Project 2 - Local Biological Response Profiles in the Lower Respiratory Tract

University Of Alabama At Birmingham, Birmingham AL

Investigators

Linked publications, trials & patents

Abstract

Approximately half of the US population continues to be impacted by pathogenic air pollutants such as[unreadable] ozone (O3), which recent epidemiologic studies suggest induces long term functional impairments in[unreadable] children. The mechanisms of exposure-related lung injury and how age and exposure history govern acute[unreadable] and chronic susceptibility in the post natal lung remain poorly understood. Novel evidence documents that[unreadable] postnatal, episodic O3 exposure profoundly alters lung growth, structure, and function in non-human[unreadable] primates. Biological effects are likely determined by the combination of O3 intrapulmonary dispersion and[unreadable] reaction/diffusion within the epithelial lining fluid (ELF), leading to generation of the local dose. The overall[unreadable] hypothesis of this program is that the age-, site-, cell-, and exposure history-related susceptibilities to acute[unreadable] versus episodic O3 result from differences in ELF-dependent interactions associated with spatial[unreadable] heterogeneities in the local dose coupled with differential regulation of the airway epithelial intracellular and[unreadable] ELF antioxidant pools.[unreadable] Project 2 focuses on the tracheobronchial airways. The overall hypothesis being addressed by Project 2 is[unreadable] that four characteristics of immature airways contribute to the heightened susceptibility of infants to oxidant[unreadable] exposure: 1) immature airway structure and cellular organization; 2) alterations in thickness of the epithelial[unreadable] lining layer; 3) local differences in levels of cellular and extracellular antioxidants; and 4) airway specific[unreadable] differences in the ability to generate an inflammatory response.[unreadable] Project 2 will pursue three specific aims:[unreadable] 1) Determine the impact of age-related differences on this site specific pattern of injury and inflammation[unreadable] following an acute episode of ozone exposure;[unreadable] 2) Determine if ozone exposure during the postnatal period of lung development alters the site specific[unreadable] pattern of injury and inflammation found after an acute episode of ozone exposure later in life;[unreadable] 3) Define the impact of ozone exposure during the postnatal period of lung development on the ability of[unreadable] airways to mount an acute inflammatory response to bacterial lipopolysaccharide (LPS) later in life.[unreadable] Our efforts will advance understanding of the fundamental mechanisms of O3-related disruption of normal[unreadable] lung development, lung injury, and susceptibility; and generate unique characterizations of lung structure[unreadable] and biochemistry.