Pathophysiology

Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with local (sinonasal) and systemic (lower-airway) inflammation. It involves persistent symptoms of1:

  • Nasal congestion
  • Facial pressure/pain
  • Rhinorrhea
  • Loss of smell

CRSwNP is generally associated with type 2 inflammation and an increase in interleukin (IL) activity, including IL-4, IL-5, IL-13, and immunoglobulin E (IgE).2 Type 2 inflammation is a pathway also implicated in several coexisting diseases—asthma, for example.1 Type 2 inflammation is present in 80% of patients with nasal polyps (NPs), which obviously leads to more severe clinical expressions of the disease; however, in the remaining 20% of the patients, other non-type 2 mechanisms—such as type 1 and type 3—may be involved.3,4

Chronic rhinosinusitis (CRS) is a heterogeneous disorder with multiple inflammatory endotypes.5 Generally, patients have bilateral benign edematous polyps from the paranasal sinuses to the nasal cavity. They also tend to show increased levels of cytokines and mediators, together with inflammatory infiltrate.1 CRSwNP is most often associated with eosinophilic inflammation, which includes elevated IgE, IL-4, and IL-5. No specific genetic or environmental factors are strongly associated with CRSwNP.1 Phenotypes and endotypes in CRS are shown below.6

Even if the inflammatory processes controlling CRSwNP are not yet fully understood, significant recent progress suggests that the disease comprises distinctive subtype groups.6,7 However, for endotyping to be clinically applicable, predictable and simply determined biomarkers referring to the intrinsic biomolecular mechanism still need to be found.8 Consequently, CRS research in this particular area has greatly intensified in recent years, and many different biomarkers for nasal polyposis have been identified, including eosinophil cytokines IL-4, IL-5, IL-13, IL-25, IL-33, metalloproteinases, bitter or sweet taste receptors, and nasal microbiome.9,10

References

  1. Bachert C, Bhattacharyya N, Desrosiers M, Khan AH. Burden of disease in chronic rhinosinusitis with nasal polyps. J Asthma Allergy. 2021;14:127-134.
  2. Maniu AA, Perde-Schrepler MI, Tatomir CB, et al. Latest advances in chronic rhinosinusitis with nasal polyps endotyping and biomarkers, and their significance for daily practice. Rom J Morphol Embryol. 2020;61:309-320.
  3. Bachert C, Akdis CA. Phenotypes and emerging endotypes of chronic rhinosinusitis. J Allergy Clin Immunol Pract. 2016;4:621-628.
  4. Cardell LO, Stjärne P, Jonstam K, Bachert C. Endotypes of chronic rhinosinusitis: impact on management. J Allergy Clin Immunol. 2020;145:752-756.
  5. Tomassen P, Vandeplas G, Van Zele T, et al. Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers. J Allergy Clin Immunol. 2016;137:1449-1456.e4.
  6. Akdis CA, Bachert C, Cingi C, et al. 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. J Allergy Clin Immunol. 2013;131:1479-1490.
  7. Naclerio R, Baroody F, Bachert C, et al. Clinical research needs for the management of chronic rhinosinusitis with nasal polyps in the new era of biologics: a National Institute of Allergy and Infectious Diseases workshop. J Allergy Clin Immunol Pract. 2020;8:1532-1549.e1.
  8. Bachert C, Marple B, Hosemann W, et al. Endotypes of chronic rhinosinusitis with nasal polyps: pathology and possible therapeutic implications. J Allergy Clin Immunol Pract. 2020;8:1514-1519.
  9. Workman AD, Kohanski MA, Cohen NA. Biomarkers in chronic rhinosinusitis with nasal polyps. Immunol Allergy Clin North Am. 2018;38:679-692.
  10. Schleimer RP. Immunopathogenesis of chronic rhinosinusitis and nasal polyposis. Annu Rev Pathol. 2017;12:331-357.

Scientific Council

Neil M. Bressler, MD

James P. Gills Professor of Ophthalmology
Professor of Ophthalmology, Johns Hopkins University School of Medicine
Wilmer Eye Institute, Johns Hopkins Medicine
Baltimore, MD

A. Paul Chous, MA, OD, FAAO

Specializing in Diabetes Eye Care & Education, Chous Eye Care Associates
Adjunct Professor of Optometry, Western University of Health Sciences
AOA Representative, National Diabetes Education Program
Tacoma, WA

Steven Ferrucci, OD, FAAO

Chief of Optometry, Sepulveda VA Medical Center
Professor, Southern California College of Optometry at Marshall B. Ketchum University
Sepulveda, CA

Julia A. Haller, MD

Ophthalmologist-in-Chief
Wills Eye Hospital
Philadelphia, PA

Allen C. Ho, MD, FACS

Director, Retina Research
Wills Eye Hospital
Professor and Chair of the Department of Ophthalmology
Thomas Jefferson University Hospitals
Philadelphia, PA

Charles C. Wykoff, MD, PhD

Director of Research, Retina Consultants of Houston
Associate Professor of Clinical Ophthalmology
Blanton Eye Institute & Houston Methodist Hospital
Houston, TX

Copyright © 2020 | CLEAR Initiative | All Rights Reserved | Website by Divigner

CLEAR Initiative

Chronic rhinosinusitis with nasal polyplosis (CRSwNP) is a chronic inflammatory disease of the nasal mucosa and paranasal sinuses that is associated with significant morbidity and reduced quality of life.

The pathophysiology of CRSwNP is associated with local and systemic inflammation, with ongoing symptoms of nasal congestion, rhinorrhea, and loss of smell. These symptoms result in a significant burden on patients.

As one of the most common medical conditions in the US, CRSwNP has a predominately type 2 inflammatory endotype. It is typically treated with medical management consisting of inhaled corticosteroids, oral corticosteroid bursts, and saline irrigation. Leukotriene antagonists and antibiotics are also used, and if medical management fails, surgical intervention is typically chosen. Additionally, biologics that target type 2 inflammation are now available. These have been or will be approved for use in these patients.

Our CLEAR program is an online tool that aims to provide clinicians and patients with up-to-date information on the presentation, prognosis, pathophysiology, and treatment strategies for individuals with CRSwNP. Our goal is to provide information that empowers clinicians and patients to speak openly about treatment decisions and improve the standard of care for patients with this challenging disease.

Thank you for visiting our website. We invite you to explore the Clinician Toolkit and Patient Toolkit links as well as our pages on CME events, a poster portal to create your own poster, links to animated videos, and much more!

This activity is provided by Med Learning Group. This activity is co-provided by Ultimate Medical Academy/Complete Conference Management (CCM).
This activity is supported by an independent medical education grant from Regeneron Pharmaceuticals, Inc. and Sanofi.

Copyright © 2019 | CLEAR Initiative | All Rights Reserved | Website by Divigner

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