Circadian variations of airway response to histamine in asthmatic subjects

In 15 clinically stable asthmatic subjects, histamine inhalation challenges were carried out on six different days, at 8, 16 and 22 h, twice at each time. On each visit, baseline functional measurements including FEV1 and forced mid-expiratory flow rates (FEF25-75%) were followed by the assessment of the concentration of histamine causing a 20% fall in FEV1 (PC20). There was no significant difference in baseline lung function tests and PC20 for visits done either at the same or different times. The correlation coefficients of PC20 for the visits at 8, 16 and 22 h were 0.95, 0.88 and 0.78 respectively. The dispersion of results of PC20 was significantly (p less than 0.05) more pronounced at 22 h than at 8 h. The cosinor analysis which depicts biologic rhythms as sinusoidal curves [8] revealed that seven subjects had detectable diurnal rhythms with acrophases (time of least excitability) at 9.8, 10.0, 11.8, 15.3, 15.4, 22.2 and 23.1 h. In five and three of these seven subjects respectively, significant rhythms of FEV1 and FEF25-75% were also detected with similar acrophases.