Landscape fire smoke airway exposure impairs respiratory and cardiac function and worsens experimental asthma.

Abstract

Millions of people are exposed to landscape fire smoke (LFS) globally, and inhalation of LFS particulate matter (PM) is associated with poor respiratory and cardiovascular outcomes. However, how LFS affects respiratory and cardiovascular function is less well understood. We aimed to characterize the pathophysiologic effects of representative LFS airway exposure on respiratory and cardiac function and on asthma outcomes. LFS was generated using a customized combustion chamber. In 8-week-old female BALB/c mice, low (25 μg/m³, 24-hour equivalent) or moderate (100 μg/m³, 24-hour equivalent) concentrations of LFS PM (10 μm and below [PM₁₀]) were administered daily for 3 (short-term) and 14 (long-term) days in the presence and absence of experimental asthma. Lung inflammation, gene expression, structural changes, and lung function were assessed. In 8-week-old male C57BL/6 mice, low concentrations of LFS PM₁₀ were administered for 3 days. Cardiac function and gene expression were assessed. Short- and long-term LFS PM₁₀ airway exposure increased airway hyperresponsiveness and induced steroid insensitivity in experimental asthma, independent of significant changes in airway inflammation. Long-term LFS PM₁₀ airway exposure also decreased gas diffusion. Short-term LFS PM₁₀ airway exposure decreased cardiac function and expression of gene changes relating to oxidative stress and cardiovascular pathologies. We characterized significant detrimental effects of physiologically relevant concentrations and durations of LFS PM₁₀ airway exposure on lung and heart function. Our study provides a platform for assessment of mechanisms that underpin LFS PM₁₀ airway exposure on respiratory and cardiovascular disease outcomes.