Controlled Human Exposure Studies

Combustion produces complex mixtures of ambient air pollutants, depending on the fuel, oxidant availability, temperature, turbulence, engine, among others. This complexity combined with the complexity of exposure to the pollutant, with variable duration, frequency, spatial position, multiple-sources and co-pollutants, activity level, and interindividual variation in susceptibility, makes it challenging to assess human health effects from exposure to ultrafine combustion particles. Controlled human exposure studies refer to those where selected study participants are exposed under controlled conditions of exposure and activity for the investigation of selected health outcomes and biomarkers. This is usually done in an exposure chamber although some studies have also attempted to control conditions in real-life settings. This design has been particularly used to investigate acute health effects from short-term exposures to combustion particles, providing mechanistic support of observations from epidemiological and animal studies. This chapter reviews and compares controlled human exposure studies in chambers, on healthy subjects, involving combustion-generated particles, which are dominated by the ultrafine size mode. In total, 64 studies including 12 chamber studies on wood smoke, 33 on diesel exhaust, 15 on concentrated ambient particles and 4 other carbonaceous particles (candles and others) were identified. The studies differ by designs (crossover or sequential), protocol definitions (with or without physical activity), particulate matter source (diesel exhaust, wood smoke or others), exposure metrics (with or without ultrafine size mode description), combustion generation conditions (for the same source), administrated doses and duration of exposure, as well as biomarkers and functional markers under study. The biological effects assessed have been mainly focused on lung function, cardiovascular function, heart rate variability, and inflammatory, oxidative stress and genotoxicity markers. The strengths and limitations of the controlled human exposure studies are revisited. The importance of the ultrafine particles is discussed and the results are compared with studies using real-life air concentrations of pollutants to generate a gradient of exposure.