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

Abstract

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: MESA (Multi-Ethnic Study of Atherosclerosis) 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) (2000-2002). Percentage emphysema, defined as percentage of lung pixels below -950 Hounsfield units, was assessed up to five times per participant via cardiac CT scan (2000-2007) and equivalent regions on lung CT scan (2010-2018). Long-term outdoor air pollutant concentrations (particulate matter with an aerodynamic diameter ⩽2.5 μm, oxides of nitrogen, and ozone) were estimated at the residential address with validated spatiotemporal 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. Measurements and Main Results: Among 6,793 participants (mean ± SD age, 62 ± 10 yr), baseline airway tree caliber was 3.95 ± 1.1 mm and median (interquartile range) of percentage emphysema was 2.88 (1.21-5.68). In adjusted analyses, 10-year emphysema progression rate was 0.75 percentage points (95% confidence interval, 0.54-0.96%) higher in the smallest compared with 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 the mechanisms of airway-alveolar homeostasis and air pollutant deposition is needed.

Keywords: air pollution; airway morphology; dysanapsis; emphysema.

Figure 1.

Participant selection. CT = computed tomography; MESA = Multi-Ethnic Study of Atherosclerosis.

Figure 2.

Stratified analysis of the association between airway tree caliber with percentage emphysema progression in fully adjusted linear mixed models. Effect estimates are expressed per 1-mm decrement in airway tree caliber.

Figure 3.

Effect modification by airway tree caliber on the association between pollution exposure and emphysema progression. The longitudinal association between time-varying exposure to air pollution and progression of emphysema on computed tomography scan is presented per interquartile range increase in pollutant concentrations. Effect estimates presented for the full cohort and per quartile of airway tree caliber, derived from fully adjusted linear mixed models incorporating interaction between airway tree caliber × pollution × time. The P value shown is the F-statistic from the three-way interaction. Quartile 1 (Q1) represents the smallest airway tree quartile. NO_x = oxides of nitrogen; O₃ = ozone; PM_2.5 = particulate matter with an aerodynamic diameter ⩽2.5 μm.