{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:24:53Z","timestamp":1792797893161,"version":"4.5.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T00:00:00Z","timestamp":1698105600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T00:00:00Z","timestamp":1698105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100012352","name":"Universit\u00e0 degli Studi di Milano","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012352","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Pediatr"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic adenoiditis (CA) is generally sustained by some infectious foci mainly located within the nasopharynx or in the deep adenoidal pads and it is characterized by a complex interplay between bacterial species. The aim of this study was to assess the efficacy and safety of the topical nasal administration of a probiotic compound based on <jats:italic>S. salivarius<\/jats:italic> 24SMB and <jats:italic>S. oralis<\/jats:italic> 89a in children with CA in terms of reduction in: the number of acute adenoidal infections (primary outcome), and in the blockage of the nasopharynx space by hypertrophic adenoids (secondary outcome). A prospective, double-blind, 1:1 randomized controlled study was performed to test the effectiveness of a 90-day treatment with Rinogermina spray (DMD ITALIA s.r.l, Rome), 1 puff each nostril twice a day for 90\u00a0days, to nasal spray placebo in children with CA (in terms of number of acute exacerbations and blockage of nasopharynx space assessed after 90\u00a0days of treatment- T1, and 90\u00a0days later- T2). The final analysis was based on 152 children (males\u2009=\u200948.0%; mean age\u2009=\u200949.2\u2009\u00b1\u200914.1\u00a0months). Compared to the baseline, no significant differences in terms of number of acute exacerbations at T1 and T2 follow-up visits were detected in both groups. After treatment, a significant reduction in the blockage of nasopharynx space by hypertrophic adenoids (0.002\u2009&lt;\u2009<jats:italic>p<\/jats:italic>-value\u2009&lt;\u20090.007) compared to the baseline was attested in the study group at T1 and T2, but not in the control group.<\/jats:p><jats:p><jats:italic>Conclusions<\/jats:italic>: Our findings document a positive effect of Rinogermina spray in achieving reduction in the blockage of nasopharynx space by hypertrophic adenoids, thus suggesting that its use into the integrated therapeutic management of children with CA could be of a certain utility.\n<jats:table-wrap><jats:table><jats:tbody>\n                    <jats:tr>\n                      <jats:td colspan=\"2\"><jats:bold>What is Known:<\/jats:bold><jats:italic>\u2022 Chronic adenoiditis in children results from an imablance in baterial homeostasis at the nasophaynx, with impairment in respiratory microbiota.<\/jats:italic><jats:italic>\u2022 The modulatory effect of target transnasal bacteriotheray by means of S. salivarius has been considered in children with chronic adenoiditis in children with recurrent acute otitis media with preliminary positive results.<\/jats:italic><\/jats:td>\n                    <\/jats:tr>\n                    <jats:tr>\n                      <jats:td colspan=\"2\"><jats:bold>What is New:<\/jats:bold><jats:italic>\u2022 This randomized controlled study, specifically designed on a cohrt of children with chronic adenoiditis, documents a certain effectiveness of the probiotic treatment in achieving a reduction in the grade of adenoidal hypertropy, compared to placebo.