Inhaled hypertonic saline produces small increases in lung function in patients with cystic fibrosis

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• Elkins MR, Robinson M, Rose BR, Harbour C, Moriarty CP, Marks GB, et al. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med 2006;354:229-40
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Elkins MR, Robinson M, Rose BR, Harbour C, Moriarty CP, Marks GB, et al. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med 2006;354:229-40 

Question Does long-term use of inhaled hypertonic saline solution improve pulmonary function in people with cystic fibrosis?

Design Double-blind, randomized, parallel-group trial.

Setting 16 adult or pediatric hospitals in Australia.

Participants 164 patients with stable cystic fibrosis (CF), at least 6 years of age (mean age 18.5 years).

Intervention Patients were randomly assigned to inhale 4 mL of either 7% hypertonic saline solution (HS) or 0.9% (control) saline solution twice daily for 48 weeks, with quinine sulfate (0.25 mg/mL) added to each solution to mask the taste. A bronchodilator was given before each dose, and other standard therapies were continued during the trial.

Outcomes The linear rate of change in pulmonary function, reflected by the forced vital capacity (FVC), forced expiratory volume in 1 second (FEV₁), and forced expiratory flow at 25% to 75% of FVC, during the 48 weeks of treatment.

Main Results The rate of change in pulmonary function did not differ significantly between groups (P = .79). However, the absolute difference in pulmonary function between groups was significant (P = .03) when averaged across all post-randomization visits in the 48-week treatment period. As compared with the control group, the HS group had significantly higher FVC (by 82 mL; 95% confidence interval, 12 to 153) and FEV₁ (by 68 mL; 95% confidence interval, 3 to 132) values but similar values of forced expiratory flow at 25% to 75% of FVC. The HS group also had significantly fewer pulmonary exacerbations (relative reduction, 56%; P = .02) and a significantly higher percentage of patients without exacerbations (76% vs 62%, P = .03, number needed to treat = 8). HS was not associated with worsening bacterial infection or inflammation.

Conclusions Hypertonic saline solution preceded by a bronchodilator is an inexpensive, safe, and effective additional therapy for patients with CF.

Commentary Previous short-term studies have demonstrated that inhalation of HS increases mucociliary transport; whether this translated into clinically relevant benefits for patients with CF was largely unclear. HS reduced the frequency of pulmonary exacerbations; an important outcome parameter in CF, in this well-designed, multicenter trial. However, inhaled antibiotic therapy in the study population differed from that used in many CF centers. Although more than 75% of patients were infected with Pseudomonas aeruginosa, less than 15% of the population received inhaled tobramycin, which also has a documented effect on pulmonary exacerbations. Improvements in FEV₁, the primary outcome parameter, were rather small, with confidence intervals of the 2 groups overlapping at all time points. No decline in pulmonary function was observed in the control group, raising the question whether the combination of isotonic saline solution with albuterol can be considered a placebo. Most of the patients included in the trial were adults, and it needs to be seen whether long-term HS inhalation will be acceptable for children. The additional treatment burden, the unpleasant taste of HS, as well as the fact that it acts as an irritant inducing cough are relevant factors in this context.