Endotypes of chronic rhinosinusitis: Impact on management

Cardell, Lars-Olaf; Stjärne, Pär; Jonstam, Karin; Bachert, Claus

doi:10.1016/j.jaci.2020.01.019

Cited by 78 publications

(76 citation statements)

References 32 publications

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“…Some mAbs have recently been proved in phase 3 trials as efficient therapy on nasal polyp size and reduction of severity of symptoms [44]. Improving the understanding of different endotypes should provide insight for determining appropriate current and new therapies [45][46][47][48]. Kim et al concluded that endotypes depend on the epithelial barrier function, epithelial cytokines, and T cell subsets [46].…”

Section: Discussionmentioning

confidence: 99%

Pathogenesis of chronic rhinosinusitis with nasal polyps: role of IL-6 in airway epithelial cell dysfunction

et al. 2020

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Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by an alteration in airway epithelial cell functions including barrier function, wound repair mechanisms, mucociliary clearance. The mechanisms leading to epithelial cell dysfunction in nasal polyps (NPs) remain poorly understood. Our hypothesis was that among the inflammatory cytokines involved in NPs, IL-6 could alter epithelial repair mechanisms and mucociliary clearance. The aim of this study was to evaluate the in vitro effects of IL-6 on epithelial repair mechanisms in a wound repair model and on ciliary beating in primary cultures of Human Nasal Epithelial Cells (HNEC). Methods: Primary cultures of HNEC taken from 38 patients during surgical procedures for CRSwNP were used in an in vitro model of wound healing. Effects of increasing concentrations of IL-6 (1 ng/mL, 10 ng/mL, and 100 ng/mL) and other ILs (IL-5, IL-9, IL-10) on wound closure kinetics were compared to cultures without IL-modulation. After wound closure, the differentiation process was characterized under basal conditions and after IL supplementation using cytokeratin-14, MUC5AC, and β IV tubulin as immunomarkers of basal, mucus, and ciliated cells, respectively. The ciliated edges of primary cultures were analyzed on IL-6 modulation by digital high-speed video-microscopy to measure: ciliary beating frequency (CBF), ciliary length, relative ciliary density, metachronal wavelength and the ciliary beating efficiency index. Results: Our results showed that: (i) IL-6 accelerated airway wound repair in vitro, with a dose-response effect whereas no effect was observed after other ILs-stimulation. After 24 h, 79% of wounded wells with IL6-100 were fully repaired, vs 46% in the IL6-10 group, 28% in the IL6-1 group and 15% in the control group; (ii) specific migration analyses of closed wound at late repair stage (Day 12) showed IL-6 had the highest migration compared with other ILs (iii) The study of the IL-6 effect on ciliary function showed that CBF and metachronal wave increased but without significant modifications of ciliary density, length of cilia and efficiency index. Conclusion: The up-regulated epithelial cell proliferation observed in polyps could be induced by IL-6 in the case of prior epithelial damage. IL-6 could be a major cytokine in NP physiopathology.

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Section: Discussionmentioning

confidence: 99%

Pathogenesis of chronic rhinosinusitis with nasal polyps: role of IL-6 in airway epithelial cell dysfunction

et al. 2020

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“…For the endotyping of CRS, the measurement of cytokines and chemokines is useful [9,37,38]. Emerging evidence has indicated that several biologics targeting Th2 cytokines as well as IgE show promise as therapeutics for severe and uncontrolled ECRS [39]. Thus, for appropriate, effective, and successful therapy, endotyping of CRS is important [9,[38][39][40].…”

Section: Discussionmentioning

confidence: 99%

“…Emerging evidence has indicated that several biologics targeting Th2 cytokines as well as IgE show promise as therapeutics for severe and uncontrolled ECRS [39]. Thus, for appropriate, effective, and successful therapy, endotyping of CRS is important [9,[38][39][40]. Recent reports using gene expression analysis and a genome-wide association study have revealed the significance of 15-LOX-1 in the pathogenesis of CRSwNP [20,21,41].…”

