Supplementary Appendix

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Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Downs SH, Schindler C, Liu L-JS, et al. Reduced exposure to PM 10 and attenuated age-related decline in lung function. N Engl J Med 2007;357:2338-47.

PM 10 and lung function 21 August 2007 online supplement Manuscript no: 07-3625 TABLE OF CONTENT 1. Detail about exposure models 2. Table E1. PM 10 exposure by SAPALDIA 1 area 3. Table E2. Mean annual decline in lung function during follow-up 4. Table E3. Mean annual change in lung function in men by area 5. Table E4. Mean annual change in lung function in women by area 6. Table E5. Effects of change in PM 10 by area (model with random slope at the area level) 7. Table E6. Effects of interval exposure to PM 10 by area (model with random slope at the area level) 8. Table E7. Weighted regression analysis for the effect of change in PM 10 on annual pulmonary function decline, with weights inversely proportional to the probability of participation in SAPALDIA 2 lung function measurements. 9. Figure E1. Change in exposure to PM 10 from SAPALDIA 1 to SAPALDIA 2 by area 1

PM 10 and lung function 21 August 2007 online supplement Manuscript no: 07-3625 Detail about exposure models Individual exposure was estimated using the PolluMap dispersion model 1. The inputs to the model included hourly meteorological and annual emission inventory data for commercial, construction, residential, agricultural activities and forestry in 1990 and 2000, respectively 1-3. The emission strengths were modeled for diurnal variation, weekday-weekend differences and seasonal variation due to heating and photochemical reactions. This model simulated pollution movements in three distinct meteorological zones to account for the topographic characteristics across Switzerland. A regional, height-dependent background concentration was added to the emission-based computed PM 10 concentration to account for long-range transported PM 10. Hourly predictions were averaged over the year to obtain annual averages for each grid cell. Each individual subject s addresses were coded using the geographic information system (GIS) and assigned to an annual concentration after matching the address codes with the concentration grid cells generated by the dispersion model for 1990 and 2000, respectively. Possible contributions to PM 10 from other pollutants were incorporated in the model as secondary PM 10. The background concentrations of secondary PM 10 including sulfate, nitrate, and ammonium, were derived from the difference between fixed site measurements and model results based on Swiss emissions only. Dispersion model predictions were evaluated against measurements at 58 fixed PM 10 stations across Switzerland and predicted at least 60% of the variability in measured values for PM 1 10. Our comparisons of measured and modeled within- and between-cities variations further indicated that the modeled variations were consistent with measured values both within and between cities 1. PM 10 in the cities of Basel, Geneva, and Lugano, consisted mostly of 2

PM 10 and lung function 21 August 2007 online supplement Manuscript no: 07-3625 urban mixtures characterised by secondary, traffic, household, regional and industrial PM 10. The two rural areas, Payerne and Wald, were affected mostly by a mixture of agricultural and industrial sources.the two Alpine areas, Davos and Montana, were mostly affected by regional background PM 10, while Aarau was affected by both the urban mixture and an agricultural/industrial mixture. There was some heterogeneity in PM 10 effects between areas which could be related to heterogeneity in sources of PM 10 between areas and over time. For example, many of the Montana participants moved from higher altitudes to lower altitudes over the follow-up; thus closer to PM sources, resulting in higher PM exposure (see Figure E1 in online supplement). In addition traffic related sources formed a higher proportion of all PM 10 sources in SAPALDIA 2 compared to SAPALDIA 1. References 1. Liu L-JS, Curjuric I, Keidel D, et al. Characterisation of source-specific air pollution exposure for a large population-based Swiss Cohort (SAPALDIA). Environ Health Perspect 2007; 115:1638-45 2. BUWAL. Modelling of PM10 and PM2.5 ambient concentrations in Switzerland 2000 and 2010. Schriftenreihe Umwelt 2003;Nr. 169. 3. BUWAL. Modellierung der PM10-Belastung in der Schweiz. Schriftenreihe Umwelt 1999;Nr 310. 3

PM 10 and lung function 21 August 2007 online supplement Manuscript no: 07-3625 Table E1. PM 10 exposure by SAPALDIA 1 area Change in PM 10 * Interval exposure to PM 10 Area n (median, IQR) [µg/m 3 ] (median, IQR) [(µg/m 3 )-years] Basel 580-7.9-9.0 ; -6.9 304.9 287.9 ; 320.3 Wald 928-4.5-4.8 ; -3.9 198.8 193.7 ; 207.3 Davos 367-3.0-3.1 ; -2.8 102.6 99.1 ; 105.8 Lugano 653-12.1-13.5 ; -10.8 394.7 380.2 ; 407.1 Montana 447-4.0-4.2 ; -3.7 136.6 127.8 ; 144.2 Payerne 661-5.0-5.3 ; -4.6 226.5 221.7 ; 231.1 Aarau 730-6.4-6.8 ; -5.8 277.8 273.0 ; 283.0 Geneva 376-6.2-7.3 ; -5.7 261.6 249.9 ; 272.3 All areas 4742-5.3-7.5 ; -4.2 237.7 197.0 ; 286.6 *Change in PM 10 = PM 10 in the year before SAPALDIA 2 PM 10 in the year before SAPALDIA 1 Interval exposure to PM 10 = sum of annual means between SAPALDIA 1 and SAPALDIA 2 4

PM 10 and lung function 21 August 2007 online supplement Manuscript no: 07-3625 Table E2. Mean annual decline in lung function during follow-up mean SD FVC [ml] -24.9 40.3 All (n=4727) FEV 1 [ml] -35.4 29.8 FEV 1 /FVC % -0.4 0.5 FEF 25-75 [ml/s] -70.8 64.5 FVC [ml] -22.4 38.0 Never smokers (n=2213) FEV 1 [ml] -32.6 28.8 FEV 1 /FVC % -0.4 0.5 FEF 25-75 [ml/s] -67.1 62.9 FEV 1 as a percentage of FVC 5

