Project 2

Chronic rhinosinusitis (CRS) affects nearly 30 million Americans, has direct costs of approximately $6B annually and is responsible for almost 500,000 surgeries per year. Investment in research on CRS has been modest and our knowledge of the epidemiology, genetics and pathogenesis of CRS is rudimentary. A major goal of the Chronic Rhinosinusitis Integrative Studies Program (CRISP) project is to perform highly collaborative studies to develop fundamental knowledge on the genetic polymorphisms responsible for CRS susceptibility and severity; the states, traits, environmental risk factors and costs of CRS; and the mechanisms of exacerbations and immunological basis of severe recalcitrant disease. CRISP has five main elements. Core A is the administrative Core led by Dr. Robert Schleimer, the PI of the program; Core B is the Clinical, Laboratory and Data Management Core led by Dr. Robert Kern; Project 1 studies the Epidemiology of CRS and is led by Dr. Brian Schwartz; Project 2 studies the Immunology of CRS and mechanisms of exacerbation and is led by Dr. Schleimer; and Project 3 focuses on the Genetics of CRS and is led by Dr. Carole Ober. Studies in Project 1 define the epidemiology of CRS in a large (>300,000) primary care population at Geisinger Health Systems (GHS). The Genetics studies in Project 3, based at the University of Chicago, utilize samples from 2000 patients and controls from Project 1 to identify CRS disease genes and to associate genetics with disease states, severity and environmental exposures. Candidate genes for genetic studies will be discovered via a novel systems genetics discovery platform based on collaboration between Project 3 and Project 2. A collaboration between Project 1 and Project 2, based at Northwestern University, will assess the pathogens associated with exacerbations of CRS and the role of autoimmunity in driving severe disease. Project 2 will also test the importance of B lineage cells and nasal autoimmune responses in the etiology of severe recalcitrant CRS. These collaborative studies will leverage an improved definition of sub-phenotypes of disease to identify unrecognized genetic susceptibilities and important molecular and cellular mechanisms responsible for the development and severity of CRS.