Abstract Rationale Cigarette smoking can cause structural and functional changes before airflow obstruction develop. The nature, frequency, and clinical consequences of acute respiratory events in younger at-risk smoking individuals is poorly understood. The SPIROMICS Study of Early COPD Progression (SOURCE) investigates younger smokers and controls to provide insight on biological mechanisms of early disease. We present predictors of acute and recurrent respiratory events requiring medical therapy during the first two years of follow-up. Methods SOURCE (ClinicalTrials.gov Identifier: NCT05033990) is an ongoing cohort study enrolling individuals aged 30-55 years with a smoking history of ≥ 10 pack-years. Recruitment employed digital and social media outreach, a centralized SOURCE website, and collaboration with specialized marketing partners to minimize enrollment bias. Participants were deeply phenotyped and endotyped using the SPIROMICS protocol. Regular telephone follow-up queried about ‘breathing problems,’ requiring or not requiring treatment, as a marker of acute respiratory events. We used an adjusted zero-inflated multivariate model incorporating demographic, clinical features, and events in the year before enrollment to predict events in the subsequent two years of follow-up. Results Among n = 690 participants (mean or percentage) age (46 yrs), female (50%), post-bronchodilator FEV1 % predicted (97.8%), chronic airways assessment test (11.3); distribution: GOLD 0 (80%), GOLD 1-2 (11%), PRISm (5%), never-smoker control group (5%), n = 89 (12.9%) reported at least one respiratory event over a median follow-up of 41 months. The frequency of events in those who experienced at least one event over the first two years is illustrated in the Figure. Respiratory events were reported by 57 (8.3% of total cohort) in the first year of follow-up and 50 (7.2% of total cohort) in the second year. In a multivariate model, sex (p = 0.008), history of asthma (p = 0.0001), smoking history (expressed as pack years, p 0.0001), CAAT (p = 0.003), chronic bronchitis symptoms (p = 0.04), and blood eosinophil count (cells/µL, p = 0.04) were predictive of an event occurring in the first two years of follow-up, while the age, post-bronchodilator FEV1 % predicted, percent of functional small airway disease (fSAD), and total number of events in the year before baseline were not predictive. Conclusion In the SOURCE cohort, 12.9% of participants experienced at least one respiratory event, with a significant minority experiencing multiple events over the first two years of follow-up. Among those who reported a respiratory event, the factors that predicted recurrent events were sex, history of asthma, the level of cigarette smoke exposure, CAAT, chronic bronchitis symptoms, and blood eosinophil count. This abstract is funded by: NIH
Bosma et al. (2026) studied this question.