Non-pulmonary effects induced by the addition of formoterol to budesonide therapy in patients with mild or moderate persistent asthma

OBJECTIVE: The present study was designed to assess the non-pulmonary effects of a 2-week treatment with the addition of formoterol to budesonide therapy in 10 patients with mild or moderate asthma. METHODS: Each patient was invited to perform a screening visit which included spirometry before and after inhalation of 12 microg formoterol with a metered dose inhaler (MDI), measurement of arterial blood pressure, baseline electrocardiography and 24-hour Holter monitoring, and a test for evaluating upper limb tremor. Patients then began bronchodilating therapy with 12 microg formoterol MDI and 400 microg budesonide Turbuhaler b.i.d. Each patient was also given a peak flowmeter and a diary in which he had to record the morning and evening values measured before taking inhaled drugs. Two weeks later, the patients repeated the same examinations; the diary card was returned 2 months after the beginning of the study. RESULTS: Adding formoterol to budesonide therapy caused a significant improvement in lung function, but neither induced any statistically significant effect on mean heart rate, nor altered the circadian rhythm of autonomic regulation nor elicited significant alterations in cardiac morphology. However, the evaluation of upper limb tremor revealed a statistically significant increase (p = 0.02). CONCLUSIONS: This study shows that adding the recommended dose of formoterol to an inhaled corticosteroid therapy does not induce significant cardiac undesirable effects, although tremor, surely due to stimulation of beta(2) receptors of the skeletal muscles, may sometimes be a limiting effect.