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Dose-related effects of formoterol on airway responsiveness to adenosine 5'-monophosphate and histamine

Dept of Respiratory Medicine and Allergy, GKT School of Medicine, King's College, London, UK

CORRESPONDENCE: R.I. Ketchell, Dept of Respiratory Medicine and Allergy, GKT School of Medicine, King's College, Bessemer Road, London, SE5 9PJ, UK. Fax: 44 2073463940. E-mail: ian.ketchell@kcl.ac.uk

Keywords: adenosine 5'-monophosphate, airway responsiveness, asthma, formoterol

Received: March 14, 2001
Accepted November 9, 2001

Inhaled short-acting ß₂-agonists provide greater protection against airway responsiveness (AR) to the mast-cell stimulus, adenosine 5'-monophosphate (AMP), than to histamine, a direct spasmogen. Both terbutaline and albuterol exhibit this mast-cell stabilizing property in a dose-dependent manner. A single dose of the long-acting ß₂-agonist formoterol has also been reported to have a mast cell-stabilizing effect, whereas salmeterol has not. To explore the dose-related actions of the long-acting ß₂-agonist formoterol on AR, the authors compared the acute effects of three doses of formoterol and terbutaline on AR to AMP and histamine.

In a double-blind, randomized, placebo-controlled, cross-over study, 25 mild, steroid naive, asthmatic subjects attended on 10 occasions. At each visit, subjects inhaled either a single dose of terbutaline (500 µg), formoterol (6, 12 or 24 µg) or a matched placebo, administered via Turbuhaler®, 30 min prior to challenge with both AMP and histamine.

Each dose of ß₂-agonist reduced AR to AMP and histamine. The bronchoprotective effects of formoterol (6 µg) and terbutaline (500 µg) were similar in magnitude in reducing AR to histamine (mean±sd: 3.6±0.3 and 3.1±0.3 doubling doses (DD)) and AR to AMP (3.5±0.5 and 3.3±0.4 DD, respectively). Overall, formoterol reduced AR to both spasmogens in a dose-dependent manner. In addition, formoterol (12 and 24 µg) provided a significantly greater protective effect against AMP than against histamine challenge. It decreased AR by 5.7±0.6 and 6.3±0.7 DD against AMP and 4.3±0.4 and 4.8±0.43 DD against histamine, respectively.

The results of this study indirectly demonstrated an in vivo dose-dependent mast-cell stabilizing effect of formoterol, in addition to functional antagonism on airway smooth muscle. This property of ß₂-agonists may have clinical benefits in asthma management.

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