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Heterogeneity of non-polypoid CRS: characterized by three distinct inflammatory patterns

Published online: December 14, 2020

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the sinonasal mucosa affecting approximately 12.5% of Americans, responsible for over 400,000 surgeries per year and a total annual cost to the US health system estimated at $22 billion. Current treatment options for CRS patients remain limited and the efficacy of treatment also varies between patients. CRS is frequently divided into two main phenotypes: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP which is a severe form of CRS is primarily characterized by a type 2 inflammatory endotype in the US and type 2 targeting biologics showed promising efficacy in patients with CRSwNP. Recent studies have reported that CRSsNP which is a common phenotype of CRS presents more heterogeneity in inflammatory endotypes than CRSwNP suggesting that different underlying mechanisms may be contributing to disease and patients’ treatment outcomes in CRSsNP. However, the molecular mechanisms of each inflammatory endotype in CRSsNP are not well defined.

In a recently published study in The Journal of Allergy and Clinical Immunology (JACI), Klingler et al. investigated the mechanisms and biomarkers associated with three key inflammatory endotypes (type 1, type 2 and type 3) underpinning CRSsNP. Sinus tissues and nasal lavage fluids were obtained from control patients and patients with CRS and the gene expression profiles in sinus tissues and biomarkers in nasal lavage fluids were determined by microarray and protein assays, respectively.

Compared to control sinus tissues, each endotype in CRSsNP presented a distinct gene signature suggesting that each inflammatory endotype is composed by distinct inflammatory cell types and is characterized by different molecular mechanisms. In the case of composition of immune cells, gene signatures suggested that type 1 CRSsNP is controlled by T cells (Th1 cells and cytotoxic T cells), NK cells and antigen presenting cells (APC); type 2 CRSsNP by eosinophils, mast cells, basophils, Th2 cells, ILC2 and APC that are also found in type 2 CRSwNP; and type 3 CRSsNP by neutrophils, Th17 cells, B cells and APC. The authors further identified novel biomarkers in nasal lavage fluids which are able to predict tissue inflammatory patterns in CRSsNP before starting treatment.

In summary, CRSsNP may have at least 3 major inflammatory endotypes that are controlled by different molecular mechanisms and inflammatory cells; the identified mechanisms in each endotype may lead to the discovery of endotype specific new therapeutic targets. Furthermore, nasal lavage biomarker assays may lead the way to personalized medicine strategies for the treatment of CRSsNP.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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