<\/jats:italic><\/jats:td>\n                    <\/jats:tr>\n                  <\/jats:tbody><\/jats:table><\/jats:table-wrap><\/jats:p>","DOI":"10.1007\/s00431-023-05192-w","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T12:02:48Z","timestamp":1698148968000},"page":"289-294","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Topical administration of S. salivarius 24SMB-S. oralis 89a in children with adenoidal disease: a double-blind controlled trial"],"prefix":"10.1007","volume":"183","author":[{"given":"Francesco","family":"Folino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Di Pasquale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Marchisio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Pignataro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Capaccio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Gaini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovica","family":"Battilocchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Bosis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Torretta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,10,24]]},"reference":[{"key":"5192_CR1","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-009-0068-4","author":"GL Marseglia","year":"2009","unstructured":"Marseglia GL, Poddighe D, Caimmi D, Marseglia A, Caimmi S, Ciprandi G, Klersy C, Pagella F, Castellazzi AM (2009) Role of adenoids and adenoiditis in children with allergy and otitis media. Curr Allergy Asthma Rep. https:\/\/doi.org\/10.1007\/s11882-009-0068-4. PMID: 19814919","journal-title":"Curr Allergy Asthma Rep"},{"key":"5192_CR2","unstructured":"Mansbach AL, Brihaye P, Casimir G, Dhooghe I, Gordts F, Halewyck S, Hanssens L, Lemkens N, Lemkens P, Leupe P, Mulier S, Van Crombrugge L, Van Der Veken P, Van Hoecke H (2012) Clinical aspects of chronic ENT inflammation in children. B-ENT.;8 Suppl 19:83\u2013101"},{"key":"5192_CR3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0463.2011.02846.x","author":"L Drago","year":"2012","unstructured":"Drago L, De Vecchi E, Torretta S, Mattina R, Marchisio P, Pignataro L (2012) Biofilm formation by bacteria isolated from upper respiratory tract before and after adenotonsillectomy. APMIS. https:\/\/doi.org\/10.1111\/j.1600-0463.2011.02846.x","journal-title":"APMIS"},{"issue":"3","key":"5192_CR4","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1007\/s10096-014-2261-1","volume":"34","author":"E Nazzari","year":"2015","unstructured":"Nazzari E, Torretta S, Pignataro L, Marchisio P, Esposito S (2015) Role of biofilm in children with recurrent upper respiratory tract infections. Eur J Clin Microbiol Infect Dis 34(3):421\u2013429. https:\/\/doi.org\/10.1007\/s10096-014-2261-1. Epub 2014 Oct 16 PMID: 25318897","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"5192_CR5","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8050671","author":"S Torretta","year":"2019","unstructured":"Torretta S, Drago L, Marchisio P, Ibba T, Pignataro L (2019) Role of biofilms in children with chronic adenoiditis and middle ear disease. J Clin Med. https:\/\/doi.org\/10.3390\/jcm8050671. PMID: 31086039","journal-title":"J Clin Med"},{"key":"5192_CR6","doi-asserted-by":"publisher","DOI":"10.1111\/apm.12254","author":"L Drago","year":"2014","unstructured":"Drago L, Cappelletti L, De Vecchi E, Pignataro L, Torretta S, Mattina R (2014) Antiadhesive and antibiofilm activity of hyaluronic acid against bacteria responsible for respiratory tract infections. APMIS. https:\/\/doi.org\/10.1111\/apm.12254","journal-title":"APMIS"},{"key":"5192_CR7","doi-asserted-by":"publisher","unstructured":"Torretta S, Marchisio P, Drago L, Baggi E, De Vecchi E, Garavello W, Nazzari E, Pignataro L, Esposito S (2012) Nasopharyngeal biofilm-producing otopathogens in children with nonsevere recurrent acute otitis media. Otolaryngol Head Neck Surg.