SELECTED ARTICLES FROM THE RECENT LITERATURE 2004

10/19/04

Meta-analysis of respiratory tolerance to regular beta agonist treatment in asthmatics

Summary
Background - Chronic regular (daily) treatment with inhaled beta agonists (IBA) in asthmatics may be associated with development of tolerance to the bronchodilating effects of these agents.

Findings - Salpeter et al of the Stanford Univ. School of Medicine in CA carried out a meta-analysis of randomized, placebo controlled trials reported from 1966 to 2003 of regular IBA used for at least one week in asthmatics. In 22 studies that met inclusion criteria, regular IBA use, compared to placebo treatment (with no prn use of IBA) was not associated with significant changes in the baseline FEV-1. However, in those treated regularly with IBA there was a significantly reduced FEV-1 response to a subsequent IBA treatment, either considered as a maximal response or a pattern of response to varying doses of the IBA. The concentration of bronchoconstrictive stimuli needed to induce a FEV-1 decrease of 20% (a marker of bronchial hyper-reactivity) was also significantly less following chronic IBA use. There was also less expression of beta-2 receptor density on the leukocytes of the chronically IBA- treated patients.

Reference
Ann Intern Med 2004;140:802-13

Editor's Comments
There has been a long-standing debate about whether chronic use of IBS adversely affects asthma outcomes. The conclusions in this meta-analysis about chronic IBA use are similar to that expressed by a number of experts in the field: 1) the overall pulmonary function in those using IBA regularly is not impressively decreased by this therapy; 2) however, the immediate bronchodilating effect of IBA is often blunted; 3) the degree of bronchial hyper-reactivity is increased.

The implication is that asthmatic patients using IBA regularly may be at increased risk for triggering of acute asthma flares by irritants, viral infections, etc. because of the increased bronchial reactivity. When an acute asthma flare occurs, inhaled albuterol will not be as beneficial. Some studies find a significant increased risk for asthma fatalities in those using IBA chronically as monotherapy. Most investigators recommend use of short acting IBA agents such as albuterol only occasionally for “rescue” purposes and for pre-exercise use in those with exercise-induced asthma. However, regular use of long-acting IBA such as salmeterol or formoterol on combination with inhaled corticosteroids (such as in Advair or Symbicort) is commonly recommended in an attempt to reduce the dose of inhaled corticosteroids needed to control asthma. Nevertheless, chronic monotherapy with long-acting IBA is not recommended after the finding of increased asthma mortality in those treated chronically with salmeterol as monotherapy in the SMART study.

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