A substantial neutrophilic inflammation as regular part of severe type 2 chronic rhinosinusitis with nasal polyps

Rethinking neutrophils and eosinophils in chronic rhinosinusitis

“…29 Indeed, a substantial neutrophilic inflammation co-occurring with-and affected by-eosinophilia was recently demonstrated in most patients with severe type 2 CRSwNP (Fig 1). 13,23 In addition, a CRS cluster analysis demonstrated elevated levels of neutrophil-related proteins, such as IL-6, IL-8, and myeloperoxidase, in patients with highly type 2 eosinophilic CRSwNP, with a severe clinical outcome. 5 For asthma it is well known that the presentation of a mixed type 2-type 17 inflammatory pattern is associated with a mixed eosinophilic-neutrophilic picture, as observed in the more severe and difficult to control asthma phenotype.…”

“…[9][10][11] Although this dichotomous type 1-type 2 classification is still valid in general, CRS endotyping has stressed the complexity of CRS with a frequent presentation of mixed inflammatory patterns and cellular diversity, making it obvious that type 1-type 2 differentiation alone is not sufficient to explain the pathophysiology. 3,5,[12][13][14][15] Eosinophilic-neutrophilic inflammation has long been presented as black and white, almost implying mutual exclusion in CRS. Recent endotype-focused studies have challenged this traditional image, showing a more versatile picture than was anticipated on the basis of cytokine profiles in both patients with CRSsNP and patients with CRSwNP.…”

“…Recent endotype-focused studies have challenged this traditional image, showing a more versatile picture than was anticipated on the basis of cytokine profiles in both patients with CRSsNP and patients with CRSwNP. 12,13 The most severe patients with CRSsNP have a predominant eosinophilic inflammation, and most patients with severe CRSwNP display a mixed pattern of eosinophilic-neutrophilic inflammation.…”

Charcot–Leyden crystals and other protein crystals driving type 2 immunity and allergy

“…Galectin-10 mRNA and protein expression, as well as the presence of extracellular CLCs have thus become markers of tissue eosinophilia and/or activation across a number of diseases. Importantly, in respiratory diseases such as asthma, CRSwNP and allergic bronchopulmonary aspergilliosis (ABPA), which can present with multiple endotypes, galectin-10 protein and CLCs are more frequently associated with a type 2 signature, and potentially a sign of intense eosinophil activation [10][11][12][13][14]. Even in COVID-19, where eosinophil activation seems to be linked to disease severity, high levels of Gal-10 were measured in critically ill compared to patients with mild disease, but so far CLCs have not been reported [15].…”

Endotypes of Chronic Rhinosinusitis; relationships to disease phenotypes, pathogenesis, clinical findings and treatment approaches.

“…Interestingly, there has been a shift in the endotype distribution over time with an increase in the degree of eosinophilia observed in NPs from Asian patients 67,68 . Furthermore, recent research suggests that neutrophilic inflammation may also play a role in the pathogenesis of Western NP 69 . Thus, it is clear that inflammatory patterns in CRSwNP show geographic variability across Europe, Asia, and Oceania 56 .…”