Norway, including 433 COPD patients (GOLD stage II-IV) and 325 controls.,Levels <20 ng/mL defined deficiency.,Season, sex, age, body mass index (BMI), smoking, GOLD stage, exacerbation frequency, arterial oxygen tension (PaO2), respiratory symptoms, depression (CES-D score≥16), comorbidities (Charlson score), treatment for osteoporosis, use of inhaled steroids, and total white blood count were examined for associations with 25(OH)D in both linear and logistic regression models.,COPD patients had an increased risk for vitamin D deficiency compared to controls after adjustment for seasonality, age, smoking and BMI.,Variables associated with lower 25(OH)D levels in COPD patients were obesity ( = −6.63), current smoking ( = −4.02), GOLD stage III- IV ( = −4.71, = −5.64), and depression ( = −3.29).,Summertime decreased the risk of vitamin D deficiency (OR = 0.22).,COPD was associated with an increased risk of vitamin D deficiency, and important disease characteristics were significantly related to 25(OH)D levels. | 1 |
The severity of chronic obstructive pulmonary disease (COPD) should not be based on the level of airflow limitation alone.,A multicomponent index such as the DOSE index (dyspnoea score (D), level of airflow obstruction (O), current smoking status (S), and exacerbations (E)) has the potential to predict important future outcomes in patients with COPD more effectively than the forced expiratory volume in one second.,Health status deterioration should be prevented in COPD patients.,To investigate whether the DOSE index can predict which patients are at risk of a clinically relevant change in health status.,A prospective cohort study was performed using data from primary and secondary care.,The DOSE score was determined at baseline and the 2-year change in the Clinical COPD Questionnaire (CCQ) score was calculated.,Linear regression analysis was performed for the effect of a high DOSE score (≥4) on the change in CCQ score.,The study population consisted of 209 patients (112 patients from primary care).,Overall, a high DOSE score was a significant predictor of a change in CCQ score after 2 years (0.41, 95% CI 0.13 to 0.70), particularly in primary care patients.,A DOSE score of ≥4 has the ability to identify COPD patients with a greater risk of future worsening in health status. | Intergenerational associations in chronic obstructive pulmonary disease (COPD) have been well recognized and may result from genetic, gene environment, or exposure to life course factors.,Consequently, adult offspring of parents with COPD may be at a greater risk of developing COPD.,The aim of this study was to review the prevalence of co-occurrence of COPD in adult offspring with one or both parents having COPD independent of specific genetic variations.,In total, five databases were searched for original studies in which prevalence of COPD was reported in both offspring (children) and one or both parents.,Studies were excluded if COPD was not clearly defined, COPD was linked to specific genetic variations, COPD was combined with other chronic respiratory conditions, or estimates included other first-degree relatives.,Data extraction (ie, sample characteristics, prevalence of COPD, and odds ratio [OR] if reported) was completed by two independent reviewers.,A meta-analysis of prevalence and OR was conducted, where possible.,Of the 3,382 citations, 129 full texts were reviewed to include eight studies (six case-control, one cross-sectional, and one cohort) reflecting either prevalence of COPD in offspring of parents with COPD (descendent approach, n=3), which ranged from 0% to 17.3%, or prevalence of people with COPD reporting positive parental history of COPD (antecedent approach, n=5), for which the pooled prevalence was 28.6%.,Offspring of people with COPD had 1.57 times greater odds (95% confidence interval =1.29-1.93; P<0.001) of having COPD compared with people not having a parental history of COPD.,The prevalence of COPD in adult offspring of people with COPD is greater than population-based estimates, and the ORs indicate a higher risk in this group.,This offers clinicians a potential strategy for opportunistic screening, early identification, and intervention in this at-risk group. | 1 |
The imbalance between pro- and anti-inflammatory immune responses plays a pivotal role in chronic obstructive pulmonary disease (COPD) development and progression.,To clarify the pathophysiological mechanisms of this disease, we performed a temporal analysis of immune response-mediated inflammatory progression in a cigarette smoke (CS)-induced mouse model with a focus on the balance between Th17 and Treg responses.,C57BL/6 mice were exposed to CS for 1, 3 or 6 months to induce COPD, and the control groups were maintained under filtered air conditions for the same time intervals.,We then performed functional (respiratory mechanics) and structural (alveolar enlargement) analyses.,We also quantified the NF-κB, TNF-α, CD4, CD8, CD20, IL-17, IL-6, FOXP3, IL-10, or TGF-β positive cells in peribronchovascular areas and assessed FOXP3 and IL-10 expression through double-label immunofluorescence.,Additionally, we evaluated the gene expression of NF-κB and TNF in bronchiolar epithelial cells.,Our CS-induced COPD model exhibited an increased proinflammatory immune response (increased expression of the NF-κB, TNF-α, CD4, CD8, CD20, IL-17, and IL-6 markers) with a concomitantly decreased anti-inflammatory immune response (FOXP3, IL-10, and TGF-β markers) compared with the control mice.,These changes in the immune responses were associated with increased alveolar enlargement and impaired lung function starting on the first month and third month of CS exposure, respectively, compared with the control mice.,Our results showed that the microenvironmental stimuli produced by the release of cytokines during COPD progression lead to a Th17/Treg imbalance. | The immunopathology of chronic obstructive pulmonary disease (COPD) is based on the innate and adaptive inflammatory immune responses to the chronic inhalation of cigarette smoking.,In the last quarter of the century, the analysis of specimens obtained from the lower airways of COPD patients compared with those from a control group of age-matched smokers with normal lung function has provided novel insights on the potential pathogenetic role of the different cells of the innate and acquired immune responses and their pro/anti-inflammatory mediators and intracellular signalling pathways, contributing to a better knowledge of the immunopathology of COPD both during its stable phase and during its exacerbations.,This also has provided a scientific rationale for new drugs discovery and targeting to the lower airways.,This review summarises and discusses the immunopathology of COPD patients, of different severity, compared with control smokers with normal lung function. | 1 |
We aimed to estimate the prevalence, healthcare costs and number of deaths among people with chronic obstructive pulmonary disease (COPD) in England and Scotland 2011-2030.,We adapted the Dutch COPD Model by using English and Scottish demographic, COPD incidence, COPD prevalence, smoking prevalence and mortality data to make projections.,In England, the prevalence of COPD was estimated to be 1.79% (95% uncertainty interval 1.77-1.81) in 2011, increasing to 2.19% (1.85-2.33) by 2030.,In Scotland, prevalence was 2.03% (1.96-2.10) in 2011 increasing to 2.20% (1.98-2.40) in 2030.,These increases were driven by more women developing COPD.,Annual direct healthcare costs of COPD in England were estimated to increase from £1.50 billon (1.18-2.50) in 2011 to £2.32 (1.85-3.08) billion in 2030.,In Scotland, costs increased from £159 million (128-268) in 2011 to £207 (165-274) million in 2030.,The deaths in England were estimated to increase from 99,200 (92,500-128,500) in 2011, to 129,400 (126,400-133,400) by 2030.,In Scotland, in 2011 there were 9,700 (9,000-12,300) deaths and 13,900 (13,400-14,500) deaths in 2030.,The number of people with COPD will increase substantially over the coming years in England and Scotland, particularly in females.,Services need to adapt to this increasing demand. | Chronic Obstructive Pulmonary Disease (COPD) influences different aspects of patient’s health-related quality of life (HRQL).,While disease-specific HRQL instruments focus on symptoms and functional impairments, generic instruments cover a broader view on health.,This study compares the generic EQ-5D-3 L and two disease-specific questionnaires (St.-George’s Respiratory Questionnaire (SGRQ-C), COPD Assessment Test (CAT)) in a comprehensive spectrum of COPD disease grades with particular attention on comorbidities and assesses the discriminative abilities of these instruments.,Using data from the baseline visit of the German COPD cohort COSYCONET, mean HRQL scores in different COPD grades were compared by linear regression models adjusting for age, sex, education, smoking status, BMI, and low vs. high number of comorbidities or a list of several self-reported comorbid conditions.,Discriminative abilities of HRQL instruments to differentiate between COPD grades were assessed by standardized mean differences.,In 2,291 subjects in COPD GOLD grades 1-4 EQ-5D-3 L utility, EQ-5D VAS, SGRQ, and CAT were found able to discriminate between COPD grades, with some limitations for the EQ-5D utility in mild disease.,Both generic and disease-specific HRQL instruments reflected the burden of comorbid conditions.,The SGRQ showed the best discrimination between COPD grades and was less influenced by comorbidities, while EQ-5D utility put a higher weight on comorbid conditions.,For all instruments, psychiatric disorders and peripheral artery disease showed the strongest negative associations with HRQL.,All HRQL instruments considered reflect considerable impairment of HRQL in COPD patients, worsening with increasing COPD grade and number of comorbidities.,Findings may support clinical assessment, choice of HRQL instrument in future studies, and parameterization of decision-analytic models.,The online version of this article (doi:10.1186/s12890-016-0238-9) contains supplementary material, which is available to authorized users. | 1 |
The measurement of C-reactive protein (CRP) to confirm the stability of COPD has been reported.,However, CRP is a systemic inflammatory biomarker that is related to many other diseases.,The objective of this study is to discover a diagnostic biomarker for COPD.,Sixty-one subjects with COPD and 15 healthy controls (10 healthy non-smokers and 5 smokers) were recruited for a 1-year follow-up study.,Data regarding the 1-year acute exacerbation frequency and changes in lung function were collected.,CRP and the identified biomarkers were assessed in the validation COPD cohort patients and healthy subjects.,Receiver operating characteristic values of CRP and the identified biomarkers were determined.,A validation COPD cohort was used to reexamine the identified biomarker.,Correlation of the biomarker with 1-year lung function decline was determined.,Proteoglycan 4 (PRG4) was identified as a biomarker in COPD.,The serum concentrations of PRG4 in COPD Global initiative for chronic Obstructive Lung Disease (GOLD) stages 1+2 and 3+4 were 10.29 ng/mL and 13.20 ng/mL, respectively; 4.99 ng/mL for healthy controls (P<0.05); and 4.49 ng/mL for healthy smokers (P<0.05).,PRG4 was more sensitive and specific than CRP for confirming COPD severity and acute exacerbation frequency.,There was no correlation between CRP and PRG4 levels, and PRG4 was negatively correlated with the 1-year change in predicted forced vital capacity percent (R2=0.91, P=0.013).,PRG4 may be a biomarker for identification of severity in COPD.,It was related to the 1-year forced vital capacity decline in COPD patients. | We investigated a potential link between genetic polymorphisms in genes XRCC1 (Arg399Gln), OGG1 (Ser326Cys), XRCC3 (Thr241Met), and XRCC4 (Ile401Thr) with the level of DNA damage and repair, accessed by comet and micronucleus test, in 51 COPD patients and 51 controls.,Peripheral blood was used to perform the alkaline and neutral comet assay; and genetic polymorphisms by PCR/RFLP.,To assess the susceptibility to exogenous DNA damage, the cells were treated with methyl methanesulphonate for 1-h or 3-h.,After 3-h treatment the % residual damage was calculated assuming the value of 1-h treatment as 100%.,The cytogenetic damage was evaluated by buccal micronucleus cytome assay (BMCyt).,COPD patients with the risk allele XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) showed higher DNA damage by comet assay.,The residual damage was higher for COPD with risk allele in the four genes.,In COPD patients was showed negative correlation between BMCyt (binucleated, nuclear bud, condensed chromatin and karyorrhexic cells) with pulmonary function and some variant genotypes.,Our results suggest a possible association between variant genotypes in XRCC1 (Arg399Gln), OGG1 (Ser326Cys), XRCC3 (Thr241Met), and XRCC4 (Ile401Thr), DNA damage and progression of COPD. | 1 |
Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease.,For each patient, four of five treatments were administered once daily for 6 weeks, with a 21-day washout between treatments: tiotropium/olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg, olodaterol 5 µg or placebo, all via the Respimat inhaler.,Primary outcomes were inspiratory capacity prior to exercise and exercise endurance time during constant work-rate cycle ergometry to symptom limitation at 75% of peak incremental work rate after 6 weeks (2 h post-dose).,295 and 291 patients were treated in MORACTO 1 and 2, respectively.,Tiotropium/olodaterol 2.5/5 and 5/5 µg provided significant improvements in inspiratory capacity versus placebo and monotherapies (p<0.0001), and significant improvements in exercise endurance time versus placebo (p<0.0001).,Intensity of breathing discomfort was reduced following both doses of tiotropium/olodaterol versus placebo (p<0.0001).,Once-daily tiotropium/olodaterol yielded improvements in lung hyperinflation versus placebo and statistically significant improvements versus monotherapies.,Tiotropium/olodaterol also showed improvements in dyspnoea and exercise tolerance versus placebo but not consistently versus monotherapies.,T/O reduces lung hyperinflation in COPD versus T, O or placebo and increases exercise endurance versus placebohttp://ow.ly/ml3G307XW6a | ‘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. | 1 |
Peak inspiratory flow (PIF) as generated through the resistance of a dry powder inhaler (DPI) device is a critical patient-dependent maneuver impacting the success of DPI medication delivery.,Despite its importance, it is not routinely measured in clinical practice.,Little is currently known about the relationship, if any, between PIF through DPI devices, routine spirometry and disease outcomes.,The aim of this study was to identify potential predictors of PIF for different DPIs from spirometric parameters and patient characteristics and explore the association between PIF and follow-up events.,A retrospective observational study at discharge among patients hospitalized for a COPD exacerbation at Attikon hospital, Athens, Greece.,Spirometry was performed using an Easy on-PC™ spirometer.,PIF was measured through four DPI resistances using the In-Check™ DIAL.,Regression analyses were used to investigate the association between PIF through resistances and spirometric parameters obtained at discharge, comorbidities and demographic parameters.,Forty-seven COPD patients (mean [±SD], age 71 [±9] years, 72% males, 51% current smokers) were included in this study.,Overall, 85% and 15% were classified as GOLD (2017) groups D and C, respectively.,Most prevalent comorbidities were hypertension (70%) and cardiovascular disease (53%).,In the final regression model, higher PIF was significantly associated with the following: higher FEV1 and % predicted peak expiratory flow (PEF) for Turbohaler® (R-squared value 0.374); higher FEV1 and diagnosis of gastroesophageal reflux disease (GERD) for Aerolizer® (R-squared value 0.209) and higher FEV1, younger age and diagnosis of ischemic heart disease (IHD) for Diskus® (R-squared value 0.350).,However, R-squared values for all three devices were weak (<0.4).,The study did not provide evidence to support the use of surrogate measurements for PIF through device resistance, which could assist in determining the appropriateness of inhaler device type.,Although PIF measurement is feasible in patients at discharge and could be a valuable addition to the standard of care in COPD management, it needs to be measured directly. | Background: Two studies were undertaken to characterize the maximal effort inhalation profiles of healthy subjects and patients with asthma or chronic obstructive pulmonary disease (COPD) through a moderate-resistance dry powder inhaler (DPI).,Correlations between inhaler-specific inhalation characteristics and inhaler-independent lung function parameters were investigated.,Methods: Healthy subjects (n = 15), patients with mild, moderate, or severe asthma (n = 45), and patients with mild, moderate, severe, or very-severe COPD (n = 60) were included in the studies.,Inhalation pressure drop versus time profiles were recorded using an instrumented ELLIPTA® DPI or bespoke resistor component with equivalent resistivity.,Inhaler-independent lung function assessments included pharyngometry, spirometry, plethysmography, and diffusion.,Results: For the inhaler-specific inhalation profiles, the mean maximal effort peak inspiratory flow rates (PIFRs) varied across the subgroups from 65.8-110.6 L/min (range: 41.6-142.9).,Peak pressure drop, PIFR, inhaled volume, and average inhalation flow rate (primary endpoints) did not differ markedly between healthy subjects and patients with asthma or mild COPD.,Moderate, severe, and very-severe COPD patients demonstrated lower mean peak pressure drops, PIFRs and inhaled volumes, which tended to decrease with increasing COPD severity.,Severe and very-severe COPD patients demonstrated shorter mean inhalation times compared with all other participants.,Inhaler-independent lung function parameters were consistent with disease severity, and statistically significant (p < 0.05) strong correlations (R > 0.7) with components of the inhaler-specific inhalation profiles were observed in the COPD cohort; correlations in the asthma cohort tended to be weaker.,Conclusions: All participants achieved a maximal effort PIFR ≥ 41.6 L/min through the moderate resistance of the ELLIPTA inhaler.,Patients with asthma achieved similar inhalation profiles to healthy subjects, but increasing COPD severity tended to reduce a patient's inhalation capability.,Correlation analyses suggest that some lung function parameters may be a useful indicator of ability to inhale efficiently through a moderate-resistance DPI, such as the ELLIPTA inhaler. | 1 |
Chronic obstructive pulmonary disease (COPD) is a chronic, irreversible disease and a leading cause of worldwide morbidity and mortality.,In Canada, COPD is the fourth leading cause of death.,This systematic review was undertaken to update healthcare professionals and decision makers regarding the recent clinical, humanistic and economic burden evidence in Canada.,A systematic literature search was conducted in PubMed, EMBASE, and Cochrane databases to identify original research published January 2000 through December 2012 on the burden of COPD in Canada.,Each search was conducted using controlled vocabulary and key words, with “COPD” as the main search concept and limited to Canadian studies, written in English and involving human subjects.,Selected studies included randomized controlled trials, observational studies and systematic reviews/meta-analyses that reported healthcare resource utilization, quality of life and/or healthcare costs.,Of the 972 articles identified through the literature searches, 70 studies were included in this review.,These studies were determined to have an overall good quality based on the quality assessment.,COPD patients were found to average 0-4 annual emergency department visits, 0.3-1.5 annual hospital visits, and 0.7-5 annual physician visits.,Self-care management was found to lessen the overall risk of emergency department (ED) visits, hospitalization and unscheduled physician visits.,Additionally, integrated care decreased the mean number of hospitalizations and telephone support reduced the number of annual physician visits.,Overall, 60-68 % of COPD patients were found to be inactive and 60-72 % reported activity restriction.,Pain was found to negatively correlate with physical activity while breathing difficulties resulted in an inability to leave home and reduced the ability to handle activities of daily living.,Evidence indicated that treating COPD improved patients’ overall quality of life.,The average total cost per patient ranged between CAN $2444-4391 from a patient perspective to CAN $3910-6693 from a societal perspective.,Furthermore, evidence indicated that COPD exacerbations lead to higher costs.,The clinical, humanistic and economic burden of COPD in Canada is substantial.,Use of self-care management programs, telephone support, and integrated care may reduce the overall burden to Canadian patients and society. | Early identification of patients with a prolonged stay due to acute exacerbation of chronic obstructive pulmonary disease (COPD) may reduce risk of adverse event and treatment costs.,This study aimed to identify predictors of prolonged stay after acute exacerbation of COPD based on variables on admission; the study also looked to establish a prediction model for length of stay (LOS).,We extracted demographic and clinical data from the medical records of 599 patients discharged after an acute exacerbation of COPD between March 2006 and December 2008 at Oslo University Hospital, Aker.,We used logistic regression analyses to assess predictors of a length of stay above the 75th percentile and assessed the area under the receiving operating characteristic curve to evaluate the model’s performance.,We included 590 patients (54% women) aged 73.2±10.8 years (mean ± standard deviation) in the analyses.,Median LOS was 6.0 days (interquartile range [IQR] 3.5-11.0).,In multivariate analysis, admission between Thursday and Saturday (odds ratio [OR] 2.24 [95% CI 1.60-3.51], P<0.001), heart failure (OR 2.26, 95% CI 1.34-3.80), diabetes (OR 1.90, 95% CI 1.07-3.37), stroke (OR 1.83, 95% CI 1.04-3.21), high arterial PCO2 (OR 1.26 [95% CI 1.13-1.41], P<0.001), and low serum albumin level (OR 0.92 [95% CI 0.87-0.97], P=0.001) were associated with a LOS >11 days.,The statistical model had an area under the receiver operating characteristic curve of 0.73.,Admission between Thursday and Saturday, heart failure, diabetes, stroke, high arterial PCO2, and low serum albumin level were associated with a prolonged LOS.,These findings may help physicians to identify patients that will need a prolonged LOS in the early stages of admission.,However, the predictive model exhibited suboptimal performance and hence is not ready for clinical use. | 1 |
Utilizing data from the Continuing to Confront COPD (chronic obstructive pulmonary disease) International Physician Survey, this study aimed to describe physicians’ knowledge and application of the GOLD (Global initiative for chronic Obstructive Lung Disease) Global Strategy for the Diagnosis, Management and Prevention of COPD diagnosis and treatment recommendations and compare performance between primary care physicians (PCPs) and respiratory specialists.,Physicians from 12 countries were sampled from in-country professional databases; 1,307 physicians (PCP to respiratory specialist ratio three to one) who regularly consult with COPD, emphysema, or chronic bronchitis patients were interviewed online, by telephone or face to face.,Physicians were questioned about COPD risk factors, prognosis, diagnosis, and treatment, including knowledge and application of the GOLD global strategy using patient scenarios.,Physicians reported using spirometry routinely (PCPs 82%, respiratory specialists 100%; P<0.001) to diagnose COPD and frequently included validated patient-reported outcome measures (PCPs 67%, respiratory specialists 81%; P<0.001).,Respiratory specialists were more likely than PCPs to report awareness of the GOLD global strategy (93% versus 58%, P<0.001); however, when presented with patient scenarios, they did not always perform better than PCPs with regard to recommending GOLD-concordant treatment options.,The proportion of PCPs and respiratory specialists providing first- or second-choice treatment options concordant with GOLD strategy for a GOLD B-type patient was 38% versus 67%, respectively.,For GOLD C and D-type patients, the concordant proportions for PCPs and respiratory specialists were 40% versus 38%, and 57% versus 58%, respectively.,This survey of physicians in 12 countries practicing in the primary care and respiratory specialty settings showed high awareness of COPD-management guidelines.,Frequent use of guideline-recommended COPD diagnostic practices was reported; however, gaps in the application of COPD-treatment recommendations were observed, warranting further evaluation to understand potential barriers to adopt guideline recommendations. | While cross-national studies have documented rates of chronic obstructive pulmonary disease (COPD) misdiagnosis among patients in primary care, US studies are scarce.,Studies investigating diagnosis among uninsured patients are lacking.,The purpose of this study is to identify patients who are over diagnosed and thus, mistreated, for COPD in a federally qualified health center.,A descriptive study was conducted for a retrospective cohort from February 2011 to June 2012.,Spirometry was performed by trained personnel following American Thoracic Society recommendations.,Patients were referred for spirometry to confirm previous COPD diagnosis or to assess uncontrolled COPD symptoms.,Airway obstruction was defined as a forced expiratory volume in the first second of expiration (FEV1) to forced vital capacity ratio less than 0.7.,Reversibility was defined as a postbronchodilator increase in FEV1 greater than 200 mL and greater than 12%.,Eighty patients treated for a previous diagnosis of COPD (n = 72) or on anticholinergic inhalers (n = 8) with no COPD diagnosis were evaluated.,The average age was 52.9 years; 71% were uninsured.,Only 17.5% (14/80) of patients reported previous spirometry.,Spirometry revealed that 42.5% had no obstruction, 22.5% had reversible obstruction, and 35% had non-reversible obstruction.,Symptoms and smoking history are insufficient to diagnose COPD.,Prevalence of COPD over diagnosis among uninsured patient populations may be higher than previously reported.,Confirming previous COPD diagnosis with spirometry is essential to avoid unnecessary and potentially harmful treatment. | 1 |
Chronic obstructive pulmonary disease (COPD) is a multicomponent condition that is characterised by airflow obstruction that is not fully reversible and is a major global cause of morbidity and mortality.,The most widely used marker of disease severity and progression is FEV1.,However, FEV1 correlates poorly with both symptoms and other measures of disease progression and thus there is an urgent need for other biological markers to better characterise individuals with COPD.,Fibrinogen is an acute phase plasma protein that has emerged as a promising biomarker in COPD.,Here we review the current clinical evidence linking fibrinogen with COPD and its associated co-morbidities and discuss its potential utility as a biomarker.,Searches for appropriate studies were undertaken on PubMed using search terms fibrinogen, COPD, emphysema, chronic bronchitis, FEV1, cardiovascular disease, exacerbation and mortality.,There is strong evidence of an association between fibrinogen and the presence of COPD, the presence and frequency of exacerbations and with mortality.,Fibrinogen is associated with disease severity but does not predict lung function decline, a measure used as a surrogate for disease activity.,The role of fibrinogen in identifying inflammatory co morbidities, particularly cardiovascular disease, remains unclear.,Fibrinogen is reduced by p38 mitogen-activated protein kinase inhibitors in individuals with stable disease and by oral corticosteroids during exacerbations.,Fibrinogen is likely to be a useful biomarker to stratify individuals with COPD into those with a high or low risk of future exacerbations and may identify those with a higher risk of mortality. | The efficacy of inhaled salmeterol plus fluticasone propionate (SFC) in patients with severe or very severe COPD is well documented.,However, there are only limited data about the influence of GOLD severity staging on the effectiveness of SFC, particularly in patients with milder disease.,TORCH was a 3-year, double-blind, placebo-controlled trial of 6112 patients with moderate/severe COPD with pre-bronchodilator FEV1 < 60% predicted (mean age 65 years, 76% male, mean 44% predicted FEV1, 43% current smokers).,To understand the relative efficacy of SFC and its components by GOLD stages, we conducted a post-hoc analysis of the TORCH dataset using baseline post-bronchodilator FEV1 to segment patients into three groups: moderate COPD (GOLD stage II and above: ≥ 50%; n = 2156), severe COPD (GOLD stage III: 30% to < 50%; n = 3019) and very severe COPD (GOLD stage IV: < 30%; n = 937).,Compared with placebo, SFC improved post-bronchodilator FEV1: 101 ml (95% confidence interval [CI]: 71, 132) in GOLD stage II, 82 ml (95% CI: 60, 104) in GOLD stage III and 96 ml (95% CI: 54, 138) in GOLD stage IV patients, and reduced the rate of exacerbations: 31% (95% CI: 19, 40) in GOLD stage II, 26% (95% CI: 17, 34) in GOLD stage III and 14% (95% CI: -4, 29) in GOLD stage IV.,SFC improved health status to a greater extent than other treatments regardless of baseline GOLD stage.,Similarly, SFC reduced the risk of death by 33% (hazard ratio [HR] 0.67; 95% CI: 0.45, 0.98) for GOLD stage II, 5% (HR 0.95; 95% CI: 0.73, 1.24) for GOLD stage III, and 30% (HR 0.70; 95% CI: 0.47, 1.05) for GOLD stage IV.,The rates of adverse events were similar across treatment arms and increased with disease severity.,Overall, there was a higher incidence of pneumonia in the fluticasone propionate and SFC arms, compared with other treatments in all GOLD stages.,In the TORCH study, SFC reduced moderate-to-severe exacerbations and improved health status and FEV1 across GOLD stages.,Treatment with SFC may be associated with reduced mortality compared with placebo in patients with GOLD stage II disease.,The effects were similar to those reported for the study as a whole.,Thus, SFC is an effective treatment option for patients with GOLD stage II COPD.,Clinicaltrial.gov registration NCT00268216; Study number: SCO30003 | 1 |
COPD often coexists with chronic conditions that may influence disease prognosis.,We investigated associations between chronic (co)morbidities and exacerbations in primary care COPD patients.,Retrospective cohort study based on 2012-2013 electronic health records from 179 Dutch general practices.,Comorbidities from patients with physician-diagnosed COPD were categorized according to International Classification of Primary Care (ICPC) codes.,Chi-squared tests, uni- and multivariable logistic, and Cox regression analyses were used to study associations with exacerbations, defined as oral corticosteroid prescriptions.,Fourteen thousand six hundred three patients with COPD could be studied (mean age 67 (SD 12) years, 53% male) for two years.,At baseline 12,826 (88%) suffered from ≥1 comorbidities, 3263 (22%) from ≥5.,The most prevalent comorbidities were hypertension (35%), coronary heart disease (19%), and osteoarthritis (18%).,Several comorbidities showed statistically significant associations with frequent (i.e., ≥2/year) exacerbations: heart failure (odds ratio [OR], 95% confidence interval: 1.72; 1.38-2.14), blindness & low vision (OR 1.46; 1.21-1.75), pulmonary cancer (OR 1.85; 1.28-2.67), depression 1.48; 1.14-1.91), prostate disorders (OR 1.50; 1.13-1.98), asthma (OR 1.36; 1.11-1.70), osteoporosis (OR 1.41; 1.11-1.80), diabetes (OR 0.80; 0.66-0.97), dyspepsia (OR 1.25; 1.03-1.50), and peripheral vascular disease (OR 1.20; 1.00-1.45).,From all comorbidity categories, having another chronic respiratory disease beside COPD showed the highest risk for developing a new exacerbation (Cox hazard ratio 1.26; 1.17-1.36).,Chronic comorbidities are highly prevalent in primary care COPD patients.,Several chronic comorbidities were associated with having frequent exacerbations and increased exacerbation risk. | Chronic obstructive pulmonary disease (COPD) is a chronic, progressive lung disease resulting from exposure to cigarette smoke, noxious gases, particulate matter, and air pollutants.,COPD is exacerbated by acute inflammatory insults such as lung infections (viral and bacterial) and air pollutants which further accelerate the steady decline in lung function.,The chronic inflammatory process in the lung contributes to the extrapulmonary manifestations of COPD which are predominantly cardiovascular in nature.,Here we review the significant burden of cardiovascular disease in COPD and discuss the clinical and pathological links between acute exacerbations of COPD and cardiovascular disease. | 1 |
Current recommendations to consider initiation of palliative care (PC) in COPD patients are often based on an expected poor prognosis.,However, this approach is not evidence-based, and which and when COPD patients should start PC is controversial.,We aimed to assess whether current suggested recommendations for initiating PC were sufficiently reliable.,We identified prognostic variables proposed in the literature for initiating PC; then, we ascertained their relationship with 1-year mortality, and finally, we validated their utility in our cohort of 697 patients hospitalized for COPD exacerbation.,From 24 articles of 499 screened, we selected 20 variables and retrieved 48 original articles in which we were able to calculate the relationship between each of them and 1-year mortality.,The number of studies where 1-year mortality was detailed for these variables ranged from 9 for previous hospitalizations or FEV1 ≤30% to none for albumin ≤25 mg/dL.,The percentage of 1-year mortality in the literature for these variables ranged from 5% to 60%.,In the validation cohort study, the prevalence of these proposed variables ranged from 8% to 64%; only 10 of the 18 variables analyzed in our cohort reached statistical significance with Cox regression analysis, and none overcame an area under the curve ≥0.7.,We conclude that none of the suggested criteria for initiating PC based on an expected poor vital prognosis in COPD patients in the short or medium term offers sufficient reliability, and consequently, they should be avoided as exclusive criteria for considering PC or at least critically appraised. | COPD is a leading cause of morbidity and mortality worldwide.,Patients suffer from refractory breathlessness, unrecognized anxiety and depression, and decreased quality of life.,Palliative care improves symptom management, patient reported health-related quality of life, cost savings, and mortality though the majority of patients with COPD die without access to palliative care.,There are many barriers to providing palliative care to patients with COPD including the difficulty in prognosticating a patient’s course causing referrals to occur late in a patient’s disease.,Additionally, physicians avoid conversations about advance care planning due to unique communication barriers present with patients with COPD.,Lastly, many health systems are not set up to provide trained palliative care physicians to patients with chronic disease including COPD.,This review analyzes the above challenges, the available data regarding palliative care applied to the COPD population, and proposes an alternative approach to address the unmet needs of patients with COPD with proactive primary palliative care. | 1 |
