Studies reporting stronger effects among men. In the 20-year prospective California Adventists Health Study, Abbey et al. (1998) linked PM10 to reduced lung function (FEV1/FVC) among nonsmoking males, and decreased FEV1 among men with parental respiratory illness. Women and never-smok- ing males displayed increased peak expira- tory flow (PEF) lability. Among males, sulfate exposures predicted reduced FEV1, and O3 exposures predicted reduced FEV1 among men with parental respiratory illness. The authors suggested gender differences in work- related exposures or possible stronger healthy worker effects among women. They confirmed that cohort men spent more time outdoors (16.1 hr/week vs. 9.2 hr/week; p < 0.0005) and suggested that outdoor exposures may trigger responses in males with genetic predis- position to respiratory illness. Galizia and Kinney (1999) found that, among Yale freshmen, growing up in areas with high (vs. low) O3 was associated with symptoms and reduced lung function among males but not among females. The authors suggested the gendered explanation that men may accumulate greater O3 exposures through outdoor physical activity. Studies reporting or mixed modifi- cation. Zeka et al. (2006) found that ambi- ent PM10 was associated with respiratory and all-cause mortality across 20 U.S. cities, using case–crossover analysis. Although modifica- tion was nonsignificant, the authors posited that sex, race, and age may indicate SES, increasing susceptibility through lesser health care access, poorer nutrition, greater stress or Gender in environmental health research violence exposures, or increasing actual expo- sures through residential proximity to high- ways or occupational coexposures. Finally, they suggest sex-linked biological differences in PM deposition. In a 13-year follow-up of Krakow adults, Jedrychowski and Krzyzanowski (1989) found that residence in higher sulfate areas better predicted FEV1 decrements among men than among women. Among women, SO2 and PM correlated with symptoms; the authors suggested that women’s greater average spent time near home produced better accuracy in exposure assessment. Gender and sex differences in respiratory health effects among children. Disentangling gender and sex effects in air pollution–health associations among children may be more complicated, because lung function growth rates (critical periods for pollution effects) differ by sex (Berhane et al. 2000). Most air pollution epidemiology studies among chil- dren examine chronic exposures, although outcomes considered vary widely, including lung function growth, wheeze, asthma onset and exacerbation, and symptoms. Studies reporting stronger effects among girls. Using baseline cross-sectional results from the Southern California Children’s Health Study (CHS) of children in grades 4, 7, and 10 in 12 communities, Peters et al. (1999) reported that air pollutants (PM10, PM2.5, acid vapor, NO2, O3) were more strongly inversely associated with lung function among girls than among boys. The authors suggested gender differences in time outdoors and play activities, and sex differences in growth rates, The authors offered gendered explanations (e.g., smoking among men may obscure pol- lution effects; Shanghai women’s lower aver- age education may confound gender and SES) and considered biological explanations, including women’s smaller airways, greater airway reactivity (Yunginger et al. 1992), and greater deposition of PM2.5 (Kohlhaufl et al. 1999; Sunyer et al. 2000). Among 6,824 adults in 10 European countries in the European Community Health Survey 2000–2002 (ECRHS I), Sunyer et al. (2006) found that home traffic intensity and outdoor NO2 better predicted chronic bron- chitis among women than among men. The authors also examined occupational exposures, which better predicted outcomes among men, separating some gendered activity pattern effects. The authors suggested sex-linked dif- ferences in hormonal status, and gender dif- ferences in coexposures, disease perception, health care access and use and differing per- ceptions of environmental quality and symp- toms by gender and education. Sunyer et al. (2000) found that older and female Barcelona adults with COPD showed greater all-cause, respiratory, and cardiovascular mortality with same-day black smoke than did younger persons and men. The authors sug- gested the reasons were a higher prevalence of frail persons among the elderly and women than among men, or biological differences, including inflammatory response [given women’s stronger response to smoking (Xu et al. 1994a, 1994b)], lung size, and airway diameter influencing PM deposition, respiratory patterns, and airway resistance (Bennett et al. 1996). Table 2. continued Study Population Studies reporting or mixed modification Emenius et al. 2003 540 Stockholm children (0–2 years of age) Gauderman et al. 1,759 children in 12 2004 Southern California communities Lin et al. 2005 6,782 Toronto, Canada children, 0–14 years of age Liu et al. 2009 182 asthmatic children 9–14 years of age in Windsor, Ontario, Canada Roemer et al. 1999 1,621 children in 14 European centers, 1993–1994 Schwartz 1989 4,300 youths (6–24 years of age), NHANES II, 1976–1980 Smith et al. 2000 44 asthmatic children (< 14 years of age) Zhao et al. 2008 1,993 pupils (11–15 years of age) in urban China Abbreviations: abs, absorbance; BS, black smoke; CH2O, formaldehyde; EC, elemental carbon; IQR, interquartile range; MMEF, median mid-expiratory flow; NR, not reported; NS, not significant; OR, odds ratio; PEFR, peak expiratory flow rate; RR, relative risk; TRS, total reduced sulfur. Key results demonstrate observed effect modification, and are not exhaustive of results reported for each study. Values in parentheses are 95% confidence interval, unless otherwise indicated. aEffects did not differ by sex, and therefore are reported here in only one column. Environmental Health Perspectives • volume 118 | number 2 | February 2010 171 Exposure metric(s) Outcome(s) of interest Risk among males Risk among females Indoor and outdoor OR for recurrent residential NO2 wheeze (high vs. low quartile) Lifetime community annual Growth in FVC average NO2, PM2.5, EC FEV1 (most vs. least polluted) MMEF 6.5 µg/m3 increase in Hospitalizations for 6-day PM10–2.5 exposure respiratory infections IQR change in same-day, Percent change in lagged SO2, NO2, O3, FEF25–75 PM2.5 24-hr measures of PM10, Change in evening PEF BS, SO2, NO2 per 100 µg/m3 Annual average SO2, NO2, TSP, O3 at monitors Daily personal NO2 exposure School indoor and outdoor SO2, NO2, O3 Change in FVC FEV1 PEF Chest tightness Asthma, wheeze OR (outdoor NO2) = 1.60 (0.78–3.26)a OR (indoor NO2) = 1.51 (0.81–2.82) β (NO2) = –95.0 (–189.4 to –0.6)a β (NO2) = –101.4 (–164.5 to –38.4) β (NO2) = –211.0 (–377.6 to –44.4) β = 1.15% ( 1.02–1.30) NR; effects did not differ by sex NR; effects did not differ by sex β = 1.18% (1.01–1.36) β (same-day NO2 ) = –2.4 (–4.3 to –0.4) NR; effects did not differ by sex β (same-day PM2.5) = 1.9 (–3.5 to –0.3) β (lag 0 SO2) = 1.9 L/min (p < 0.05) β (lag 0 BS) = 0.7 L/min (p < 0.10) β (lag 2 PM2.5) = –0.5 L/min (NS) β (NO2) = –2.94 (p = 0.0004) β (NO2) = –3.09 (p = 0.0003) β (NO2) = –3.23 (p = 0.0019) OR = 1.29 (1.16, 1.43) OR (wheeze, indoor SO2) = 1.18 (1.03–1.35)a OR (wheeze, indoor CH2O) = 1.24 (1.03–1.48) β (lag 0 SO2) = 1.4 (NS) β (lag 0 BS) = 0.2 (NS) β (lag 2 PM2.5) = 1.2 (p < 0.05) NR; effects did not differ by sex NR; effects did not differ by sex NR; effects did not differ by sex