Endotypes and phenotypes of chronic rhinosinusitis: A PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology
Chronic rhinosinusitis (CRS) is a complex disease consisting of several disease variants with different underlying pathophysiologies. Limited knowledge of the mechanisms of these disease subgroups is possibly the greatest obstacle in understanding the causes of CRS and improving treatment. It is generally agreed that there are clinically relevant CRS phenotypes defined by an observable characteristic or trait, such as the presence or absence of nasal polyps. Defining the phenotype of the patient is useful in making therapeutic decisions. However, clinical phenotypes do not provide full insight into all underlying cellular and molecular pathophysiologic mechanisms of CRS. Recognition of the heterogeneity of CRS has promoted the concept that CRS consists of multiple groups of biological subtypes, or “endotypes,” which are defined by distinct pathophysiologic mechanisms that might be identified by corresponding biomarkers. Different CRS endotypes can be characterized by differences in responsiveness to different treatments, including topical intranasal corticosteroids and biological agents, such as anti–IL-5 and anti-IgE mAb, and can be based on different biomarkers that are linked to underlying mechanisms. CRS has been regarded as a single disease entity in clinical and genetic studies in the past, which can explain the failure to identify consistent genetic and environmental correlations. In addition, better identification of endotypes might permit individualization of therapy that can be targeted against the pathophysiologic processes of a patient's endotype, with potential for more effective treatment and better patient outcomes.
Key words: Chronic rhinosinusitis, endotypes, phenotypes, cytokines, biological agents, treatment, diagnosis, IgE, nasal polyps,pathophysiology
Abbreviations used: ARS, Acute rhinosinusitis, BAFF, B cell–activating factor of the TNF family, CRS, Chronic rhinosinusitis, CRSwNP,Chronic rhinosinusitis with nasal polyps, CRSsNP, Chronic rhinosinusitis without nasal polyps, CT, Computed tomography, EPOS, European Position Paper on Rhinosinusitis and Nasal Polyps, MMP, Matrix metalloproteinase, NP, Nasal polyp, SE, Staphylococcus aureusexotoxin/enterotoxin, STAT3, Signal transducer and activator of transcription 3, TIMP, Tissue inhibitor of metalloproteinases, TJ, Tight junction, TLR, Toll-like receptor, TRAIL, TNF-related apoptosis-inducing ligand
Disclosure of potential conflict of interest: C. A. Akdis receives research support from Novartis, PREDICTA, the Swiss National Science Foundation, MeDALL, the Global Allergy and Asthma European Network, and the Christine Kühne-Center for Allergy Research and Education; has consulted for Actellion, Aventis, Stallergenes, and Allergopharma; is president of the European Academy of Allergy and Clinical Immunology; is a fellow and interest group member of the American Academy of Allergy, Asthma & Immunology (AAAAI); is a former committee member of the Global Allergy and Asthma European Network; and is the director of the Christine Kühne-Center for Allergy Research and Education. C. Bachert has received research support from Novartis and GlaxoSmithKline. M. S. Dykewicz has consultant arrangements with Boehringer Ingelheim, Ista, and Merck. R. M. Naclerio has received travel support from AAAAI; has board memberships with Merck, TEVA, and Sunovion; has received grants from TEVA, Johnson & Johnson, and Kalypsis; and has received payment for lectures from TEVA and Sunovion. R. P. Schleimer has consultant arrangements with Intersect ENT, GlaxoSmithKline, Allakos, and Aurasense; has received research support from the National Institutes of Health; and has received stock/stock options from Allakos. D. Ledford has received travel support from AAAAI; has consultant arrangements with Genentech; and has received payment for lectures from Meda and Genentech. The rest of the authors declare that they have no relevant conflicts of interest.
PII: S0091-6749(13)00367-9
doi:10.1016/j.jaci.2013.02.036
© 2013 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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Volume 131, Issue 6 , Pages 1479-1490, June 2013
Volume 131, Issue 6 , Pages 1479-1490, June 2013
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