Lisbeth Marianne Thøstesen1, Lone Graff Stensballe2, Gitte Thybo Pihl3, Jesper Kjærgaard4, Nina Marie Birk5, Thomas Nørrelykke Nissen5, Aksel Karl Georg Jensen6, Peter Aaby7, Annette Wind Olesen8, Dorthe Lisbeth Jeppesen5, Christine Stabell Benn9, Poul-Erik Kofoed3. 1. Department of Pediatrics, Kolding Hospital, and the Institute of Regional Health Research, University of Southern Denmark, Kolding, Denmark. Electronic address: lmje@dadlnet.dk. 2. Department of Paediatrics and Adolescent Medicine, Juliane Marie Centret, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 3. Department of Pediatrics, Kolding Hospital, and the Institute of Regional Health Research, University of Southern Denmark, Kolding, Denmark. 4. Research Unit for Women's and Childrens' Health, Department of Paediatrics and Adolescent Medicine, Juliane Marie Centret, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 5. Department of Pediatrics, Copenhagen University Hospital, Hvidovre, Denmark. 6. Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, and the Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark. 7. Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark. 8. Department of Obstetrics and Gynecology, Odense University Hospital, Odense, Denmark. 9. Research Center for Vitamins and Vaccines (CVIVA), Statens Serum Institut, Copenhagen, and OPEN, Institute of Clinical Research, University of Southern Denmark/Odense University Hospital, Odense, Denmark.
Abstract
BACKGROUND:Recurrent wheeze (RW) is frequent in childhood. Studies have suggested that BCG vaccination can have nonspecific effects, reducing general nontuberculosis morbidity, including respiratory tract infections and atopic diseases. The mechanisms behind these nonspecific effects of BCG are not fully understood, but a shift from a TH2 to a TH1 response has been suggested as a possible explanation. OBJECTIVE: We hypothesized that BCG at birth would reduce the cumulative incidence of RW during the first year of life. METHODS: The Danish Calmette Study is a multicenter randomized trial conducted from 2012-2015 at 3 Danish hospitals. The 4262 newborns of 4184 included mothers were randomized 1:1 to BCG (SSI strain 1331) or to a no-intervention control group within 7 days of birth; siblings were randomized together as one randomization unit. Exclusion criteria were gestational age of less than 32 weeks, birth weight of less than 1000 g, known immunodeficiency, or no Danish-speaking parent. Information was collected through telephone interviews and clinical examinations at 3 and 13 months of age; data collectors were blind to randomization group. RW was defined in several ways, with the main definition being physician-diagnosed and medically treated RW up to 13 months of age. RESULTS: By 13 months, 211 (10.0%) of 2100 children in the BCG group and 195 (9.4%) of 2071 children in the control group had received a diagnosis of RW from a medical doctor and received antiasthma treatment (relative risk, 1.07; 95% CI, 0.89-1.28). Supplementary analyses were made, including an analysis of baseline risk factors for development of RW. CONCLUSION: Neonatal BCG had no effect on the development of RW before 13 months of age.
RCT Entities:
BACKGROUND: Recurrent wheeze (RW) is frequent in childhood. Studies have suggested that BCG vaccination can have nonspecific effects, reducing general nontuberculosis morbidity, including respiratory tract infections and atopic diseases. The mechanisms behind these nonspecific effects of BCG are not fully understood, but a shift from a TH2 to a TH1 response has been suggested as a possible explanation. OBJECTIVE: We hypothesized that BCG at birth would reduce the cumulative incidence of RW during the first year of life. METHODS: The Danish Calmette Study is a multicenter randomized trial conducted from 2012-2015 at 3 Danish hospitals. The 4262 newborns of 4184 included mothers were randomized 1:1 to BCG (SSI strain 1331) or to a no-intervention control group within 7 days of birth; siblings were randomized together as one randomization unit. Exclusion criteria were gestational age of less than 32 weeks, birth weight of less than 1000 g, known immunodeficiency, or no Danish-speaking parent. Information was collected through telephone interviews and clinical examinations at 3 and 13 months of age; data collectors were blind to randomization group. RW was defined in several ways, with the main definition being physician-diagnosed and medically treated RW up to 13 months of age. RESULTS: By 13 months, 211 (10.0%) of 2100 children in the BCG group and 195 (9.4%) of 2071 children in the control group had received a diagnosis of RW from a medical doctor and received antiasthma treatment (relative risk, 1.07; 95% CI, 0.89-1.28). Supplementary analyses were made, including an analysis of baseline risk factors for development of RW. CONCLUSION: Neonatal BCG had no effect on the development of RW before 13 months of age.
Authors: Nina Marie Birk; Thomas Nørrelykke Nissen; Jesper Kjærgaard; Hans Jacob Hartling; Lisbeth Marianne Thøstesen; Poul-Erik Kofoed; Lone Graff Stensballe; Andreas Andersen; Ole Pryds; Mihai G Netea; Christine Stabell Benn; Susanne Dam Nielsen; Dorthe Lisbeth Jeppesen Journal: Sci Rep Date: 2017-09-29 Impact factor: 4.379
Authors: Samira Imran; Melanie R Neeland; Rebecca Shepherd; Nicole Messina; Kirsten P Perrett; Mihai G Netea; Nigel Curtis; Richard Saffery; Boris Novakovic Journal: iScience Date: 2020-05-17
Authors: Matthias V Kopp; Cathleen Muche-Borowski; Michael Abou-Dakn; Birgit Ahrens; Kirsten Beyer; Katharina Blümchen; Petra Bubel; Adam Chaker; Monika Cremer; Regina Ensenauer; Michael Gerstlauer; Uwe Gieler; Inga-Marie Hübner; Fritz Horak; Ludger Klimek; Berthold V Koletzko; Sybille Koletzko; Susanne Lau; Thomas Lob-Corzilius; Katja Nemat; Eva M J Peters; Antonio Pizzulli; Imke Reese; Claudia Rolinck-Werninghaus; Elien Rouw; Bianca Schaub; Sebastian Schmidt; Jens-Oliver Steiß; Anne Kathrin Striegel; Zsolt Szépfalusi; Dietmar Schlembach; Thomas Spindler; Christian Taube; Valérie Trendelenburg; Regina Treudler; Ulrich Umpfenbach; Christian Vogelberg; Martin Wagenmann; Anke Weißenborn; Thomas Werfel; Margitta Worm; Helmut Sitter; Eckard Hamelmann Journal: Allergol Select Date: 2022-03-04