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


Journal

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
ISSN: 1873-5010
Titre abrégé: J Cyst Fibros
Pays: Netherlands
ID NLM: 101128966

Informations de publication

Date de publication:
11 2020
Historique:
received: 22 05 2020
revised: 08 07 2020
accepted: 09 07 2020
pubmed: 17 7 2020
medline: 21 10 2021
entrez: 17 7 2020
Statut: ppublish

Résumé

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. 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. 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 32669217
pii: S1569-1993(20)30801-8
doi: 10.1016/j.jcf.2020.07.009
pmc: PMC7736104
mid: NIHMS1613327
pii:
doi:

Substances chimiques

Saline Solution, Hypertonic 0

Banques de données

ClinicalTrials.gov
['NCT01031706']

Types de publication

Journal Article Randomized Controlled Trial Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

942-948

Subventions

Organisme : NIDDK NIH HHS
ID : P30 DK065988
Pays : United States
Organisme : NHLBI NIH HHS
ID : P50 HL084934
Pays : United States

Informations de copyright

Copyright © 2020. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

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

Auteurs

Scott H Donaldson (SH)

University of North Carolina School of Medicine at Chapel Hill, NC, Pulmonary and Critical Care Medicine, Chapel Hill, USA. Electronic address: scott_donaldson@med.unc.edu.

T Danielle Samulski (T)

University of North Carolina School of Medicine at Chapel Hill, NC, Pulmonary and Critical Care Medicine, Chapel Hill, USA.

Caroline LaFave (C)

University of North Carolina School of Medicine at Chapel Hill, NC, Pulmonary and Critical Care Medicine, Chapel Hill, USA; Department of Pediatrics, Chapel Hill, USA.

Kirby Zeman (K)

Center for Environmental Medicine, Asthma and Lung Biology, Chapel Hill, USA.

Jihong Wu (J)

Center for Environmental Medicine, Asthma and Lung Biology, Chapel Hill, USA.

Aaron Trimble (A)

University of North Carolina School of Medicine at Chapel Hill, NC, Pulmonary and Critical Care Medicine, Chapel Hill, USA.

Agathe Ceppe (A)

University of North Carolina School of Medicine at Chapel Hill, NC, Pulmonary and Critical Care Medicine, Chapel Hill, USA.

William D Bennett (WD)

University of North Carolina School of Medicine at Chapel Hill, NC, Pulmonary and Critical Care Medicine, Chapel Hill, USA; Center for Environmental Medicine, Asthma and Lung Biology, Chapel Hill, USA.

Stephanie D Davis (SD)

Department of Pediatrics, Chapel Hill, USA.

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Classifications MeSH