Acute exacerbation of idiopathic pulmonary fibrosis associated with air pollution exposure

Abstract

Acute exacerbations of idiopathic pulmonary fibrosis are associated with high mortality and are of unknown cause. The effect of air pollution on exacerbations of interstitial lung disease is unknown. This study aims to define the association of air pollution exposure with acute exacerbation of idiopathic pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis and corresponding air pollution data were identified from a longitudinal cohort. Air pollution exposures were assigned to each patient for ozone, nitrogen dioxide, particulate matter, sulfur dioxide and carbon monoxide based on geo-coded residential addresses. Cox proportional hazards models were used to estimate the association of air pollution exposures and acute exacerbations. Acute exacerbation was significantly associated with antecedent 6-week increases in mean level, maximum level and number of exceedances above accepted standards of ozone (hazard ratio (HR) 1.57, 95% CI 1.09-2.24; HR 1.42, 95% CI 1.11-1.82; and HR 1.51, 95% CI 1.17-1.94, respectively) and nitrogen dioxide (HR 1.41, 95% CI 1.04-1.91; HR 1.27, 95% CI 1.01-1.59; and HR 1.20, 95% CI 1.10-1.31, respectively). Increased ozone and nitrogen dioxide exposure over the preceding 6 weeks was associated with an increased risk of acute exacerbation of idiopathic pulmonary fibrosis, suggesting that air pollution may contribute to the development of this clinically meaningful event.

FIGURE 1

Ozone (O₃) and nitrogen dioxide (NO₂) exposure and risk of acute exacerbation. Mean levels, maximum levels and number of exceedances above standards for O₃ and NO₂ exposure over a 6-week period were associated with significantly increased risk for acute exacerbation of idiopathic pulmonary fibrosis. There was no association of particulate matter <10 µm in aerodynamic diameter (PM₁₀), carbon monoxide (CO) or sulfur dioxide (SO₂) exposure with acute exacerbation risk. There were no exceedances above CO or SO₂ standards. HR: hazard ratio.

FIGURE 2

Secondary sensitivity analyses for a) ozone and b) nitrogen dioxide exposures and risk of acute exacerbation, which show a consistent relationship with acute exacerbation across multiple cumulative exposure periods. HR: hazard ratio.