Oral Bacterial Extract for the Prevention of Wheezing Lower Respiratory Tract Illness

Summary

The primary objective of this study is to evaluate if Broncho-Vaxom® given to high risk infants for 10 days, monthly, for two consecutive years can increase time to occurrence of the first episode of wheezing lower respiratory tract illness (WLRI) during a three year observation period off therapy.

Timeline

Start

2017-01-01

Primary completion

2026-01-30

Completion

2026-01-30

Publications

• Background Ahanchian H, Jones CM, Chen YS, Sly PD. Respiratory viral infections in children with asthma: do they matter and can we prevent them? BMC Pediatr. 2012 Sep 13;12:147. doi: 10.1186/1471-2431-12-147.
• Background Azad MB, Coneys JG, Kozyrskyj AL, Field CJ, Ramsey CD, Becker AB, Friesen C, Abou-Setta AM, Zarychanski R. Probiotic supplementation during pregnancy or infancy for the prevention of asthma and wheeze: systematic review and meta-analysis. BMJ. 2013 Dec 4;347:f6471. doi: 10.1136/bmj.f6471.
• Background Becker A, Watson W, Ferguson A, Dimich-Ward H, Chan-Yeung M. The Canadian asthma primary prevention study: outcomes at 2 years of age. J Allergy Clin Immunol. 2004 Apr;113(4):650-6. doi: 10.1016/j.jaci.2004.01.754.
• Background Beydon N, Davis SD, Lombardi E, Allen JL, Arets HG, Aurora P, Bisgaard H, Davis GM, Ducharme FM, Eigen H, Gappa M, Gaultier C, Gustafsson PM, Hall GL, Hantos Z, Healy MJ, Jones MH, Klug B, Lodrup Carlsen KC, McKenzie SA, Marchal F, Mayer OH, Merkus PJ, Morris MG, Oostveen E, Pillow JJ, Seddon PC, Silverman M, Sly PD, Stocks J, Tepper RS, Vilozni D, Wilson NM; American Thoracic Society/European Respiratory Society Working Group on Infant and Young Children Pulmonary Function Testing. An official American Thoracic Society/European Respiratory Society statement: pulmonary function testing in preschool children. Am J Respir Crit Care Med. 2007 Jun 15;175(12):1304-45. doi: 10.1164/rccm.200605-642ST. No abstract available.
• Background Bisgaard H, Hermansen MN, Buchvald F, Loland L, Halkjaer LB, Bonnelykke K, Brasholt M, Heltberg A, Vissing NH, Thorsen SV, Stage M, Pipper CB. Childhood asthma after bacterial colonization of the airway in neonates. N Engl J Med. 2007 Oct 11;357(15):1487-95. doi: 10.1056/NEJMoa052632.
• Background Bluestone JA, Auchincloss H, Nepom GT, Rotrosen D, St Clair EW, Turka LA. The Immune Tolerance Network at 10 years: tolerance research at the bedside. Nat Rev Immunol. 2010 Nov;10(11):797-803. doi: 10.1038/nri2869.
• Background Bousquet J, Anto J, Auffray C, Akdis M, Cambon-Thomsen A, Keil T, Haahtela T, Lambrecht BN, Postma DS, Sunyer J, Valenta R, Akdis CA, Annesi-Maesano I, Arno A, Bachert C, Ballester F, Basagana X, Baumgartner U, Bindslev-Jensen C, Brunekreef B, Carlsen KH, Chatzi L, Crameri R, Eveno E, Forastiere F, Garcia-Aymerich J, Guerra S, Hammad H, Heinrich J, Hirsch D, Jacquemin B, Kauffmann F, Kerkhof M, Kogevinas M, Koppelman GH, Kowalski ML, Lau S, Lodrup-Carlsen KC, Lopez-Botet M, Lotvall J, Lupinek C, Maier D, Makela MJ, Martinez FD, Mestres J, Momas I, Nawijn MC, Neubauer A, Oddie S, Palkonen S, Pin I, Pison C, Rance F, Reitamo S, Rial-Sebbag E, Salapatas M, Siroux V, Smagghe D, Torrent M, Toskala E, van Cauwenberge P, van Oosterhout AJ, Varraso R, von Hertzen L, Wickman M, Wijmenga C, Worm M, Wright J, Zuberbier T. MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine. Allergy. 2011 May;66(5):596-604. doi: 10.1111/j.1398-9995.2010.02534.x. Epub 2011 Jan 24.
