Nebulised hypertonic saline for cystic fibrosis

 

Abstract

Background

Impaired mucociliary clearance characterises lung disease in cystic fibrosis (CF). Hypertonic saline (HS) enhances mucociliary clearance in vitro and may lessen the destructive inflammatory process in the airways.

Objectives

To investigate the effects of nebulised HS in CF compared to placebo or other treatments for mucociliary clearance.

Search methods

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

Most recent search: 31 July 2008.

Selection criteria

Controlled trials assessing HS compared to placebo or other mucolytic therapy, for any duration or dose regimen in people with CF (any age or disease severity).

Data collection and analysis

Two authors independently reviewed all identified trials and data; and assessed trial quality.

Main results

Twelve trials (442 participants, aged 6 to 46 years) were included; five excluded and two await classification.

In two placebo-controlled trials, HS (3% to 7%, 10 ml twice-a-day) significantly increased forced expiratory volume at one second (FEV₁) at four weeks, mean difference (MD) 4.15 (95% CI 1.14 to 7.16); but not significantly after 48 weeks, MD 2.31 (95% CI -2.72 to 7.34). Two trials compared a similar dose of HS to recombinant deoxyribonuclease (RhDNAse). One three-week trial showed a non-significant difference, MD 1.60 (95% CI -7.96 to 11.16). However, in the second trial, after 12 weeks, RhDNAse led to a greater increase in FEV₁ than HS (5 ml twice-daily), in participants with moderate to severe lung disease, MD 8.00 (95% CI 2.00 to 14.00).

One 48-week placebo-controlled trial showed significant improvements in frequency of antibiotic use and quality of life; also that HS did not increase the concentration of Pseudomonas aeruginosa or Staphylococcus aureus.

Authors' conclusions

Treatment with 7% HS for 48 weeks showed a small improvement in FEV₁ at four weeks; however, this was not sustained at 48 weeks (primary outcome measure of the only long-term trial). Unlike RhDNAse, HS can't, in the long term, be said to improve lung function. However, it did improve quality of life and reduce pulmonary exacerbations. Delivered following a bronchodilator, HS appears inexpensive and safe with no increased infection risk.

We believe there is sufficient evidence to recommend using HS in CF; qualifying this we highlight that the only long-term trial failed to demonstrate a significant difference in its primary outcome (lung function) with improvements only in secondary outcomes.

 

Plain language summary

Salt water (3% or more salt) inhaled as a fine mist through a mask or mouthpiece for cystic fibrosis

People with cystic fibrosis produce mucus in their lungs and airways (passages to the lungs) which is hard to clear. This leads to infections and damage to the airways. Chest physiotherapy or drugs (e.g. deoxyribonuclease) or both are used to try and clear this mucus. Nebulised hypertonic saline is water (with a concentration of 3% or more salt) inhaled as a fine mist through a mask or mouthpiece. The review includes twelve trials with a total of 442 people. We found that 10 ml of saline at 3% to 7% concentration, twice-a-day, helped clear mucus without major adverse effects. Treatment after 48 weeks with hypertonic saline at 7% inhaled twice per day reduces episodes of chest infection and is linked to improved lung function, improved quality of life and better attendance at school or work. However, it had a limited effect on improving lung function. At this stage the authors believe there is enough evidence to recommend the use of hypertonic saline in cystic fibrosis. However we would like to point out that the only long term trial did not determine its primary outcome (lung function) and saw improvements only in secondary outcomes.