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Treatment with inhaled hypertonic saline was shown to be both safe and effective for improving breathing in infants with cystic fibrosis (CF) in a study from Germany.

Change in lung clearance index (LCI) from baseline to week 52 was larger in infants treated with hypertonic saline, at -0.6 compared to -0.1 in isotonic saline-treated infants (P<0.05), Mirjam Stahl, MD, of the University of Heidelberg in Germany, and colleagues reported.

Twice daily inhalation of 6.0% hypertonic saline and 0.9% isotonic saline were both generally well tolerated, and the number of adverse events did not differ between the two groups (P=0.49), they wrote in the.

While hypertonic saline has been shown to benefit older babies and children with CF, the randomized controlled trial is the first to examine the treatment -- which involves a sterilized solution of hypertonic saline inhaled in nebulized form for the purpose of thinning mucus in the airways -- in infants with the progressive, inherited lung disorder. Prior studies in mice and children with CF showed the treatment to decrease mucous plugging that can lead to airway obstruction and infections.

The study is also the first to show that two measures of quantitative outcome -- LCI and chest magnetic resonance imaging (MRI) -- are feasible for use in clinical trials involving very young infants with CF.

"Several studies from teams worldwide investigating infants and preschool children with CF identified by newborn screening revealed that CF lung disease starts in the first months of life, leaving only a narrow window of opportunity for preventive therapeutic interventions," Stahl said in a statement.

She noted that by delaying the onset and progression of lung disease associated with CF, hypertonic saline may be a promising therapeutic strategy for infants and children with the disease.

In the PRESIS (Preventative Inhalation of Hypertonic Saline in Infants With CF) study, researchers randomized 42 young infants (<4 months old) with CF being treated at one of five sites in Germany to receive twice daily hypertonic saline at a 6.0% salt concentration (n=21) or isotonic saline at a concentration of 0.9% (n=21).

In addition to evaluating treatment efficacy, the researchers examined whether LCI and chest MRI (used to determine efficacy), can be safely performed on infants.

"So far, trials testing the safety and efficacy of preventive therapies starting in the first months of life in infants with CF have been hampered by the lack of quantitative outcome measures of lung disease in this challenging age group," Stahl and colleagues wrote.

They added that a series of recent studies suggest that LCI, which is a measure of ventilation homogeneity derived from multiple-breath washout, may be a useful measure of lung function, disease progression, and response to therapy in infants. Likewise, chest MRI has been shown to be sensitive for detecting early abnormalities in lung structure in infants with CF.

Among the other key findings from PRESIS:

• Weight gain was improved in the hypertonic saline-treated infants (P<0.05)
• Pulmonary exacerbations and chest MRI scores did not differ between the two groups

"PRESIS is the first randomized controlled trial testing feasibility, safety, and initial efficacy of preventive treatment of lung disease initiated in the first months of life in infants with CF using LCI and MRI as quantitative outcome measures of early lung disease," the researchers wrote. "This study demonstrates that randomized controlled trials starting in early infancy including regular treatment with inhalation solutions and repeated LCI and MRI measurements over a period of 12 months are feasible and well accepted by the parents."

The findings also indicate that early intervention had beneficial effects on lung function and thriving among infants with CF, and the study suggested that LCI is a more sensitive measure of response to treatment than MRI morphology scores or pulmonary exacerbations in infants with CF, the researchers wrote.

"This initial randomized controlled trial supports that preventive treatment with inhaled hypertonic saline starting in the first months of life is safe and has therapeutic benefits on lung function and thriving of CF infants," Stahl and colleagues concluded. "These data support the conduct of future randomized controlled trials to determine safety and efficacy of preventive treatment strategies that have the potential to delay or prevent progressive lung damage in patients with CF."

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