Abstract

Purpose: Exposures to ambient air pollutants may prime the lung enhancing risk of acute respiratory distress syn-drome (ARDS) in sepsis. Our objective was to determine the association of short-, medium-, and long-term pollutant exposures and ARDS risk in critically ill sepsis patients.

Methods: We analyzed a prospective cohort of 1858 critically ill patients with sepsis, and estimated short- (3 days), medium- (6 weeks), and long- (5 years) term exposures to ozone, nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), particulate matter < 2.5 μm (PM2.5), and PM < 10 μm (PM10) using weighted averages of daily levels from monitors within 50 km of subjects’ residences. Subjects were followed for 6 days for ARDS by the Berlin Criteria. The association between each pollutant and ARDS was determined using multivariable logistic regression adjusting for preselected confounders. In 764 subjects, we measured plasma concentrations of inflammatory proteins at pres-entation and tested for an association between pollutant exposure and protein concentration via linear regression.

Results: ARDS developed in 754 (41%) subjects. Short- and long-term exposures to SO2, NO2, and PM2.5 were associ-ated with ARDS risk (SO2: odds ratio (OR) for the comparison of the 75–25th long-term exposure percentile 1.43 (95% confidence interval (CI) 1.16, 1.77); p < 0.01; NO2: 1.36 (1.06, 1.74); p = 0.04, PM2.5: 1.21 (1.04, 1.41); p = 0.03). Long-term exposures to these three pollutants were also associated with plasma interleukin-1 receptor antagonist and soluble tumor necrosis factor receptor-1 concentrations.

Conclusion: Short and long-term exposures to ambient SO2, PM2.5, and NO2 are associated with increased ARDS risk in sepsis, representing potentially modifiable environmental risk factors for sepsis-associated ARDS.

Keywords: Acute respiratory distress syndrome, Acute lung injury, Sepsis, Air pollution

John P. Reilly1,2* , Zhiguo Zhao4, Michael G. S. Shashaty1,2, Tatsuki Koyama4, Tiffanie K. Jones1,2,3, Brian J. Anderson1,2, Caroline A. Ittner1,2, Thomas Dunn1,2, Todd A. Miano3, Oluwatosin Oniyide1,2, John R. Balmes7,8, Michael A. Matthay8,9, Carolyn S. Calfee8,9, Jason D. Christie1,2,3, Nuala J. Meyer1,2 and Lorraine B. Ware5,