BUCM循證醫學精視角 - 【Cochrane簡語概要】增加吸入性皮質類固醇的劑量或繼續常規劑量治療成人和兒童哮喘發作－鑽石舞台

關鍵信息

遵循治療計劃並在哮喘發作開始時使用含有增加劑量的吸入性皮質類固醇的吸入器，而不是使用含有穩定劑量的吸入器的患者，病情同樣可能惡化，並需要口服類固醇。雖然其他的益處和危害還不確定，但總的來說，在 "盲式吸入器 "的研究中，受試者和研究人員不知道誰服用了含有增加劑量的吸入性皮質類固醇，因此該研究並未表明這種方法對輕到中度哮喘患者有益。值得注意的是，由於沒有使用盲式吸入器，在最近的研究中發現了對控制不佳的哮喘更有利的結果。

（圖片來自Children's Mercy Hospital）

什麼是哮喘？

哮喘是一種常見的長期肺部疾病，會引起咳嗽、呼吸急促和喘息。哮喘患者經常經歷症狀的短期惡化，即所謂的「發作」，症狀從輕微到危及生命。

為什麼這對哮喘患者很重要？

哮喘發作對哮喘患者來說是可怕的，往往需要在家裡或醫院進行緊急治療。了解如何在症狀出現的第一時間最好地控制哮喘發作是至關重要的，可以避免需要口服類固醇或到醫院進行緊急治療。

吸入性皮質類固醇是一種常見的哮喘的治療方法，每天服用以減少哮喘發作的可能性。向哮喘患者提供書面行動計劃，告訴他們如果症狀惡化時該怎麼辦，這些計劃有時建議短期增加吸入性皮質類固醇的劑量，以使症狀恢復控制。

我們想知道什麼？

我們研究了在哮喘症狀惡化時增加吸入性皮質類固醇的劑量是否能減少進一步治療的需要，以及這樣做是否有任何傷害。

我們做了什麼？

我們檢索了所有隨機分配每天吸入皮質類固醇的哮喘患者在症狀惡化時服用盲法吸入器的研究。盲法吸入器要麼增加吸入性皮質類固醇的常規劑量，要麼保持不變。我們感興趣的是，被分配到增加劑量的患者中，是否更少的患者會出現哮喘發作。我們以兩種方式衡量哮喘發作：需要口服皮質性類固醇的患者，以及需要在急診科或醫院進行緊急護理的患者。我們還研究了與穩定劑量相比，增加吸入性皮質類固醇的劑量是否會導致更多的不良事件。

我們對文獻進行了廣泛的檢索，並由兩名研究人員獨立評估，以判斷它們是否應該被納入研究。同時記錄關於這些研究、受試者和治療策略的信息。使用最新的方法匯總研究結果，並評估每項研究結果的可信程度。最後我們將每項綜合結果依據其證據質量分為高質量、中等質量、低質量或極低質量證據。

我們發現了什麼？

我們納入了9項輕中度哮喘患者的隨機對照試驗（受試者被隨機分配到兩個或兩個以上治療組中的一個研究）。其中5項研究針對成年人，4項研究針對兒童。

使用吸入器同時增加吸入皮質類固醇劑量的患者病情惡化的可能性與使用吸入器同時使用安慰劑（模擬治療）或正常劑量的患者一樣，需要口服皮質類固醇一個療程。這一主要結果有一定的可信度，但很難判斷增加劑量對其他類型的非計劃護理（看醫生或去醫院）或對縮短哮喘發作時間是否有益。發生不良事件的結果表明，保持吸入穩定劑量的皮質類固醇可能更安全，但該結果的可信度為極低。

證據的局限性是什麼？

研究開始時，受試者吸入皮質類固醇的劑量、治療組的劑量增加了多少、被告知開始使用吸入器的時間和方式，以及他們被允許服用的其他藥物都各不相同。只有大約一半的受試者真正需要使用研究用的吸入器，當我們只觀察這些人時，似乎會有一點益處，但是由於研究結果不同，且存在較高的偏倚風險，該研究可信度極低。

儘管在研究過程中沒有很多受試者需要去醫院或急診科就診，可正因如此，我們很難判斷短期內增加吸入性皮質類固醇是否有價值，我們的證據質量為低或極低。研究報告的傷害並不一致，綜合結果也非常不確定。

本證據的時效性如何？

本綜述的證據更新至2021年12月20日，這些研究發表於1998年至2018年。

作者結論:

對患有輕中度哮喘的成人和兒童進行的雙盲試驗的證據表明，在病情惡化的第一時間，增加ICS劑量不太可能顯著減少對口服皮質類固醇的需求。與保持劑量穩定相比，不能排除ICS增加劑量的其他臨床重要益處和潛在傷害，因為置信區間較寬，試驗中存在偏倚風險，以及必須做出綜合分析的假設。1998年至2018年期間納入的的研究反映了不斷發展的臨床實踐和研究方法，數據不支持對基線劑量、倍增量、哮喘嚴重程度和時間等效應修正因素進行徹底調查。本系統綜述未納入從務實的、非盲法研究中所獲得的最新證據，這些證據表明，在哮喘控制不佳的患者中，增加較大劑量有益。有必要對盲法試驗和非盲法試驗之間的差異進行系統評價，利用穩健的方法評估偏倚風險，以便為決策者提供最完整的證據觀點。

作者:Kew KM, Flemyng E, Quon BS, Leung C；譯者：袁瑞，武漢大學第二臨床學院；審校：靳英輝，武漢大學中南醫院循證與轉化醫學中心；編輯排版：索于思，北京中醫藥大學循證醫學中心

相關文章鏈接

【Cochrane簡語概要】幫助哮喘患者按處方服藥的數字化技術

【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.