The impact of dosage timing for inhaled corticosteroids in asthma: a randomised three-way crossover trial.

Aligning the timing of drug administration with rhythms in disease (chronotherapy) may improve therapeutic efficacy.

将药物给药时间与疾病节律同步（时间治疗学）可能会提高治疗效果。

We aimed to evaluate the impact of dosage timing for inhaled corticosteroids in asthma.

我们的目标是评估吸入性皮质类固醇剂量给药时间对哮喘的影响。

Methods

This is a randomised three-way crossover trial. Participants with mild to moderate atopic asthma were randomised to beclometasone dipropionate: (1) 400 µg once daily between 08:00 and 09:00 (ODAM); (2) 400 µg once daily between 15:00 and 16:00 (ODPM); and (3) 200 µg twice daily between 08:00 and 09:00 and between 20:00 and 21:00 (BD) for 28 days, with a 2 week washout period in between treatment periods.

这是一项随机的三向交叉试验。轻度至中度异位性哮喘患者被随机分配接受以下三种治疗方案之一：(1) 每日一次在08:00至09:00之间吸入400微克的倍他米松二丙酸酯（ODAM）；(2) 每日一次在15:00至16:00之间吸入400微克的倍他米松二丙酸酯（ODPM）；以及(3) 每日两次，分别在08:00至09:00和20:00至21:00之间吸入200微克的倍他米松二丙酸酯（BD），为期28天，每个治疗周期之间有2周的洗脱期。

Six-hourly spirometry and biomarkers were measured over 24 hours following the run-in period and at the end of each treatment period.

在基线期后，每6小时进行一次肺功能测量和生物标志物检测，持续24小时，并在每个治疗期结束时进行同样的测量。

Results

Of 25 participants, 21 completed all regimens.

在25名参与者中，有21人完成了所有治疗方案。

ODPM was superior in improving 22:00 FEV1 (median (IQR): +160 (+70, +270) ml) compared with ODAM (-20 (-80, +230) ml) and BD (+80 (-20, +200) ml).

ODPM在改善22:00 FEV1（中位数（四分位数间距）：+160（+70，+270）毫升）方面优于ODAM（-20（-80，+230）毫升）和BD（+80（-20，+200）毫升）。

ODPM resulted in better overnight (22:00 and 04:00) suppression in blood eosinophil counts compared with BD and ODAM.

ODPM在夜间（22:00和04:00）血液嗜酸性粒细胞计数的抑制方面优于BD和ODAM。

All regimens improved asthma control and reduced fractional exhaled nitric oxide and serum cortisol levels with no difference among dosing regimens.

所有方案均改善了哮喘控制，并降低了呼出气一氧化氮分数和血清皮质醇水平，各剂量方案之间无差异。

Conclusions

ODPM better suppresses the nocturnal dip in lung function and peak of blood eosinophil counts compared with BD and ODAM; this was without an increase in adverse events.

与每日两次和每日一次早晨方案相比，每日一次午夜方案更好地抑制了夜间肺功能下降和血液嗜酸性粒细胞计数峰值；这并未导致不良事件的增加。

Future trials are warranted to validate these findings in real-life settings and to determine which population may best benefit from chronotherapy.

未来的研究是必要的，以在现实环境中验证这些发现，并确定哪些人群可能从时间治疗学中获得最佳益处。