Effects of fluticasone vs. fluticasone/salmeterol on airway calibre and airway hyperresponsiveness in mild persistent asthma.

Abstract

AIMS:

Inhaled corticosteroids alone or in combination with long acting beta2-agonists are indicated for use in mild persistent asthmatics. We set out to evaluate effects on airway hyperresponsiveness (AHR) and airway calibre using hydrofluoroalkane fluticasone/salmeterol (FP/SM) vs. double the dose of fluticasone alone (FP).

METHODS:

Fourteen mild persistent asthmatics completed a randomized double-blind crossover study with 1-week run-in and washout periods prior to treatments. Subjects received 3 weeks of FP 250 microg or FP 125 microg/SM 25 microg as 1 puff twice daily. Methacholine PD20 and lung function were measured after both baseline and treatment periods.

RESULTS:

There were no significant differences in baseline values prior to randomized treatments. Compared with pooled baseline, FP/SM and FP conferred improvements (P < 0.05) on methacholine PD20: 2.5 (95% confidence interval 1.7, 3.2) and 1.6 (0.8-2.3) doubling dose improvements, respectively; between FP/SM vs. FP there was a 0.9 (0.4, 1.4) doubling dose difference (P < 0.05). For forced expiratory volume in 1 s (FEV1), forced mid-expiratory flow (FEF25-75) and morning peak expiratory flow (PEF), FP/SM but not FP conferred improvements (P < 0.05) compared with pooled baseline, with FP/SM being greater than FP (P < 0.05): differences in FEV1 of 7.2% (3.8, 10.6) predicted, FEF25-75 of 11.2% (6.3, 16.1) predicted, and morning PEF of 17 L x min(-1)(1-32).

CONCLUSIONS:

FP/SM conferred improvements on AHR and airway calibre, while twice the dose of FP improved only AHR in patients with mild asthma. The differential effects of FP/SM and FP suggest separate but complementary actions of the two moieties on airway inflammation and smooth muscle stabilization. This may explain the beneficial effects of combination inhalers on exacerbations.

• Authors: Graeme P Currie, Suvi Stenback, Brian J Lipworth
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 56 Issue 1 Pg. 11-7 (Jul 2003) ISSN: 0306-5251 [Print] England
• PMID: 12848770 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Androstadienes
• Bronchoconstrictor Agents
• Bronchodilator Agents
• Methacholine Chloride
• Nitric Oxide
• Salmeterol Xinafoate
• Creatinine
• Fluticasone
• Albuterol
• Hydrocortisone

Topics

• Adult
• Albuterol (administration & dosage, analogs & derivatives)
• Androstadienes (administration & dosage)
• Asthma (drug therapy, physiopathology)
• Bronchi (drug effects)
• Bronchoconstrictor Agents
• Bronchodilator Agents (administration & dosage)
• Creatinine (urine)
• Cross-Over Studies
• Double-Blind Method
• Female
• Fluticasone
• Forced Expiratory Volume (drug effects)
• Humans
• Hydrocortisone (urine)
• Male
• Methacholine Chloride
• Nitric Oxide (analysis)
• Peak Expiratory Flow Rate (drug effects)
• Salmeterol Xinafoate