Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers

• Published in: Journal of allergy and clinical immunology Vol. 137; no. 5; pp. 1449 - 1456.e4
• Main Authors: Tomassen, Peter, Vandeplas, Griet, Van Zele, Thibaut, Cardell, Lars-Olaf, Arebro, Julia, Olze, Heidi, Förster-Ruhrmann, Ulrike, Kowalski, Marek L., Olszewska-Ziąber, Agnieszka, Holtappels, Gabriele, De Ruyck, Natalie, Wang, Xiangdong, Van Drunen, Cornelis, Mullol, Joaquim, Hellings, Peter, Hox, Valerie, Toskala, Elina, Scadding, Glenis, Lund, Valerie, Zhang, Luo, Fokkens, Wytske, Bachert, Claus
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2016; Elsevier Limited
• Subjects: Adult; Allergies; Allergy and Immunology; asthma; Bacterial Toxins - immunology; Biomarkers - analysis; Case-Control Studies; Chronic Disease; Chronic rhinosinusitis; Cluster Analysis; Cystic fibrosis; Cytokines - immunology; Endoscopy; endotypes; Enterotoxins - immunology; Female; Genotype & phenotype; Humans; Immunoglobulin E - immunology; inflammation; Male; nasal polyps; Peroxidase - immunology; Principal Component Analysis; Principal components analysis; Rhinitis - immunology; Sinusitis - immunology; Staphylococcus aureus; Staphylococcus aureus - immunology; Studies; Surgery; endotypes; Chronic rhinosinusitis; ECP; inflammation; CRS; nasal polyps; SE-IgE; asthma; CRSwNP; cluster analysis; MPO; CRSsNP; Eosinophilic cationic protein; Staphylococcus aureus enterotoxin–specific IgE; Chronic rhinosinusitis without nasal polyps; Chronic rhinosinusitis with nasal polyps; Myeloperoxidase
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2015.12.1324

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. 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. In this multicenter case-control study patients with CRS and control subjects underwent surgery, and tissue was analyzed for IL-5, IFN-γ, IL-17A, TNF-α, IL-22, IL-1β, IL-6, IL-8, eosinophilic cationic protein, myeloperoxidase, TGF-β1, IgE, Staphylococcus aureus enterotoxin–specific IgE, and albumin. We used partition-based clustering. 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 TH17 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. 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.