Online Data Supplement. Early life exposure to traffic-related air pollution and lung function in adolescence

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1 Online Data Supplement Early life exposure to traffic-related air pollution and lung function in adolescence Authors: Erica S. Schultz MD, Jenny Hallberg PhD, Prof Tom Bellander PhD, Anna Bergström PhD, Prof Matteo Bottai ScD, Flaminia Chiesa MSc, Per M. Gustafsson MD,Olena Gruzieva MD, Per Thunqvist MD,, Prof Göran Pershagen MD, Erik Melén MD

2 Supplementary appendix List of Contents Text:... 1 Air pollution exposure assessment... 1 Definitions of potential confounders and covariates... 2 Selection of confounders... 3 Tables:... 4 E1. Equations for the main unstratified models E2. Distribution of selected exposure characteristics among all children in the cohort (N=4089) and the children included in the present study on air pollution exposure and lung function at 16 years (n=2278) E3a. Associations of NOx (per 10 µg/m³) during different time periods of life with spirometry measurements in all subjects and stratified by gender E3b. Associations of PM 10 (per 5 µg/m³) during different time periods of life with spirometry measurements in all subjects and stratified by gender Figure legends:... 8 E1. Distribution of personal time weighted average traffic-no x and PM 10 in present study population during different time periods of life E2. Association of traffic-no x exposure during first year of life with FEV 1 at 16 years (n=2211) References:... 8

3 Air pollution exposure assessment A methodology developed to estimate long-term source-specific exposure was used for assessment of traffic air pollution exposure. (1, 2) The method entails geocoding of a person s address information and using an emission inventory together with dispersion models to estimate outdoor levels of selected pollutants from relevant emission sources over time at different geographic locations. Residential, day care, and school addresses were obtained from the postal questionnaires, complemented with the Swedish tax authority records, and transformed into geographic coordinates by using a property register developed and managed by the Swedish mapping, cadastral, and land registration authority. Temporally and spatially resolved emission calculations were based on the emission inventory of the Stockholm and Uppsala Air Quality Management Association. This database has been updated yearly since It entails detailed information about emissions from various sources, such as road and ferry traffic, petrol stations, industrial areas, and households.(3) For the present study, emissions from local road traffic were included by using particles with an aerodynamic diameter of less than 10 µm (PM 10 ) as a marker for road dust and nitrogen oxides (NOx) as a marker of exposure to exhaust particles. The road-traffic emissions of NOx are described by using emission factors for different vehicles and road types obtained from the EVA model of the Swedish National Road Administration.(4) Emission factors for PM 10, which originate mainly from studded tires wear as well as from abrasion of brakes and tires, were obtained using NOx as quantitative tracer for traffic emissions.(5, 6) The annual mean concentrations of NOx and PM 10 were calculated by using a Gaussian air quality dispersion model and a wind model, both of which are part of the Airviro Air Quality Management System (SMHI, Norrköping, Sweden; The calculations were performed with a 25-m resolution for the dense populated areas of inner city, and 100-m or 500-m grid for the rest of urban and rural areas, respectively. No assessment could be performed for 9 % of the addresses as they were located outside the modelling area. Measurements at air quality monitoring stations are regularly used to validate the estimated air pollution concentrations from the dispersion modeling.(7, 8) Emission databases for NOx concentrations were available for the years 1990, 1995, 2000, 2002, 2003, 2004, 2006, 2010 and Interpolation of the model calculation was made to obtain NOx concentrations for all years during the study period. PM 10 model calculations were only performed for the year 2004, when the most complete database was available, and applied to all years during the observation period. The estimated levels of NOx and PM 10 were re-scaled based on measured traffic flow in and out of the regional center of Stockholm to compensate for trends in traffic volumes. Air pollution concentrations are estimated 2 m above ground level and the model treats buildings by using a roughness parameter, resulting in underestimation of concentrations in street canyons with heavy traffic.(9) A street canyon contribution was therefore calculated for addresses within 30 m from the most polluted street segments in the Stockholm inner city with multistory houses on both sides by using the Airviro street canyon model ( Age- and municipality-specific information on the time children were at day care and school facilities was used to estimate the time-weighted average exposure to NOx and PM 10. E3

