The aim of this study was to evaluate the effects of pleuran (β-glucan isolated from Pleurotus ostreatus) on asthma control and respiratory morbidity in children on conventional GINA-based asthma treatment who had partially controlled perennial asthma. A double-blind, placebo-controlled multicentre clinical trial with a 2-arm, parallel design was conducted across three countries; 230 children aged 7 to 17 years were randomised (1:1) into an active group (receiving a pleuran/vitamin C combination) or a placebo group (receiving vitamin C only). This study consisted of 24 weeks of treatment (2 capsules a day) and then 24 weeks of follow-up. The primary endpoints included the effects of active treatment versus placebo on asthma control and respiratory tract infections (RTIs). Secondary endpoints included changes in the following measures: number of asthma exacerbations, with or without respiratory infection; quality of life of both asthmatic children and their caregivers; spirometric indices; fractional exhaled nitric oxide (FeNO) levels; safety after 24 weeks of treatment and also after the full 48-week study period. Overall, 206 children completed this study; 113 of these children were in the active group and received a pleuran/vitamin C combination for 24 weeks. After the 24-week treatment period, children below 12 years of age who were in the active group achieved significant improvements in asthma control compared to those in the placebo group (21.8 ± 3.5 vs. 20.3 ± 4.0; P = 0.02); while children at least 12 years old who were in the active group reported lower numbers of RTIs (0.7 ± 1.0 vs. 1.9 ± 1.7; P = 0.002) compared to children of this age in the placebo group. In addition, children below 12 years of age in the active group showed a significant decrease in asthma exacerbations compared to those in the placebo group (2.5 ± 1.6 vs. 3.3 ± 1.9; P = 0.05). At the end of the 48-week trial, a statistically significant improvement in asthma control was observed in 84.7% of children who received pleuran/vitamin C treatment compared to 67.0% of children who received vitamin C only (P = 0.01). The pleuran/vitamin C combined treatment was safe and well-tolerated, and no related serious adverse events were reported. This study highlights the favourable safety profile of pleuran/vitamin C supplementation and demonstrates positive effects of this treatment on asthma control and RTI incidence in children with allergic perennial asthma that was partially controlled by conventional therapy.

Department of Allergy and Clinical Immunology Faculty of Medicine University of Ostrava Ostrava Czech Republic

Department of Allergy and Clinical Immunology St Elisabeth's Oncology Institute Bratislava Slovakia

Department of Clinical Pharmacy and Pharmacology University of Groningen Groningen The Netherlands

Department of Internal Diseases and Oncological Chemotherapy Faculty of Medicine in Katowice Medical University of Silesia Katowice Poland

Department of Lung Diseases and Rheumatology Medical University of Lublin Lublin Poland

Department of Microbial Genetics Institute of Molecular Biology Slovak Academy of Sciences Bratislava Slovakia

Department of Microbiology Faculty of Medicine Slovak Medical University Bratislava Slovakia

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

Department of Paediatric Pulmonology and Phthisiology Faculty of Medicine Slovak Medical University National Institute of Children's Diseases Bratislava Slovakia

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

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

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

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The Global Asthma Report 2022. Int. J. Tuberc. Lung Dis.26, 1–104 (2022). PubMed

Global Strategy for Asthma Management and Prevention, 2023. (Global Initiative for Asthma (GINA), 2023).

Spergel, J. M. From atopic dermatitis to asthma: the atopic march. Ann. Allergy Asthma Immunol.105, 99–106 (2010). PubMed

Lommatzsch, M. Immune modulation in asthma: Current concepts and future strategies. Respiration99, 566–576 (2020). PubMed PMC

Menzies-Gow, A. et al. An expert consensus framework for asthma remission as a treatment goal. J. Allergy Clin. Immunol.145, 757–765 (2020). PubMed

Papi, A. et al. The ICQ asthma algorithm: Inhaled corticosteroid Containing resCUE (ICQ) treatment for present and future asthma management. Allergy77, 1325–1327 (2022). PubMed

