Background: There are limited data regarding the relationship between interstitial lung disease (ILD) and the natural course of COVID-19. In this study, we investigate whether patients with ILD are more susceptible to COVID-19 than those without ILD and evaluate the impact of ILD on disease severity in patients with COVID-19.Methods: A nationwide cohort of patients with COVID-19 (n=8070) and a 1:15 age-, sex- and residential area-matched cohort (n=121 050) were constructed between 1 January 2020 and 30 May 2020 in Korea. We performed a nested case–control study to compare the proportions of patients with ILD between the COVID-19 cohort and the matched cohort. Using the COVID-19 cohort, we also evaluated the risk of severe COVID-19 in patients with ILDversusthose without ILD.Results: The proportion of patients with ILD was significantly higher in the COVID-19 cohort than in the matched cohort (0.8%versus0.4%; p<0.001). The odds of having ILD was significantly higher in the COVID-19 cohort than in the matched cohort (adjusted OR 2.02, 95% CI 1.54–2.61). Among patients in the COVID-19 cohort, patients with ILD were more likely to have severe COVID-19 than patients without ILD (47.8%versus12.6%), including mortality (13.4%versus2.8%) (all p<0.001). The risk of severe COVID-19 was significantly higher in patients with ILD than in those without ILD (adjusted OR 2.23, 95% CI 1.24–4.01).Conclusion: The risks of COVID-19 and severe presentation were significantly higher in patients with ILD than in those without ILD.

Introduction: Chronic systemic corticosteroid (CS) therapy is associated with an increased risk of mortality in patients with many chronic diseases. However, it has not been elucidated whether chronic systemic CS therapy is associated with increased mortality in patients with asthma. The aim of this study was to determine the effects of chronic systemic CS therapy on long-term mortality in adult patients with asthma.Methods: A population-based matched cohort study of males and females aged ≥18 years with asthma was performed using the Korean National Health Insurance Service database from 2005 to 2015. Hazard ratio (HR) with 95% confidence interval for all-cause mortality among patients in the CS-dependent cohort (CS use ≥6 months during baseline period) relative to those in the CS-independent cohort (CS use <6 months during baseline period) was evaluated.Results: The baseline cohort included 466 941 patients with asthma, of whom 8334 were CS-dependent and 458 607 were CS-independent. After 1:1 matching, 8334 subjects with CS-independent asthma were identified. The HR of mortality associated with CS-dependent asthma relative to CS-independent asthma was 2.17 (95% CI 2.04–2.31). In patients receiving low-dose CS, the HR was 1.84 (95% CI 1.69–2.00); in patients receiving high-dose CS, the HR was 2.56 (95% CI 2.35–2.80).Conclusions: In this real-world, clinical practice, observational study, chronic use of systemic CS was associated with increased risk of mortality in patients with asthma, with a significant dose–response relationship between systemic CS use and long-term mortality.

Rationale: Inhaled corticosteroids (ICS) are commonly prescribed with long-acting β2-agonists (LABA) in chronic obstructive pulmonary disease (COPD). To date, the effects of ICS therapy on the airway microbiome in COPD are unknown. Objectives: To determine the effects of ICS/LABA on the airway microbiome of patients with COPD. Methods: Clinically stable patients with COPD were enrolled into a 4-week run-in period during which ICS was discontinued and all participants were placed on formoterol (Form) 12 μg twice daily (BID). The participants were then randomized to budesonide/formoterol (Bud + Form; 400/12 μg BID), fluticasone/salmeterol (Flu + Salm; 250/50 μg BID), or formoterol only (12 μg BID) for 12 weeks. Participants underwent bronchoscopy before and after the 12-week treatment period. The primary endpoint was the comparison of changes in the airway microbiome over the trial period between the ICS/LABA and LABA-only groups. Measurements and Main Results: Sixty-three participants underwent randomization: Bud + Form (n = 20), Flu + Salm (n = 22), and Form (n = 21) groups; 56 subjects completed all visits. After the treatment period, changes in α-diversity were significantly different across groups, especially between Flu + Salm and Form groups (Δrichness: P = 0.02; ΔShannon index: P = 0.03). Longitudinal differential abundance analyses revealed more pronounced microbial shifts from baseline in the fluticasone (vs. budesonide or formoterol only) group. Conclusions: Fluticasone-based ICS/LABA therapy modifies the airway microbiome in COPD, leading to a relative reduction in α-diversity and a greater number of bacterial taxa changes. These data may have implications in patients who develop pneumonia on ICS. Clinical trial registered with www.clinicaltrials.gov(NCT02833480).

