PROPHYLACTIC EFFECT OF A PROBIOTIC INTERVENTION IN CHILDREN PRONE TO ACUTE UPPER RESPIRATORY TRACT INFECTIONS: A RANDOMIZED CONTROLLED TRIAL
Article PDF

Keywords

Prevention, Pediatrics, Ear-Nose-Throat Infections, Resistance Index, Probiotics

Abstract views: 533
PDF Downloads: 256

How to Cite

Marushko , Y., Hyshchak , T., & Todyka , Y. (2021). PROPHYLACTIC EFFECT OF A PROBIOTIC INTERVENTION IN CHILDREN PRONE TO ACUTE UPPER RESPIRATORY TRACT INFECTIONS: A RANDOMIZED CONTROLLED TRIAL . Medical Science of Ukraine (MSU), 17(3), 51-65. https://doi.org/10.32345/2664-4738.3.2021.06

Abstract

Relevance. Upper respiratory tract infections (URTIs) are common in children and often progress with secondary complications such as otitis media, bronchitis, or pneumonia, especially in children with recurrent URTIs. Probiotics displayed immunomodulatory effects in children and adults, supporting immune functions to prevent winter diseases or common colds.

Objectives. We assessed the effectiveness of a 6-week prophylaxis with probiotics (Lactobacillus helveticus Rosell®-52, Bifidobacterium infantis Rosell®-33 and Bifidobacterium bifidum Rosell®-71) for preventing primary infections and/or secondary complications in URTI-prone children.

Methods. URTI-prone children were randomly divided into the probiotics (3×10CFU/day; 6 weeks) or control arm (no preventive intervention). The number of URTIs, duration and related complications were monitored for 6 months. Resistance index, number of medical visits, and antibiotics prescriptions were also recorded.

Results. After 2 months, probiotics reduced the number of URTIs (-2.34±0.13 vs -0.24±0.14; P<0.0001) and duration in (-1.13 ±0.18 vs -0.18±0.18 days; P=0.0011), and the number of secondary complications (-53% vs -5.8%; RR 0.5313 95% CI [0.3534, 0.7986] P= 0.0058). Probiotic lowered resistance index (P<0.0001), number of medical consultations with specialized physicians (P=0.0033) and antibiotics prescriptions (P<0.0001).

Conclusions. Overall, a 6-week prophylaxis with combined probiotic (Lactobacillus helveticus Rosell®-52, Bifidobacterium infantis Rosell®-33 and Bifidobacterium bifidum Rosell®-71) in URTI-prone children exerted a significant and clinically important health benefit, decreasing the number and duration of URTI episodes and secondary complications and reducing the resistance index to a near-normal value. Furthermore, potential societal benefits of reducing health care use and inadequate antibiotic prescriptions in children favours the use of this probiotic product as a preventive strategy against URTIs and their consequences in frequently sick children.

This trial was retrospectively registered on ClinicalTrials.gov (NCT04525040).

https://doi.org/10.32345/2664-4738.3.2021.06
Article PDF

References

Simoes EAF, Cherian T, Chow J, Shahid-Salles SA, Laxminarayan R, John TJ. Acute Respiratory Infections in Children. In: B.J. Jamison DT, Measham AR, et al. (Ed.), Disease Control Priorities in Developing Countries. 2nd edition. Washington (DC): The International Bank for Reconstruction and Development / The World Bank. New York, Oxford University Press, 2006.

