RATIONALE:Chronic obstructive pulmonary disease (COPD) risk profiles have been described in populations consisting of or including older adults, leaving factors associated with COPD in younger adults overlooked. OBJECTIVES:To determine patient profiles of younger adults with COPD. METHODS:A cohort study was conducted using population-based survey data linked to health administrative data from Ontario, Canada, from 2007 to 2018. Younger adults (age 35-55 yr) newly diagnosed with COPD were matched to controls without COPD. Multivariable conditional logistic regression models were used to identify statistically significant predictors of COPD. To contextualize results, the analysis was repeated in older adults. RESULTS:There were 1,094 younger adults newly diagnosed with COPD. In adjusted analysis, previous influenza or pneumonia, higher level of comorbidity, a mental health condition, and a history of asthma independently predicted COPD diagnosis in younger adults. With the exception of mental health conditions, these same variables predicted COPD diagnosis in older adults. However, male sex, lower income, a history of respiratory disease other than asthma, and being overweight or underweight predicted COPD diagnosis in older but not in younger adults. CONCLUSIONS:Having a mental health condition was associated with COPD in younger adults, whereas male sex, lower income, a history of respiratory disease other than asthma, and being overweight or underweight did not. This new knowledge can be used to dispel stereotypes about COPD. They also suggest that different screening criteria should be considered for younger adults.

Purpose:Time to biologic initiation for the treatment of severe asthma (SA) is affected by many factors, including ease of access to biologics, which is often subject to approval by regulatory authorities and reimbursement criteria by relevant agencies. We investigated the association between ease of biologic access (using the biologic accessibility score [BACS] as a proxy) and post-biologic asthma outcomes, including remission. Methods:This ecological study, using data from CHRONICLE (a US severe asthma registry), the International Severe Asthma Registry (ISAR), and the Optimum Patient Care Research Database (OPCRD), included patients with SA from 21 countries. Associations at the country level, between BACS, a composite score of prescription criteria for biologics in SA, and the proportion of patients with a favorable asthma outcome 1-year post-biologic in each setting (ie ISAR country or in the CHRONICLE or OPCRD datasets) were tested. Several definitions of favorable outcome were used, including proportion of patients who achieved clinical remission (defined using 2, 3 and 4 domains), experienced no exacerbations, had well- or partly controlled asthma, a percent predicted forced expiratory volume in 1 second (ppFEV1) or percent predicted peak expiratory flow rate (ppPEFR) ≥80%, and no long-term oral corticosteroid (LTOCS) use. Results:A total of 9,183 patients were included. A higher BACS (as a proxy of easier access to biologics) was associated with a higher likelihood of achieving clinical remission (p≤0.001), no exacerbations (p<0.001), well- or partly controlled asthma (p=0.047), a ppFEV1 or ppPEFR ≥80% (p=0.004), and no need for LTOCS (p=0.045) 1 year post-biologic initiation. Conclusion:Easier access to biologics for patients with SA, a prerequisite for shorter time-to-initiation, was associated with a greater probability of achieving clinical remission and other favorable asthma outcomes. Initiating biologics earlier in the asthma disease course may help unlock greater therapeutic potential in SA. These findings warrant confirmation in additional studies to further establish the causal relationship between biologic accessibility, timing of initiation, and clinical outcomes in SA.

Despite decades of research and advocacy, the quality of care for chronic obstructive pulmonary disease (COPD) remains poor. Millions of patients fail to receive appropriate care, and fundamental changes are needed to improve care quality and patient outcomes. Guided by the Triple Aim of 1) improving population health, 2) improving individual patient experience, and 3) reducing per capita costs for care, population health management strategies aim to redesign healthcare. By adapting the delivery, coordination, and payment of high-quality services, population health management strategies hold promise to improve care for the large and heterogeneous COPD population. This workshop included a multidisciplinary panel of patients, payers, health system leaders, pulmonologists, primary care providers, pharmacists, nurses, and researchers to envision future models of care that achieve population health management for COPD. Past research demonstrates the effectiveness of population-based health system interventions to improve COPD case finding, primary and specialty care integration, inpatient management, and post-discharge services among patients with COPD. Sustaining these interventions will require value-based payment arrangements and adaptations to clinical care processes. The field will need to define meaningful outcomes and tailor appropriate team member roles and responsibilities. As part of healthcare redesign, workshop members recommended adopting effective strategies to encourage personalized high-quality decision-making (eg, nudges) and employ study designs that rigorously and quickly test interventions (eg, pragmatic and adaptive designs). To ensure patient centeredness, it will be essential to incorporate patient and caregiver perspectives and leadership into redesign efforts.

