Inhalation of Nebulized Diesel Particulate Matter: A Safety Trial in Healthy Humans

Abstract

Diesel particulate matter (DPM) has adverse health effects. Examining the underlying pathophysiological mechanisms would be facilitated by the introduction of an exposure method that is safe, portable, and cost-effective. The purpose of this study was to establish a novel method to study DPM exposure via nebulization and an inhalation dose that was safe, yet capable of eliciting an inflammatory response. Ten participants enrolled in this nonblinded, nonrandomized study. Subjects inhaled nebulized 0.9% saline and increasing doses of DPM suspended in 0.9% saline (75, 150, and 300 μg) in a sequential manner. FEV1was measured repeatedly during the first 2 h after exposure and blood, oximetry, sputum, and heart rate were taken before, 2 h, and 24 h after inhalation challenge. DPM inhalation was well-tolerated at all doses. A decrease in FEV1was observed after each inhalation challenge (including saline). Inhalation of 300 μg DPM produced a significantly different FEV1response curve. An increase in particle inclusion-positive sputum macrophages for all DPM doses confirmed that the nebulized particles were reaching the lower airways. Serum GM-CSF was elevated after exposures to 150 and 300 μg DPM. No other inflammatory changes were detected. DPM inhalation via nebulizer is a safe method of delivering low doses of DPMs in healthy people.