4 Definitions of potential confounders and covariates Socioeconomic status at birth and at 8 years: Socioeconomic status for the household according to dominance order in three classes. (0 = Blue collar worker, 1 = White collar worker, (incl. Liberal professional practician with university graduate jobs),2 = Other (student, housewife/man, person on a disability pension, unemployed) (For Table E1 the group Other has been replaced by missing.) Heredity: Mother and/or father with doctor s diagnosis of asthma and asthma medication and/or doctor s diagnosis of hay fever in combination with furred pets- and/or pollen allergy at the time of questionnaire 0. Maternal smoking during pregnancy or at baseline (2 months): The mother smoked at least one cigarette per day at the time of questionnaire 0 and/or smoked at least one cigarette per day in any point of time during the pregnancy. Environmental tobacco smoke exposure (ETS): Any of the parents smoked daily at the time of questionnaire 8 or 16. (Independent of the amount of cigarettes). Adolescence smoking at sixteen years: Smoking regularly or sometimes at time of questionnaire 16. Breastfeeding: Exclusively breast fed. (Number of months) Older siblings: Older siblings in household/family at time of questionnaire 0. Ethnicity: Father and/or mother born outside of Scandinavia, i.e. outside of Sweden, Finland, Norway and Denmark Asthma at 0-2 years: > 3 episodes of wheezing between birth and 2 years of age, combined either with inhaled steroids or signs of hyper-reactivity without ongoing cold. Asthma at 16 years: At least four episodes of wheeze in the last 12 months prior to the date of answering the questionnaire at 16 years or at least one episode in combination with prescription of inhaled corticosteroids. Sensitized at 16 years: The blood samples taken at 16 years of age were analyzed with Phadiatop [a mixture of common airborn allergens: birch, timothy, mugwort, cat, dog, horse, mold and house dust mite] and fx5 (a mixture of common food allergens: cow s milk, egg white, soy bean, peanut, cod fish and wheat) (ImmunoCAP System, Phadia AB, Uppsala, Sweden).(10) Sera with an IgE value equal to or greater than 0.35 ku/l were regarded as positive. Self-reported puberty status at sixteen years: Classified in to one of five mutually exclusive categories: pre-, early-, mid-, late- or post puberty based on Petersen and colleagues.(11) Data were collected on seven measures as skin changes, linear growth spurt, pubic hair growth (for boys and girls), voice change, beard growth (for boys), breast development, and menarche (for girls). Multiple pubertal characteristics were then included to establish a pubertal staging. E4

5 For boys, all characteristics contributed equally. Girls reporting menarche were considered to be in late- or post puberty, regardless of other characteristics. Selection of confounders Our base model was adjusted for age, height, gender, and municipality at birth. In addition, socioeconomic status at birth and at eight years, parental allergy and/or asthma, maternal smoking during pregnancy or at baseline, passive smoking at eight and sixteen years, adolescence smoking at sixteen years, breastfeeding, older siblings, ethnicity, gestational age, birth weight, maternal age at delivery, weight at examination, and self-reported puberty status at sixteen years were evaluated as potential confounders. Only variables that led to greater than 10 % change in the β coefficient and likelihood ratio test differed significantly (p<0.05) from a more parsimonious model, were considered in final model. E5

6 Table E1: Equations for the main unstratified models. Model type Equation Reported results Linear mean regression* ( ) [ ] in Figure 1, Figure E2 (only 0-1 year NO x ) & Tables E3a and E3b Mixed effect model ( ) [ ] in Tables E3a and E3b with time interaction ( ) [ ] ( ) in Tables E3a and E3b Life-course models Sensitive period ( ) [ ] in Table 2 Critical period ( ) [ ] in Table 2 Accumulation, Linear ( ) [ ] in Table 2 Accumulation, Categorical ll ( ) [ ] in Table 2 Saturated** ( ) [ ] in Table 2 Logistic regression ( ) in Figure 2 (only 0-1 year) Definitions of abbreviations: PM 10 = particulate matter with aerodynamic diameter <10 µg/m³; NO x = nitrogen oxides; TRAP = Traffic related air pollution (i.e., PM 10 or NO x ); LLN = lower limit of normal for FEV 1 defined as below times the standard deviation. Range of subscripts: ; j = 0-1 years, 1-8 years or 8-16 years (only one time period at the time in each analysis); * TRAP as continuous variable; [covariates i ] : : random intercept; [covariates ik ] : ; indicates age at clinical investigation (8 or 16 years). NOx are for each time period dichotomized (0=low exposed, 1=high exposed) on median for years 1-8, corresponding to 10.9µg/m³ in life-course model. represents the number of times the i-th individual is highly exposed during follow-up; time. ll represents the indicator for the h-th level of the variable;, corresponding to, is left out of the model as reference category.** Trajectories of dichotomized NOx exposure, gives 8 different trajectories: ; I_traj ih represents the indicator variable for the trajectory h, h = 2,..., 8, on the i-th individual; I_traj i1 is left out of the model as reference category. TRAP is dichotomized on median for years 1-8, corresponding to 10.9µg/m³ for NO x and 4.4 µg/m³ for PM 10. E6

