Proof of concept evaluation of trough airway hyper-responsiveness following regular racemic or levosalbutamol in genotype-stratified steroid-treated persistent asthmatics
Asthmatic patients receiving inhaled corticosteroids may take frequent add-on therapy with salbutamol despite on-demand prescription. Frequent salbutamol use can be detrimental in asthma. The isomeric formulation of salbutamol and the beta-2 adrenoceptor 16 genotype may also influence this phenomenon. We performed a randomised, double-blind, placebo-controlled, triple crossover, proof of concept trial comparing 2 weeks of regular therapy with inhaled racemic salbutamol (200�g qid); levosalbutamol (100�g qid); or placebo on trough methacholine PC20 6 hours post dose (the primary outcome) in 30 persistent asthmatics (15 each were homozygous Arg16 and Gly16) all receiving inhaled corticosteroids. There was no worsening of airway hyper-responsiveness at trough to methacholine after 2 weeks regular exposure to either racemic (p=0.53) or levosalbutamol (p=0.84) compared to placebo; nor between genotypes - as doubling dilution (dd) difference in methacholine PC20 from placebo: salbutamol/Arg16 = 0.36dd (95% CI: -0.43, 1.15); salbutamol/Gly16 = 0.01dd (95% CI: -0.47, 0.49); levosalbutamol/Arg16 = -0.01dd (95% CI: -0.89, 0.87); levosalbutamol/Gly16 = 0.28dd (95% CI: -0.22, 0.77). Both active treatments improved morning PEF in Gly16 (p=0.04 overall) but not Arg16 patients (p=0.50 overall); while evening PEF improved in both Gly16 (p<0.001 overall) and Arg16 patients (p=0.006 overall). In conclusion, regular exposure to either racemic or levosalbutamol for 2 weeks added to inhaled corticosteroids did not cause worsening of airway hyper-responsiveness at trough compared to placebo; with no difference seen between beta-2 adrenoceptor 16 genotypes.
Описание
Proof of concept evaluation of trough airway... [Clin Sci (Lond). 2013] - PubMed - NCBI
%0 Journal Article
%1 Anderson_2013_ClinSci(Lond)
%A Anderson, W J
%A Short, P M
%A Williamson, P A
%A Morrison, A E
%A Palmer, C
%A Tavendale, R
%A Lipworth, B J
%D 2013
%J Clin Sci (Lond)
%K asthma ligands salbutamol stereoisomeric
%R 10.1042/CS20130213
%T Proof of concept evaluation of trough airway hyper-responsiveness following regular racemic or levosalbutamol in genotype-stratified steroid-treated persistent asthmatics
%U http://www.ncbi.nlm.nih.gov/pubmed/23829494
%X Asthmatic patients receiving inhaled corticosteroids may take frequent add-on therapy with salbutamol despite on-demand prescription. Frequent salbutamol use can be detrimental in asthma. The isomeric formulation of salbutamol and the beta-2 adrenoceptor 16 genotype may also influence this phenomenon. We performed a randomised, double-blind, placebo-controlled, triple crossover, proof of concept trial comparing 2 weeks of regular therapy with inhaled racemic salbutamol (200�g qid); levosalbutamol (100�g qid); or placebo on trough methacholine PC20 6 hours post dose (the primary outcome) in 30 persistent asthmatics (15 each were homozygous Arg16 and Gly16) all receiving inhaled corticosteroids. There was no worsening of airway hyper-responsiveness at trough to methacholine after 2 weeks regular exposure to either racemic (p=0.53) or levosalbutamol (p=0.84) compared to placebo; nor between genotypes - as doubling dilution (dd) difference in methacholine PC20 from placebo: salbutamol/Arg16 = 0.36dd (95% CI: -0.43, 1.15); salbutamol/Gly16 = 0.01dd (95% CI: -0.47, 0.49); levosalbutamol/Arg16 = -0.01dd (95% CI: -0.89, 0.87); levosalbutamol/Gly16 = 0.28dd (95% CI: -0.22, 0.77). Both active treatments improved morning PEF in Gly16 (p=0.04 overall) but not Arg16 patients (p=0.50 overall); while evening PEF improved in both Gly16 (p<0.001 overall) and Arg16 patients (p=0.006 overall). In conclusion, regular exposure to either racemic or levosalbutamol for 2 weeks added to inhaled corticosteroids did not cause worsening of airway hyper-responsiveness at trough compared to placebo; with no difference seen between beta-2 adrenoceptor 16 genotypes.
@article{Anderson_2013_ClinSci(Lond),
abstract = {Asthmatic patients receiving inhaled corticosteroids may take frequent add-on therapy with salbutamol despite on-demand prescription. Frequent salbutamol use can be detrimental in asthma. The isomeric formulation of salbutamol and the beta-2 adrenoceptor 16 genotype may also influence this phenomenon. We performed a randomised, double-blind, placebo-controlled, triple crossover, proof of concept trial comparing 2 weeks of regular therapy with inhaled racemic salbutamol (200�g qid); levosalbutamol (100�g qid); or placebo on trough methacholine PC20 6 hours post dose (the primary outcome) in 30 persistent asthmatics (15 each were homozygous Arg16 and Gly16) all receiving inhaled corticosteroids. There was no worsening of airway hyper-responsiveness at trough to methacholine after 2 weeks regular exposure to either racemic (p=0.53) or levosalbutamol (p=0.84) compared to placebo; nor between genotypes - as doubling dilution (dd) difference in methacholine PC20 from placebo: salbutamol/Arg16 = 0.36dd (95% CI: -0.43, 1.15); salbutamol/Gly16 = 0.01dd (95% CI: -0.47, 0.49); levosalbutamol/Arg16 = -0.01dd (95% CI: -0.89, 0.87); levosalbutamol/Gly16 = 0.28dd (95% CI: -0.22, 0.77). Both active treatments improved morning PEF in Gly16 (p=0.04 overall) but not Arg16 patients (p=0.50 overall); while evening PEF improved in both Gly16 (p<0.001 overall) and Arg16 patients (p=0.006 overall). In conclusion, regular exposure to either racemic or levosalbutamol for 2 weeks added to inhaled corticosteroids did not cause worsening of airway hyper-responsiveness at trough compared to placebo; with no difference seen between beta-2 adrenoceptor 16 genotypes.},
added-at = {2013-07-19T13:15:43.000+0200},
author = {Anderson, W J and Short, P M and Williamson, P A and Morrison, A E and Palmer, C and Tavendale, R and Lipworth, B J},
biburl = {https://www.bibsonomy.org/bibtex/24250ca182460003675bc35666370efdc/madmicha},
description = {Proof of concept evaluation of trough airway... [Clin Sci (Lond). 2013] - PubMed - NCBI},
doi = {10.1042/CS20130213},
interhash = {f0b41d80cfde0fe4e4f038d0aff806f9},
intrahash = {4250ca182460003675bc35666370efdc},
journal = {Clin Sci (Lond)},
keywords = {asthma ligands salbutamol stereoisomeric},
month = jul,
pmid = {23829494},
timestamp = {2013-08-26T08:26:21.000+0200},
title = {Proof of concept evaluation of trough airway hyper-responsiveness following regular racemic or levosalbutamol in genotype-stratified steroid-treated persistent asthmatics},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23829494},
year = 2013
}