Chronic obstructive pulmonary disease (COPD) is a respiratory condition characterised by dyspnoea, excessive sputum production, chronic cough, bronchitis and emphysema.,Functionally, exercise tolerance is poor for people with COPD and is linked to difficulty in performing daily tasks.,More specifically, exercise difficulties are due partly to dyspnoea and lower limb skeletal muscle dysfunction.,The benefit of exercise that does not exacerbate the disease while improving exercise tolerance is salient.,Whole-body vibration (WBV) is a mode of physical activity known to improve muscular function of the lower limbs, yet efficacy has not been investigated for a WBV intervention conducted in a home-based setting for people with COPD.,This clinically registered trial is a non-randomised placebo cross-over intervention based in the home of each participant (ACTRN12612000508875).,Participants diagnosed with COPD will complete a six-week WBV intervention and then after a two-week washout period, will complete a six-week placebo training intervention.,Participants will complete sessions twice a week.,The duration of the trial is 14 weeks.,Community-dwelling older adults with COPD will provide informed voluntary consent to participate.,Outcome measures will include immediate, acute, and long-term responses to exercise.,Quantifying responses to WBV among people with COPD will allow discussion of efficacy of WBV as a mode of physical activity.,The skill required by the participant to perform physical activity with WBV is not demanding and may enhance habitual sustainability.,The results of this trial could be used to support further research in both clinical and community settings.,Australian New Zealand Clinical Trials Registry (ANZCTR12612000508875) | Previous small studies suggested SBOT may be ineffective in relieving breathlessness after exercise in COPD.,34 COPD patients with FEV1 <40% predicted and resting oxygen saturation ≥93% undertook an exercise step test 4 times.,After exercise, patients were given 4 l/min of oxygen from a simple face mask, 4 l/min air from a face mask (single blind), air from a fan or no intervention.,Average oxygen saturation fell from 95.0% to 91.3% after exercise.,The mean time to subjective recovery was 3.3 minutes with no difference between treatments.,The mean Borg breathlessness score was 1.5/10 at rest, rising to 5.1/10 at the end of exercise (No breathlessness = 0, worst possible breathlessness = 10).,Oxygen therapy had no discernable effect on Borg scores even for 14 patients who desaturated below 90%. 15 patients had no preferred treatment, 7 preferred oxygen, 6 preferred the fan, 3 preferred air via a mask and 3 preferred room air.,This study provides no support for the idea that COPD patients who are not hypoxaemic at rest derive noticeable benefit from oxygen therapy after exercise.,Use of air from a mask or from a fan had no apparent physiological or placebo effect. | 1 |
Smoking cessation is a key intervention for all smokers with chronic obstructive pulmonary disease (COPD).,Poor treatment adherence is a challenge in clinical practice that might contribute to the lower efficacy of medication (eg, oral drug).,However, it is unclear what factors will influence adherence among smokers with COPD.,This study was based on an open-label randomized controlled trial (RCT) of varenicline and bupropion for smoking cessation among patients with COPD in China.,The medication was given for 12 weeks, and visits and assessments were conducted at weeks 0, 1, 2, 4, 6, 9, 12, and 24.,We assessed whether the adherence to smoking cessation treatment affects the smoking cessation efficacy and evaluated predictors of adherence.,A total of 136 participants were recruited from February 2019 to June 2020, and analyzed using the intention-to-treat (ITT) method.,In this study, 48.5% (66/136) of the total participants had good adherence to smoking cessation, and good adherence significantly improved the efficacy of smoking cessation (OR=9.60, 95% CI 4.02-22.96, P < 0.001).,After adjusting for age, gender, nationality, education, and marital status, we found older age, higher education level, having more previous quitting attempts, stronger self-efficacy and preparation in quitting smoking, recognizing hazards of smoking, longer duration of COPD, and higher St.,George’s Respiratory Questionnaire (SGRQ) scores were relevant to good adherence (P < 0.05).,To our best knowledge, this is the first study to evaluate adherence to smoking cessation treatment among patients with COPD in China.,Our study found that good adherence to smoking cessation treatment significantly improved the smoking cessation efficacy, and predictors of adherence were evaluated.,We call on the medical community to pay attention to the adherence to smoking cessation among patients with COPD. | The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally. | 1 |
Inhaled medications are the cornerstone of treatment and management of asthma and COPD.,However, inhaler device errors are common among patients and have been linked with reduced symptom control, an increased risk of exacerbations, and increased healthcare utilisation.,These observations have prompted GINA (Global INitiative for Asthma) and GOLD (Global initiative for chronic Obstructive Lung Disease) to recommend regular assessment of inhaler technique in a bid to improve therapeutic outcomes.,To better define the relationship between device errors and health outcomes (clinical outcomes, quality of life, and healthcare utilisation) in asthma and COPD, we conducted a systematic review of the literature, with a particular focus on the methods used to assess the relationship between device errors and outcomes.,Sixteen studies were identified (12 in patients with asthma, one in patients with COPD, and three in both asthma and COPD) with varying study designs, endpoints, and patient populations.,Most of the studies reported that inhalation errors were associated with worse disease outcomes in patients with asthma or COPD.,Patients who had a reduction in errors over time had improved outcomes.,These findings suggest that time invested by healthcare professionals is vital to improving inhalation technique in asthma and COPD patients to improve health outcomes. | This study aims to identify factors associated with poor adherence to COPD treatment in patients receiving a fixed-dose combination (FDC) of inhaled corticosteroids and long-acting β2-agonist (ICS/LABA), focusing on the importance of inhaler devices.,We conducted a retrospective and multicenter study based on a review of medical registries between 2007 and 2012 of COPD patients (n=1,263) treated with ICS/LABA FDC, whose medical devices were either dry powder inhalers (DPIs) or pressurized metered-dose inhalers (pMDI).,Medication adherence included persistence outcomes through 18 months and medication possession ratios.,Data on exacerbations, comorbidities, demographic characteristics, and health care resource utilization were also included as confounders of adherence.,The analyses revealed that COPD patients whose medication was delivered through a DPI were less likely to have medication adherence compared to patients with pMDI, after adjusting for confounding factors, especially active ingredients.,Younger groups of patients were less likely to be adherent compared to the oldest group.,Smoker men were less likely to be adherent compared to women and non-smokers.,Comorbidities decreased the probability of treatment adherence.,Those patients that visited their doctor once a month were more likely to adhere to their medication regimen; however, suboptimal adherence was more likely to occur among those patients who visited more than three times per month their doctor.,We also found that worsening of COPD is negatively associated with adherence.,According to this study, inhaler devices influence patients’ adherence to long-term COPD medication.,We also found that DPIs delivering ICS/LABA FDC had a negative impact on adherence.,Patients’ clinic and socioeconomic characteristics were associated with adherence. | 1 |
The relationship between physical activity, disease severity, health status and prognosis in patients with COPD has not been systematically assessed.,Our aim was to identify and summarise studies assessing associations between physical activity and its determinants and/or outcomes in patients with COPD and to develop a conceptual model for physical activity in COPD.,We conducted a systematic search of four databases (Medline, Embase, CINAHL and Psychinfo) prior to November 2012.,Teams of two reviewers independently selected articles, extracted data and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess quality of evidence.,86 studies were included: 59 were focused on determinants, 23 on outcomes and 4 on both.,Hyperinflation, exercise capacity, dyspnoea, previous exacerbations, gas exchange, systemic inflammation, quality of life and self-efficacy were consistently related to physical activity, but often based on cross-sectional studies and low-quality evidence.,Results from studies of pharmacological and non-pharmacological treatments were inconsistent and the quality of evidence was low to very low.,As outcomes, COPD exacerbations and mortality were consistently associated with low levels of physical activity based on moderate quality evidence.,Physical activity was associated with other outcomes such as dyspnoea, health-related quality of life, exercise capacity and FEV1 but based on cross-sectional studies and low to very low quality evidence.,Physical activity level in COPD is consistently associated with mortality and exacerbations, but there is poor evidence about determinants of physical activity, including the impact of treatment. | Guidelines recommend that symptoms as well as lung function should be monitored for the management of patients with chronic obstructive pulmonary disease (COPD).,However, limited data are available regarding the longitudinal change in dyspnea, and it remains unknown which of relevant measurements might be used for following dyspnea.,We previously consecutively recruited 137 male outpatients with moderate to very severe COPD, and followed them every 6 months for 5 years.,We then reviewed and reanalyzed the data focusing on the relationships between the change in dyspnea and the changes in other clinical measurements of lung function, exercise tolerance tests and psychological status.,Dyspnea with activities of daily living was assessed with the Oxygen Cost Diagram (OCD) and modified Medical Research Council dyspnea scale (mMRC), and two dimensions of disease-specific health status questionnaires of the Chronic Respiratory Disease Questionnaire (CRQ) and the St.,George’s Respiratory Questionnaire (SGRQ) were also used.,Dyspnea at the end of exercise tolerance tests was measured using the Borg scale.,The mMRC, CRQ dyspnea and SGRQ activity significantly worsened over time (p < 0.001), but the OCD did not (p = 0.097).,Multiple regression analyses revealed that the changes in the OCD, mMRC, CRQ dyspnea and SGRQ activity were significantly correlated to changes in forced expiratory volume in one second (FEV1) (correlation of determination (r2) = 0.05-0.19), diffusing capacity for carbon monoxide (r2 = 0.04-0.08) and psychological status evaluated by Hospital Anxiety and Depression Scale (r2 = 0.14-0.17), although these correlations were weak.,Peak Borg score decreased rather significantly, but was unrelated to changes in clinical measurements.,Dyspnea worsened over time in patients with COPD.,However, as different dyspnea measurements showed different evaluative characteristics, it is important to follow dyspnea using appropriate measurements.,Progressive dyspnea was related not only to progressive airflow limitation, but also to various factors such as worsening of diffusing capacity or psychological status.,Changes in peak dyspnea at the end of exercise may evaluate different aspects from other dyspnea measurements. | 1 |
Lungs of smokers and chronic obstructive pulmonary disease (COPD) are severely compromised and are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attack.,The dangerous combination of enhanced SARS-CoV-2 attachment receptor protein ACE2 along with an increase in endocytic vacuoles will enable viral attachment, entry, and replication.,The objective of the study was to identify the presence of SARS-CoV-2 host attachment receptor angiotensin-converting enzyme-2 (ACE2) along with endocytic vacuoles, early endosome antigen-1 (EEA1), late endosome marker RAB7, cathepsin-L, and lysosomal associated membrane protein-1 (LAMP-1) as lysosome markers in the airways of smokers and COPD patients.,The study design was cross-sectional and involved lung resections from 39 patients in total, which included 19 patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I or GOLD stage II COPD, of which 9 were current smokers with COPD (COPD-CS) and 10 were ex-smokers with COPD (COPD-ES), 10 were normal lung function smokers, and 10 were never-smoking normal controls.,Immunostaining for ACE2, EEA1, RAB7, and cathepsin-L was done.,A comparative description for ACE2, EEA1, RAB7, and cathepsin-L expression pattern is provided for the patient groups.,Furthermore, staining intensity for LAMP-1 lysosomes was measured as the ratio of the LAMP-1-stained areas per total area of epithelium or subepithelium, using Image ProPlus v7.0 software.,LAMP-1 expression showed a positive correlation to patient smoking history while in COPD LAMP-1 negatively correlated to lung function.,The active presence of ACE2 protein along with endocytic vacuoles such as early/late endosomes and lysosomes in the small airways of smokers and COPD patients provides evidence that these patient groups could be more susceptible to COVID-19. | With great interest we read and commend the study done by Russo et al. [1], highlighting their findings that nicotine induces an increase in angiotensin-converting enzyme 2 (ACE-2) expression in human bronchial epithelial cells (HBEpC) and is mediated by α7-subtype nicotinic receptors (α7-nAChR).,It raises the concern that all electronic nicotine-delivery systems may put users at greater risk of succumbing to coronavirus disease 2019 (COVID-19).,Absolute cessation of any tobacco product in any form: implications for COVID-19https://bit.ly/3cyk9ra | 1 |
