Background: Diesel engines are widely used in modern industry (including transportation, mining, and construction). Of the many components of exhaust, the health effects of Diesel Particulate Matter (DPM) are of particular concern because they are readily respirable, penetrating the alveolar spaces, eliciting inflammation locally and systemically. Understanding how DPMs exert their pulmonary and vascular effects and what levels are critical for inducing health consequences is important, not only to assist in the development of treatment strategies, but also in developing accurate exposure standards for workers. Currently there are facilities capable of developing and maintaining the current devices used to study inhaled particulate pollution. To facilitate research in this area, a more practical method is required which is safe, portable and costeffective. Nebulizers are commonly used to deliver medication to the lower airways by producing fine and ultrafine aerosol droplets. We suggest that nebulization of DPM will be a safe and effective way of delivering DPM to the lower airways.
Central Hypothesis: Inhalation of DPMs via nebulization is a safe method to deliver DPMs for experimental study.
Secondary objectives: i) establish a novel, portable method for exposure to DPMs; ii) identify the lowest effective dose of DPMs capable of eliciting inflammatory responses in the airways and blood; iii) characterize the local and systemic inflammatory responses to DPMs.
Methods: Ten healthy subjects who were non-smokers were studied. This was a nonblinded, non-randomized study consisting of four arms. As a safety trial, subjects were examined by a physician prior to study entry and inhalation of diesel was done in a sequential manner, starting with the lowest dose. All laboratory results were examined by a physician prior to inhalation of the next dose. For each arm of the study, subjects visited the lab on three consecutive days: Measures of blood, blood pressure, oximetry, sputum heart rate and FEV₁ were taken on each day. Day 2 was the inhalation challenge ; subjects inhaled either nebulized saline 0.9% (placebo) or three different concentrations of DPMs suspended in 0.9% saline (75,150 and 300μg/ml). Only one dose was delivered per week. Doses were given in a sequential order starting with saline then 75, 150 and 300μg of DPM.
Results: DPM inhalation was well tolerated at all doses. No adverse events occurred. A slight but significant decrease in FEV₁ was observed after each dose with a mean average drop from saline of 0, 1.1, 2.6 % for DPM75, DPM 150 and DPM300. A significant increase in the number of positive macrophage particle inclusions in the sputum at the 2h time point for all of the DPM doses was observed (p<0.05) and a significant increase in serum levels of GM-CSF at 24h following inhalation of DPM150ug (p<0.05). This increase in GM-CSF persisted to baseline levels prior to inhalation of DPM300 and after 24h post-inhalation of DPM300.
Conclusion: DPM inhalation via nebulizer is a safe method of studying DPMs in healthy people.