Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:137

Article

Tomassen, Peter¹  Vandeplas, Griet¹  Van Zele, Thibaut¹  Cardell, Lars-Olaf²  Arebro, Julia²  Olze, Heidi³  Foerster-Ruhrmann, Ulrike³  Kowalski, Marek L.⁴  Olszewska-Ziaber, Agnieszka⁴  Holtappels, Gabriele¹  De Ruyck, Natalie¹  Wang, Xiangdong⁵  Van Drunen, Cornelis⁶  Mullol, Joaquim⁷  Hellings, Peter⁸  Hox, Valerie⁸  Toskala, Elina⁹  Scadding, Glenis¹⁰  Lund, Valerie¹⁰  Zhang, Luo⁵  Fokkens, Wytske⁶  Bachert, Claus^1,2 

[1] Univ Ghent, Upper Airway Res Lab, De Pintelaan 185, B-9000 Ghent, Belgium

[2] Karolinska Inst, CLINTEC, Div ENT Dis, Stockholm, Sweden

[3] Charite Univ Med Berlin, Dept Otorhinolaryngol, Berlin, Germany

[4] Med Univ Lodz, Dept Immunol Rheumatol & Allergy, Lodz, Poland

[5] Capital Med Univ, Beijing Tongren Hosp, Dept Otorhinolaryngol Head & Neck Surg, Beijing, Peoples R China

[6] Univ Amsterdam, Acad Med Ctr, Dept Otorhinolaryngol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands

[7] Hosp Clin Barcelona, Clin & Expt Resp Immunoallergy, IDIBAPS, Barcelona, Spain

[8] Univ Hosp Leuven, Dept Otorhinolaryngol Head & Neck Surg, Louvain, Belgium

[9] Temple Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Philadelphia, PA 19122 USA

[10] Royal Natl Throat Nose & Ear Hosp, London, England

关键词: Chronic rhinosinusitis;    nasal polyps;    endotypes;    cluster analysis;    inflammation;    asthma;   

DOI  :  10.1016/j.jaci.2015.12.1324

来源: Elsevier

【 摘 要 】

Background: Current phenotyping of chronic rhinosinusitis (CRS) into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) might not adequately reflect the pathophysiologic diversity within patients with CRS. Objective: We sought to identify inflammatory endotypes of CRS. Therefore we aimed to cluster patients with CRS based solely on immune markers in a phenotype-free approach. Secondarily, we aimed to match clusters to phenotypes. Methods: In this multicenter case-control study patients with CRS and control subjects underwent surgery, and tissue was analyzed for IL-5, IFN-gamma, IL-17A, TNF-alpha, IL-22, IL-1 beta, IL-6, IL-8, eosinophilic cationic protein, myeloperoxidase, TGF-beta 1, IgE, Staphylococcus aureus enterotoxin-specific IgE, and albumin. We used partition-based clustering. Results: Clustering of 173 cases resulted in 10 clusters, of which 4 clusters with low or undetectable IL-5, eosinophilic cationic protein, IgE, and albumin concentrations, and 6 clusters with high concentrations of those markers. The group of IL-5-negative clusters, 3 clusters clinically resembled a predominant chronic rhinosinusitis without nasal polyps (CRSsNP) phenotype without increased asthma prevalence, and 1 cluster had a T(H)17 profile and had mixed CRSsNP/CRSwNP. The IL-5-positive clusters were divided into a group with moderate IL-5 concentrations, a mixed CRSsNP/CRSwNP and increased asthma phenotype, and a group with high IL-5 levels, an almost exclusive nasal polyp phenotype with strongly increased asthma prevalence. In the latter group, 2 clusters demonstrated the highest concentrations of IgE and asthma prevalence, with all samples expressing Staphylococcus aureus enterotoxin-specific IgE. Conclusion: Distinct CRS clusters with diverse inflammatory mechanisms largely correlated with phenotypes and further differentiated them and provided a more accurate description of the inflammatory mechanisms involved than phenotype information only.

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