Circadian Variation of Bronchial Caliber and Antigen-induced Late Asthmatic Response: Conclusion

Circadian Variation of Bronchial Caliber and Antigen-induced Late Asthmatic Response: ConclusionTwo patients (patients 1 and 6) had wider circadian FEVj variation, with marked decrement at 2 am, than that seen in the other 4 patients during the control period. Nevertheless, the decrement in the FEVj at 2 am in the 2 patients following both morning and evening provocation seemed less variable than that in the others. It may be explained by the fact that the level of bronchial responsiveness before provocation, expressed as the amplitude of the circadian FEV, variation, does not necessarily correlate with the magnitude of the LAR. Also, a partial explanation may be the selection of patients who had maximum bronchial obstruction with similar levels of FEVj. In the present study to investigate the temporal consistency between the maximum LAR and the trough of the amplified circadian variation, all the significant bronchial obstruction following the provocation had to be clinically tolerable without bronchodilators to avoid artificial influences on the bronchial caliber as much as possible. Smaller amounts of inhaled antigen as the stimulus and different levels of anti-inflammatory mechanisms in each patient could cause most maximum bronchial obstruction to be of similar severity.
Mohiuddin and Martin reported that the LAR following the evening challenge was more severe than that following the morning challenge in their four adult patients who all had a dual asthmatic response. Occurring IARs may depend on the degree of bronchial responsiveness before provocation and the strength of the stimulus. On the other hand, occurring LARs may depend on exacerbation of bronchial inflammation and an increased degree of bronchial responsiveness following the provocation. The asthmatic children in the present study had simply isolated LARs, and the difference in the magnitude of the LAR between the morning and the evening challenges was insignificant. Isolated LARs following antigen inhalation are usual in asthmatic children, although the exact reasons are unclear. The dose of the inhaled antigen might not be enough to cause an IAR but might be enough to cause bronchial inflammation with an increase in bronchial responsiveness and a subsequent LAR. Also, the lack of immediate bronchial constriction in the evening might ameliorate a further increase in bronchial responsiveness and decrease in bronchial caliber related to the clock hour.
Since childrens bronchial responsiveness and bronchial caliber often change at short intervals,1 made the control and the antigen challenge studies over two consecutive days to minimize the variability of the baseline bronchial caliber. Also, I used mainly the lowest FEVi following the bronchial provocation as a marker of the LAR, since the FEV! is hardly capable of disclosing an accurate beginning and ending of small airway obstruction based on inflammation. The hour of the lowest FEV! was determined by visual inspection. Cosinor analysis, a standard method to evaluate circadian rhythm, may lose its accuracy in detecting a phase of rhythm, because acute exacerbation of bronchial inflammation and subsequent bronchial obstruction induced by artificial bronchial provocation might impair the genuine pattern of the circadian variation of bronchial caliber. The 4-h interval in consecutive FEV! measurements for 48 h, which was tolerable for the children, might also reduce the accuracy of the FEVi time course.

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