Symptomatic Chronic Obstructive Pulmonary Disease Research Articles

Development and validation of reference equations for dual-energy x-ray absorptiometry-derived measures of fat-free mass in adults aged 45-85 years: Results from the Canadian Longitudinal Study on Aging.

Reference equations for fat-free (FFM) and lean soft tissue mass (LM) measures obtained from dual-energy x-ray absorptiometry (DEXA) are important for the interpretation of body composition. This study developed and validated reference equations for FFM and LM using DEXA from the Canadian Longitudinal Study on Aging. Reference equations were developed using data from a random population-based sample of ostensibly healthy and functionally independent adults aged 45-85years. Reference equations for absolute (accounting for age, sex, height, and body mass) and height-adjusted (accounting for age, sex, and body mass index) measures of FFM and LM were developed using quantile regression. Reference equations were respectively developed and validated in derivation (80%) and validation cohorts (20%). Reference equations were applied to symptomatic adults with self-reported chronic obstructive pulmonary disease (COPD) or heart disease to assess discriminant validity; and compared with other published equations to assess performance. Bland-Altman analyses and Lin's concordance correlation coefficients were utilised to assess agreement. Reference equations for 5th, 10th, 50th, 90th, and 95th percentiles were developed for DEXA-derived estimates of FFM and LM based on 1,881 healthy participants (57%male) aged 55years [IQR: 50-61]. Reference equations performed comparably in the validation cohort and discriminated reference values between healthy adults and people with symptomatic COPD or heart disease. Previously published reference equations tended to over- or under-predict estimates of LM compared with the current reference equations. This study provides a comprehensive and validated set of reference equations for estimating and interpreting FFM and LM from DEXA in Canadian adults aged 45-85 years.

Association between Increased Risk of Pneumonia with ICS in COPD: A Continuous Variable Analysis of Patient Factors from the IMPACT Study.

Despite the proven benefits of inhaled corticosteroid (ICS)-containing triple therapy for chronic obstructive pulmonary disease (COPD), clinicians limit patient exposure to ICS due to the risk of pneumonia. However, there are multiple factors associated with the risk of pneumonia in patients with COPD. This posthoc analysis of IMPACT trial data aims to set the risks associated with ICS into a context of specific patient-related factors that contribute to the risk of pneumonia. The 52-week, double-blind IMPACT trial randomized patients with symptomatic COPD and ≥1 exacerbation in the prior year 2:2:1 to once-daily fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI), FF/VI or UMEC/VI. Annual rate of on-treatment pneumonias in the intent-to-treat population associated with age, body mass index (BMI), percent predicted forced expiratory volume in 1s (FEV1) and blood eosinophil count (BEC) was evaluated. This analysis revealed that the annual rate of pneumonia showed the lowest risk at the age of 50years. The 95% confidence intervals (CI) between ICS-containing and non-ICS containing treatments diverged in ages > 63years, suggesting a significantly increased ICS-related risk in older patients. In contrast, the annual rate of pneumonia rose in both groups below BMI of 22.5kg/m2, but above that, there was no relationship to pneumonia rate and no differential effect between the two groups. The relationship between BEC and pneumonia was flat up to > 300/µL cells with ICS-containing treatment and then rose. In contrast, the rate of pneumonia with non-ICS containing treatment appeared to increase at a lower level of BEC (~ 200/µL). There was little evidence of a differential effect of older age, lower BMI, lower FEV1 and BEC on the pneumonia rate between ICS-containing and non-ICS containing treatments. This analysis points to the need for a balanced approach to risk versus benefit in the use of ICS-containing treatments in COPD. IMPACT ClinicalTrials.gov number, NCT02164513.

Quantifying uptake and completion of pulmonary rehabilitation programs in people with chronic obstructive pulmonary disease known to tertiary care.

People with symptomatic chronic obstructive pulmonary disease (COPD) benefit from pulmonary rehabilitation programs (PRPs), but program attrition is common. For people with COPD who presented to tertiary care and appeared appropriate for a PRP, we prospectively mapped their PRP journey, explored factors influencing attendance to pre-program assessment and captured program attrition. Of the 391 participants, 31% (95% CI 27 to 36) were referred to a PRP (n = 123; age 68 ± 10years, 62 males [50%], FEV1 45 ± 19%predicted). Of those referred, 94 (76% [69 to 84]) attended a pre-program assessment. Ex-smokers and those who had a healthcare professional (HCP) explain they would be referred were more likely to attend a pre-program assessment (odds ratio [95%CI]; 2.6 [1.1 to 6.1]; and 4.7 [1.9 to 11.7], respectively). Of the 94 who attended, 63 (67% [58 to 77]) commenced; and of those who commenced, 35 (56% [43 to 68]) completed a PRP. All who completed (n = 35, 100%) were provided at least one strategy to maintain training-related gains. Attrition occurs throughout the PRP journey. Interactions with HCPs about PRPs positively influenced attendance. Understanding how HCPs can best contextualise PRPs to encourage referral acceptance and uptake is an important area for further work.

