Intrathoracic Adipose Tissue and Airway Structure, Lung Function, and Respiratory Symptoms: The Framingham Heart Study

Background: Obesity is associated with airway disease, but the contribution of specific thoracic adipose depots remains unclear. We examined whether intrathoracic adipose tissue (ITAT), defined as adipose tissue within the thoracic cavity excluding pericardial adipose tissue (PAT), was associated with airway phenotypes. Methods: We included Framingham Heart Study participants with CT-derived thoracic adipose tissue measures. Cross-sectional associations of ITAT with CT-based airway wall and lumen measurements, spirometry, and respiratory symptoms were evaluated using multivariable regression. Primary analyses used sex-specific ITAT z-scores and adjusted for waist circumference to account for central obesity. Secondary analyses examined sex-specific ITAT quintiles and compared ITAT and PAT in individual-depot and mutually adjusted models. Results: Among 2,825 adult participants (52.0% female), after adjustment for waist circumference, each 1-SD higher ITAT, relative to the sex-specific distribution, was associated with greater segmental ({beta} [95% CI]: 0.010 mm [0.006, 0.014]) and subsegmental airway wall thickness (0.006 mm [0.002, 0.009]), narrower segmental airway lumen diameter (-0.049 [-0.088, -0.011]), lower FEV1 percent predicted (-1.92 percentage points [-2.72, -1.12]), and higher odds of wheezing (OR [95% CI]: 1.16 [1.02, 1.31]) and dyspnea (1.22 [1.05, 1.42]). Associations were similar after further adjustment for PAT and across ITAT quintiles. In contrast, PAT was not independently associated with airway structural measures after adjustment for ITAT. Conclusion: Higher ITAT volume was associated with greater airway wall thickness and narrower airway lumen, as well as lower FEV1 and greater respiratory symptoms, independent of central obesity and pericardial adiposity. These findings support a depot-specific association of ITAT with airway disease.