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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
European Respiratory Society
2019
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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. |
format | Online Article Text |
id | pubmed-9488801 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | European Respiratory Society |
record_format | MEDLINE/PubMed |
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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