Abstract Overview: This research study will leverage established datasets from nationwide longitudinal lung studies to characterize multi-volume mechanical changes affecting airway and chest wall pathophysiology in chronic obstructive pulmonary disease (COPD) in the presence of emphysema, small airway disease, low bone density, and sarcopenia. Emphysema, air trapping, airway counts and geometry, and multi-volume determined metrics of functional small airway disease (fSAD) have been well investigated. However, changes in airway and chest wall deformation between two lung volumes in COPD and their interactions in the presence of different comorbidities have not been explored. This study will characterize unique subtypes of COPD-related abnormalities in airway and chest wall deformation between inspiratory and expiratory lung volumes, identify their associations in COPD and comorbidities, and assess their impacts on disease progression and clinical outcomes. Methods: Inspiratory and expiratory chest CT scans will be used to define metrics of transverse (Δair-T) and longitudinal (Δair-L) airway deformation and caudocranial (Δwall-CC) and mediolateral (Δwall-ML) chest wall deformation between two lung volumes. Data of healthy never-smokers in the Multi-Ethnic Study of Atherosclerosis Lung (MESALung) will be used to build normative models of different deformation metrics. Genetic Epidemiology of COPD (COPDGene) study data will be used to characterize different subtypes of abnormalities in multi- volume airway and chest wall deformation in COPD. This project will achieve three aims. Aim 1 develops normative models of airway and chest wall deformation metrics, computes participant- and metric-specific standardized scores of deviations from expected values and identifies unique subtypes of lung volume associated airway and chest wall deformation in COPD. Aim 2 characterizes the associations of airway and chest wall subtypes in COPD with demographics, disease severity, radiographic markers, physical activity, smoking status and history, low bone density, and sarcopenia. Aim 3 investigates the associations of 5-year lung function change and clinical outcome metrics with different airway and chest wall subtypes. Novelty: (i) Characterization of novel subtypes of abnormalities in multi-volume airway and chest wall deformation in COPD and assessment of their clinical relevance. (ii) Automation of multi-volume CT-based airway and chest wall deformation metrics. (iii) Normative models of airway and chest wall deformation metrics. Strengths: Established longitudinal data repositories, multi-disciplinary expertise of the research team, and strong preliminary data. Deliverables and Significance: (i) CT-based characterization of new airway and chest wall deformation subtypes will facilitate understanding mechanical changes affecting airway and chest wall pathophysiology and their associations with COPD comorbidities and assessment of their impacts on disease progres...