Chronic rhinosinusitis (CRS) is a major human health problem which significantly reduces quality of life. While various microorganisms have been implicated in CRS, there is little or no rational basis for the widespread prescribing of antibiotics and corticosteroids for its treatment. The overall goal of this study is therefore to determine the effects of antibiotics and corticosteroids on the sinus microbiome, host inflammation and clinical outcome in chronic rhinosinusitis. In the proposed research we will develop, for the first time, a unilateral animal (rabbit) model of CRS that accurately reflects the chronic nature of this disease. This model will provide a unique opportunity to systematically evaluate the effect of antibiotics and corticosteroids on the sinonasal microbiota and the associated inflammatory response. Information on the clinical outcomes obtained from these experiments, coupled with in-depth analyses of our existing clinical and microbiome data sets, should refine future treatments for CRS.