\u00a0https:\/\/doi.org\/10.1177\/0194599812438169. Epub 2012 Feb 21.PMID:\u00a022357644","DOI":"10.1177\/0194599812438169"},{"key":"5192_CR8","doi-asserted-by":"publisher","DOI":"10.1177\/0194599810394955","author":"S Torretta","year":"2011","unstructured":"Torretta S, Drago L, Marchisio P, Mattina R, Clemente IA, Pignataro L (2011) Diagnostic accuracy of nasopharyngeal swabs in detecting biofilm-producing bacteria in chronic adenoiditis: a preliminary study. Otolaryngol Head Neck Surg. https:\/\/doi.org\/10.1177\/0194599810394955. PMID: 21493370","journal-title":"Otolaryngol Head Neck Surg"},{"key":"5192_CR9","doi-asserted-by":"publisher","DOI":"10.1177\/000348941312200206","author":"S Torretta","year":"2013","unstructured":"Torretta S, Drago L, Marchisio P, Gaffuri M, Clemente IA, Pignataro L (2013) Topographic distribution of biofilm-producing bacteria in adenoid subsites of children with chronic or recurrent middle ear infections. Ann Otol Rhinol Laryngol. https:\/\/doi.org\/10.1177\/000348941312200206. PMID: 23534125","journal-title":"Ann Otol Rhinol Laryngol"},{"key":"5192_CR10","doi-asserted-by":"publisher","DOI":"10.1038\/ni1526","author":"EG Pamer","year":"2007","unstructured":"Pamer EG (2007) Immune responses to commensal and environmental microbes. Nat Immunol. https:\/\/doi.org\/10.1038\/ni1526. PMID: 17952042","journal-title":"Nat Immunol"},{"key":"5192_CR11","doi-asserted-by":"publisher","unstructured":"Folino F, Ruggiero L, Capaccio P, Coro I, Aliberti S, Drago L, Marchisio P,\u00a0Torretta S (2020) Upper respiratory tract microbiome and otitis media intertalk: lessons from the literature..J Clin Med 9(9):2845. https:\/\/doi.org\/10.3390\/jcm9092845. PMID:\u00a032887458","DOI":"10.3390\/jcm9092845"},{"key":"5192_CR12","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000002895","author":"F Folino","year":"2021","unstructured":"Folino F, Fattizzo M, Ruggiero L, Oriano M, Aliberti S, Blasi F, Gaffuri M, Marchisio P, Torretta S (2021) Nasopharyngeal microbiota analysis in healthy and otitis-prone children: focus on history of spontaneous tympanic membrane perforation. Pediatr Infect Dis J. https:\/\/doi.org\/10.1097\/INF.0000000000002895","journal-title":"Pediatr Infect Dis J"},{"key":"5192_CR13","doi-asserted-by":"publisher","unstructured":"Jensen A, Fag\u00f6-Olsen H, S\u00f8rensen CH, Kilian M (2013) Molecular mapping to species level of the tonsillar crypt microbiota associated with health and recurrent tonsillitis. PLoS One.\u00a0https:\/\/doi.org\/10.1371\/journal.pone.0056418","DOI":"10.1371\/journal.pone.0056418"},{"key":"5192_CR14","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2006.037309","author":"A Swidsinski","year":"2007","unstructured":"Swidsinski A, G\u00f6ktas O, Bessler C, Loening-Baucke V, Hale LP, Andree H, Weizenegger M, H\u00f6lzl M, Scherer H, Lochs H (2007) Spatial organisation of microbiota in quiescent adenoiditis and tonsillitis. J Clin Pathol. https:\/\/doi.org\/10.1136\/jcp.2006.037309","journal-title":"J Clin Pathol"},{"key":"5192_CR15","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis024","author":"M Hilty","year":"2012","unstructured":"Hilty M, Qi W, Brugger SD, Frei L, Agyeman P, Frey PM, Aebi S, M\u00fchlemann K (2012) Nasopharyngeal microbiota in infants with acute otitis media. J Infect Dis. https:\/\/doi.org\/10.1093\/infdis\/jis024","journal-title":"J Infect Dis"},{"key":"5192_CR16","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-015-2491-x","author":"P Marchisio","year":"2015","unstructured":"Marchisio P, Santagati M, Scillato M, Baggi E, Fattizzo M, Rosazza C, Stefani S, Esposito S, Principi N (2015) Streptococcus salivarius 24SMB administered by nasal spray for the prevention of acute