Asthma is the most common chronic airway disease worldwide, imposing substantial clinical, societal, and economic burden. Asthma is generally defined as a heterogeneous clinical syndrome characterised by fluctuating respiratory symptoms and variable expiratory airflow limitation. Despite this definition, asthma misdiagnosis remains high; 20-70% of individuals with asthma remain undiagnosed and untreated, and approximately 30% of those labelled as having asthma do not have the disease. Objective evidence, alongside variability of symptoms, is essential to support a diagnosis of asthma. However, international guidelines vary in the selection, sequencing, and interpretation of diagnostic tests, reflecting differences in methodology, health-care infrastructure, test availability, and health-economic considerations. Demonstration of variable expiratory airflow remains central to most pathways, whereas guidance on type 2 inflammatory biomarkers is inconsistent. No single test reliably confirms or excludes asthma, necessitating multi-test diagnostic approaches. Implementing guideline recommendations in routine practice is challenging. Barriers include temporal variability of symptoms and physiology, insufficient patient symptom recognition, restricted access to objective testing, and the presence of multimorbidity. This Personal View summarises the similarities and differences in diagnostic pathways across major guidelines, examines the challenges of applying these recommendations, and looks to future developments and potential solutions. We call for a coordinated international effort to advance diagnostic innovation and generate the high-quality evidence needed to transform asthma diagnosis.

Mucus plugs have been previously recognized as an important pathological feature in asthma and chronic obstructive pulmonary disease (COPD), but their clinical role in these diseases has not been explored in depth until recently. Mucus plug formation is driven by mucus hyperconcentration, changes in mucus viscoelastic properties, impaired clearance, and mucociliary collapse. Scoring systems, such as the bronchopulmonary segment mucus plug score, have been used to associate greater mucus plug burden with poor clinical outcomes. Additional scoring methods obtained through quantitative image processing are currently under development. Mucus plug burden has been associated with greater exacerbations and spirometric decline in both asthma and COPD, as well as greater mortality in COPD. Recently, mucus plug burden has been used as an endpoint in clinical trials to evaluate the effectiveness of biologic therapies in asthma; multiple biologic therapies demonstrated decreases in mucus plug burden and associated improvements in spirometry with treatment. Together, these data suggest that mucus plugs may be a treatable trait in asthma and COPD. Mucus plug burden has current clinical, phenotypic, and predictive utility and shows promise as a future biomarker. Increased incorporation into clinical trials, expanded evidence of treatment effect, and standardization of methodology and imaging protocols will be needed. Computed tomographic detection of mucus plug burden is ready for greater incorporation into both research outcomes and clinical care.

Obstructive airway disease is associated with sleep disturbances. We aimed to assess the relationship between lung function and sleep disorder symptoms using cross-sectionally collected data between March 2017 and August 2021 from the Undiagnosed Chronic Obstructive Pulmonary Disease and Asthma Population study, a prospective community-based multi-site case-finding study. Undiagnosed Chronic Obstructive Pulmonary Disease and Asthma Population study participants with respiratory symptoms but without diagnosed lung disease who completed spirometry and the Global Sleep Assessment Questionnaire were included. We conducted multivariate linear regression models for forced expiratory volume in 1 s, forced vital capacity and forced expiratory volume in 1 s/forced vital capacity by Global Sleep Assessment Questionnaire responses adjusted for confounders. The same models were employed to examine respiratory symptoms, as reported on the St George's Respiratory Questionnaire and Chronic Obstructive Pulmonary Disease Assessment Test, by Global Sleep Assessment Questionnaire responses. Logistic regression models were used to assess the association of undiagnosed obstructive airway disease with sleep symptoms. Amongst 2093 adults included in the study, 48.3% were female and the median age was 63 years (interquartile range 53-72). Two-hundred and five (9.79%) subjects met spirometry criteria for undiagnosed chronic obstructive pulmonary disease, and 191 (9.13%) for undiagnosed asthma. There were no significant associations between spirometry measures and sleep symptoms (p > 0.5), controlling for age, sex, body mass index, smoking and comorbidities. Those with undiagnosed asthma were more likely to report insomnia "at least sometimes" versus "never" (odds ratio 2.58, 95% confidence interval: 1.27-6.19, p = 0.02). Respiratory symptoms were associated with sleep symptoms, with significant (p < 0.05) increases in St George's Respiratory Questionnaire and Chronic Obstructive Pulmonary Disease Assessment Test scores in those reporting most sleep symptoms. Overall, we found an association between undiagnosed asthma and insomnia, and between respiratory and sleep disorder symptoms.

