Abstract
Background: Adenosine monophosphate (AMP) acts indirectly via primed airway mast cells to induce bronchial hyperresponsiveness which in turn correlates with eosinophilic asthmatic inflammation and atopic disease expression. We evaluated single and chronic dosing effects of levocetirizine (LEV) on the primary outcome of AMP bronchoprovocation.
Methods: 15 atopic asthmatics were randomised in double-blind, cross-over fashion to receive for 1 week either LEV 5mg or placebo (PL) with 1 week washout periods. AMP PC20 was measured after each washout at baseline and at 4 - 6 hours following the first and last doses of each randomised treatment.
Results: Baseline mean values for LEV vs. PL were similar for pre-challenge FEV1 (% predicted): 83 vs. 82, and for AMP PC20 (mg/ml): 45 vs. 45 respectively. Pre-challenge FEV1 for LEV vs. PL was similar following the first dose: 86 vs. 82, or the last dose: 85 vs. 83 respectively. There were significant improvements (p < 0.05) in AMP PC20 for LEV vs. PL following the first dose: 123 vs. 48; a 1.4 doubling dilution difference, and the last dose: 127 vs. 53; a 1.2 doubling dilution difference. AMP PC20 also improved (p < 0.05) with the first and last doses of LEV but not PL, vs. respective baseline values, with there being no difference in the degree of protection between first and last doses.
Conclusion: LEV as single and chronic dosing conferred similar improvements in brochial hyperresponsiveness to AMP challenge, which was unrelated to pre-challenge airway calibre. Further studies are required to evaluate longer-term effects of LEV on asthma exacerbations.