Treatment with inhaled hypertonic saline was shown to be safe and effective in improving respiration in cystic fibrosis (CF) infants in a study in Germany.
The change in baseline pulmonary clearance rate (LCI) for week 52 was higher in children treated with hypertonic saline solution at -0.6 compared to -0.1 in children treated with isotonic saline solution (P<0.05), Mirjam Stahl, MD, of the University of Heidelberg, Germany, and colleagues reported.
Twice daily inhalation of 6.0% hypertonic saline solution and 0.9% isotonic saline solution were generally well tolerated, and the number of adverse events did not differ between the two groups (P= 0.49), they wrote in the American Journal of Respiratory and Critical Medicine.
While hypertonic saline has been shown to benefit older infants and children with CF, the randomized clinical trial is the first to examine the treatment – which involves a sterile solution of hypertonic saline solution inhaled in order to reduce airway mucus . – in children with progressive and hereditary lung disease. Previous studies in mice and children with CF have shown treatment to decrease mucus clogging that can lead to airway obstruction and infections.
The study is also the first to show that two measures of quantitative outcome – LCI and magnetic resonance imaging (MRI) – are feasible for use in clinical trials involving very young children with CF.
"Several studies from teams around the world investigating infants and preschoolers with CF identified by neonatal screening revealed that CF lung disease begins in the first few months of life, leaving only a narrow window of opportunity for preventive therapeutic interventions," said Stahl in a statement.
She noted that by delaying the onset and progression of CF-associated lung disease, hypertonic saline may be a promising therapeutic strategy for infants and children with CF.
In the PRESIS (Preventive Inhalation of Hypertonic Saline Inhalation in CF infants) study, researchers randomized 42 infants (<4 months old) with CF undergoing treatment at one of five sites in Germany to receive hypertonic saline solution twice a day at 6 % (n = 21) or 0.9% isotonic saline solution (n = 21).
In addition to assessing the efficacy of the treatment, the researchers examined whether LCI and chest MRI (used to determine efficacy) can be safely performed in infants.
"So far, trials that test the safety and efficacy of preventive therapies from the first months of life in children with CF have been hampered by the lack of quantitative measures of lung disease in this challenging age group," Stahl and colleagues write.
They added that a number of recent studies suggest that LCI, which is a measure of the homogeneity of lavage ventilation with multiple breaths, may be a useful measure of lung function, disease progression, and response to therapy in infants. Similarly, magnetic resonance imaging of the thorax was sensitive to detect early abnormalities in the pulmonary structure in CF infants.
Among the other key discoveries of PRESIS:
- The gain in weight was improved in infants treated with hypertonic saline solution (P<0.05)
- Pulmonary exacerbations and chest MRI scores did not differ between the two groups
"PRESIS is the first randomized controlled trial testing the viability, safety and efficacy of early preventive treatment of lung disease initiated in the first months of life in CF infants using LCI and MRI as quantitative measures of early lung disease," the researchers write. . "This study demonstrates that randomized clinical trials initiated in early childhood, including regular treatment with inhalation solutions and repeated measures of ICL and MRI over a 12-month period, are feasible and well accepted by parents."
The results also indicate that early intervention had beneficial effects on lung function and prosperity among CF children, and the study suggested that LCI is a more sensitive measure of response to treatment than MR morphologic scores or pulmonary exacerbations in children with CF. .
"This initial randomized controlled trial supports that the preventive treatment with inhaled hypertonic saline from the first months of life is safe and has therapeutic benefits in the lung function and in the prosperity of children with CF," concluded Stahl et al. "These data support future randomized controlled trials to determine the safety and efficacy of preventive treatment strategies that have the potential to delay or prevent progressive lung damage in CF patients."
The study was supported by grants from the Dietmar Hopp Foundation and the German Federal Ministry of Education and Research. Solutions and inhalation devices used in the study were provided by PARI Pharma.
2018-09-11T00: 00: 00-0400