otitis media in otitis-prone children. Eur J Clin Microbiol Infect Dis. https:\/\/doi.org\/10.1007\/s10096-015-2491-x","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"5192_CR17","doi-asserted-by":"publisher","DOI":"10.23736\/S0026-4946.18.05182-4","author":"F Di Pierro","year":"2018","unstructured":"Di Pierro F, Risso P, Poggi E, Timitilli A, Bolloli S, Bruno M, Caneva E, Campus R, Giannattasio A (2018) Use of Streptococcus salivarius K12 to reduce the incidence of pharyngo-tonsillitis and acute otitis media in children: a retrospective analysis in not-recurrent pediatric subjects. Minerva Pediatr. https:\/\/doi.org\/10.23736\/S0026-4946.18.05182-4","journal-title":"Minerva Pediatr"},{"key":"5192_CR18","unstructured":"Di Pierro F, Colombo M, Giuliani MG, Danza ML, Basile I, Bollani T, Conti AM, Zanvit A, Rottoli AS (2016) Effect of administration of Streptococcus salivarius K12 on the occurrence of streptococcal pharyngo-tonsillitis, scarlet fever and acute otitis media in 3 years old children.Eur Rev Med Pharmacol Sci 20(21):4601\u20134606"},{"key":"5192_CR19","doi-asserted-by":"publisher","unstructured":"Gregori G, Righi O, Risso P, Boiardi G, Demuru G, Ferzetti A, Galli A, Ghisoni M, Lenzini S, Marenghi C, Mura C, Sacchetti R, Suzzani L (2016) Reduction of group A beta-hemolytic streptococcus pharyngo-tonsillar infections associated with use of the oral probiotic Streptococcus salivarius K12: a retrospective observational study. Ther Clin Risk Manag. https:\/\/doi.org\/10.2147\/TCRM.S96134","DOI":"10.2147\/TCRM.S96134"},{"key":"5192_CR20","doi-asserted-by":"publisher","unstructured":"Tano K, Olofsson C, Grahn-H\u00e5kansson E, Holm SE (1999) In vitro inhibition of S. pneumoniae, nontypable H. influenzae and M. catharralis by alpha-hemolytic streptococci from healthy children.Int J Pediatr Otorhinolaryngol. https:\/\/doi.org\/10.1016\/s0165-5876(98)00174-8","DOI":"10.1016\/s0165-5876(98)00174-8"},{"key":"5192_CR21","doi-asserted-by":"publisher","unstructured":"La Mantia I, Varricchio A, Di Girolamo S, Minni A, Passali GC, Ciprandi G (2019) The role of bacteriotherapy in the prevention of adenoidectomy. Eur Rev Med Pharmacol Sci. https:\/\/doi.org\/10.26355\/eurrev_201903_17348","DOI":"10.26355\/eurrev_201903_17348"},{"key":"5192_CR22","doi-asserted-by":"publisher","unstructured":"Karpova EP, Karpycheva IE, Tulupov DA (2015) Prophylaxis of chronic adenoiditis in the children. Vestn Otorinolaringol. https:\/\/doi.org\/10.17116\/otorino201580643-45","DOI":"10.17116\/otorino201580643-45"},{"key":"5192_CR23","doi-asserted-by":"publisher","unstructured":"La Mantia I, Varricchio A, Ciprandi G (2017) Bacteriotherapy with Streptococcus salivarius 24SMB and Streptococcus oralis 89a nasal spray for preventing recurrent acute otitis media in children: a real-life clinical experience. Int J Gen Med. https:\/\/doi.org\/10.2147\/IJGM.S137614","DOI":"10.2147\/IJGM.S137614"},{"key":"5192_CR24","doi-asserted-by":"publisher","unstructured":"Burton JP, Chilcott CN, Wescombe PA, Tagg JR (2010) Extended safety data for the oral cavity probiotic Streptococcus salivarius K12. Probiotics Antimicrob Proteins. https:\/\/doi.org\/10.1007\/s12602-010-9045-4","DOI":"10.1007\/s12602-010-9045-4"},{"key":"5192_CR25","doi-asserted-by":"publisher","unstructured":"Burton JP, Cowley S, Simon RR, McKinney J, Wescombe PA, Tagg JR (2011) Evaluation of safety and human tolerance of the oral probiotic Streptococcus salivarius K12: a randomized, placebo-controlled, double-blind study. Food Chem Toxicol. https:\/\/doi.org\/10.1016\/j.fct.2011.06.038","DOI":"10.1016\/j.fct.2011.06.038"},{"key":"5192_CR26","doi-asserted-by":"publisher","unstructured":"Wilcox CR, Stuart B, Leaver