Effect of reproterol either alone or combined with disodium cromoglycate on airway responsiveness to methacholine.
Regular use of inhaled beta2-agonists might lead to tolerance as reflected in a loss of bronchoprotection. In vitro-data suggest that this might be prevented by disodium cromoglycate (DSCG). Therefore, we studied the effect of the beta2-agonist reproterol in combination with DSCG. In a cross-over design, 19 subjects with airway hyperresponsiveness inhaled either placebo, 1mg reproterol, 2 mg DSCG, or 1mg reproterol plus 2 mg DSCG 4x daily over 2 weeks. Treatment periods were separated by > or = 7 days. Before and at the end of periods, lung function and methacholine responsiveness were determined in the morning, and 6h later the bronchodilator effect and the protection against methacholine-induced bronchoconstriction. Reproterol or DSCG or their combination did not exert detrimental effects on lung function, airway responsiveness, or bronchodilator capacity. However, bronchoprotection was significantly reduced (p < 0.05) after treatment with placebo, reproterol or reproterol plus DSCG, the respective changes being 0.59, 0.96 and 1.37 doubling concentrations. All changes were small as compared to intraindividual variability. In this model all treatments except with DSCG caused a significant but small loss of protection against methacholine-induced bronchoconstriction. Thus, tolerance was not prevented by 2 weeks of additional treatment with DSCG, in contrast to in vitro findings.
Kanniess
Frank
F
Pulmonary Research Institute Hospital Grosshansdorf, Center for Pneumology and Thoracic Surgery, D-22927 Grosshansdorf, Germany. f.kanniess@pulmoresearch.de
Jörres
Rudolf A
RA
Magnussen
Helgo
H
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000517:prevention & control*; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004205:Cromolyn Sodium / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D009921:Metaproterenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016210:Methacholine Chloride; D008875:Middle Aged; D013806:Theophylline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D004338:Drug Combinations; D016210:Methacholine Chloride; C014792:reproterol; D009921:Metaproterenol; D013806:Theophylline; D004205:Cromolyn Sodium