Worldwide nearly 3 million people die from chronic obstructive pulmonary disease (COPD) every year.,Integrated disease management (IDM) improves quality of life for COPD patients and can reduce hospitalization.,Self-management of COPD through eHealth is an effective method to improve IDM and clinical outcomes.,The objective of this implementation study was to investigate the effect of 3 chronic obstructive pulmonary disease eHealth programs applied in primary care on health status.,The e-Vita COPD study compares different levels of integration of Web-based self-management platforms in IDM in 3 primary care settings.,Patient health status is examined using the Clinical COPD Questionnaire (CCQ).,The parallel cohort design includes 3 levels of integration in IDM (groups 1, 2, 3) and randomization of 2 levels of personal assistance for patients (group A, high assistance, group B, low assistance).,Interrupted time series (ITS) design was used to collect CCQ data at multiple time points before and after intervention, and multilevel linear regression modeling was used to analyze CCQ data.,Of the 702 invited patients, 215 (30.6%) registered to a platform.,Of these, 82 participated in group 1 (high integration IDM), 36 in group 1A (high assistance), and 46 in group 1B (low assistance); 96 participated in group 2 (medium integration IDM), 44 in group 2A (high assistance) and 52 in group 2B (low assistance); also, 37 participated in group 3 (no integration IDM).,In the total group, no significant difference was found in change in CCQ trend (P=.334) before (-0.47% per month) and after the intervention (-0.084% per month).,Also, no significant difference was found in CCQ changes before versus after the intervention between the groups with high versus low personal assistance.,In all subgroups, there was no significant change in the CCQ trend before and after the intervention (group 1A, P=.237; 1B, P=.991; 2A, P=.120; 2B, P=.166; 3, P=.945).,The e-Vita eHealth-supported COPD programs had no beneficial impact on the health status of COPD patients.,Also, no differences were found between the patient groups receiving different levels of personal assistance.,Netherlands Trial Registry NTR4098; http://www.trialregister.nl/trialreg/admin/rctview.asp?,TC=4098 (Archived by WebCite at http://www.webcitation.org/6sbM5PayG) | 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 |
Chronic obstructive pulmonary disease (COPD) is combination of progressive lung diseases.,The diagnosis of COPD is generally based on the pulmonary function testing, however, difficulties underlie in prognosis of smokers or early stage of COPD patients due to the complexity and heterogeneity of the pathogenesis.,Computational analyses of omics technologies are expected as one of the solutions to resolve such complexities.,We obtained transcriptomic data by in vitro testing with exposures of human bronchial epithelial cells to the inducers for early events of COPD to identify the potential descriptive marker genes.,With the identified genes, the machine learning technique was employed with the publicly available transcriptome data obtained from the lung specimens of COPD and non-COPD patients to develop the model that can reflect the risk continuum across smoking and COPD.,The expression levels of 15 genes were commonly altered among in vitro tissues exposed to known inducible factors for earlier events of COPD (exposure to cigarette smoke, DNA damage, oxidative stress, and inflammation), and 10 of these genes and their corresponding proteins have not previously reported as COPD biomarkers.,Although these genes were able to predict each group with 65% accuracy, the accuracy with which they were able to discriminate COPD subjects from smokers was only 29%.,Furthermore, logistic regression enabled the conversion of gene expression levels to a numerical index, which we named the “potential risk factor (PRF)” index.,The highest significant index value was recorded in COPD subjects (0.56 at the median), followed by smokers (0.30) and non-smokers (0.02).,In vitro tissues exposed to cigarette smoke displayed dose-dependent increases of PRF, suggesting its utility for prospective risk estimation of tobacco products.,Our experimental-based transcriptomic analysis identified novel genes associated with COPD, and the 15 genes could distinguish smokers and COPD subjects from non-smokers via machine-learning classification with remarkable accuracy.,We also suggested a PRF index that can quantitatively reflect the risk continuum across smoking and COPD pathogenesis, and we believe it will provide an improved understanding of smoking effects and new insights into COPD. | Gene expression profiling (GEP) in cells obtained from peripheral blood has shown that this is a very useful approach for biomarker discovery and for studying molecular pathogenesis of prevalent diseases.,While there is limited literature available on gene expression markers associated with Chronic Obstructive Pulmonary Disease (COPD), the transcriptomic picture associated with critical respiratory illness in this disease is not known at the present moment.,By using Agilent microarray chips, we have profiled gene expression signatures in the whole blood of 28 COPD patients hospitalized with different degrees of respiratory compromise.12 of them needed of admission to the ICU, whilst 16 were admitted to the Respiratory Medicine Service.,GeneSpring GX 11.0 software was used for performing statistical comparisons of transcript levels between ICU and non-ICU patients.,Ingenuity pathway analysis 8.5 (IPA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to select, annotate and visualize genes by function and pathway (gene ontology).,T-test showed evidence of 1501 genes differentially expressed between ICU and non-ICU patients.,IPA and KEGG analysis of the most representative biological functions revealed that ICU patients had increased levels of neutrophil gene transcripts, being [cathepsin G (CTSG)], [elastase, neutrophil expressed (ELANE)], [proteinase 3 (PRTN3)], [myeloperoxidase (MPO)], [cathepsin D (CTSD)], [defensin, alpha 3, neutrophil-specific (DEFA3)], azurocidin 1 (AZU1)], and [bactericidal/permeability-increasing protein (BPI)] the most representative ones.,Proteins codified by these genes form part of the azurophilic granules of neutrophils and are involved in both antimicrobial defence and tissue damage.,This “neutrophil signature” was paralleled by the necessity of advanced respiratory and vital support, and the presence of bacterial infection.,Study of transcriptomic signatures in blood suggests an essential role of neutrophil proteases in COPD patients with critical respiratory illness.,Measurement and modulation of the expression of these genes could present an option for clinical monitoring and treatment of severe COPD exacerbations.,The online version of this article (doi:10.1186/1756-0500-5-401) contains supplementary material, which is available to authorized users. | 1 |
To evaluate the clinical implementation of pharmacotherapy recommendations for chronic obstructive pulmonary disease (COPD) based on the Global Initiative for chronic obstructive lung disease (GOLD) guidelines, in a longitudinal setting.,This is a sub-analysis of a prospective, non-interventional cohort study including patients with confirmed mild-to-very-severe COPD from seven pulmonary outpatient clinics in Switzerland.,Follow-up visits took place annually for up to 7 years, from October 2010 until December 2016.,For each visit, we evaluated the compliance of the prescribed pharmacotherapy with the concurrently valid GOLD guideline.,We investigated whether step-ups or step-downs in GOLD stage or risk-group were accompanied by concordant changes in prescribed medication.,Groups were compared via ANOVA.,Data of 305 patients (62±7 years, 66% men) were analysed.,In 59.1% of visits, the prescribed medication conformed to the respective valid GOLD-guideline.,Patients with very severe COPD were most likely to receive pharmacotherapy in compliance with guidelines.,Step-ups and step-downs in risk group, requiring escalation, or de-escalation of pharmacotherapy, were noticed in 24 and 43 follow-up visits, respectively.,Step-ups were adequately implemented in 4 (16.7%) and step-downs in six cases (14.0%).,The compliance of COPD-pharmacotherapy with GOLD-guidelines is suboptimal, especially in lower risk groups.,The high rates of missed out treatment-adjustments suggest that the familiarity of physicians with guidelines leaves room for improvement. | 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 |
Grouping COPD subjects into clinical phenotypes might be useful for the management of the disease, but the clinical implications of such classification are still not totally clear, especially regarding prognosis.,The primary objective of this study was to assess whether the mortality rates were different between four predefined clinical phenotypes.,This is a retrospective, observational study carried out at the COPD clinic of a University Hospital.,A total of 891 COPD patients were classified, according to the Spanish COPD guidelines, into the following four phenotypes: asthma-COPD overlap (ACO; 75 subjects), nonexacerbator (NONEX; 531 subjects), exacerbator with chronic bronchitis (EXCB; 194 subjects), and exacerbator with emphysema (EXEMPH; 91 subjects).,We compared the mortality outcomes between the phenotypes.,After a follow-up of 48.4±25.2 months, there were 194 deaths (21.8%).,There were significant differences in all-cause mortality between phenotypes.,The ACO phenotype had the best long-term prognosis, whereas EXEMPH had the highest risk of death.,NONEX and EXCB mortality figures were in between the other two groups.,We also found some differences in the causes of death, and patients with EXEMPH were at a higher risk of dying because of COPD itself.,The differences in mortality did not seem related to the classification into phenotypes in itself but to disparities in COPD severity and comorbidity load between groups.,Classifying COPD patients according to several predefined clinical phenotypes can identify clusters of subjects with different mortality outcomes.,Some phenotypes are associated with a specific cause of death.,The mechanisms that underlie these differences seem to be related to COPD severity and comorbidities. | 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. | 1 |
