INTRODUCTION: Recurrent respiratory tract infections (RRTIs) are common in childhood and impose substantial socioeconomic burden. β-Glucans, particularly pleuran from Pleurotus ostreatus, demonstrate immunomodulatory properties through the pathogen-associated molecular pattern receptor interactions. This study evaluated a novel chewable pleuran-based supplement with vitamin D and zinc for preventing respiratory infections in children with RRTIs. METHODS: This international, multicentre, randomised, double-blind, placebo-controlled trial enrolled 249 children with RRTIs from Slovakia, Czech Republic, and Serbia. Participants received either pleuran-based supplement (IMG® with vitamin D and zinc) or active placebo (vitamin D and zinc) for 3 months during respiratory infection season (October-March). Primary endpoint was total respiratory tract infections (RTIs). Secondary endpoints included RTI subtypes, RTI duration, missed school days, and safety evaluations. RESULTS: In total, 217 children completed the study (104 active, 113 placebo). The active group experienced significantly fewer total RTIs versus placebo (2.35 ± 1.25 vs. 2.77 ± 1.78; P = 0.042), representing 15.2% reduction over 3 months. Common cold episodes were reduced by 18.6% (1.53 ± 1.22 vs. 1.88 ± 1.25; P = 0.040). Effects were pronounced in children over 6 years (P = 0.026 for total RTIs; P = 0.005 for common cold) and evident after the first month (P = 0.037). Tonsillopharyngitis showed significant reductions in frequency (P = 0.003) and duration (P = 0.009). Post hoc analysis of children enrolled at respiratory season onset confirmed significant reductions in common cold frequency (P = 0.004) and duration (P = 0.023). The supplement demonstrated excellent tolerability with 98.7% compliance and only mild adverse events. CONCLUSION: Chewable pleuran-based supplement with vitamin D and zinc significantly reduced respiratory tract infections in children with RRTIs, with rapid onset and favourable safety profile, demonstrating therapeutic potential in this vulnerable population. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT06974747.

Children's Hospital for Lung Diseases and Tuberculosis University Clinical Hospital Center Dr Dragiša Mišović Dedinje Belgrade Serbia

Clinic of Allergy and Clinical Immunology Clinical Centre of Serbia Belgrade Serbia

Clinic of Paediatric Respiratory Diseases and Tuberculosis National Institute of Paediatric Tuberculosis and Respiratory Diseases Dolny Smokovec Jessenius Faculty of Medicine Comenius University in Bratislava Martin Slovakia

Department of Allergology and Pediatrics Medical University of Lublin Lublin Poland

Department of Allergology University Children's Hospital Belgrade Serbia

Department of Endoscopic and Surgical ENT Institute of Health Protection of Mother and Children of Serbia Belgrade Serbia

Department of Microbiology Faculty of Medicine Slovak Medical University 833 03 Bratislava Slovakia

Department of Microbiology Immunology and Transplantation KU Leuven Catholic University of Leuven Louvain Belgium

Department of Paediatrics Agel Hospital Ostrava Vítkovice Ostrava Czech Republic

Department of Paediatrics and Adolescent Medicine Jessenius Faculty of Medicine in Martin University Hospital in Martin Comenius University in Bratislava Martin Slovakia

Department of Pathological Physiology Jessenius Faculty of Medicine University Teaching Hospital Comenius University in Bratislava Martin Slovakia

Department of Respiratory Medicine 1st Faculty of Medicine Charles University and Thomayer Hospital Prague Czech Republic

Dept Clin Pharm and Pharmacol Univ Groningen Univ Med Ctr Groningen Groningen Netherlands

Faculty of Medicine University of Belgrade Belgrade Serbia

Faculty of Pharmacy in Novi Sad University Business Academy Novi Sad Novi Sad Serbia

Institute of Clinical Immunology and Medical Genetics Jessenius Faculty of Medicine in Martin University Hospital Martin Comenius University in Bratislava Martin Slovakia

Institute of Molecular Biology Slovak Academy of Sciences Dubravska Cesta 21 845 51 Bratislava Slovakia

PRO BABY Ltd Bratislava Slovakia

Zobrazit více v PubMed

Toivonen L, Karppinen S, Schuez-Havupalo L, et al. Burden of recurrent respiratory tract infections in children: a prospective cohort study. Pediatr Infect Dis J. 2016;35:e362–9. PubMed DOI

Chiappini E, Santamaria F, Marseglia GL, et al. Prevention of recurrent respiratory infections: inter-society consensus. Ital J Pediatr. 2021;47:211. PubMed DOI PMC

Esposito S, Musio A. Immunostimulants and prevention of recurrent respiratory tract infections. J Biol Regul Homeost Agents. 2013;27:627–36. PubMed

Esposito S, Jones MH, Feleszko W, et al. Prevention of new respiratory episodes in children with recurrent respiratory infections: an expert consensus statement. Microorganisms. 2020;8:1810. PubMed DOI PMC

Esposito S, Soto-Martinez ME, Feleszko W, Jones MH, Shen KL, Schaad UB. Nonspecific immunomodulators for recurrent respiratory tract infections, wheezing and asthma in children: a systematic review of mechanistic and clinical evidence. Curr Opin Allergy Clin Immunol. 2018;18:198–209. PubMed DOI PMC

Jesenak M, Hrubisko M, Chudek J, et al. Beneficial effects of pleuran on asthma control and respiratory tract-infection frequency in children with perennial asthma. Sci Rep. 2023;15:7146. DOI

Jesenak M, Hrubisko M, Majtan J, Rennerova Z, Banovcin P. Anti-allergic effect of pleuran (β-glucan from Pleurotus ostreatus) in children with recurrent respiratory tract infections. Phytother Res. 2014;28:471–4. PubMed DOI

Jesenak M, Majtan J, Rennerova Z, Kyselovic J, Banovcin P, Hrubisko M. Immunomodulatory effect of pleuran (β-glucan from Pleurotus ostreatus) in children with recurrent respiratory tract infections. Int Immunopharmacol. 2013;15:395–9. PubMed DOI

Jesenak M, Sanislo L, Kuniakova R, Rennerova Z, Buchanec J, Banovcin P. Imunoglukan P4H® in the prevention of recurrent respiratory infections in childhood. Cesk Pediatr. 2010;73:639–47.

