Main and interaction effects of gaseous and particulate pollutants on respiratory health in children

Background: The adverse effect of gaseous and particulate pollutants on respiratory health in children constitutes a major public health concern worldwide. Children, especially infants, are particularly susceptible to the detrimental effect of inhaled pollutants due their immature respiratory system. To reduce the burden of respiratory morbidity in children, it must be better understood which gaseous and particulate pollutants threaten children’s respiratory health, particularly in infancy, and what the underlying mechanisms are. Furthermore, biomarker-based analysis must be advanced to improve the diagnosis and treatment of respiratory effects of gaseous and particulate pollutants in children.
Aim: The first aim of this thesis was to further elucidate whether and how air pollution, greenness, and pollen impact the respiratory systems of healthy infants. The second aim was to advance biomarker-based analysis of respiratory morbidity using exhaled breath. More specifically, we aimed to further standardize real-time breath analysis with secondary electrospray-high resolution mass spectrometry (SESI-HRMS) and to evaluate its use for non-invasive prediction of oxidative stress and airway inflammation in children.
Methods: Flexible regression models were applied to investigate the associations of individual air pollution, greenness, and pollen exposure with the nasal microbiota and respiratory symptoms, respectively, in infants of the Basel-Bern Infant Lung Development (BILD) cohort. Two standardization studies in adults were conducted to benchmark breath analysis with SESI-HRMS and to demonstrate an interoperability framework for this method. Prediction of urinary oxidative stress and airway inflammation markers using this method was tested in children from smoking and non-smoking households.
Results: We found that air pollution impacts the nasal microbiota during infancy and that pollen exposure increases the risk of respiratory symptoms during this vulnerable time. As expected, effect sizes were rather small. Breath analysis with SESI-HRMS showed promising potential for detection of such small effects. As proof of principle, we have shown that even low levels of oxidative stress in children can be predicted with real-time SESI-HRMS.
Conclusion: This thesis provides relevant novel evidence on the association of gaseous and particulate pollutants with respiratory morbidity in children. Our results suggest that the effect of pollen and air pollution on respiratory morbidity in children results from an interplay of various risk factors, interactions, and mechanisms in the respiratory system that is more complex than expected. Effective environmental policies lowering pollen and air pollution exposure are required, to reduce the burden of respiratory morbidity in infants. Furthermore, accurate monitoring of processes in the lungs triggered by gaseous and particulate pollutants is necessary, to prevent the development and progression of respiratory diseases in children. Using oxidative stress as an example, real-time breath analysis with SESI-HRMS has shown promising potential for the detection of even small changes in the airway at molecular level.