View at:

PubMed: https://www.ncbi.nlm.nih.gov/books/NBK11728/

Toivonen L, Karppinen S, Schuez-Havupalo L, Teros-Jaakkola T, Vuononvirta J, Mertsola J, He Q, Waris M, Peltola V. Burden of Recurrent Respiratory Tract Infections in Children: A Prospective Cohort Study. Pediatr Infect Dis J. 2016; 35(12): e362-e369. DOI: 10.1097/inf.0000000000001304

View at:

Publisher Site: https://journals.lww.com/pidj/Abstract/2016/12000/Burden_of_Recurrent_Respiratory_Tract_Infections.4.aspx

PubMed: https://pubmed.ncbi.nlm.nih.gov/27455443/

Schaad UB. Prevention of paediatric respiratory tract infections: emphasis on the role of OM-85. European Respiratory Review. 2005; 14: 74-7. DOI:10.1183/09059180.05.00009506

View at:

Publisher Site: https://err.ersjournals.com/content/14/95/74

Dehn Lunn A. Reducing inappropriate antibiotic prescribing in upper respiratory tract infection in a primary care setting in Kolkata, India. BMJ Open Quality. 2018; 7(4): e000217. DOI: 10.1136/bmjoq-2017-000217

View at:

Publisher Site: https://bmjopenquality.bmj.com/content/7/4/e000217

PubMed: https://pubmed.ncbi.nlm.nih.gov/30555928/

PubMed Central: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267302/

Marushko YV, Shef GG, Polkovnichenko LN, Moshkina TV. [Therapeutic approaches for acetone syndrome in children]. Child's health. 2012; 1(36): 4-5. [in Russian]

View at:

Publisher Site: http://www.mif-ua.com/archive/article/26007

Cyberleninka: https://cyberleninka.ru/article/n/terapevticheskie-podhody-pri-atsetonemicheskom-sindrome-u-detey

URL: https://cyberleninka.ru/article/n/terapevticheskie-podhody-pri-atsetonemicheskom-sindrome-u-detey/viewer

Messina F, Clavenna A, Cartabia M, Piovani D, Bortolotti A, Fortino I, Merlino L, Bonati M. Antibiotic prescription in the outpatient paediatric population attending emergency departments in Lombardy, Italy: a retrospective database review. BMJ Paediatrics Open. 2019; 3(1): e000546. DOI: 10.1136/bmjpo-2019-000546

View at:

Publisher Site: https://bmjpaedsopen.bmj.com/content/3/1/e000546

PubMed: https://pubmed.ncbi.nlm.nih.gov/31909220/

PubMed Central: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937000/

Miao R, Wan C, Wang Z, Zhu Y, Zhao Y, Zhang L, Liu J, Qin J, Xia J, Yan H. Inappropriate antibiotic prescriptions among pediatric inpatients in different type hospitals. Medicine (Baltimore). 2020; 99(2): e18714. DOI:10.1097/md.0000000000018714

View at:

Publisher Site: https://journals.lww.com/md-journal/Fulltext/2020/01100/Inappropriate_antibiotic_prescriptions_among.73.aspx

PubMed: https://pubmed.ncbi.nlm.nih.gov/31914082/

PubMed Central: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959949/

Shutova OV. [Acetonemic syndrome in children: diagnosis and management]. Modern pediatrics. 2018; 2: 114-23. [in Russian]. DOI:10.15574/SP.2018.90.114.

View at:

Publisher Site: https://med-expert.com.ua/journals/publishing-activity/sovremennaya-pediatriya/sovremennaja-pediatrija-sp-%E2%84%962-2018/

URL: https://med-expert.com.ua/journals/wp-content/uploads/2018/06/19.pdf

Stoieva TV, Titkova OV, Sytnik VV, Kartashova VO, Synenko VV, Radiuk LP. [Correction of metabolic disorders in secondary acetonemic syndrome on the background of acute respiratory infection in children]. Child's Health. 2018; 13(8): 736-42. [in Russian], DOI: 10.22141/2224-0551.13.8.2018.154153.

