A four week trial of hypertonic saline in children with mild cystic fibrosis lung disease: Effect on mucociliary clearance and clinical outcomes.
BACKGROUND
Hypertonic saline (HS) is commonly prescribed for children with cystic fibrosis (CF) despite the absence of strong data indicating clinical efficacy in a population with mild lung disease. We hypothesized that HS treatment would result in a sustained improvement in mucociliary clearance (MCC) in children with CF who had minimal lung disease, thus providing evidence for a biologically relevant effect that also may be associated with clinical improvements.


METHODS
We performed a randomized, placebo controlled, double blind study of 6% versus 0.12% sodium chloride, delivered three-times daily with an eFlow nebulizer for 4 weeks. MCC was measured using gamma scintigraphy at baseline, 2-hours after the first study treatment, and ~12-hours after the final dose (at day 28). Spirometry, respiratory symptoms (CFQ-R), and safety were also assessed.


RESULTS
Study treatments were generally well tolerated and safe. HS (6% sodium chloride) resulted in a significant, sustained improvement from baseline in whole lung clearance after 4 weeks of therapy (p = 0.014), despite absence of a prolonged single-dose effect after the initial dose. This sustained change (12 hrs after prior dose) was significantly greater when compared to placebo (0.12% sodium chloride) treatment (p = 0.016). Improvements in spirometry with HS did not reach statistical significance but correlated with MCC changes.


CONCLUSIONS
The observed sustained improvement in MCC with HS suggests that this treatment may yield health benefits, even in relatively mildly affected children with CF. Highlighting this physiologic finding is important due to the lack of meaningful, validated endpoints in this population.
['Donaldson|Scott H|SH|', 'Danielle Samulski|T|T|', 'LaFave|Caroline|C|', 'Zeman|Kirby|K|', 'Wu|Jihong|J|', 'Trimble|Aaron|A|', 'Ceppe|Agathe|A|', 'Bennett|William D|WD|', 'Davis|Stephanie D|SD|']
D000280:Administration, Inhalation D002648:Child D003550:Cystic Fibrosis D004311:Double-Blind Method D005260:Female D006801:Humans D008297:Male D009079:Mucociliary Clearance D009330:Nebulizers and Vaporizers D012462:Saline Solution, Hypertonic
Hypertonic saline Cystic fibrosis Mucociliary clearance Clinical trials Clinicaltrials.gov registration number: NCT01031706