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Randomized Controlled Trial
. 2020 Nov;19(6):942-948.
doi: 10.1016/j.jcf.2020.07.009. Epub 2020 Jul 12.

A four week trial of hypertonic saline in children with mild cystic fibrosis lung disease: Effect on mucociliary clearance and clinical outcomes

Scott H Donaldson  1 , T Danielle Samulski  2 , Caroline LaFave  3 , Kirby Zeman  4 , Jihong Wu  4 , Aaron Trimble  2 , Agathe Ceppe  2 , William D Bennett  5 , Stephanie D Davis  6
Affiliations
Randomized Controlled Trial

A four week trial of hypertonic saline in children with mild cystic fibrosis lung disease: Effect on mucociliary clearance and clinical outcomes

Scott H Donaldson et al. J Cyst Fibros. 2020 Nov.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT01031706.

Keywords: Clinical trials; Clinicaltrials.gov registration number: NCT01031706; Cystic fibrosis; Hypertonic saline; Mucociliary clearance.

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Conflict of interest statement

Declartion of Competing Interest The authors have no relevant conflicts of interest to disclose.

Figures

Figure 1:
Figure 1:
Study flow diagram
Figure 2 –
Figure 2 –
Spaghetti plots (left) showing individual AveClr90 values at baseline and after 4 weeks of treatment by treatment group. In right panel, scatter plots with mean and 95% CI demonstrate the mean change in AveClr90 between baseline and after 4 weeks of treatment in placebo and HS groups. Unpaired Student’s t-test revealed significant treatment effect (p = 0.016).
Figure 3:
Figure 3:
Correlation between change in MCC (AveClr90) and FEV1 % predicted after 4 weeks of HS treatement. Pearson R2 = 0.67; p = 0.002
See this image and copyright information in PMC

References

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