Circadian rhythm in total pulmonary resistance of asthmatic children. Effects of a beta-agonist agent

Six children (boys and girls, 8 to 13 years old) with allergic asthma (AA) had their total pulmonary resistance (R1) measured at four fixed times (0730, 1130, 1630 and 2230 hr), before and again 10 min after a 2 mg orciprenaline (beta-agonist) aerosol inhalation. R1 was measured by means of the esophageal balloon technique. Subjects were socially synchronized in May with a diurnal activity from 0700 to 2100 and a nocturnal rest. Patients had had no asthma attacks and had received no medication for 8-15 days. Time series were analyzed according to conventional (t-tested mean time point differences) ANOVA, and cosinor methods. The 24 hr adjusted means (cm H2O.l/s +/- SEM) were 5.7 +- 0.4 in seven previously documented healthy children. 7.4 +/- 1.2 in AA before orciprenaline, and 4.9 +/- 0.2 in healthy children, 5.2 +/- 0.8 in AA after beta-agonist inhalation. Circadian rhythms were detected in both groups before but not after treatment. The treatment had its maximal effect on R1 around 0730 (when bronchial patency is close to its trough) and had no effect around 1630 (peak time of airway patency) in both groups (P less than 0.01; ANOVA). Thus, inhaled orciprenaline was mainly effective around 0730 and to a lesser extent around 2230 whereas there was no detectable effect during the day (1230 and 1630).