TY - JOUR
T1 - A four week trial of hypertonic saline in children with mild cystic fibrosis lung disease
T2 - Effect on mucociliary clearance and clinical outcomes
AU - Donaldson, Scott H.
AU - Danielle Samulski, T.
AU - LaFave, Caroline
AU - Zeman, Kirby
AU - Wu, Jihong
AU - Trimble, Aaron
AU - Ceppe, Agathe
AU - Bennett, William D.
AU - Davis, Stephanie D.
N1 - Publisher Copyright:
© 2020
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - Clinical trials
KW - Clinicaltrials.gov registration number: NCT01031706
KW - Cystic fibrosis
KW - Hypertonic saline
KW - Mucociliary clearance
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U2 - 10.1016/j.jcf.2020.07.009
DO - 10.1016/j.jcf.2020.07.009
M3 - Article
C2 - 32669217
AN - SCOPUS:85087811657
SN - 1569-1993
VL - 19
SP - 942
EP - 948
JO - Journal of Cystic Fibrosis
JF - Journal of Cystic Fibrosis
IS - 6
ER -