• Background Carroll KN, Gebretsadik T, Griffin MR, Wu P, Dupont WD, Mitchel EF, Enriquez R, Hartert TV. Increasing burden and risk factors for bronchiolitis-related medical visits in infants enrolled in a state health care insurance plan. Pediatrics. 2008 Jul;122(1):58-64. doi: 10.1542/peds.2007-2087.
• Background Castro-Rodriguez JA, Holberg CJ, Wright AL, Martinez FD. A clinical index to define risk of asthma in young children with recurrent wheezing. Am J Respir Crit Care Med. 2000 Oct;162(4 Pt 1):1403-6. doi: 10.1164/ajrccm.162.4.9912111.
• Background Collet JP, Ducruet T, Kramer MS, Haggerty J, Floret D, Chomel JJ, Durr F. Stimulation of nonspecific immunity to reduce the risk of recurrent infections in children attending day-care centers. The Epicreche Research Group. Pediatr Infect Dis J. 1993 Aug;12(8):648-52. doi: 10.1097/00006454-199308000-00005.
• Background Del-Rio-Navarro BE, Espinosa Rosales F, Flenady V, Sienra-Monge JJ. Immunostimulants for preventing respiratory tract infection in children. Cochrane Database Syst Rev. 2006 Oct 18;2006(4):CD004974. doi: 10.1002/14651858.CD004974.pub2.
• Background De Prost Y - Clinical Study Report (BV-2002/1) Multicentric, randomized, double-blind, placebo-controlled study of the efficacy and safety of Broncho-Vaxom® (OM-85 BV) in children suffering from atopic dermatitis. - Clinical Study Report (30 January 2008).
• Background Ege MJ, Mayer M, Normand AC, Genuneit J, Cookson WO, Braun-Fahrlander C, Heederik D, Piarroux R, von Mutius E; GABRIELA Transregio 22 Study Group. Exposure to environmental microorganisms and childhood asthma. N Engl J Med. 2011 Feb 24;364(8):701-9. doi: 10.1056/NEJMoa1007302.
• Background Evans SE, Scott BL, Clement CG, Larson DT, Kontoyiannis D, Lewis RE, Lasala PR, Pawlik J, Peterson JW, Chopra AK, Klimpel G, Bowden G, Hook M, Xu Y, Tuvim MJ, Dickey BF. Stimulated innate resistance of lung epithelium protects mice broadly against bacteria and fungi. Am J Respir Cell Mol Biol. 2010 Jan;42(1):40-50. doi: 10.1165/rcmb.2008-0260OC. Epub 2009 Mar 27.
• Background FDA Center for Drug Evaluation and Research (CDER) - Orally Inhaled and Intranasal Corticosteroids: Evaluation of the Effects on Growth in Children. Guidance for Industry: March 2007.
• Background Fernandes RM, Bialy LM, Vandermeer B, Tjosvold L, Plint AC, Patel H, Johnson DW, Klassen TP, Hartling L. Glucocorticoids for acute viral bronchiolitis in infants and young children. Cochrane Database Syst Rev. 2013 Jun 4;2013(6):CD004878. doi: 10.1002/14651858.CD004878.pub4.
• Background Gadomski AM, Brower M. Bronchodilators for bronchiolitis. Cochrane Database Syst Rev. 2010 Dec 8;(12):CD001266. doi: 10.1002/14651858.CD001266.pub2.
• Background Guilbert TW, Morgan WJ, Krawiec M, Lemanske RF Jr, Sorkness C, Szefler SJ, Larsen G, Spahn JD, Zeiger RS, Heldt G, Strunk RC, Bacharier LB, Bloomberg GR, Chinchilli VM, Boehmer SJ, Mauger EA, Mauger DT, Taussig LM, Martinez FD; Prevention of Early Asthma in Kids Study,Childhood Asthma Research and Education Network. The Prevention of Early Asthma in Kids study: design, rationale and methods for the Childhood Asthma Research and Education network. Control Clin Trials. 2004 Jun;25(3):286-310. doi: 10.1016/j.cct.2004.03.002.
