Systemic and cardiovascular effects of airway injury and inflammation: Ultrafine particle exposure in humans

The concentration of particles in the ambient air is associated with deaths from cardiovascular disease, and determining the biologic mechanisms invol ved has been identified as a high-priority research need. Hypotheses have f ocused on the possibility of direct cardiac effects, or indirect effects re lated to inflammatory responses, including increased blood viscosity or inc reased blood coagulability. Ultrafine particles (UFPs; those smaller than 1 00 nm) may be important in cardiovascular effects because of their very hig h deposition efficiency in the pulmonary region, and their high propensity to penetrate the epithelium and reach interstitial sites. We have initiated human clinical studies of the health effects of UFPs using a mouthpiece ex posure system. Healthy, nonsmoking subjects 18-55 years of age are exposed at rest for 2 hr to 10 mug/m(3) carbon UFPs and to filtered air as a contro l. Preliminary findings indicate a relatively high overall deposition fract ion (0.66 +/- 0.12 by particle number) consistent with model predictions an d an absence of particle associated symptoms or changes in lung function. P lanned studies examine responses in susceptible subject groups, and the eff ects of particles of varying composition. Human clinical studies using mode l particles will complement other approaches such as epidemiologic, animal exposure, and in vitro studies in determining the mechanisms for heath effe cts related to ambient particle exposure.