【Cochrane简语概要】增加吸入性皮质类固醇的剂量或继续常规剂量治疗成人和儿童哮喘发作

关键信息

遵循治疗计划并在哮喘发作开始时使用含有增加剂量的吸入性皮质类固醇的吸入器，而不是使用含有稳定剂量的吸入器的患者，病情同样可能恶化，并需要口服类固醇。虽然其他的益处和危害还不确定，但总的来说，在 "盲式吸入器 "的研究中，受试者和研究人员不知道谁服用了含有增加剂量的吸入性皮质类固醇，因此该研究并未表明这种方法对轻到中度哮喘患者有益。值得注意的是，由于没有使用盲式吸入器，在最近的研究中发现了对控制不佳的哮喘更有利的结果。

（图片来自Children's Mercy Hospital）

什么是哮喘？

哮喘是一种常见的长期肺部疾病，会引起咳嗽、呼吸急促和喘息。哮喘患者经常经历症状的短期恶化，即所谓的“发作”，症状从轻微到危及生命。

为什么这对哮喘患者很重要？

哮喘发作对哮喘患者来说是可怕的，往往需要在家里或医院进行紧急治疗。了解如何在症状出现的第一时间最好地控制哮喘发作是至关重要的，可以避免需要口服类固醇或到医院进行紧急治疗。

吸入性皮质类固醇是一种常见的哮喘的治疗方法，每天服用以减少哮喘发作的可能性。向哮喘患者提供书面行动计划，告诉他们如果症状恶化时该怎么办，这些计划有时建议短期增加吸入性皮质类固醇的剂量，以使症状恢复控制。

我们想知道什么？

我们研究了在哮喘症状恶化时增加吸入性皮质类固醇的剂量是否能减少进一步治疗的需要，以及这样做是否有任何伤害。

我们做了什么？

我们检索了所有随机分配每天吸入皮质类固醇的哮喘患者在症状恶化时服用盲法吸入器的研究。盲法吸入器要么增加吸入性皮质类固醇的常规剂量，要么保持不变。我们感兴趣的是，被分配到增加剂量的患者中，是否更少的患者会出现哮喘发作。我们以两种方式衡量哮喘发作：需要口服皮质性类固醇的患者，以及需要在急诊科或医院进行紧急护理的患者。我们还研究了与稳定剂量相比，增加吸入性皮质类固醇的剂量是否会导致更多的不良事件。

我们对文献进行了广泛的检索，并由两名研究人员独立评估，以判断它们是否应该被纳入研究。同时记录关于这些研究、受试者和治疗策略的信息。使用最新的方法汇总研究结果，并评估每项研究结果的可信程度。最后我们将每项综合结果依据其证据质量分为高质量、中等质量、低质量或极低质量证据。

我们发现了什么？

我们纳入了9项轻中度哮喘患者的随机对照试验（受试者被随机分配到两个或两个以上治疗组中的一个研究）。其中5项研究针对成年人，4项研究针对儿童。

使用吸入器同时增加吸入皮质类固醇剂量的患者病情恶化的可能性与使用吸入器同时使用安慰剂（模拟治疗）或正常剂量的患者一样，需要口服皮质类固醇一个疗程。这一主要结果有一定的可信度，但很难判断增加剂量对其他类型的非计划护理（看医生或去医院）或对缩短哮喘发作时间是否有益。发生不良事件的结果表明，保持吸入稳定剂量的皮质类固醇可能更安全，但该结果的可信度为极低。

证据的局限性是什么？

研究开始时，受试者吸入皮质类固醇的剂量、治疗组的剂量增加了多少、被告知开始使用吸入器的时间和方式，以及他们被允许服用的其他药物都各不相同。只有大约一半的受试者真正需要使用研究用的吸入器，当我们只观察这些人时，似乎会有一点益处，但是由于研究结果不同，且存在较高的偏倚风险，该研究可信度极低。

尽管在研究过程中没有很多受试者需要去医院或急诊科就诊，可正因如此，我们很难判断短期内增加吸入性皮质类固醇是否有价值，我们的证据质量为低或极低。研究报告的伤害并不一致，综合结果也非常不确定。

本证据的时效性如何？

本综述的证据更新至2021年12月20日，这些研究发表于1998年至2018年。

作者结论: 

对患有轻中度哮喘的成人和儿童进行的双盲试验的证据表明，在病情恶化的第一时间，增加ICS剂量不太可能显著减少对口服皮质类固醇的需求。与保持剂量稳定相比，不能排除ICS增加剂量的其他临床重要益处和潜在伤害，因为置信区间较宽，试验中存在偏倚风险，以及必须做出综合分析的假设。1998年至2018年期间纳入的的研究反映了不断发展的临床实践和研究方法，数据不支持对基线剂量、倍增量、哮喘严重程度和时间等效应修正因素进行彻底调查。本系统综述未纳入从务实的、非盲法研究中所获得的最新证据，这些证据表明，在哮喘控制不佳的患者中，增加较大剂量有益。有必要对盲法试验和非盲法试验之间的差异进行系统评价，利用稳健的方法评估偏倚风险，以便为决策者提供最完整的证据观点。

