Clougherty exposures, and use of personal care and cleaning products. Nickel dermatitis and hand eczema are far more prevalent among women than men in Western countries, likely because of chronic exposures from jewelry (Meding 2000). Indoor fossil fuel burning for cooking in developing countries drasti- cally increases kitchen PM2.5 concentrations (Dionisio et al. 2008; Rumchev et al. 2007); because women generally perform more cook- ing in these societies, they suffer elevated respiratory symptoms (Behera 1997), asthma (Qureshi 1994), chronic bronchitis (Pandey 1984), chronic obstructive pulmonary dis- ease (COPD) (Ramirez-Venegas et al. 2006), pneumoconiosis (Grobbelaar and Bateman 1991), tuberculosis, lung cancer (Behera and Balamugesh 2005), and mortality (Lopez et al. 2006). Accordingly, stove-replacement interventions have effectively reduced expo- sures and improved women’s health in these settings (Khushk et al. 2005; McCracken et al. 2007). Gendered home activities shape exposures to cooking exhaust and cleaning products, behaviors and home characteristics that vary by social class, climate, and culture. Residence-based exposure estimates may bet- ter capture exposures among homemakers and thus may be more accurate for women than men in most societies. Exposure to dose. Sex differences in dermal absorption and lung function (Becklake and Kauffmann 1999; Ernstgard et al. 2002) influ- ence contaminant uptake. Skin metabolizes some xenobiotics, modifying their toxicity (Bashir and Maibach 2002); this character- istic differs by sex and is influenced by gen- dered dermal exposures (e.g., topical creams, cosmetics, jewelry). Respiratory absorption of airborne gases (Jones and Lam 2006) and gas–blood barrier permeability (Brauner et al. 2009) also differ by sex. Gender Concentration Exposure Dose Effective dose Health outcome Sex Figure 1. Possible roles of gender and sex in shap- ing observed relationships between air pollution and health. Gender affects the presence of the exposure itself (e.g., cosmetic use), whereas bio- logical sex differences determine the consequent dose (e.g., through dermal thickness and perme- ability). Sex differences in biological transport and target organs determine health outcomes, potentially modified by gendered (behavioral) coexposures and their sequelae. 168 Dose to effective dose. Sex determines the availability of target organs and hormonal systemic regulation. Only in women are pat- terns in ovarian cancer or pregnancy outcomes observable; only in men can testicular cancer patterns be observed. Kinetics and toxicity of chemicals in women’s bodies vary across the life course, during menarche, pregnancy, lacta- tion, and menopause (Roberts and Silbergeld 1995; Silbergeld et al. 1988); gastrointestinal cadmium accumulation increases with low iron stores (Åkesson et al. 2002), common during pregnancy and among women of reproductive age (Gunshin et al. 1997). Estradiol and tes- tosterone influence transport of environmen- tally derived chemicals and accumulation in the brain, kidney, liver, and intestines (Morris et al. 2003); mercury retention in kidneys can be three times higher among women than men (Barregård et al. 1999; Hultman and Nielsen 2001). During pregnancy (a sex-linked state), activity and exposure patterns change (Nethery et al. 2009), and hormonal changes affect toxi- cant transport throughout the body. Effective dose to health outcome. Sex-linked biological differences influence disease etiol- ogy after organ exposure. Women have more arsenic-induced kidney and bladder cancers than do men in regions with arsenic in drink- ing water, likely because of reduced chemi- cal excretion during pregnancy and lactation (Concha et al. 1998). Sex-linked hormonal status alters vascular effects of diesel exhaust (Prisby et al. 2008). Coexposures from gen- dered behaviors (e.g., alcohol and tobacco use, cardiovascular exercise) modify the biologi- cal fate of environmentally derived chemicals and organ resiliency. Sex and gender effects can interact; sex-linked pregnancy outcomes (observable only among women) are modi- fied by gendered behaviors (e.g., smoking, occupational endocrine disruptors, hairspray exposures) (Ormond et al. 2008). Gender differences in health-care seeking and illness behaviors influence the progression of environ- mentally derived illness. Current Evidence of Effect Modification by Sex in Air Pollution Epidemiology Search Methods A PubMed (National Library of Medicine 2009) search, performed in July 2009, retrieved all publications in the database identifiable using the terms “respiratory” and “nitrogen dioxide” (or “NO2”) and any of the following terms: “sex” (n = 41 citations), “gen- der” (n = 8), “women and men” (or “men and women”) (n = 243), or “girls and boys” (or vice versa) (n = 8). Another search retrieved all publications identifiable using “fine par- ticulate matter” (“PM2.5”) and “respiratory” and any of the following terms: “sex” (n = 11), “gender” (n = 5), “women and men” (or vice versa) (n = 65), or “girls and boys” (or vice versa) (n = 2). Only respiratory outcomes were considered (i.e., diagnosed respiratory illness, symptoms, lung function, respiratory mortal- ity), although the findings and models may apply to other outcomes. Papers examining noninhalation pathways were also excluded; thus, effects of prenatal air pollution exposures on infant and child health (which may differ- entially affect boys) are not considered here. Of the 383 publications identified, seven review articles were eliminated, along with 30 duplicate citations identified by multiple search criteria, 42 publications not available in English, 50 publications on noninhalation path- ways or nonrespiratory outcomes, 13 publica- tions on nonhuman species, and 32 publications not primarily examining air pollution exposures. Abstracts of the remaining 209 publications were reviewed to determine whether effect mod- ification by sex was tested; if the abstract was unclear, the original publication was consulted. Most publications reported only sex- adjusted effects or examined only one sex. Only 37 unique publications examined air pol- lution effect modification by sex (summarized in Tables 1 and 2). Given vast differences in analytic methods, outcomes, exposure intensi- ties, and durations—with few studies exploring any combination thereof—meta-analysis was not appropriate. It is beyond the scope of this review to assess the magnitude of effect modi- fication, which varies by study design and out- come measure. Most (not all) of the reviewed publications reported odds ratios or risk ratios, with interactions on the multiplicative scale. Authors also used varying statistical criteria for “significant” interactions (here, p < 0.05 unless otherwise stated). Issues in assessment of inter- actions for epidemiology have been detailed elsewhere (Knol et al. 2009). The qualitative review documents the widely varying explanations offered to explain observed modifications—as such, only papers in which authors offered such interpretations are included. Accordingly, the results described here, and summarized in Tables 1 and 2, are not exhaustive, but represent effect modifica- tion as reported by the authors. Only a few studies took additional analytic steps to exam- ine sources of difference that may account for observed effect modification. Search Results Because gender differences in behaviors, expo- sures, or coexposures (e.g., diet, smoking) and biological factors (e.g., hormonal composition) change over the life course, studies are summa- rized separately for adults and children. Gender and sex differences in respiratory health effects among adults. Studies report- ing stronger effects among women. Studies of residential air pollution exposures suggest ovlume 118 | number 2 | February 2010 • Environmental Health Perspectives