Understanding the Paradox of Asthma Medications

A new study helps to explain the paradox that occurs when asthmatics treated with bronchodilating beta-agonist drugs such as albuterol, ventolin, and salbutamol develop increased sensitivity to airway constriction, worsening their condition. The findings were reported in the August 15, 2003, issue of the Journal of Clinical Investigation.

The beta-agonist drugs cause airway relaxation and reduce airway responsiveness to nonspecific contractile stimuli by binding to the beta2-adrenergic receptor (beta2AR). However, some studies have shown that regular scheduled can result in a loss of control over asthma, resulting in longer attacks and a hyper-responsive airway. Although evidence suggested that desensitization of the beta2AR is responsible, the new study reveals that persistent high-level activation of the beta2AR leads to increased expression of phospholipase C-beta (PLC-beta) in airway smooth muscle. This induces cross talk between beta2AR signaling pathways that makes the airway hyper-responsive.

Therapeutics that target PLC-beta may have substantial benefit in the treatment of asthma, especially when chronic beta-agonist use is prescribed, concluded Stephen Liggett and colleagues from the University of Cincinnati (OH, USA) who conducted the study.

In an accompanying commentary, doctors from the Harvard School of Public Health (Boston, MA, USA) noted that this is "just the tip of the iceberg” and that "understanding the panoply of beta2AR-mediated events in airway smooth muscle might lead to the design of new agonists that avoid negative effects of beta2AR activation while enhancing events that lead to relaxation.”




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Univ. of Cincinnati