Controlled human exposures to ambient pollutant particles in susceptible populations

Epidemiologic studies have established an association between exposures to air pollution particles and human mortality and morbidity at concentrations of particles currently found in major metropolitan areas [1]. This association has been documented in numerous investigations around the world and is remarkably consistent [1-8]. The adverse effects of particulate matter (PM) include both pulmonary and extrapulmonary morbidity and mortality. It is estimated that the daily cardiopulmonary mortality increased by 0.3% for each 10-μg/m3 increase in PM10 (particulate matter < 10 μm in aerodynamic diameter). For long term cardiopulmonary mortality, the estimate was 6% for each 10-μg/m3 increase in annual average exposure to PM2.5 (PM < 2.5 μm) [5]. The risk is especially high in the elderly and patients with chronic obstructive lung disease, asthma, coronary artery disease, congestive heart failure and frequent arrhythmias [9-14]. The adverse pulmonary effects after PM exposure include increased hospital admissions, pulmonary infections, asthma attacks, and exacerbations of chronic obstructive pulmonary disease [10,15]. The extrapulmonary adverse effects of PM are primarily cardiac diseases [1,5,16,17] and vascular diseases (e.g., ischemic stroke) [18-21].Controlled human exposures have been used to support the association between PM exposure and adverse health effects observed in epidemiological studies. Earlier controlled human exposure studies invariably enrolled young healthy subjects. These studies largely confirmed the capability for PM to produce adverse health effects shown in epidemiological studies. In the last few years, more studies involving susceptible populations (e.g., elderly and patients with coronary artery disease, chronic obstructive lung disease and asthma) have been published [22-27]. It is somewhat surprising that many studies showed that these susceptible populations seem less responsive to PM exposure compared to healthy individuals. This paper wil