D30-11 Obesity Masks Airway Remodeling: Restriction-driven Elevation of Fev1/fvc in a Lung Cancer Screening Cohort

Abstract Introduction In obese smokers, there is a paradox between the impact of mechanical restriction on FEV1/FVC ratio and effects of airway inflammation reflected in CT parameters (airway wall thickness at 10mm internal perimeter Pi10, percentage of low attenuation areas less than -950 Hounsfield units %LAA-950, airway caliber at generation 6 AC). Preserved Ratio Impaired Spirometry (PRISm), characterized by impaired FEV1 with ratio of FEV1/FVC 0.7, is associated with higher body mass index (BMI). Due to overlapping risk factors, lung cancer screening (LCS) programs offer an opportunity to further assess disease and imaging characteristics of PRISm. Methods 310 participants attending LCS consented to an observational study. Electronic medical record (EMR) data and pre-bronchodilator spirometry were collected with CT imaging (image analysis: Coreline AVIEW COPD). 193 participants were included in the analysis, excluding EMR diagnosis of asthma (n = 75 EMR diagnosis of COPD) to explore the relationship between BMI, Pi10 and FEV1/FVC to quantify how restriction-driven elevation of FEV1/FVC ratio in overweight/obese individuals may attenuate the obstructive signal of airway remodeling. BMI group was categorized as Normal (BMI 25kg/m2) vs Overweight/Obese (≥25kg/m2); Pi10, AC and %LAA-950 were derived from CT. Multivariable linear regression modeled FEV1/FVC as the dependent variable with Pi10, BMI group, %LAA-950, AC and clinical covariates. Effect modification was assessed via Pi10×BMI interaction; confounding was evaluated by change-in-estimate of Pi10 after adding BMI and by likelihood ratio tests of nested models. Secondary analyses modeled FEV1 and FVC separately to clarify whether BMI-driven restriction (FVC reduction) explains ratio inflation. Results Overweight/Obese participants exhibited higher FEV1/FVC (+0.33, 95% CI −0.02, 0.68, p = 0.066), consistent with restriction-related physiology, and higher Pi10 (+0.125, 95% CI 0.018, 0.232, p = 0.023) independent of airway caliber and inspiratory lung volume. Pi10 was associated with FEV1/FVC in normal BMI (+0.087, 95% CI 0.009, 0.166, p = 0.030), but this association was lower in overweight/obese participants (interaction: −0.066, 95% CI −0.146, 0.015, p = 0.109; slope: +0.022). Addition of BMI to the model reduced the Pi10 coefficient by 24% (0.0487 vs 0.0370; LR = 7.06, p = 0.008). Conclusion The association between Pi10 and FEV1/FVC is confounded and modified by BMI. Overweight/Obese participants show restriction-driven elevation of FEV1/FVC ratio (positive BMI effect) and dampened Pi10-ratio slope (negative interaction), masking the obstructive signal of airway remodeling. BMI increases Pi10 independent of AC and lung volume. These findings underscore the need for inclusion of BMI and inflation-adjusted models when assessing airway disease. This abstract is funded by: AstraZeneca