Plasma sterols and vitamin D are correlates and predictors of ozone-induced inflammation in the lung: A pilot study

BACKGROUND: Ozone (O(3)) exposure causes respiratory effects including lung function decrements, increased lung permeability, and airway inflammation. Additionally, baseline metabolic state can predispose individuals to adverse health effects from O(3). For this reason, we conducted an exploratory study to examine the effect of O(3) exposure on derivatives of cholesterol biosynthesis: sterols, oxysterols, and secosteroid (25-hydroxyvitamin D) not only in the lung, but also in circulation. METHODS: We obtained plasma and induced sputum samples from non-asthmatic (n = 12) and asthmatic (n = 12) adult volunteers 6 hours following exposure to 0.4ppm O(3) for 2 hours. We quantified the concentrations of 24 cholesterol precursors and derivatives by UPLC-MS and 30 cytokines by ELISA. We use computational analyses including machine learning to determine whether baseline plasma sterols are predictive of O(3) responsiveness. RESULTS: We observed an overall decrease in the concentration of cholesterol precursors and derivatives (e.g. 27-hydroxycholesterol) and an increase in concentration of autooxidation products (e.g. secosterol-B) in sputum samples. In plasma, we saw a significant increase in the concentration of secosterol-B after O(3) exposure. Machine learning algorithms showed that plasma cholesterol was a top predictor of O(3) responder status based on decrease in FEV1 (>5%). Further, 25-hydroxyvitamin D was positively associated with lung function in non-asthmatic subjects and with sputum uteroglobin, whereas it was inversely associated with sputum myeloperoxidase and neutrophil counts. CONCLUSION: This study highlights alterations in sterol metabolites in the airway and circulation as potential contributors to systemic health outcomes and predictors of pulmonary and inflammatory responsiveness following O(3) exposure.