Recovery from Bronchoconstriction and Bronchodilator Tolerance

Until recently, researchers believed that tolerance or tachyphylaxis to the bronchodilator effects of beta-agonists did not occur. However, recent studies examining the recovery from bronchoconstriction have clearly shown that an impaired response to beta-agonists occurs in patients who have been using regular beta-agonist treatment. This tolerance develops with both long- and short-acting beta-agonists and is not affected by treatment with inhaled steroids. It develops rapidly, reaching a maximum within 1 wk of starting beta-agonists, and has been demonstrated after methacholine, hypertonic saline, mannitol, and exercise-induced bronchoconstriction. The observed reduction in the bronchodilator response is proportional to the severity of bronchoconstriction. Therefore, although individuals with stable asthma show little evidence of tolerance, those with severe bronchospasm have a markedly reduced bronchodilator response to beta-agonists. Almost all asthmatics show evidence of tolerance when tested in the setting of bronchoconstriction, although the extent of this tolerance varies. The reasons for this interindividual variation are not understood. Bronchodilator tolerance is difficult to study in the clinical setting because nearly every patient has used multiple doses of beta-agonist before seeking medical attention. However, there is compelling evidence that the response to rescue beta-agonist treatment is reduced in those who use regular long- or short-acting beta-agonists. The extent to which this phenomenon contributes to asthma morbidity and mortality remains to be determined.