• Background Guilbert TW, Morgan WJ, Zeiger RS, Mauger DT, Boehmer SJ, Szefler SJ, Bacharier LB, Lemanske RF Jr, Strunk RC, Allen DB, Bloomberg GR, Heldt G, Krawiec M, Larsen G, Liu AH, Chinchilli VM, Sorkness CA, Taussig LM, Martinez FD. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med. 2006 May 11;354(19):1985-97. doi: 10.1056/NEJMoa051378.
• Background Halterman JS, Aligne CA, Auinger P, McBride JT, Szilagyi PG. Inadequate therapy for asthma among children in the United States. Pediatrics. 2000 Jan;105(1 Pt 3):272-6.
• Background Holt PG, Sly PD, Martinez FD, Weiss ST, Bjorksten B, von Mutius E, Wahn U. Drug development strategies for asthma: in search of a new paradigm. Nat Immunol. 2004 Jul;5(7):695-8. doi: 10.1038/ni0704-695.
• Background Jackson DJ. The role of rhinovirus infections in the development of early childhood asthma. Curr Opin Allergy Clin Immunol. 2010 Apr;10(2):133-8. doi: 10.1097/ACI.0b013e3283352f7c.
• Background Jackson DJ, Gangnon RE, Evans MD, Roberg KA, Anderson EL, Pappas TE, Printz MC, Lee WM, Shult PA, Reisdorf E, Carlson-Dakes KT, Salazar LP, DaSilva DF, Tisler CJ, Gern JE, Lemanske RF Jr. Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children. Am J Respir Crit Care Med. 2008 Oct 1;178(7):667-72. doi: 10.1164/rccm.200802-309OC. Epub 2008 Jun 19.
• Background Juniper EF, Guyatt GH, Feeny DH, Ferrie PJ, Griffith LE, Townsend M. Measuring quality of life in children with asthma. Qual Life Res. 1996 Feb;5(1):35-46. doi: 10.1007/BF00435967.
• Background Klassen AF, Landgraf JM, Lee SK, Barer M, Raina P, Chan HW, Matthew D, Brabyn D. Health related quality of life in 3 and 4 year old children and their parents: preliminary findings about a new questionnaire. Health Qual Life Outcomes. 2003 Dec 22;1:81. doi: 10.1186/1477-7525-1-81.
• Background Kusel MM, de Klerk NH, Kebadze T, Vohma V, Holt PG, Johnston SL, Sly PD. Early-life respiratory viral infections, atopic sensitization, and risk of subsequent development of persistent asthma. J Allergy Clin Immunol. 2007 May;119(5):1105-10. doi: 10.1016/j.jaci.2006.12.669. Epub 2007 Mar 13.
• Background Lau S. What is new in the prevention of atopy and asthma? Curr Opin Allergy Clin Immunol. 2013 Apr;13(2):181-6. doi: 10.1097/ACI.0b013e32835eb7b1.
• Background Maier RM, Palmer MW, Andersen GL, Halonen MJ, Josephson KC, Maier RS, Martinez FD, Neilson JW, Stern DA, Vercelli D, Wright AL. Environmental determinants of and impact on childhood asthma by the bacterial community in household dust. Appl Environ Microbiol. 2010 Apr;76(8):2663-7. doi: 10.1128/AEM.01665-09. Epub 2010 Feb 12.
• Background Mansbach JM, Camargo CA Jr. Respiratory viruses in bronchiolitis and their link to recurrent wheezing and asthma. Clin Lab Med. 2009 Dec;29(4):741-55. doi: 10.1016/j.cll.2009.07.011.
• Background Martinez FD. The connection between early life wheezing and subsequent asthma: The viral march. Allergol Immunopathol (Madr). 2009 Sep-Oct;37(5):249-51. doi: 10.1016/j.aller.2009.06.008.
• Background Martinez FD. New insights into the natural history of asthma: primary prevention on the horizon. J Allergy Clin Immunol. 2011 Nov;128(5):939-45. doi: 10.1016/j.jaci.2011.09.020.
• Background McMahon AW, Levenson MS, McEvoy BW, Mosholder AD, Murphy D. Age and risks of FDA-approved long-acting beta(2)-adrenergic receptor agonists. Pediatrics. 2011 Nov;128(5):e1147-54. doi: 10.1542/peds.2010-1720. Epub 2011 Oct 24.
• Background Mitchell H, Senturia Y, Gergen P, Baker D, Joseph C, McNiff-Mortimer K, Wedner HJ, Crain E, Eggleston P, Evans R 3rd, Kattan M, Kercsmar C, Leickly F, Malveaux F, Smartt E, Weiss K. Design and methods of the National Cooperative Inner-City Asthma Study. Pediatr Pulmonol. 1997 Oct;24(4):237-52. doi: 10.1002/(sici)1099-0496(199710)24:43.0.co;2-h.