7 Table E2. Distribution of selected exposure characteristics among all children in the cohort (N=4089) and the children included in the present study on air pollution exposure and lung function at 16 years (n=2278). Confidence intervals constructed by applying finite population correction factor. Covariates * Full Cohort (N=4089) Study population at 16 years (n=2278 ) n % n % 95% CI Male gender to 49.1 Socioeconomic status of parents White collar worker to 86.6 Heredity Parents with allergy and/or asthma to 33.3 Ethnicity Any parents born outside of Scandinavia to 17.0 Mother smoking during pregnancy or at to 12.8 months of child Mother smoking during pregnancy to 12.0 Environmental tobacco smoke exposure at to years Adolescence smoking at 16 years to Asthma at 0-2 years to 10.6 Asthma at 16 years to 7.7 Mean SD Mean SD 95% CI Birth weight (grams) to 3533 Birth lengths (cm) to 50.2 Gestational age (weeks) to 39.5 Exposure concentration during year 0-1 NO x (µg/m³) to 22.0 PM 10 (µg/m³) to 6.0 * Covariates relate to the first year of child s life if not other stated Data include subjects with data on spirometry at 16 years, municipality at birth, sex, age, weight, height at 16yr examination, as well as exposure information for first year of life. Data includes subjects answering at 16 year questionnaire, corresponding to 3034, 3108 and 3115 for environmental tobacco smoke, own smoking and asthma respectively. Definition of abbreviations: NO x = nitrogen oxides. PM 10 = particulate matter with aerodynamic diameter <10 µg/m³. E7

8 Table E3a. Associations of NO x (per 10 µg/m³) during different time periods of life with spirometry measurements in all subjects and stratified by gender Beta 95% Confidence Interval Lung function Exposure time periods measurements Year 0-1 Years 1-8 Years 8-16 All subjects At 16 years* FEV 1 (ml) (-33.6;2.0) (-37.7;12.6) -9.0 (-43.2;25.1) FVC (ml) (-30.7;9.4) (-39.4;17.7) (-58.0;19.1) FEV 1 /FVC (%) -0.1 (-0.3;0.2) -0.0 (-0.4;0.3) 0.1 (-0.4;0.6) z- FEV (-0.07;0.01) (-0.08;0.03) (-0.09;0.05) 8 and 16 yrs FEV 1 FEV 1 (ml) (-26.4;1.4) (-33.0;5.1) (-41.8;10.1) Change 8 to 16 (ml) -0.3 (-12.4;11.9) 9.3 (-12.2;30.7) 23.5 (-10.1;57.1) Males At 16 years* FEV 1 (ml) (-59.1;-1.7) (-55.8;31.1) -7.0 (-62.3;48.3) FVC (ml) (-49.9;14.6) (-65.5;33.2) (-84.9;40.7) FEV 1 /FVC (%) -0.3 (-0.7;0.1) -0.1 (-0.7;0.5) 0.1 (-0.6;0.9) z- FEV (-0.11;-0.00) (-0.11;0.06) (-0.12;0.09) 8 and 16 yrs FEV 1 FEV 1 (ml) (-44.8; -1.7) (-45.1;18.2) -9.4 (-49.8;31.0) Change 8 to 16 (ml) 0.6 (-19.7; 1.0) 18.5 (-16.1;53.1) 23.7 (-27.3;74.7) Females At 16 years* FEV 1 (ml) 0.9 (-20.3;22.1) (-38.0;18.0) (-51.6;29.0) FVC (ml) 1.0 (-23.2;25.2) 1.2 (-33.1;30.7) (-59.4;31.5) FEV 1 /FVC (%) 0.1 (-0.2;0.5) -0.0 (-0.5; 0.4) -0.0 (-0.7;0.6) z- FEV (-0.05;0.06) (-0.09;0.05) (-0.12;0.08) 8 and 16 yrs FEV 1 FEV 1 (ml) -0.3 (-17.4;16.8) (-34.3;9.6 ) (-53.0;10.8) Change 8 to 16 (ml) 0.3 (-12.7;13.3) 2.8 (-17.3;23.0) 20.0 (-13.2;53.2) Definition of abbreviations: FEV 1 = forced expiratory volume during 1 second. FVC = forced vital capacity. z = z- score of respective lung function measurement based on reference equations from GLI NO x = nitrogen oxides. *Calculated by linear regression, adjusted for age, gender, height, weight, and municipality at birth Adjusted for municipality at birth Longitudinal equations calculated with mixed effects models included time dependent covariates (height, age, weight) and fixed covariate (municipality at birth as well as gender in unstratified analyses) E8

