The Journal of Allergy and Clinical Immunology: In Practice
Review and Feature ArticleEndotypes of Chronic Rhinosinusitis with Nasal Polyps: Pathology and Possible Therapeutic Implications
Section snippets
The Rationale for Endotyping
Nasal polyps—also referred to as chronic rhinosinusitis with nasal polyps (CRSwNP)—may vary in their clinical expression from slowly to rapidly growing sinus disease, may appear early or late in life, may or may not be associated with late-onset asthma, and may or may not respond well to the currently established treatment modalities including topical glucocorticosteroids (GCSs), courses of oral GCSs, or conventional endoscopic sinus surgery (ESS). These clinical traits are different from the
Endotyping of CRS Based on Biomarkers and Clinical Traits: On the way to Precision Medicine
The currently most accepted endotyping approach was published in 2016,11 based on an unbiased cluster analysis of inflammatory cytokines and mediators such as eosinophilic cationic protein (ECP) and myeloperoxidase, and IgE. This resulted in 3 groups, a non–type 2 mostly chronic rhinosinusitis without (sine) nasal polyps (CRSsNP) (comprising type 1 and type 3 immune reactions), and a moderate and a severe type 2 mostly CRSwNP, with the severe type demonstrating significantly higher
Therapeutic Implications for Pharmacotherapy and Surgery
The treatment aim is the long-term management of patients with CRSwNP, reducing disease burden and risks of disease such as recurrence and asthma, by combining various strategies. Endotyping should guide the selection of treatments from pharmacotherapy over surgery to biologics. However, as this area is new and only partially established, only limited evidence is available and randomized trials comparing the current versus an endotype-based approach are lacking. The arguments for an
Biologics: State of the Art
It is evident that biologics targeting type 2 cytokines such as free IgE, IL-4, IL-5, and IL-13 or their receptors are only indicated in type 2 CRSwNP. We therefore need to identify indicators to increase the likelihood of type 2 immune reactions in an individual patient (Table I). Dupilumab phase 3 results in 2 studies with more than 700 patients over 24 and 52 weeks have recently been published43 after a successful proof-of-concept (PoC) study before.44 Approximately 2 of 3 patients had
Conclusion
It is obvious that the management of CRS, specifically severe CRSwNP, gets considerably more complex and asks additional skills, including the interpretation of endoscopy and CT scanning after former surgery, the indication for revision or possibly reboot surgery, and a good understanding of disease immunology and resulting indications for biologics. Often, patients do suffer from additional manifestations of type 2 immune reactions, including atopic dermatitis or eosinophil esophagitis, so
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2023, Otolaryngologic Clinics of North AmericaCitation Excerpt :The underlying pathophysiology that mediates most cases of CRSwNP and asthma is characterized by eosinophilia and elevated levels of the proeosinophilic cytokines interleukin (IL)-4, IL-5, IL-13, and immunoglobulin E (IgE).6 This is termed type 2 pattern of inflammation, and is seen in 80% of Caucasian patients with CRSwNP, and up to 94% of patients with comorbid asthma7; a combination of nasal polyps, asthma, and a blood eosinophil greater than 300 cells/mm3 further increases the likelihood.7 Non-type 2 inflammation is more commonly linked with CRS without nasal polyps (CRSsNP), and in CRSwNP in patients from Asian countries,8 which is driven by neutrophils and IL-17 subunits, although this is changing over time.8–10
Prognostic factors for polyp recurrence in chronic rhinosinusitis with nasal polyps
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No funding was received for this work.
Conflicts of interest: C. Bachert received speaker fees and is a member of advisory boards for Sanofi, Novartis, Astra-Zeneca, and GSK. The rest of the authors declare that they have no relevant conflicts of interest.