Beach J R, Stenton S C, Connolly M J, Walters E H, Hendrick D J
Chest Unit, Newcastle General Hospital, University of Newcastle upon Tyne, UK.
Thorax. 1995 Mar;50(3):235-9. doi: 10.1136/thx.50.3.235.
A number of studies have suggested that diurnal variation in airways responsiveness underlies the circadian rhythm of ventilatory function in asthma. Measurements of airways responsiveness are therefore often performed at standardised times in order to avoid this possible effect, but this is not practical for epidemiological studies. Refractoriness to methacholine has also been reported and this, too, could confound the results of methacholine tests repeated over short intervals. This investigation was carried out to evaluate the possible magnitude of diurnal variation and refractoriness in repeated measures of airways responsiveness to methacholine.
To investigate diurnal variation in airways responsiveness, 24 asthmatic subjects aged 18-45 underwent five methacholine tests over three days which were not necessarily consecutive: day 1 at 08:00 hours; day 2 at 08:00 hours, 14:00 hours, 20:00 hours; day 3 at 20:00 hours. To investigate refractoriness a retrospective analysis was undertaken of all paired methacholine tests performed in individuals within our unit between 1984 and 1990 where there had been no intervention likely to affect the results.
The first investigation revealed no diurnal change in airways responsiveness although there was a change in FEV1. Mean PD20 did, however, increase 1.57 fold from 08:00 hours on day 1 to 08:00 hours on day 2 for subjects studied on consecutive days. The second investigation confirmed that a test interval of up to 24 hours (but not of 48 or more hours) was associated with a refractory index (PD20 test 2/PD20 test 1) of > 1.
No diurnal variation in airways responsiveness was detected for measurements made between 08:00 hours and 20:00 hours, but an interval between successive tests of up to 24 hours was associated with refractoriness. Diurnal variation is not likely to exert an important confounding effect on methacholine tests carried out between 08:00 hours and 20:00 hours, but confounding could result from refractoriness if tests are repeated at intervals up to 24 hours.
多项研究表明，气道反应性的昼夜变化是哮喘通气功能昼夜节律的基础。因此，为避免这种可能的影响，气道反应性测量通常在标准化时间进行，但这在流行病学研究中并不实用。也有报道称存在对乙酰甲胆碱的不应性，这也可能混淆短时间内重复进行的乙酰甲胆碱试验结果。本研究旨在评估重复测量气道对乙酰甲胆碱反应性时昼夜变化和不应性的可能程度。
为研究气道反应性的昼夜变化，24名年龄在18 - 45岁的哮喘患者在三天内（不一定连续）接受了五次乙酰甲胆碱试验：第1天08:00；第2天08:00、14:00、20:00；第3天20:00。为研究不应性，对1984年至1990年间在我们单位内进行的所有成对乙酰甲胆碱试验进行回顾性分析，这些试验中没有可能影响结果的干预措施。
首次研究显示气道反应性无昼夜变化，尽管第一秒用力呼气容积（FEV1）有变化。然而，连续研究的受试者中，平均使FEV1下降20%所需乙酰甲胆碱累积剂量（PD20）从第1天08:00到第2天08:00增加了1.57倍。第二项研究证实，长达24小时（但不是48小时或更长时间）的试验间隔与不应性指数（PD20试验2/PD20试验1）>1相关。
在08:00至20:00之间进行的测量未检测到气道反应性的昼夜变化，但连续试验间隔长达24小时与不应性相关。昼夜变化不太可能对08:00至20:00之间进行的乙酰甲胆碱试验产生重要的混杂影响，但如果试验间隔长达24小时重复进行，不应性可能导致混杂。