9 Table E3b. Associations of PM 10 (per 5 µg/m³) during different time periods of life with spirometry measurements in all subjects and stratified by gender Beta 95% Confidence Interval Lung function Exposure time periods measurements Year 0-1 Years 1-8 Years 8-16 All subjects At 16 years* FEV 1 (ml) (-86.6;17.9) (-75.1;20.7) (-52.4;25.4) FVC (ml) -7.9 (-66.9;51.2) -9.3 (-63.7;45.0) (-61.9;26.0) FEV 1 /FVC (%) 0.3 (-1.10;0.44) -0.3 (-1.0;0.4) 0.0 (-0.6;0.6) z- FEV (-0.17;0.05) (-0.15;0.04) (-0.12;0.05) 8 and 16 yrs FEV 1 FEV 1 (ml) (-73.4;7.9) (-69.5;2.8) 19.9 (-49.5;9.7) Change 8 to 16 (ml) 1.4 (-29.0;31.9) 19.1 (-20.7;59.0) 23.4 (-14.7;61.5) Males At 16 years* FEV 1 (ml) (-140.8;27.1) (-100.0;60.9) (-81.2;43.0) FVC (ml) -7.7 (-102.3;86.8) (-106.8;77.0) (-100.9;39.6) FEV 1 /FVC (%) -1.1 (-2.2;0.0) (-1.45;0.77) -0.0 (-0.9;0.9) z- FEV (-0.26;0.05) (-0.18;0.12) (-0.15;0.08) 8 and 16 yrs FEV 1 FEV 1 (ml) (-113.7;11.6) (-81.7;34.9) (-65.4;25.7) Change 8 to 16 (ml) 4.3 (-46.7;55.3) 26.6 (-36.0;89.2) 19.1 (-38.5;76.7) Females At 16 years* FEV 1 (ml) -7.3 (-69.8;55.3) (-86.1;22.7) (-57.2;35.9) FVC (ml) -1.6 (-72.7;69.6) -1.0 (-62.8;60.9) -8.7 (-61.5;44.1) FEV 1 /FVC (%) 0.4 (-0.6;1.5) (-1.21;0.63) -0.0 (-0.8;0.8) z- FEV (-0.16;0.14) (-0.20;0.06) (-0.13;0.09) 8 and 16 yrs FEV 1 FEV 1 (ml) (-63.5;37.2) (-80.6;4.9) (-59.7;14.1) Change 8 to 16 (ml) -0.7 (-33.3;31.8) 7.6 (-30.6;45.9) 21.1 (-16.6;58.9) Definition of abbreviations: FEV 1 = forced expiratory volume during 1 second. FVC = forced vital capacity. z = z-score of respective lung function measurement based on ref equation from GLI PM 10 = particulate matter with aerodynamic diameter <10 µg/m³. *Calculated by linear regression, adjusted for age, gender, height, weight, and municipality at birth Adjusted for municipality at birth Longitudinal equations calculated with mixed effects models included time dependent covariates (height, age, weight) and fixed covariate (municipality at birth and gender) E9

