Advances in the Knowledge of the Underlying Airway Remodeling Mechanisms in Chronic Rhinosinusitis Based on the Endotypes: A Review

Chronic rhinosinusitis (CRS) is a chronic inflammatory condition of the nasal and paranasal sinus mucosa that affects up to 10% of the population worldwide. CRS is the most representative disease of the upper respiratory tract where airway remodeling occurs, including epithelial damage, thickening of the basement membrane, fibrosis, goblet cell hyperplasia, subepithelial edema, and osteitis. CRS is divided into two phenotypes according to the presence or absence of nasal polyps: CRS with nasal polyp (CRSwNP) and CRS without nasal polyps (CRSsNP). Based on the underlying pathophysiologic mechanism, CRS is also classified as eosinophilic CRS and non-eosinophilic CRS, owing to Type 2 T helper (Th2)-based inflammation and Type 1 T helper (Th1)/Type 17 T helper (Th17) skewed immune response, respectively. Differences in tissue remodeling in CRS are suggested to be based on the clinical phenotype and endotypes; this is because fibrosis is prominent in CRSsNP, whereas edematous changes occur in CRSwNP, especially in the eosinophilic type. This review aims to summarize the latest information on the different mechanisms of airway remodeling in CRS according to distinct endotypes.

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Inflammation and Endotyping in Chronic Rhinosinusitis—A Paradigm Shift

Medicina ◽

10.3390/medicina55040095 ◽

2019 ◽

Vol 55 (4) ◽

pp. 95 ◽

Cited By ~ 10

Author(s):

Sinead Ahern ◽

Anders Cervin

Keyword(s):

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Treatment Options ◽

Cell Types ◽

Nasal Passage ◽

Appropriate Treatment ◽

Chronic Inflammatory Condition ◽

Inflammatory Profile

Chronic rhinosinusitis (CRS) is a heterogeneous chronic inflammatory condition of the paranasal sinuses and nasal passage. It is characterized as inflammation of the sinonasal passage, presenting with two or more symptoms (nasal blockage, secretions, facial pain and headaches) for more than 12 weeks consecutively. The disease is phenotypically differentiated based on the presence of nasal polyps; CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Traditionally, CRSwNP has been associated with a type 2 inflammatory profile, while CRSsNP has been associated with a type 1 inflammatory profile. Extensive work in characterizing the inflammatory profiles of CRS patients has challenged this dichotomy, with great variation both between and within populations described. Recent efforts of endotyping CRS based on underlying pathophysiology have further highlighted the heterogeneity of the disease, revealing mixed inflammatory profiles coordinated by a number of inflammatory cell types. This review will highlight the current understanding of inflammation in CRS, and discuss the importance and impact of refining this understanding in the development of appropriate treatment options for CRS sufferers.

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Release of Type 2 Cytokines by Epithelial Cells of Nasal Polyps

Journal of Immunology Research ◽

10.1155/2016/2643297 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 13

Author(s):

Monica Boita ◽

Caterina Bucca ◽

Giuseppe Riva ◽

Enrico Heffler ◽

Giovanni Rolla

Keyword(s):

Immune Response ◽

Epithelial Cells ◽

Chronic Rhinosinusitis ◽

Cell Cultures ◽

Nasal Polyps ◽

Dermatophagoides Pteronyssinus ◽

Poly I:C ◽

Type 2 Cytokines ◽

Sinus Mucosa

Background. T2 inflammation of chronic rhinosinusitis with nasal polyps (CRSwNP) may be influenced by epithelial cytokines release (TSLP, IL-25, and IL-33). We investigated the release of TSLP, IL-25, and IL-33 by epithelial CRSwNP cells compared to epithelial sinus mucosa cells of patients with chronic rhinosinusitis without nasal polyps (CRSsNP).Methods. IL-25, IL-33, and TSLP were measured by ELISA in the supernatant of cell cultures derived by CRSwNP (9 patients, 6 atopic) and CRSsNP (7 patients, 2 atopic) in baseline condition and following stimulation withDermatophagoides pteronyssinus(DP),Aspergillus fumigatus(AF), and poly(I:C).Results. CRSwNP epithelial cells released increased levels of IL-25 (from 0.12 ± 0.06 pg/ml to 0.27 ± 0.1 pg/ml,p<0.01) and TSLP (from 0.77 ± 0.5 pg/ml to 2.53 ± 1.17 pg/ml,p<0.001) following poly(I:C) stimulation, while CRSsNP epithelial cells released increased levels of IL-25 and IL-33 following AF and DP stimulation, respectively (IL-25: from 0.18 ± 0.07 pg/ml to 0.51 ± 0.1 pg/ml,p<0.001; IL-33: from 2.57 ± 1.3 pg/ml to 5.7 ± 3.1 pg/ml,p<0.001).Conclusions. CRSwNP epithelial cells release TSLP and IL-25 when stimulated by poly(I:C) but not by DP or AF, suggesting that viral infection may contribute to maintain and amplify the T2 immune response seen in CRSwNP.

