The theme of this proposed SCOR program is to investigate the etiology and pathogenesis of airway disease in children from rural communities. We chose this theme for the following reasons: 1) asthma is the most common chronic illness in children; 2) the rural setting introduces unique environmental exposures that are known to play a role in the development of airway disease; 3) environmental models of asthma provide an ideal opportunity to investigate fundamental issues in childhood asthma such as the biological origin and persistence of airway disease; and 4) this theme builds on existing scientific expertise and ensures a highly interactive program. Since grain dust and endotoxin are common in the rural setting and both are associated with acute and chronic forms of airway disease, we have used these very relevant exposures to further focus the projects in our proposed SCOR program. The end result is a highly integrated and focused program that, in aggregate, will substantially enhance our understanding of airway disease in children. The primary hypothesis unifying this research program is that understanding the etiology and pathogenesis of airway disease in children from rural communities will provide the scientific rationale to develop primary, secondary, and tertiary preventive programs that reduce the morbidity and mortality of asthma in the rural setting. The project specific hypotheses within this SCOR proposal are: . Project 1: Environmental intervention is an essential component of an asthma intervention program that must be coordinated with other improvements in health care to reduce the prevalence and severity of asthma among children from rural communities. . Project 2: Many of the biologic features of acute and reversible airway inflammation are fundamental to the development of chronic grain dust induced airway disease. . Project 3: Mechanisms that initiate, promote, and resolve grain dust induced inflammation may be distinct from those mechanisms involved in LPS induced airway inflammation. . Project 4: Respiratory syncytial virus infection up-regulates the response of airway epithelium to LPS.

P01ES009607

1998-11-01

2004-10-31