View at:

Publisher Site: http://www.mif-ua.com/archive/article/47021

URL: http://childshealth.zaslavsky.com.ua/article/view/154153

Williams MR, Greene G, Naik G, Hughes K, Butler CC, Hay AD. Antibiotic prescribing quality for children in primary care: an observational study. British Journal of General Practice. 2018; 68(667): e90-e96. DOI: 10.3399/bjgp18X694409

View at:

Publisher Site: https://bjgp.org/content/68/667/e90

PubMed: https://pubmed.ncbi.nlm.nih.gov/29335323/

PubMed Central: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774968/

O'Connor R, O'Doherty J, O'Regan A, Dunne C. Antibiotic use for acute respiratory tract infections (ARTI) in primary care; what factors affect prescribing and why is it important? A narrative review. Ir J Med Sci. 2018; 187(4): 969-86. DOI: 0.1007/s11845-018-1774-5

View at:

Publisher Site: https://link.springer.com/article/10.1007%2Fs11845-018-1774-5

PubMed: https://pubmed.ncbi.nlm.nih.gov/29532292/

PubMed Central: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209023/

Zoorob R, Sidani MA, Fremont RD, Kihlberg C. Antibiotic use in acute upper respiratory tract infections. Am Fam Physician. 2012; 86(9): 817-22.

View at:

PubMed: https://pubmed.ncbi.nlm.nih.gov/23113461/

FAO/WHO. Guidelines for the Evaluation of Probiotics in Food. 2002.

View at:

Publisher Site: https://www.who.int/foodsafety/fs_management/en/probiotic_guidelines.pdf.

Feleszko W, Marengo R, Vieira AS, Ratajczak K, Mayorga Butrón JL. Immunity-targeted approaches to the management of chronic and recurrent upper respiratory tract disorders in children. Clinical Otolaryngology. 2019; 44(4): 502-10. DOI: 10.1111/coa.13335.

View at:

Publisher Site: ps://onlinelibrary.wiley.com/doi/10.1111/coa.13335

PubMed: https://pubmed.ncbi.nlm.nih.gov/30920131/

PubMed Central: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850198/

Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014; 11(8): 506-14. DOI: 10.1038/nrgastro.2014.66

View at:

Publisher Site: https://www.nature.com/articles/nrgastro.2014.66

PubMed: https://pubmed.ncbi.nlm.nih.gov/24912386/

Li L, Wang F, Liu Y, Gu F. Intestinal microbiota dysbiosis in children with recurrent respiratory tract infections. Microb Pathog. 2019; 136: 103709. DOI: 10.1016/j.micpath.2019.103709

View at:

Publisher Site: https://linkinghub.elsevier.com/retrieve/pii/S0882401019307867

PubMed: https://pubmed.ncbi.nlm.nih.gov/31494301/

Azad MAK, Sarker M, Wan D. Immunomodulatory Effects of Probiotics on Cytokine Profiles. Biomed Res Int. 2018: 8063647. DOI: 10.1155/2018/8063647

View at:

Publisher Site: https://www.hindawi.com/journals/bmri/2018/8063647/

Luo A, Leach ST, Barres R, Hesson LB, Grimm MC, Simar D. The Microbiota and Epigenetic Regulation of T Helper 17/Regulatory T Cells: In Search of a Balanced Immune System. Front Immunol. 2017; 8: 417. DOI: 10.3389/fimmu.2017.00417

View at:

Publisher Site: https://www.frontiersin.org/articles/10.3389/fimmu.2017.00417/full

PubMed: https://pubmed.ncbi.nlm.nih.gov/28443096/

PubMed Central: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385369/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385369/

Hao Q, Dong BR, Wu T. Probiotics for preventing acute upper respiratory tract infections. Cochrane Database Syst Rev. 2015; (2): Cd006895. DOI: 10.1002/14651858.CD006895.pub3

View at:

Publisher Site: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006895.pub3/full

PubMed: https://pubmed.ncbi.nlm.nih.gov/25927096/

King S, Glanville J, Sanders ME, Fitzgerald A, Varley D. Effectiveness of probiotics on the duration of illness in healthy children and adults who develop common acute respiratory infectious conditions: a systematic review and meta-analysis. Br J Nutr. 2014; 112(1): 41-54. DOI: 10.1017/s0007114514000075

View at:

Publisher Site: https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/effectiveness-of-probiotics-on-the-duration-of-illness-in-healthy-children-and-adults-who-develop-common-acute-respiratory-infectious-conditions-a-systematic-review-and-metaanalysis/4382D42135F5C78FFA96E5F4C581944D

