Cellular mechanisms underlying steroid-resistant asthma. (18th October 2019)

• Record Type: Journal Article
• Authors: Wadhwa, Ridhima; Dua, Kamal; Adcock, Ian M.; Horvat, Jay C.; Kim, Richard Y.; Hansbro, Philip M.
• Is Part Of: European respiratory review. Volume 28:Number 153(2019)
• Publication Date: 2019-10-18
• Subjects: Respiratory organs -- Diseases -- Periodicals; Respiratory Tract Diseases; Respiratory organs -- Diseases; Respiratory organs -- Diseases -- Treatment; Electronic journals; Periodical; Periodicals; Periodicals; 616.2
• DOI: 10.1183/16000617.0096-2019
• Languages: English
• ISSNs: 0905-9180

Abstract

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. Severe steroid-resistant asthma is a significant clinical problem and recent advances in understanding the mechanisms of pathogenesis enable the identification of novel therapeutic approaches http://bit.ly/2mQpF3n