Genetic and Epigenetic Associations with Pre–Chronic Obstructive Pulmonary Disease Lung Function Trajectories
David Martino, Dinh Bui, Shuai Li, Sabrina Idrose, Jennifer L. Perret, Adrian J. Lowe, Caroline Lodge, Gayan Bowatte, Yuben Moodley, Paul S. Thomas, Graeme R. Zosky, Philip M. Hansbro, John W. Holloway, Cecilie Svanes, Rosa Faner, E. Haydn Walters, Shyamali C. Dharmage
Abstract
Understanding the molecular mechanisms of lung function trajectories that progress to chronic obstructive pulmonary disease (COPD) (pre-COPD trajectories), especially those with a rapidly declining phenotype, should inform preventive interventions. The Tasmanian Longitudinal Health Study (TAHS) previously defined life-course lung function trajectories by serial spirometry in a cohort of all seven-year-old school children in the state of Tasmania recruited in 1968 and followed up to age 53 years (1). Of the six pre-bronchodilator FEV1 lifetime trajectories identified, three collectively accounted for 75% of chronic obstructive pulmonary disease (COPD) prevalence at age 53 years (2). These high-risk trajectories were: 1) early below average lung function (with usual rate of subsequent decline), 2) persistently low, and 3) early below average lung function with accelerated decline. The TAHS cohort provides a unique opportunity to investigate molecular factors associated with disadvantaged trajectories, and we conducted a pilot study in this cohort to characterize associations with COPD high-risk trajectories to inform more extensive longitudinal studies in the future.