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Cellular mechanisms underlying steroid-resistant asthma

Severe steroid-resistant asthma is clinically important, as patients with this form of the disease do not respond to mainstay corticosteroid therapies. The heterogeneity of this form of asthma and poor understanding of the pathological mechanisms involved hinder the identification of therapeutic tar...

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Autores principales: Wadhwa, Ridhima, Dua, Kamal, Adcock, Ian M., Horvat, Jay C., Kim, Richard Y., Hansbro, Philip M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: European Respiratory Society 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9488801/
https://www.ncbi.nlm.nih.gov/pubmed/31636089
http://dx.doi.org/10.1183/16000617.0096-2019
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author Wadhwa, Ridhima
Dua, Kamal
Adcock, Ian M.
Horvat, Jay C.
Kim, Richard Y.
Hansbro, Philip M.
author_facet Wadhwa, Ridhima
Dua, Kamal
Adcock, Ian M.
Horvat, Jay C.
Kim, Richard Y.
Hansbro, Philip M.
author_sort Wadhwa, Ridhima
collection PubMed
description Severe steroid-resistant asthma is clinically important, as patients with this form of the disease do not respond to mainstay corticosteroid therapies. The heterogeneity of this form of asthma and poor understanding of the pathological mechanisms involved hinder the identification of therapeutic targets and the development of more effective therapies. A major limiting factor in the understanding of severe steroid-resistant asthma is the existence of multiple endotypes represented by different immunological and inflammatory phenotypes, particularly in adults. Several clinical and experimental studies have revealed associations between specific respiratory infections and steroid-resistant asthma in adults. Here, we discuss recent findings from other authors as well as our own studies that have developed novel experimental models for interrogating the association between respiratory infections and severe steroid-resistant asthma. These models have enabled the identification of new therapies using macrolides, as well as several novel disease mechanisms, including the microRNA-21/phosphoinositide 3-kinase/histone deacetylase 2 axis and NLRP3 inflammasomes, and highlight the potential of these mechanisms as therapeutic targets.
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spelling pubmed-94888012022-11-14 Cellular mechanisms underlying steroid-resistant asthma Wadhwa, Ridhima Dua, Kamal Adcock, Ian M. Horvat, Jay C. Kim, Richard Y. Hansbro, Philip M. Eur Respir Rev Lung Science Conference Review Severe steroid-resistant asthma is clinically important, as patients with this form of the disease do not respond to mainstay corticosteroid therapies. The heterogeneity of this form of asthma and poor understanding of the pathological mechanisms involved hinder the identification of therapeutic targets and the development of more effective therapies. A major limiting factor in the understanding of severe steroid-resistant asthma is the existence of multiple endotypes represented by different immunological and inflammatory phenotypes, particularly in adults. Several clinical and experimental studies have revealed associations between specific respiratory infections and steroid-resistant asthma in adults. Here, we discuss recent findings from other authors as well as our own studies that have developed novel experimental models for interrogating the association between respiratory infections and severe steroid-resistant asthma. These models have enabled the identification of new therapies using macrolides, as well as several novel disease mechanisms, including the microRNA-21/phosphoinositide 3-kinase/histone deacetylase 2 axis and NLRP3 inflammasomes, and highlight the potential of these mechanisms as therapeutic targets. European Respiratory Society 2019-10-18 /pmc/articles/PMC9488801/ /pubmed/31636089 http://dx.doi.org/10.1183/16000617.0096-2019 Text en Copyright ©ERS 2019. https://creativecommons.org/licenses/by-nc/4.0/This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.
spellingShingle Lung Science Conference Review
Wadhwa, Ridhima
Dua, Kamal
Adcock, Ian M.
Horvat, Jay C.
Kim, Richard Y.
Hansbro, Philip M.
Cellular mechanisms underlying steroid-resistant asthma
title Cellular mechanisms underlying steroid-resistant asthma
title_full Cellular mechanisms underlying steroid-resistant asthma
title_fullStr Cellular mechanisms underlying steroid-resistant asthma
title_full_unstemmed Cellular mechanisms underlying steroid-resistant asthma
title_short Cellular mechanisms underlying steroid-resistant asthma
title_sort cellular mechanisms underlying steroid-resistant asthma
topic Lung Science Conference Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9488801/
https://www.ncbi.nlm.nih.gov/pubmed/31636089
http://dx.doi.org/10.1183/16000617.0096-2019
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