Modeling long-term effects attributed to nitrogen dioxide (NO₂) and sulfur dioxide (SO₂) exposure on asthma morbidity in a nationwide cohort in Israel

ABSTRACT

Studies have provided extensive documentation that acutely elevated environmental exposures contribute to chronic health problems. However, only attention has been paid to the effects of modificate of exposure assessment methods in environmental health investigations, leading to uncertainty and gaps in our understanding of exposure– and dose–response relationships. The goal of the present study was to evaluate whether average or peak concentration exerts a greater influence on asthma outcome, and which of the exposure models may better explain various physiological responses generated by nitrogen dioxide (NO₂) or sulfur dioxide (SO₂) air pollutants. The effects of annual NO₂ and SO₂ exposures on asthma prevalence were determined in 137,040 17-year-old males in Israel, who underwent standard health examinations before induction to military service during 1999–2008. Three alternative models of cumulative exposure were used: arithmetic mean level (AM), average peak concentration (APC), and total number of air pollution exposure episodes (NEP). Air pollution data for NO₂ and SO₂ levels were linked to the residence of each subject and asthma prevalence was predicted using bivariate logistic regression. There was significant increased risk for asthma occurrence attributed to NO₂ exposure in all models with the highest correlations demonstrated using the APC model. Data suggested that exposure–response is better correlated with NO₂ peak concentration than with average exposure concentration in subjects with asthma. For SO₂, there was a weaker but still significant exposure response association in all models. These differences may be related to differences in physiological responses including effects on different regions of the airways following exposure to these pollutants. NO₂, which is poorly soluble in water, penetrates deep into the bronchial tree, producing asthmatic manifestations such as inflammation and increased mucus production as a result of high gaseous concentrations in the lung parenchyma. In contrast, SO₂, which is highly water soluble, exerts its effects rapidly in the upper airways, leading to similar limited correlations at all levels of exposure with fewer asthmatic manifestations observed. These data indicate that differing exposure assessment methods may be needed to capture specific disease consequences associated with these air pollutants.

Acknowledgments

The authors acknowledge assistance and information provided by Dr. Levana Kordova and Ms. Ela Green (Israel Ministry of Environmental Protection), Ashkelon, Ashdod-Yavneh, Hedera, and Haifa Unions of Towns for environmental protection, and Israel Electric Corporation. Our gratitude is also due to Ms. Natalya Rybnikova (Department of Natural Resources & Environment Management, Faculty of Management, University of Haifa) for her help with processing of air pollution data. We thank Shifra Fraifeld for her editorial assistance during manuscript preparation.