Influence of short- and long-term inhalation of salbutamol on lung function and beta 2-adrenoceptors of mononuclear blood cells in asthmatic children.

Clinical observations have shown that some asthma patients develop tachyphylaxis to beta-sympathomimetic drugs. As down-regulation of the number of beta-adrenoceptors in different human tissues after exposure to catecholamines and beta-adrenergic drugs is well known, we investigated whether a interrelation exists between beta-adrenoceptor down-regulation and clinically detectable beta-adrenergic subsensitivity during beta-sympathomimetic treatment. The following results were obtained: 1. beta 2-Sympathomimetic inhalation treatment with salbutamol in therapeutic doses led to a significant down-regulation of beta 2-adrenoceptors and consecutive cyclic adenosine monophosphate response to isoprenaline. This effect was already detectable after short-term treatment of 3-7 days in 9 asthmatic children. 2. In the long-term study over 6 months, salbutamol inhalation in 12 asthmatic children led to a significant down-regulation of beta-adrenoceptor binding sites on mononuclear blood cells (MNC) from 1539 +/- 91 to 1115 +/- 99 after 14 days, remaining in this range thereafter. 3. The mean airway resistance (Raw) of these 12 patients decreased significantly within 14 days from 8.1 +/- 0.8 to 5.7 +/- 0.5 cm H2O/l/s to remain stable throughout the 6 months of salbutamol treatment. The differences in Raw before and immediately after inhalation of 0.2 mg salbutamol (2 puffs) were unchanged during the study period. It is concluded, that long-term inhalative treatment with salbutamol over a period of 6 months does not result in refractoriness to beta-adrenergic drugs in the airways of asthmatic children, even though a significant down-regulation of beta 2-receptors on peripheral MNC occurs.