Rationale: The Undiagnosed COPD and Asthma Population trial showed that early diagnosis and treatment of asthma and chronic obstructive pulmonary disease (COPD) by pulmonologists improved healthcare use, respiratory symptoms, and quality of life. Objectives: To determine if the benefits of early diagnosis and treatment were greater in individuals with more advanced disease or in individuals with asthma as opposed to COPD. We also assessed whether pulmonologist-directed care benefited asthma and COPD subgroups equally. Methods: Case finding was used to identify adults with undiagnosed chronic respiratory symptoms in the community. A total of 508 newly diagnosed participants with COPD or asthma were randomized to receive pulmonologist-care intervention or usual care. Low and high disease burden categories for the St. George's Respiratory Questionnaire (SGRQ) and COPD Assessment Test were defined using a median-split of baseline scores, and minimal clinically important difference thresholds were used to define significant responses. Benefits of pulmonologist care were assessed by evaluating treatment effects within subgroups and by assessing treatment-by-subgroup interactions. Measurements and Main Results: Patients with higher disease burden at diagnosis were more likely to benefit from early diagnosis and treatment compared with those with lower disease burden. A total of 71% of those with high disease burden showed an improvement in COPD Assessment Test score by ⩾2 points over 12 months compared with 47% with low disease burden (odds ratio, 2.78; 95% confidence interval, 1.90-4.07; P < 0.001). Similar results were seen for SGRQ and FEV1 improvements. In contrast, responses to early diagnosis and treatment were similar for those with asthma versus COPD. Individuals with asthma randomized to undergo pulmonologist-directed care showed greater 1-year improvements in COPD Assessment Test score, SGRQ score, 36-item Short Form score, and FEV1 compared with individuals randomized to receive primary care. However, individuals with COPD experienced similar improvements regardless of whether their treatment was managed by a pulmonologist or primary care provider. Treatment-by-disease interaction terms were not statistically significant. Conclusions: Patients with greater disease burden who exhibited more advanced and symptomatic asthma and COPD at the time of diagnosis benefited more from earlier diagnosis and treatment. Patients with asthma tended to derive greater benefit from pulmonologist-directed care than patients with COPD.

BACKGROUND:Duchenne muscular dystrophy (DMD) is associated with impaired airway clearance and chest wall restriction, treated with lung volume recruitment (LVR) therapy. This study evaluated adherence patterns to LVR over 2 years in a cohort of boys with DMD. METHODS:Participants were included from the intervention arm of STEADFAST, a multi-centre randomized controlled trial of twice-daily LVR over 2 years in boys with DMD, 6-16 years with baseline forced vital capacity percent predicted (FVC%) ≥ 30% (Clinicaltrials. gov # NCT01999075). Adherence data were downloaded from a data logger on the LVR equipment and defined as LVR use at least daily on >50% of days. Logistic regression models evaluated associations between adherence and change in FVC%, rate of symptoms and change in quality of life (QOL) over 24 months. RESULTS:Fourteen of 33 boys (42.4%) were adherent to LVR. Among those non-adherent in the first 3 months, only one became adherent to LVR. Adherent participants tended to have lower baseline FVC % predicted than non-adherent individuals (median 77.2 (IQR (17.8) vs 89.7 (18.8) %; p = 0.08). The odds ratio for adherence was 1.02 (95% CI 0.97-1.08, p = 0.4) per unit increase in FVC%, and 0.08 (95% CI 0.001-11.7, p = 0.307) for each additional symptom/month over 24 months, adjusting for baseline age and ambulatory status. Adherence was not associated with QOL. CONCLUSIONS:Long-term LVR adherence was associated with early LVR usage pattern, but not change in lung function, symptoms or QOL. These findings underscore the importance of early support and education to promote long-term LVR adherence.

Chronic obstructive pulmonary disease (COPD) affects more than 400 million people, continues to be the third cause of death worldwide, and has substantial regional variations in prevalence, risk factors, and temporal trends. COPD is associated with major socioeconomic and health consequences, with low-income and middle-income countries contributing the most to its growing burden. COPD prevalence among women is projected to increase, while that among men will decrease. This difference is possibly because tobacco consumption among women is decreasing at a slower rate than among men. Also, women are more likely to be exposed to other risk factors such as biomass combustion products. Most COPD cases are preventable given the role that smoking and environmental factors play in its development. Knowledge of the causes of COPD in different areas of the globe could provide new insights to address the geographical disparity of the disease and thus make COPD prevention a reality. It is important to implement preventive health policies that might mitigate the expected increase in COPD in women in low-income and middle-income countries and have already proven successful in some regions with high prevalence of the disease. In addition, a reduction in the huge burden of underdiagnosed COPD is necessary to offer effective secondary and tertiary preventive interventions.

