Effects of sodium hyaluronate in children with recurrent upper respiratory tract infections: results of a randomised controlled study.

Hyaluronic acid is a major component of many extracellular matrices that plays a role in the regulation of vasomotor tone and mucous gland secretion, and in the modulation of the inflammatory process in upper and lower airways. This pilot study was aimed at evaluating the effects of nasal washes with 9 mg nebulised sodium hyaluronate given for 15 days per month over 3 months in 75 paediatric patients with recurrent upper respiratory tract infections (URTI). Eligible patients were randomized to treatment with nasal washes containing 9 mg sodium hyaluronate plus saline solution or saline alone, according to an open-label, parallel group design, with blind observer assessment. Ciliary motility, which was assessed based on a 0-3 point rating scale (0 = absent, 1 = less than 5 minutes, 2 = greater than or equal to 5 and ≤ 10 minutes, 3 = greater than 10 minutes) was the primary study endpoint. The secondary efficacy variables included cytological (presence of neutrophils, eosinophils and mast cells), microbiological (presence of bacteria and mycetes), endoscopical (presence of adenoid hypertrophy and biofilm) and clinical (presence of rhinitis, post-nasal drip, nasal dyspnoea) parameters. The two treatment groups (mean age 7.5 years, 53percent of males) were comparable for baseline data, except a higher mean age in the control group than in the treated group. Treatment with 9 mg sodium hyaluronate was associated with significantly greater improvements (p less than 0.001 between groups) in primary outcome ciliary motility [odds ratio (OR) 13.61; 95 percent CI 4.51-41.00 in the univariate regression analysis that examined the probability of improvement]. Treatment with 9 mg sodium hyaluronate was also significantly superior to saline alone in adenoid hypertrophy (p less than 0.001; OR 14.72; 95 percent CI 4.74-45.68), presence of bacteria (p = 0.026; OR 2.95; 95 percent CI 1.15-7.55), neutrophils (p = 0.002; OR 4.51; 95 percent CI 1.75-11.62), rhinitis (p = 0.040; OR 10.47; 95 percent CI 3.10-35.31), nasal dyspnoea (p = 0.047; OR 3.80; 95 percent CI 1.09-13.19) and biofilm (p = 0.049; OR 9.90; 95 percent CI 2.61-37.47). Advantages of 9 mg of sodium hyaluronate over control on post-nasal drip and presence of mycetes (although evident) did not reach the level of statistical significance. The superiority of the treated group over saline alone was confirmed in a multivariate logistic regression analysis that took into account age as confounding factor. The number of days of absence from school was significantly lower in the 9 mg sodium hyaluronate group compared to controls (p less than 0.001 between groups). A 3-month intermittent treatment with 9 mg sodium hyaluronate with nasal washes plus saline solution was associated with significant improvements in ciliary motility and in cytological, microbiological, endoscopic and clinical outcomes compared to saline, in children with recurrent URTI.