Lactoferrin in the Prevention of Recurrent Respiratory Infections in Preschool Children: A Prospective Randomized Study
Angela Pasinato, Mario Fama, Giovanni Tripepi, Colin Gerard Egan, Eugenio Baraldi
Children, doi:10.3390/children11020249
Few studies have evaluated the effect of bovine lactoferrin (bLf) on reducing respiratory infections in preschool children. This randomized controlled trial evaluated the effect of bLf in preschool children with recurrent respiratory infections. Participants were randomly assigned bLf (n = 25) or control (n = 25). Outcomes included respiratory infection episodes (RIEs), symptom duration, school absence and medication. Fifty children aged 4.2 ± 0.1 years were included. During the active 4-month phase, median number of RIEs was reduced by 50% in the bLf group [1-episode, interquartile range (IQR): 0-2] vs. control (2, IQR: 1-3; p = 0.02). The proportion of participants with >3 RIEs was significantly lower in bLf (n = 1, 4%) vs. control (n = 7, 28%) with 80% lower odds of upper RIEs in the bLf arm (odds ratio: 0.20, 95% CI:0.06-0.74, p = 0.015). The duration of symptoms (3 vs. 6, p = 0.009) and days absent from school (3 vs. 6, p = 0.15) were lower in the active arm. Over the 2-month follow-up, no significant differences were observed between groups for infection episodes, symptom duration or school absence. However, bLf-treated children received significantly less corticosteroids over the entire 6-month study period (32% vs. 60%; p = 0.047). bLf supplementation significantly reduced the frequency and duration of RIEs in children with decreased corticosteroid use.
Funding: No funding was obtained for the undertaking of this non-profit study. Pharmaguida Srl supplied lactoferrin for the treatment of children for the entire duration of the study. No commercial entity was involved in data collection, analysis and interpretation of results.
Institutional Review Board Statement: The study was approved on 28/10/2022 by the Ethics Committee per le Sperimentazioni Cliniche della Provincia di Vicenza, Italy (Protocol number 113083). This study was performed in accordance to the ethical standards laid down in the 1975 Declaration of Helsinki. Informed Consent Statement: Parents or guardians provided written informed consent.
Conflicts of Interest: The authors declare no conflicts of interest.
References
Ali, Hasan, Kow, Merchant, Lactoferrin Reduces the Risk of Respiratory Tract Infections: A Meta-Analysis of Randomized Controlled Trials, Clin. Nutr. ESPEN,
doi:10.1016/j.clnesp.2021.08.019Berthon, Williams, Williams, Wood, Effect of Lactoferrin Supplementation on Inflammation, Immune Function, and Prevention of Respiratory Tract Infections in Humans: A Systematic Review and Meta-Analysis, Adv. Nutr,
doi:10.1093/advances/nmac047Campione, Lanna, Cosio, Rosa, Conte et al., Lactoferrin against SARS-CoV-2: In Vitro and In Silico Evidences, Front. Pharmacol,
doi:10.3389/fphar.2021.666600Chen, Chai, Li, Zhang, Xie et al., Effect of Bovine Lactoferrin from Iron-Fortified Formulas on Diarrhea and Respiratory Tract Infections of Weaned Infants in a Randomized Controlled Trial, Nutrition,
doi:10.1016/j.nut.2015.08.010Chiappini, Santamaria, Marseglia, Marchisio, Galli et al., Prevention of Recurrent Respiratory Infections: Inter-Society Consensus, Ital. J. Pediatr,
doi:10.1186/s13052-021-01150-0De La Rosa, Yang, Tewary, Varadhachary, Oppenheim, Lactoferrin Acts as an Alarmin to Promote the Recruitment and Activation of APCs and Antigen-Specific Immune Responses, J. Immunol,
doi:10.4049/jimmunol.180.10.6868Eldeniz, Gul, Yorulmaz, Guner, Keles et al., Evaluation of the 10 Warning Signs in Primary and Secondary Immunodeficient Patients, Front. Immunol,
doi:10.3389/fimmu.2022.900055Fiore, Napoleone, Careddu, Meglio, Fiocchi et al., Le Infezioni Respiratorie Ricorrenti. I Consigli Della FIMP, Il Med. Pediatra
García-Montoya, Cendón, Arévalo-Gallegos, Rascón-Cruz, Lactoferrin a Multiple Bioactive Protein: An Overview, Biochim. Biophys. Acta,
doi:10.1016/j.bbagen.2011.06.018Hwang, Kruzel, Actor, Cho, Expressed Recombinant Human Lactoferrin as an Adjuvant for BCG, Int. J. Immunopathol. Pharmacol,
doi:10.1177/0394632015599832King, Cummings, Guo, Trivedi, Readmond et al., A Double-Blind, Placebo-Controlled, Pilot Study of Bovine Lactoferrin Supplementation in Bottle-Fed Infants, J. Pediatr. Gastroenterol. Nutr,
doi:10.1097/01.mpg.0000243435.54958.68Li, Wu, Berseth, Harris, Richards et al., Improved Neurodevelopmental Outcomes Associated with Bovine Milk Fat Globule Membrane and Lactoferrin in Infant Formula: A Randomized, Controlled Trial, J. Pediatr,
doi:10.1016/j.jpeds.2019.08.030Mattia, Generally Recognized as Safe (GRAS) Notification 000423 for Cow's Milk-Derived Lactoferrin
Motoki, Mizuki, Tsukahara, Miyakawa, Kubo et al., Effects of Lactoferrin-Fortified Formula on Acute Gastrointestinal Symptoms in Children Aged 12-32 Months: A Randomized, Double-Blind, Placebo-Controlled Trial, Front. Pediatr,
doi:10.3389/fped.2020.00233Rai, Adelman, Zhuang, Rai, Boettcher et al., Longitudinal Changes in Lactoferrin Concentrations in Human Milk: A Global Systematic Review, Crit. Rev. Food Sci. Nutr,
doi:10.1080/10408398.2011.642422Rascón-Cruz, Espinoza-Sánchez, Siqueiros-Cendón, Nakamura-Bencomo, Arévalo-Gallegos et al., Lactoferrin: A Glycoprotein Involved in Immunomodulation, Anticancer, and Antimicrobial Processes, Molecules,
doi:10.3390/molecules26010205Rosa, Tripepi, Naldi, Aimati, Santangeli et al., Ambulatory COVID-19 Patients Treated with Lactoferrin as a Supplementary Antiviral Agent: A Preliminary Study, J. Clin. Med,
doi:10.3390/jcm10184276Salaris, Scarpa, Elli, Bertolini, Guglielmetti et al., Protective Effects of Lactoferrin against SARS-CoV-2 Infection In Vitro, Nutrients,
doi:10.3390/nu13020328Schaad, Esposito, Razi, Diagnosis and Management of Recurrent Respiratory Tract Infections in Children: A Practical Guide, Arch. Pediatr. Infect. Dis,
doi:10.5812/pedinfect.31039Siqueiros-Cendón, Arévalo-Gallegos, Iglesias-Figueroa, García-Montoya, Salazar-Martínez et al., Immunomodulatory Effects of Lactoferrin, Acta Pharmacol. Sin,
doi:10.1038/aps.2013.200Zuccotti, Trabattoni, Morelli, Borgonovo, Schneider et al., Immune Modulation by Lactoferrin and Curcumin in Children with Recurrent Respiratory Infections, J. Biol. Regul. Homeost. Agents
