Should treatments for asthma be aimed at the airway smooth muscle?

Abstract

The airway smooth muscle (ASM) cell is an important part of the airway wall of asthma patients because of its increased contractile properties, which appear to be enhanced in this condition and which contribute to airflow obstruction and bronchial hyper-responsiveness. ASM cells are also abnormal in asthma with increased expression of certain chemokines, with increased proliferation rate, numbers and size. β-adrenergic agonists and corticosteroids are the two most important treatments for asthma; other drugs used are leukotriene receptor antagonists and theophylline. Combination therapy of β-adrenergic agonists and corticosteroids has become the treatment of choice for moderate-to-severe asthma. β-adrenergic agonists cause relaxation of ASM cells, leading to a decrease in airflow obstruction of asthma and acute relief of symptoms. Corticosteroids also have direct effects on ASM cells. It is postulated that the effect of anti-inflammatory agents on ASM cells is the most important determinant of the therapeutic effects of these agents. Targeting the ASM cell in asthma could be the focus of therapies for asthma. Specific delivery of active agents to ASM cells may also be part of this strategy.

Keywords::

• airway smooth muscle cell
• airway wall remodeling
• asthma
• β-adrenergic agonist
• corticosteroid
• leukotriene receptor antagonist

Financial & competing interests disclosure

KF Chung has received honoraria for participating on Advisory Board meetings and Consultancy regarding products for asthma and COPD for GSK, Astra-Zeneca, Merck, MundiPharma, Trinity-Chiesi, Novartis, Celgene and Gilead. KF Chung has participated in clinical trials of asthma and COPD treatments funded by Asthmatyx (bronchial thermoplasty study) and Novartis, and received unrestricted research funds from GSK. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.