• Background Morgan WJ, Crain EF, Gruchalla RS, O'Connor GT, Kattan M, Evans R 3rd, Stout J, Malindzak G, Smartt E, Plaut M, Walter M, Vaughn B, Mitchell H; Inner-City Asthma Study Group. Results of a home-based environmental intervention among urban children with asthma. N Engl J Med. 2004 Sep 9;351(11):1068-80. doi: 10.1056/NEJMoa032097.
• Background Navarro RP, Schaecher KL, Rice GK. Asthma management guidelines: updates, advances, and new options. J Manag Care Pharm. 2007 Aug;13(6 Suppl D):S3-11; quiz S12-3. doi: 10.18553/jmcp.2007.13.s6-d.1.
• Background Navarro S, Cossalter G, Chiavaroli C, Kanda A, Fleury S, Lazzari A, Cazareth J, Sparwasser T, Dombrowicz D, Glaichenhaus N, Julia V. The oral administration of bacterial extracts prevents asthma via the recruitment of regulatory T cells to the airways. Mucosal Immunol. 2011 Jan;4(1):53-65. doi: 10.1038/mi.2010.51. Epub 2010 Sep 1.
• Background NHIS (2011)] National Health Interview Survey Data - Current Asthma Population Estimates. National Center for Health Statistics (NCHS), Centers for Disease Control and Prevention Hyattsville, MD: http://www.cdc.gov/asthma/nhis/2011/data.htm
• Background NHLBI. National Asthma Education and Prevention Program: Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma; NIH Publication Number 08-5846. October 2007.
• Background Parola C, Salogni L, Vaira X, Scutera S, Somma P, Salvi V, Musso T, Tabbia G, Bardessono M, Pasquali C, Mantovani A, Sozzani S, Bosisio D. Selective activation of human dendritic cells by OM-85 through a NF-kB and MAPK dependent pathway. PLoS One. 2013 Dec 30;8(12):e82867. doi: 10.1371/journal.pone.0082867. eCollection 2013.
• Background Principi N - Clinical Study Report (BV-2005/01) Double-Blind, Placebo-Controlled, Randomised Clinical Study of Broncho-Vaxom in Children Suffering from Recurrent Upper Respiratory Tract Infections. - Clinical Study Report (2 October 2012a).
• Background Pasquali C, Salami O, Taneja M, Gollwitzer ES, Trompette A, Pattaroni C, Yadava K, Bauer J, Marsland BJ. Enhanced Mucosal Antibody Production and Protection against Respiratory Infections Following an Orally Administered Bacterial Extract. Front Med (Lausanne). 2014 Oct 30;1:41. doi: 10.3389/fmed.2014.00041. eCollection 2014.
• Background Principi N - Clinical Study Report (EBV09/01) Double-Blind, Placebo-Controlled, Randomised Clinical Study of Broncho-Vaxom® Drops in Children Suffering from Recurrent Respiratory Tract Infections. - Clinical Study Report (23 October 2012b).
• Background Razi CH, Harmanci K, Abaci A, Ozdemir O, Hizli S, Renda R, Keskin F. The immunostimulant OM-85 BV prevents wheezing attacks in preschool children. J Allergy Clin Immunol. 2010 Oct;126(4):763-9. doi: 10.1016/j.jaci.2010.07.038.
• Background Riedler J, Braun-Fahrlander C, Eder W, Schreuer M, Waser M, Maisch S, Carr D, Schierl R, Nowak D, von Mutius E; ALEX Study Team. Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet. 2001 Oct 6;358(9288):1129-33. doi: 10.1016/S0140-6736(01)06252-3.
• Background Schaad UB. OM-85 BV, an immunostimulant in pediatric recurrent respiratory tract infections: a systematic review. World J Pediatr. 2010 Feb;6(1):5-12. doi: 10.1007/s12519-010-0001-x. Epub 2010 Feb 9.
