Chest. 2005 Jan;127(1):308-17.

Randomized, double-blind, placebo-controlled study.

Nineteen participants were recruited. Stable clinical status with mild pulmonary disease. Mean age 13.1 years (range 6 - 19 years). Participants were paired by age and sex, and then each member of the pair was randomly assigned to the treatment or placebo groups. One participant in the placebo group dropped out 'just before the trial began', and was not included in the analysis.

Nebulized buffered reduced GSH versus nebulized placebo. GSH was buffered with sodium bicarbonate and dosed at 66mg/kg body weight. Placebo was composed of sodium chloride dosed at 15mg/kg body weight, and quinine at 25-30 μg/kg body weight. Participants

Primary outcome measures: FEV1(% predicted), FVC (% predicted), FEF25-75 (% predicted), PEF. General wellness (1 = poor, 2 = fair, 3 = good, 4 = excellent) Usual stamina (1 = poor, 2 = fair, 3 = good, 4 = excellent) Improvement (1 = significantly worse, 2 = a bit worse, 3 = about the same, 4 = a bit better, 5 = significantly better). The baseline measure for each of the subjective measures was taken as the 'average of the first 5 days of the trial', and the 'end of trial measure' was taken as the 'average of last 5 days of the trial'. Adverse events. Sputum viscosity (1 = very thin, 2 = slightly sticky, 3 = very sticky) Cough frequency (1 = no cough, 2 = infrequent, 3 = several times per day, 4 = every hour) Secondary outcome measures: FEV1, FVC and FEF25-75 were measured once prior to starting the intervention period, and once after completing the intervention period. PEF was measured by the participant twice daily throughout the study. Objective - BMI, 6-min walk distance (m). These objective measures were recorded once prior to starting the intervention and once after completing the intervention. Sputum color (scale ranging from 1 = clear to 6 = blood streaked) Sputum amount (1=scant, 2 = <1 teaspoon), 3 = >1 teaspoon) Subjective:

Mean change for peak flow was -6.5 L/min for the placebo group and +33.7 L/min for the GSH group (p = 0.04), and self-reported average improvement on a scale from 1 to 5 (1 being much worse and 5 being much better) was 2.8 for placebo and 4.7 for GSH (p = 0.004). Of the 13 primary and secondary outcomes examined, 11 outcomes favored the treatment group over the placebo group (p = 0.002), indicating a general tendency of improvement in the GSH group. No adverse events in the treatment group were noted.

This pilot study indicates the promise of nebulized buffered GSH to ameliorate CF disease, and longer, larger, and improved studies of inhaled GSH are warranted.