Rationale: Cough is a common symptom of undiagnosed respiratory conditions. Objectives: To investigate cough in adults with undiagnosed respiratory symptoms and its association with quality of life (QoL), sleep quality, and healthcare utilization for respiratory illness. Methods: We used a case-finding strategy to find community-dwelling adults with respiratory symptoms but no previous history of diagnosed lung disease. Pre and postbronchodilator spirometry determined if participants met diagnostic criteria for asthma, chronic obstructive pulmonary disease (COPD), or preserved ratio impaired spirometry, or if they had normal spirometry. Twelve questions from the Asthma Screening Questionnaire, COPD Assessment Test, and the St. George's Respiratory Questionnaire were used to develop a cough score. The 36-Item Short Form Survey and Global Sleep Assessment Questionnaire were used to assess QoL and sleep quality, respectively. Results: Adults with undiagnosed respiratory symptoms (n = 2,857; mean score, 57.8; 95% confidence interval [CI], 56.9 to 58.6) reported higher cough scores than age-matched control subjects (n = 231; mean score, 17.7; 95% CI, 15.6 to 19.8). Participants found to have asthma (n = 265; mean score, 61.0; 95% CI, 58.2 to 63.7) and COPD (n = 330; mean score, 61.8; 95% CI, 59.3 to 64.3) had higher cough scores than those with preserved ratio impaired spirometry (n = 172; mean score, 54.5; 95% CI, 51.1 to 58.0) or normal spirometry (n = 2,090; mean score, 57.0; 95% CI, 56.0 to 58.0). Higher cough scores were associated with decreased QoL (lower 36-Item Short Form Survey score; regression coefficient, -0.19; 95% CI, -0.22 to -0.17; P < 0.001), worse sleep quality (higher Global Sleep Assessment Questionnaire score; regression coefficient, 0.16; 95% CI, 0.14 to 0.18; P < 0.001), and higher healthcare utilization for respiratory illness (incidence rate ratio, 1.007; 95% CI, 1.004 to 1.010; P < 0.001). Conclusions: In adults with undiagnosed respiratory symptoms, cough was most severe in those with undiagnosed asthma or COPD and was independently associated with worse QoL, impaired sleep quality, and higher healthcare utilization for respiratory illness.

BACKGROUND:Asthma with low levels of type 2 (T2) biomarkers is poorly understood. OBJECTIVE:To characterize severe asthma phenotypes and compare changes in asthma outcomes from pre- to postbiologic treatment along a gradient of T2 involvement. METHODS:This was a registry-based cohort study including data from 24 countries. Biomarker distribution (blood eosinophil count, fractional exhaled nitric oxide, and IgE) was quantified before biologic initiation. Clusters were identified using a 5-component Gaussian finite mixture model and phenotypically characterized. Changes in asthma and health care utilization outcomes between 1-year pre- and postbiologic initiation were compared between clusters and by biologic class. RESULTS:Among 3675 patients, 5 biomarker clusters were identified along a gradient of T2 involvement: cluster A with the lowest T2 involvement (16.4%), cluster B (20.4%), cluster C (22.9%), cluster D (30.3%), and cluster E with the highest T2 involvement (10.0%). In multivariable analysis, biologic use was associated with improved outcomes in all clusters but tended to be better at the higher end of the T2 spectrum. For example, patients in cluster C had a significantly greater increase in forced expiratory volume in 1 second compared with cluster A (difference 0.16 L [95% confidence interval: 0.08, 0.25]; P < .001). The odds of uncontrolled asthma were approximately 0.6 for all clusters compared with cluster A. Overall, exacerbation rates were lower, and greater improvements in lung function and asthma control were noted for anti-IL-5/5 receptor (R) (but not anti-IgE or anti-IL-4Rα) for all clusters compared with cluster A. CONCLUSION:T2-targeting biologics have utility in the management of asthma with low T2 involvement, but more effective therapies are needed. Further research is warranted to identify specific pathogenic pathways at the lower end of the T2 spectrum that can be effectively targeted by biologics.

