Inflammatory Endotypes of Chronic Rhinosinusitis in the Korean Population: Distinct Expression of Type 3 Inflammation

Jin-Young Min; Jin Youp Kim; Chung Man Sung; Seon Tae Kim; Hyun-Jin Cho; Sue Jean Mun; Sung-Woo Cho; Sang Duk Hong; Gwanghui Ryu; Kyoung Rai Cho; Young Hyo Kim; Soo Kyoung Park; Dong-Kyu Kim; Dong Hoon Lee; Sung Jae Heo; Ki-Il Lee; Su Jin Kim; Sangjun Lee; Ji-Hun Mo; Seung-Heon Shin; Dae Woo Kim

doi:10.4168/aair.2023.15.4.437

Inflammatory Endotypes of Chronic Rhinosinusitis in the Korean Population: Distinct Expression of Type 3 Inflammation

Allergy Asthma Immunol Res. 2023 Jul;15(4):437-450. doi: 10.4168/aair.2023.15.4.437. Epub 2023 Jan 26.

Authors

Jin-Young Min^#¹, Jin Youp Kim^#², Chung Man Sung^#³, Seon Tae Kim⁴, Hyun-Jin Cho⁵, Sue Jean Mun⁶, Sung-Woo Cho⁷, Sang Duk Hong⁸, Gwanghui Ryu⁸, Kyoung Rai Cho⁹, Young Hyo Kim¹⁰, Soo Kyoung Park¹¹, Dong-Kyu Kim¹², Dong Hoon Lee¹³, Sung Jae Heo¹⁴, Ki-Il Lee¹⁵, Su Jin Kim¹⁶, Sangjun Lee¹⁷, Ji-Hun Mo¹⁸, Seung-Heon Shin¹⁹, Dae Woo Kim²⁰

Affiliations

¹ Department of Otorhinolaryngology-Head and Neck Surgery, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Korea.
² Department of Otorhinolaryngology-Head and Neck Surgery, Dongguk University Ilsan Hospital, Goyang, Korea.
³ Department of Otolaryngology-Head and Neck Surgery, Chonnam National University Hospital and Chonnam National University Medical School, Gwangju, Korea.
⁴ Department of Otolaryngology-Head and Neck Surgery, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea.
⁵ Department of Otorhinolaryngology, Gyeongsang National University Hospital and Gyeongsang National University School of Medicine, Jinju, Korea.
⁶ Department of Otorhinolaryngology, Pusan National University Yangsan Hospital, Busan, Korea.
⁷ Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
⁸ Department of Otorhinolaryngology-Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
⁹ Departments of Otorhinolaryngology-Head and Neck Surgery, Sanggye Paik Hospital, College of Medicine, Inje University, Seoul, Korea.
¹⁰ Kimyounghyo ENT Clinic, Incheon, Korea.
¹¹ Department of Otorhinolaryngology-Head and Neck Surgery, Chungnam National University School of Medicine, Daejeon, Korea.
¹² Department of Otorhinolaryngology-Head and Neck Surgery, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Korea.
¹³ Department of Otorhinolaryngology-Head and Neck Surgery, Chonnam National University Hwasun Hospital, Chonnam, Korea.
¹⁴ Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, Kyungpook National University, Daegu, Korea.
¹⁵ Department of Otorhinolaryngology-Head and Neck Surgery, Konyang University College of Medicine, Daejeon, Korea.
¹⁶ Department of Otorhinolaryngology-Head and Neck Surgery, National Medical Center, Seoul, Korea.
¹⁷ Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
¹⁸ Department of Otorhinolaryngology, Dankook University College of Medicine, Cheonan, Korea.
¹⁹ Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Daegu Catholic University, Daegu, Korea. hsseung@cu.ac.kr.
²⁰ Department of Otorhinolaryngology-Head and Neck Surgery, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea. kicubi73@gmail.com.

^# Contributed equally.

Abstract

Purpose: Cluster analyses on inflammatory markers of chronic rhinosinusitis (CRS) in Asians from multicenter data are lacking. This multicenter study aimed to identify the endotypes of CRS in Koreans and to evaluate the relationship between the endotypes and clinical parameters.

Methods: Nasal tissues were obtained from patients with CRS and controls who underwent surgery. The endotypes of CRS were investigated by measuring interleukin (IL)-5, interferon (IFN)-γ, IL-17A, IL-22, IL-1β, IL-6, IL-8, matrix metalloproteinase-9, eotaxin-3, eosinophil cationic protein, myeloperoxidase (MPO), human neutrophil elastase (HNE), periostin, transforming growth factor-β1, total immunoglobulin E (IgE), and staphylococcal enterotoxin (SE)-specific IgE. We performed hierarchical cluster analysis and evaluated the phenotype, comorbidities, and Lund-Mackay computed tomography (LM CT) score in each cluster.

Results: Five clusters and 3 endotypes were extracted from 244 CRS patients: cluster 1 had no upregulated mediators compared to the other clusters (mild mixed inflammatory CRS); clusters 2, 3, and 4 had higher concentrations of neutrophil-associated mediators including HNE, IL-8, IL-17A, and MPO (T3 CRS); and cluster 5 had higher levels of eosinophil-associated mediators (T2 CRS). SE-specific IgE was undetectable in T3 CRS and had low detectable levels (6.2%) even in T2 CRS. The CRS with nasal polyps (CRSwNP) phenotype and LM CT scores showed no significant differences between T2 and T3 CRS, while the incidence of comorbid asthma was higher in T2 CRS than T3 CRS. In T3 clusters, higher levels of neutrophilic markers were associated with disease severity and CRSwNP phenotype.

Conclusions: In Koreans, there is a distinct T3 CRS endotype showing a high proportion of CRSwNP and severe disease extent, along with T2 CRS.

Keywords: Asians; biomarker; cluster analysis; multicenter study; nasal polyps; sinusitis; surgery.

Abstract

Grants and funding