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Selective subsensitization of beta-adrenergic receptors in central airways of asthmatics and normal subjects during long-term therapy with inhaled salbutamol.

Abstract
In five subjects with mild asthma and in five normal subjects, we determined the effect of a 4 wk course of inhaled salbutamol (albuterol), 200 micrograms q.i.d., on (1) acute bronchodilator responsiveness, (2) bronchial sensitivity to inhaled histamine, (3) beta-adrenergic protection against histamine-induced bronchospasm, and (4) beta-receptor density of peripheral blood lymphocytes. We observed a diminution in central airway bronchodilator responsiveness (as measured by airway conductance responses) to acutely inhaled salbutamol and to subcutaneous terbutaline in both groups of subjects, although only the response to subcutaneous terbutaline was statistically significant (p less than 0.02). On the other hand, no impairment of small airway bronchodilator responsiveness was noted in either group of subjects when responses were measured as partial expiratory flow rates at 60% below total lung capacity. These findings suggest the development of selective subsensitization of beta-receptors in the larger central airways, where a proportionately greater amount of the inhaled beta-agonist aerosol would necessarily be deposited. A greater loss of protection against histamine-induced bronchospasm was seen in asthmatics than in normals (approximately twofold), although the difference was not significant. A modest but not significant reduction in peripheral blood lymphocyte beta-receptor density was observed by the end of the 4 wk treatment period. The possibility that the observed changes in bronchodilator responsiveness might influence the morbidity and mortality associated with bronchial asthma is discussed.
AuthorsM E Conolly, D P Tashkin, K K Hui, M R Littner, R N Wolfe
JournalThe Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 70 Issue 6 Pg. 423-31 (Dec 1982) ISSN: 0091-6749 [Print] UNITED STATES
PMID6292279 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Bronchodilator Agents
  • Receptors, Adrenergic
  • Receptors, Adrenergic, beta
  • Terbutaline
  • Albuterol
Topics
  • Administration, Intranasal
  • Adult
  • Albuterol (administration & dosage, adverse effects, therapeutic use)
  • Asthma (drug therapy, physiopathology)
  • Bronchial Spasm (drug therapy, physiopathology)
  • Bronchodilator Agents (administration & dosage, adverse effects, therapeutic use)
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Injections, Subcutaneous
  • Long-Term Care
  • Male
  • Receptors, Adrenergic (drug effects)
  • Receptors, Adrenergic, beta (drug effects)
  • Tachyphylaxis
  • Terbutaline (administration & dosage, therapeutic use)

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