Single and short-term dosing effects of levocetirizine on adenosine monophosphate bronchoprovocation in atopic asthma

Abstract

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.

Figures

Figure 1

Study design schematic depicting washout and randomized treatment periods, with study visits V0 – V6

Figure 2

Individual data for AMP PC20 as doubling dilution shift from respective baseline after washout, showing placebo and levocetirizine values for first and last doses, joined for each individual. Horizontal lines depict mean values for each first and last dose of randomized treatments. Levocetirizine significantly improved (P < 0.05) AMP PC20vs placebo for first and last doses