PubMed: https://pubmed.ncbi.nlm.nih.gov/24780623/

PubMed Central: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4054664/

Ozen M, Kocabas Sandal G, Dinleyici EC. Probiotics for the prevention of pediatric upper respiratory tract infections: a systematic review. Expert Opin Biol Ther. 2015; 15(1): 9-20. DOI: 10.1517/14712598.2015.980233

View at:

Publisher Site: https://www.tandfonline.com/doi/abs/10.1517/14712598.2015.980233?journalCode=iebt20

PubMed: https://pubmed.ncbi.nlm.nih.gov/25430686/

Wang Y, Li X, Ge T, Xiao Y, Liao Y, Cui Y, Zhang Y, Ho W, Yu G, Zhang T. Probiotics for prevention and treatment of respiratory tract infections in children: A systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2016; 95: e4509. DOI: 10.1097/md.0000000000004509

View at:

Publisher Site: https://journals.lww.com/md-journal/Fulltext/2016/08020/Probiotics_for_prevention_and_treatment_of.90.aspx

PubMed: https://pubmed.ncbi.nlm.nih.gov/27495104/

PubMed Central: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979858/

Cazzola M, Pham-Thi N, Kerihuel JC, Durand H, Bohbot S. Efficacy of a synbiotic supplementation in the prevention of common winter diseases in children: a randomized, double-blind, placebo-controlled pilot study. Ther Adv Respir Dis. 2010. 4: 271-8. DOI: 10.1177/1753465810379010

View at:

Publisher Site: https://journals.sagepub.com/doi/10.1177/1753465810379010

PubMed: https://pubmed.ncbi.nlm.nih.gov/20729255/

PubMed Central:

Cazzola M, Tompkins TA, Matera MG. Immunomodulatory impact of a synbiotic in T(h)1 and T(h)2 models of infection. Ther Adv Respir Dis. 2010; 4(5): 259-70. DOI: 10.1177/1753465810379009

View at:

Publisher Site: https://journals.sagepub.com/doi/10.1177/1753465810379009

PubMed: https://pubmed.ncbi.nlm.nih.gov/20929951/

MacPherson C, Audy J, Mathieu O, Tompkins TA. Multistrain Probiotic Modulation of Intestinal Epithelial Cells' Immune Response to a Double-Stranded RNA Ligand, Poly(I·C). Appl Environ Microbiol. 2014; 80(5): 1692-700. DOI: 10.1128/aem.03411-13

View at:

Publisher Site: https://journals.asm.org/doi/10.1128/AEM.03411-13

PubMed: https://pubmed.ncbi.nlm.nih.gov/24375132/

PubMed Central: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3957618/

MacPherson CW, Shastri P, Mathieu O, Tompkins TA, Burguière P. Genome-Wide Immune Modulation of TLR3-Mediated Inflammation in Intestinal Epithelial Cells Differs between Single and Multi-Strain Probiotic Combination. PLoS One. 2017; 12(1):e0169847. DOI:10.1371/journal.pone.0169847

View at:

Publisher Site: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0169847

PubMed: https://pubmed.ncbi.nlm.nih.gov/28099447/

PubMed Central: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242491/

Stojković A, Simović A, Bogdanović Z, Banković D, Poskurica M. Clinical trial/experimental study (consort compliant): Optimal time period to achieve the effects on synbiotic-controlled wheezing and respiratory infections in young children. Srp Arh Celok Lek. 2016; 144(1-2): 38-45. DOI: 10.2298/sarh1602038s.

