Chest
Volume 85, Issue 1, January 1984, Pages 34-38
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Assessment of Tachyphylaxis following Prolonged Therapy of Asthma with Inhaled Albuterol Aerosol

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Controversy exists concerning possible tachyphylaxis of the acute bronchodilating effect of albuterol, especially with regard to the duration of its acute bronchodilating action. We evaluated 140 patients with bronchial asthma in a prospective double-blind controlled study of possible tachyphylaxis to albuterol aerosol as compared to isoproterenol aerosol. We demonstrated statistically significant tachyphylaxis with regard to duration of acute bronchodilating effect. We believe that this tachyphylaxis is not clinically significant because there was no tachyphylaxis with regard to peak bronchodilating effect and because the duration of bronchodilating effect remains significantly greater, both quantitatively and statistically, when compared to isoproterenol aerosol. Moreover, it appeared that most of the tachyphylaxis was present at four weeks of therapy. There was a small increment of tachyphylaxis after eight weeks of therapy, but no further increase in tachyphylaxis was demonstrated after 13 weeks of inhaled albuterol therapy. We therefore feel that clinically significant tachyphylaxis to inhaled albuterol aerosol must be quite unusual and that chronic therapy with inhaled albuterol aerosol is probably both safe and efficacious for bronchospastic disorders.

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METHODS

One hundred forty patients were evaluated at eight different centers. The number of patients evaluated at each center varied from 11 to 32. Twenty-eight patients from one center were excluded from the final statistical analysis because the results obtained from this center were at such striking variance with the results obtained from the seven other centers. Even though it is statistically invalid to analyze the variant center's results along with the overall results, the inclusion of these

RESULTS

Figures 1, 2, and 3, derived from Tables 3 and 4, indicate that there is evidence of tachyphylaxis after inhaling two puffs of albuterol aerosol four times a day for 91 days. This is true, however, only with regard to the duration of significant bronchodilator response, but not with regard to peak bronchodilator effect, although there was an absolute drop of 0.139 L (16 percent) from 0.875 L at week zero to 0.736 L at week 13. Quantitatively the amount of tachyphylaxis with respect to the

DISCUSSION

It has been accepted practice in the United States to use long-duration beta2 specific adrenergic aerosols, specifically isoetherine and metaproterenol, as therapy for a variety of bronchospastic pulmonary disorders. However, previously published reports about tachyphylaxis with adrenergic agonists have raised reasonable concern about this therapy, particularly when the use of adrenergic aerosol inhalers has been abused. Fortunately, there have been no reports of “epidemics” of asthmatic deaths

ACKNOWLEDGMENT

The authors thank Miss Nicolette Cavallaro for her editorial assistance in the preparation of this manuscript.

REFERENCES (11)

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Supported by a grant from the Schering-Plough Research Division, Bloomfield, New Jersey.

Manuscript received April 12, 1982; revision accepted July 18.

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