title: Increased bronchial hyperresponsiveness after inhaling salbutamol during 1 year is not caused by subsensitization to salbutamol.
abstract: Recently, it was suggested that long-term administration of an inhaled beta 2-agonist might increase bronchial hyperresponsiveness (BHR) to histamine, possibly as a consequence of subsensitization to the inhaled beta 2-agonist. To test this hypothesis, we studied two groups of patients with asthma or with chronic obstructive pulmonary disease. An experimental group of 15 patients, inhaling 400 micrograms of salbutamol four times daily during 1 year and subsequently 40 micrograms of ipratropium bromide four times daily for 6 months, and a control group, consisting of 22 patients with the opposite treatment regimen. The BHR, the response in FEV1 to cumulative doses of salbutamol, and the number of beta 2-adrenoceptors and antagonist affinity of these receptors on circulating lymphocytes were assessed at the start of the study and at 6-month intervals for 1 1/2 years. The BHR increased significantly (p = 0.001) during the year salbutamol was inhaled and returned to about the value at the start of the study after inhaling ipratropium bromide for 6 months. No change occurred in the bronchodilating responses to cumulative doses of salbutamol, nor was any change observed in the number and the affinity of beta 2-adrenoceptors on lymphocytes. It was concluded that long-term use of salbutamol caused a small but significant increase in BHR. The increase in BHR was not caused by subsensitization of beta 2-adrenoceptors to salbutamol.
authors.affiliation: Department of Family Medicine, Nijmegen University, The Netherlands.
authors.forename: C P
authors.initials: CP
authors.lastname: van Schayck
authors.forename: S J
authors.initials: SJ
authors.lastname: Graafsma
authors.forename: M B
authors.initials: MB
authors.lastname: Visch
authors.forename: E
authors.initials: E
authors.lastname: Dompeling
authors.forename: C
authors.initials: C
authors.lastname: van Weel
authors.forename: C L
authors.initials: CL
authors.lastname: van Herwaarden
mesh_terms: D000280:Administration, Inhalation; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000097:blood / Q000188:drug therapy; D001980:Bronchi / Q000187:drug effects*; D001985:Bronchial Provocation Tests; D004361:Drug Tolerance; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D009241:Ipratropium / Q000627:therapeutic use; D008137:Longitudinal Studies; D008173:Lung Diseases, Obstructive / Q000097:blood / Q000188:drug therapy; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D012130:Respiratory Hypersensitivity
chemical_list: D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D009241:Ipratropium; D000420:Albuterol