Proof of concept evaluation of trough airway hyper-responsiveness following regular racemic or levosalbutamol in genotype-stratified steroid-treated persistent asthmatic patients

William J. Anderson, Philip M. Short, Peter A. Williamson, Ashley E. Morrison, Colin Palmer, Roger Tavendale, Brian J. Lipworth (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    2 Citations (Scopus)

    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 (200µg qid); levosalbutamol (100µg 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
    Original languageEnglish
    Pages (from-to)75-83
    Number of pages9
    JournalClinical Science
    Volume126
    Issue number1
    Early online date5 Jul 2013
    DOIs
    Publication statusPublished - 1 Jan 2014

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