scholarly journals Distinct type 2-high inflammation associated molecular signatures of chronic rhinosinusitis with nasal polyps with comorbid asthma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ming Wang ◽  
Xiangting Bu ◽  
Ge Luan ◽  
Liqing Lin ◽  
Yang Wang ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Distinct Type ◽  
Molecular Signatures

scholarly journals Distinct Type 2-high Inflammation Associated Molecular Signatures of Chronic Rhinosinusitis with Nasal Polyps with Comorbid Asthma

2020 ◽  
Author(s):  
Ming Wang ◽  
Xiangting Bu ◽  
Ge Luan ◽  
Liqing Lin ◽  
Yang Wang ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Nasal Polyps ◽  
Acid Metabolism ◽  
Distinct Type ◽  
Arachidonic Acid Metabolism ◽  
Eosinophil Infiltration ◽  
Phenotypic Traits ◽  
Molecular Signatures ◽  
Type 2 Cytokines

Abstract Background: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and comorbid asthma have more severe disease and are difficult to treat. However, the molecular endotypes associated with CRSwNP with comorbid asthma (CRSwNP+AS) are not clear. This study aimed to investigate the characteristics of type 2 inflammation and the molecular signatures associated with CRSwNP+AS. Methods: A total of 195 subjects; including 65 CRSwNP+AS patients, 99 patients with CRSwNP-alone, and 31 healthy control subjects; were enrolled in the study. Nasal tissues from patients with CRSwNP+AS, CRSwNP-alone and control subjects were assessed for infiltration of inflammatory cells and concentrations of total IgE. Whole-transcriptome sequencing was performed and differentially expressed (DE) mRNAs and long non-coding RNAs (lncRNAs) and their associated pathways were analyzed. The correlations between type 2 cytokines and local eosinophils, tissue IgE, and transcriptome signatures were evaluated. Results: Significantly higher local eosinophil infiltration and higher levels of total IgE were found in nasal tissues from CRSwNP+AS patients than in nasal tissues from CRSwNP-alone patients. Furthermore, atopy and recurrence were significantly more frequent in patients with CRSwNP+AS than in patients with CRSwNP-alone (62.5% vs 28.6% and 66.7% vs 26.9%, respectively). RNA sequencing analysis identified 1988 common DE-mRNAs, and 176 common DE-lncRNAs shared by CRSwNP+AS versus control and CRSwNP-alone versus control. Weighted gene coexpression network analysis (WGCNA) identified LINC01146 as hub lncRNA dysregulated in both subtypes of CRSwNP. Overall, 968 DE-mRNAs and 312 DE-lncRNAs were identified between CRSwNP+AS and CRSwNP-alone. Both pathway enrichment analysis and WGCNA indicated that the phenotypic traits of CRSwNP+AS were mainly associated with higher activities of arachidonic acid metabolism, type 2 cytokines related pathway and fibrinolysis pathway, and lower activity of IL-17 signalling pathway. Furthermore, the expression of type 2 cytokines; IL5 and IL13, was positively correlated with local eosinophil infiltration, tissue IgE level, and the expression of DE-mRNAs that related to arachidonic acid metabolism. Moreover, WGCNA identified HK3-006 as hub lncRNA in yellow module that most positively correlated with phenotypic traits of CRSwNP+AS. Conclusions: Patients with CRSwNP+AS have distinct type 2-high inflammation-associated molecular signatures in nasal tissues compared to patients with CRSwNP-alone.

scholarly journals Distinct Type 2-high Inflammation Associated Molecular Phenotypes of Chronic Rhinosinusitis with Nasal Polyps with Comorbid Asthma

2020 ◽  
Author(s):  
Ming Wang ◽  
Xiangting Bu ◽  
Ge Luan ◽  
Liqing Lin ◽  
Yang Wang ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Acid Metabolism ◽  
Distinct Type ◽  
Arachidonic Acid Metabolism ◽  
Phenotypic Traits ◽  
Th2 Cytokines ◽  
Molecular Phenotypes

