Mechanisms and treatments for severe, steroid-resistant allergic airway disease and asthma

Philip M. Hansbro, Richard Y. Kim, Malcolm R. Starkey, Chantal Donovan, Kamal Dua, Jemma R. Mayall, Gang Liu, Nicole G. Hansbro, Jodie L. Simpson, Lisa G. Wood, Jeremy A. Hirota, Darryl A. Knight, Paul S. Foster, Jay C. Horvat

Research output: Contribution to journalReview ArticleOtherpeer-review

72 Citations (Scopus)

Abstract

Severe, steroid-resistant asthma is clinically and economically important since affected individuals do not respond to mainstay corticosteroid treatments for asthma. Patients with this disease experience more frequent exacerbations of asthma, are more likely to be hospitalized, and have a poorer quality of life. Effective therapies are urgently required, however, their development has been hampered by a lack of understanding of the pathological processes that underpin disease. A major obstacle to understanding the processes that drive severe, steroid-resistant asthma is that the several endotypes of the disease have been described that are characterized by different inflammatory and immunological phenotypes. This heterogeneity makes pinpointing processes that drive disease difficult in humans. Clinical studies strongly associate specific respiratory infections with severe, steroid-resistant asthma. In this review, we discuss key findings from our studies where we describe the development of representative experimental models to improve our understanding of the links between infection and severe, steroid-resistant forms of this disease. We also discuss their use in elucidating the mechanisms, and their potential for developing effective therapeutic strategies, for severe, steroid-resistant asthma. Finally, we highlight how the immune mechanisms and therapeutic targets we have identified may be applicable to obesity-or pollution-associated asthma.

Original languageEnglish
Pages (from-to)41-62
Number of pages22
JournalImmunological Reviews
Volume278
Issue number1
DOIs
Publication statusPublished - Jul 2017
Externally publishedYes

Keywords

  • infection
  • novel therapies
  • obesity
  • pollution
  • severe asthma
  • steroid resistance

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