Alteration of the Circadian Rhythm in Peak Expiratory Flow of Nocturnal Asthma Following Nighttime Transdermal β₂‐adrenoceptor Agonist Tulobuterol Chronotherapy

Abstract

We investigated the efficacy of nighttime transdermal tulobuterol (β₂‐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 4 h 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 04:00 h, 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.

• Nocturnal asthma
• Chronotherapy
• Circadian rhythm
• Peak expiratory flow
• Transdermal β₂‐adrenoceptor agonist