Furthermore, the maximum bronchial obstruction following antigen inhalation occurred between 10 pm and 6 am whenever the bronchial challenge was made. In particular, bronchial obstruction at 2 am was maximum or near maximum in both challenge studies. Antigen inhalation and the subsequent increase in bronchial responsiveness often amplify the circadian variation, and a downward arm of the circadian variation begins in the late afternoon and terminates between 10 pm and 6 am, generally around 2 am. Therefore, from the visual inspection of the FEV! time course, the maximum LAR was indistinguishable from the trough of further transiently amplified circadian variation following the antigen inhalation at any time. These findings suggest that the amplified circadian variation may have a relationship with the LAR and that the downward arm of that variation may participate in causing the LAR. canadian family pharmacy online
Since bronchial smooth muscle relaxant partially ameliorates the LAR, the LAR results from not only submucosal edema and intraluminal mucous retention but also smooth muscle contraction. In an LAR with a large amplitude, smooth muscle contraction may be especially important. In the present study, submucosal edema and mucous retention following the provocation might partially explain the progressive bronchial obstruction with late onset; however, they hardly explained the fact that the maximum or near maximum LAR occurred around 2 am regardless of the provocation hour, since their circadian rhythms were obscure. The phenomenon might be explained by the change in tone of smooth muscle, which was under the control of synergistic circadian rhythms of bronchial responsiveness, autonomic nerve, and endocrine systems.
The FEVi at 24 h after the antigen inhalation did not recover to the level before inhalation in 8 out of 12 challenges, and the clock hour of the maximum LAR following the morning challenge was significantly earlier than that following the evening challenge. Also, the LAR does not always continue more than 24 h. These findings suggest that the amplified circadian variation of the bronchial caliber only partially participates in causing the LAR. Bronchial edema and intraluminal retention of increased secretions may participate in causing the LAR in most cases, as earlier studies reported. A direct effect of acute bronchial edema on bronchial caliber is not negligible, especially in a child whose bronchial caliber is absolutely small. Bronchial edema in a process of inflammation is supposed to start by 2 to 4 h, reaches a peak at 6 to 12 h, and subsides by 24 h after the bronchial provocation. In the present study the peak bronchial obstruction due to edema might range from 4 pm to 10 pm in the morning challenge and from 12 midnight to 6 am in the evening challenge. If I take the effect of edema on bronchial caliber into consideration, the clock hour of maximum bronchial obstruction (maximum LAR) may be more similar, around 2 am, in the morning and the evening challenges.