Yildiz, Y. & Yavuz, A. Y. Complementary and alternative medicine use in children with asthma. Complement. Ther. Clin. Pract.43, 101353 (2021). PubMed

Shaw, A., Thompson, E. A. & Sharp, D. Complementary therapy use by patients and parents of children with asthma and the implications for NHS care: a qualitative study. BMC Health Serv. Res.6, 76 (2006). PubMed PMC

Esposito, S. et al. Prevention of new respiratory episodes in children with recurrent respiratory infections: an expert consensus statement. Microorganisms8, 1810 (2020). PubMed PMC

Wang, Q. et al. β-Glucans: Relationships between modification, conformation and functional activities. Molecules22, 257 (2017). PubMed PMC

Wzorek-Łyczko, K., Woźniak, W., Piwowarczyk, A. & Kuchar, E. The anti-infective effect of β-glucans in children. Int. J. Vitam. Nutr. Res.10.1024/0300-9831/a000793 (2023). PubMed

Jesenak, M. et al. Imunoglukan P4H® in the prevention of recurrent respiratory infections in childhood. Cesk. Pediatr.73, 639–647 (2010).

Jesenak, M. et al. Immunomodulatory effect of pleuran (β-glucan from Pleurotus ostreatus) in children with recurrent respiratory tract infections. Int. Immunopharmacol.15, 395–399 (2013). PubMed

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.21, 99–104 (2017).

Grau, J. S., Sirvent, L. P., Inglés, M. M. & Urgell, M. R. Betaglucanos de Pleurotus ostreatus en la prevención de infecciones respiratorias recurrentes. Acta Pediatr. Esp.73, 186–193 (2015).

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.28, 471–474 (2014). PubMed

Jesenak, M., Banovcin, P., Rennerova, Z. & Majtan, J. β-Glucans in the treatment and prevention of allergic diseases. Allergol. Immunopathol. (Madr.)42, 149–156 (2014). PubMed

Sarinho, E. et al. Production of interleukin-10 in asthmatic children after Beta-1-3-glucan. Allergol. Immunopathol. (Madr.)37, 188–192 (2009). PubMed

Global Strategy for Asthma Management and Prevention, 2016. (Global Initiative for Asthma (GINA), 2016).

Karacsonyi, S. & Kuniak, L. Polysaccharides of Pleurotus ostreatus: isolation and structure of pleuran, an alkali-insoluble β-D-glucan. Carbohydr. Polym.24, 107–111 (1994).

Nathan, R. A. et al. Development of the asthma control test: a survey for assessing asthma control. J. Allergy Clin. Immunol.113, 59–65 (2004). PubMed

Schatz, M. et al. Asthma Control Test: reliability, validity, and responsiveness in patients not previously followed by asthma specialists. J. Allergy Clin. Immunol.117, 549–556 (2006). PubMed

Liu, A. H. et al. Development and cross-sectional validation of the Childhood Asthma Control Test. J. Allergy Clin. Immunol.119, 817–825 (2007). PubMed

Liu, A. H. et al. The Childhood Asthma Control Test: Retrospective determination and clinical validation of a cut point to identify children with very poorly controlled asthma. J. Allergy Clin. Immunol.126, 267–273 (2010). PubMed

Levin, J. C. et al. Improvement in asthma control and inflammation in children undergoing adenotonsillectomy. Pediatr. Res.75, 403–408 (2014). PubMed PMC

Juniper, E. F. et al. Measuring quality of life in children with asthma. Qual. Life Res.5, 35–46 (1996). PubMed

Juniper, E. F. et al. Measuring quality of life in the parents of children with asthma. Qual. Life Res.5, 27–34 (1996). PubMed

De Marco Castro, E., Calder, P. C. & Roche, H. M. β-1,3/1,6-glucans and immunity: state of the art and future directions. Mol. Nutr. Food Res.65, e1901071 (2021). PubMed PMC

Sima, P. & Vetvicka, V. β-Glucan in allergies. Am. J. Immunol.13, 73–80 (2017).

