PMID- 33629532 OWN - NLM STAT- MEDLINE DCOM- 20211025 LR - 20220902 IS - 2042-6984 (Electronic) IS - 2042-6976 (Print) IS - 2042-6976 (Linking) VI - 11 IP - 9 DP - 2021 Sep TI - Olfactory cleft mucus inflammatory proteins in CRS: a case-control study. PG - 1321-1335 LID - 10.1002/alr.22770 [doi] AB - 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. (c)2021 ARSAAOA, LLC. CI - (c) 2021 ARS-AAOA, LLC. FAU - Smith, Timothy L AU - Smith TL AUID- ORCID: 0000-0002-6424-7083 AD - Division of Rhinology and Sinus/Skull Base Surgery, Department of Otolaryngology-Head and Neck Surgery, Oregon Health & Science University, Portland, OR. FAU - Schlosser, Rodney J AU - Schlosser RJ AD - Division of Rhinology and Sinus Surgery, Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, SC. AD - Department of Surgery, Ralph H. Johnson VA Medical Center, Charleston, SC. FAU - Soler, Zachary M AU - Soler ZM AD - Division of Rhinology and Sinus Surgery, Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, SC. FAU - Mace, Jess C AU - Mace JC AD - Division of Rhinology and Sinus/Skull Base Surgery, Department of Otolaryngology-Head and Neck Surgery, Oregon Health & Science University, Portland, OR. FAU - Mattos, Jose L AU - Mattos JL AUID- ORCID: 0000-0001-8766-1626 AD - Division of Rhinology and Sinus Surgery, Department of Otolaryngology-Head and Neck Surgery, University of Virginia, Charlottesville, VA. FAU - Ramakrishnan, Vijay R AU - Ramakrishnan VR AUID- ORCID: 0000-0003-2748-0705 AD - Department of Otolaryngology, Head and Neck Surgery, University of Colorado-Anschutz Medical Campus, Aurora, CO. FAU - Beswick, Daniel M AU - Beswick DM AUID- ORCID: 0000-0001-8612-5442 AD - Department of Otolaryngology, Head and Neck Surgery, University of Colorado-Anschutz Medical Campus, Aurora, CO. FAU - Alt, Jeremiah A AU - Alt JA AUID- ORCID: 0000-0003-0560-5028 AD - Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Utah, Salt Lake City, UT. FAU - Mulligan, Jennifer K AU - Mulligan JK AD - Division of Pulmonary, Critical Care & Sleep Medicine, University of Florida, Gainesville, FL. LA - eng GR - R01 DC005805/DC/NIDCD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20210224 PL - United States TA - Int Forum Allergy Rhinol JT - International forum of allergy & rhinology JID - 101550261 SB - IM MH - Case-Control Studies MH - Chronic Disease MH - Cross-Sectional Studies MH - Humans MH - Mucus MH - *Nasal Polyps MH - *Rhinitis/epidemiology MH - *Sinusitis PMC - PMC8382803 MID - NIHMS1659121 OTO - NOTNLM OT - chronic disease OT - inflammation OT - olfaction OT - outcome assessment (health care) OT - sinusitis OT - smell, proteins COIS- Potential Conflicts of Interest: None of the following are affiliated with this study. Z.M.S.: Olympus, OptiNose, Regeneron, Healthy Humming, and Novartis (consultant). J.A.A.: Medtronic and GlycoMira Therapeutics (consultant). R.J.S.: OptiNose, Olympus, Stryker, Regeneron, and Healthy Humming (consultant). V.R.R.: OptiNose and Medtronic, Inc, (consultant). D.M.B: Medtronic (consultant). EDAT- 2021/02/26 06:00 MHDA- 2021/10/26 06:00 PMCR- 2022/09/01 CRDT- 2021/02/25 05:53 PHST- 2020/12/14 00:00 [revised] PHST- 2020/08/25 00:00 [received] PHST- 2020/12/28 00:00 [accepted] PHST- 2021/02/26 06:00 [pubmed] PHST- 2021/10/26 06:00 [medline] PHST- 2021/02/25 05:53 [entrez] PHST- 2022/09/01 00:00 [pmc-release] AID - 10.1002/alr.22770 [doi] PST - ppublish SO - Int Forum Allergy Rhinol. 2021 Sep;11(9):1321-1335. doi: 10.1002/alr.22770. Epub 2021 Feb 24.