To compare the rate of moderate to severe exacerbations between triple therapy and dual therapy or monotherapy in patients with chronic obstructive pulmonary disease (COPD).,Systematic review and meta-analysis of randomised controlled trials.,PubMed, Embase, Cochrane databases, and clinical trial registries searched from inception to April 2018.,Randomised controlled trials comparing triple therapy with dual therapy or monotherapy in patients with COPD were eligible.,Efficacy and safety outcomes of interest were also available.,Data were collected independently.,Meta-analyses were conducted to calculate rate ratios, hazard ratios, risk ratios, and mean differences with 95% confidence intervals.,Quality of evidence was summarised in accordance with GRADE methodology (grading of recommendations assessment, development, and evaluation).,21 trials (19 publications) were included.,Triple therapy consisted of a long acting muscarinic antagonist (LAMA), long acting β agonist (LABA), and inhaled corticosteroid (ICS).,Triple therapy was associated with a significantly reduced rate of moderate or severe exacerbations compared with LAMA monotherapy (rate ratio 0.71, 95% confidence interval 0.60 to 0.85), LAMA and LABA (0.78, 0.70 to 0.88), and ICS and LABA (0.77, 0.66 to 0.91).,Trough forced expiratory volume in 1 second (FEV1) and quality of life were favourable with triple therapy.,The overall safety profile of triple therapy is reassuring, but pneumonia was significantly higher with triple therapy than with dual therapy of LAMA and LABA (relative risk 1.53, 95% confidence interval 1.25 to 1.87).,Use of triple therapy resulted in a lower rate of moderate or severe exacerbations of COPD, better lung function, and better health related quality of life than dual therapy or monotherapy in patients with advanced COPD.,Prospero CRD42018077033. | Severe exacerbations of COPD, ie, those leading to hospitalization, have profound clinical implications for patients and significant economic consequences for society.,The prevalence and burden of severe COPD exacerbations remain high, despite recognition of the importance of exacerbation prevention and the availability of new treatment options.,Severe COPD exacerbations are associated with high mortality, have negative impact on quality of life, are linked to cardiovascular complications, and are a significant burden on the health-care system.,This review identified risk factors that contribute to the development of severe exacerbations, treatment options (bronchodilators, antibiotics, corticosteroids [CSs], oxygen therapy, and ventilator support) to manage severe exacerbations, and strategies to prevent readmission to hospital.,Risk factors that are amenable to change have been highlighted.,A number of bronchodilators have demonstrated successful reduction in risk of severe exacerbations, including long-acting muscarinic antagonist or long-acting β2-agonist mono- or combination therapies, in addition to vaccination, mucolytic and antibiotic therapy, and nonpharmacological interventions, such as pulmonary rehabilitation.,Recognition of the importance of severe exacerbations is an essential step in improving outcomes for patients with COPD.,Evidence-based approaches to prevent and manage severe exacerbations should be implemented as part of targeted strategies for disease management. | 1 |
Pulmonary emphysema is a phenotypic component of chronic obstructive pulmonary disease (COPD) which carries substantial morbidity and mortality.,We explored the association between emphysema and body height in 726 patients with COPD using computed tomography as the reference diagnostic standard for emphysema.,We applied univariate analysis to look for differences between patients with emphysema and those without, and multivariate logistic regression to identify significant predictors of the risk of emphysema.,As covariates we included age, sex, body height, body mass index, pack-years of smoking, and forced expiratory volume in one second (FEV1) as percent predicted.,The overall prevalence of emphysema was 52%.,Emphysemic patients were significantly taller and thinner than non-emphysemic ones, and featured significantly higher pack-years of smoking and lower FEV1 (P < 0.001).,The prevalence of emphysema rose linearly by 10-cm increase in body height (r2 = 0.96).,In multivariate analysis, the odds of emphysema increased by 5% (95% confidence interval, 3 to 7%) along with one-centimeter increase in body height, and remained unchanged after adjusting for all the potential confounders considered (P < 0.001).,The odds of emphysema were not statistically different between males and females.,In conclusion, body height is a strong, independent risk factor for emphysema in COPD. | Chronic obstructive pulmonary disease (COPD) reduces exercise capacity, but lung function parameters do not fully explain functional class and lung-heart interaction could be the explanation.,We evaluated echocardiographic predictors of mortality and six minutes walking distance (6MWD), a marker for quality of life and mortality in COPD.,Ninety COPD patients (GOLD criteria) were evaluated by body plethysmography, 6MWD and advanced echocardiography parameters (pulsed wave tissue Doppler and speckle tracking).,Mean 6MWD was 403 (± 113) meters.,All 90 subjects had preserved left ventricular (LV) ejection fraction 64.3% ± 8.6%.,Stroke volume decreased while heart rate increased with COPD severity and hyperinflation.,In 66% of patients, some degree of diastolic dysfunction was present.,Mitral tissue Doppler data in COPD could be interpreted as a sign of low LV preload and not necessarily an intrinsic impairment in LV relaxation/compliance.,Tricuspid regurgitation (TR) increased with COPD severity and hyperinflation.,Age (p < 0.001), BMI (p < 0.001), DLCO SB (p < 0.001) and TR (p 0.005) were independent predictors of 6MWD and a multivariable model incorporating heart function parameters (adjusted r2 = .511) compared well to a model with lung function parameters alone (adjusted r2 = .475).,LV global longitudinal strain (p = 0.034) was the only independent predictor of mortality among all baseline, body plethysmographic and echocardiographic variables.,Among subjects with moderate to severe COPD and normal LVEF, GLS independently predicted all-cause mortality.,Exercise tolerance correlated with standard lung function parameters only in univariate models; in subsequent models including echocardiographic parameters, longer 6MWD correlated independently with milder TR, better DLCO SB, younger age and lower BMI.,We extended the evidence on COPD affecting cardiac chamber volumes, LV preload, heart rate, as well as systolic and diastolic function.,Our results highlight lung-heart interaction and the necessity of cardiac evaluation in COPD. | 1 |
Multimorbidity has already become common in primary care and will be a challenge in the future.,Primary care in Sweden participates to a great extent in the care of patients with two severe, chronic conditions: chronic obstructive pulmonary disease (COPD) and heart failure.,Both conditions are characterized by high mortality and often coexist.,Age, sex, heart failure and other comorbidities are considered to be the major predictors of mortality in patients with COPD.,We aimed to study the impact of heart failure, other comorbidities, age and sex on mortality in patients with COPD.,A register-based, prospective cohort study conducted in Blekinge County in Sweden with about 150,000 inhabitants.,The study population was comprised of people aged ≥35 years.,The data about diagnoses of COPD and heart failure came from the 2007 health care register, in which we found 984 individuals with a diagnosis of COPD.,Date of death was collected from January 1st, 2008 -August 31st, 2015.,The diagnosis-based Adjusted Clinical Groups (ACG) Case-Mix System 7.1 was used to describe comorbidity.,Each individual was assigned one of six comorbidity levels called resource utilization bands (RUB) graded from 0 to 5.,Estimated eight year mortality in patients with COPD and coexisting heart failure was seven times higher than in patients with COPD alone - odds ratio 7.06 (95% CI 3.88-12.84).,Adjusting for age and male sex resulted in odds ratio 3.75 (95% CI 1.97-7.15).,Further adjusting for other comorbidities resulted in odds ratio 3.26 (95% CI 1.70-6.25).,The mortality was strongly associated with the highest comorbidity level - RUB 5 where the odds ratio was 5.19 (95% CI 2.59-10.38).,Heart failure has an important impact on mortality in patients with COPD.,The mortality in patients with COPD and coexisting heart failure was strongly associated with age, male sex and other comorbidities.,Of those three predictors, only other comorbidities can be influenced.,Heart failure and other comorbidities should be recognized early and properly treated in order to improve survival in patients with coexisting COPD and heart failure. | Early identification of people at risk of developing COPD is crucial for implementing preventive strategies.,We aimed to systematically review and assess the performance of all published models that predicted development of COPD.,A search was conducted to identify studies that developed a prediction model for COPD development.,The Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies was followed when extracting data and appraising the selected studies.,Of the 4,481 records identified, 30 articles were selected for full-text review, and only four of these were eligible to be included in the review.,The only consistent predictor across all four models was a measure of smoking.,Sex and age were used in most models; however, other factors varied widely.,Two of the models had good ability to discriminate between people who were correctly or incorrectly classified as at risk of developing COPD.,Overall none of the models were particularly useful in accurately predicting future risk of COPD, nor were they good at ruling out future risk of COPD.,Further studies are needed to develop new prediction models and robustly validate them in external cohorts. | 1 |
The combination of aclidinium bromide, a long-acting anticholinergic, and formoterol fumarate, a long-acting beta2-agonist (400/12 μg twice daily) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease (COPD), and is approved in the European Union as a maintenance treatment.,The effect of this combination on symptoms of COPD and exacerbations is less well established.,We examined these outcomes in a pre-specified analysis of pooled data from two 24-week, double-blind, parallel-group, active- and placebo-controlled, multicentre, randomised Phase III studies (ACLIFORM and AUGMENT).,Patients ≥40 years with moderate to severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <70 % and FEV1 ≥30 % but <80 % predicted normal) were randomised (ACLIFORM: 2:2:2:2:1; AUGMENT: 1:1:1:1:1) to twice-daily aclidinium/formoterol 400/12 μg or 400/6 μg, aclidinium 400 μg, formoterol 12 μg or placebo via Genuair™/Pressair®.,Dyspnoea (Transition Dyspnoea Index; TDI), daily symptoms (EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [E-RS] questionnaire), night-time and early-morning symptoms, exacerbations (Healthcare Resource Utilisation [HCRU] and EXACT definitions) and relief-medication use were assessed.,The pooled intent-to-treat population included 3394 patients.,Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 (all p < 0.05).,Over 24 weeks, significant improvements in E-RS total score, overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with aclidinium/formoterol 400/12 μg versus placebo and both monotherapies (all p < 0.05).,The rate of moderate or severe HCRU exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg compared with placebo (p < 0.05) but not monotherapies; the rate of EXACT-defined exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg versus placebo (p < 0.01) and aclidinium (p < 0.05).,Time to first HCRU or EXACT exacerbation was longer with aclidinium/formoterol 400/12 μg compared with placebo (all p < 0.05) but not the monotherapies.,Relief-medication use was reduced with aclidinium/formoterol 400/12 μg versus placebo and aclidinium (p < 0.01).,Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo, aclidinium and formoterol in patients with moderate to severe COPD.,Furthermore, aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo.,NCT01462942 and NCT01437397 (ClinicalTrials.gov),The online version of this article (doi:10.1186/s12931-015-0250-2) contains supplementary material, which is available to authorized users. | Pulmonary rehabilitation (PR) is an important treatment option for chronic obstructive pulmonary disease (COPD) patients and might contribute to a reduction in exacerbation and exacerbation-related hospitalization rate.,In this prospective study, all COPD patients that completed a comprehensive pulmonary rehabilitation program (PRP) between June 2006 and December 2012 were included.,Self-reported exacerbation and hospitalization frequency 1 year before PR was retrospectively recorded.,During the year following PR, exacerbation and hospitalization frequency was recorded with questionnaires.,For 343 patients, complete information on exacerbation and hospitalization rate was obtained.,The mean number of exacerbations decreased significantly after participating in a PRP by 1.37 exacerbations/year (95% confidence interval 1.029 to 1.717) from 4.56±3.26 exacerbations in the year preceding PR to 3.18±2.53 in the year following PR (P<0.0005).,The number of hospitalizations due to exacerbations decreased significantly by 0.68 hospitalizations/year (95% confidence interval 0.467 to 0.903) from 1.48±1.84 in the year preceding PR to 0.80±1.31 hospitalizations/year in the year following PR (P<0.0005).,The proportion of patients with a frequent exacerbation type (more than two exacerbations/year) was reduced by 24%.,Multivariate regression analysis to explore determinants that might predict reduction in exacerbation frequency or change in exacerbation pattern did not reveal clinically useful predictors, although patients with more exacerbations before PR had the highest potential for reduction.,In a large population of severely impaired COPD patients with high exacerbation rates, a significant reduction in exacerbation and hospitalization frequency was observed after participation in a comprehensive PRP. | 1 |
