Olfactory and Middle Meatal Cytokine Levels Correlate With Olfactory Function in Chronic Rhinosinusitis

Objectives/Hypothesis: The etiology of chronic rhinosinusitis (CRS)-associated olfactory loss is unclear, but may result from inflammatory changes in the olfactory epithelium that result in signaling dysfunction or loss of olfactory neurons. Several proinflammatory cytokines have been associated with CRS, but their expression within the olfactory cleft microenvironment and association with olfactory function is unknown. Study Design: Prospective case-control study. Methods: Mucus was collected from the olfactory cleft and middle meatus of 31 CRS without nasal polyps subjects, 36 CRS with nasal polyps (CRSwNP) subjects, and 12 healthy controls. Olfactory function was assessed using the validated Smell Identification Test (SIT). Site-specific levels of 14 cytokines/chemokines (interleukin [IL]-1 beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17A, tumor necrosis factor-alpha, Eotaxin, RANTES [regulated on activation, normal T cell expressed and secreted]) were assessed using a multiplex flow cytometric bead assay and correlated with SIT scores. Results: Mucus cytokine levels in the olfactory cleft were strongly or moderately correlated with levels in the middle meatus for all but one measured inflammatory mediators. SIT scores were inversely correlated with levels of IL-2 (P = .006), IL-5 ( P < .0001), IL-6 (P = .0009), IL-10 (P < .0001), and IL-13 (P < .0001), with significance largely driven by CRSwNP patients. Conclusions: The inflammatory microenvironment within the olfactory cleft mirrors that within the middle meatus. Elevated levels of IL-2, IL-5, IL-6, IL-10, and IL-13 in olfactory cleft mucus are associated with reduced olfactory identification scores in CRS patients. Altered levels of select olfactory mucus cytokines could potentially have deleterious effects on olfactory neuron function and turnover.