10 Figure legends Figure E1: Distribution of personal time weighted average traffic-nox and PM 10 in present study population during different time periods of life. The box indicates IQR, with the inner line on the median. Vertical bars indicate data outside the upper and lower quartiles up to 1 5 times IQR from the box. The dark blue circles outliers. Data available for 2279 individuals during first year of life, 2033 for years 1 to 8, and 2114 for years 8 to 16. NO x = nitrogen oxides. PM 10 = particulate matter with aerodynamic diameter <10 µg/m³ Figure E2: Association of traffic-nox exposure during first year of life with FEV 1 at 16 years (n=2212) and NOx exposure distribution in the present studypopulation. Calculated with linear regression using the median NO x exposure as a reference (17.5 µg/m³). Adjusted for gender, age, height, weight, and municipality at birth. FEV 1 = Forced expiratory during one second. NOx= nitrogen oxides. References 1. Nordling E, Berglind N, Melen E, Emenius G, Hallberg J, Nyberg F, Pershagen G, Svartengren M, Wickman M, Bellander T. Traffic-related air pollution and childhood respiratory symptoms, function and allergies. Epidemiology 2008; 19: Bellander T, Berglind N, Gustavsson P, Jonson T, Nyberg F, Pershagen G, Jarup L. Using geographic information systems to assess individual historical exposure to air pollution from traffic and house heating in Stockholm. Environ Health Perspect 2001; 109: Johansson C, Hadenius A, Johansson PÅ, Jonson T. The Stockholm Study on Health effects of Air Pollution and Its Economic Consequences. Part I. NO2 and Particulate Matter in Stockholm.: Stockholm Environment and Health Protection Administration, Box 8136, Stockholm, Sweden. Available: [accessed 11 September 2010]; 1999 No. AQMA Report 6: Hammarström U, Karlsson B. Costs and exhaust emissions for road planning (Fordonskostnader och avgasemissioner för vägplanering, EVA). Swedish National Road and Transport research Institute, S Linköping, Sweden, Report T 150 (in Swedish); Omstedt G, Bringfelt B, Johansson C. A model for vehicle-induced non-tailpipe emissions of particles along Swedish roads. Atmospheric Environment 2005; 39: Ketzel M, Omstedt G, Johansson C, During I, Pohjolar M, Oettl D, Gidhagen L, Wahlin P, Lohmeyer A, Haakana M, Berkowicz R. Estimation and validation of PM2.5/PM10 exhaust and nonexhaust emission factors for practical street pollution modelling. Atmospheric Environment 2007; 41: Johansson C, Andersson C, Bergström R, Krecl P. Exposure to particles due to local and non-local sources in Stockholm - Estimates based on modelling and measurements Department of Applied Environmental Science, Stockholm University. ITM 2008: Accessed 10 June Eneroth K, Johansson C, Bellander T. EXPOSURE - Comparison between Measurements and Calculations Based on Exposure Modelling. Report LVF 2006:12. Accessed 11 June Gidhagen L, Johansson C, Langner J, Foltescu VL. Urban scale modeling of particle number concentration in Stockholm. Atmospheric Environment 2005; 39: Wickman M, Asarnoj A, Tillander H, Andersson N, Bergstrom A, Kull I, Melen E, Pershagen G, Ahlstedt S, Lilja G, van Hage M. Childhood-to-adolescence evolution of IgE antibodies to E10

11 pollens and plant foods in the BAMSE cohort. J Allergy Clin Immunol Feb;133(2): doi: /j.jaci Epub 2013 Oct Petersen AC, Crockett L, Richards M, Boxer A. A self-report measure of pubertal status: Reliability, validity, and initial norms. J Youth Adolesc 1988; 17: E11

12 NOx concentrations, µg/m³ PM10 concentrations, µg/m³ Age 0-1 Ages 1-8 Ages 8-16 Age 0-1 Ages 1-8 Ages 8-16

13 100 P = Mean Difference of FEV1, ml Percent NOx exposure during first year of life, µg/m³

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