19 Does Developmental Status and age of the Lung Influence the Hazard Elicited by Exposure to Both Indoor and Outdoor Pollutants?

Abstract

Abstract Many in vitro studies that focus upon lung toxicology use models that assume, or are specifically based upon adult lung structure, function, and physiology. Yet, the most vulnerable groups of the human population (i.e., young, elderly, and diseased) have an altered lung structure and function. Notably, the developing lung (in utero) and infant lungs exhibit notable differences in term of cell type, number, ratio, organ size and surface area. Recent work has identified the detrimental implications of being exposed to AP while the lung is developing. To elucidate the mechanisms associated with AP exposure to the developing lung, the aim of this study will create and characterise an in vitro model of the foetal human bronchial region composed of cells physiologically appropriate to various stages of development, as well as an older child’s airway, notably the developing alveoli. This will allow us to determine the developmental effects of air pollution particles at an air-liquid interface (ALI) utilising a physiologically relevant aerosol exposure and standardised particulate aiming to mimic indoor and outdoor air pollution. For this work, a global approach will be utilised to determine up and down regulation of various pathways associated with both development and exposure to AP. A further aim will include comparison with an “adult” lung to analysis the potential developmental implications exposure to AP may illicit. This project is funded by the recently initiated RESPIRE project (NE/W002264/1), as part of the SPF Clean Air Programme.