Abnormal corticosteroid signalling in airway smooth muscle: mechanisms and perspectives for the treatment of severe asthma

Summary Growing in vivo evidence supports the concept that airway smooth muscle produces various immunomodulatory factors that could contribute to asthma pathogenesis via the regulation of airway inflammation, airway narrowing and remodelling. Targeting ASM using bronchial thermoplasty has provided...

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Bibliographic Details
Published in:Clinical and experimental allergy 2015-11, Vol.45 (11), p.1637-1646
Main Authors: Chachi, L., Gavrila, A., Tliba, O., Amrani, Y.
Format: Article
Language:English
Subjects:
Adrenal Cortex Hormones - metabolism
Adrenal Cortex Hormones - therapeutic use
Animals
Asthma - drug therapy
Asthma - immunology
Asthma - metabolism
Cytokines - metabolism
Drug Resistance
Humans
Immunologic Factors - metabolism
Immunomodulation
Muscle, Smooth - metabolism
Signal Transduction
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Summary:Summary Growing in vivo evidence supports the concept that airway smooth muscle produces various immunomodulatory factors that could contribute to asthma pathogenesis via the regulation of airway inflammation, airway narrowing and remodelling. Targeting ASM using bronchial thermoplasty has provided undeniable clinical benefits for patients with uncontrolled severe asthma who are refractory to glucocorticoid therapy. The present review will explain why the failure of glucocorticoids to adequately manage patients with severe asthma could derive from their inability to affect the immunomodulatory potential of ASM. We will support the view that ASM sensitivity to glucocorticoid therapy can be blunted in severe asthma and will describe some of the factors and mechanisms that could be responsible for glucocorticoid insensitivity.
ISSN:0954-7894
1365-2222
DOI:10.1111/cea.12577