The effect of inhaled extrafine beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide on distal and central airway indices, assessed using Functional Respiratory Imaging in COPD (DARWiIN)

BackgroundThis study, in patients with symptomatic chronic obstructive pulmonary disease (COPD), explored switching therapy from non-extrafine high-dose inhaled corticosteroid/long-acting β2-agonist (ICS/LABA; fluticasone propionate/salmeterol [FP/SLM]) to extrafine medium-dose beclometasone dipropionate/formoterol fumarate dihydrate/glycopyrronium (BDP/FF/G), both via dry-powder inhaler. Functional Respiratory Imaging, a quantitative computed tomography method with 3D reconstructions of pulmonary anatomy, was used to assess airway geometry and lung function.MethodsPatients receiving a stable ICS/LABA regimen for ≥ 8 weeks were switched to FP/SLM 500/50 µg, one inhalation twice-daily (high-dose ICS) for 6 weeks. After baseline assessments (Visit 2 [V2]), therapy was switched to BDP/FF/G 100/6/10 µg, two inhalations twice-daily (medium-dose ICS) for 6 weeks, followed by V3. The primary endpoints were percentage changes in specific image-based airway volume (siVaw) and resistance (siRaw) from baseline to predose at V3 (i.e., chronic effects), assessed at total lung capacity (TLC) in central and distal lung regions. Secondary endpoints included siVaw and siRaw changes from pre-dose to post-dose at V2, and from pre-dose to post-dose at V3 at TLC (i.e., acute effects), and chronic and acute changes in siVaw and siRaw at functional residual capacity (FRC). Pre-dose forced expiratory volume in 1 s (FEV1) and COPD Assessment Test (CAT) were also assessed.ResultsThere were no significant changes in pre-dose siVaw or siRaw at TLC from baseline to V3, although at FRC there was a significant decrease in mean siRaw in the distal airways (− 63.6%; p = 0.0261). In addition, in the distal airways there were significant acute effects at TLC on mean siVaw and siRaw (siVaw: 39.8% and 62.6%; siRaw: − 51.1% and − 57.2%, V2 and V3, respectively; all p < 0.001) and at FRC at V2 (siVaw: 77.9%; siRaw: − 67.0%; both p < 0.001). At V3, the mean change in pre-dose FEV1 was 62.2 mL (p = 0.0690), and in CAT total score was − 3.30 (p < 0.0001).ConclusionsIn patients with symptomatic COPD receiving high-dose ICS/LABA, adding a long-acting muscarinic antagonist while decreasing the ICS dose by switching to medium-dose extrafine BDP/FF/G was associated with improved airway indices, especially in the distal airways, together with improvements in respiratory health status.Trial registration ClinicalTrials.gov (NCT04876677), first posted 6th May 2021

The Clinical Characteristics and Outcomes in Non-Frequent Exacerbation Patients with Chronic Obstructive Pulmonary Disease in the Chinese Population.

We analyzed the clinical characteristics and outcomes in non-frequent exacerbation patients with chronic obstructive pulmonary disease (COPD). In this retrospective cohort study, we enrolled patients with stable COPD from 12 hospitals. Non-frequent exacerbation was defined as less than two times of exacerbations in the past year. The non-frequent exacerbation patients were classified into less and more symptomatic groups based on the COPD Assessment Test (CAT) and modified Medical Research Council (mMRC). Finally, the non-frequent exacerbation patients with less and more symptomatic were classified into the long-acting muscarinic antagonist (LAMA), long-acting β2-agonist (LABA)+inhaled corticosteroids (ICS), LABA+LAMA, and LABA+LAMA+ICS groups. Minimum clinically important difference (MCID) was defined as a CAT score decrease of ≥ 2 during six months of follow-up. We recorded the number of exacerbations and mortality during one year of follow-up. A total of 834 (67.5%) non-frequent exacerbation patients with COPD were included in this study. The non-frequent exacerbation patients had a higher education level and body mass index (BMI), and lower CAT and mMRC scores (P<0.05). In addition, the non-frequent exacerbation patients had lower mortality and risk of future exacerbation, and were more likely to attain MCID (P<0.05). Furthermore, the non-frequent exacerbation patients with more symptomatic COPD treated with LABA+LAMA or LABA+LAMA+ICS were more likely to attain MCID and had a lower risk of future exacerbation (P<0.05). However, there were no significant differences among the different inhalation therapies in non-frequent exacerbation patients with less symptomatic COPD. The non-frequent exacerbation patients with COPD had a higher education level and BMI, a lower symptom burden, and better outcomes. In addition, LABA+LAMA should be recommended to non-frequent exacerbation patients with more symptomatic COPD, while mono-LAMA should be recommended to non-frequent exacerbation patients with less symptomatic COPD as the initial inhalation therapy.

