B56-02 Acute Symptom Responses to Diesel Exhaust Exposure in Asthmatics: A Randomized Controlled Trial With Single-Dose Budesonide Pretreatment

Rationale Diesel exhaust (DE) exposure increases oxidative stress in the lungs, which may enhance symptoms and ultimately result in exacerbation of lung diseases. Budesonide, an inhaled corticosteroid, may reduce DE-induced oxidative stress and associated symptoms, particularly with sustained use. We conducted a human exposure study to evaluate the effects of DE exposure and a single budesonide inhalation on study participants’ reported symptoms. Hypothesis Exposure to DE will increase symptoms relative to filtered air, but will be unaffected by a single inhalation of budesonide. Methods We conducted a 4-arm crossover, double-blinded, randomized, controlled human exposure study in 13 asthmatic participants, with a ≥ 4-week washout between exposures (NCT03615742). Participants inhaled either from an empty inhaler (placebo (P)) or a total of 1.6mg of Budesonide (Bud), immediately prior to exposure to either filtered air (FA) or DE for 2 hours. This generated 4 conditions: FA with placebo (FA-P); FA with Budesonide (FA-Bud); DE (standardized to 300µg/m3 of PM2.5) with placebo (DE-P); and DE with Budesonide (DE-Bud). A standardized 19-question symptom survey covering eye, nose, chest, body, and neurological symptoms was completed before each exposure and at 2 and 4 hours after each exposure. Questions were scored between 0 for no symptoms and 100 for severe symptoms according to a visual analogue scale. Sums of the discrete scores for each category of symptoms were analyzed relative to FA-P, using mixed-effects models. Results No significant differences were identified in pre-exposure symptom scores across the conditions. Across all symptom categories combined, both DE-Bud (p = 0.03) and DE-P (p = 0.08) increased scores at 2 hours after exposure. This early response was driven predominantly by significant effects on eye symptoms (p = 0.04 and 0.01 for DE-P and DE-Bud, respectively). Although there was a trend towards increases with DE exposure, nose, chest, body and neurological symptoms were not significantly affected. No significant effects were seen at 4 hours across any of the conditions or symptoms categories. Conclusions Our results suggest that DE exposure only affects symptoms acutely. The predominant body area affected was the eyes. A single dose of budesonide did not significantly reduce symptoms. These findings suggest that a single corticosteroid administration may be insufficient to counteract DE-induced symptoms. We hypothesize that a longer course of inhaled corticosteroids would reduce pollution-induced symptoms in obstructive respiratory disease (NCT06552364).