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 an additional 30 patients who underwent prospective olfactory testing prior to sinonasal procedures.

Methods: Tissue biopsies were processed for analysis of inflammatory markers using quantitative real time polymerase chain reaction (qRT-PCR). Ipsilateral olfactory performance was assessed using the Sniffin' Sticks (Burghart, Wedel, Germany) threshold component and the University of Pennsylvania Smell Identification Test (Sensonics, Haddon Heights, NJ). Age-adjusted data was correlated with inflammatory marker expression and clinical measures of obstruction from computed tomography and endoscopy.

Results: Gene expression of the eosinophil marker CLC (Charcot Leyden crystal protein) was elevated in superior turbinate (ST) tissue in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) compared to ST and inferior turbinate 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; P = 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, and radiographic and endoscopic findings with olfactory threshold, CLC was the only significantly correlated variable (P < 0.05).

Conclusion: 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.

Level of evidence: NA. Laryngoscope, 127:2210-2218, 2017.

Keywords: Eosinophils; chronic rhinosinusitis; olfactory dysfunction.

Figure 1

Anatomic depiction of the sinonasal cavity and olfactory tract. The left side of the image represents normal anatomy, and the right side of the image demonstrates inflammatory changes that occur in CRSwNP.

Figure 2

Relative expression of RNA markers of A) CLC- a marker for eosinophils, B) IL-5, and C) Eotaxin-1 in superior and inferior turbinate tissue in normal controls, patients with CRSsNP and with CRSwNP. In this representation, more negative numbers signify higher concentrations of CLC. For reference, relative expression of these markers is also shown in polyp tissue. ** p <0.01, *** p < 0.001, ****p <0.0001.

Figure 3

Correlation between the relative expression of CLC and the relative expression of the pro-eosinophil cytokine A) IL-5, and chemokine B) Eotaxin-1 in ST tissue. C) Correlation between CLC gene expression and ECP protein in sinonasal tissue.

Figure 4

Relative expression of neural markers A) GAP-43, and B) OMP from a representative sample of IT and ST biopsies. A specimen was deemed to contain olfactory neuroepithelium if the relative expression was outside the lower limit of the 95% CI for IT biopsies (solid line). From this data, 59% and 43% of samples were deemed to have ON by GAP-43 and OMP analysis respectively.

Figure 5

Correlation between performance on tests of A) olfactory threshold (Sniffin Sticks deviation from the age/sex-matched mean), and B) olfactory discrimination (UPSIT deviation from the age/sex-matched mean), and relative expression of markers for eosinophilia in tissue biopsies of the superior turbinate in normal controls, and patients with CRSsNP and CRSwNP.