AIMS: Adenosine monophosphate (AMP) acts indirectly via primed airway mast cells to induce bronchial hyper-responsiveness, which in turn correlates with eosinophilic asthmatic inflammation and atopic disease expression. We evaluated single and short-term dosing effects of a modern histamine H1-receptor antagonist, levocetirizine, given at the usual clinically recommended dose, on the primary outcome of AMP bronchoprovocation. METHODS:Fifteen atopic asthmatics were randomized in double-blind, cross-over fashion to receive for 1 week either levocetirizine 5 mg or placebo. There was a 1-week washout period prior to each randomized treatment. The provocative concentration of AMP producing a 20% fall in FEV1 (PC20) was measured after each washout at baseline and at 4-6 h following the first and last doses of each randomized treatment. RESULTS: Baseline mean +/- SEM values after washout prior to each randomized treatment comparing levocetirizine vs placebo were not significantly different for prechallenge FEV1 (% predicted) 83 +/- 4 vs 82 +/- 4, or AMP PC20 (mg ml(-1)) 45 +/- 24 vs 45 +/- 22, respectively. Airway calibre as prechallenge FEV1 for levocetirizine vs placebo was not significantly different following the first dose 86 +/- 4 vs 82 +/- 4, or the last dose 85 +/- 4 vs 83 +/- 4, respectively. There were significant improvements (P < 0.05) in AMP PC20 comparing levocetirizine vs placebo following the first dose 123 +/- 73 vs 48 +/- 24, a 1.4 doubling dilution difference (95% CI 0.8, 1.9), and the last dose 127 +/- 74 vs 53 +/- 29, a 1.2 doubling dilution difference (95% CI 0.5, 2.0). AMP PC20 was also improved (P < 0.05) by the first and last doses of levocetirizine but not placebo, vs respective baseline values, with there being no difference in the degree of protection between first and last doses. CONCLUSIONS: Single and short-term dosing with levocetirizine conferred similar improvements in bronchial hyper-responsiveness to AMP challenge, which was unrelated to prechallenge airway calibre. Further studies are indicated to evaluate the longer-term effects of levocetirizine on asthma exacerbations.
RCT Entities:
AIMS: Adenosine monophosphate (AMP) acts indirectly via primed airway mast cells to induce bronchial hyper-responsiveness, which in turn correlates with eosinophilic asthmatic inflammation and atopic disease expression. We evaluated single and short-term dosing effects of a modern histamine H1-receptor antagonist, levocetirizine, given at the usual clinically recommended dose, on the primary outcome of AMP bronchoprovocation. METHODS: Fifteen atopic asthmatics were randomized in double-blind, cross-over fashion to receive for 1 week either levocetirizine 5 mg or placebo. There was a 1-week washout period prior to each randomized treatment. The provocative concentration of AMP producing a 20% fall in FEV1 (PC20) was measured after each washout at baseline and at 4-6 h following the first and last doses of each randomized treatment. RESULTS: Baseline mean +/- SEM values after washout prior to each randomized treatment comparing levocetirizine vs placebo were not significantly different for prechallenge FEV1 (% predicted) 83 +/- 4 vs 82 +/- 4, or AMP PC20 (mg ml(-1)) 45 +/- 24 vs 45 +/- 22, respectively. Airway calibre as prechallenge FEV1 for levocetirizine vs placebo was not significantly different following the first dose 86 +/- 4 vs 82 +/- 4, or the last dose 85 +/- 4 vs 83 +/- 4, respectively. There were significant improvements (P < 0.05) in AMP PC20 comparing levocetirizine vs placebo following the first dose 123 +/- 73 vs 48 +/- 24, a 1.4 doubling dilution difference (95% CI 0.8, 1.9), and the last dose 127 +/- 74 vs 53 +/- 29, a 1.2 doubling dilution difference (95% CI 0.5, 2.0). AMP PC20 was also improved (P < 0.05) by the first and last doses of levocetirizine but not placebo, vs respective baseline values, with there being no difference in the degree of protection between first and last doses. CONCLUSIONS: Single and short-term dosing with levocetirizine conferred similar improvements in bronchial hyper-responsiveness to AMP challenge, which was unrelated to prechallenge airway calibre. Further studies are indicated to evaluate the longer-term effects of levocetirizine on asthma exacerbations.
Authors: Graeme P Currie; Daniel K C Lee; Kay Haggart; Caroline E Bates; Brian J Lipworth Journal: Am J Respir Crit Care Med Date: 2002-11-27 Impact factor: 21.405
Authors: M Van Den Berge; R J Meijer; H A Kerstjens; D M de Reus; G H Koëter; H F Kauffman; D S Postma Journal: Am J Respir Crit Care Med Date: 2001-06 Impact factor: 21.405
Authors: M van den Berge; H A Kerstjens; R J Meijer; D M de Reus; G H Koëter; H F Kauffman; D S Postma Journal: Am J Respir Crit Care Med Date: 2001-10-01 Impact factor: 21.405