Comparative effects of a fixed combination of reproterol hydrochloride and disodium cromoglycate with each agent alone on antigen-induced airway responses in sheep.
The purpose of this study was to compare the effectiveness of an eight day treatment with clinically relevant doses of a fixed combination of the beta 2 mimetic reproterol hydrochloride and disodium cromoglycate with each agent given alone against antigen-induced early (EAR) and late airway responses (LAR) as well as post-antigen-induced airway hyperresponsiveness (AHR) in allergic sheep. Animals were treated in a randomized fashion with either the inhaled combination (n = 6), reproterol hydrochloride alone (n = 6), disodium cromoglycate alone (n = 6), or placebo (n = 8). Treatments (two puffs from a metered dose inhaler) were given three times a day for 7 days and once on the 8th day 1 h before airway challenge with Ascaris suum antigen. In the placebo trial, antigen challenge resulted in EAR and LAR as measured by increases in specific lung resistance; these changes were followed 24h later by AHR to inhaled carbachol. With respect to the placebo trial, treatment with reproterol hydrochloride reduced the EAR (P < 0.05) and blocked the LAR (P < 0.05), but had no effect on the post-challenge AHR. Treatment with disodium cromoglycate also reduced the EAR (P < 0.05), blocked the LAR (P < 0.05), and blocked the post-antigen-induced AHR (P < 0.05). Treatment with the fixed combination reduced the EAR (P < 0.05), blocked the LAR (P < 0.05), and blocked the post-antigen-induced AHR (P < 0.05). Comparison of the different agents indicated that the fixed combination gave significantly increased protection against the EAR than either agent alone, gave slightly better (P < 0.05) protection against the late response than cromolyn sodium and gave better protection against post-antigen-induced AHR than reproterol hydrochloride alone. These results suggest that a fixed combination of a beta 2-mimetic and disodium cromoglycate provides some increased protection against antigen-induced airway responses when compared to either agent alone in a controlled laboratory setting.
Abraham
W M
WM
Division of Pulmonary Disease and Critical Care Medicine, University of Miami at Mount Sinai Medical Center, Miami Beach, Florida 33140, USA. abraham@msmc.com
Sabater
J R
JR
Szelenyi
S
S
Bähre
M
M
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019540:Area Under Curve; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology / Q000517:prevention & control; D001985:Bronchial Provocation Tests; D001993:Bronchodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004205:Cromolyn Sodium / Q000494:pharmacology* / Q000627:therapeutic use; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D009921:Metaproterenol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D012756:Sheep; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D000318:Adrenergic beta-Agonists; D000336:Aerosols; D018926:Anti-Allergic Agents; D001993:Bronchodilator Agents; D004338:Drug Combinations; C014792:reproterol; D009921:Metaproterenol; D013806:Theophylline; D004205:Cromolyn Sodium