Cardiovascular Prognosis of Subclinical Chronic Obstructive Pulmonary Disease in Patients with Suspected or Confirmed Coronary Artery Disease.

Chronic obstructive pulmonary disease (COPD) worsens prognosis in patients with coronary artery disease (CAD). However, the cardiovascular prognosis in patients with stable or mildly symptomatic COPD remains unclear. Here, we sought to determine the long-term cardiovascular events in patients with subclinical or early-stage COPD with concomitant CAD. This was a longitudinal analytical study involving 117 patients with suspected or established CAD who underwent assessment of pulmonary function by spirometry and who were followed up for six years (March 2015-January 2021). The patients were divided into two groups, one comprising COPD (n=44) and the other non-COPD (n=73) patients. Cox regression was used to evaluate the association between COPD and cardiovascular events, with adjustment for the established CAD risk factors, and the effect size was measured by the Cohen test. COPD patients were older (p=0.028), had a greater frequency of diabetes (p=0.026), were more likely to be smokers (p<0.001), and had higher modified Medical Research Council scores (p<0.001). There was no difference between the groups regarding gender, body mass index, hypertension, dyslipidemia, family history of CAD, and type of angina. CAD frequency and the proportion of patients with severe and multivessel CAD were significantly higher among COPD than among non-COPD patients (all p<0.001). At six-year follow-up, patients with COPD were more likely to have experienced adverse cardiovascular events than those without COPD (p<0.001; effect size, 0.720). After adjusting for established CAD risk factors, COPD occurrence remained an independent predictor for long-term adverse cardiovascular events (OR: 5.13; 95% CI: 2.29-11.50; p<0.0001). COPD was associated with increased severity of coronary lesions and a greater number of adverse cardiovascular events in patients with suspected or confirmed CAD. COPD remained a predictor of long-term cardiovascular events in stable patients with subclinical or early-stage of COPD, independently of the established CAD risk factors.

Estimating the Prevalence of AATD Patients in the UK to Identify Underdiagnosis and Determine the Eligibility for Potential Augmentation Therapy.

Alpha 1 antitrypsin deficiency (AATD) is a genetic risk factor for chronic obstructive pulmonary disease (COPD). Whilst testing for the condition is relatively simple, there is a disconnect in published literature between genetic epidemiology and numbers of patients known to specialists. This makes planning services for patients difficult. We aimed to estimate the number of patients likely to have lung disease eligible for specific AATD therapy within the UK. The THIN database was used to determine the prevalence of AATD and symptomatic COPD. This, and published rates of AATD were used to extrapolate THIN data to the population size of the UK to give an indicative population size for symptomatic AATD patients who have lung disease. The Birmingham AATD registry was used to describe age at diagnosis, rate of lung disease and symptomatic lung disease for patients with PiZZ (or equivalent) AATD, together with the time from symptom onset to diagnosis, in order to aid interpretation of the THIN data and improve modeling. THIN data showed COPD prevalence of 3%, and AATD prevalence of 0.005-0.2%, depending on how stringently AATD diagnostic codes were applied. The majority of Birmingham AATD patients were diagnosed between the ages 46-55, whilst patients recorded in THIN tended to be older. The rate of COPD was similar in the THIN and Birmingham patients diagnosed with AATD. Modelling to the size of the UK demonstrated a likely symptomatic AATD population of between 3016 and 9866 people. AATD is likely to be under-diagnosed in the UK. Based on projected patient numbers an expansion to specialist services is desirable, in particular if specific therapy for AATD such as augmentation were to be introduced to the healthcare system.

The effects of different inhalation therapies on less symptomatic chronic obstructive pulmonary disease patients in a Chinese population: a real-world study

