Abstract Rationale Cigarette smoking can cause structural and functional changes before respiratory symptoms or spirometrically defined airflow obstruction develops and is observed. Airway disease in younger at-risk adult smokers is poorly characterized. We suspected that these individuals experience acute respiratory events similar to acute exacerbations of COPD. Methods The SPIROMICS Study of Early COPD Progression (SOURCE) is an ongoing observational study of individuals aged 30-55 years with a smoking history of ≥ 10 pack-years. The recruitment strategy employed targeted social media marketing campaigns to minimize enrollment bias. Participants were deeply pheno- and endotyped using the SPIROMICS protocol, collecting clinical, physiological, imaging, blood, nasal, and sputum parameters. Regular telephone follow-up asked about ‘breathing problems’ as a marker of acute respiratory events. For this analysis, we focused on respiratory events involving health care encounters or new treatment with antibiotics or oral steroids (in the absence of urgent care visit). Results Among 690 SOURCE participants, 89 (12.9%) reported at least one acute respiratory event during the first two years of follow-up. Selected demographic and clinical characteristics of those reporting events compared to those without events are presented in the table below. Individuals reporting respiratory events were of similar age at study entry, more likely to be female, exhibit a higher CAAT score, more frequently reported chronic bronchitis symptoms, more often reported ‘asthma’ diagnosed by a physician and had greater cigarette smoke exposure at enrollment. Mean blood eosinophil counts were higher in those with events, with no difference in extent of functional small airways disease (fSAD) by matched inspiratory-expiratory computed tomographic CT scan. Although those with respiratory events had lower post-bronchodilator FEV1% predicted, the majority of each group were without airflow obstruction (GOLD 0/pre-COPD in 73% of those with events and 80.5% of those without events). Nevertheless, of the 89 individuals with events, 23 (25.8%) required emergency department visits or hospitalization. Conclusion In a cohort of younger ever-smoking individuals with modest evidence of airways disease, a significant minority of individuals reported respiratory events over 2 years. Those experiencing respiratory events had an increased burden of disease compared to those without events. These observations provide further strong evidence of clinically significant airways disease in younger ever-smoking individuals, independent of development of airflow obstruction. They suggest that respiratory events in these individuals are likely related to specific host characteristics and do not occur randomly across the population, based solely on encounters with triggers such as viral pathogens. This abstract is funded by: NHLBI
Kanamgode et al. (Fri,) studied this question.