Document Detail

Salbutamol-induced increased airway responsiveness to allergen and reduced protection versus methacholine: dose response.
MedLine Citation:
PMID:  8568137     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Two adverse effects of inhaled beta 2-agonists are increased airway responsiveness to allergen and tolerance to the bronchoprotective effect of beta 2-agonists versus bronchoconstrictors (e.g., methacholine). OBJECTIVE: We studied three doses of inhaled salbutamol, 200, 400, and 800 micrograms/day, to determine dose-response curves for these two adverse effects. METHODS: Ten atopic patients with mild, stable asthma free of all asthma medications, allergen exposure, and respiratory tract infection for at least 4 weeks participated in a double-blind, random-order, crossover study. There were four 1-week treatment periods with a 1-week washout period: placebo, salbutamol 200 micrograms, 400 micrograms and 800 micrograms per day. After each treatment, we assessed FEV1, bronchodilation 10 minutes after administration of 200 micrograms of salbutamol, methacholine PC20, methacholine dose-shift after administration of 200 micrograms of salbutamol, and allergen PC20. RESULTS: There was no significant difference in baseline FEV1, bronchodilation, or methacholine PC20. The methacholine dose shift was maximum after the placebo (3.4 +/- 0.22 doubling doses) and was significantly greater (p < 0.01) than all salbutamol regimens (2.2 to 2.6), which were not significantly different from each other (p > 0.05). Allergen PC20 was significantly lower (p < 0.02) after salbutamol 800 micrograms/day (geometric mean = 288 protein nitrogen units [PNU]/ml) than each of the other treatments (447 to 550 PNU/ml), which were not significantly different from each other (p > 0.05). CONCLUSION: Significant increase in airway responsiveness to allergen occurred only with the largest dose of inhaled salbutamol (800 micrograms/d); however, tolerance to the acute bronchoprotective effect of salbutamol was observed with all the three salbutamol regimens, even 200 micrograms/day. This suggests different mechanisms may be operative in producing these two effects.
R Bhagat; V A Swystun; D W Cockcroft
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of allergy and clinical immunology     Volume:  97     ISSN:  0091-6749     ISO Abbreviation:  J. Allergy Clin. Immunol.     Publication Date:  1996 Jan 
Date Detail:
Created Date:  1996-03-06     Completed Date:  1996-03-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1275002     Medline TA:  J Allergy Clin Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  47-52     Citation Subset:  AIM; IM    
Department of Medicine, Royal University Hospital, Saskatoon, Saskatchewan, Canada.
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MeSH Terms
Adrenergic beta-Agonists / adverse effects*
Albuterol / adverse effects*
Allergens / administration & dosage,  immunology*
Asthma / drug therapy*,  immunology
Bronchial Provocation Tests
Bronchoconstrictor Agents / administration & dosage*
Cross-Over Studies
Dose-Response Relationship, Drug
Double-Blind Method
Drug Tolerance
Methacholine Chloride / administration & dosage*
Middle Aged
Reg. No./Substance:
0/Adrenergic beta-Agonists; 0/Allergens; 0/Bronchoconstrictor Agents; 18559-94-9/Albuterol; 62-51-1/Methacholine Chloride

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