Genetic and Epigenetic Associations with Pre-Chronic Obstructive Pulmonary Disease Lung Function Trajectories

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.