Beta-agonists Are Safe

Ending a 5-year debate about the appropriate use of inhaled beta-agonists in treating asthma, researchers from the NIH-sponsored Asthma Clinical Research Network (ACRN) have shown that for mild asthmatics, taking inhaled beta-agonists at regular intervals for an extended period is safe.

That is, no tolerance to the beneficial effects of albuterol were seen, and there was no diminished asthma control seen with 16 weeks of QID dosing of albuterol (Sept. 19, 1996 NEJM).

These are not trivial findings, since regular use of beta-agonists was blamed for the increase in asthma severity, hospitalization, and death rates seen world-wide. There had been studies suggesting adverse effects of beta-agonists, but these studies included mild and moderate asthmatics.

Also, epidemiological studies showing an association between beta-agonists and asthma mortality might be explained by:

1. regular beta-agonist use is a marker for those with severe disease and who are more likely to die from asthma;
2. some of these studies were done in countries where fenoterol was widely used - the mortality could have been due to this particular beta-agonist.

However, the ACRN study also showed that there was no particular clinical benefit seen in those taking QID albuterol versus those asthmatics taking only PRN albuterol. In a sense, the QID dosing only added to the overall cost of treating these patients.

Consequently, the recently released NIH-guidelines for the diagnosis and management of asthma still recommend PRN use of beta-agonists - both for cost reasons and so that clinicians can use the frequency of PRN beta-agonist use as a guide for therapy. That is, the guidelines recommend that those patients requiring more than twice a week PRN beta-agonist use should increase (or start) there anti-inflammatory therapy (inhaled steroids, cromolyn, nedocromil, or leukotriene modifiers).

The above study suggests that beta-agonists, if needed, should not be withheld from mild asthmatics. However, there still are theoretical concerns (e.g., down-regulation of beta-receptors) about beta-agonist overuse in moderate to severe asthmatics.