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Journal of Allergy and Clinical Immunology

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Endotyping chronic rhinosinusitis based on olfactory cleft mucus biomarkers - 05/05/21

Doi : 10.1016/j.jaci.2021.01.021 
Zachary M. Soler, MD, MSc a, Rodney J. Schlosser, MD a, b, Todd E. Bodner, PhD c, Jeremiah A. Alt, MD, PhD d, Vijay R. Ramakrishnan, MD e, Jose L. Mattos, MD, MPH f, Jennifer K. Mulligan, PhD g, Jess C. Mace, MPH h, Timothy L. Smith, MD, MPH h, ⁎
a Division of Rhinology and Sinus Surgery, Department of Otolaryngology—Head and Neck Surgery, Medical University of South Carolina, Charleston, SC 
b Department of Surgery, Ralph H. Johnson VA Medical Center, Charleston, SC 
c Department of Psychology, Portland State University, Portland, Ore 
d Division of Otolaryngology—Head and Neck Surgery, Department of Surgery, University of Utah, Salt Lake City, Utah 
e Department of Otolaryngology, Head and Neck Surgery, University of Colorado-Anschutz Medical Campus, Aurora, Colo 
f Division of Rhinology and Sinus Surgery, Department of Otolaryngology—Head and Neck Surgery, University of Virginia, Charlottesville, Va 
g Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of Florida, Gainesville, Fla 
h Division of Rhinology and Sinus/Skull Base Surgery, Department of Otolaryngology—Head and Neck Surgery, Oregon Health and Science University, Portland, Ore 

∗Corresponding author: Timothy L. Smith, MD, MPH, Oregon Health and Science University, Department of Otolaryngology—Head and Neck Surgery, 3181 SW Sam Jackson Park Road, PV-01, Portland, OR 97239.Oregon Health and Science UniversityDepartment of Otolaryngology—Head and Neck Surgery3181 SW Sam Jackson Park RoadPV-01PortlandOR97239

Abstract

Background

Although chronic rhinosinusitis (CRS) is considered the most treatable form of olfactory dysfunction, there has been relatively little clinical attention focused on assessing endotypes as they pertain to olfactory loss.

Objectives

The goal of this study was to explore inflammatory endotypes in CRS using an unsupervised cluster analysis of olfactory cleft (OC) biomarkers in a phenotype-free approach.

Methods

Patients with CRS were prospectively recruited and psychophysical olfactory testing, Questionnaire of Olfactory Dysfunction (QOD-NS), and bilateral OC endoscopy were obtained. Mucus was collected from the OC and evaluated for 26 biomarkers using principal component analysis. Cluster analysis was performed using only OC biomarkers and differences in olfactory measures were compared across clusters.

Results

A total of 198 subjects (128 with CRS and 70 controls) were evaluated. Evaluation of OC biomarkers indicated 6 principal components, explaining 69.50% of the variance, with type 2, mixed type 1/Th17-cell, growth factor, and neutrophil chemoattractant inflammatory signatures. A total of 10 clusters were identified that differed significantly in frequency of controls, and subjects with CRS with nasal polyps, and subjects with CRS without nasal polyps across the clusters (likelihood ratio test,  ; P < .001). Olfactory measures differed significantly across clusters, including olfactory testing, QOD-NS, and OC endoscopy (P < .001 for all).

Conclusions

Clustering based solely on OC biomarkers can organize patients into clinically meaningful endotypes that discriminate between subjects with CRS and controls. Validation studies are necessary to confirm these findings and further refine olfactory endotypes.

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Key words : Cluster analysis, translational medical research, chronic disease, patient-reported outcome measures, sinusitis, smell

Abbreviations used : CRS, CRSsNP, CRSwNP, CT, OC, OCES, OD, PC, QOD-NS, QOL, SNOT-22, TDI


Plan


 Clinical trial registration: Determinants of Olfactory Dysfunction in Chronic Rhinosinusitis (NCT02720653) is registered at www.clinicaltrials.gov.
 Supported by the National Institute on Deafness and Other Communication Disorders (grants R03 DC013651-01 [principal investigator: Z.M.S.], R01 DC005805 [principal investigators: T.L.S. and Z.M.S.], K23DC014747 [principal investigator: V.R.R.] to Z.M.S., R.J.S., T.E.B., J.A.A., V.R.R., J.K.M., J.C.M., and T.L.S.); the National Institute of Allergy and Infectious Disease (grants R01 AI34698 and R01 AI144364 [to J.K.M.]). These funding organizations did not contribute to the design or conduct of this study, preparation, review, approval of, or decision to submit this manuscript for publication.
 Disclosure of potential conflict of interest: None of the following consultancy positions or grant support are affiliated with this investigation or manuscript: Z. M. Soler has been a consultant for Olympus Medical Systems, OptiNose US Inc, Genentech, Lyra Therapeutics, and Sinusonic. R. J. Schlosser: has been a consultant for ENT Stryker, Medtronic Systems Inc, Healthy Humming, GlaxoSmithKline, Sanofi, and Optinose US Inc; and has received grants from ENT Stryker, Healthy Humming, GlaxoSmithKline, Sanofi, and Optinose US Inc. J. A. Alt has been a consultant for OptiNose US Inc, Medtronic Inc, and GlycoMira Therapeutics, Inc. V. R. Ramakrishnan has been a consultant for OptiNose US Inc and Medtronic Systems Inc; and has served as an Advisory Board member for Genentech, Novartis, and GlaxoSmithKline. The rest of the authors declare that they have no relevant conflicts of interest.


© 2021  American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 147 - N° 5

P. 1732 - mai 2021 Retour au numéro
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