Acetylcysteine and carbocysteine for acute upper and lower respiratory tract infections in paediatric patients without chronic broncho-pulmonary disease

 

Abstract

Background

Acetylcysteine and carbocysteine are the most commonly prescribed mucolytic drugs in many European countries. To our knowledge, no systematic review has been published on their efficacy and safety for acute upper and lower respiratory tract infections (ARTIs) in children without chronic broncho-pulmonary disease.

Objectives

The objective was to assess the efficacy and safety and to establish a benefit-risk ratio of acetylcysteine and carbocysteine as symptomatic treatments for ARTIs in children without chronic broncho-pulmonary disease.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, issue 4) which contains the Acute Respiratory Infections (ARI) Group's Specialized Register, MEDLINE (1966 to 2008), EMBASE (1980 to 2008); Micromedex (2008), Pascal (1987 to 2004), and Science Citation Index (1974 to 2008).

Selection criteria

To study efficacy, we used randomised controlled trials (RCTs) comparing the use of acetylcysteine or carbocysteine versus placebo either alone or as an add-on therapy.

To study safety, we also used trials comparing the use of acetylcysteine or carbocysteine versus active treatment or no treatment and case reports.

Data collection and analysis

At least two review authors extracted data and assessed trial quality. We performed a subgroup analysis of children younger than two years of age.

Main results

Six trials involving 497 participants were included to study efficacy. They showed some benefit from mucolytic agents, although differences were of little clinical relevance. No conclusion was drawn about the subgroup of infants younger than two years because the data were unavailable. Thirty-four studies including the previous six trials involving 2064 children were eligible to study safety. Overall safety was good but very few data were available to evaluate safety in infants younger than two years. However, 48 cases of paradoxically increased bronchorrhoea observed in infants were reported to the French pharmacovigilance system.

Authors' conclusions

The results of this review have to be interpreted with caution because it was based on a limited number of participants included in studies whose methodological quality is questionable. Acetylcysteine and carbocysteine seem to have a limited efficacy and appear to be safe in children older than two years. These results should take into consideration the fact that acetylcysteine and carbocysteine are prescribed for self-limiting diseases (for example, acute cough, bronchitis). Regarding children younger than two years, given concerns about safety, these drugs should only be used for ARTIs in the context of an RCT.

 

Plain language summary

Mucolytic drugs to treat acute upper and lower respiratory tract infections in children without chronic broncho-pulmonary disease

Acetylcysteine and carbocysteine are the most commonly prescribed mucolytic drugs. This systematic review aimed at assessing their efficacy and safety for treating acute upper and lower respiratory tract infections (ARTIs) in children without chronic broncho-pulmonary disease. A subgroup analysis among patients younger than two years was performed.

Forty-nine studies met the inclusion criteria. Six trials involving 497 participants were included to study efficacy and compared acetylcysteine or carbocysteine to placebo. Thirty-four studies including the previous six were eligible to study safety and involved 2064 paediatric patients.

The results of this review suggest actual but limited efficacy of acetylcysteine and carbocysteine and a good overall safety among children older than two years of age. However, the number of patients included was limited and the methodological quality was questionable. These results should also take into consideration the fact that acetylcysteine and carbocysteine are prescribed for self-limiting diseases (e.g., acute cough, bronchitis). Regarding children younger than two years, given concerns about safety, these drugs should only be used for ARTIs in the context of a randomised controlled trial.

 

摘要

背景

乙醯半胱氨酸(acetylcysteine)和羧甲基半胱氨酸(carbocysteine)用於治療無慢性支氣管肺疾病兒童的急性上，下呼吸道感染

乙醯半胱氨酸和羧甲基半胱氨酸是許多歐洲國家最常使用的化痰藥。但是據我們所知，目前並沒有用於無慢性支氣管肺疾病兒童的急性上下呼吸道感染時療效和安全性的系統性的回顧。

目標

本文的目的是評估有效性和安全性，並建立乙醯半胱氨酸和羧甲基半胱氨酸用於無慢性支氣管肺疾病兒童之急性上下呼吸道感染時症狀治療的利益風險比。

搜尋策略

我們檢索了考科藍對照試驗註冊中心 (CENTRAL)(考科藍圖書館 2007年第4期)，其中包含急性呼吸道感染群的專科註冊，MEDLINE醫學文獻資料庫(1966年至2008年)，EMBASE醫學文摘庫(1980年至2008年), Micromedex(2008年)，Pascal(1987年至2004年)，和科學引文索引(1974年至2008年)。

選擇標準

針對療效的研究，我們使用隨機對照試驗比較使用乙醯半胱氨酸或羧甲基半胱氨酸加上安慰劑或單獨使用安慰劑治療;針對安全性的研究，我們利用試驗比較乙?半胱氨酸或羧甲基半胱氨酸與積極治療或沒有治療和個案報告。

資料收集與分析

至少有兩位作者回顧並提取數據和評估試驗的品質。我們進行了一組年齡小於2歲兒童的子群體分析。

主要結論

共有6個試驗，497人參加療效的研究。化痰藥劑雖有一些助益但是差異並不足以達到臨床意義。小於2歲嬰兒的子群體分析?因為數據無法取得而沒有結論。包含上述6個的34個試驗，共2064名兒童參與安全性研究，整體而言安全性是好的，但2歲以下嬰兒的資料極少。法國藥物警戒系統曾接獲48例報告陳述嬰兒使用化痰藥反而會造成大量支氣管黏性分泌物(bronchorrhoea)。

作者結論

這份文獻回顧審查的結果必須謹慎解讀，因為參加的人數有限而研究方法令人存疑。乙醯半胱氨酸或羧甲基半胱氨酸的療效有限，而只有在2歲以上的兒童才安全。這些結果讓我們思考乙醯半胱氨酸以及羧甲基半胱氨酸是否是用在自限性疾病才有效(例如，急性咳嗽，支氣管炎)。至於兩歲以下的嬰兒，因為考慮到安全性，這些藥物只能用於隨機對照試驗中的急性呼吸道感染症。

翻譯人

本摘要由臺灣大學附設醫院蕭慈慧翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

化痰藥用於治療無慢性支氣管肺疾病兒童的急性上下呼吸道感染: 乙醯半胱氨酸和羧甲基半胱氨酸是最常使用的化痰藥物。本系統性回顧的目的是在評估它們使用於無慢性支氣管肺疾病兒童的急性上下呼吸道感染時的療效和安全性，同時也做了小於2歲嬰兒的子群體分析。有49個試驗符合收案標準，療效的試驗比較乙醯半胱氨酸或羧甲基半胱氨酸和安慰劑的作用包含其中6個臨床試驗，497名參加者。安全性的試驗包含前面6個試驗在內的34個試驗，2064名兒童。文獻審查結果表明實際效果有限，而用於大於2歲的兒童整體來說還算安全;收案的病人人數有限而研究方法令人質疑。這些結果讓我們思考乙醯半胱氨酸以及羧甲基半胱氨酸是否用在自限性疾病才有效(例如，急性咳嗽，支氣管炎)。至於兩歲以下的嬰兒，因為考慮到安全性，這些藥物只能用於隨機對照試驗中的急性呼吸道感染症。