Nebulized and oral thiol derivatives for pulmonary disease in cystic fibrosis

 

Abstract

Background

Cystic fibrosis is an inherited condition resulting in thickened, sticky respiratory secretions. Respiratory failure, due to recurrent pulmonary infection and inflammation, is the most common cause of mortality. Muco-active therapies (e.g. dornase alfa and nebulized hypertonic saline) may decrease sputum viscosity, increase airway clearance of sputum, reduce infection and inflammation and improve lung function. Thiol derivatives, either oral or nebulized, have shown benefit in other respiratory diseases. Their mode of action is likely to differ according to the route of administration. There are several thiol derivatives, and it is unclear which of these may be beneficial in cystic fibrosis.

Objectives

To evaluate the efficacy and safety of nebulized and oral thiol derivatives in people with cystic fibrosis.

Search methods

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches, hand searches of relevant journals, abstract books and conference proceedings.

Most recent search: 08 October 2010.

Selection criteria

Randomized and quasi-randomized controlled trials comparing nebulized or oral thiol derivatives to placebo or another thiol derivative in people with cystic fibrosis.

Data collection and analysis

The authors independently assessed trials for inclusion, analysed methodological quality and extracted data.

Main results

Searches identified 18 trials; eight (seven older than 10 years) (234 participants) are included. Three trials of nebulized thiol derivatives were identified (one compared 20% n-acetylcysteine to 2% n-acetylcysteine; another compared sodium-2-mercaptoethane sulphonate to 7% hypertonic saline; and another compared glutathione to 4% hypertonic saline). Although generally well-tolerated with no significant adverse effects, there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments.

Five studies of oral thiol derivatives were identified. Three studies compared n-acetylcysteine to placebo; one compared n-acetylcysteine, ambroxol and placebo; and one compared carbocysteine to ambroxol. Oral thiol derivatives were generally well-tolerated with no significant adverse effects, however there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments.

Authors' conclusions

We found no evidence to recommend the use of either nebulized or oral thiol derivatives in people with cystic fibrosis. There are very few good quality trials investigating the effect of these medications in cystic fibrosis, and further research is required to investigate the potential role of these medications in improving the outcomes of people with cystic fibrosis.

 

Plain language summary

Compounds which can break down the structure of mucus for lung disease in cystic fibrosis

Cystic fibrosis is a genetic disorder which mainly affects the lungs. Chest infections recur in people with cystic fibrosis due to a build up of thick sputum (phlegm) in the air passages. Several treatments, including thiol derivatives, aim to loosen this sputum and so improve lung function and reduce the frequency of chest infections. Thiol derivatives may be either nebulized (breathed in) or oral (by mouth). They have been shown to help in other lung conditions, such as chronic obstructive pulmonary disease. This review aims to find out if there is enough evidence to recommend the nebulized or oral thiol derivatives for people with cystic fibrosis. We included eight trials; three assessed the effect of nebulized thiol derivatives. Of the nebulized studies, one compared 20% n-acetylcysteine to 2% n-acetylcysteine; another compared sodium-2-mercaptoethane sulphonate to 7% hypertonic saline; and the other compared glutathione to 4% hypertonic saline. Nebulized thiol derivatives were generally well-tolerated with no major adverse effects. However they showed no significant improvements in any of our outcome measures.

Five included studies assessed the effects of oral thiol derivatives.Three of these studies compared oral n-acetylcysteine to placebo; one compared oral n-acetylcysteine, oral ambroxol and placebo; and one compared oral carbocysteine and oral ambroxol (no placebo). None of the studies showed an overall significant benefit in any of the outcome measures of this review. Oral thiol derivatives were generally well-tolerated with no major adverse effects.

In summary, the studies included in the review did not provide any evidence that nebulized or oral thiol derivatives were either beneficial or harmful to people with cystic fibrosis. Further research investigating the effects of thiol derivatives in people with cystic fibrosis is required before their use can be recommended.

