The effects of inhaled formoterol on the autonomic nervous system in adolescents with asthma

Abstract

Background: The safety of long-acting beta-2-adrenergic agonists is increasingly questioned by physicians. Although formoterol is frequently used in childhood, its effects on the autonomic cardiovascular system have not been studied. Objective: To investigate the effects of inhaled formoterol on autonomic nervous system using heart rate variability in adolescents with persistent asthma. Methods: Electrocardiography of 20 asthmatic adolescents (1220 years) was monitored for 5 specific days. The first day served as basal measurement, and the 2nd and 3rd days reflected the effects of a single and 2 doses of formoterol, respectively. From days 4 to 29, patients received regular treatment with formoterol/budesonide and were monitored on days 30 and 31 to evaluate the development of cardiac and respiratory tolerance after single-dose and 2 doses of formoterol, respectively. Electrocardiographs were analyzed for heart rate, heart rate variability (both time and frequency domain parameters), and spirometry tests were performed. Results: Inhalation of single-dose formoterol increased heart rate and decreased heart rate variability parameters (ratio of the normal-to-normal [NN] interals changing in excess of 50 ms to total of NN intervals [pNN50], total power [TP][ms], TP[ln]) compared with the corresponding baseline values during the first 12 hours of the day. The heart rate variability parameters (pNN50, TP[ms], TP[ln], root mean square of differences between adjacent NN intervals) during the first 12 hours were increased on the 30th day compared with the 2nd day and decreased on the 31st day compared with the 30th day. Conclusion: Single-dose formoterol inhalation decreases cardiovagal responsiveness and increases the sympathetic tone in cardiac autonomous control, and regular use of formoterol causes development of tolerance to these effects. However, additive doses of formoterol cause loss of this tolerance. © 2011 American College of Allergy, Asthma & Immunology.