Background The Global Initiative for Chronic Obstructive Lung Disease (GOLD) document suggests that patients with chronic obstructive pulmonary disease (COPD) should be divided into a less symptomatic group. Moreover, single-inhaled drugs are recommended as initial inhalation therapy for them. However, many less symptomatic patients are provided double or triple-inhaled drugs as initial therapy in the real world. This study aimed to describe the inhalation prescriptions and compare the effects of different inhalation therapies on less symptomatic COPD patients. Patients and methods This was an observational study. Stable COPD patients were recruited and divided into a less symptomatic group including Groups A and C based on the GOLD 2019 document. We collected the data of inhalation therapies prescriptions. Then, the patients were classified into long-acting muscarinic antagonist (LAMA), long-acting β2-agonist (LABA) + inhaled corticosteroid (ICS), LABA + LAMA, and LABA + LAMA + ICS groups. All the patients were followed up for 1 year to collect exacerbation and mortality data. Results We found that only 45.4% of patients in Group A and 43.6% of patients in Group C received reasonable inhalation therapy in reference to the GOLD document. In addition, the LAMA group had a higher forced expiratory volume in one second (FEV1), FEV1%pred, FEV1/forced vital capacity and peak expiratory flow compared with LABA + ICS, LABA + LAMA and LABA + LAMA + ICS groups. However, we did not find any significant differences of exacerbation, hospitalization and mortality during the follow-up among different inhalation therapies groups on less symptomatic COPD patients. Conclusion Over half of the less symptomatic patients received inhalation therapy that were inconsistent with the GOLD document recommendations in a Chinese population in the real world. In fact, the single inhaled drug of LAMA should be recommended and pulmonary function is not a good indicator for the choice of initial inhalation therapy in less symptomatic COPD patients. KEY MESSAGES Over half of the less symptomatic COPD patients received inhalation therapy that were inconsistent with the GOLD document recommendations in a Chinese population in the real world. The clinicians should offer a single inhaled drug of LAMA to less symptomatic COPD patients and pulmonary function is not a good indicator for the choice of initial inhalation therapy.

Mortality Risk and Serious Cardiopulmonary Events in Moderate-to-Severe COPD: Post Hoc Analysis of the IMPACT Trial.

In the InforMing the Pathway of COPD Treatment (IMPACT) trial, single-inhaler fluticasone furoate (FF) /umeclidinium (UMEC) /vilanterol (VI) significantly reduced severe exacerbation rates and all-cause mortality (ACM) risk versus UMEC/VI among patients with chronic obstructive pulmonary disease (COPD). This post hoc analysis aimed to define the risk of ACM during and following a moderate/severe exacerbation, and further determine the benefit-risk profile of FF/UMEC/VI versus FF/VI and UMEC/VI using a cardiopulmonary composite adverse event (AE) endpoint. The 52-week, double-blind IMPACT trial randomized patients with symptomatic COPD and ≥1 exacerbation in the prior year 2:2:1 to once-daily FF/UMEC/VI 100/62.5/25mcg, FF/VI 100/25mcg, or UMEC/VI 62.5/25mcg. Post hoc endpoints included the risk of ACM during, 1-90 and 91-365 days post moderate or severe exacerbation and time-to-first cardiopulmonary composite event. Of the 10,355 patients included, 5034 (49%) experienced moderate/severe exacerbations. Risk of ACM was significantly increased during a severe exacerbation event compared with baseline (hazard ratio [HR]: 41.22 [95% confidence interval (CI) 26.49-64.15]; p<0.001) but not significantly different at 1-90 days post-severe exacerbation (HR: 2.13 [95% CI: 0.86-5.29]; p=0.102). Moderate exacerbations did not significantly increase the risk of ACM during or after an exacerbation. Cardiopulmonary composite events occurred in 647 (16%), 636 (15%), and 356 (17%) patients receiving FF/UMEC/VI, FF/VI, and UMEC/VI, respectively; FF/UMEC/VI significantly reduced cardiopulmonary composite event risk versus UMEC/VI by 16.5% (95% CI: 5.0-26.7; p=0.006). Results confirm a substantial mortality risk during severe exacerbations, and an underlying CV risk. FF/UMEC/VI significantly reduced the risk of a composite cardiopulmonary AE versus UMEC/VI.

Cost-Effectiveness of Once-Daily Single-Inhaler COPD Triple Therapy in Spain: IMPACT Trial.

Given between-country differences in healthcare systems, treatment costs, and disease management guidelines, country-specific cost-effectiveness analyses are important. This study evaluated the cost-effectiveness of once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI and UMEC/VI among patients with symptomatic chronic obstructive pulmonary disease (COPD) at risk of exacerbations from a Spanish healthcare system perspective. Baseline data and treatment effects from the IMPACT trial were populated into the validated GALAXY COPD progression model. Utilities were estimated using Spanish observational data. Direct healthcare costs (2019 €) were informed by Spanish public sources. A 3% discount rate for costs and benefits was applied. The time horizon and treatment duration were 3 years (base case). One-way sensitivity, scenario, and probabilistic sensitivity analyses were performed. FF/UMEC/VI treatment resulted in fewer exacerbations over 3 years (4.130 vs 3.648) versus FF/VI, with a mean (95% confidence interval [CI]) incremental cost of €444 (€149, €713) per patient and benefit of 0.064 (0.053, 0.076) quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio (ICER) of €6887 per QALY gained. FF/UMEC/VI was a dominant treatment strategy versus UMEC/VI, resulting in fewer exacerbations (4.130 vs 3.360), with a mean (95% CI) incremental cost of -€450 (-€844, -€149) and benefit of 0.054 (0.043, 0.064) QALYs. FF/UMEC/VI was cost-effective versus FF/VI and UMEC/VI across all analyses. FF/UMEC/VI was predicted to be a cost-effective treatment option versus FF/VI or UMEC/VI in symptomatic COPD patients at risk of exacerbations in Spain, across all scenarios and sensitivity analyses.

