Pilot Randomized Controlled Trial Evaluating the Effect of Hypertonic Saline With and Without Hyaluronic Acid in Reducing Inflammation in Cystic Fibrosis

Abstract

Background: Hypertonic saline (HS) has been established as a therapy aimed at restoring the surface liquid of airways liquid and enhancing mucociliary clearance in patients with cystic fibrosis (CF). A formula containing 7% HS and 0.1% hyaluronic acid (HA) is also available, basing its use on the protective effects of HA against elastin injury and on its greater ease of administration (i.e., the perceived acceptability of inhalation). This study explores the effect of HA+HS in reducing the inflammation of airways, by measuring cytokine levels in sputum, its safety profile, and the prevalence of commonly reported symptoms like cough, throat irritation, and saltiness.

Methods: In a pilot, double-blind, randomized controlled, parallel-group, 1:1 trial, clinically stable CF patients older than 6 years of age and with a FEV₁pred. >40% were randomized to one of the treatment arms, HS or HS+HA, to be administered twice a day at home. Clinical data, inflammatory markers (IL-1β, IL-6, IL-8, IL-10, TNF-α, VEGF) in sputum, and judgments on the tolerability and pleasantness were collected at the beginning and after 28 days.

Results: HA+HS had no significant effect on inflammatory markers versus HS alone, as shown by broad confidence intervals. In the HS+HA group, the highest decrement from baseline values was observed for IL-1β (-58.8%) followed by VEGF (-49.9%), whereas in the HS group a significant increment of IL-10 levels (+83.0%; p = 0.011) was the only significant finding. Prevalence of unfavorable scores was 36.8% in HA+HS versus 55% in HS group (p = 0.207); no significant differences were detected in the prevalence of moderate/severe symptoms of cough, saltiness, and throat irritation in pulmonary functions tests after 28 days.

Conclusions: HS+HA administration in CF patients does not show any significant effects on lung inflammation and function as compared to HS alone.

Keywords: clinical trial; cystic fibrosis; cytokines; hyaluronic acid; hypertonic saline; lung function.