Abstract Background Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and comorbid asthma have more severe disease and are difficult to treat. However, the phenotypes especially the molecular phenotypes of CRSwNP with comorbid asthma (CRSwNP+AS) are not clear. This study aimed to investigate the molecular phenotypes associated with CRSwNP+AS. Methods Nasal tissues from patients with CRSwNP+AS, CRSwNP-alone and control subjects were assessed with infiltrated inflammatory cells and concentrations of total IgE, and performed whole-transcriptome sequencing. Differentially expressed mRNAs (DE-mRNAs) and lncRNAs (DE-lncRNAs) and their associated pathways were analyzed. The correlations between type 2 cytokines and local eosinophils, tissue IgE, and transcriptome signatures were evaluated. Results More local eosinophils infiltration and higher levels of total IgE were found in nasal tissues from CRSwNP+AS than from CRSwNP-alone. RNA sequencing analysis identified 1988 common DE-mRNAs, and 176 common DE-lncRNAs shared by CRSwNP+AS versus control and CRSwNP-alone versus control. Weighted gene coexpression network analysis (WGCNA) identified LINC01146 as hub lncRNA dysregulated in both subtypes of CRSwNP. We identified 968 DE-mRNAs and 312 DE-lncRNAs between CRSwNP+AS and CRSwNP-alone. Both pathway enrichment analysis and WGCNA indicated that the phenotypic traits of CRSwNP+AS were mainly associated with higher activities of arachidonic acid metabolism, Th2 cytokines related pathway and fibrinolysis pathway, and oppositely lower activities of IL-17 signaling pathway. We further showed that the expression of Th2 cytokines, IL5 and IL13, were positively correlated with local eosinophils infiltration, tissue IgE level, and the expression of DE-mRNAs that related to arachidonic acid metabolism. Moreover, WGCNA identified HK3-006 as hub lncRNA in yellow module that most positively correlated with phenotypic traits of CRSwNP+AS. Conclusions Patients with CRSwNP+AS have distinct type 2-high inflammation and its associated transcriptome signatures in nasal tissues compared to patients with CRSwNP alone.

Biological therapy of chronic rhinosinusitis

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

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

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

scholarly journals Dupilumab: new opportunities for the treatment of asthma and chronic rhinosinusitis with nasal polyps

2021 ◽  
Vol 18 (1) ◽  
pp. 18-31
Author(s):  
Miramgul E. Dyneva ◽  
Gulyumkhan E. Aminova ◽  
Oksana Kurbacheva ◽  
Natalya I. Il'ina
Keyword(s):  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Human Monoclonal Antibody ◽  
High Rate ◽  
Cytokine Signaling ◽  
Main Task ◽  
Receptor Complexes ◽  
Target Individual ◽  
Type 2 Inflammation

Airway inflammation plays a key role in asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The inflammatory process can vary in intensity thus affecting the clinical picture of the disease and, most importantly, the effectiveness of therapy. Today, there is still a high rate of growth in the incidence of asthma and CRSwNP and dissatisfaction with the effectiveness of existing therapy for severe forms of asthma, especially when asthma is associated with CRSwNP, so the main task is to find new approaches to diagnosis and therapy. The development of biologics is a promising step forward in achieving control of severe and poorly controlled asthma and recurrent CRSwNP that target individual and specific components of inflammation. One of the latest monoclonal antibodies is Dupilumab that has shown significant success in the treatment of asthma and CRSwNP. Dupilumab is a fully human monoclonal antibody directed against the -subunit of the Il-4 interleukin receptor (IL-4R), common to both IL-4 and IL-4/IL-13 receptor complexes. This contributes to the suppression of type 2 cytokine signaling (IL-4 and IL-13), since the IL-4/IL-13/STAT6 signaling pathway plays a crucial role in type 2-inflammation. Currently, Dupilumab is approved for the treatment of severe asthma and CRSwNP, so this article summarizes the main information about Dupilumab and its effectiveness in these diseases, as well as presents the results of clinical observation.

scholarly journals Enhanced Type 2 Immune Reactions by Increased IL-22/IL-22Ra1 Signaling in Chronic Rhinosinusitis With Nasal Polyps

2020 ◽  
Vol 12 (6) ◽  
pp. 980
Author(s):  
Dong-Kyu Kim ◽  
Ara Jo ◽  
Hee-Suk Lim ◽  
Jin Youp Kim ◽  
Kyoung Mi Eun ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Immune Reactions

scholarly journals Inflammation and Endotyping in Chronic Rhinosinusitis—A Paradigm Shift

Medicina ◽  
2019 ◽  
Vol 55 (4) ◽  
pp. 95 ◽  
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.

scholarly journals Type 2 inflammation in chronic rhinosinusitis without nasal polyps: Another relevant endotype

2020 ◽  
Vol 146 (2) ◽  
pp. 337-343.e6
Author(s):  
Tim Delemarre ◽  
Gabriele Holtappels ◽  
Natalie De Ruyck ◽  
Nan Zhang ◽  
Hans Nauwynck ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Type 2 Inflammation
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