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Cellular mechanisms underlying steroid-resistant asthma

  • Ridhima Wadhwa
  • , Kamal Dua
  • , Ian M. Adcock
  • , Jay C. Horvat
  • , Richard Y. Kim
  • , Philip M. Hansbro
  • Centenary Institute
  • University of Technology Sydney
  • Hunter Medical Research Institute, Australia
  • Imperial College London

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

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.

Original languageEnglish
Article number190096
JournalEuropean Respiratory Review
Volume28
Issue number153
DOIs
StatePublished - Sep 2019
Externally publishedYes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

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