Chronic rhinosinusitis (CRS) is one of the most common causes of impaired olfaction, including subtypes with and without nasal polyps (CRSwNP and CRSsNP). Although olfactory dysfunction is highly prevalent in patients with CRS, very little is known about its immunopathology and current clinical staging of CRS often fails to correlate with olfactory dysfunction. As a result, impaired smell is often overlooked clinically and remains one of the most troubling and difficult features of the disease to treat. Prior studies of olfactory dysfunction in CRS have shown few correlations with specific immune or clinical parameters. Investigations of the immune profile have focused upon the presence of inflammatory cells in sinus mucosa as opposed to the olfactory cleft. Computed tomography (CT) and endoscopic measures of CRS have also been poor predictors of olfactory dysfunction, again, likely because they focus upon measuring severity of inflammation in the paranasal sinuses with no attention paid to the olfactory cleft. Similarly, the most commonly utilized CRS-specific QOL instruments include few if any questions related to olfaction. Thus, it is not surprising that these relatively broad measures of CRS disease severity fail to predict olfactory dysfunction. This cross-sectional study will perform detailed objective olfactory testing in patients with CRS and relate these findings with refined clinical measures of olfactory-specific disease severity to include the inflammatory cytokine profile of the olfactory cleft, olfactory specific quality-of-life (QOL), and CT and endoscopic grading of the olfactory cleft. The overarching focus of this proposal is to identify clinically-relevant, olfactory-specific measures f disease severity which correlate with objective olfactory dysfunction.
Aim 1 will determine whether local cytokine profiles correlate with objective olfactory function in patients with CRS. Our hypothesis is that pro-inflammatory cytokines will correlate with objective olfactory testing and this profile will differ between CRS subtypes. We expect CRSwNP to display a more Th2-skewed profile, CRSsNP a mixed Th1/Th2 profile, and there to be some overlap of involved cytokines between subgroups.
Aim 2 will determine whether olfactory-specific disease severity measures correlate with objective olfactory function and compare this to existing CRS-specific measures. Our hypothesis is that olfactory-specific disease severity measures will correlate with objective olfactory function more robustly than broad, non-specific measures for both CRSwNP and CRSsNP subtypes. Findings from this study will provide important preliminary data for a planned R01 submission which will longitudinally examine those factors, clinical and immunologic, which impact olfaction and predict response to medical and surgical treatment. This data will lay the groundwork for future mechanistic studies of olfactory dysfunction to determine the cellular sources and specific pathways for key olfactory-related cytokines and determine whether targeted reduction results in improved olfaction.
Olfactory dysfunction is one of the defining features of chronic rhinosinusitis and is associated with significant declines in health-related quality-of-life. This proposal seeks to characterize the inflammatory cytokine profile associated with olfactory dysfunction in chronic rhinosinusitis and identify those clinical disease severity metrics which best predict olfactory loss. This data will guide the design of future studies which will explore whether targeted cytokine reduction improves olfaction and will allow for development of predictive models of olfactory dysfunction in chronic rhinosinusitis.
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