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death and disability worldwide, but before the development of several new pharmacological treatments little could be done for COPD patients.,Recognition that these new treatments could significantly improve the prognosis for COPD patients has radically changed clinical management guidelines from a palliative philosophy to an aggressive approach intended to reduce chronic symptoms, improve quality of life and prolong survival.,These new treatments have also sparked interest in COPD cost-effectiveness research.,Most COPD cost-effectiveness studies have been based on clinical trial populations, limited to direct medical costs, and used standard analysis methods such as Markov modelling, and they have usually found that newer therapies have favourable cost effectiveness.,However, new insights into the clinical progression of COPD bring into question some of the assumptions underlying older analyses.,In this review, we examine clinical factors unique to COPD and recent changes in clinical perspectives that have important implications for pharmacoeconomic analyses.,The main parameters explored include (i) the high indirect medical costs for COPD and their relevance in assessing the societal benefits of new therapy; (ii) the importance of acute deteriorations in COPD, known as exacerbations, and approaches to modelling the cost benefit of exacerbation reduction; (iii) quality/utility instruments for COPD; (iv) the prevalence of co-morbid conditions and confounding between COPD and co-morbid disease utilization; (v) the limitations of Markov modelling; and (vi) the problem of outliers. | The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.,The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada.,Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified.,The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.,The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively.,The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th.,The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first.,Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.,The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation.,Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality. | 1 |
COPD-6™ is a lung function testing device for a rapid pre-spirometry testing to screen-out at-risk individuals not having COPD and indicating those at risk.,The aim of this study was to validate COPD-6™ lung function testing (index test) in general practice in discriminating patients with COPD out of the population at risk - smokers/ex-smokers with no previous diagnosis of COPD, using measurements at tertiary care as reference standard.,Consecutive 227 subjects (115 women, 185 smokers/42 ex-smokers, ≥20 pack-years) with no previous diagnosis of COPD, aged 52.5 (SD 6.8) years from 26 general practitioners (GPs) were recruited, lung function tested with COPD-6™, referred to the tertiary institution for repeated COPD-6™ testing followed by spirometry with a bronchodilator (salbutamol), examination, and pulmonologist consultation for the diagnosis and severity of COPD.,COPD was diagnosed in 43 subjects (18.9 %), with an AUC of 0.827 (95 % CI 0.769-0.875, P < 0.001) for the diagnosis of COPD when lung function was measured using COPD-6™ in GP’s office with a specificity of 100 % (95 % CI, 97.95-100 %) but a very low sensitivity of 32.56 % (95 % CI, 20.49-47.48 %).,Significant agreement for forced expiratory volume in 1 s measured at GP’s office and at lung function lab was found (mean difference 0.01 L, p = 0.667) but not for other measured parameters (p < 0.001 for all).,Our study results point out that active case finding in a population at risk for COPD should be instituted (almost 20 % of undiagnosed COPD).,Based on our results lung function testing with COPD-6™ can substitute spirometry testing in cases where it is not readily available to the patient/physician taken into account that the traditional FEV1/FEV6 cutoff value of <0.7 is not the only criterion for diagnosis and/or further referral.,ClinicalTrials.gov Identifier NCT01550679 Registered 28 September 2014, retrospectively registered | Spirometry is required to confirm a chronic obstructive pulmonary disease (COPD) diagnosis, but it is difficult to perform in resource-limited settings.,This study aimed to evaluate symptom-based questions for screening of individuals with COPD among Chinese populations.,We recruited 3969 adult subjects from the First Affiliated Hospital of Nanjing Medical University.,Spirometric measurements of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were collected to confirm the COPD diagnosis.,A symptom-based questionnaire was administered to collect data related to COPD.,The sensitivity and specificity together with the area under the curve (AUC) were calculated.,The traditional IPAG eight-item questionnaire yielded an AUC of 0.80(95% CI: 0.78-0.82), with a sensitivity of 67.8% and specificity of 76.8%.,After removing and adding questions, a revised eleven-item questionnaire exhibited a significantly increased diagnostic accuracy, with an AUC of 0.85(95% CI: 0.84-0.87).,At the inflection point of the curve, it demonstrated a sensitivity of 82.5% and specificity of 72.9%.,We showed that the revised symptom-based questionnaire could be used to screen individuals with a high likelihood of COPD among Chinese populations.,Further validation is required before we claim it is a useful diagnostic for primary care populations. | 1 |
Data regarding osteoporosis in COPD patients in Taiwan remain limited.,The primary end point of this study was to evaluate the prevalence and risk factors of osteoporosis in COPD patients in Taiwan.,The secondary end point was to examine the association between osteoporosis and health-related quality of life (HRQL) in COPD patients.,This prospective cross-sectional study enrolled 125 COPD patients (mean age 73.6 years, forced expiratory volume in 1 second [FEV1] 1.19±0.43 L) who had bone mineral-density measurements performed consecutively.,Demographic data, lung function, and HRQL including modified Medical Research Council dyspnea scale, St George’s Respiratory Questionnaire, oxygen-cost diagram, Center for Epidemiologic Studies - depression scale, and COPD Assessment Test scores were recorded.,A total of 50 (40%) participants were diagnosed as having osteoporosis.,In a multivariate logistic regression model including age, smoking amount (pack-year), body mass index (BMI), and FEV1, only BMI (odds ratio 0.824, 95% confidence interval 0.73-0.93; P=0.002) and FEV1 (odds ratio 0.360, 95% confidence interval 0.13-0.98; P=0.046) were negatively associated with an increased risk of osteoporosis in COPD patients.,In addition, COPD patients with osteoporosis had significantly higher modified Medical Research Council dyspnea scale scores (1.7±0.8 vs 1.4±0.8, P=0.046), St George’s Respiratory Questionnaire scores (36.6 vs 28.0, P=0.01), and COPD Assessment Test scores (14.7±8 vs 11.5±7, P=0.019), and lower oxygen-cost diagram score (4.8±1.8 vs 5.4±1.6, P=0.045) than patients without osteoporosis.,The prevalence of osteoporosis in COPD patients was high at a community hospital in Taiwan.,BMI and FEV1 were the independent risk factors for osteoporosis in COPD.,In addition, COPD patients with osteoporosis had worse HRQL than those without osteoporosis. | The purpose of our study was to examine the association of prior outpatient use of statins and angiotensin converting enzyme (ACE) inhibitors on mortality for subjects ≥ 65 years of age hospitalized with acute COPD exacerbations.,We conducted a retrospective national cohort study using Veterans Affairs administrative data including subjects ≥65 years of age hospitalized with a COPD exacerbation.,Our primary analysis was a multilevel model with the dependent variable of 90-day mortality and hospital as a random effect, controlling for preexisting comorbid conditions, demographics, and other medications prescribed.,We identified 11,212 subjects with a mean age of 74.0 years, 98% were male, and 12.4% of subjects died within 90-days of hospital presentation.,In this cohort, 20.3% of subjects were using statins, 32.0% were using ACE inhibitors or angiotensin II receptor blockers (ARB).,After adjusting for potential confounders, current statin use (odds ratio 0.51, 95% confidence interval 0.40-0.64) and ACE inhibitor/ARB use (0.55, 0.46-0.66) were significantly associated with decreased 90-day mortality.,Use of statins and ACE inhibitors prior to admission is associated with decreased mortality in subjects hospitalized with a COPD exacerbation.,Randomized controlled trials are needed to examine whether the use of these medications are protective for those patients with COPD exacerbations. | 1 |
The characteristics and natural history of GOLD B COPD patients are not well described.,The clinical characteristics and natural history of GOLD B patients over 1 year in a multicentre cohort of COPD patients in the COPDMAP study were assessed.,We aimed to identify the subgroup of patients who progressed to GOLD D (unstable GOLD B patients) and identify characteristics associated with progression.,Three hundred seventy COPD patients were assessed at baseline and 12 months thereafter.,Demographics, lung function, health status, 6 min walk tests and levels of systemic inflammation were assessed.,Students t tests and Mann Whitney-U tests were used.,One hundred seven (28.9%) of patients were categorised as GOLD B at baseline.,These GOLD B patients had similar FEV1 to GOLD A patients (66% predicted).,More GOLD B patients were current smokers (p = 0.031), had chronic bronchitis (p = 0.0003) and cardiovascular comorbidities (p = 0.019) compared to GOLD A.,At 12 months, 25.3% of GOLD B patients progressed to GOLD D.,These patients who progressed (unstable patients) had worse health status and symptoms (SGRQ-C Total, 50.0 v 41.1, p = 0.019 and CAT, 21.0 v 14.0, p = 0.006) and lower FEV1 (60% v 69% p = 0.014) at baseline compared to stable patients who remained in GOLD B.,Unstable GOLD B patients who progressed to GOLD D had a higher level of symptoms at baseline.,A high symptom burden may predict an increased likelihood of disease progression in GOLD B patients.,The online version of this article (doi:10.1186/s12890-017-0384-8) contains supplementary material, which is available to authorized users. | The 2013 GOLD classification system for COPD distinguishes four stages: A (low symptoms, low exacerbation risk), B (high symptoms, low risk), C (low symptoms, high risk) and D (high symptoms, high risk).,Assessment of risk is based on exacerbation history and airflow obstruction, whatever results in a higher risk grouping.,The previous system was solely based on airflow obstruction.,Earlier studies compared the predictive performance of new and old classification systems with regards to mortality and exacerbations.,The objective of this study was to compare the ability of both classifications to predict the number of future (total and severe) exacerbations and mortality in a different patient population, and to add an outcome measure to the comparison: lung function decline.,Patient-level data from the UPLIFT trial were used to analyze 4-year survival in a Weibull model, with GOLD stages at baseline as covariates.,A generalized linear model was used to compare the numbers of exacerbations (total and severe) per stage.,Analyses were repeated with stages C and D divided into substages depending on lung function and exacerbation history.,Lung function decline was analysed in a repeated measures model.,Mortality increased from A to D, but there was no difference between B and C.,For the previous GOLD stages 2-4, survival curves were clearly separated.,Yearly exacerbation rates were: 0.53, 0.72 and 0.80 for stages 2-4; and 0.35, 0.45, 0.58 and 0.74 for A-D.,Annual rates of lung function decline were: 47, 38 and 26 ml for stages 2-4 and 44, 48, 38 and 39 for stages A-D.,With regards to model fit, the new system performed worse at predicting mortality and lung function decline, and better at predicting exacerbations.,Distinguishing between the sub-stages of high-risk led to substantial improvements.,The new classification system is a modest step towards a phenotype approach.,It is probably an improvement for the prediction of exacerbations, but a deterioration for predicting mortality and lung function decline.,ClinicalTrials.gov NCT00144339 (September 2, 2005).,The online version of this article (doi:10.1186/1471-2466-14-163) contains supplementary material, which is available to authorized users. | 1 |
