Digestive Diseases and Sciences

, Volume 59, Issue 7, pp 1502–1508 | Cite as

Children with Celiac Disease Are More Likely to Have Attended Hospital for Prior Respiratory Syncytial Virus Infection

  • Anna Röckert TjernbergEmail author
  • Jonas F. Ludvigsson
Original Article


Background and Aim

The purpose of this study was to examine the association between celiac disease (CD) and prior respiratory syncytial virus (RSV) infection or any viral bronchiolitis.


This was a retrospective case–control study. During 2006–2008 small intestinal biopsy data were collected from Sweden’s 28 pathology departments. We identified 3,835 children diagnosed with CD (villous atrophy, Marsh stage 3) before the age of 2 years in 1987 or later. Using conditional logistic regression we calculated odds ratios (ORs) for having a prior diagnosis of respiratory syncytial virus or other viral bronchiolitis compared to 19,102 age- and sex-matched controls.


Of the 3,835 children with CD, 36 (0.9 %) had a prior diagnosis of RSV compared to 117/19,102 (0.6 %) matched controls. This corresponded to an OR of 1.46 (95 % CI 1.03–2.07). ORs were similar in girls and boys. The highest ORs were seen in children developing early CD (before 1 year of age (OR 1.82; 95 % CI 0.91–3.62). Prior record of any type of viral bronchiolitis was found in 3.4 % (132/3,835) of individuals with CD and in 2.0 % (390/19,102) of the matched controls corresponding to an OR of 1.60 (95 % CI 1.33–1.92).


Children with CD diagnosed <2 years of age were more likely to have attended hospital for a prior RSV infection or any viral bronchiolitis than other children.


Autoimmunity Bronchiolitis Child Coeliac Infant Inflammation Respiratory syncytial virus 



Celiac disease


Confidence interval


Odds ratio


Respiratory syncytial virus


Villous atrophy



ART was funded by Kalmar County Council. JFL was supported by grants from The Swedish Society of Medicine, the Swedish Research Council—Medicine (522-2A09-195), the Swedish Celiac Society, and the Fulbright Commission.

Conflict of interest


Ethical standard

This project (2006/633-31/4) was approved by the Research Ethics Committee of the Karolinska Institute, Sweden on June 14, 2006.