Rennerova Z, Picó Sirvent L, Carvajal Roca E, et al. Beta-(1,3/1,6)-D-glucan from Pleurotus ostreatus in the prevention of recurrent respiratory tract infections: an international, multicentre, open-label, prospective study. Front Pediatr. 2022;10:999701. PubMed DOI PMC

Bergendiova K, Tibenska E, Majtan J. Pleuran (β-glucan from Pleurotus ostreatus) supplementation, cellular immune response and respiratory tract infections in athletes. Eur J Appl Physiol. 2011;111:2033–40. PubMed DOI

Kunc P, Fabry J, Matiscakova M, et al. Effect of a pleuran-based supplement on salivary IgA secretion in children with recurrent respiratory infections. Curr Ther Res Clin Exp. 2025;102:100780. https://doi.org/10.1016/j.curtheres.2025.100780 . PubMed DOI PMC

Strickley RG. Pediatric oral formulations: an updated review of commercially available pediatric oral formulations since 2007. J Pharmacol Sci. 2019;108:1335–65. DOI

De Martino M, Ballotti S. The child with recurrent respiratory infections: normal or not? Pediatr Allergy Immunol. 2007;18:13–8. PubMed DOI

Karacsonyi S, Kuniak L. Polysaccharides of Pleurotus ostreatus: isolation and structure of pleuran, an alkali-insoluble β-D-glucan. Carbohydr Polym. 1994;24:107–11. DOI

Brown GD, Gordon S. Immune recognition of fungal β-glucans. Cell Microbiol. 2005;7:471–9. PubMed DOI

Pasnik J, Slemp A, Cywinska-Bernas A, Zeman K, Jesenak M. Preventive effect of pleuran (β-glucan isolated from Pleurotus ostreatus) in children with recurrent respiratory tract infections-open-label prospective study. Curr Pediatr Res. 2017;21:99–104.

Vetvicka V, Vannucci L, Sima P, Richter J. Beta glucan: supplement or drug? From laboratory to clinical trials. Molecules. 2019;24:1251. PubMed DOI PMC

Leentjens J, Quintin J, Gerretsen J, Kox M, Pickkers P, Netea MG. The effects of orally administered beta-glucan on innate immune responses in humans, a randomized open-label intervention pilot-study. PLoS ONE. 2014;9:e108794. PubMed DOI PMC

Zdrenghea MT, Makrinioti H, Bagacean C, Bush A, Johnston SL, Stanciu LA. Vitamin D modulation of innate immune responses to respiratory viral infections. Rev Med Virol. 2017;27. https://doi.org/10.1002/rmv.1909 .

Vlieg-Boerstra B, de Jong N, Meyer R, et al. Nutrient supplementation for prevention of viral respiratory tract infections in healthy subjects: a systematic review and meta-analysis. Allergy. 2022;77:1373–88. PubMed DOI

Raju A, Luthra G, Shahbaz M, et al. Role of vitamin D deficiency in increased susceptibility to respiratory infections among children: a systematic review. Cureus. 2022;14:e29205. PubMed PMC

Mandlik R, Mughal Z, Khadilkar A, et al. Occurrence of infections in schoolchildren subsequent to supplementation with vitamin D-calcium or zinc: a randomized, double-blind, placebo-controlled trial. Nutr Res Pract. 2020;14:117–26. PubMed DOI

Gielen V, Sykes A, Zhu J, et al. Increased nuclear suppressor of cytokine signaling 1 in asthmatic bronchial epithelium suppresses rhinovirus induction of innate interferons. J Allergy Clin Immunol. 2015;136:177–88. PubMed DOI PMC

Van Leuven JT, Gonzalez AJ, Ijezie EC, et al. Rhinovirus reduces the severity of subsequent respiratory viral infections by interferon-dependent and -independent mechanisms. mSphere. 2021;6:e0047921.

Durrani SR, Montville DJ, Pratt AS, et al. Innate immune responses to rhinovirus are reduced by the high-affinity IgE receptor in allergic asthmatic children. J Allergy Clin Immunol. 2012;130:489–95. PubMed DOI PMC

Shukla SD, Shastri MD, Vanka SK, et al. Targeting intercellular adhesion molecule-1 (ICAM-1) to reduce rhinovirus-induced acute exacerbations in chronic respiratory diseases. Inflammopharmacology. 2022;30:725–35. PubMed DOI PMC

van Riet-Nales DA, Wang S, Saint-Raymond A, Robert JL. The EMA quality guideline on the pharmaceutical development of medicines for paediatric use. Int J Pharm. 2012;435:132–4. PubMed DOI

Zhou X, Wu Y, Zhu Z, et al. Mucosal immune response in biology, disease prevention and treatment. Signal Transduct Target Ther. 2025;10:7. PubMed DOI PMC

Zobrazit více v PubMed

ClinicalTrials.gov
NCT06974747