title: Elucidating novel disease mechanisms in severe asthma.
abstract: Corticosteroids are broadly active and potent anti-inflammatory agents that, despite the introduction of biologics, remain as the mainstay therapy for many chronic inflammatory diseases, including inflammatory bowel diseases, nephrotic syndrome, rheumatoid arthritis, chronic obstructive pulmonary disease and asthma. Significantly, there are cohorts of these patients with poor sensitivity to steroid treatment even with high doses, which can lead to many iatrogenic side effects. The dose-limiting toxicity of corticosteroids, and the lack of effective therapeutic alternatives, leads to substantial excess morbidity and healthcare expenditure. We have developed novel murine models of respiratory infection-induced, severe, steroid-resistant asthma that recapitulate the hallmark features of the human disease. These models can be used to elucidate novel disease mechanisms and identify new therapeutic targets in severe asthma. Hypothesis-driven studies can elucidate the roles of specific factors and pathways. Alternatively, 'Omics approaches can be used to rapidly generate new targets. Similar approaches can be used in other diseases.
authors.affiliation: Priority Research Centre for Healthy Lungs and Hunter Medical Research Institute, University of Newcastle , Newcastle, New South Wales, Australia.
authors.forename: Richard Y
authors.initials: RY
authors.lastname: Kim
authors.affiliation: Priority Research Centre for Healthy Lungs and Hunter Medical Research Institute, University of Newcastle , Newcastle, New South Wales, Australia.
authors.forename: Brittany
authors.initials: B
authors.lastname: Rae
authors.affiliation: Priority Research Centre for Healthy Lungs and Hunter Medical Research Institute, University of Newcastle , Newcastle, New South Wales, Australia.
authors.forename: Rachel
authors.initials: R
authors.lastname: Neal
authors.affiliation: Priority Research Centre for Healthy Lungs and Hunter Medical Research Institute, University of Newcastle , Newcastle, New South Wales, Australia.
authors.forename: Chantal
authors.initials: C
authors.lastname: Donovan
authors.affiliation: Priority Research Centre for Healthy Lungs and Hunter Medical Research Institute, University of Newcastle , Newcastle, New South Wales, Australia.
authors.forename: James
authors.initials: J
authors.lastname: Pinkerton
authors.affiliation: Priority Research Centre for Healthy Lungs and Hunter Medical Research Institute, University of Newcastle , Newcastle, New South Wales, Australia.
authors.forename: Lohis
authors.initials: L
authors.lastname: Balachandran
authors.affiliation: Priority Research Centre for Healthy Lungs and Hunter Medical Research Institute, University of Newcastle , Newcastle, New South Wales, Australia.
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Starkey
authors.affiliation: Priority Research Centre for Healthy Lungs and Hunter Medical Research Institute, University of Newcastle , Newcastle, New South Wales, Australia.
authors.forename: Darryl A
authors.initials: DA
authors.lastname: Knight
authors.affiliation: Priority Research Centre for Healthy Lungs and Hunter Medical Research Institute, University of Newcastle , Newcastle, New South Wales, Australia.
authors.forename: Jay C
authors.initials: JC
authors.lastname: Horvat
authors.affiliation: Priority Research Centre for Healthy Lungs and Hunter Medical Research Institute, University of Newcastle , Newcastle, New South Wales, Australia.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Hansbro