Single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol versus dual therapy in current and former smokers with COPD: IMPACT trial post hoc analysis

BackgroundSmoking is the major risk factor for chronic obstructive pulmonary disease (COPD). In IMPACT, single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy significantly reduced moderate/severe exacerbation rates and improved lung function and health status versus FF/VI or UMEC/VI in COPD patients. This post hoc analysis investigated trial outcomes by smoking status. MethodsIMPACT was a double-blind, 52-week trial. Patients aged ≥40 years with symptomatic COPD and ≥1 moderate/severe exacerbation in the prior year were randomized 2:2:1 to FF/UMEC/VI 100/62.5/25 μg, FF/VI 100/25 μg, or UMEC/VI 62.5/25 μg. Endpoints assessed by smoking status at screening included rate and risk of moderate/severe exacerbations, change from baseline in trough forced expiratory volume in 1 s, and St George's Respiratory Questionnaire total score at Week 52. Safety was also assessed. ResultsOf the 10,355 patients in the intent-to-treat population, 3,587 (35%) were current smokers. FF/UMEC/VI significantly reduced on-treatment moderate/severe exacerbation rates versus FF/VI and UMEC/VI in current (rate ratio 0.85 [95% confidence interval: 0.77–0.95]; P = 0.003 and 0.86 [0.76–0.98]; P = 0.021) and former smokers (0.85 [0.78–0.91]; P < 0.001 and 0.70 [0.64–0.77]; P < 0.001). FF/UMEC/VI significantly reduced time-to-first on-treatment moderate/severe exacerbation versus FF/VI and UMEC/VI in former smokers, and versus FF/VI in current smokers. Similar trends were seen for lung function and health status. Former smokers receiving inhaled corticosteroid-containing therapy had higher pneumonia incidence than current smokers. ConclusionsFF/UMEC/VI improved clinical outcomes versus dual therapy regardless of smoking status. Benefits of FF/UMEC/VI versus UMEC/VI were greatest in former smokers, potentially due to relative corticosteroid resistance in current smokers. Clinical trial registrationGSK (CTT116855/NCT02164513).

Diagnostic Accuracy of Optic Nerve Sheath Diameter Measured With Ocular Ultrasonography in Acute Attack of Chronic Obstructive Pulmonary Disease.

The study aimed to evaluate intracranial pressure changes by measuring ONSD before and after treatment in patients with chronic obstructive pulmonary disease (COPD). The study was designed as a prospective analysis, in which 56 COPD in acute exacerbation and 50 volunteers. COPD severity was determined by the Dyspnea Scale of Modified Medical Research Council (mMRC). Measurements were made with ocular ultrasonography and linear probe in both eyes. Both the right and left ONSDs were higher in the patient compared to the control (P=.017) and regressed after the treatment (P=.021). In the ROC analysis for the predictability of COPD, right eye ONSDs showed a predictive potential for COPD with %75.7 specificity and %68.1 sensitivity at 0.455 cut-off (AUC: 0.727; P=.0001; %95CI: 0.609-0.833). Similar to the right eye, the left ONSD presented %74.4 specificity and %67 sensitivity at 0.505 cut-off value (AUC: 0.718; P=.0001; %95CI: 0.608-0.841). The ONSD measurement that was with the help of ocular ultrasonography can be a useful diagnostic tool for symptomatic COPD presenting with an acute attack.

Effect of Recent Exacerbation History on the Efficacy of Once-Daily Single-Inhaler Fluticasone Furoate/Umeclidinium/Vilanterol Triple Therapy in Patients with Chronic Obstructive Pulmonary Disease in the FULFIL Trial.

