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Effect of regular salmeterol treatment on albuterol-induced bronchoprotection in mild asthma.
Am J Respir Crit Care Med. 1997 Sep; 156(3 Pt 1):988-91.AJ

Abstract

There is increasing evidence for the development of tolerance to the bronchoprotective effects of inhaled beta 2-agonists against bronchoconstrictor stimuli in asthma. With short-acting beta 2-agonists, this is more readily demonstrable using indirectly acting agents such as adenosine monophosphate (AMP), which may act via mast cell degranulation, than using methacholine (MCh), implying more rapid mast cell than smooth muscle desensitization. Desensitization may be greater with the long-acting beta 2-agonist, salmeterol, given its greater duration of receptor occupancy. In a double-blind, placebo-controlled crossover study, we investigated the effect of regular salmeterol on the protection conferred by albuterol using MCh- and AMP-induced bronchoconstriction. Sixteen mild asthmatic subjects not using inhaled glucocorticoids were randomized to treatment for 2 wk with inhaled salmeterol (50 micrograms b.i.d. via diskhaler) or identical placebo. Provocative concentrations of MCh and AMP causing a 20% fall in FEV1 (PC20) were measured 15 min after 200 micrograms albuterol, both before and after treatment. Mean MCh PC20 after albuterol decreased significantly after 2 wk of salmeterol treatment (mean 2.2 mg/ml before to 1.1 +/- 1.2 mg/ml after) compared with placebo (2.9 +/- 1.3 mg/ml before to 2.6 +/- 1.3 mg/ml after; p < 0.05), but this fell just short of statistical significance when analyzed as change in doubling dilutions (1.1 +/- 0.4 versus 0.18 +/- 0.4; p = NS). Mean PC20 to AMP was not significantly affected (mean 27.5 +/- 1.5 mg/ml prior to salmeterol treatment and 9.5 +/- 1.5 mg/ml after treatment; p = NS compared with placebo). Thus, regular salmeterol treatment led to loss of bronchoprotection by albuterol to MCh but not to AMP challenge, implying an absence of mast cell beta 2-adrenoceptor downregulation with regular salmeterol therapy.

Authors+Show Affiliations

Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.No affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9310023

Citation

Yates, D H., et al. "Effect of Regular Salmeterol Treatment On Albuterol-induced Bronchoprotection in Mild Asthma." American Journal of Respiratory and Critical Care Medicine, vol. 156, no. 3 Pt 1, 1997, pp. 988-91.
Yates DH, Worsdell M, Barnes PJ. Effect of regular salmeterol treatment on albuterol-induced bronchoprotection in mild asthma. Am J Respir Crit Care Med. 1997;156(3 Pt 1):988-91.
Yates, D. H., Worsdell, M., & Barnes, P. J. (1997). Effect of regular salmeterol treatment on albuterol-induced bronchoprotection in mild asthma. American Journal of Respiratory and Critical Care Medicine, 156(3 Pt 1), 988-91.
Yates DH, Worsdell M, Barnes PJ. Effect of Regular Salmeterol Treatment On Albuterol-induced Bronchoprotection in Mild Asthma. Am J Respir Crit Care Med. 1997;156(3 Pt 1):988-91. PubMed PMID: 9310023.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of regular salmeterol treatment on albuterol-induced bronchoprotection in mild asthma. AU - Yates,D H, AU - Worsdell,M, AU - Barnes,P J, PY - 1997/10/6/pubmed PY - 1997/10/6/medline PY - 1997/10/6/entrez SP - 988 EP - 91 JF - American journal of respiratory and critical care medicine JO - Am. J. Respir. Crit. Care Med. VL - 156 IS - 3 Pt 1 N2 - There is increasing evidence for the development of tolerance to the bronchoprotective effects of inhaled beta 2-agonists against bronchoconstrictor stimuli in asthma. With short-acting beta 2-agonists, this is more readily demonstrable using indirectly acting agents such as adenosine monophosphate (AMP), which may act via mast cell degranulation, than using methacholine (MCh), implying more rapid mast cell than smooth muscle desensitization. Desensitization may be greater with the long-acting beta 2-agonist, salmeterol, given its greater duration of receptor occupancy. In a double-blind, placebo-controlled crossover study, we investigated the effect of regular salmeterol on the protection conferred by albuterol using MCh- and AMP-induced bronchoconstriction. Sixteen mild asthmatic subjects not using inhaled glucocorticoids were randomized to treatment for 2 wk with inhaled salmeterol (50 micrograms b.i.d. via diskhaler) or identical placebo. Provocative concentrations of MCh and AMP causing a 20% fall in FEV1 (PC20) were measured 15 min after 200 micrograms albuterol, both before and after treatment. Mean MCh PC20 after albuterol decreased significantly after 2 wk of salmeterol treatment (mean 2.2 mg/ml before to 1.1 +/- 1.2 mg/ml after) compared with placebo (2.9 +/- 1.3 mg/ml before to 2.6 +/- 1.3 mg/ml after; p < 0.05), but this fell just short of statistical significance when analyzed as change in doubling dilutions (1.1 +/- 0.4 versus 0.18 +/- 0.4; p = NS). Mean PC20 to AMP was not significantly affected (mean 27.5 +/- 1.5 mg/ml prior to salmeterol treatment and 9.5 +/- 1.5 mg/ml after treatment; p = NS compared with placebo). Thus, regular salmeterol treatment led to loss of bronchoprotection by albuterol to MCh but not to AMP challenge, implying an absence of mast cell beta 2-adrenoceptor downregulation with regular salmeterol therapy. SN - 1073-449X UR - https://www.unboundmedicine.com/medline/citation/9310023/Effect_of_regular_salmeterol_treatment_on_albuterol_induced_bronchoprotection_in_mild_asthma_ L2 - http://www.atsjournals.org/doi/full/10.1164/ajrccm.156.3.9610051?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -