Impact of the environment and lifestyle on the respiratory health of adolescents : application of non‐invasive biomarkersof airway damage or inflammation

(eng) In this project we investigated whether lung‐specific biomarkers measureable via non‐invasive methods allow an evaluation of the respiratory system and an assessment of the impact of factors related to everyday’s environment (wood fuel use) or lifestyle (cigarette smoking). The mechanistic understanding related to changed levels of the Clara cell protein (CC16) in serum and their relationship to changes of the Clara cell population in the lung was further elaborated in 2 in vivo studies. In an inhalation experiment with rats, CC16 in serum was found to be a very sensitive marker of permeability changes of the lung epithelial barrier. In an in vivo model investigating the interaction of elemental carbon ultrafine particles and allergy, the levels of CC16 in BALF and serum paralleled morphological changes in the respiratory tract. This demonstrated the relevance of the Clara cell population with respect to the inflammatory status of the lung and the usefulness of monitoring CC16 in BALF or serum as a marker of the lung status. A battery of non‐invasive markers, i.e. CC16 in nasal lavage fluid and serum, albumin in nasal lavage fluid, surfactant associated protein D (SPD) in serum, and nitric oxide (NO) in exhaled breath was used in 2 cross‐sectional studies on adolescents. We demonstrated the usefulness and sensitivity of two noninvasive approaches, i.e. CC16 in nasal lavage fluid and NO in exhaled breath, to detect early changes in the respiratory system of adolescent smokers well before the appearance of changes in the deeper lung or altered lung function parameters. In a study on non‐smoking adolescents, wood fuel use showed to be associated with a decrease of the CC16 to SPD ratio in serum; a change suggesting epithelial changes in the respiratory tract. Additionally, higher frequencies of asthma, hay fever and sensitization against pollen were observed among adolescents with wood fuel use. Using non‐invasive approaches enabled us to screen a large study population and to identify significant and objective differences in the status of the respiratory system between exposed and non‐exposed adolescents (non‐smokers vs. smoker or no wood fuel use vs. wood fuel use). Exploratory studies investigating the applicability of the exhaled breath condensate showed that the methodological requirements to make the assay robust too burdensome to foresee a powerful diagnostic application of this assay in the near future. Overall, we were able to illustrate that non‐invasive biomarkers have the potential to allow the successful screening of large study populations or the repeated measurements of diseased individuals by yielding objective data with high sensitivity. Nevertheless, before these approaches can be routinely used, the methodological performance and robustness of the assays will have to be further improved and the mechanistic investigations which contribute to the understanding of the different parameters influencing the assay outcome will have to be continued.