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 use of nebulized or oral thiol derivatives for people with cystic fibrosis. We included nine trials; three assessed the effect of nebulized thiol derivatives. Of the nebulized trials, 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.

Six included trials assessed the effects of oral thiol derivatives.Three of these trials 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 trials 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 trials 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.

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.

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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 strategy: 

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: 13 June 2013.

We also conducted a PubMed search on 26 February 2013 for relevant published articles.

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 risk of bias and extracted data.

Main results: 

Searches identified 23 trials; nine trials (255 participants) are included, of these seven trials are more than 10 years old. 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.

Six trials of oral thiol derivatives were identified. Three trials compared N-acetylcysteine to placebo; one compared N-acetylcysteine, ambroxol and placebo; one compared carbocysteine to ambroxol; and one compared low and high-dose N-acetylcysteine. 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.

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