View at:

Publisher Site: http://www.doiserbia.nb.rs/Article.aspx?ID=0370-81791602038S#.YT7F850zZPY

PubMed: https://pubmed.ncbi.nlm.nih.gov/27276856/

Karpova EP, Zaplatnikov AL, Tulupov DA. [Immunoprophylaxis of infections of the upper respiratory tract in the frequently ill children]. Vestn Otorinolaringol. 2015; 80: 80-84. [in Russian]. DOI: 10.17116/otorino201580580-84

View at:

Publisher Site: https://www.mediasphera.ru/issues/vestnik-otorinolaringologii/2015/5/

Publisher Site: https://www.mediasphera.ru/issues/vestnik-otorinolaringologii/2015/5/030042-466820150517

URL: https://www.mediasphera.ru/issues/vestnik-otorinolaringologii/2015/5/downloads/ru/030042-466820150517

Altman DG. Statistics and ethics in medical research. Misuse of statistics is unethical. Br Med J. 1980; 281(6249): 1182-4. DOI: 10.1136/bmj.281.6249.1182

View at:

Publisher Site: https://www.bmj.com/content/281/6249/1182

PubMed: https://pubmed.ncbi.nlm.nih.gov/7427629/

PubMed Central: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1714517/

Gerasimov SV, Ivantsiv VA, Bobryk LM, Tsitsura OO, Dedyshin LP, Guta NV, Yandyo BV. Role of short-term use of L. acidophilus DDS-1 and B. lactis UABLA-12 in acute respiratory infections in children: a randomized controlled trial. Eur J Clin Nutr. 2016; 70(4): 463-9. DOI: 10.1038/ejcn.2015.171

View at:

Publisher Site: https://www.nature.com/articles/ejcn2015171

PubMed: https://pubmed.ncbi.nlm.nih.gov/26463725/

De Andres J, Manzano S, Garcia C, Rodriguez JM, Espinosa-Martos I, Jimenez E. Modulatory effect of three probiotic strains on infants' gut microbial composition and immunological parameters on a placebo-controlled, double-blind, randomised study. Benef Microbes. 2018; 9(4): 573-584. DOI: 10.3920/bm2017.0132

View at:

Publisher Site: https://www.wageningenacademic.com/doi/10.3920/BM2017.0132

PubMed: https://pubmed.ncbi.nlm.nih.gov/29726280/

Manzano S, De Andres J, Castro I, Rodriguez JM, Jimenez E, Espinosa-Martos I. Safety and tolerance of three probiotic strains in healthy infants: a multi-centre randomized, double-blind, placebo-controlled trial. Benef Microbes. 2017; 8(4): 569-78. DOI: 10.3920/bm2017.0009

View at:

Publisher Site: https://www.wageningenacademic.com/doi/10.3920/BM2017.0009

PubMed: https://pubmed.ncbi.nlm.nih.gov/28555502/

Pantović F. Serum immunoglobulin levels in children with respiratory infections who used a synbiotic dietary supplement. PONS Medical Journal. 2013; 10(1): 7-11.

View at:

URL: https://scindeks-clanci.ceon.rs/data/pdf/1820-2411/2013/1820-24111301007P.pdf

Dykstra NS, Hyde L, Adawi D, Kulik D, Ahrne S, Molin G, Jeppsson B, MacKenzie A, Mack DR. Pulse probiotic administration induces repeated small intestinal Muc3 expression in rats. Pediatr Res. 2011; 69(3): 206-11. DOI: 10.1203/PDR.0b013e3182096ff0.

View at:

Publisher Site: https://www.nature.com/articles/pr9201140

PubMed: https://pubmed.ncbi.nlm.nih.gov/21135754/

Godwin NS, Hyde L, Mack DR. Intestinal mucin gene modulation in vivo using orally administered probiotic bacteria: 212. Journal of Pediatric Gastroenterology and Nutrition. 2005; 41(4): 558-9. DOI: 10.1097/01.mpg.0000182068.89890.95

View at:

Publisher Site: https://journals.lww.com/jpgn/toc/2005/10000

Publisher Site:: https://journals.lww.com/jpgn/Fulltext/2005/10000/INTESTINAL_MUCIN_GENE_MODULATION_IN_VIVO_USING.235.aspx

Semanticscholar: https://www.semanticscholar.org/paper/INTESTINAL-MUCIN-GENE-MODULATION-IN-VIVO-USING-212-Godwin-Hyde/adca85be9a5ae7573cdd0e89125797f0d31e0107

