Review Exposure Assessment in Cohort Studies of Childhood Asthma Victoria H. Arrandale,1 Michael Brauer,2 Jeffrey R. Brook,1,3 Bert Brunekreef,4 Diane R. Gold,5 Stephanie J. London,6 J. David Miller,7 Halûk Özkaynak,8 Nola M. Ries,9 Malcolm R. Sears,10 Frances S. Silverman,1 and Tim K. Takaro11 1Dalla Lana School of Public Health, Gage Occupational and Environmental Health Unit, University of Toronto, Toronto, Ontario, Canada; 2School of Environmental Health, University of British Columbia, Vancouver, British Columbia, Canada; 3Environment Canada, Air Quality Research Division, Toronto, Ontario, Canada; 4Institute for Risk Assessment Sciences, Division of Environmental Epidemiology, Utrecht University, Utrecht, the Netherlands; 5Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA; 6National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA; 7College of Natural Sciences, Carleton University, Ottawa, Ontario, Canada; 8U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA; 9Health Law Institute, University of Alberta, Edmonton, Alberta, Canada, Faculty of Law and School of Health Information Science, University of Victoria, Victoria, British Columbia, Canada; 10Firestone Institute for Respiratory Health, McMaster University, Hamilton, Ontario, Canada; 11Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada Background : The environment is suspected to play an important role in the development of childhood asthma. Cohort studies are a powerful observational design for studying exposure–response relationships, but their power depends in part upon the accuracy of the exposure assessment. o Bjectiv : The purpose of this paper is to summarize and discuss issues that make accurate expo- sure assessment a challenge and to suggest strategies for improving exposure assessment in longitu- dinal cohort studies of childhood asthma and allergies. ysnthei d at : Exposures of interest need to be prioritized, because a single study cannot measure all potentially relevant exposures. Hypotheses need to be based on proposed mechanisms, critical time windows for effects, prior knowledge of physical, physiologic, and immunologic development, as well as genetic pathways potentially influenced by the exposures. Modifiable exposures are most important from the public health perspective. Given the interest in evaluating gene–environment interactions, large cohort sizes are required, and planning for data pooling across independent stud- ies is critical. Collection of additional samples, possibly through subject participation, will permit secondary analyses. Models combining air quality, environmental, and dose data provide exposure estimates across large cohorts but can still be improved. words c onclusions : Exposure is best characterized through a combination of information sources. Improving exposure assessment is critical for reducing measurement error and increasing power, which increase confidence in characterization of children at risk, leading to improved health outcomes. k ey : childhood asthma, cohort studies, exposure assessment. Environ Health Perspect 119:591–597 (2011). doi:10.1289/ehp.1002267 [Online 16 November 2010] There is a growing interest in advancing our understanding of environmental exposures that influence the development of disease. Asthma is a complex and heterogeneous syndrome, with a variable phenotype characterized by chronic airway inflammation, reversible airflow limita- tion, airway hyperreactivity, and excess mucous secretion (Bosse and Hudson 2007; von Mutius 2008). Multiple genes have been associated with the development of asthma (Ober and Hoffjan 2006), as have numerous exposures (Miller and Ho 2008) [see Supplemental Material, Table 1 (doi:10.1289/ehp.1002267)]. The environment clearly influences the development of allergies and asthma, because having a particular gene or combination of genes does not guarantee the development of these conditions. Occupational asthma like- wise points toward the role of environment in disease development (Bernstein et al. 2006), as do the changes in asthma prevalence in the past 30–40 years (Platts-Mills et al. 2005; von Mutius 1998) . Gene and environment interactions are also suspected in asthma and allergies (Hunter 2005), as are epigenetic mechanisms (Baccarelli et al. 2009; Nawrot and Adcock 2009). However, knowledge about how environmental exposures participate in epigenetic mechanisms is in its infancy (Baccarelli et al. 2009; Miller and Ho 2008; Nawrot and Adcock 2009). Longitudinal cohort studies are the most powerful observational study design for study- ing exposure–response relationships pertain- ing to disease development. Because of the relatively long observation period for cohort studies, it is also possible to undertake inter- vention studies to investigate selective avoid- ance and disease outcomes (Clayton and McKeigue 2001). Examples of this approach can be found in the Prevention and Incidence of Asthma and Mite Allergy study (PIAMA) (Brunekreef et al. 2002) as well as the Canadian Allergy Primary Prevention Study (CAPPS) (Becker et al. 2004). Cohort studies have drawbacks: They are expensive and time consuming, and investiga- tors must carefully plan the exposure assess- ment component (Rothman and Greenland 1998). Researchers must think critically about what can be measured, when to measure it, and the associated costs, because improved exposure assessment will lead to decreased measurement error and significantly increased Environmental Health Perspectives • volume 119 | number 5 | May 2011 study power (Armstrong 1996; London 2007; Wong et al. 2003). Knowledge about which environmental exposures and behaviors confer risk is impor- tant because many environmental exposures are modifiable and thus preventable. Understanding the biological mechanisms that underlie the development of disease is necessary for the design of effective environmental interventions and therapeutics. The identification of causal exposures depends on accurate measurement of both exposures and outcomes; this is a challenge for many reasons, summarized in Supplemental Material, Table 2 (doi:10.1289/ehp.1002267). Quantifying environmental exposures in cohort studies is complex and involves diffi- cult decisions, including tradeoffs in the short and long term. Researchers designing cohort studies of childhood asthma must prioritize their research questions and refine exposure assessment strategy to ensure that their study makes a meaningful contribution. Address correspondence to J.R. Brook, Environment Canada, 4905 Dufferin Sreet, Toronto, ON, Canada M3H 5T4. Telephone: (416) 739-4916. Fax: (416) 739-4281. E-mail: Jeff.Brook@ec.gc.ca Supplemental Material is available online (doi:10. 1289/ehp.1002267 via http://dx.doi.org/). We acknowledge the input and participation of all the attendees at the 2008 AllerGen Exposure Assessment Workshop: R. Allen, S. Arbes, E. Avol, K. Bartlett, C. Carlsten, N. Cherry, S. Dell, J. Duncan, G. Evans, L. Fritscher, M. Gibson, B. Greene, J.Guernsey, J. Heinrich, F. Kaplan, C. Karr, M. Loewen, P. Paré, M. Perzanowski, R. Rosseau, J. Scott, A. Smargiassi, M. Speck, P. Subbarrao, B. Urch, and A.Wheeler. This work was supported by AllerGen NCE Inc. (the Allergy, Genes and Environment Network), a member of the Networks of Centres of Excellence Canada program. The views expressed in this manuscript are those of the authors and are not intended to represent the views or policies of either their institutions or their sources of support. The manuscript has been sub- jected to U.S. Environmental Protection Agency review and approved for publication. Mention of trade names or commercial products does not consti- tute endorsement or recommendation for use. The authors declare they have no actual or potential competing financial interests. Received 7 April 2010; accepted 16 November 2010. 591