Effectiveness and safety of hypertonic saline inhalation combined with exercise training in patients with chronic obstructive pulmonary disease: a randomized trial.

BACKGROUND Inhaled hypertonic saline is used for bronchial challenge and sputum induction in patients with chronic obstructive pulmonary disease (COPD). We studied the effects of saline aerosol inhalation before each exercise session in an 8-week pulmonary rehabilitation program. METHODS This was a double-blind randomized parallel controlled trial, conducted at an out-patient clinic. Sixty-eight subjects with COPD (mean age 67 +/- 6.5 y, percent of predicted FEV(1) 47 +/- 21) were randomized to inhale either 3% hypertonic saline (34 subjects) or normal saline (34 subjects) before each exercise session in an 8-week exercise program that had 3 sessions per week. We measured 6-min walk distance, dyspnea, and quality of life (with the Medical Outcomes Study 36-item short-form health survey). RESULTS After the 8-week exercise program, both groups' mean 6-min walk distance had significantly increased: from 195 +/- 92 m to 251 +/- 97 m (P < .001) in the hypertonic-saline group, and from 237 +/- 93 m to 441 +/- 121 m in the normal-saline group (P < .001). The normal-saline group had greater improvement than the hypertonic-saline group (P < .001). Dyspnea score improved from 3.1 +/- 0.9 to 2.3 +/- 0.8 (P < .01) in the hypertonic-saline group, and from 3.5 +/- 0.2 to 2.3 +/- 1.0 (P < .01) in the normal-saline group. Quality of life also significantly improved, except for the physical-functioning and social aspect domains in the hypertonic-saline group. Adverse effects (cough or bronchospasm) occurred in 4 patients (12%) in the hypertonic-saline group. CONCLUSIONS The improvement in 6-min walk distance was greater with normal saline than with hypertonic saline. Hypertonic saline was associated with adverse effects. It is unclear whether the only predictor of improved functional exercise capacity was exercise training. (ClinicalTrials.gov number, NCT00639236.).