Clougherty hormonal factors, and respiratory mechanisms. Using longitudinal CHS analyses, Gauderman et al. (2004) found deficits in FEV1 growth from 10 to 18 years of age associated with community NO2, PM2.5, and acid vapor not significantly differing by sex. McConnell et al. (2002) reported higher asthma risk with out- door sports participation in higher O3 areas in the CHS cohort, especially among girls, and suggested that higher ventilation during play may increase exposures. In a U.S. study, Neas et al. (1991) reported stronger associations between home indoor NO2 and respiratory symptoms among girls than among boys 7–11 years of age. The authors cited reports of stronger effects among girls, including a British study linking gas stove use to symptoms among girls (Melia et al. 1977), a paper reporting FEV75 (75th percentile) decrements of 1.1% among girls 9–13 years of age but slight increases among boys (Hasselblad et al. 1981), and a British study linking kitchen NO2 and gas stoves to greater reductions in PEF and forced expira- tory flow between 25th and 75th percentile (FEF25–75) among girls (Florey et al. 1979). Among Dutch children 7–12 years of age, Brunekreef et al. (1997) found that truck traf- fic and black smoke at schools were associated with lung function reductions only among girls, and van Vliet et al. (1997) found that residential distance from freeway, truck traf- fic density, and school black smoke measures better predicted chronic respiratory symptoms among girls than among boys, after account- ing for SES and home exposures. In both studies, the authors contrast their results with evidence of stronger passive smoke effects among boys. However, these studies examine in utero exposures and noninhalation path- ways (Cuijpers et al. 1995; Cunningham et al. 1994), and suggest that, because boys exhibit more symptoms overall, air pollution effects may be obscured by other respiratory “noise” (Pershagen et al. 1995). Among 673 adults and 106 children in Haarlem, the Netherlands, Oosterlee et al. (1996) reported significant associations between living along busy (vs. quiet) streets and asthma or dyspnea only among girls. They suggested that boys’ higher total respiratory symptoms may mask pollution effects, and considered gendered factors (e.g., passive smoking, activity patterns, coexposures) in their analysis. In Oslo, Norway, Oftedal et al. (2008) found that lifetime residential NO2, PM10, and PM2.5 among 9- and 10-year-old chil- dren was associated with lower PEF, more strongly among girls, only slightly attenuated by SES adjustment. The authors suggested biological explanations (e.g., girls experi- ence growth spurts earlier, captured within this follow-up, or hormonal status may alter girls’ responses) and suggested unmeasured 172 SES-related confounders (e.g., gendered sports participation). In a case–control study in Stockholm, Pershagen et al. (1995) reported significant associations between outdoor home NO2 and gas stove use on wheezing bronchitis only among girls, despite boys’ higher wheezing prevalence. Outdoor NO2, gas stove use, and smoking conferred multiplicative risks in girls but not in boys, after SES adjustment. The authors reported consistency with prior studies, indicated that results were unlikely due to selection bias or misclassification, and acknowledged a need for activity data to explore gender differences. Rosenlund et al. (2009) found asso- ciations between chronic residential NO2 exposure and lung function to be stronger among Roman girls than boys 9–14 years of age; mean FEV1 and FEF25–75 decrements were approximately four times greater in girls than boys, corroborating other studies (Cesaroni et al. 2008; Kulkarni et al. 2006; Li et al. 2003; Neas et al. 1991; Nordling et al. 2008; Oftedal et al. 2008; Pershagen et al. 1995). The authors indicated complexi- ties in comparing childhood cohorts differing by age, pubertal status, pollution mixtures, study designs, and susceptibilities and noted that the consistency of results across Europe reporting stronger air pollution effects among girls, meriting further investigation. Studies reporting stronger effects among boys. In the Traffic-Related Air Pollution on Childhood Asthma (TRAPCA) study, Gehring et al. (2002) reported stronger associations between residential PM2.5 and symptoms (e.g., cough without infection, cough at night) among boys than among girls 0–2 years of age. The authors suggested that differences in total symptoms, masking pollution effects, were important or that, given sex differences in lung development, infant girls have larger airways relative to body size and lesser airway resistance. In a prospective cohort study of annual mean total suspended particle (TSP) and SO2 exposures among preadolescent children in Krakow, Poland, Jedrychowski et al. (1999) reported stronger associations with FVC and FEV1 among boys than among girls. The authors noted sex-differing lung growth rates, producing different critical periods for pollution effects. Studies reporting or mixed effect modification. In a 3-year prospective study of children in Mexico City, Mexico, Rojas- Martinez et al. (2007) associated elevated PM10, NO2, and O3 with reduced lung func- tion among boys and girls. Interquartile range increases in NO2 predicted FEV1 declines in girls, whereas increases in PM10 predicted FEV1 declines among boys. Elevated O3 predicted FEV1 decreases three times larger among girls than among boys, unexplained by SES. The authors compared these findings with CHS results on sex-differing lung function growth and suggested higher O3 exposures among children spending time outdoors (Gauderman et al. 2000; McConnell et al. 2002). In Toronto (Ontario, Canada), respiratory hospitalizations were significantly associated with PM2.5–10 among boys and girls, with PM10 among boys, and with NO2 among girls (Lin et al. 2005). The authors proposed sex-linked explanations: Boys have smaller airways relative to lung volume and differ in smooth muscle, vascular function, and hormonal status. Discussion Among adults, evidence of effect modification by sex remains uncertain; studies of older adults and those using residential exposure estimates suggest stronger effects among women. The range of plausible explanations is very broad, including sex-linked biological factors related to lung volume, deposition, reactivity, and hor- monal influences on chemical transport and systemic regulation. Gendered explanations include confounding or modification by smok- ing behaviors, job-related chemical exposures, differential accuracy in residence-based expo- sure assignment, exposures to indoor allergens and cleaning agents, and differing exposure and response to psychosocial stressors. Refined distinction between sex and gender may eluci- date these associations. Studies of younger children suggest stron- ger associations among boys; older childhood cohorts suggest the opposite. Age-related trends may be linked to sex-differing lung function growth rates (Gold et al. 1994) and differences in airway function at birth, which suggest lower respiratory volumes and greater airway resistance among boys (Stocks et al. 1997). At older ages, gendered activities may also shape pollution response. Gender, sex, and multiple exposures. Environmental exposures are complex. Traffic- related air pollution includes gaseous species and PM from combustion, tire and brake wear, resuspended roadway dusts, and salts (Schauer et al. 2006). Pollution exposures occur in mul- tiplicity, and polluted neighborhoods often also suffer poverty, crime, and lower access to health-related resources (Morello-Frosch and Shenassa 2006). In workplaces, chemical exposures co-vary with heat, noise, and strain, acting recursively and synergistically on work- ers’ health (MacDonald et al. 2001). Gender analysis fits into environmental health under this multiple exposures framework. There is growing interest in pollution effect modifi- cation by SES (Jerrett et al. 2004; O’Neill et al. 2003) and chronic stress (Chen et al. 2008; Clougherty et al. 2006, 2007; Morello- Frosch and Shenassa 2006). Likewise, SES is a complex mix of social and physical stressors accumulating over the life course (Romieu ovlume 118 | number 2 | February 2010 • Environmental Health Perspectives