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The tumor necrosis factor family molecules LIGHT and lymphotoxins in sinus mucosa of patients with chronic rhinosinusitis with or without nasal polyps

Cytokine ◽

10.1016/j.cyto.2021.155594 ◽

2021 ◽

pp. 155594

Author(s):

Jae Woong Hwang ◽

Young Chan Kim ◽

Ho Young Lee ◽

Ki Jeong Lee ◽

Tae Hoon Kim ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Family ◽

Sinus Mucosa ◽

Necrosis Factor

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Biological therapy of chronic rhinosinusitis

Otorinolaryngologie a foniatrie ◽

10.48095/ccorl2021109 ◽

2021 ◽

Vol 70 (2) ◽

pp. 109-114

Author(s):

Zuzana Balatková ◽

Zdeněk Knížek ◽

Jan Vodička ◽

Jan Plzák

Keyword(s):

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Biological Therapy ◽

Immunoglobulin E ◽

Sinus Surgery ◽

Therapeutic Choice ◽

First Choice ◽

Intranasal Steroids

The aim of this paper is to present an up-to-date information about therapeutical options in chronic rhinosinusitis with nasal polyps. First choice therapy is a long term regular application of intranasal steroids in combination with salinic solution douches. If this treatment is not eff ective enough, then the pulses of systemic steroids are indicated. If the sufficient control of the disease is not achieved, then surgery is a therapeutic choice; it means functional endoscopic sinus surgery in the extent corresponding to the extension of the sinus disease. However, there remains a certain group of patients in whom the results with this treatment are not optimal. The type 2 immunopathological response affects relevantly the course of the disease. Nowadays, the research is done in this field. Specific agents, which are able to block circulating inflammatory mediators or bind receptors for these mediators are developed and studied. The results of the studies having been completed by now are promising. Keywords: biological therapy – chronic rhinosinusitis – nasal polyps – dupilumab – immunoglobulin E – interleukin

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Dupilumab Reduces Blood, Urine, and Nasal Biomarkers of Type 2 Inflammation in Patients With Chronic Rhinosinusitis With Nasal Polyps in the Phase 3 SINUS-52 Trial

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2019.12.324 ◽

2020 ◽

Vol 145 (2) ◽

pp. AB185

Author(s):

Claus Bachert ◽

Seong Cho ◽

Tanya Laidlaw ◽

Brian Swanson ◽

Sivan Harel ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Phase 3 ◽

Type 2 Inflammation

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P505 DUPILUMAB EFFECT ON TYPE 2 INFLAMMATION BIOMARKERS IN CHRONIC RHINOSINUSITIS WITH NASAL POLYPS AND NSAID-ERD

Annals of Allergy Asthma & Immunology ◽

10.1016/j.anai.2020.08.163 ◽

2020 ◽

Vol 125 (5) ◽

pp. S48

Author(s):

A. White ◽

S. Fujieda ◽

T. Takabayashi ◽

N. Daizadeh ◽

Y. Deniz ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Type 2 Inflammation

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Possible Role of TGF – B Pathways in Schizophrenia / Moguća Uloga TTGF - B Signalnih Puteva U Shizofreniji

Serbian Journal of Experimental and Clinical Research ◽

10.1515/sjecr-2015-0038 ◽

2016 ◽

Vol 17 (1) ◽

pp. 3-8 ◽

Cited By ~ 2

Author(s):

Milica Borovcanin ◽

Ivan Jovanovic ◽

Slavica Djukic Dejanovic ◽

Gordana Radosavljevic ◽

Nebojsa Arsenijevic ◽

...

Keyword(s):

Meta Analysis ◽

Psychotic Episode ◽

T Helper ◽

Helper Cell Type ◽

State Marker ◽

Valuable Marker ◽

Anti Inflammatory

AbstractThe phenomenological uniqueness of each patient with schizophrenia is determined by complex symptomatology, particularly the overlapping of symptoms and their prominence in certain phases of this mental disorder. Establishing biological markers is an important step in the further objectivisation and quantification of schizophrenia. Identifying the cytokine profiles that precede a psychotic episode could direct the strategies for relapse prevention and be useful in predicting disease progression and treatment response. In the context of infl ammation, TGF-β exerts potent anti-inflammatory and immunosuppressive functions by inhibiting pro-inflammatory cytokine synthesis, but it can also have pro-inflammatory functions through its stimulatory effects on inflammatory Th17 cells. It has been shown that the T helper cell type-1 and type-17 responses are reduced and type-2 response is increased in patients with schizophrenia. Both data from the literature and our results also indicate the presence of an anti-inflammatory response through production of the TGF-β regulatory cytokine. A meta-analysis of plasma cytokine alterations suggested that TGF-β is the state marker for acute exacerbation of schizophrenia, and we showed that TGF-β can also be a valuable marker for psychosis. Hyperactivity of TGF-β signalling pathways in schizophrenia may be both a neuroprotective mechanism and a possible therapeutic target.

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