BackgroundIn the FULFIL trial, once-daily single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) resulted in reduced moderate/severe exacerbation rates and conferred significant improvements in lung function and health status in patients with chronic obstructive pulmonary disease (COPD) versus twice-daily budesonide/formoterol (BUD/FOR) dual therapy.MethodsFULFIL was a Phase III, randomized, double-blind, double-dummy, parallel-group study. Patients ≥40 years of age with symptomatic COPD were randomized 1:1 to FF/UMEC/VI 100/62.5/25 mcg or BUD/FOR 400/12 mcg. In this post hoc analysis, patients were categorized by exacerbation history in the year prior to study entry (≥1 moderate/severe exacerbation [recent exacerbation] versus no recent exacerbation). Endpoints included annual rate of on-treatment moderate/severe exacerbations up to Week 24, annual rate of on-treatment severe exacerbations up to Week 24, change from baseline in trough forced expiratory volume in 1 second at Week 24, and change from baseline in health status as measured by St George’s respiratory questionnaire total score at Week 24.ResultsOf the 1810 patients in the intent-to-treat population, 1180 (65%) had one or more moderate/severe exacerbation in the year prior to entry, while 630 (35%) patients did not. FF/UMEC/VI versus BUD/FOR significantly reduced moderate/severe exacerbation rates in the recent exacerbation subgroup (mean annualized rate: 0.19 vs 0.29; rate ratio [95% confidence interval [CI]]: 0.64: [0.45, 0.91]; p=0.014) and numerically reduced moderate/severe exacerbation rates in the no recent exacerbation subgroup (mean annualized rate: 0.29 vs 0.43; rate ratio [95% CI]: 0.67 [0.43, 1.04]; p=0.073). Severe exacerbation rates were numerically reduced with FF/UMEC/VI versus BUD/FOR treatment across both subgroups. FF/UMEC/VI conferred significant improvements in lung function and health status versus BUD/FOR, regardless of recent exacerbation history.ConclusionFF/UMEC/VI reduced moderate/severe and severe exacerbation rates and improved lung function and health status versus BUD/FOR in patients with symptomatic COPD, regardless of recent exacerbation history.

Feasibility of a pulmonary rehabilitation programme for patients with symptomatic chronic obstructive pulmonary disease in Georgia: a single-site, randomised controlled trial from the Breathe Well Group

ObjectivesTo assess the feasibility of delivering a culturally tailored pulmonary rehabilitation (PR) programme and conducting a definitive randomised controlled trial (RCT).DesignA two-arm, randomised feasibility trial with a mixed-methods process evaluation.SettingSecondary...

The Efficacy and Cost-Effectiveness of Umeclidinium/Vilanterol versus Tiotropium in Symptomatic Patients with Chronic Obstructive Pulmonary Disease.

Both long-acting muscarinic antagonists (LAMAs) and long-acting β2-agonists (LABAs) are widely used in the treatment of chronic obstructive pulmonary disease (COPD). A novel LAMA/LABA combination of umeclidinium/vilanterol (UMEC/VI; 62.5 μg/25 μg) is approved for chronic obstructive pulmonary disease (COPD) treatment. This study aimed to assess the efficacy and cost-effectiveness of UMEC/VI versus tiotropium (TIO) 18 μg in symptomatic patients with COPD from the perspective of the Chinese National Healthcare System. A simple analysis included three studies in the meta-analysis that compared UMEC/VI with TIO. A Markov model was developed to estimate the cost-effectiveness of UMEC/VI compared with TIO treatment in symptomatic patients with COPD. First, utilities, clinical efficacy, and adverse events obtained from the literature were utilized as model inputs. Costs were from Chinese average data, including local data. Costs were expressed in dollars based on 2020 prices. Then, the model outputs including drug costs, other medical costs, and total costs, and quality-adjusted life years (QALYs) were estimated. Costs and outcomes were discounted at a 5% annual rate. Furthermore, incremental cost-effective ratios (ICERs) were analyzed. Finally, the influences of changing parameters on the uncertainty of the results were assessed by means of one-way and probabilistic sensitivity analyses. This study revealed that UMEC/VI treatment had a higher rate of clinical efficacy in comparison with TIO, and the differences in the rate of adverse events between the two treatments were not significant. The results indicated that UMEC/VI was superior to TIO, which provided an increase in QALYs (0.002) and a total cost savings of $765.67 per patient over 3 years. In the base case, the ICER of UMEC/VI is -$397468.04/QALY compared with TIO, suggesting that UMEC/VI may be considered a dominant option over TIO. According to the Chinese medical system, the probability of UMEC/VI being cost-effective was 61.6% at a willingness-to-pay (WTP) of $31554/QALY. Sensitivity analyses confirmed that the results were robust. UMEC/VI could be considered a cost-effective treatment compared with TIO in symptomatic COPD patients from the Chinese National Healthcare System perspective. These results may help decision-makers in China when making judgements on which treatments to administer.

Non-respiratory symptom dominance is associated with depression in patients with chronic obstructive pulmonary disease