• Background Sigurs N, Bjarnason R, Sigurbergsson F, Kjellman B. Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7. Am J Respir Crit Care Med. 2000 May;161(5):1501-7. doi: 10.1164/ajrccm.161.5.9906076.
• Background Sly PD, Kusel M, Holt PG. Do early-life viral infections cause asthma? J Allergy Clin Immunol. 2010 Jun;125(6):1202-5. doi: 10.1016/j.jaci.2010.01.024. Epub 2010 Mar 20.
• Background Spertini F - Clinical Study Report (BV-2007/03) Efficacy of Broncho-Vaxom® in Allergic Rhinitis: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Study. - Clinical Study Report (31 July 2009)
• Background Strickland DH, Holt PG. T regulatory cells in childhood asthma. Trends Immunol. 2011 Sep;32(9):420-7. doi: 10.1016/j.it.2011.06.010. Epub 2011 Jul 27.
• Background Strickland DH, Judd S, Thomas JA, Larcombe AN, Sly PD, Holt PG. Boosting airway T-regulatory cells by gastrointestinal stimulation as a strategy for asthma control. Mucosal Immunol. 2011 Jan;4(1):43-52. doi: 10.1038/mi.2010.43. Epub 2010 Jul 28.
• Background Thorburn K, Harigopal S, Reddy V, Taylor N, van Saene HK. High incidence of pulmonary bacterial co-infection in children with severe respiratory syncytial virus (RSV) bronchiolitis. Thorax. 2006 Jul;61(7):611-5. doi: 10.1136/thx.2005.048397. Epub 2006 Mar 14.
• Background Tuvim MJ, Evans SE, Clement CG, Dickey BF, Gilbert BE. Augmented lung inflammation protects against influenza A pneumonia. PLoS One. 2009;4(1):e4176. doi: 10.1371/journal.pone.0004176. Epub 2009 Jan 12.
• Background von Mutius E, Vercelli D. Farm living: effects on childhood asthma and allergy. Nat Rev Immunol. 2010 Dec;10(12):861-8. doi: 10.1038/nri2871. Epub 2010 Nov 9.
• Background Wildfire JJ, Gergen PJ, Sorkness CA, Mitchell HE, Calatroni A, Kattan M, Szefler SJ, Teach SJ, Bloomberg GR, Wood RA, Liu AH, Pongracic JA, Chmiel JF, Conroy K, Rivera-Sanchez Y, Busse WW, Morgan WJ. Development and validation of the Composite Asthma Severity Index--an outcome measure for use in children and adolescents. J Allergy Clin Immunol. 2012 Mar;129(3):694-701. doi: 10.1016/j.jaci.2011.12.962. Epub 2012 Jan 12.
• Background Yasuda Y, Matsumura Y, Kasahara K, Ouji N, Sugiura S, Mikasa K, Kita E. Microbial exposure early in life regulates airway inflammation in mice after infection with Streptococcus pneumoniae with enhancement of local resistance. Am J Physiol Lung Cell Mol Physiol. 2010 Jan;298(1):L67-78. doi: 10.1152/ajplung.00193.2009. Epub 2009 Sep 25.
• Background Yoo J, Tcheurekdjian H, Lynch SV, Cabana M, Boushey HA. Microbial manipulation of immune function for asthma prevention: inferences from clinical trials. Proc Am Thorac Soc. 2007 Jul;4(3):277-82. doi: 10.1513/pats.200702-033AW.
• Background Yunginger JW, Reed CE, O'Connell EJ, Melton LJ 3rd, O'Fallon WM, Silverstein MD. A community-based study of the epidemiology of asthma. Incidence rates, 1964-1983. Am Rev Respir Dis. 1992 Oct;146(4):888-94. doi: 10.1164/ajrccm/146.4.888.
• Background Zeiger RS, Mauger D, Bacharier LB, Guilbert TW, Martinez FD, Lemanske RF Jr, Strunk RC, Covar R, Szefler SJ, Boehmer S, Jackson DJ, Sorkness CA, Gern JE, Kelly HW, Friedman NJ, Mellon MH, Schatz M, Morgan WJ, Chinchilli VM, Raissy HH, Bade E, Malka-Rais J, Beigelman A, Taussig LM; CARE Network of the National Heart, Lung, and Blood Institute. Daily or intermittent budesonide in preschool children with recurrent wheezing. N Engl J Med. 2011 Nov 24;365(21):1990-2001. doi: 10.1056/NEJMoa1104647.

Drugs

Indications