Jerrett et al. proportional hazards assumption by introduc- ing interactions of time with all covariates. Results Table 1 shows descriptive statistics for the cohort and the assigned exposures. In this sample, 48% were male, the median age was 60 years, and about 47% were current or former smokers. Figure 1 presents a map showing the average of two main exposure models for NO2. Figure 2 shows the cumulative dis- tribution of mean (2002 and 2004) NO2 Table 1. Characteristics of subjects and their neighborhoods. Characteristic No. of subjects Males Age Smoking Never Former Current FVC (% predicted) FEV1 (% predicted) BMI Diagnosed with asthma Diagnosed with COPD Diagnosed with IHD Diagnosed with diabetes Median household income (CD$1,000) Residence within 50 m of major road or 100 m from highway Interpolated NO2 (ppb) (average of 2002 and 2004 sampling) Interpolated PM2.5 (µg/m3) Interpolated O3 (ppb) Nonaccidental deaths (no.) Circulatory deaths (ICD-9-CM codes 400–449) (no.) Respiratory deaths (ICD-9-CM codes 460–519) (no.) Values are no. (%) or 25th percentile, median, and 75th percentile. exposures among the study subjects. Because of meteorologic variability, the magnitude of the 2-week average NO2 concentrations dif- fered between seasons, and there were small differences in the predictors derived from LUR. However, the spatial patterns derived from the two season-specific LUR models were similar because the underlying pattern in NOx emissions, influenced largely by the distribution of traffic, changes little over time. The prediction surfaces followed a similar spatial pattern of high concentrations in the downtown and around the major highways, Measure 2,360 1,128 (48) 49, 60, 69 1,248 (53) 842 (36) 270 (11) 77, 93, 105 61, 82, 99 462 (20) 698 (30) 1,129 (48) 412 (17) 33, 39, 50 570 (24) 23.8, 27.3, 31.5 20.8, 22.9, 24.8 8.64, 8.71, 8.83 17.5, 18.3, 18.8 299 82 75 Lake Ontario Subject locations NppOb2 mean (2002, 2004) 10.8–15 15.1–20 20.1–25 25.1–30 30.1–67.3 0 125 25 5 75 10Kilometers Figure 1. Average NO2 levels based on two LUR models calibrated from 2002 fall and 2004 spring monitor- ing campaigns with 143 monitors. Approximate subject coordinates are shifted to protect privacy. 774 ovlume 117 | number 5 | May 2009 • Environmental Health Perspectives with lower concentrations in the northeast of the city, where there is a zoo and relatively little human habitation or traffic. The two surfaces were highly correlated after assign- ment to the subject (Pearson’s r = 0.73), and were averaged for inclusion in the regression model [see Supplemental Material, Appendix, for more detail (http://www.ehponline.org/ members/2009/11533/suppl.pdf)]. There were 10,500 person-years of follow- up in the cohort. Table 2 shows the results of the Cox survival models for the relations between interpolated NO2 and all-cause, circulatory, and respiratory mortality. The fourth column lists mortality from all nonac- cidental causes except those in the first two columns. The first line of Table 2 shows mod- els adjusted only for age and sex. The next line adds potential clinical confounders, including BMI and percent predicted forced vital capac- ity (FVC), expressed as a percentage of the normal value. We found no significant asso- ciation between mortality and forced expira- tory volume in the first second (FEV1) when FVC was included in the models. In the next line, we adjusted the models for smoking in three categories (i.e., never, ever, or current smoking) followed by adjustment for all the previous variables and the DI. Finally, as a sensitivity analysis, we added the chronic dis- eases COPD, IHD, and diabetes. All-cause mortality was elevated in relation to the 4 ppb interquartile range (IQR) of NO2, with RRs ranging from 1.29 for the minimal adjustment model to 1.17 for the model with inclusion of all the control variables and adjust- ment for clustering within the census tract of residence. Confounding variables generally reduced the size of the NO2 effect, as expected. Including chronic diseases confounded the rela- tionship mildly, lowering significance to slightly below conventional levels [hazard ratio (HR) = 1.15; 95% confidence interval (CI), 0.99–1.33]. Circulatory mortality was associated with NO2 in all models. In the model with maxi- mal control for confounding, the RR signifi- cantly increased by about 40% over the IQR se1.0 u l a v O20.8 N f o n0.6 o i t r o po0.4 r p e iv0.2 t a l u um 0 C 10 15 20 25 30 35 Mean of 2002 and 2004 NO2 measurements (ppb) Figure 2. The cumulative distribution of mean NO2 exposures among study subjects. The vertical lines are the 25th, 50th, and 75th percentiles of the distribution.