Hypertonic Saline Minimizes Structural Lung Damage in Children Aged 3-6 Years with Cystic Fibrosis

19 May, 22

Introduction

In the Saline Hypertonic in Preschoolers (SHIP) study, inhaled 7% hypertonic saline improved the lung clearance index in children aged 3–6 years with cystic fibrosis, but it remained unclear whether improvement is also seen in structural lung disease.

Aim

We aimed to assess the effect of inhaled hypertonic saline on chest CT imaging in children aged 3–6 years with cystic fibrosis in this SHIP-CT study.

Method

Study Design

Multicenter, randomized, double-blind, controlled, parallel-group trial.

Patient Profile

Children aged between 3 to 6 years diagnosed with cystic fibrosis
Cooperated with chest CT imaging
Comply with daily nebulizer treatment

Treatment Strategy

The eligible children were recruited from 23 cystic fibrosis centres in Spain, Denmark, the Netherlands, Italy, France, Belgium, the USA, Canada, and Australia.
Cohort was randomized 1:1 to receive inhaled 2 puffs of 100 ?g salbutamol followed by 4mL of either 7% hypertonic saline or 0·9% isotonic saline twice per day for 48 weeks.
Randomization was stratified by age in North America and Australia, and by age and country in Europe.
The children were followed up for 48 weeks with study visits at enrollment and at weeks 12, 24, 36 and 48.
Chest CT scans were obtained at baseline and at 48 weeks and scored using the Perth-Rotterdam Annotated Grid Morphometric Analysis for Cystic Fibrosis (PRAGMA-CF) method.
Analysis was by intention-to-treat.

End Points

% Of total lung volume occupied by abnormal airways (PRAGMA-CF %Disease) measured by chest CT at 48 weeks.

Adverse events (AEs).

Results

Out of 134 children who were screened initially, 116 were included in the final analysis.
The children were randomized to hypertonic saline (n=56) or isotonic saline (n=60).
There were 12 drop-outs (7 in the hypertonic saline group and 5 in the isotonic saline group).
Median age at screening was 55 months.
% Disease values at 48 weeks per treatment group were adjusted for mean baseline % disease values and baseline age.
Mean PRAGMA-CF %Disease at 48 weeks in the hypertonic saline group was 0·88% vs 1·55% in the isotonic saline group (mean difference 0·67%; p=0·0092).
The number of AEs reported in the hypertonic saline group was 563 and 622 in the isotonic saline group.
Most AEs in both groups were rated as mild, and the most common AEs were cough, nasal congestion, fever and rhinorrhea.

Conclusions

Inhaled hypertonic saline for 48 weeks improved the trajectories of structural airway changes as measured by chest CT scans as compared to isotonic saline in children aged 3–6 years with cystic fibrosis.
This SHIP-CT study concluded that hypertonic saline is a safe and therapeutic option to minimize the structural lung damage in children aged 3-6 years with cystic fibrosis.

Lancet Respir Med. 2022 Mar. Doi:10.1016/S2213-2600(21)00546-4.