Diamant, Z. & Page, C. P. Heparin and related molecules as a new treatment for asthma. Pulm. Pharmacol. Ther.13, 1–4 (2000). PubMed

Suzuki, Y., Adachi, Y., Ohno, N. & Yadomae, T. Th1/Th2-Balancing immunomodulating activity of gel-forming (1–>3)-beta-glucans from fungi. Biol. Pharm. Bull.24, 811–819 (2001). PubMed

Baran, J., Allendorf, D. J., Hong, F. & Ross, G. D. Oral beta-glucan adjuvant therapy converts nonprotective Th2 response to protective Th1 cell-mediated immune response in mammary tumor-bearing mice. Folia Histochem. Cytobiol.45, 107–114 (2007). PubMed

Kim, I. S. et al. Oral administration of β-Glucan and Lactobacillus plantarum alleviates atopic dermatitis-like symptoms. J. Microbiol. Biotechnol.29, 1693–1706 (2019). PubMed

Dillon, S. et al. Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance. J. Clin. Invest.116, 916–928 (2006). PubMed PMC

Nathan, A. T., Peterson, E. A., Chakir, J. & Wills-Karp, M. Innate immune responses of airway epithelium to house dust mite are mediated through beta-glucan-dependent pathways. J. Allergy Clin. Immunol.123, 612–618 (2009). PubMed PMC

Sung, N. Y. et al. Anti-allergic effect of low molecular weight β-glucan prepared by λ-irradiation. Food Sci. Biotechnol.20, 841–844 (2011).

Ku, S. K. et al. Effect of β-glucan originated from Aureobasidium pullulans on asthma induced by ovalbumin in mouse. Arch. Pharm. Res.35, 1073–1081 (2012). PubMed

Talbott, S. M., Talbott, J. A., Talbott, T. L. & Dingler, E. β-Glucan supplementation, allergy symptoms, and quality of life in self-described ragweed allergy sufferers. Food Sci. Nutr.1, 90–101 (2013). PubMed PMC

Miraglia Del Giudice, M. et al. Resveratrol plus carboxymethyl-β-glucan may affect respiratory infections in children with allergic rhinitis. Pediatr. Allergy Immunol.25, 724–728 (2014). PubMed

Marosi, A. & Stiesmeyer, J. Improving pediatric asthma patient outcomes by incorporation of effective interventions. J. Asthma38, 681–690 (2001). PubMed

Bochner, B. S., Undem, B. J. & Lichtenstein, L. M. Immunological aspects of allergic asthma. Annu. Rev. Immunol.12, 295–335 (1994). PubMed

Larsen, J. M. et al. Children with asthma by school age display aberrant immune responses to pathogenic airway bacteria as infants. J. Allergy Clin. Immunol.133, 1008–1013 (2014). PubMed

Lukacs, N. W. & Huang, Y. J. Microbiota–immune interactions in asthma pathogenesis and phenotype. Curr. Opin. Immunol.66, 22–26 (2020). PubMed PMC

Frey, A. et al. More than just a barrier: the immune functions of the airway epithelium in asthma pathogenesis. Front. Immunol.11, 761 (2020). PubMed PMC

Price, J. F. Issues in adolescent asthma: what are the needs?. Thorax51, S13–S17 (1996). PubMed PMC

Couriel, J. Asthma in adolescence. Paediatr. Respir. Rev.4, 47–54 (2003). PubMed

Majtan, J. Pleuran (β-glucan from Pleurotus ostreatus ): an effective nutritional supplement against upper respiratory tract infections?. Med. Sport Sci.59, 57–61 (2012). PubMed

Jesenak, M., Urbancikova, I. & Banovcin, P. Respiratory tract infections and the role of biologically active polysaccharides in their management and prevention. Nutrients9, E779 (2017). PubMed PMC

Darrow, L. A. et al. Air pollution and acute respiratory infections among children 0–4 years of age: an 18-year time-series study. Am. J. Epidemiol.180, 968–977 (2014). PubMed PMC

Rennerova, Z. 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.10, 999701 (2022). PubMed PMC

Ogra, P. L. Ageing and its possible impact on mucosal immune responses. Ageing Res. Rev.9, 101–106 (2010). PubMed

Meng, F. Baker’s yeast beta-glucan decreases episodes of common childhood illness in 1 to 4 year old children during cold season in China. J. Nutr. Food Sci.6, 518 (2016).