Ho NK, Hawley SP, Ossa JC, Mathieu O, Tompkins TA, Johnson-Henry KC, Sherman PM. Immune signalling responses in intestinal epithelial cells exposed to pathogenic Escherichia coli and lactic acid-producing probiotics. Benef Microbes. 2013; 4(2): 195-209. DOI: 10.3920/BM2012.0038

View at:

Publisher Site: https://www.wageningenacademic.com/doi/10.3920/BM2012.0038

PubMed: https://pubmed.ncbi.nlm.nih.gov/23443951/

Kuugbee ED, Shang X, Gamallat Y, Bamba D, Awadasseid A, Suliman MA, Zang S, Ma Y, Chiwala G, Xin Y, Shang D. Structural Change in Microbiota by a Probiotic Cocktail Enhances the Gut Barrier and Reduces Cancer via TLR2 Signaling in a Rat Model of Colon Cancer. Dig Dis Sci. 2016; 61(10): 2908-20. DOI: 10.1007/s10620-016-4238-7

View at:

Publisher Site: https://link.springer.com/article/10.1007%2Fs10620-016-4238-7

PubMed: https://pubmed.ncbi.nlm.nih.gov/27384052/

Easo JG, Measham MJ, Munroe J, Green-Johnson JM. Immunostimulatory Actions of Lactobacilli: Mitogenic induction of antibody production and spleen cell proliferation by Lactobacillus delbrueckii subsp. bulgaricus and Lactobacillus acidophil. Food and Agricultural Immunology. 2002; 14(1):73-83. DOI:10.1080/09540100220137682

View at:

Publisher Site: https://www.tandfonline.com/doi/abs/10.1080/09540100220137682

Europe PMC: http://europepmc.org/article/AGR/IND23279609

Chen L, Ouyang L, Liao W, Zhang W. Mucous membrane immunity enhanced by taking Biostime probiotics. Chinese Journal of Microecology. 2007; 2: 137-41.

View at:

Publisher Site: https://www.oriprobe.com/journals/zgwstxzz/2007_2.html

URL: http://caod.oriprobe.com/articles/12048652/Mucous_membrane_immunity_enhanced_by_taking_Biostime_probiotics.htm

Semantic scholar: https://www.semanticscholar.org/paper/Mucous-membrane-immunity-enhanced-by-taking-Wen-hui/403b05f76a5a06fa9c7da6c56ca86193fb6ac05b

Peng L, Liang Y, Ming Z. Observation on the efficacy of Montmorillonite Powder and Synbiotics Probiotics for Children non-infectious diarrhea. Hebei Medical Journal. 2015; 12: 1846-7.

View at:

Publisher Site: https://www.oriprobe.com/journals/hbyy/2015_12.html

URL: http://caod.oriprobe.com/articles/46223681/meng_tuo_shi_san_yu_he_sheng_yuan_yi_sheng_jun_lian_he_zhi_liao_xiao_e.htm

Xiao L, Gong C, Ding Y, Ding G, Xu X, Deng C, Ze X, Malard P, Ben X. Probiotics maintain intestinal secretory immunoglobulin A levels in healthy formula-fed infants: a randomised, double-blind, placebo-controlled study. Benef Microbes. 2019;10(7): 729-39. DOI: 10.3920/BM2019.0025

View at:

Publisher Site: https://www.wageningenacademic.com/doi/10.3920/BM2019.0025

PubMed: https://pubmed.ncbi.nlm.nih.gov/31965842/

Denny FW. Jr. The clinical impact of human respiratory virus infections. Am J Respir Crit Care Med. 1995; 152(4 Pt 2): S4-12. DOI: 10.1164/ajrccm/152.4_Pt_2.S4

View at:

Publisher Site: https://www.atsjournals.org/doi/abs/10.1164/ajrccm/152.4_Pt_2.S4

PubMed: https://pubmed.ncbi.nlm.nih.gov/7551411/

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.