 

摘要

背景

有肺部疾病的囊狀纖維化病人之噴霧型和口服thiol衍生物治療

囊狀纖維化是一種遺傳疾病，會導致濃稠黏液的產生。肺部反覆性感染及發炎導致呼吸衰竭，是最主要的死因。活化黏液治療(如dornase alfa和生理食鹽水噴霧吸入)可以稀釋痰液黏稠度，清除痰液讓呼吸道順暢，減少感染及發炎，改善肺部功能。Thiol衍生物無論是口服或噴霧型治療，在其他呼吸道疾病已有明顯的療效，根據給藥途徑其作用機制是有所不同的。有幾種Thiol衍生物，當中有哪些是對於囊性纖維化病人具療效，到現在還不知道。

目標

評估噴霧thiol衍生物和口服thiol衍生物治療對於囊狀纖維化病人之療效及安全性。

搜尋策略

我們搜尋了Cochrane囊狀纖維化和遺傳性疾病的試驗登錄文獻，其包括全面性的電子資料庫檢索，人工檢索相關期刊、會議手冊。 最後搜索日期：2008年11月。

選擇標準

囊狀纖維化病人以隨機或半隨機對照試驗，接受噴霧型或口服thiol 衍生物治療，與安慰劑或另一種thiol衍生物的比較。

資料收集與分析

作者獨立分析適合納入的臨床試驗，分析研究方法的品質和收集數據。

主要結論

我們搜尋了18個試驗;8個(有7個年齡超過10歲)(包含234位病人)包括在內。當中3個噴霧型thiol derivatives治療試驗,分別比較(1)20%nacetylcysteine和2%nacetylcysteine(2)sodium−2mercaptoethane sulphonate和7%高張鹽水，以及(3)glutathione和4%高張鹽水。另被歸納於5個口服thiol derivatives試驗中，有3個研究比較 (1)口服nacetylcysteine和安慰劑 (2)nacetylcysteine、ambroxol和安慰劑(3)carbocysteine和ambroxol。在這些接受試驗患者中，不管是接受口服或噴霧型Thiol derivatives治療，一般耐受性良好，無重大不良事件，不過目前卻沒有證據能顯示臨床上有顯著的療效。

作者結論

我們並沒有足夠的證據可建議囊狀纖維化病人去使用噴霧型thiol derivatives治療或口服thiol derivatives。由於很少高品質的臨床試驗文獻，研究囊狀纖維化病人使用這些藥物的效果，所以需要進一步研究探討這些藥物的潛在作用，以改善囊狀纖維化病人的預後。

翻譯人

本摘要由臺灣大學附設醫院吳麗卿翻譯。

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

總結

囊狀纖維化是一種遺傳性疾病，主要是影響肺部。由於囊狀纖維化病人的肺部有濃稠痰液堆積，造成反覆感染。有幾種治療方式，包括Thiol derivatives，目的是化痰及改善肺功能，降低反覆肺部感染的次數。Thiol derivatives可以是噴霧治療(呼吸)或口服(經口)。這些治療已被證明可以幫助肺部疾病的病人，例如：慢性阻塞性肺部疾病。這篇回顧的目的是為了找出是否有足夠的證據去建議囊狀纖維化病人，使用噴霧吸入或口服thiol衍生物。 我們收納了8個試驗;有3個是使用噴霧型Thiol derivatives治療，分別比較20% nacetylcysteine和2% nacetylcysteine， sodium−2mercaptoethane sulphonate和7% 高張生理食鹽水，以及glutathione和4%高張生理食鹽水。另被歸納於5個口服thiol derivatives試驗中，有3個研究比較(1)口服nacetylcysteine和安慰劑(2)nacetylcysteine、ambroxol和安慰劑(3)carbocysteine和ambroxol。結果顯示，不管是使用噴霧型Thiol derivatives或口服thiol derivatives治療，雖具有良好的耐受性，無重大不良事件，卻沒有顯著的療效。 總結，這份研究中包括的試驗並未能證明噴霧型thiol derivatives治療或口服thiol derivatives，對於囊性纖維化病人是有幫助還是有害的。那些藥物在被推薦使用前, 則需要進一步研究藥物對病人使用的影響。