H, Lown M, Willcox M, Moore M, Little P (2019) Effectiveness of the probiotic Streptococcus salivarius K12 for the treatment and\/or prevention of sore throat: a systematic review..Clin Microbiol Infect. https:\/\/doi.org\/10.1016\/j.cmi.2018.12.031","DOI":"10.1016\/j.cmi.2018.12.031"},{"key":"5192_CR27","doi-asserted-by":"publisher","unstructured":"Tagg JR, Dierksen KP (2003) Bacterial replacement therapy: adapting \u2018germ warfare\u2019 to infection prevention. Trends Biotechnol. https:\/\/doi.org\/10.1016\/S0167-7799(03)00085-4","DOI":"10.1016\/S0167-7799(03)00085-4"},{"issue":"1","key":"5192_CR28","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s13052-020-0798-4","volume":"46","author":"S Manti","year":"2020","unstructured":"Manti S, Parisi GF, Papale M, Licari A, Salpietro C, Miraglia Del Giudice M, Marseglia GL, Leonardi S (2020) Bacteriotherapy with Streptococcus salivarius 24SMB and Streptococcus oralis 89a nasal spray for treatment of upper respiratory tract infections in children: a pilot study on short-term efficacy. Ital J Pediatr 46(1):42. https:\/\/doi.org\/10.1186\/s13052-020-0798-4","journal-title":"Ital J Pediatr"},{"issue":"1 Suppl","key":"5192_CR29","doi-asserted-by":"publisher","first-page":"67","DOI":"10.26355\/eurrev_201903_17352","volume":"23","author":"D Passali","year":"2019","unstructured":"Passali D, Passali GC, Vesperini E, Cocca S, Visconti IC, Ralli M, Bellussi LM (2019) The efficacy and tolerability of Streptococcus salivarius 24SMB and Streptococcus oralis 89a administered as nasal spray in the treatment of recurrent upper respiratory tract infections in children. Eur Rev Med Pharmacol Sci 23(1 Suppl):67\u201372. https:\/\/doi.org\/10.26355\/eurrev_201903_17352","journal-title":"Eur Rev Med Pharmacol Sci"},{"issue":"1","key":"5192_CR30","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1186\/s12879-018-3576-9","volume":"18","author":"A Bidossi","year":"2018","unstructured":"Bidossi A, De Grandi R, Toscano M, Bottagisio M, De Vecchi E, Gelardi M, Drago L (2018) Probiotics Streptococcus salivarius 24SMB and Streptococcus oralis 89a interfere with biofilm formation of pathogens of the upper respiratory tract. BMC Infect Dis 18(1):653. https:\/\/doi.org\/10.1186\/s12879-018-3576-9","journal-title":"BMC Infect Dis"}],"container-title":["European Journal of Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00431-023-05192-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00431-023-05192-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00431-023-05192-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T05:13:47Z","timestamp":1707455627000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00431-023-05192-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,24]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["5192"],"URL":"https:\/\/doi.org\/10.1007\/s00431-023-05192-w","relation":{},"ISSN":["1432-1076"],"issn-type":[{"value":"1432-1076","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,24]]},"assertion":[{"value":"23 May 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 September 2023","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 September 2023","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 October 2023","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The protocol was approved by the Ethics Committee \u201cMilano Area 2\u201d (protocol number AC-TAR-2018) on September 10, 2018, and the research was carried out in line with standard directives from the Ethics Committee \u201cMilano Area 2.\u201d","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"ST: advisor for Sanofi and GSK. All other authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}