Mechanisms of Particulate Toxicity: Health Effects in Susceptible Humans

Particulate air pollution is an issue of global health importance, being a major component of air pollution, and having been associated with increased human cardiorespiratory morbidity and mortality. Individuals with asthma could be particularly susceptible to the respiratory health effects of particulate air pollution, due to the airway inflammation and hyper-reactivity components of the disease. This project was designed to test the hypothesis that airway inflammation would be increased, and spirometric pulmonary function (SPF) and heart rate variability (HRV), would be decreased as a function of a single particle exposure, and to a larger degree, as a function of a combined particle and O3 exposure and a serial particle exposure, compared to filter air exposure. This project consisted of two controlled human exposure experiments. Experiment One: (N = 15; subjects with asthma); Exposure conditions were separate single (4 hr) exposures to each of Filtered-Air (FA); carbon particles and ammonium particles [300 mg/m] (P); P and O3 [0.2 ppm] (PO). Experiment Two: (N = 10; subjects with asthma); separate single exposures to FA; and P; and three serial-day exposures to P (P3). Bronchoscopy was conducted 18 hr postexposure (final exposure in P3), SPF was measured immediately preand postexposure and 18 hr post-exposure, and HRV was measured immediately pre-exposure and during the final 25 min of the exposure. Experiment One: In PO, compared to FA and/or P, in the airway lavages there were significantly higher inflammation-related cell numbers (neutrophils, lymphocytes, eosinophils), protein concentrations (total protein, granulocyte-monocyte colony stimulating factor, C-reactive protein), and cytokine gene expression (interluekin-8 and –10); significantly lower SPF (forced vital capacity, forced expired volume in 1 s; FEV1); and significantly lower heart rate variability (time domain, and low and high frequency domain). In both PO and P, compared to FA, there was significantly lower SPF (forced expired volume between 25-75% of FVC; FEF25-75). For P, compared to FA, there was significantly lower HRV (low frequency domain). Experiment Two: In P3 compared to both FA and P, in the airway lavages there was a significantly lower cell number (lymphocytes), and in P compared to FA, there was a significantly higher cell number (epithelial cells). With-in P3 at 18 hr post-exposure three, compared to post-exposure two and preand post-exposure three, there was significantly lower SPF (FEV1). With-in the P3 condition at 18 hr post-exposure three, compared to both preand post-exposure two, there was significantly lower SPF (FEF2575). The results of this project indicate that in individuals with asthma, both single and serial exposures to carbon and ammonium nitrate particles can result in significant decreases in SPF, a low number of changes in airway cell distribution and HRV, and no changes in cytokine protein or gene expression. However, combined exposure to particles and O3, in addition to decreases in SPF, produces increases in several inflammatory associated cells, increases in protein and gene expression, and multiple changes in HRV. It is expected that for the combined exposure these changes are due, at least primarily, to the O3 component of the exposure environment. Further studies are required to investigate the health effects and control mechanisms of these changes in both healthy and other susceptible individuals.