Endotype-driven precision medicine in chronic rhinosinusitis

ABSTRACT

Introduction: Chronic rhinosinusitis (CRS) is a heterogeneous disease spectrum with variable phenotypes and endotypes that are not well characterized. Conventional treatment options are insufficient; recent research in precision medicine focuses on providing endotype-driven care based on underlying mechanisms.

Areas covered: A comprehensive overview of CRS phenotypes and endotypes is provided. Biomarkers have been identified to predict prognosis and guide personalized pharmacotherapy, surgery, and innovative treatments. For CRS with nasal polyps (CRSwNP), type 2-targeting biologics, such as anti-IgE, anti-IL4Rα, and anti-IL5 antibodies, have been explored in clinical trials.

Expert opinion: In addition to differences in immunopathogenic mechanisms and responses to medical and surgical interventions, CRS endotypes vary according to geography and ethnicity and their distributions change over time. Endotype-driven integrated care is a promising approach. Our current understanding of type 2 inflammation is well ahead of that of other endotypes. Biomarkers of type 2 inflammation show good predictive ability for corticosteroid responsiveness and disease recurrence. Type 2-targeted treatments are effective for CRSwNP based on clinical trials. The identification of patient subsets and effective biomarkers is important for optimizing biotherapeutic strategies. Further studies should focus on non-type 2 inflammation-targeted treatment approaches and the safety of biologics for routine clinical use.

KEYWORDS:

• Biologics
• biomarker
• chronic rhinosinusitis
• corticosteroids
• endotype
• nasal polyps
• recurrence
• type 2 inflammation

Article Highlights

• CRS is an inflammatory disease spectrum with various phenotypes and endotypes; these endotypes vary according to geography and ethnicity, and their distributions shift over time.

• Tissue eosinophil percentages/counts are still among the most reliable predictors for the recurrence, prognosis, and steroid responsiveness of CRS.

• Further studies should focus on immunologic cytokines and nasal microbiota to improve our understanding and management of CRS.

• The identification of suitable biomarkers and development of endotype-targeted therapies are future directions in precision medicine for CRS.

• Biologics targeting type 2 inflammation are the focus of ongoing clinical trials for CRSwNP.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by grants from the Beijing Advanced Innovation Center for Food Nutrition and Human Health [Beijing Technology and Business University (BTBU) 20181045] The Program for Changjiang Scholars and Innovative Research Team [IRT13082] National Key R&D Program of China [2018YFC0116800] National Key R&D Program of China [2016YFC20160905200] National Science and Technology Infrastructure Program of China during the 12th Five-Year Plan Period [2014BAI07B04] National Natural Science Foundation of China [81420108009; 81970850; 81630023; 81570895; 81870698 and 81400444] Research of Capital Health Security and Cultivation [Z18110700160000] Beijing Municipal Administration of Hospitals’ Mission Plan [SML20150203] Beijing Municipal Administration of Hospitals’ Innovation Program of Clinical Techniques [XMLX201816] Beijing Hundred-Thousand-Ten Thousand Founding Program [2018A10] Beijing Municipal Administration of Hospitals’ Youth Programme [QML20150202].