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.
Abstract
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
Footnotes
Provenance: Commissioned article, peer reviewed.
Conflict of interest: R. Wadhwa has nothing to disclose.
Conflict of interest: K. Dua has nothing to disclose.
Conflict of interest: I.M. Adcock has nothing to disclose.
Conflict of interest: J.C. Horvat has nothing to disclose.
Conflict of interest: R.Y. Kim has nothing to disclose.
Conflict of interest: P.M. Hansbro reports grants to develop inflammasome inhibitors for therapeutic use.
Support statement: R.Y. Kim is supported by a Fellowship from Lung Foundation Australia and Boehringer Ingelheim. P.M. Hansbro is supported by a Fellowship from the National Health and Medical Research Council of Australia (NHMRC #1079187).
- Received August 1, 2019.
- Accepted September 19, 2019.
- Copyright ©ERS 2019.
This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.