IntroductionDepression is a common and important comorbidity in patients with chronic obstructive pulmonary disease (COPD). Depressive status is associated with a high COPD assessment test (CAT) total score, but it is difficult to distinguish patients with depression from those with severe symptomatic COPD. We hypothesized that a non-respiratory symptom-dominant elevation in CAT score is associated with depression in patients with COPD. MethodsA total of 226 patients in the KYOTO cohort in Japan and 924 patients in the Korea COPD Subgroup Study (KOCOSS) cohort in the Republic of Korea were analyzed. Depression was diagnosed based on a PHQ-9 (patient health questionnaire-9) ≥5 in the KYOTO cohort and a BDI-II (Beck Depression Inventory-II) ≥17 in the KOCOSS cohort. Sums of respiratory symptoms (Q1-Q4; Q1234) and non-respiratory symptoms (Q5-Q8; Q5678) from CAT items were analyzed. ResultsFifty-three (23.5%) patients in the KYOTO cohort and 111 (11.2%) patients in the KOCOSS cohort were identified as having depression. Fifty-five patients (24.3%) in the KYOTO cohort and 249 patients (26.9%) in the KOCOSS cohort showed non-respiratory symptom dominance (Q1234 ≤ Q5678), and they had a significantly higher prevalence of depression than did patients with respiratory symptom dominance (Q1234 > Q5678). Multivariable logistic regression analysis showed that both the CAT total score and Q1234 ≤ Q5678 were significantly associated with depression in both cohorts. Moreover, even in symptomatic patients (CAT total score ≥10), these significant associations were preserved. ConclusionNon-respiratory symptom dominance in CAT is a suspicious feature for depression in patients with COPD.

Comparing Clinical Outcomes of Tiotropium/Olodaterol, Umeclidinium/Vilanterol, and Indacaterol/Glycopyrronium Fixed-Dose Combination Therapy in Patients with Chronic Obstructive Pulmonary Disease in Taiwan: A Multicenter Cohort Study.

BackgroundLong-acting beta-agonists (LABA) and long-acting muscarinic antagonists (LAMA) combination therapy improved lung function and health-related quality-of-life and reduced exacerbation rates and dyspnea in symptomatic chronic obstructive pulmonary disease (COPD) patients. We compared the real-world effects of three fixed-dose LABA/LAMA combinations for COPD in Taiwan.MethodsThis multicenter, retrospective study evaluated 1-year outcomes after LABA/LAMA combination therapy in patients with symptomatic COPD. Exacerbations and symptoms of COPD, lung functions, and therapy escalation were compared among patients using tiotropium/olodaterol, umeclidinium/vilanterol and indacaterol/glycopyrronium. Propensity score matching (PSM) was applied to balance the baseline characteristics.ResultsData of 1,617 patients were collected. After PSM, time to first moderate-to-severe COPD exacerbation was comparable among three groups, while the annualized rates of the exacerbation (episodes/patient/year) in patients receiving tiotropium/olodaterol (0.19) or umeclidinium/vilanterol (0.17) were significantly lower than those receiving indacaterol/glycopyrronium (0.38). COPD-related symptoms were stable over the treatment period, and there was no significant difference in the changes of symptom scores including CAT and mMRC among three groups at the end of the study period.ConclusionThis study presented valuable real-world outcome in terms of exacerbation and treatment response of COPD patients treated with fixed-dose LABA/LAMA regimens in Taiwan. The annualized rates of moderate-to-severe exacerbation in patients receiving tiotropium/olodaterol or umeclidinium/vilanterol were significantly lower than those receiving indacaterol/glycopyrronium, though the time to first moderate-to-severe exacerbation was similar among different fixed-dose LABA/LAMA combinations.

Evaluating Triple Therapy Treatment Pathways in Chronic Obstructive Pulmonary Disease (COPD): A Machine-Learning Predictive Model.

PurposeInhaled triple therapy (TT) comprising a long-acting muscarinic antagonist, long-acting β2 agonist, and inhaled corticosteroid is recommended for symptomatic chronic obstructive pulmonary disease (COPD) patients, or those at risk of exacerbation. However, it is not well understood which patient characteristics contribute most to future exacerbation risk. This study assessed patient predictors associated with future exacerbation time following initiation of TT.Patients and MethodsThis retrospective cohort study used data from the Optum™ Clinformatics™ Data Mart, a large health claims database in the United States. COPD patients who initiated TT between January 2008 and March 2018 (index) were eligible. Patients were required to be aged ≥18 years at index and have continuous enrollment for the 12 months prior to index (baseline) and the 12 months following index (follow-up). Patients who had received TT during baseline were excluded. Data from eligible patients were analyzed using a reverse engineering forward simulation machine learning platform to predict future COPD exacerbation time.ResultsData from 73,625 patients were included. The model found that prior exacerbation was largely correlated with post-index exacerbation time; patients who had ≥4 exacerbation episodes during baseline had an average increase of 32.4 days post-index exacerbation, compared with patients with no exacerbations during baseline. Likewise, ≥2 inpatient visits (effect size 27.1 days), the use of xanthines (effect size 11.5 days), or rheumatoid arthritis (effect size 6.4 days) during baseline were associated with increased exacerbation time. Conversely, diagnosis of anemia (effect size –5.68 days), or oral corticosteroids in the past month (effect size –3.43 days) were associated with reduced exacerbation time.ConclusionFrequent prior exacerbations, healthcare resource utilization, xanthine use, and rheumatoid arthritis were the strongest factors predicting the future increase of exacerbations. These results improve our understanding of exacerbation risk among COPD patients initiating triple therapy.

