Airway Tree Caliber and Susceptibility to Pollution-associated Emphysema: MESA Air and Lung Studies

Rationale: Airway tree morphology varies in the general population and may modify the distribution and uptake of inhaled pollutants. Objectives: We hypothesized that smaller airway caliber would be associated with emphysema progression and would increase susceptibility to air pollutant-associated emphysema progression. Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) is a general population cohort of adults 45-84 years old from six U.S. communities. Airway tree caliber was quantified as the mean of airway lumen diameters measured from baseline cardiac computed tomography (CT) (2000-02). Percent emphysema, defined as percentage of lung pixels below −950 Hounsfield units, was assessed up to 5 times per participant via cardiac CT scan (2000-07) and equivalent regions on lung CT scan (2010-18). Long-term outdoor air pollutant concentrations (PM2.5, NOx, O3) were estimated at residential address with validated spatio-temporal models. Linear mixed models estimated the association between airway tree caliber and emphysema progression; modification of pollutant-associated emphysema progression was assessed using multiplicative interaction terms. Main Results: Among 6,793 participants (mean±SD age: 62±10 years), baseline airway tree caliber was 3.95±1.1 mm and median (interquartile range) of percent emphysema was 2.88 (1.21-5.68). In adjusted analyses, 10-year emphysema progression rate was 0.75 percentage points (95%CI 0.54-0.96%) higher in the smallest compared to largest airway tree caliber quartile. Airway tree caliber also modified air pollutant-associated emphysema progression. Conclusions: Smaller airway tree caliber was associated with accelerated emphysema progression and modified air pollutant-associated emphysema progression. A better understanding of mechanisms of airway-alveolar homeostasis and air pollutant deposition are needed.