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Clinical Investigations: ASTHMA |

Repeated Dosing Effects of Mediator Antagonists in Inhaled Corticosteroid-Treated Atopic Asthmatic Patients*

Daniel K. C. Lee; Catherine M. Jackson; Kay Haggart; Brian J. Lipworth
Author and Funding Information

*From the Asthma and Allergy Research Group, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, UK.

Correspondence to: Brian J. Lipworth, MD, Asthma and Allergy Research Group, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK; e-mail: b.j.lipworth@dundee.ac.uk



Chest. 2004;125(4):1372-1377. doi:10.1378/chest.125.4.1372
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Published online

Background: The anti-inflammatory effects of repeated dosing with mediator antagonists as add-on therapy to that with inhaled corticosteroids (ICSs) in patients with asthma remain to be fully established.

Objective: We elected to evaluate the effects of repeated dosing with fexofenadine (FEX) and montelukast (ML) at clinically recommended doses in ICS-treated asthmatic patients using adenosine monophosphate (AMP) bronchial challenge as the primary outcome.

Methods: Eighteen atopic asthmatic patients receiving a mean (± SEM) dose of 631 ± 104 μg daily of ICSs, which remained unchanged throughout the entire study, were randomized in double-blind, cross-over fashion to receive FEX, 180 mg, ML, 10 mg, or placebo (PL) for 1 week. There was a 1-week washout period prior to each randomized treatment. Measurements of the provocative concentration of a substance (ie, AMP) causing a 20% fall in FEV1 (PC20) were made after each washout period and randomized treatment period.

Results: The values for AMP PC20 after the washout period prior to each randomized treatment were not significantly different (FEX, 74 ± 15 mg/mL; ML, 73 ± 18 mg/mL; PL, 71 ± 19 mg/mL). There were significant improvements (p < 0.05) in AMP PC20 with the use of FEX (127 ± 38 mg/mL) and ML (121 ± 27 mg/mL) compared to PL (78 ± 23 mg/mL). Spontaneous recovery after AMP challenge, as determined by area under the 60-min time-response curve, was significantly enhanced (p < 0.05) with the use of ML (352 ± 95%.min) and FEX (758 ± 140%.min) compared to PL (683 ± 134%.min). Both FEX and ML significantly suppressed (p < 0.05) the levels of exhaled nitric oxide, while only ML significantly reduced (p < 0.05) the peripheral blood eosinophil count compared to PL. Morning and evening peak expiratory flow were significantly higher (p < 0.05), and the frequency of salbutamol rescue was significantly reduced (p < 0.05) with FEX and ML compared to PL.

Conclusion: Repeated dosing with FEX and ML as add-on therapy improved AMP PC20 and other surrogate inflammatory markers along with asthma diary outcomes in ICS-treated atopic asthmatic patients. Further studies are indicated to evaluate the long-term add-on effects of FEX on asthma exacerbations.

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