Section: Discussionmentioning

confidence: 99%

“…Recent reports using gene expression analysis and a genome-wide association study have revealed the significance of 15-LOX-1 in the pathogenesis of CRSwNP [20,21,41]. Although the appearance of NPs may be similar, the pathophysiological features of NPs show heterogeneity and are complicated [7,39]. The JESREC study could distinguish ECRS (eosinophilic inflammation) and non-ECRS (neutrophilic inflammation) based on both the pathological and clinical features.…”

Section: Discussionmentioning

confidence: 99%

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Enhanced 15-Lipoxygenase 1 Production is Related to Periostin Expression and Eosinophil Recruitment in Eosinophilic Chronic Rhinosinusitis

et al. 2020

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Background: The pathological features of chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) tissues include an eosinophilic infiltration pattern (eosinophilic CRS (ECRS)) or a less eosinophilic pattern (non-ECRS). Recently, it has been suggested that 15-lipoxygenase 1 (15-LOX-1) may have significant roles in allergic disease; however, the significance of 15-LOX-1 in CRS is not well understood. The objective of this study was to demonstrate the expression of 15-LOX-1 in CRS. Methods: The mRNA expression levels of 15-LOX-1 and periostin in nasal tissues were measured by quantitative real-time polymerase chain reaction. We also performed an immunofluorescence study of nasal tissues. Cells of the Eol-1 eosinophilic leukemic cell line were stimulated with interleukin-33 to test the induction of 15-LOX-1. Results: The expression level of 15-LOX-1 mRNA in nasal polyps (NPs) was significantly higher in ECRS patients than in non-ECRS patients. The immunofluorescence study revealed that both airway epithelial cells and eosinophils in NPs expressed 15-LOX-1. A significant correlation was seen between the number of eosinophils and the mRNA expression levels of 15-LOX-1 and periostin in nasal polyps. Moreover, interleukin-33 enhanced 15-LOX-1 expression in Eol-1 cells. Conclusions: 15-LOX-1 was shown to be a significant molecule that facilitates eosinophilic inflammation in ECRS.

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“…Рекомендуется проводить анализ эффективности терапии через 16 недель после старта. Самым чувствительным клиническим показателем является обоняние, улучшение которого может быть зарегистрировано уже на 4-8 неделе от начала использования биологической терапии [33]. Достижение улучшений по всем 5 критериям оценки будет свидетельствовать об отличном ответе, по 3-4 критериям среднем ответе, по 1-2 критериям плохом ответе и, соответственно, отсутствие изменений по всем критериям оценки будет свидетельствовать об отсутствии ответа.…”

Section: ;19;3(106)unclassified

Unresolved issues of management of patients with severe allergic rhinitis and nasal polyposis. The possibilities of anti-IgE therapy

Emelyanov¹,

Ilina²,

Карнеева³

et al. 2020

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The current state of the patients’ management with nasal polyposis and allergic rhinitis has become the basis for a deep analysis of the currently available data on the prevalence of diseases (with a focus on severe forms), as well, available possibilities and disadvantages of conservative therapy are considered. The approaches to assessing the severity and control of diseases and the influence of an uncontrolled course on the quality of the patients’ life are presented. Particular attention is paid to a new class of drugs – monoclonal antibodies, which might change the patients’ treatment paradigm of severe uncontrolled course of allergic rhinitis and nasal polyposis. The efficacy and safety issues of immunobiological therapy are discussed on the example of the IgE-targeted medicine omalizumab. The potential place of the drug in the treatment of the mentioned above forms of nasal polyposis and allergic rhinitis is indicated.

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Endotypes of chronic rhinosinusitis: Impact on management

Cited by 78 publications

References 32 publications

Pathogenesis of chronic rhinosinusitis with nasal polyps: role of IL-6 in airway epithelial cell dysfunction

Pathogenesis of chronic rhinosinusitis with nasal polyps: role of IL-6 in airway epithelial cell dysfunction

Enhanced 15-Lipoxygenase 1 Production is Related to Periostin Expression and Eosinophil Recruitment in Eosinophilic Chronic Rhinosinusitis

Unresolved issues of management of patients with severe allergic rhinitis and nasal polyposis. The possibilities of anti-IgE therapy

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