Background:Diagnosing pulmonary embolism (PE) in patients with acute exacerbation of COPD (AECOPD) is challenging. Finding predictors of PE could help improve diagnostic management of patients with AECOPD. The aim was to evaluate the association between AECOPD purulence status and the presence of PE. Methods:A systematic review with meta-analysis was conducted. Medline, Embase and CENTRAL were searched from inception to April 2024 for randomised trials, cohort or cross-sectional studies reporting on the prevalence of PE according to AECOPD purulence status. Relative risks with 95% confidence intervals of PE according to AECOPD purulence status and pooled proportions of PE with their 95% confidence intervals were calculated according to AECOPD purulence status. Results:From 7059 citations identified, 14 studies (5056 participants) were included. The prevalence of PE varied between 0.4% and 33.2% across studies. The relative risk of PE was not statistically significantly lower in patients with purulent AECOPD compared to patients with nonpurulent/unknown aetiology AECOPD (relative risk 0.64, 95% CI 0.26-1.55; I2=88.0%). The pooled proportion of PE was 7.3% (95% CI 2.4-14.7%; I2=94.7%) and 13.3% (95% CI 8.0-19.7%; I2=96.0%) in studies including patients with purulent AECOPD and nonpurulent/unknown aetiology AECOPD, respectively. Conclusion:The relative risk of PE was lower, but not statistically significant, in patients with purulent AECOPD compared to patients with nonpurulent/unknown aetiology AECOPD. Further studies are needed to confirm the association between PE and AECOPD purulence status and to assess its potential role in predicting PE.

Objectives To assess how changes in outpatient services during the first year of the COVID-19 pandemic were related to acute healthcare use (emergency department or hospitalizations) for individuals with asthma or chronic obstructive pulmonary disease (COPD). Methods We conducted an observational study using health administrative data in Ontario (Canada) from January 2016 to March 2021 on all adults with diagnosed asthma or COPD. We used monthly time series auto-regressive integrated moving-average (ARIMA) and pre-pandemic monthly rates (January 2016 to February 2020) to calculate projected rates (i.e., a pandemic had not occurred) during the pandemic (March 2020 to March 2021), and Quasi-Poisson models with two-way interaction to estimate crude and adjusted rate ratios. Results In the first pandemic year, in individuals with asthma or COPD, outpatient visit rates started lower than projected (Mar-May 2020), returned to projected in the middle of the year (Jun-Aug 2020) and then rose to higher than projected between Sep 2020 and Mar 2021: observed rates of 80,293 per 100,000 persons vs. projected 74,192 (95% CI: 68,926-79,868) in individuals with asthma, and 92,651 vs. projected 85,871 (95% CI: 79,975-92,207) in individuals with COPD. Acute care rates remained below projected during the first pandemic year. While pulmonary function test (PFT) rates remained below projected during the first pandemic year, in both populations, a decrease in acute care visits during the pandemic, compared to pre-pandemic, was noted during months with the highest PFT rates (interaction p-values < 0.0001). Conclusions Despite asthma and COPD being ambulatory-care sensitive conditions, lower rates of outpatient visits during the beginning of the pandemic were not associated with increased rates of acute care use. Lower PFT rates were associated with higher acute care visit rates, suggesting that access to PFT during pandemic is likely important for individuals with asthma or COPD.

The rapid growth in popularity of e-cigarettes over the past decade has prompted concerns about their impact on long-term respiratory health. Small airway injury is suspected to be a direct consequence of e-cigarette use and may be quantifiable by novel structural and functional diagnostic modalities. In a multicentre observational longitudinal study, participants will be enrolled in either an adolescent (ages ≥12 and <19 years) or an adult arm (≥19 years old) and followed over 3 years across three time points (baseline, 18 months and 36 months). In the adolescent arm, a total of 50 e-cigarette and 50 non-e-cigarette users will be enrolled across 4 sites. In the adult arm, a total of 100 e-cigarette users, 100 non-e-cigarette users, and an additional 100 combustible cigarette-only users and 100 dual combustible cigarette-e-cigarette users will be enrolled across 5 sites. Participants will undergo respiratory questionnaires, pulmonary function tests, oscillometry, cardiopulmonary exercise testing, hyperpolarised 129-xenon gas MRI and blood collection. In adolescent participants only, multiple breath washout and induced sputum collection will be performed. Adult participants will also undergo inspiratory/expiratory chest CT and bronchoscopy. The primary endpoint will be a composite of small airway dysfunction according to oscillometry, cardiopulmonary testing and/or chest imaging parameters. This protocol has been approved by The University of British Columbia-Providence Health Care Research Ethics Board (Certificate H24-00374). The use of hyperpolarised 129-xenon gas in this study has been approved by Health Canada (Certificate HC6-024-c291776). Written documentation of informed consent will be required prior to study initiation. We will seek to enrol adolescent participants who are capable of providing informed consent with an optional support statement from a parent encouraged but not required. Study findings will be disseminated to medical/scientific audiences through scientific conferences and published manuscripts respecting the Strengthening the Reporting of Observational Studies in Epidemiology statement, to youths through outreach events at high schools and community programmes and through social media, and to adults through lung health community events. NCT06819969.