Tolerance to Beta₂-Agonist Treatment after Regular Use in People with Asthma

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The summary below is from the full report titled "Meta-Analysis: Respiratory Tolerance to Regular ß₂-Agonist Use in Patients with Asthma." It is in the 18 May 2004 issue of Annals of Internal Medicine (volume 140, pages 802-813). The authors are S.R. Salpeter, T.M. Ormiston, and E.E. Salpeter.

What is the problem and what is known about it so far?

People with asthma develop intermittent contraction of the muscle in the walls of the tubes (airways, or bronchi) that bring air to the lungs. Breathing becomes difficult when the airways contract. Some people with asthma have infrequent symptoms, others have severe symptoms on most days, and most are somewhere in between. Triggers of asthma symptoms include smoke, infection, allergic reactions, cold weather, and exercise. In some people, the triggers are unclear. Fortunately, there is effective treatment for asthma. Asthma drugs fall into 2 categories: drugs that control asthma over the long term, making attacks less frequent, and drugs that help during asthma attacks by relaxing the airways. Beta₂-agonists are inhaled drugs that help during asthma attacks by relaxing the airways. Beta₂-agonists may also have benefits related to the airway inflammation that occurs in asthma. Although beta₂-agonists can improve symptoms during an asthma attack, there is concern that people who use them regularly develop tolerance to them. Tolerance means that the beta₂-agonists lose some of their effectiveness.

Why did the researchers do this particular study?

To summarize what previous studies have shown about the development of tolerance in people with asthma who use beta₂-agonists regularly.

Who was studied?

The authors combined data from 22 previous studies that included a total of 323 patients with asthma.

How was the study done?

The researchers examined data from 22 previous studies that had people take either beta₂-agonists or placebo regularly for at least 1 week. Placebo was an inhaled drug that appeared identical to the beta₂-agonists but contained no active ingredients. The studies then measured the responses of both groups to subsequent doses of beta₂-agonists by looking at a variety of measures of beta₂-agonist effectiveness.

What did the researchers find?

The researchers found that patients who used beta₂-agonists regularly for at least 1 week were less responsive to the effects of subsequent doses of beta₂-agonists than were patients who took placebo. Regular users developed tolerance to the effects of beta₂-agonist on both bronchial relaxation and inflammation. In fact, regular users demonstrated more airway inflammation than those who took placebo.

What were the limitations of the study?

The studies did not measure actual patient outcomes such as number or severity of asthma attacks and did not include a group of patients who used the drugs only as needed. For these reasons, this analysis cannot assess whether taking beta₂-agonists as needed is worse than not taking any beta₂-agonist at all.

What are the implications of the study?

Doctors and patients should consider using beta₂-agonists to treat asthma only during asthma attacks.

Read all Rapid Responses

Susceptibility to Tolerance and ß₂-Adrenoceptor Polymorphism

Daniel K C Lee, et al.

Annals Online, 27 Jul 2004 [Full text]