Int Arch Occup Environ Health (2011) 84:591–600 people of the same age on level ground, or (3) if they had to stop for breath when walking on level ground at one’s own pace. Lung function measurement using spirometry After height and weight were measured by nurse-inter- viewers, lung function was assessed according to American Thoracic Society guidelines (ATS 1995) using an EasyOne spirometer (NDD Medical Technologies, Zurich, Switzer- land) in diagnostic mode. The same trained technician used the same spirometer in Antofagasta and Arica. Subjects were instructed to take as deep a breath as possible and then blow as hard and long as possible into the spirometer. Following a demonstration and practice with the mouth- piece, they performed tests in a sitting position with active coaching. The main lung function values assessed were forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). The maneuver was repeated until the EasyOne indicated satisfactory results were achieved (e.g., FEV1 and FVC within 200 ml of previous values) or the participant chose to stop. Each subject’s best trial (largest sum of FEV1 and FVC) was included in analyses. Spi- rometry data were reviewed by a pulmonologist (JB). Arsenic exposure assessment Municipal drinking water records used in previous studies (Ferreccio et al. 2000; Smith et al. 2006) were linked with each participant’s residential history to obtain age-speciﬁc estimates of arsenic exposure. The drinking water database included over 15,000 arsenic measurements in Antofagasta and 11 other cities in northern Chile between 1962 and 1990, when concentrations transitioned from high to low. In initial analyses, high exposure in early life was deﬁned as drinking water containing [800 lg/l arsenic before age 10. The unexposed group included mostly long-term residents of Arica. In our main analyses, the unexposed group also included eight subjects who either moved to Antofagasta (from lower exposure areas) after age 10 or who lived in Antofagasta but were over age 10 during the high exposure period. Sensitivity analyses were conducted to evaluate whether changing cut-offs deﬁning ‘‘high exposure’’ (e.g., 800, 200, or 50 lg/l) and ‘‘early-life’’ (e.g., in utero, 10, or 18 years old) had any impact on results. Exposure–response was assessed both by using early-life arsenic concentration as a continuous variable in models and by stratifying sub- jects into low, medium, and high exposure categories. Statistical methods We analyzed data using SAS 9.2 (SAS Institute Inc., Cary, NC). Student’s t-tests were used to compare the means of 593 continuous variables. We conducted one-tailed tests of sig- niﬁcance for pulmonary outcomes because of the clear direction of a priori hypotheses regarding arsenic. Otherwise, two-tailed tests were used. Lung function mean residuals (observed values minus age-, sex-, and height-predicted val- ues) and percentages (observed values divided by predicted values) were calculated for subjects with and without high early-life arsenic exposure. Predicted values for northern Chile were not available, so we used those of Mexican Americans in NHANES III (Hankinson et al. 1999). These are within 3% of reference values obtained from the PLATINO study of 5 large Latin American cities (Perez-Padilla et al. 2006). The choice of reference was not critical because our purpose was to compare arsenic exposed and unexposed, for whom the same reference values were used. Both univariate and multivariate models were per- formed. We did not enter age, sex, or height in the multi- variate models of lung function because ‘‘unadjusted’’ values were residuals and percentages of age-, sex-, and height-predicted values. Final linear models adjusted for ever regularly smoking and variables that were both (1) associated with pulmonary function in other studies and (2) different between the arsenic-exposed and arsenic-unex- posed groups in this study (Table 1). These were entered dichotomously: childhood secondhand tobacco smoke (Moshammer et al. 2006); wood, charcoal, or kerosene fuel use in childhood home (Fullerton et al. 2008); occupational air pollution (Blanc et al. 2009); and university graduation, as an indicator of socioeconomic status (Prescott and Vestbo 1999). Adjusted differences between arsenic- exposed and arsenic-unexposed subjects were similar (within 2% predicted FEV1) when potential confounders were entered as continuous variables (e.g., cigarettes per day, age started smoking) or multiple indicator variables (e.g., for education: (1) graduating high school, (2) some post-high school, (3) graduating university). Adjusting for outdoor air pollution, adult secondhand smoke, prior diag- nosis of respiratory illness including pulmonary tuberculo- sis, obesity (BMI [ 30 kg/m2) at time of interview, number of spirometry maneuvers attempted, or having reproducible spirometry (difference between highest 2 FEV1 and FVC values B200 ml) likewise had little impact on results. Prevalence odds ratios (PORs) for respiratory symptoms were calculated using the Wald method of logistic regres- sion. Adjusted models included the same variables used for spirometry outcomes, plus age (in years) and sex. Results As expected, participants reported nearly exclusive use of municipal sources in this desert region. Of the 32 subjects exposed to [800 lg/l arsenic in drinking water before age 123