Effect of formoterol with or without budesonide in repeated low-dose allergen challenge

¹ Division of Respiratory Medicine and Allergy, Dept of Medicine at Karolinska University Hospital Huddinge; and Centre for Allergy Research at Karolinska Institutet, SE-171 77 Stockholm, Sweden
² Cityakuten, Stockholm
³ AstraZeneca Sweden
⁴ Division of Physiology, The National Institute of Environmental Medicine; and Centre for Allergy Research at Karolinska Institutet, SE-171 77 Stockholm, Sweden

^* To whom correspondence should be addressed. E-mail: barbro.dahlen{at}ki.se.

	Abstract

The use of combination therapy in mild asthma is debated. We evaluated the effects of formoterol alone and formoterol/budesonide combination inhaler on asthma deterioration induced by repeated low-dose allergen exposure.

Fifteen subjects with intermittent allergic asthma inhaled low doses of allergen on 7 consecutive weekdays in a three-period, cross-over, double-blind, double dummy, comparison between formoterol Turbuhaler 4.5µg, budesonide 160 µg·formoterol^-1 4.5 µg Turbuhaler, and placebo, each taken as two puffs 30 minutes after allergen dosing. Outcome variables were: provocative dose of methacholine causing a 20% fall in FEV₁(PD₂₀), exhaled nitric oxide (F_ENO), sputum eosinophils and prostaglandin D₂, and diary card recordings of symptoms (0–10), short-acting beta₂-agonist use and evening FEV₁.

With placebo treatment, allergen exposure caused significant increases in airway hyperresponsiveness (geom mean(CV) PD₂₀: 397(98) µg before vs 168(82) after), F_ENO (mean(SD): 46(31) ppb before vs 73(46) after) and asthma symptom score (mean(SD): 0.39(0.55) before vs 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.