Research Respiratory Health Effects of Airborne Particulate Matter: The Role of Particle Size, Composition, and Oxidative Potential—The RAPTES Project Maciej Strak,1,2 Nicole A.H. Janssen,1 Krystal J. Godri,3,4 Ilse Gosens,1 Ian S. Mudway,3 Flemming R. Cassee,1 Erik Lebret,1,2 Frank J. Kelly,3 Roy M. Harrison,4,5 Bert Brunekreef,2,6 Maaike Steenhof,2 and Gerard Hoek 2 1National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands; 2Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, Netherlands; 3MRC-HPA Centre for Environmental Health, King’s College London, London, United Kingdom; 4Division of Environmental Health and Risk Management, University of Birmingham, Birmingham, United Kingdom; 5Center of Excellence in Environmental Studies, King Abdulaziz University, Jeddah, Saudi Arabia; 6Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, Netherlands Background : Specific characteristics of particulate matter (PM) responsible for associations with respiratory health observed in epidemiological studies are not well established. High correlations among, and differential measurement errors of, individual components contribute to this uncertainty. o Bjectivs : We investigated which characteristics of PM have the most consistent associations with acute changes in respiratory function in healthy volunteers. Msdohte : We used a semiexperimental design to accurately assess exposure. We increased exposure contrast and reduced correlations among PM characteristics by exposing volunteers at five different locations: an underground train station, two traffic sites, a farm, and an urban background site. Each of the 31 participants was exposed for 5 hr while exercising intermittently, three to seven times at dif- ferent locations during March–October 2009. We measured PM10, PM2.5, particle number concentra- tions (PNC), absorbance, elemental/organic carbon, trace metals, secondary inorganic components, endotoxin content, gaseous pollutants, and PM oxidative potential. Lung function [FEV1 (forced expi- ratory volume in 1 sec), FVC (forced vital capacity), FEF25–75 (forced expiratory flow at 25–75% of vital capacity), and PEF (peak expiratory flow)] and fractional exhaled nitric oxide (FENO) were measured before and at three time points after exposure. Data were analyzed with mixed linear regression. r esult : An interquartile increase in PNC (33,000 particles/cm3) was associated with an 11% [95% confidence interval (CI): 5, 17%] and 12% (95% CI: 6, 17%) FENO increase over baseline immediately and at 2 hr postexposure, respectively. A 7% (95% CI: 0.5, 14%) increase persisted until the following morning. These associations were robust and insensitive to adjustment for other pollutants. Similarly consistent associations were seen between FVC and FEV1 with PNC, NO2 (nitrogen dioxide), and NOx (nitrogen oxides). c onclusi : Changes in PNC, NO2, and NOx were associated with evidence of acute airway inflammation (i.e., FENO) and impaired lung function. PM mass concentration and PM10 oxidative potential were not predictive of the observed acute responses. k ey words : air pollution, experimental exposure, FENO, FEV1, FVC, oxidative potential, PM, ultrafine particles. Environ Health Perspect 120:1183–1189 (2012). http://dx.doi.org/10.1289/ ehp.1104389 [Online 2 May 2012] Positive associations between airborne particulate matter (PM) and respiratory health have been observed in epidemiological studies (Brunekreef and Holgate 2002; Pope and Dockery 2006). In most studies, effects were linked to PM10 and PM2.5 (particulate matter < 10 µm and 2.5 µm in aerodynamic diameter, respectively). Fewer studies have reported health effects associated with exposure to coarse (PM2.5–10; Brunekreef and Forsberg 2005) and ultrafine (PM0.1; Ibald-Mulli et al. 2002) particles. Depending on sources, there is a significant heterogeneity in PM composition, which is reflected in in vitro and in vivo toxicological studies (Valavanidis et al. 2008). Current knowledge does not allow precise quantification of the health effects of individual PM components or of PM emissions from different sources [Brunekreef 2010; World Health Organization (WHO) 2007], although various PM characteristics, such as surface area of particles, transition metal content, surface absorbed organic components, and biological products (endotoxin), have been proposed. A measure of oxidative potential (OP) of PM has gained attention as a more integrative measure of biological response (Ayres et al. 2008). OP is an attractive measure because it integrates the effects of multiple individual PM components on health. There is currently, however, very limited evidence in epidemiological studies that the OP of PM predicts health effects better than individual components (Ayres et al. 2008). Disentangling the independent health effects of individual PM characteristics in epi- demiological studies is often limited by high correlations between air pollution compo- nents (Brunekreef 2010). Different degrees of measurement error for different air pollu- tion components related to characterizing exposure at a central monitoring location is another problem because more consistent associations tend to be found with air pollu- tion components with less measurement error (Zeger et al. 2000). Controlled experimental exposure studies in laboratory settings cannot Environmental Health Perspectives • volume 120 | number 8 | August 2012 wholly represent the complexity of ambi- ent PM exposures and are largely restricted to individual air pollutants or defined mix- tures (e.g., diesel engine exhaust). Moreover, experimental concentrations are often higher than those encountered in real-world situa- tions, and the concentration levels used are constant rather than (highly) variable. Building on recommendations of a recent WHO workshop (WHO 2007), we addressed these uncertainties using a semiexperimental design as part of the RAPTES project (Risk of Airborne Particles: a Toxicological– Epidemiological hybrid Study). We studied health effects of short-term exposure of healthy volunteers to ambient PM at real-world loca- tions with well-established differences in PM characteristics (Strak et al. 2011). The aim of the study was to assess the independent contribution of specific PM characteristics to various health outcomes. Here, we focus on acute changes in respiratory health parameters. We hypothesized that PM10 OP would have a stronger and more consistent relationship with airway inflammation and lung function than other measured PM characteristics because oxidative stress is an important mechanism of PM health effects. Methods Study design. We exposed healthy human volunteers to ambient PM at five locations with different PM characteristics. A detailed Address correspondence to B. Brunekreef, Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80178 3508TD, Utrecht, Netherlands. Telephone: 31 30 2539494. Fax: 31 30 2539499. E-mail: B.Brunekreef@uu.nl Supplemental Material is available online (http:// dx.doi.org/10.1289/ehp.1104389). We thank all study participants. We also thank J. Boere, P. Fokkens, D. Leseman, L. van den Burg, V. Huijgen, M. Kleintjes, M. Meijerink, and J. Musters for their excellent support in data collection; E. van Otterloo for his help with participant recruit- ment; and M. Groothoff for medical supervision. The RAPTES (Risk of Airborne Particles: a Toxicological–Epidemiological hybrid Study) project was funded by the National Institute for Public Health and the Environment (RIVM) Strategic Research Program (S630002). The authors declare they have no actual or potential competing financial interests. Received 23 August 2011; accepted 2 May 2012. 1183