Olfactory cleft mucus proteins associated with olfactory dysfunction in a cohort without chronic rhinosinusitis

Int Forum Allergy Rhinol. 2019 Oct;9(10):1151-1158. doi: 10.1002/alr.22391. Epub 2019 Aug 23.

Abstract

Background: Olfactory dysfunction (OD) is a common problem, affecting up to 20% of the general population. Previous studies identified olfactory cleft mucus proteins associated with OD in chronic rhinosinusitis (CRS) but not in a healthy population. In this study we aimed to identify olfactory cleft mucus proteins associated with olfaction in individuals without sinus disease.

Methods: Subjects free of sinus disease completed medical history questionnaires that collected data regarding demographics, comorbidities, and past exposures. Olfactory testing was performed using Sniffin' Sticks, evaluating threshold, discrimination, and identification. Olfactory cleft mucus (OC) and, in select cases, inferior turbinate mucus (IT) were collected with Leukosorb paper and assays performed for 17 proteins, including growth factors, cytokines/chemokines, cell-cycle regulators, and odorant-binding protein (OBP).

Results: Fifty-six subjects were enrolled in the study, with an average age of 47.8 (standard deviation [SD], 17.6) years, including 33 females (58.9%). The average threshold/discrimination/identification (TDI) score was 30.3 (SD, 6.4). In localization studies, OBP concentrations were significantly higher in OC than IT mucus (p = 0.006). Cyclin-dependent kinase inhibitor 2A (CDKN2A/p16INK4a), basic fibroblast growth factor (bFGF), chemokine ligand 2 (CCL2/MCP-1), granulocyte macrophage colony-stimulating factor (GM-CSF), and chemokine ligand 20 (CCL20/MIP-3a) all inversely correlated with overall TDI (all rho ≥ -0.479, p ≤ 0.004). Stem cell factor (SCF) correlated positively with overall TDI (rho = 0.510, p = 0.002).

Conclusion: Placement of Leukosorb paper is relatively site-specific for olfactory proteins and it is feasible to collect a variety of olfactory cleft proteins that correlate with olfactory function. Further study is required to determine mechanisms of OD in non-CRS subjects.

Keywords: anosmia; cytokines; growth factor; hyposmia; nasal mucosa; olfaction; olfactory disorders; olfactory test.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Chronic Disease
  • Cohort Studies
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Diagnosis, Differential
  • Female
  • Fibroblast Growth Factor 2 / metabolism
  • Humans
  • Male
  • Middle Aged
  • Mucus / metabolism*
  • Nasal Cavity / pathology*
  • Olfaction Disorders / diagnosis
  • Olfaction Disorders / metabolism*
  • Olfactory Mucosa / metabolism*
  • Olfactory Mucosa / pathology
  • Receptors, Odorant / metabolism
  • Rhinitis / diagnosis
  • Rhinitis / metabolism*
  • Sinusitis / diagnosis
  • Sinusitis / metabolism*

Substances

  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Receptors, Odorant
  • odorant-binding protein
  • Fibroblast Growth Factor 2