Abstract from the application submitted under RFA 16-1:
Impact of Exposure to Air Pollution on Asthma: a Multi-Exposure Assessment
Marie Pedersen, University of Copenhagen
Asthma is the most common chronic disease in children. There is growing experimental and epidemiological evidence that exposure to ambient air pollution from combustion such as motor vehicle emissions not only exacerbates existing asthma, but also contributes to the development of asthma. Asthma has a complex multifactorial etiology, which is still not fully understood, as multiple factors starting from fetal life, may interact. Some of these factors may be correlated, share sources and biological pathways resulting in joint effects that are greater than additive. Thus, the potential for confounding and multiple modifications of the ambient air pollution exposure effects on asthma is very high. The role of early-life exposure to ambient air pollution on the asthma pandemic remains poorly understood due to the lack of large, comprehensive, longitudinal birth cohort studies with sufficient long follow-up and assessment of multiple exposures to air pollution including outdoor and indoor sources.
The aim of the proposed research is to test the hypothesis that early-life exposure to air pollution from multiple outdoor and indoor sources have individual and joint effects on risk of development of asthma in children and adolescents. Furthermore, I seek to determine the mechanistic basis for these effects by studying changes in lung function, inflammation, immunological markers and airway DNA methylation.
Through a number of large longitudinal birth cohort studies relying on state-of-the-art methods I will test this hypothesis. Unique material on individual health, home, home neighborhood and personal characteristics from National registers will be used for prospective studies of all children and adolescents born in Denmark since 1997 (N=1,152,175) together with detailed questionnaire data from the Danish National Birth Cohort (DNBC, N=90,000) and repeated measurements of lung function and biomarkers from the COPenhagen Prospective Studies on Asthma in Childhood (COPSAC, N=1,000). Early-life exposure to outdoor air pollution with nitrogen dioxide (NO2), nitrogen dioxides (NOX), particulate matter (PM10 and PM2.5 from all sources and for the first time also from wood stoves), carbon monoxide (CO), elemental carbon (EC), black carbon (BC), organic carbon, (OC), ozone (O3), sulphur dioxide (SO2) and ammonium (NH4) will be estimated at home addresses with validated and novel prediction models. Register and questionnaire data on asthma incidence from birth to 18 years of age (i.e. hospitalization, medicine prescriptions and parental records of doctor-diagnosis), home characteristics (e.g. type of house, heating source, cooking, ventilation, pets), home neighborhood (e.g. urban vs. rural, distance to farm) will be evaluated. Confounding and effect modification by personal characteristics (e.g. family history of asthma, smoking, breast feeding, parity, SES, pets, obesity) and exposures will be considered. Traditional (e.g. one pollutant and two-pollutant models) and advanced, more efficient, statistical methods will be evaluated to assess the independent and joint effects of exposures to air pollution from multiple sources.
The proposed studies will be the first to consider all of these issues in such a comprehensive manner. These elegant and complementary studies offer unique opportunities to better understand the role of specific sources of air pollution on asthma development and the mechanisms of the asthma pandemic. My long-term objective is to provide new information needed for risk assessment. This information will be useful to better target strategies for protection of respiratory health, to understand and to reduce the risk associated with different sources of air pollution. The findings may have profound implications for public health, given the large burden associated with asthma and the ubiquity of air pollution exposure worldwide.