Associations Between Inflammatory Endotypes and Clinical Presentations in Chronic Rhinosinusitis

Abstract

Background: Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by mucosal inflammation in the nose and paranasal sinuses. Inflammation in CRS is also heterogeneous and is mainly characterized by type 2 (T2) inflammation, but subsets of patients show type 1 (T1) and type 3 (T3) inflammation. Whether inflammatory endotypes are associated with clinical phenotypes has yet to be explored in detail.

Objective: To identify associations between inflammatory endotypes and clinical presentations in CRS.

Methods: We compared 121 patients with nonpolypoid CRS (CRSsNP) and 134 patients with polypoid CRS (CRSwNP) and identified inflammatory endotypes using markers including IFN-γ (T1), eosinophil cationic protein (T2), Charcot-Leyden crystal galectin (T2), and IL-17A (T3). We collected clinical parameters from medical and surgical records and examined whether there were any associations between endotype and clinical features.

Results: The presence of nasal polyps, asthma comorbidity, smell loss, and allergic mucin was significantly associated with the presence of T2 endotype in all patients with CRS. The T1 endotype was significantly more common in females, and the presence of pus was significantly associated with T3 endotype in all patients with CRS. We further analyzed these associations in CRSsNP and CRSwNP separately and found that smell loss was still associated with T2 endotype and pus with the T3 endotype in both CRSsNP and CRSwNP. Importantly, patients with CRS with T2 and T3 mixed endotype tended to have clinical presentations shared by both T2 and T3 endotypes.

Conclusions: Clinical presentations are directly associated with inflammatory endotypes in CRS. Identification of inflammatory endotypes may allow for more precise and personalized medical treatments in CRS.

Keywords: Chronic rhinosinusitis; Clinical presentation; Endotype-phenotype association; Inflammatory endotype.

Conflict of interest statement

Competing interests: The authors declare no conflict of interest as to the interpretation and presentation of this manuscript.

Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.

Patterns of inflammatory endotypes in CRS.

Figure 2.. Odds ratio for clinical presentations within endotypes in all CRS.

Multivariate logistic regression analysis with predictor endotype controlling for age, sex, asthma, atopy and NP and the corresponding odds ratio (OR), 95% confidence interval (CI) and p-value for headache/migraine (n=230), smell loss (n=230) and intra-operative pus (n=217) in CRS. * p

Figure 3.. Endotype-phenotype associations in CRSsNP and CRSwNP.

Association of clinical presentations with the absence and/or presence of all T1, T2 or T3 endotypes in CRSsNP (A) and CRSwNP (B). * p

Figure 4.. Endotype-phenotype association in single, mixed and untypeable endotypes of CRSsNP and CRSwNP.

Comparison of clinical presentations between untypeable, single or mixed endotypes in CRSsNP (A) and CRSwNP (B). * p