Hypertonic saline inhalation using a nebulizer reduced pulmonary exacerbations in patients with cystic fibrosis and decreased their absenteeism from school, work, and their usual activities, researchers found in two separate randomized clinical trials.
The trials provided the first evidence of the long-term efficacy of this safe and relatively inexpensive treatment. The therapy appears to work by restoring the volume of liquid on the airway surfaces, which is depleted because of excessive absorption of salt from the airway lumen. This rehydration seems to produce a sustained acceleration of mucus clearance, both groups of investigators theorized.
In the first study, 164 adults and children with stable cystic fibrosis (CF) were randomly assigned to inhale 4 mL of either hypertonic (7%) saline plus a taste-masking agent or a control solution (isotonic saline) plus a taste-masking agent via nebulizer twice a day for 48 weeks. A bronchodilator was administered before each treatment to prevent or minimize narrowing of CF patients' hyperresponsive airways during nebulizer therapy, reported Dr. Mark R. Elkins, of Royal Prince Alfred Hospital, Sydney, Australia, and the University of Sydney, and his associates.
The treatment had only a moderate effect on lung function as measured by forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1), and no apparent effect on the typical decline in lung function over the course of the year-long study. However, it had “dramatic” effects on several clinical factors, they noted (N. Engl. J. Med. 2006;354:229–40).
The mean number of symptom exacerbations was 1.32 per person in the treatment group, compared with 2.74 per control subject. The mean duration of exacerbations was 22 days in the treatment group, compared with 69 days in the control group. And the length of time spent free of exacerbations, expressed as “48-week exacerbation-free survival rate,” was 41% in the treatment group, compared with 16% in the controls. All of these differences were highly statistically significant. Similarly, antibiotic use during exacerbations was much lower for the active treatment group.
Patients in the active treatment group reported a mean of 7 days (range, 0–21) when they could not participate in school, work, or usual activities, compared with a mean of 24 days (range, 12–48) for the controls. The treatment group also scored significantly higher on quality of life measures.
The treatment did not alter the levels of Pseudomonas aeruginosa or Staphylococcus aureus in the sputum, nor did it affect the rate of acquisition of these organisms, Burkholderia cepacia, Stenotrophomonas maltophilia, Candida albicans, aspergillus species, or Hemophilus influenzae.
In the other clinical trial, investigators reasoned that slowing the absorption of nebulized hypertonic saline by premedicating CF patients with amiloride, a sodium channel blocker, would enhance patient response by extending the duration of airway rehydration. Twenty-four CF patients aged 14 years and older were randomized to pretreatment with either amiloride or a taste-masked placebo, followed by hypertonic saline via nebulizer four times daily for 14 days. All the subjects received a bronchodilator via inhaler 30–60 minutes before the nebulizer treatment.
The study confirmed that hypertonic saline improved CF symptoms, lung function, and quality of life, reported Dr. Scott H. Donaldson and Dr. William D. Bennett of the University of North Carolina at Chapel Hill Cystic Fibrosis Research and Treatment Center and their associates. Perhaps as important, the treatment hastened the rate of mucus clearance from the lungs and “produced a larger and more sustained increase in the volume of airway surface liquid” in CF patients than in healthy controls (N. Engl. J. Med. 2006;354:241–50).
The findings suggest inhaled hypertonic saline may be an option for CF patients, Dr. Felix Ratjen of the University of Toronto said in an editorial comment accompanying the publication of both reports.
It was previously shown that hypertonic saline inhalation increased mucociliary transport in CF patients—but the effect was presumed to be short-lived because sodium deposited on epithelial surfaces would be taken up rapidly. The new research shows that the treatment “not only had a prolonged effect on the amount of airway surface liquid in epithelial cells … but also resulted in a sustained improvement of mucociliary transport,” Dr. Ratjen said (N. Engl. J. Med. 2006;354:291–3).
Dr. Ratjen noted that the treatment has an unpleasant taste, induces coughing, and would add at least 30 minutes to patients' daily treatment schedules.