598 the convenience method of participant recruitment, raising concerns about inference and interpretation of results. Although the problem of arsenic in drinking water in northern Chile has been publicized, most information has been on cancer. Our experience is that very few people in the study cities know about the possible role of arsenic in non-malignant respiratory disease. This suggests that peo- ple with respiratory problems in Antofagasta (the exposed city) would not be more likely to participate than people with respiratory problems in Arica (the unexposed city), and differential selection is unlikely to account for the effects we identiﬁed. A second weakness of this study is that most exposed and unexposed subjects were not assessed concurrently. However, effect estimates remained similar in analyses conﬁned to those who were. Confounding due to smoking is unlikely to account for the effects identiﬁed in this study for 2 reasons. First, entering smoking information into multivariate models had little impact on the association between arsenic and lung function. Second, to explain the observed 8–12% decrease in FEV1, virtually all of the arsenic-exposed subjects would have to have smoked, while all unexposed would have to have been never smokers. In actuality, the 2 groups had similar smoking histories, and these Chilean smokers consumed fewer cigarettes per day than their U.S. coun- terparts (CDC 2005). Although arsenic-exposed subjects had slightly less reproducibility of spirometry, less edu- cation, and more childhood secondhand smoke exposure, none of these variables were associated with decreased lung function in this study, and adjusting for them had little effect on results. The arsenic-exposed and arsenic-unex- posed cities (Antofagasta and Arica) have historically had similar air pollution, industry (e.g., no large coal-ﬁred power plant nearby), trafﬁc patterns (e.g., 1 major high- way), geography (coastal desert), sociodemographics, and dietary patterns (INE 2002). Particulate matter of mass median aerodynamic diameter B10 lm (PM10) measure- ments, available for the past 10 years, are similar both at city centers and across neighborhoods of Antofagasta (mean 40.4, range 29.7–51.9 lg/m3) and Arica (mean 40.9, range 32.5–48.6 lg/m3). Nitrogen dioxide (NO2) levels are low in both cities, with annual averages around 8–12 lg/ m3 (CENMA 2008; SETEC 2008). Although some arsenic exposures in this area also occur through air and food, these are minor compared to drinking water (Ferreccio and Sancha 2006). Except for the nearly 100-fold contrast in past arsenic exposure, the 2 cities appear similar in all covariates related to lung function. Although confounding cannot be completely ruled out, it seems unlikely that some unknown confounder could cause the lung function decrements observed in subjects with high early-life arsenic exposures, similar in magnitude to decades of heavy smoking. 123 Int Arch Occup Environ Health (2011) 84:591–600 Federal and state regulations in the United States man- date protection of susceptible subgroups such as pregnant women and children. Without relevant studies, however, the U.S. Environmental Protection Agency has been unable to incorporate data on the long-term health effects of early- life exposures into any of its drinking water standards (Landrigan et al. 2004). A lack of epidemiologic data is particularly problematic for addressing environmental exposures such as arsenic, for which there are major dif- ferences between humans and laboratory animals in metabolism, co-exposures, and potency (NRC 2001). Several human studies have assessed the impacts of early- life environmental exposures, but these have typically involved short follow-up periods, small numbers of study subjects, or small effect sizes. For example, dioxins in breast milk were linked to a lower FEV1/FVC ratio in Danish children (mean age 8.2 years), but the sample size was only 29 (ten Tusscher et al. 2001). In a meta-analysis involving 53,879 children, parental smoking was linked to respiratory symptoms, but relative risks were generally low (around 1.15) (Pattenden et al. 2006). In a subsample of 22,712 of these children with valid lung function data, maternal smoking during pregnancy was linked to a 1% decrease in FEV1 and essentially no change in FVC (Moshammer et al. 2006). In a longitudinal study on out- door air pollution in southern California, the mean differ- ence in FEV1 growth from age 10 to 18 between the most exposed city (PM10 = 68 lg/m3) and the least exposed city (PM10 = 17 lg/m3) was 82 ml. Similar effects were seen for PM2.5, NO2, and acid vapor (Gauderman et al. 2004). In the current study, we observed 4-fold larger FEV1 decre- ments (335 ml) nearly 40 years after high arsenic expo- sures ended. Conclusions This study provides the ﬁrst evidence that in utero and childhood exposure to arsenic in drinking water is associ- ated with long-term lung function deﬁcits and shortness of breath in humans. The magnitude of the decrease in both FEV1 and FVC suggests that early-life arsenic exposure could have effects similar to smoking throughout adult- hood and greater effects than secondhand smoke or air pollution. Nonetheless, certain potential biases—especially those related to non-random selection of subjects—were not controlled for and cannot be excluded. These results should be conﬁrmed in a larger study with participants who are representative of the source population. A larger study could also investigate the effects of lower exposures as well as effect modiﬁcation and confounding by factors such as diet, occupational exposures, smoking, and gender. The public health importance lies in the enormous morbidity