Chronic hyperplastic eosinophilic sinusitis (CHES) is an inflammatory disease characterized by the accumulation of eosinophils, fibroblasts, mast cells, goblet cells, and stromal tissue. Many immune and pathological features of CHES are shared with asthma including the accumulation of eosinophils but also the presence of T helper lymphocytes having the Th2-like phenotype, and even the same prominent subepithelial basement membrane thickening. Many patients with asthma have CHES and, even though a lower proportion of CHES subjects have asthma, the presence of CHES defines individuals at high risk for its development. Together, these observations suggest that CHES and asthma represent the same disease process involving the upper and lower airways, respectively. It is virtually universally accepted dogma that CHES influences the severity of asthma and that interventions that ameliorate CHES improve asthma. However, this concept is based on observation studies that are highly flawed insofar as respiratory viruses and allergens are important precipitants of both CHES and asthma, suggesting that the apparent association between worsening sinusitis and asthma is merely an epiphenomenon of the shared inflammatory insult. Intervention studies are even more flawed as there has never been a controlled study addressing the actual influence of sinusitis treatment on the natural history of asthma and these subjects all received interventions for their asthma. Each of the mechanisms that have been proposed by which sinus disease could influence the lungs is similarly flawed. It is our hypothesis that sinusitis does influence asthma and that this occurs through its ability to direct a systemic inflammatory response that includes the production and recirculation of Th2-like lymphocytes, eosinophils, basophils/mast cells, and fibrocytes between the sinuses, sinusassociated lymphatic tissue, bone marrow, and the lungs. It is imperative that it be categorically determined whether sinusitis does influence asthma, the mechanistic basis for this association, and, as such, whether further efforts to treat sinusitis is an appropriate intervention in patients with severe persistent asthma. These studies will utilize a sinus allergen challenge to produce a sinusitis exacerbation and surgical intervention to ameliorate sinusitis severity in subjects with sinusitis and asthma.
These specific aims should unambiguously address different aspects of the putative connection between sinusitis and asthma.
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