Transcriptome analysis in patients with asthma after inhaled combination therapy with long-acting β2-agonists and corticosteroids

Liang, Yaru; Tzeng, I‐Shiang; Hsieh, Po‐Chun; Kuo, Chan‐Yen; Huang, Shiang-Yu; Yang, Mei‐Chen; Wu, Yao‐Kuang; Cui, Lan

doi:10.7150/ijms.76013

Cited by 4 publications

(3 citation statements)

References 31 publications

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“…Liang et al reported ICS/LABAs treatment reduced airway inflammation and remodeling, but did not completely suppress allergic stimulation related pathways in treated patients. IgE levels after treatment also showed a decreasing trend, but without statistical significance 58 . However, our target predicted mRNA, IL-4, IL-10, and FCER2, were not reported in this RNA transcription study.…”

Section: Discussionmentioning

confidence: 92%

Differentially expressed microRNAs in peripheral blood cell are associated with downregulated expression of IgE in nonallergic childhood asthma

Lee

Wang

Lin

et al. 2023

Sci Rep

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Childhood asthma is a heterogeneous disease characterized by chronic airway inflammation, leading to a broad range of clinical presentations. Nonallergic asthma is asthma without allergic sensitization. Both clinical manifestations and immunopathological mechanisms of nonallergic childhood asthma were rarely investigated. We aimed to compare the clinical features between nonallergic and allergic childhood asthma and apply microRNA to explore the underlying mechanism of nonallergic childhood asthma. We enrolled 405 asthmatic children (76 nonallergic, 52 allergic with total IgE < 150 IU/mL and 277 allergic with total IgE > 150 IU/mL). Clinical characteristics were compared between groups. Comprehensive miRNA sequencing (RNA-seq) was performed using peripheral blood from 11 nonallergic and 11 allergic patients with elevated IgE, respectively. Differentially expressed miRNA (DEmiRNA) were determined with DESeq2. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis was performed to determine functional pathways involved. Publicly available mRNA expression data was applied to investigate the predicted target mRNA networks via Ingenuity Pathway Analysis (IPA). The average age of nonallergic asthma was significantly younger (5.614 ± 2.743 vs 6.676 ± 3.118 years-old). Higher severity and worse control were more common in nonallergic asthma (two-way ANOVA, P < 0.0001). Long-term severity was higher, and intermittent attacks persisted in nonallergic patients. We identified 140 top DEmiRNAs based on false discovery rate (FDR) q-value < 0.001. Forty predicted target mRNA gene were associated with nonallergic asthma. The enriched pathway based on GO included Wnt signaling pathway. IgE expression was predicted to be downregulated by a network involving simultaneous interaction with IL-4, activation of IL-10 and inhibition of FCER2. Nonallergic childhood asthma were distinct in their younger age, higher long-term severity and more persistent course. Differentially expressed miRNA signatures associate with downregulation of total IgE expression and predicted target mRNA genes related molecular networks contribute to canonical pathways of nonallergic childhood asthma. We demonstrated the negative role of miRNAs involved in regulating IgE expression indicating differences between asthma phenotypes. Identification of biomarkers of miRNAs could contribute to understand the molecular mechanism of endotypes in nonallergic childhood asthma, which can potentially allow delivery of precision medicine to pediatric asthma.

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Section: Discussionmentioning

confidence: 92%

Differentially expressed microRNAs in peripheral blood cell are associated with downregulated expression of IgE in nonallergic childhood asthma

Lee

Wang

Lin

et al. 2023

Sci Rep

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“…The use of Inhaled Corticosteroids/ Long-Acting Beta2 Agonists (ICS/LABAs) is known to reduce airway inflammatory and remodeling pathways. For instance, in post-ICS-LABA treatment, there's a noted downregulation in the expression of various elements like nuclear receptor transcription coactivator, N-acetyltransferase, protein tyrosine kinase, nuclear receptor, and RNA polymerase II-activating transcription factor [158].…”

Section: The Role Of Standard Therapy In Airway Remodeling (Lama)mentioning

confidence: 99%

The New Paradigm: The Role of Proteins and Triggers in the Evolution of Allergic Asthma

Baglivo,

Quaranta,

Dragonieri

et al. 2024

Preprint

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Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. The rise in airways epithelial barrier permeability alters the tissue homeostasis and allows the allergen and other external agents penetration. Different factors contribute to barrier impairment, such as eosinophilic infiltrate and allergens proteases action: the eosinophilic cationic proteins and the allergens' proteolytic activity have a central role in contributing to epithelial damage. In the airways, the allergens proteases degrade the epithelial junctional proteins allowing the allergen penetration and the uptake by dendritic cells. The increase in allergen-immune system interactions induce the release of the alarmins and the activation of type 2 inflammatory pathways causing, or worsening, the main symptoms at skin, bowel and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic proteases-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance and progression. We further will explore clinical and radiological potential biomarkers of airways remodeling in allergic asthma patients.

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“…The use of Inhaled Corticosteroids/Long-Acting Beta2 Agonists (ICS/LABAs) is known to reduce airway inflammatory and remodeling pathways. For instance, in post-ICS-LABA treatment, a noted downregulation has been reported in the expression of various elements like nuclear receptor transcription coactivator, N-acetyltransferase, protein tyrosine kinase, nuclear receptor, and RNA polymerase II-activating transcription factor [ 157 ].…”

Section: Relevant Therapeutic Options and New Potential Therapeutic T...mentioning

confidence: 99%

The New Paradigm: The Role of Proteins and Triggers in the Evolution of Allergic Asthma

Baglivo,

Quaranta,

Dragonieri

et al. 2024

IJMS

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Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. Rises in the epithelial barrier permeability of airways alter tissue homeostasis and allow the penetration of allergens and other external agents. Different factors contribute to barrier impairment, such as eosinophilic infiltration and allergen protease action—eosinophilic cationic proteins’ effects and allergens’ proteolytic activity both contribute significantly to epithelial damage. In the airways, allergen proteases degrade the epithelial junctional proteins, allowing allergen penetration and its uptake by dendritic cells. This increase in allergen–immune system interaction induces the release of alarmins and the activation of type 2 inflammatory pathways, causing or worsening the main symptoms at the skin, bowel, and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic protease-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance, and progression. Moreover, we will explore potential clinical and radiological biomarkers of airway remodeling in allergic asthma patients.

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Transcriptome analysis in patients with asthma after inhaled combination therapy with long-acting β2-agonists and corticosteroids

Cited by 4 publications

References 31 publications

Differentially expressed microRNAs in peripheral blood cell are associated with downregulated expression of IgE in nonallergic childhood asthma

Differentially expressed microRNAs in peripheral blood cell are associated with downregulated expression of IgE in nonallergic childhood asthma

The New Paradigm: The Role of Proteins and Triggers in the Evolution of Allergic Asthma

The New Paradigm: The Role of Proteins and Triggers in the Evolution of Allergic Asthma

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