15 January, 2019

Early life exposure to traffic-related air pollution and lung function in adolescense. A birth-cohort study Erica S Schultz MD, PhD-student J.Hallberg, T.Bellander, A.Bergström, M.Bottai, O.Gruzieva, P.Thunqvist, M.Wickman, G.Pershagen, E.Melén

Background Lung function is an easily measurable and reliable indicator of the physiological state of lungs and airways Lung function also predicts mortality in the general population Studies indicate that adverse long-term effects of traffic related air pollution occur on lung function growth in children Possible pathway: Air Pollutants → Free radicals → Oxidative stress → Airway inflammation → Lung function impairment Lung function is an easily measurable and reliable indicator of the physiological state of lungs and airways. Lung function also predicts mortality in the general population, even among non-smokers with only modesdtly reduced lung function. Evidence that adverse long-term effects of Traffic Related Air Pollution (TRAP) occur on lung function growth in children Possible pathway: Air Pollutants → Free radicals → Oxidative stress → Airway inflammation → Lung function impairment Ref 1. Wilk Genet epidemiology 2000, ref2, Schunrmann HJ, Chest 2000, ref3, Gauderman Nejm 2004 or Lancet 2007 15 January, 2019

Key issue Time periods of exposure and susceptibility 15 January 2019

AJRCCM 2012;186(12):1286-91 15 January 2019

Aims To investigate the effect of individual long term exposure to air pollution from traffic on children’s lung function at 16 yrs of age To clarify if critical time periods of exposure and susceptible populations can be identified

Exposure questionnaire 4,089 - 100% Material and Methods Exposure questionnaire 4,089 - 100% 8 year follow up Questionnaire 3431 84 % Spirometry 2613 64 % Blood 2461 60% 1 year questionnaire 3,925 - 96% 12 year questionnaire 2900 – 71% 2 year questionnaire 3,843 - 94% 16 year follow up Questionnaire 3200 78% Spirometry 2400 59% Blood 2500 61% 4 year follow up Questionnaire 3720 91 % Dust 3610 97 % PEF 2966 80 % Blood 2614 66 % My study population comprise of study participants with full set of confounders mainly derivied from Exposure questionnaire (0 years), spirometry data from 16 years as well as all air pollution exposure time periods available. 15 January 2019

Air pollution Assessment Address history Geocoding NOₓ from traffic On this slide, I am going to try and explain the method of this historical air pollution assessment. First, we used data on the residential history of each subject, which they reported in the questionnaire. Then we translated all addresses into geographical coordinates (using GIS and a regional address database.) These coordinates were then linked to dispersion models for different air pollutants, and they describe the geographical distribution of air pollution in different geographical resolutions, down to resolutions of 25 m grids. These dispersion models are based on historical emission databases Then, we did a linear interpolation for the years between these emission databases for each address, and we finally end up with an individual level of different air pollutants for each subject in the study. Individual air pollution exposure for Nox and PM10 up to 8 years of age is available for more than 4000 children. Nox (NO2 NO) is directly emitted from fuel combustion. Reduced since introduction of cleaning techniques in power plant and catalytic converters in petrol cars. (Historical emission databases for NOx were available for the years 1990, 1995, 2000, 2002-2004,2006 and 2010) Pm10, particles equal or less than 10 um in diameter. Largest mass is derived from organc or inorganic fragments in dust of from road and vehicle wear. (fine particles are emitted from combustion processes of fossil fuel. 2008 Dispersion modelling based on emission databases Median NOx = 17 ɥg/m³ 15 januari 2019

Exposure time windows First year of life 1-4 years 4-8 years 12-16 is upcoming 15 January 2019

Results FEV1 at 16 years in relation to traffic-NOx exposure in different time periods of life First year of life 1-4 years 4-8 years 8-12 years Adjusted for age, gender, height, heritability of allergic diseases, smoking, and municipality. 15 January 2019

FEV1 at 16 years in relation to traffic-NOx exposure in the first year of life 15 January 2019

Association between first year of life exposure to NOx and FEV1 less then 80% of predicted OR 2.3 (95% CI 0.9 to 6.5). Associations were also suggested between first year of life exposure to NOx and clinically important lung function deficits of less than 80% of predicted FEV1 with an odds ratio of 2.3 (95% CI 0.9 to 6.5). For 5% lowest percentile of zscore FEV1 the corresponding odds ratio is1.8 (95%CI 0.8 to 4.2) *Prediction based on age,height,gender and weight and interactions of gender with age, height and weight. 15 January 2019

Conclusion Our results indicate that exposure to traffic-related air pollution during infancy negatively affects lung function in adolescents at 16 years of age. 15 January 2019

Acknowledgements We thank all participating children and parents in BAMSE 15 January 2019

Thank you! Erica S Schultz MD, PhD-student Unit of Environmental Epidemiology Institute of Environmental Medicine Karolinska Institutet