Sodium channel blockers for cystic fibrosis

 

Abstract

Background

People with cystic fibrosis (CF) have increased transport of the salt, sodium across their airway lining. Over-absorption of sodium results in the dehydration of the liquid that lines the airway surface and is a primary defect in people with CF.

Objectives

To determine whether the topical administration of drugs that block sodium transport improves the respiratory condition of people with CF.

Search methods

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. We contacted principal investigators known to work in the field, previous authors and pharmaceutical companies who manufacture ion transport agents for unpublished or follow-up data.

Most recent search of the Group's register: 26th August 2009.

Selection criteria

Published or unpublished randomised controlled trials (RCTs) or quasi-randomised controlled trials of sodium channel blockers compared to placebo or another sodium channel blocker or the same sodium channel blocker at a different dosing regimen.

Data collection and analysis

Two authors independently extracted data. Meta-analysis was limited due to differing study designs.

Main results

Five RCTs, with a total of 226 participants, examining the topical administration of the short-acting sodium channel blocker, amiloride, compared to placebo were identified as eligible for inclusion in the review. In three studies over six months, there was a significant difference found in the difference in relative change in FVC in favour of placebo (weighted mean difference 1.51% (95% confidence interval -2.77 to -0.25), although heterogeneity was evident. A two-week study demonstrated that hypertonic saline with amiloride pre-treatment did not result in a significant improvement in respiratory function or mucus clearance, in contrast to pre-treatment with placebo. There were no significant differences identified in other clinically relevant outcomes.

Authors' conclusions

We found no evidence that the topical administration of a short-acting sodium channel blocker improves respiratory condition in people with cystic fibrosis and some limited evidence of deterioration in lung function.

 

Plain language summary

Drugs to control the movement of salt in the lungs of people with cystic fibrosis

Usually salt is absorbed from liquid on the surface of the lungs to stop fluid building up there. In cystic fibrosis too much salt is absorbed and there is little liquid left on the airway surfaces. As a result people with cystic fibrosis have problems clearing their lungs of sticky secretions. Thus the lungs are left open to infection. Drugs applied directly to the lungs may prevent too much salt being absorbed. This may lead to better clearance of mucus and less lung infection and damage. The review includes five studies with a total of 226 participants. All studies looked at short-acting drugs applied directly to the lungs compared to placebo. When the results from three studies over six months were combined, the placebo group showed a slower rate of decline in forced vital capacity than the treatment group. However, each of these differed in their results. A further study showed that people receiving a sodium channel blocker before receiving hypertonic saline did not achieve better lung function or mucus clearance than those receiving placebo before hypertonic saline. We found no evidence that short-acting sodium channel blockers administered directly to the lungs improve respiratory status in people with cystic fibrosis. There was even some limited evidence of a decline in lung function. Trials of long-acting sodium channel blockers are ongoing.

 

摘要

背景

肺部囊狀纖維化(cystic fibrosis, CF)與鈉離子通道阻斷劑(Sodium channel blockers)

CF病人的氣道內襯會增加對鹽分的吸收。過度吸收鈉離子造成氣道內襯的液體層有脫水的現象，這也是CF最主要的問題。

目標

評估使用局部藥物阻斷鈉離子運輸對於CF病人的呼吸系統是否有所改善。

搜尋策略

我們搜尋了Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register 資料庫；其中包含了電子資料庫的搜尋、相關期刊的手動搜尋，以及相關學術會議摘要。我們向在這領域工作的主要工作者，先前的作者，以及藥商公司，聯繫已取得沒有發表的以及後續追蹤的資料。最近的搜尋日期: 2009年8月26日

選擇標準

我們收納發表或是尚未發表的論文鈉離子阻斷劑比上安慰劑或是不同劑量的鈉離子阻斷劑之隨機對照試驗(randomised controlled trials；RCTs)或是半隨機對照試驗(quasirandomised controlled trials)。

資料收集與分析

本文2位作者各自獨立作業獲得資料。而因為研究方法的不同造成進行統合分析的困難

主要結論

我們收納了總共包含226位病人的5份隨機對照研究。藥物使用包含短效型鈉離子阻斷劑，amiloride以及安慰劑並合於本文獻回顧的收納標準因此予以納入。儘管研究具有異質性，其中3個隨機對照研究中，包含完整6個月的藥物使用，計算呼吸功能(FVC)發現安慰劑組FVC有較大的變化(利用普通反轉方插法[generic inverse variance, CIV]分析FVC加權平均差; 1.51% (95% confidence interval −2.77 to −0.25)。一個為期2週的研究顯示，相對於以安慰劑治療前，高滲鹽水與阿米洛利治療並沒有顯著改善呼吸功能或清除粘液。而在其它臨床相關的結果上並沒有顯著的不同。

作者結論

根據這些文獻的現有的證據，我們無法證明局部鈉離子阻斷劑對囊狀纖維化病人的呼吸系統是有助益的，一些有限的證據顯示反而會造成肺功能的惡化。

翻譯人

本摘要由臺灣大學附設醫院李咏馨翻譯。

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

總結

利用藥物控制CF病患肺部鹽分：通常鹽份吸收肺部表面液體並且阻止了液體聚集。在CF病人中，吸收了太多鹽份，造成呼吸道表面僅有一點液體。因此，CF病人在清除其肺部黏稠分泌物方面會有問題，因此，肺部容易造成感染。利用藥品應用於肺部可能可以減少鹽份吸收。這可能可以清除粘液並且減少肺部感染和傷害。文獻回顧範圍包括5項研究，總計為226位參與者。所有研究著重短效藥物與安慰劑直接應用於肺部之比較。當合併了3個超過6個月的研究結果，顯示安慰劑組相較於治療組，其用力肺活量(forced vital capacity �FVC)下降比率較慢。然而，各研究結果不盡相同。進一步的研究顯示，相較於安慰劑，病人在接受高張生理食鹽水之前先使用鈉離子阻斷劑並無法助於清除黏液。我們並沒有找到短效鈉離子阻斷劑對於改善呼吸道狀況的證據。對於肺功能降低的證據仍然有限，而長效的鈉離子阻斷劑試驗正在進行中。