Abstract Rationale Airway mucus plugs are prevalent in asthma and COPD and associated with increased respiratory symptoms and mortality. Paradoxically, while higher BMI is associated with airway disease in COPD, lower BMI has been associated with increased mucus plugs. However, causality remains uncertain as severe COPD may lead to weight loss. To assess potential causality, we examined associations of measured and genetically determined BMI with mucus plugs burden in a community-based cohort. Methods We included Framingham Heart Study participants with chest CT and genetic data. Mucus plugs in medium- to large-sized airways were visually scored per lung segment (1 if present, 0 if absent; total score 0-18). We calculated for each participant a BMI polygenic score (PGSBMI) aggregating effects of BMI-related genetic variants based on large genome-wide association studies. We examined associations of measured BMI and PGSBMI with total lung, upper-lobe, and lower-lobe mucus plugs using logistic regression (presence) and zero-inflated negative binomial regression (mucus plugs score), adjusting for age, sex, smoking status, pack-years, familial relatedness; PGS models additionally adjusted for principal components of genetic ancestry. To assess whether associations differed by lung regions, we tested an interaction between BMI and lobe location. Results Among 2,469 participants (mean age 57.3 years, 50.3% female, 6.4% current and 45.1% former smokers, mean BMI 28.4 kg/m²), mucus plugs were present in 22.1% (total lung), 14.5% (upper lobes), and 11.8% (lower lobes). A one-standard-deviation increase in measured BMI was associated with lower odds of mucus plugs presence in total lung (odds ratio OR 0.64, 95% CI 0.57-0.72), upper-lobe (OR 0.64, 95% CI 0.56-0.74), and lower-lobe (OR 0.65, 95% CI 0.55-0.76), and lower rate of mucus plugs score (total lung: incidence rate ratio IRR 0.67, 95% CI 0.61-0.75); upper-lobe: IRR 0.73, 95% CI 0.65-0.83; lower-lobe: IRR 0.76, 95% CI 0.65-0.88). Consistent with measured BMI, PGSBMI showed inverse associations for mucus plugs presence (total lung: OR 0.87, 95% CI 0.78-0.96; upper-lobe: OR 0.86, 95% CI 0.76-0.97; lower-lobe: OR 0.89, P = 0.07) and for mucus plugs score (total lung: IRR 0.82, 95% CI 0.74-0.91; upper-lobe: IRR 0.88, 95% CI 0.78-0.98; lower-lobe: IRR 0.89, P = 0.08). No interaction between measured BMI and lobe location was observed (P = 0.61). Conclusions In this population-based cohort, both measured and genetically predicted BMI were inversely associated with airway mucus plugs burden, supporting a potential protective effect of higher BMI against mucus plugging. Consistent associations across lung regions suggest a systemic rather than region-specific mechanism. This abstract is funded by: This work is supported by a Parker B. Francis Fellowship for Pulmonary Research and a Boston University Department of Medicine Career Investment Award
Zhang et al. (Fri,) studied this question.