Circadian rhythm in airway responsiveness and airway tone in patients with mild asthma

To determine the characteristics and reproducibility of circadian rhythms of airway responsiveness to histamine and methacholine and their relationship to airway tone in patients with mild asthma, we studied nine subjects with complaints of nighttime awakening due to dyspnea and/or cough at least once a week. Their mean age was 31.4 yr (range 17-65) and their mean daytime FEV₁ was 99 ± 14 (SD) % predicted. Forced expiratory volume in 1 s (FEV₁) and the provocative concentrations of histamine and methacholine necessary to decrease FEV₁ by 20% (PC₂₀FEV₁) were determined every 4 h for 13 consecutive measurements. Three subjects were measured with histamine, three with methacholine, and three with both histamine and methacholine. Data were evaluated on an individual basis. PC₂₀FEV₁ to histamine and methacholine showed significant and reproducible circadian variations in all cases (P < 0.01 each) with a mean amplitude of 1.00 ± 0.17 (SD) doubling concentrations for histamine and 1.35 ± 0.29 doubling concentrations for methacholine. The amplitude of PC₂₀FEV₁ was significantly larger (P < 0.05) and the time of maximum responsiveness was significantly earlier (P < 0.05) with methacholine compared with histamine. FEV₁ showed significant (P < 0.05) circadian variations in three of nine subjects, and peak expiratory flow rate showed variations in two subjects. Correlation between the variations of FEV₁ and PC₂₀FEV₁ was significant (P < 0.05) in 5 of 12 cases. From our observations we conclude that in mild asthmatic patients with nocturnal symptoms circadian variation in airway responsiveness to histamine or methacholine 1) appears to be more pronounced and more consistently present than circadian variation in airway tone, 2) is a reproducible phenomenon, and 3) does not appear to be causally linked to circadian variation in airway tone.