Over 50% of the US population, more than 162 million people, live with unhealthy levels of ozone. This includes 38 million children. Ozone disrupts lung development, changes lung structure, and exacerbates respiratory disease. Reduced lung functional growth has been found in young adults with histories of ozone exposure as children. Our central hypothesis is that ozone-induced lung remodeling during lung development interacts with other air pollution exposures, such as particulate matter, to contribute to lung disease in adulthood. This R21 is a key initial step towards our long term goal of addressing this hypothesis in a subsequent larger application. Our goal in this application is to establish the extent of ozone-induced distal lung alteration, identify key mechanisms of ozone altered lung growth and to demonstrate the effect of these structural changes on deposition and clearance of a model inhaled ultrafine tracer particle. We will use unique animal, exposure and measurement methods we developed to address existing research gaps about ozone effects on airway and alveolar remodeling. In particular we will define target and nontarget regions of ozone induced lung remodeling and will study the mechanisms of the ozone induced cellular changes including glutathione depletion. We will use juvenile and adult, male and female rats exposed to ozone or filtered air (FA) in 2 Specific Aims that will: 1) Define changes in distal lung structure induced by ozone exposure and 2) Quantify the effect of ozone induced distal lung remodeling on particle deposition and clearance in the lung. A better understanding of the mechanisms and effects of distal lung remodeling in response to ozone exposure during lung development and reduced lung function in adulthood will support regulations that improve human health and will aid in designing therapies to treat ozone-reduced lung function.
Ozone exposure disrupts lung development, changes lung structure, and exacerbates respiratory disease. Yet we understand little about the mechanisms involved in ozone-induced lung remodeling. The goal of this project is to understand how early life exposure to ozone changes lung structure and predisposes to increased adverse effects of particulate matter through increased deposition and decreased clearance.
