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.

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.

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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 (along with defective chloride secretion) 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 strategy: 

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: 19 December 2013.

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.