Superior turbinate eosinophilia correlates with olfactory deficit in chronic rhinosinusitis patients

Abstract

Objective To evaluate if molecular markers of eosinophilia in olfactory enriched mucosa are associated with olfactory dysfunction. Study Design Cross-sectional study of tissue biopsies from 99 patients, and a further 30 patients who underwent prospective olfactory testing prior to sinonasal procedures. Methods Tissue biopsies were processed for analysis of inflammatory markers using qRT-PCR. Ipsilateral olfactory performance was assessed using the Sniffin Sticks threshold component and the UPSIT and age-adjusted data was correlated with inflammatory marker expression and clinical measures of obstruction from CT and endoscopy. Results Gene expression of the eosinophil marker CLC (Charcot Leyden crystal protein) was elevated in superior turbinate (ST) tissue in CRS with nasal polyps (CRSwNP) compared to ST and inferior turbinate (IT) tissue in CRS without nasal polyps (CRSsNP) and control patients (all p < 0.001 respectively). CLC in ST tissue was correlated with IL-5 and eotaxin-1 expression (all p<0.001; r = 0.65 and 0.49 respectively). CLC expression was strongly correlated with eosinophilic cationic protein levels (p<0.001; r=0.-76) and ST CLC expression was inversely related to olfactory threshold (p = 0.002, r = −0.57) and discrimination scores (p = 0.05, r = −0.42). In multiple linear regression of CLC gene expression, polyp status, radiographic and endoscopic findings with olfactory threshold, CLC was the only significantly correlated variable (p<0.05). Conclusions Markers of eosinophils are elevated in the ST of patients with CRSwNP and correlate with olfactory loss. These findings support the hypothesis that olfactory dysfunction in CRS correlates local eosinophil influx into the olfactory cleft.

Correlation of mucus inflammatory proteins and olfaction in chronic rhinosinusitis

“…Although the inflammation seen in OC histopathology usually mirrored that seen in the sinus mucosa proper, OC inflammation was not seen in all patients with CRS. Additional studies have demonstrated similar histopathologic changes in the OC of patients with CRS, with several recent studies highlighting the potential impact of local eosinophilia …”

“…The most important limitation is the difficulty performing an olfactory biopsy. A number of studies described techniques to harvest OC mucosa, some in the clinic setting, but none indicated widespread adoption . Furthermore, these biopsies, by necessity, sample a focal region of the OC cleft on a single side.…”

“…Additional studies have demonstrated similar histopathologic changes in the OC of patients with CRS, with several recent studies highlighting the potential impact of local eosinophilia. 10,13 Biopsies of OC mucosa have advantages, but there are distinct drawbacks that limit their clinical usefulness. The most important limitation is the difficulty performing an olfactory biopsy.…”

“…A number of studies described techniques to harvest OC mucosa, some in the clinic setting, but none indicated widespread adoption. 10,[13][14][15] Furthermore, these biopsies, by necessity, sample a focal region of the OC cleft on a single side. Given the often patchy geographic distribution of OC mucosa and potential asymmetry of CRS involvement, a focused biopsy may not be representative.…”

A prospective analysis evaluating tissue biopsy location and its clinical relevance in chronic rhinosinusitis with nasal polyps

“…9–13 It is additionally recognized that the presence of NP and eosinophilia at the time of sinus surgery are also associated with increased rates of postsurgical medication use, recurrence, and revision sinus surgery. 14–20 Thus, accurately identifying patients at risk for recurrence is important for tailoring individualized treatment plans.…”