A pilot randomized controlled trial evaluating a resveratrol/β‐glucan nasal spray for preventing respiratory symptoms in preschool children with recurrent wheezing

BACKGROUND: Respiratory tract infections (RTIs) are a leading cause of morbidity in preschool children, particularly in those with recurrent wheezing. Natural compounds such as resveratrol and carboxymethyl-β-glucan have shown immunomodulatory, antiviral, and anti-inflammatory activity, supporting their potential role in preventing pediatric airway infections. OBJECTIVE: To evaluate the efficacy, safety, and tolerability of Linfovir®, a nasal spray containing resveratrol and carboxymethyl-β-glucan, in reducing respiratory infectious symptoms in preschool children with recurrent respiratory infections and wheezing. METHODS: This multicenter, randomized, double-blind, placebo-controlled trial enrolled children aged 2-6 years with a history of recurrent respiratory infections. Participants were randomized 1:1 to receive Linfovir® or placebo once daily for 12 weeks, with follow-up at 16 weeks. Primary and secondary outcomes including days with respiratory symptoms, number of infections, antibiotic courses, and medical visits were recorded via the VIRAPP® electronic diary. RESULTS: Eighty-two children were included in the Full Analysis Set. The primary endpoint was not statistically significant. However, a numerical reduction in days with respiratory symptoms was observed in the resveratrol/β-glucan nasal spray group compared with placebo (15.0 vs. 20.4 days in the FAS population), corresponding to an approximate 26% relative difference. Similar non-significant patterns favoring the intervention were observed for infectious episodes, antibiotic courses, and medical visits. Treatment adherence was high in both groups, and no serious adverse events occurred. CONCLUSIONS: In this pilot randomized controlled trial, the resveratrol/β-glucan nasal spray was safe and well tolerated. Although the study did not show a statistically significant effect on the primary endpoint, the observed numerical differences consistently favored the intervention. These findings should be interpreted as exploratory and hypothesis-generating and require confirmation in larger adequately powered studies.