PM 10 and lung function 23 August 2007 online supplement Manuscript no: 07-3625 Table E3. Mean annual change in lung function in men by area FVC [ml] FEV 1 [ml] FEV 1 /FVC % FEF 25-75 [ml/s] Area n change SD change SD change SD change SD Basel 270-43 56-37 38-0.1 0.5-42 75 Wald 443-17 42-32 33-0.4 0.4-76 71 Davos 183-39 46-43 32-0.3 0.5-63 66 Lugano 264-18 42-34 31-0.4 0.5-78 70 Montana 215-61 42-71 31-0.5 0.4-122 65 Payerne 282-26 40-37 32-0.4 0.5-64 68 Aarau 350-33 39-40 26-0.3 0.4-67 59 Geneva 170-6 37-35 26-0.6 0.4-95 57 Mean 2177-29 46-40 33-0.4 0.5-74 70 6

PM 10 and lung function 23 August 2007 online supplement Manuscript no: 07-3625 Table E4. Mean annual change in lung function in women by area FVC [ml] FEV 1 [ml] FEV 1 /FVC % FEF 25-75 [ml/s] Area n change SD change SD change SD change SD Basel 310-28 40-26 29-0.1 0.5-37 57 Wald 485-17 32-28 25-0.4 0.5-68 54 Davos 184-28 36-34 23-0.3 0.5-61 53 Lugano 389-16 30-32 25-0.5 0.5-78 63 Montana 232-48 37-57 24-0.5 0.4-105 55 Payerne 379-13 31-27 24-0.5 0.5-62 56 Aarau 380-24 28-32 21-0.4 0.4-61 51 Geneva 206-3 30-27 27-0.7 0.6-86 65 Mean 2565-21 34-32 26-0.4 0.5-68 59 7

PM 10 and lung function 23 August 2007 online supplement Manuscript no: 07-3625 Table E5. Effects* of change in PM 10 by area (model with random slope at the area level) FVC [ml] FEV 1 [ml] FEV 1 /FVC % FEF 25-75 [ml/s] Basel -2.4 3.3 0.13 22.2 Wald 0.5 3.6 0.09 14.0 Davos 0.9 3.9 0.11 14.5 Lugano -1.4 2.3 0.04 5.6 Montana 1.9 3.6-0.01 8.6 Payerne 1.0 3.7 0.07 19.0 Aarau 0.7 3.0 0.01 3.5 Geneva 1.4 3.5 0.01 11.0 * Attenuation of mean annual decline for a 10 μg/m 3 decrease in the average level of PM 10 between SAPALDIA 1 and 2. 8

PM 10 and lung function 23 August 2007 online supplement Manuscript no: 07-3625 Table E6. Effects* of interval exposure to PM 10 by area (model with random slope at the area level) FVC [ml] FEV 1 [ml] FEV 1 /FVC % FEF 25-75 [ml/s] Basel 5.2 7.1 0.13 22.9 Wald 5.2 6.5 0.02 10.7 Davos 5.2 7.2 0.11 20.1 Lugano 5.2 6.2-0.02 4.6 Montana 5.2 7.6 0.04 22.8 Payerne 5.2 6.9 0.08 18.7 Aarau 5.2 7.1 0.05 15.6 Geneva 5.2 7.1 0.06 18.8 * Attenuation of mean annual decline for a 109 (μg/m 3 )-years decrement in interval exposure to PM 10 between SAPALDIA 1 and 2. The variance of random slope was estimated to be 0 for FVC 9

PM 10 and lung function 23 August 2007 online supplement Manuscript no: 07-3625 Table E7. Weighted regression analysis for the effect of change in PM 10 on annual pulmonary function decline, with weights inversely proportional to the probability of participation in SAPALDIA 2 lung function measurements. Group Lung function parameter Effects for a 10 µg/m 3 decrease in PM 10 between SAPALDIA 1 (1991) and SAPALDIA 2 (2002) 95% CI Effect lower upper p-value FVC [ml] - 1.19-5.2 3.0 0.87 All (n=4742) FEV 1 [ml] 2.9-0.4 5.8 0.09 FEV 1 /FVC % 0.07-0.02 0.12 0.011 FEF 25-75 [ml/s] 12.7 4.7 18.6 0.001 FVC [ml] 1.4-4.2 6.9 0.65 Never smokers (n=2213) FEV 1 [ml] 4.3-0.4 8.3 0.073 FEV 1 /FVC % 0.07-0.011 0.14 0.14 FEF 25-75 [ml/s] 13.9 2.9 22.6 0.011 The weighted regression analysis gives more weight to participants with characteristics resembling those of non-participants thereby providing an indication of how results might have looked with complete participation. 10

PM 10 and lung function 23 August 2007 online supplement Manuscript no: 07-3625 Figure E1. Change in exposure to PM 10 from SAPALDIA 1 to SAPALDIA 2 by area 100% 90% 80% 70% 2421 60% 50% 40% 30% 20% 10% 115 301 446 1078 263 118 Geneva Aarau Payerne Montana Lugano Davos Wald Basel 0% <-15-15 --12-12 --9-9 --6-6 --3-3 -0 >=0 Change in PM 10 The dashed line shows the number of participants from all areas in each PM 10 change category, while the stacked bars show percent of participants from each SAPALDIA 1 area in the category. For example, 115 subjects experienced PM 10 decrements of more than 15 μg/m 3 since SAPALDIA 1; most of these participants resided in Lugano. Similarly, 118 subjects experienced PM 10 increments since SAPALDIA 1; most of these subjects resided in Davos, Montana and Wald. 11