[Bronchial adrenergic receptors and asthma. Tachyphylaxis and its prevention]

The majority of the clinical studies in healthy volunteers have shown that chronic inhalation or oral intake of sympathomimetics causes tachyphylaxis of the bronchial beta adrenergic receptors. We have observed in healthy subjects individual differences in the propensity to develop beta-adrenergic tachyphylaxis during a prolonged treatment with sympathomimetics. There was no relation between the development of beta-adrenergic tachyphylaxis and changes in bronchial responsiveness to methacholine. The problem is much more complex in the asthmatic patients. Several well controlled studies have however shown that chronic administration of sympathomimetics results in a significantly decreased sensitivity of the bronchial beta adrenergic receptor. This tachyphylaxis is mainly demonstrable as a shorter duration of action of the sympathomimetics. The clinical relevance of the beta adrenergic tachyphylaxis induced by prolonged treatment with sympathomimetics is probably minimal and has no relation with the relative resistance to sympathomimetics observed during acute severe asthma. Corticosteroids, given orally or parenterally, restore the sensitivity of the beta adrenergic receptors. In a double blind, placebo controlled study in healthy subjects we have observed that ketotifen prevents the development of a tachyphylaxis of the bronchial beta adrenergic receptor during prolonged treatment with inhaled sympathomimetics.