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

• Published in: The European respiratory journal Vol. 19; no. 4; pp. 611 - 616
• Main Authors: Ketchell, R.I, Jensen, M.W, Spina, D, O'Connor, B.J
• Format: Journal Article
• Language: English
• Published: Leeds Eur Respiratory Soc 01.04.2002; Maney
• Subjects: Adenosine Monophosphate; Adrenergic beta-Agonists - administration & dosage; Adrenergic beta-Agonists - pharmacology; Adult; Airway Resistance - drug effects; Biological and medical sciences; Bronchial Provocation Tests; Bronchoconstriction - drug effects; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Ethanolamines - administration & dosage; Ethanolamines - pharmacology; Female; Formoterol Fumarate; Histamine; Humans; Male; Mast Cells - drug effects; Medical sciences; Pharmacology. Drug treatments; Respiratory system; Terbutaline; Human; Hyperreactivity; Respiratory disease; Bronchodilator; Bronchus; β2-Adrenergic receptor; β-Adrenergic receptor agonist; Exploration; Asthma; Histamine; Chemotherapy; Lung function; Treatment; Formoterol; Obstructive pulmonary disease
• ISSN: 0903-1936; 1399-3003
• DOI: 10.1183/09031936.02.00332001

Inhaled short-acting β 2 ‐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 β 2 ‐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 β 2 ‐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 β 2 ‐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 β 2 ‐agonists may have clinical benefits in asthma management.