Predictors of Airway Dysanapsis in Early Life (PADEL)

About This Grant

PROJECT SUMMARY/ABSTRACT Chronic obstructive pulmonary disease (COPD) accounts for 6% of all deaths worldwide and is potentially preventable, with well-described but poorly elucidated childhood origins. Improved understanding of early life origins of COPD could lead to interventions to substantially reduce morbidity and mortality from COPD, particularly in high-risk populations. Dysanapsis refers to a mismatch between airway tree caliber and lung volume that arises early in life. Our research team recently identified that dysanapsis is: 1) prevalent among older adults, 2) is a major predictor of COPD risk – exceeding tobacco smoke and other established risk factors, and 3) is not fully explained by genetics. We also know that there are heterogenous structural presentations of dysanapsis. However, the early life origins of dysanapsis are poorly understood. This R01 study will leverage 8 longitudinal birth cohorts of children to examine the relationship between early- life exposures and events and both structural (imaging-confirmed) and functional (spirometry-assessed) dysanapsis throughout childhood and adolescence to identify modifiable risk factors and help reduce risk of COPD in future generations at risk. Building on our preliminary data showing that magnetic resonance imaging (MRI) is as accurate as computed tomography (CT) at identifying dysanapsis, we will integrate state-of-the-art lung MRI data with extensive early-life exposure and lung function data. Aim 1 will establish relationships between early life dysanapsis and childhood lung function trajectories, and their relationship to structural dysanapsis at late adolescence. Aim 2 will determine if individual-level factors, specifically obesity and viral infections, contribute to functional dysanapsis (spirometry-assessed) and distinct structural subtypes of dysanapsis (imaging-confirmed). Aim 3 will examine community-level factors and associations with functional dysanapsis (spirometry-assessed). This study aligns with NHLBI’s strategic objective to investigate factors accounting for health differences among populations. We will establish the early-life risk factors that contribute to airway-to-lung phenotypes and enhance our understanding of the utility of both imaging- and spirometry-based measures of dysanapsis. Moreover, our findings will inform targeted interventions in high-risk groups of children to reduce their subsequent risk of COPD.