Study 2
Mark R. Elkins, M.H.Sc., Michael Robinson, Ph.D., Barbara R. Rose, Ph.D., Colin Harbour, Ph.D., Carmel P. Moriarty, R.N., Guy B. Marks, Ph.D., Elena G. Belousova, M.Appl.Sc., Wei Xuan, Ph.D., Peter T.P. Bye, Ph.D.
National Hypertonic Saline in Cystic Fibrosis (NHSCF) Study Group
The New England Journal of Medicine, 2006;354:229-40
A Controlled Trial of Long-Term Inhaled Hypertonic Saline in Patients with Cystic Fibrosis
Background
Inhaled hypertonic saline acutely increases mucociliary clearance and, in short-term trials, improves lung function in people with cystic fibrosis. We tested the safety and efficacy of inhaled hypertonic saline in a long-term trial.
Methods
In this double-blind, parallel-group trial, 164 patients with stable cystic fibrosis who were at least six years old were randomly assigned to inhale 4 ml of either 7 percent hypertonic saline or 0.9 percent (control) saline twice daily for 48 weeks, with quinine sulfate (0.25 mg per milliliter) added to each solution to mask the taste. A bronchodilator was given before each dose, and other standard therapies were continued during the trial.
Results
The primary outcome measure, the rate of change (slope) in lung function (ref lected by the forced vital capacity [FVC], forced expiratory volume in one second [FEV1], and forced expiratory flow at 25 to 75 percent of FVC [FEF25 –75]) during the 48 weeks of treatment, did not differ significantly between groups (P = 0.79). However, the absolute difference in lung function between groups was significant (P = 0.03) when averaged across all post-randomization visits in the 48-week treatment period. As compared with the control group, the hypertonic-saline group had significantly higher FVC (by 82 ml; 95 percent confidence interval, 12 to 153) and FEV1 (by 68 ml; 95 percent confidence interval, 3 to 132) values, but similar FEF25–75 values. The hypertonic-saline group also had significantly fewer pulmonary exacerbations (relative reduction, 56 percent; P = 0.02) and a significantly higher percentage of patients without exacerbations (76 percent, as compared with 62 percent in the control group; P = 0.03). Hypertonic saline was not associated with worsening bacterial infection or inflammation.
Conclusions
Hypertonic saline preceded by a bronchodilator is an inexpensive, safe, and effective additional therapy for patients with cystic fibrosis.