A Pooled Analysis of Mortality in Patients with COPD Receiving Dual Bronchodilation with and without Additional Inhaled Corticosteroid

BackgroundRecent studies report a lower mortality rate during treatment with long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA)/inhaled corticosteroid (ICS) versus LAMA/LABA in patients with symptomatic chronic obstructive pulmonary disease (COPD) and a history of exacerbations.ObjectiveWe compared time to all-cause mortality with LAMA/LABA versus LAMA/LABA/ICS in patients with mild-to-very-severe COPD and a predominantly low exacerbation risk.MethodsData were pooled from six randomized controlled trials (TONADO 1/2, DYNAGITO, WISDOM, UPLIFT and TIOSPIR; LAMA/LABA: n = 3156, LAMA/LABA/ICS: n = 11,891). Analysis was on-treatment and data were censored at 52 weeks. Patients on LAMA/LABA/ICS received ICS prior to study entry, which was not withdrawn at randomization. Patients on LAMA/LABA/ICS were propensity score (PS)-matched to patients on LAMA/LABA who had not previously received ICS; covariates included age, sex, geographical region, smoking status, post-bronchodilator forced expiratory volume in 1 second percent predicted, exacerbation history in previous year, body mass index and time since diagnosis. Time to all-cause mortality was assessed using Cox proportional hazard regression models.ResultsAfter PS matching, 3133 patients on LAMA/LABA and 3133 patients on LAMA/LABA/ICS were analyzed. Fewer than 20% of patients reported ≥2 exacerbations in the prior year (LAMA/LABA: 19.1%; LAMA/LABA/ICS: 19.0%). There were 41 (1.3%) deaths on LAMA/LABA and 45 (1.4%) deaths on LAMA/LABA/ICS. No statistically significant difference in time to death was observed between treatment arms (hazard ratio for LAMA/LABA 1.06; 95% confidence intervals 0.68, 1.64; P = 0.806). Sensitivity analyses conducted using different covariates or in an intent-to-treat population showed similar results.ConclusionThis pooled analysis of over 6000 patients with mild-to-very-severe COPD and predominantly low exacerbation risk showed no differences in mortality with LAMA/LABA versus LAMA/LABA/ICS, suggesting that the survival benefit of triple therapy seen in some recent studies may be specific to a high-risk population. This supports current Global Initiative for Chronic Obstructive Lung Disease recommendations that triple therapy should be reserved for the subpopulations of patients who need it the most (eg, those with an eosinophilic phenotype and a high risk of exacerbations) to avoid ICS overuse.

Higher COPD Assessment Test Score Associated With Greater Exacerbations Risk: A Post Hoc Analysis of the IMPACT Trial.

In the InforMing the PAthway of COPD Treatment (IMPACT) trial, single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) reduced moderate/severe exacerbation rates versus FF/VI and UMEC/VI in patients with chronic obstructive pulmonary disease (COPD). This post hoc analysis tested the relationship between baseline health status, risk of future exacerbations, and efficacy outcomes. IMPACT was a Phase 3, double-blind, 52-week trial in patients with symptomatic COPD (COPD Assessment Test [CAT] score ≥10) and ≥1 moderate/severe exacerbation in the prior year randomized 2:2:1 to FF/UMEC/VI 100/62.5/25mcg, FF/VI 100/25mcg, or UMEC/VI 62.5/25mcg. Annual rate of on-treatment moderate/severe exacerbations, lung function, and safety were analyzed by continuous baseline CAT score. Moderate/severe exacerbation rates increased with increasing baseline CAT scores in FF/UMEC/VI and UMEC/VI arms. There was a very small increase in on-treatment pneumonia rates at higher baseline CAT scores across all treatment arms. FF/UMEC/VI reduced moderate/severe exacerbation rates versus UMEC/VI (i.e., the inhaled corticosteroid effect) consistently across the range of CAT scores. The reduction with FF/UMEC/VI versus FF/VI (i.e., the long-acting muscarinic antagonist effect) was greatest at lower CAT scores and appeared lesser at higher CAT scores. Improvements in lung function were observed with FF/UMEC/VI versus FF/VI and UMEC/VI, regardless of baseline CAT score. The CAT score was predictive of exacerbation risk. Worse baseline health status was associated with higher moderate/severe exacerbation and pneumonia rates. Irrespective of baseline CAT score, FF/UMEC/VI improved lung function, and reduced the annual moderate/severe exacerbation rates versus dual therapy. Results indicate an overall favorable benefit-risk profile of triple versus dual therapy, irrespective of CAT score. Clinical Trial Registration:GSK (CTT116855/NCT02164513).