Olfactory cleft mucus inflammatory proteins in CRS: a case-control study

Timothy L Smith; Rodney J Schlosser; Zachary M Soler; Jess C Mace; Jose L Mattos; Vijay R Ramakrishnan; Daniel M Beswick; Jeremiah A Alt; Jennifer K Mulligan

doi:10.1002/alr.22770

Olfactory cleft mucus inflammatory proteins in CRS: a case-control study

Int Forum Allergy Rhinol. 2021 Sep;11(9):1321-1335. doi: 10.1002/alr.22770. Epub 2021 Feb 24.

Authors

Timothy L Smith¹, Rodney J Schlosser^{2

3}, Zachary M Soler², Jess C Mace¹, Jose L Mattos⁴, Vijay R Ramakrishnan⁵, Daniel M Beswick⁵, Jeremiah A Alt⁶, Jennifer K Mulligan⁷

Affiliations

¹ Division of Rhinology and Sinus/Skull Base Surgery, Department of Otolaryngology-Head and Neck Surgery, Oregon Health & Science University, Portland, OR.
² Division of Rhinology and Sinus Surgery, Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, SC.
³ Department of Surgery, Ralph H. Johnson VA Medical Center, Charleston, SC.
⁴ Division of Rhinology and Sinus Surgery, Department of Otolaryngology-Head and Neck Surgery, University of Virginia, Charlottesville, VA.
⁵ Department of Otolaryngology, Head and Neck Surgery, University of Colorado-Anschutz Medical Campus, Aurora, CO.
⁶ Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Utah, Salt Lake City, UT.
⁷ Division of Pulmonary, Critical Care & Sleep Medicine, University of Florida, Gainesville, FL.

Abstract

Background: Multiple hypotheses are evolving that suggest several, potentially overlapping etiologies for olfactory dysfunction (OD) in chronic rhinosinusitis (CRS). Understanding inflammatory cytokine profiles of the olfactory cleft (OC) and their association with olfactory function is foundational for future clinical care and research.

Methods: This cross-sectional, case-control study evaluates associations among OC mucus inflammatory proteins, psychophysical olfactory testing, and computed tomography (CT) analysis of the OC and sinuses. Normative reference intervals were determined for each protein and odds ratios (ORs) were used to compare proportions of altered expression between CRS without nasal polyposis (CRSsNP) and CRS without nasal polyposis (CRSwNP).

Results: Case subjects with CRS (n = 151) and controls (n = 74) were evaluated. A majority of OC proteins tested were found within detectable ranges for cases and controls. The CRS cohort had significantly higher concentrations for 23 of 26 proteins. CRS cases with abnormal levels of C-C motif chemokine ligand 2 (CCL2), CCL3, interleukin 5 (IL5), IL10, and IL13 associated with greater olfactory deficits. The prevalence of elevated IL5 and IL13 in anosmic patients was 64.6% and 62.5%, respectively (p < 0.004). CRS cases with the highest odds of elevated expression in CRSwNP were IL5 (OR = 10.83) and IL13 (OR = 8.36). However, both IL5 and IL13 were still elevated in approximately 14% of CRSsNP patients. The highest magnitude of correlation between the total percent of OC opacification was found to be with IL5 (r = 0.543; p < 0.001), whereas other moderate correlations were noted with immunoglobulin E (IgE), IL10, and IL13.

Conclusion: This study confirmed that OC inflammatory proteins vary both by disease phenotype and in their association with OD. Type 2 inflammatory mediators are increased in CRS, especially within the CRSwNP group. However, a substantial proportion of CRSsNP also express type 2 inflammatory mediators. Further research is necessary to understand the complex roles OC mucous inflammatory proteins might play in defining endotype and in impacting CRS-related OD. ©2021 ARSAAOA, LLC.

Keywords: chronic disease; inflammation; olfaction; outcome assessment (health care); sinusitis; smell, proteins.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Case-Control Studies
Chronic Disease
Cross-Sectional Studies
Humans
Mucus
Nasal Polyps*
Rhinitis* / epidemiology
Sinusitis*

Grants and funding

R01 DC005805/DC/NIDCD NIH HHS/United States