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Not to underestimate neutrophilic inflammation in type 2 nasal polyposis

Published: September 16, 2020

Chronic rhinosinusitis (CRS) is a chronic inflammation of the sinonasal mucosa that affects up to 15% of the Caucasian population. The severity of the underlying inflammation often makes it difficult to treat every patient satisfactorily. In general, patients who develop nasal polyps (Chronic Rhinosinusitis with Nasal Polyps, CRSwNP) have the most persistent and severe disease, requiring repeated surgeries and oral glucocorticosteroids. They also display an underlying inflammation that is traditionally characterized by a type 2 inflammatory pattern with massive infiltration and activation of eosinophils. Although biologics targeting type 2 cytokines have proved successful in many patients, there is still a subset that remains refractory to such therapy. Recent studies in asthma, allergy and CRS suggest a possible role for neutrophils in the pathogenesis of severe type 2 airway inflammation.

In a recent research article in The Journal of Allergy and Clinical Immunology (JACI), Delemarre and colleagues characterized the neutrophilic inflammation and its relationship to eosinophilic inflammation in severe type 2 sinus disease. Sinus tissue samples of patients with Chronic Rhinosinusitis without Nasal Polyps (CRSsNP) and CRSwNP patients and healthy controls were obtained and examined for their expression of inflammatory cytokines and analyzed for the infiltration, activation and extracellular trap formation of neutrophils and eosinophils.

These tissue samples demonstrated a more differentiated pattern of neutrophilic and eosinophilic infiltration than anticipated based on cytokine profiles among all CRS patients, with a mixed neutrophilic-eosinophilic infiltration in most of the patients with a severe type 2 immune response. Further analysis in this subgroup demonstrated substantial neutrophilic inflammation, characterized by activated neutrophils, elevated proteolytic activity of neutrophilic proteases elastase and cathepsin G, and increased levels of neutrophil-associated proteins such as MPO, IL-6 and IL-8. Interestingly, among CRSwNP patients with a severe type 2 inflammation, the neutrophilic infiltration was closely associated with eosinophil extracellular trap formation and the deposition of Charcot-Leyden crystals - both hallmarks of eosinophilic activation, but independent of IL-17. A considerable fraction of neutrophils was also found to generate extracellular traps in the tissue of CRSwNP patients, mainly at the edges of denuded epithelium and with signs of bacterial colonization.

To summarize, Delemarre and colleagues showed that the contribution of neutrophils – by themselves or in combination with eosinophilic inflammation – could be more important than initially thought, especially in a type 2 context. The observed mixed neutrophilic-eosinophilic inflammation could result in an aggravation of inflammation in the most severe CRSwNP patients, leading to insensitivity to glucocorticosteroids and type 2 biologics.

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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