Adult Life Course Trajectories of Lung Function and the Development of Interstitial Lung Abnormalities: The CARDIA Lung Study.

Background: Interstitial lung abnormalities (ILA) are radiologic findings of increased lung density or fibrosis in individuals without clinical interstitial lung disease (ILD) and are associated with increased mortality and progression to ILD. Understanding physiologic trajectories of lung function preceding ILA diagnosis may illuminate early mechanisms of lung injury. Methods: We recruited participants from the Coronary Artery Risk Development in Young Adults (CARDIA) Lung Study, a prospective cohort of adults enrolled at ages 18-30 years and followed longitudinally for 25 years. Percent predicted forced vital capacity (ppFVC) was measured at five study visits over 20 years. Individual ppFVC trajectories were estimated using random coefficient models. Person-specific slopes were incorporated into logistic regression models to examine associations with visually detected ILA on chest CT at exam year 25. Models were adjusted for age, sex, race, body mass index, pack-years of smoking, and study center. Results: Among 3,136 participants with complete data, 57 (1.8%) had ILA at mean age 51 years. In univariable and multivariable models, individuals with ILA had greater cumulative decline in ppFVC over the 20 years preceding diagnosis. Each 10% absolute decline in ppFVC was associated with more than twice the odds of ILA (adjusted OR 2.21, 95% confidence interval 1.47-3.31, p = 0.0001). Conclusions: Greater longitudinal decline in FVC from early adulthood was strongly associated with the presence of ILA at midlife. These findings suggest that physiologic impairments precede radiologic evidence of subclinical parenchymal lung abnormalities, underscoring the potential of life course lung function trajectories to identify individuals at risk for developing ILD.