Airway remodeling is a key characteristic of chronic asthma, particularly in patients with a fixed airflow limitation. The mechanisms underlying airway remodeling are poorly understood, and no therapeutic option is available. The Wnt/β-catenin signaling pathway is involved in various physiological and pathological processes, including fibrosis and smooth muscle hypertrophy. In this study, we investigated the roles of Wnt/β-catenin signaling in airway remodeling in patients with asthma. Wnt7a mRNA expression was prominent in induced sputum from patients with asthma compared with that from healthy controls. Next, we induced a chronic asthma mouse model with airway remodeling features, including subepithelial fibrosis and airway smooth muscle hyperplasia. Higher expression of Wnt family proteins and β-catenin was detected in the lung tissue of mice with chronic asthma compared to control mice. Blocking β-catenin expression with a specific siRNA attenuated airway inflammation and airway remodeling. Decreased subepithelial fibrosis and collagen accumulation in the β-catenin siRNA-treated mice was accompanied by reduced expression of transforming growth factor-β. We further showed that suppressing β-catenin in the chronic asthma model inhibited smooth muscle hyperplasia by downregulating the tenascin C/platelet-derived growth factor receptor pathway. Taken together, these findings demonstrate that the Wnt/β-catenin signaling pathway is highly expressed and regulates the development of airway remodeling in chronic asthma.

Previous studies have suggested that respiratory virus infections may be associated with new-onset asthma. However, whether coronavirus disease 2019 (COVID-19) is associated with an increased risk of new-onset asthma remains unclear. We aimed to evaluate whether recent COVID-19 infection increases the risk of new-onset asthma and whether COVID-19 vaccination could mitigate this risk. We constructed three different study designs using the Korean National Health Insurance claim-based database: Study 1: COVID-19 diagnosed participants (COVID-19 cohort) and their matched controls; Study 2: COVID-19 vaccinated participants (vaccination cohort) and their matched controls; Study 3: vaccination cohort and their matched controls, excluding participants diagnosed with COVID-19. In Study 1, 1.6% of the COVID-19 cohort and 0.7% of the matched cohort developed new-onset asthma, with incidences of 31.28 and 14.55 per 1,000 person-years, respectively (p<0.001). COVID-19 cohort had a higher risk of new-onset asthma (adjusted hazard ratio [aHR], 2.14; 95% confidence interval [CI], 1.88-2.45) than matched controls. In Study 2, vaccination cohort had a lower risk of new-onset asthma than matched controls (aHR, 0.82; 95% CI, 0.76-0.89). However, among participants without a COVID-19 diagnosis, COVID-19 vaccination was not associated with a reduced risk of new-onset asthma in Study 3 (aHR, 0.95; 95% CI, 0.87-1.04). In subgroup analysis, the risk of new-onset asthma was significantly lower in fully vaccinated participants and higher in older individuals and in those with diabetes mellitus compared to their counterparts. COVID-19 was associated with a higher incidence of new-onset asthma, which might be preventable by COVID-19 vaccination.

Bronchiectasis is one of the common chronic respiratory diseases and associated with respiratory morbidity and mortality. However, neither its prevalence nor its etiology is well-defined. We aimed to estimate the prevalence and risk factors of bronchiectasis in adults. In a retrospective study, we analyzed radiologic findings on chest computed tomography (CT) images performed as part of a health-screening program. From January to December 2008, 1,409 (24.6%) of 5,727 participants in the screening program of a health promotion center at a university hospital underwent chest CT scans based on the subject's decision. Bronchiectasis was diagnosed, if there was abnormal bronchial dilatation in any area of both lungs on chest CT. Respiratory symptoms, smoking status, and past medical history were also analyzed to define clinical characteristics and risk factors of bronchiectasis. Of 1,409 patients (aged 23-86 years), who were screened for respiratory diseases using chest CT for one year in a health promotion center, 129 patients (9.1%) were diagnosed with bronchiectasis. The prevalence of bronchiectasis was higher in females than in males (11.5% vs. 7.9%, p = 0.022) and increased with age. Respiratory symptoms were reported in 53.7% of subjects. Previous history of tuberculosis (TB) (OR 4.61, 95% CI 2.39-8.88, p = 0.001) and age (OR 2.49, 95% CI 1.56-3.98, p = 0.001) were significantly associated with bronchiectasis. This retrospective analysis of chest CT findings in health screening examinees revealed a very high prevalence of bronchiectasis in adults. Previous TB infection is one of the major causes of bronchiectasis.