A Controlled Trial of Long-Term Inhaled Hypertonic Saline in Patients With Cystic Fibrosis

N Engl J Med. 2006 Jan 19;354(3):229-40. doi: 10.1056/NEJMoa043900.

Abstract

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 (reflected 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. (ClinicalTrials.gov number, NCT00271310.)

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absenteeism
  • Administration, Inhalation
  • Adolescent
  • Adult
  • Albuterol / therapeutic use
  • Anti-Bacterial Agents / therapeutic use
  • Bronchodilator Agents / therapeutic use
  • Child
  • Cough / etiology
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / physiopathology
  • Disease-Free Survival
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Isotonic Solutions
  • Male
  • Maximal Midexpiratory Flow Rate / drug effects
  • Premedication
  • Saline Solution, Hypertonic / administration & dosage*
  • Saline Solution, Hypertonic / adverse effects
  • Sodium Chloride / administration & dosage
  • Sodium Chloride / adverse effects
  • Treatment Outcome
  • Vital Capacity / drug effects

Substances

  • Anti-Bacterial Agents
  • Bronchodilator Agents
  • Isotonic Solutions
  • Saline Solution, Hypertonic
  • Sodium Chloride
  • Albuterol

Associated data

  • ClinicalTrials.gov/NCT00271310