Traffic-related air pollution (TRAP) is associated with a variety of adverse health effects. Although a central role has been proposed for oxidative stress, elucidating underlying mechanisms remains an area of active investigation. Experimental work has demonstrated that glucocorticoid stress hormones are potential mediators of pulmonary and systemic pollutant effects of both particulate and gaseous pollutants (Thomson 2019), but direct evidence of TRAP-dependent stress axis activation is lacking. Moreover, although oxidative stress is a regulator of glucocorticoid signaling (Okamoto et al. 1999), involvement in pollutant-induced stress axis activation is unknown. In population studies, nitrogen dioxide was associated with a flattened salivary cortisol profile in adolescents (Wing et al. 2018) and higher awakening cortisol and flattened profile in 45 to 85-y-old adults (Hajat et al. 2019), suggesting potential TRAP-related impacts. The present study evaluated whether short-term exposure to diesel exhaust increases plasma cortisol levels and considered effect modification by sex, asthma status, antioxidant gene variants, and antioxidant treatment.
The study was approved by the University of British Columbia, Vancouver Coastal Health Research Institute, and Health Canada ethics review boards, and registered at clinicaltrials.gov (trial NCT01699204). Each participant provided written informed consent. Study details, including exclusion criteria, diet and medications, questionnaires, assessment of airway hyperresponsiveness, and genotyping, are provided elsewhere (Carlsten et al. 2014). In brief, study participants [n = 19; mean age 28 (range 19-46), 14 with doctor-diagnosed asthma (7 females, 7 males), and 5 without (3 females, 2 males); all free from current use of inhaled corticosteroids or long-acting [[beta].sub.2] agonists, from regular use of bronchodilators, and from vitamin A, C, or E supplementation] took N-acetylcysteine (NAC; 600 mg) or placebo capsules three times daily for 6 d. On day 6, participants were exposed for 2 h to filtered air or diesel exhaust, producing three experimental conditions [filtered air with placebo (FAP), diesel exhaust with placebo (DEP), and diesel exhaust with NAC (DEN)], using a randomized, double-blind, crossover design that included a minimum 2-wk washout period between exposures. The protocol is nearly identical to another in which analysis of questionnaires demonstrated that participants were effectively blinded to exposures (Carlsten et al. 2013). Diesel exhaust was generated using a 6.0-kW diesel generator operated to simulate on-road emissions and diluted to maintain a nominal particulate concentration of 300 [micro]g/[m.sup.3] [fine particulate matter (PM) with aerodynamic diameter less than or equal to 2.5 [micro]m...