Mah, E., Kaden, V. N., Kelley, K. M. & Liska, D. J. Soluble and insoluble yeast β-glucan differentially affect upper respiratory tract infection in marathon runners: A double-blind, randomized placebo-controlled trial. J. Med. Food23, 416–419 (2020). PubMed

Zhong, X. et al. Immunomodulatory effect and biological significance of β-glucans. Pharmaceutics15, 1615 (2023). PubMed PMC

Bedirli, A. et al. Beta-glucan attenuates inflammatory cytokine release and prevents acute lung injury in an experimental model of sepsis. Shock27, 397–401 (2007). PubMed

Wang, G. et al. β-glucan induces training immunity to promote antiviral activity by activating TBK1. Viruses15, 1204 (2023). PubMed PMC

Chen, P. C., Hsieh, M. H., Kuo, W. S., Wu, L. S. & Wang, J. Y. Trained immunity and macrophage reprogramming in allergic disorders. Cell. Mol. Immunol.20, 1084–1086 (2023). PubMed PMC

Wegmann, M. Trained immunity in allergic asthma. J. Allergy Clin. Immunol.151, 1471–1473 (2023). PubMed

Foppiano, F. & Schaub, B. Childhood asthma phenotypes and endotypes: a glance into the mosaic. Mol. Cell. Pediatr.10, 9 (2023). PubMed PMC

Conrad, L. A., Cabana, M. D. & Rastogi, D. Defining pediatric asthma: phenotypes to endotypes and beyond. Pediatr. Res.90, 41–51 (2021). PubMed PMC

Tan, D. J. et al. Biomarkers of asthma relapse and lung function decline in adults with spontaneous asthma remission: a population-based cohort study. Allergy78, 957–967 (2023). PubMed PMC

Pakkasela, J. et al. Age-specific incidence of allergic and non-allergic asthma. BMC Pulm. Med.20, 9 (2020). PubMed PMC

Pyrgos, G., Horowitz, E., Joyner, D., Malveaux, F. & Togias, A. Symptom triggers in an adolescent asthma population. J. Allergy Clin. Immunol.113, S305 (2004).

Kansen, H. M. et al. Perceived triggers of asthma impair quality of life in children with asthma. Clin. Exp. Allergy49, 980–989 (2019). PubMed PMC

Landeo-Gutierrez, J. & Celedón, J. C. Chronic stress and asthma in adolescents. Ann. Allergy Asthma Immunol.125, 393–398 (2020). PubMed PMC

Kaplan, A., Hardjojo, A., Yu, S. & Price, D. Asthma across age: Insights from primary care. Front. Pediatr.7, 162 (2019). PubMed PMC

Fasola, S. et al. Asthma comorbidities: Frequency, risk factors, and associated burden in children and adolescents. Children9, 1001 (2022). PubMed PMC

Ronco, L. et al. Do not forget asthma comorbidities in pediatric severe asthma!. Front Pediatr.10, 932366 (2022). PubMed PMC

Feleszko, W., Jartti, T. & Bacharier, L. B. Current strategies for phenotyping and managing asthma in preschool children. Curr. Opin. Allergy Clin. Immunol.22, 107–114 (2022). PubMed

Garden, F. L., Simpson, J. M., Mellis, C. M., Marks, G. B., CAPS Investigators. Change in the manifestations of asthma and asthma-related traits in childhood: a latent transition analysis. Eur. Respir. J.47, 499–509 (2016). PubMed

Ghalibaf, M. H. E. et al. The effects of vitamin C on respiratory, allergic and immunological diseases: an experimental and clinical-based review. Inflammopharmacology31, 653–672 (2023). PubMed PMC