QVA149 is a once-daily (o.d.) inhaled dual bronchodilator containing a fixed-dose combination of the long-acting β2-agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium for the treatment of COPD.,The QUANTIFY study compared QVA149 with a free-dose bronchodilator combination of tiotropium plus formoterol (TIO+FOR) in improving health-related quality of life (HRQoL) of patients with COPD.,This multicentre, blinded, triple-dummy, parallel-group, non-inferiority study randomised patients aged ≥40 years with moderate-to-severe COPD (post-bronchodilator forced expiratory volume in 1 s (FEV1) ≥30% to <80% predicted) to QVA149 110/50 µg o.d. or TIO 18 µg o.d.,+ FOR 12 µg twice daily (1:1) for 26 weeks.,The primary endpoint was to demonstrate non-inferiority in HRQoL assessed using St George's Respiratory Questionnaire-COPD (SGRQ-C).,The prespecified non-inferiority margin was 4 units.,Secondary endpoints included Transition Dyspnoea Index (TDI) score, pre-dose FEV1, forced vital capacity (FVC) and safety.,Of the 934 patients randomised (QVA149=476 and TIO+FOR=458), 87.9% completed the study.,At week 26, non-inferiority was met for SGRQ-C (QVA149 vs TIO+FOR; difference: -0.69 units; 95% CI −2.31 to 0.92; p=0.399).,A significantly higher percentage of patients achieved a clinically relevant ≥1 point improvement in TDI total score with QVA149 (49.6%) versus TIO+FOR (42.4%; p=0.033).,QVA149 significantly increased pre-dose FEV1 (+68 mL, 95% CI 37 mL to 100 mL; p<0.001) and FVC (+74 mL, 95% CI 24 mL to 125 mL; p=0.004) compared with TIO+FOR at week 26.,The incidence of adverse events was comparable between both treatments (QVA149=43.7% and TIO+FOR=42.6%).,QVA149 is non-inferior to TIO+FOR in improving HRQoL, with clinically meaningful and significant improvements in breathlessness and lung function in patients with COPD.,NCT01120717. | Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.,Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks.,Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.,In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment.,Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies.,Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg.,Incidence of adverse events was comparable between the FDCs and the mono-components.,These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.,Lung function and symptomatic benefits of daily tiotropium+olodaterol fixed-dose combination in moderate to very severe COPDhttp://ow.ly/DIKiY | 1 |
Chronic obstructive pulmonary disease (COPD) is a multicomponent disorder that leads to substantial disability, impaired quality of life, and increased mortality.,Although the majority of COPD patients are first diagnosed and treated in primary care practices, there is comparatively little information on the management of COPD patients in primary care.,A web-based pilot survey was conducted to evaluate the primary care physician’s, or general practitioner’s (GP’s), knowledge, understanding, and management of COPD in twelve territories across the Asia-Pacific region, Africa, eastern Europe, and Latin America, using a 10-minute questionnaire comprising 20 questions and translated into the native language of each participating territory.,The questionnaire was administered to a total of 600 GPs (50 from each territory) involved in the management of COPD patients and all data were collated and analyzed by an independent health care research consultant.,This survey demonstrated that the GPs’ understanding of COPD was variable across the territories, with large numbers of GPs having very limited knowledge of COPD and its management.,A consistent finding across all territories was the underutilization of spirometry (median 26%; range 10%-48%) and reliance on X-rays (median 14%; range 5%-22%) for COPD diagnosis, whereas overuse of blood tests (unspecified) was particularly high in Russia and South Africa.,Similarly, there was considerable underrecognition of the importance of exacerbation history as an important factor of COPD and its initial management in most territories (median 4%; range 0%-22%).,Management of COPD was well below guideline-recommended levels in most of the regions investigated.,The findings of this survey suggest there is a need for more ongoing education and information, specifically directed towards GPs outside of Europe and North America, and that global COPD guidelines appear to have limited reach and application in most of the areas studied. | 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 |
Since the Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups A-D were introduced, the lung function changes according to group have been evaluated rarely.,We investigated the rate of decline in annual lung function in patients categorized according to the 2014 GOLD guidelines.,Patients with COPD included in the Korean Obstructive Lung Disease (KOLD) prospective study, who underwent yearly postbronchodilator spirometry at least three times, were included.,The main outcome was the annual decline in postbronchodilator forced expiratory volume in 1 second (FEV1), which was analyzed by random-slope and random-intercept mixed linear regression.,A total 175 participants were included.,No significant postbronchodilator FEV1 decline was observed between the groups (−34.4±7.9 [group A]; −26.2±9.4 [group B]; −22.7±16.0 [group C]; and −24.0±8.7 mL/year [group D]) (P=0.79).,The group with less symptoms (−32.3±7.2 vs −25.0±6.5 mL/year) (P=0.44) and the low risk group (−31.0±6.1 vs −23.6±7.7 mL/year) (P=0.44) at baseline showed a more rapid decline in the postbronchodilator FEV1, but the trends were not statistically significant.,However, GOLD stages classified by FEV1 were significantly related to the annual lung function decline.,There was no significant difference in lung function decline rates according to the GOLD groups.,Prior classification using postbronchodilator FEV1 predicts decline in lung function better than does the new classification. | The efficacy of inhaled salmeterol plus fluticasone propionate (SFC) in patients with severe or very severe COPD is well documented.,However, there are only limited data about the influence of GOLD severity staging on the effectiveness of SFC, particularly in patients with milder disease.,TORCH was a 3-year, double-blind, placebo-controlled trial of 6112 patients with moderate/severe COPD with pre-bronchodilator FEV1 < 60% predicted (mean age 65 years, 76% male, mean 44% predicted FEV1, 43% current smokers).,To understand the relative efficacy of SFC and its components by GOLD stages, we conducted a post-hoc analysis of the TORCH dataset using baseline post-bronchodilator FEV1 to segment patients into three groups: moderate COPD (GOLD stage II and above: ≥ 50%; n = 2156), severe COPD (GOLD stage III: 30% to < 50%; n = 3019) and very severe COPD (GOLD stage IV: < 30%; n = 937).,Compared with placebo, SFC improved post-bronchodilator FEV1: 101 ml (95% confidence interval [CI]: 71, 132) in GOLD stage II, 82 ml (95% CI: 60, 104) in GOLD stage III and 96 ml (95% CI: 54, 138) in GOLD stage IV patients, and reduced the rate of exacerbations: 31% (95% CI: 19, 40) in GOLD stage II, 26% (95% CI: 17, 34) in GOLD stage III and 14% (95% CI: -4, 29) in GOLD stage IV.,SFC improved health status to a greater extent than other treatments regardless of baseline GOLD stage.,Similarly, SFC reduced the risk of death by 33% (hazard ratio [HR] 0.67; 95% CI: 0.45, 0.98) for GOLD stage II, 5% (HR 0.95; 95% CI: 0.73, 1.24) for GOLD stage III, and 30% (HR 0.70; 95% CI: 0.47, 1.05) for GOLD stage IV.,The rates of adverse events were similar across treatment arms and increased with disease severity.,Overall, there was a higher incidence of pneumonia in the fluticasone propionate and SFC arms, compared with other treatments in all GOLD stages.,In the TORCH study, SFC reduced moderate-to-severe exacerbations and improved health status and FEV1 across GOLD stages.,Treatment with SFC may be associated with reduced mortality compared with placebo in patients with GOLD stage II disease.,The effects were similar to those reported for the study as a whole.,Thus, SFC is an effective treatment option for patients with GOLD stage II COPD.,Clinicaltrial.gov registration NCT00268216; Study number: SCO30003 | 1 |
Little is known about the effect of ambient fine particulate matter (PM2.5) on chronic obstructive pulmonary disease (COPD) in China.,The objective of this study was to explore the short-term effects of PM2.5 on outpatient and inpatient visits for COPD in Beijing, China.,A total of 3,503,313 outpatient visits and 126,982 inpatient visits for COPD between January 1, 2010, and June 30, 2012, were identified from the Beijing Medical Claim Data for Employees.,A generalized additive Poisson model was applied to estimate the percentage change with 95% confidence interval (CI) in hospital visits for COPD in relation to an interquartile range (IQR) (90.8 μg/m3) increase in PM2.5 concentrations.,Short-term exposure to PM2.5 was significantly associated with increased use of COPD-related health services.,There were clear exposure-response associations of PM2.5 with COPD outpatient and inpatient visits.,An IQR increase in the concurrent day PM2.5 concentrations was significantly associated with a 2.38% (95% CI, 2.22%-2.53%) and 6.03% (95% CI, 5.19%-6.87%) increase in daily outpatient visits and inpatient visits, respectively.,Elderly people were more sensitive to the adverse effects.,The estimated risk was higher during the warm season compared to the cool season.,Short-term exposure to PM2.5 was associated with increased risk of hospital visits for COPD.,Our findings contributed to the limited evidence concerning the effects of ambient PM2.5 on COPD morbidity in developing countries.,The online version of this article (10.1186/s12940-018-0369-y) contains supplementary material, which is available to authorized users. | Objectives: This paper reports on the findings of a population-based study to evaluate the relationship between atmospheric fine particulate matter (PM2.5) levels and hospital admissions for chronic obstructive pulmonary disease (COPD) in southwestern Taiwan over a three-year period, 2008-2010.,Methods: Data on hospital admissions for COPD and PM2.5 levels were obtained from the National Health Insurance Research database (NHIRD) and the Environmental Protection Administration from 2008 to 2010, respectively.,The lag structure of relative risks (RRs) of hospital admissions for COPD was estimated using a Poisson regression model.,Results: During the study period, the overall average hospitalization rate of COPD and mean 24-h average level of PM2.5 was 0.18% and 39.37 μg/m3, respectively.,There were seasonal variations in PM2.5 concentrations in southwestern Taiwan, with higher PM2.5 concentrations in both spring (average: 48.54 μg/m3) and winter (49.96 μg/m3) than in summer (25.89 μg/m3) and autumn (33.37 μg/m3).,Increased COPD admissions were significantly associated with PM2.5 in both spring (February-April) and winter (October-January), with the relative risks (RRs) for every 10 μg/m3 increase in PM2.5 being 1.25 (95% CI = 1.22-1.27) and 1.24 (95% CI = 1.23-1.26), respectively, at a lag zero days (i.e., no lag days).,Lag effects on COPD admissions were observed for PM2.5, with the elevated RRs beginning at lag zero days and larger RRs estimates tending to occur at longer lags (up to six days, i.e., lag 0-5 days).,Conclusions: In general, findings reveal an association between atmospheric fine particulate matter (PM2.5) and hospital admissions for COPD in southwestern Taiwan, especially during both spring and winter seasons. | 1 |
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