Burioka Naoto, Miyata Masanori, Endo Masahiro, Fukuoka Yasushi, Suyama Hisashi, Nakazaki Hirofumi, Igawa Katsutoshi, Shimizu Eiji
Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, 36-1 Nishimachi, Yonago 683-8504, Japan.
Chronobiol Int. 2005;22(2):383-90. doi: 10.1081/cbi-200053587.
We investigated the efficacy of nighttime transdermal tulobuterol (beta2-adrenoceptor agonist) chronotherapy for nocturnal asthma by assessing changes both in the frequency of symptoms and features of the circadian rhythm in peak expiratory flow (PEF), a measure of airway caliber. Thirteen patients with nocturnal asthma were evaluated before and during tulobuterol patch chronotherapy, applied once daily in the evening for 6 consecutive days. Patients were asked to record their PEF every 4h between 03:00 and 23:00 h for one day. Circadian rhythms in PEF were examined by group-mean cosinor analysis. The group average PEF at 03:00 h, the time during the 24 h when PEF is generally the poorest, before the application of the chronotherapy, when asthma was unstable and nocturnal symptoms frequent, was 276 +/- 45 L/min. Application of the tulobuterol patch at nighttime significantly increased (p < 0.001) the 03:00 h group average PEF to 363 +/- 67 L/min. Significant circadian rhythms in PEF were observed during the span of study when nocturnal symptoms were frequent as well as with the use of the tulobuterol patch. Before the initiation of tulobuterol chronotherapy, the bathyphase (trough time of the circadian rhythm) in PEF narrowed to around 04:00h, and the group circadian amplitude was 28.8 L/min. In contrast, the group circadian amplitude significantly (p < 0.01) decreased to 10.4 L/min, and the 24 h mean PEF increased significantly with tulobuterol patch chronotherapy. These changes indicate that tulobuterol chronotherapy significantly increased both the level and stability of airway function over the 24 h. The circadian rhythm in PEF varied with the severity and frequency of asthmatic symptoms with and without the nighttime application of the tulobuterol patch medication. We conclude that the parameters of the circadian rhythm of PEF proved useful both in determining the need for and effectiveness of tulobuterol chronotherapy for nocturnal asthma.
我们通过评估症状频率变化以及作为气道管径指标的呼气峰值流速（PEF）昼夜节律特征，研究了夜间经皮妥洛特罗（β2肾上腺素能受体激动剂）时间疗法对夜间哮喘的疗效。13例夜间哮喘患者在妥洛特罗贴剂时间疗法前及治疗期间接受评估，该疗法每晚应用一次，连续应用6天。要求患者在一天的03:00至23:00期间每4小时记录一次PEF。通过组均值余弦分析检查PEF的昼夜节律。在时间疗法应用前，哮喘不稳定且夜间症状频繁时，03:00（24小时内PEF通常最差的时间）的组平均PEF为276±45升/分钟。夜间应用妥洛特罗贴剂显著提高（p<0.001）03:00的组平均PEF至363±67升/分钟。在夜间症状频繁以及使用妥洛特罗贴剂的研究期间，观察到PEF有显著的昼夜节律。在开始妥洛特罗时间疗法前，PEF的低谷期（昼夜节律的低谷时间）缩短至约04:00，组昼夜振幅为28.8升/分钟。相比之下，组昼夜振幅显著（p<0.01）降至10.4升/分钟，且妥洛特罗贴剂时间疗法使24小时平均PEF显著增加。这些变化表明妥洛特罗时间疗法显著提高了24小时内气道功能的水平和稳定性。无论是否夜间应用妥洛特罗贴剂药物，PEF的昼夜节律都随哮喘症状的严重程度和频率而变化。我们得出结论，PEF昼夜节律参数在确定夜间哮喘妥洛特罗时间疗法的必要性和有效性方面均被证明是有用的。