作者:Kew KM, Flemyng E, Quon BS, Leung C；译者：袁瑞，武汉大学第二临床学院；审校：靳英辉，武汉大学中南医院循证与转化医学中心；编辑排版：索于思，北京中医药大学循证医学中心

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【Cochrane Plain Language Summary】

Increasing the dose of inhaled steroids or continuing the usual dose to treat asthma attacks in adults and children

Key messages

People who follow an action plan to take an inhaler containing an increased dose inhaled corticosteroids at the start of an asthma attack instead of a stable dose are probably as likely to worsen and need oral steroids. Other benefits and harms are uncertain, but overall studies that used 'blinded inhalers' so participants and staff were unaware of who received an increased dose did not suggest a benefit for people with mild to moderate asthma. It should be noted that more favourable results for poorly controlled asthma have been found in recent studies that were not eligible for this review because blinded inhalers were not used.

What is asthma?

Asthma is a common, long-term lung condition that causes cough, shortness of breath, and wheezing. People with asthma often experience short-term worsening of symptoms known as exacerbations, or 'attacks', that range from mild to life-threatening.

Why is this important for people with asthma?

Asthma attacks are frightening for people with asthma and often require urgent treatment at home or in hospital. Knowing how best to control asthma attacks at the first sign of symptoms is important to avoid the need for oral steroids or emergency treatment in hospital.

Inhaled corticosteroids are a common treatment for asthma that are taken daily to reduce the likelihood of attacks occurring. Written action plans are given to people with asthma to tell them what to do if their symptoms do worsen, and these sometimes recommend a short-term increase in the dose of inhaled corticosteroids to get symptoms back under control. 

What did we want to find out?

We looked at whether increasing the dose of inhaled corticosteroids when asthma symptoms worsen reduces the need for further treatment, and if there are any harms with doing so. 

What did we do?

We looked for all studies that randomly allocated people with asthma taking a daily inhaled corticosteroid to take a blinded inhaler if their symptoms worsened. The blinded inhaler either increased their usual dose of inhaled corticosteroid or kept it the same. We were interested in whether fewer people allocated to receive an increased dose went on to have an asthma attack. We measured asthma attacks in two ways: those needing a course of oral steroids, and those needing urgent care in the emergency department or in hospital. We also looked at whether the increased inhaled corticosteroids doses led to more adverse events compared with a stable dose.

We conducted broad searches, and two researchers independently evaluated studies to judge if they should be included. We recorded information about the studies, participants, and treatment strategies. We used the latest methods for bringing the results together and assessing how much each study result could be trusted. We rated each combined result as high, moderate, low, or very low quality, depending on how confident we were that it was reliable.

What did we find?

We included nine randomised controlled trials (studies where participants are randomly assigned to one of two or more treatment groups) of people with mild to moderate asthma. Five studies looked at adults, and four looked at children. 

People who were given the inhaler with an increased dose of inhaled corticosteroid were about as likely to get worse and need a course of oral corticosteroids as those who were given an inhaler with a placebo (dummy treatment) or their usual dose. We have moderate confidence in this main result, but it was much more difficult to tell whether there was a benefit of a dose increase for other types of unscheduled care (seeing a doctor or going to hospital) or for reducing the duration of the attack. The results for adverse events suggest that it may be safer to keep inhaled corticosteroids stable, but we had very low confidence in the results.

What are the limitations of the evidence?

Studies varied in the dose of inhaled corticosteroids people were taking at the start of the study, how much the dose was increased in the treatment group, when and how people were told to start the inhaler, and what other medicines they were allowed to take. Only about half the participants actually needed to take the study inhaler, and when we looked just at those people, it appeared that there might be a small benefit, but we had very low confidence because the study results varied and there was a high risk of bias.

Whilst not many people needed to go to hospital or visit the emergency department during the course of the studies, this made it difficult to tell if a short-term increase in inhaled corticosteroids is worthwhile, and our confidence in the evidence was low or very low. Studies did not report harms consistently, and the combined results were very uncertain.

How up-to-date is this evidence?

The review is current to 20 December 2021, and the studies were published between 1998 and 2018.

Authors' conclusions: 

Evidence from double-blind trials of adults and children with mild to moderate asthma suggests there is unlikely to be an important reduction in the need for oral steroids from increasing a patient's ICS dose at the first sign of an exacerbation. Other clinically important benefits and potential harms of increased doses of ICS compared with keeping the dose stable cannot be ruled out due to wide confidence intervals, risk of bias in the trials, and assumptions that had to be made for synthesis. Included studies conducted between 1998 and 2018 reflect evolving clinical practice and study methods, and the data do not support thorough investigation of effect modifiers such as baseline dose, fold increase, asthma severity and timing. The review does not include recent evidence from pragmatic, unblinded studies showing benefits of larger dose increases in those with poorly controlled asthma. A systematic review is warranted to examine the differences between the blinded and unblinded trials using robust methods for assessing risk of bias to present the most complete view of the evidence for decision makers.

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