Asthma Phenotypes Defined From Parameters Obtained During Recovery From a Hospital-Treated Exacerbation

Qiu, Rihuang; Xie, Jiaxing; Chung, Kian Fan; Li, Naijian; Yang, Zujun; He, Mei; Li, Jing; Chen, Rongchang; Zhong, Nanshan; Zhang, Qingling

doi:10.1016/j.jaip.2018.02.012

Cited by 25 publications

(16 citation statements)

References 27 publications

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“…Like CRSwNP, asthma is also a complex and heterogeneous disease, and two major endotypes of asthma, type 2-high asthma and type 2-low asthma, have been described, based on underlying airway immune-mediated inflammation [34,35]. In this regard approximately 50% to 60% of all patients with severe asthma in Europe and the United States account for type 2-high asthma, compared to 38.5% of the severe asthmatic patients with type 2-high asthma in China [36][37][38][39]. Thus, whilst it is possible that generally more Western patients with CRSwNP + AS are also likely to be characterised with type 2-high inflammation than Asian patients CRSwNP + AS, this nevertheless needs to be confirmed in well-designed multicenter studies in the future.…”

Section: Discussionmentioning

confidence: 99%

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

Wang

Luan

et al. 2020

Clin Transl Allergy

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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 CRSwNP-alone patients, 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.

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Section: Discussionmentioning

confidence: 99%

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

Wang

Luan

et al. 2020

Clin Transl Allergy

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show abstract

“…Like CRSwNP, asthma is also a complex and heterogeneous disease, and two major endotypes of asthma, type 2-high asthma and type 2-low asthma, have been described, based on underlying airway immunemediated in ammation [34,35]. In this regard approximately 50% to 60% of all patients with severe asthma in Europe and the United States account for type 2-high asthma, compared to 38.5% of the severe asthmatic patients with type 2-high asthma in China [36][37][38][39]. Thus, whilst it is possible that generally more Western patients with CRSwNP+AS are also likely to be characterised with type 2-high in ammation than Asian patients CRSwNP+AS, this nevertheless needs to be con rmed in well-designed multicenter studies in the future.…”

Section: Discussionmentioning

confidence: 99%

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

Wang

Luan

et al. 2020

Preprint

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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.

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“…In contrast to childhood‐onset disease, adult‐onset asthma frequently presents as a nonatopic and eosinophilic condition, 1‐6 although it shares similar clinical and physiological features. This phenotype of asthma is closely associated with other adult‐onset eosinophilic airway diseases such as nonsteroidal anti‐inflammatory drug (NSAID)‐exacerbated airway disease (N‐ERD) and CRSwNP/eosinophilic CRS, as well as an eosinophilic systemic disease, eosinophilic granulomatosis with polyangiitis (EGPA) (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Adult‐onset eosinophilic airway diseases

Asano

Ueki

Tamari

et al. 2020

Allergy

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Allergic diseases in the upper and the lower airways such as allergic rhinitis and atopic asthma are usually accompanied by local eosinophilia and sometimes by peripheral blood eosinophilia. Chronic rhinosinusitis with nasal polyps (CRSwNP) and nonatopic asthma are also characterized by local and systemic eosinophilia; however, there are substantial differences in the age of onset and the presence of atopy. Atopic asthma and allergic rhinitis develop during childhood in most cases and mediated by type 1 hypersensitivity reactions to allergen(s), as are other childhood-onset allergic diseases such as food allergies and eczema. Patients often develop these diseases consecutively as an allergic march (Figure 1), suggesting the presence of common genetic backgrounds and pathophysiology. In contrast to childhood-onset disease, adult-onset asthma frequently presents as a nonatopic and eosinophilic condition, 1-6

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Asthma Phenotypes Defined From Parameters Obtained During Recovery From a Hospital-Treated Exacerbation

Cited by 25 publications

References 27 publications

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

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

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

Adult‐onset eosinophilic airway diseases

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