The use of combination therapy in mild asthma is debated. The current authors evaluated the effects of formoterol alone and a formoterol/budesonide combination inhaler on asthma deterioration induced by repeated low-dose allergen exposure.
In total, 15 subjects with intermittent allergic asthma inhaled low doses of allergen on seven consecutive weekdays in a three-period, crossover, double-blind, double-dummy comparison between formoterol 4.5 μg TurbuhalerTM, budesonide 160 μg/formoterol 4.5 μg TurbuhalerTM and placebo, each taken as two puffs 30 min after allergen dosing. The outcome variables were: provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (PD20), exhaled nitric oxide fraction (FeNO), sputum eosinophils and prostaglandin D2, and diary card recordings of symptoms (on a scale of 0–10), short-acting β2-agonist use and evening forced expiratory volume in one second (FEV1).
With placebo treatment, allergen exposure caused significant increases in airway hyperresponsiveness (geometric mean (coefficient of variation) PD20: 397 (98) μg before versus 168 (82) μg after), FeNO (mean±sd 46±31 ppb before versus 73±46 ppb after) and asthma symptom score (mean±sd 0.39±0.55 before versus 0.68±0.67 after). Budesonide/formoterol abolished these changes and significantly improved baseline FEV1. Formoterol alone, while providing symptom relief, was no better than placebo in protecting against the allergen-induced increase in airway inflammation.
Signs of deteriorating asthma, provoked by low-dose allergen, are prevented by short-term use of budesonide/formoterol but not by temporary use of formoterol alone.
- Airway hyperresponsiveness
- allergic asthma
- exhaled nitric oxide
- inhaled corticosteroids
- long-acting β-agonists
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