  1. 1.
    Ludvigsson JF, Green PH. Clinical management of coeliac disease. J Intern Med. 2011;269:560–571.PubMedCrossRefGoogle Scholar
  2. 2.
    Dieterich W, Laag E, Schopper H, et al. Autoantibodies to tissue transglutaminase as predictors of celiac disease [see comments]. Gastroenterology. 1998;115:1317–1321.PubMedCrossRefGoogle Scholar
  3. 3.
    Marild K, Fredlund H, Ludvigsson JF. Increased risk of hospital admission for influenza in patients with celiac disease: a nationwide cohort study in Sweden. Am J Gastroenterol. 2010;105:2465–2473.PubMedCrossRefGoogle Scholar
  4. 4.
    Thomas HJ, Wotton CJ, Yeates D, Ahmad T, Jewell DP, Goldacre MJ. Pneumococcal infection in patients with coeliac disease. Eur J Gastroenterol Hepatol. 2008;20:624–628.PubMedCrossRefGoogle Scholar
  5. 5.
    Ludvigsson JF, Sanders DS, Maeurer M, Jonsson J, Grunewald J, Wahlstrom J. Risk of tuberculosis in a large sample of patients with coeliac disease–a nationwide cohort study. Aliment Pharmacol Ther. 2011;33:689–696.PubMedCrossRefGoogle Scholar
  6. 6.
    Sapone A, Lammers KM, Casolaro V, et al. Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity. BMC Med. 2011;9:23.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Stene LC, Honeyman MC, Hoffenberg EJ, et al. Rotavirus infection frequency and risk of celiac disease autoimmunity in early childhood: a longitudinal study. Am J Gastroenterol. 2006;101:2333–2340.PubMedCrossRefGoogle Scholar
  8. 8.
    Jabri B, Sollid LM. Tissue-mediated control of immunopathology in coeliac disease. Nat Rev Immunol. 2009;9:858–870.PubMedCrossRefGoogle Scholar
  9. 9.
    Tregoning JS, Schwarze J. Respiratory viral infections in infants: causes, clinical symptoms, virology, and immunology. Clin Microbiol Rev. 2010;23:74–98.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Hall CB. The burgeoning burden of respiratory syncytial virus among children. Infect Disord Drug Targets. 2012;12:92–97.PubMedCrossRefGoogle Scholar
  11. 11.
    Nair H, Nokes DJ, Gessner BD, et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet. 2010;375:1545–1555.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Gutierrez-Achury J, Coutinho de Almeida R, Wijmenga C. Shared genetics in coeliac disease and other immune-mediated diseases. J Intern Med. 2011;269:591–603.PubMedCrossRefGoogle Scholar
  13. 13.
    Smyth DJ, Plagnol V, Walker NM, et al. Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med. 2008;359:2767–2777.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Ludvigsson JF, Otterblad-Olausson P, Pettersson BU, Ekbom A. The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research. Eur J Epidemiol. 2009;24:659–667.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Ludvigsson JF, Andersson E, Ekbom A, et al. External review and validation of the Swedish national inpatient register. BMC Public Health. 2011;11:450.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Ludvigsson JF, Brandt L, Montgomery SM, Granath F, Ekbom A. Validation study of villous atrophy and small intestinal inflammation in Swedish biopsy registers. BMC Gastroenterol. 2009;9:19.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Pais WP, Duerksen DR, Pettigrew NM, Bernstein CN. How many duodenal biopsy specimens are required to make a diagnosis of celiac disease? Gastrointest Endosc. 2008;67:1082–1087.PubMedCrossRefGoogle Scholar
  18. 18.
    Ludvigsson JF, Brandt L, Montgomery SM. Symptoms and signs in individuals with serology positive for celiac disease but normal mucosa. BMC Gastroenterol. 2009;9:57.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Ludvigsson JF, Montgomery SM, Ekbom A, Brandt L, Granath F. Small-intestinal histopathology and mortality risk in celiac disease. JAMA. 2009;302:1171–1178.PubMedCrossRefGoogle Scholar
  20. 20.
    Ivarsson A, Hernell O, Stenlund H, Persson LA. Breast-feeding protects against celiac disease. Am J Clin Nutr. 2002;75:914–921.PubMedGoogle Scholar
  21. 21.
    Lebwohl B, Green PH, Murray JA, Ludvigsson JF. Season of birth in a nationwide cohort of coeliac disease patients. Arch Dis Child. 2013;98:48–51.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Ivarsson A, Persson LA, Nystrom L, et al. Epidemic of coeliac disease in Swedish children [see comments]. Acta Paediatr. 2000;89:165–171.PubMedCrossRefGoogle Scholar
  23. 23.
    Olen O, Bihagen E, Rasmussen F, Ludvigsson JF. Socioeconomic position and education in patients with coeliac disease. Dig Liver Dis. 2012;44:471–476.PubMedCrossRefGoogle Scholar
  24. 24.
    Marild K, Stephansson O, Montgomery S, Murray JA, Ludvigsson JF. Pregnancy outcome and risk of celiac disease in offspring: a nationwide case-control study. Gastroenterology. 2012;142(39–45):e33.Google Scholar
  25. 25.
    Nielsen HE, Siersma V, Andersen S, et al. Respiratory syncytial virus infection–risk factors for hospital admission: a case-control study. Acta Paediatr. 2003;92:1314–1321.PubMedCrossRefGoogle Scholar
  26. 26.
    Cnattingius S, Ericson A, Gunnarskog J, Kallen B. A quality study of a medical birth registry. Scand J Soc Med. 1990;18:143–148.PubMedGoogle Scholar
  27. 27.
    Welander A, Tjernberg AR, Montgomery SM, Ludvigsson J, Ludvigsson JF. Infectious disease and risk of later celiac disease in childhood. Pediatrics. 2010;125:e530–e536.PubMedCrossRefGoogle Scholar
  28. 28.
    Sandberg-Bennich S, Dahlquist G, Kallen B. Coeliac disease is associated with intrauterine growth and neonatal infections. Acta Paediatr. 2002;91:30–33.PubMedCrossRefGoogle Scholar
  29. 29.
    Glezen WP, Taber LH, Frank AL, Kasel JA. Risk of primary infection and reinfection with respiratory syncytial virus. Am J Dis Child. 1986;140:543–546.PubMedGoogle Scholar
  30. 30.
    Simoes EA. Environmental and demographic risk factors for respiratory syncytial virus lower respiratory tract disease. J Pediatr. 2003;143:S118–S126.PubMedCrossRefGoogle Scholar
  31. 31.
    Akobeng AK, Ramanan AV, Buchan I, Heller RF. Effect of breast feeding on risk of coeliac disease: a systematic review and meta-analysis of observational studies. Arch Dis Child. 2006;91:39–43.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Szajewska H, Chmielewska A, Piescik-Lech M, et al. Systematic review: early infant feeding and the prevention of coeliac disease. Aliment Pharmacol Ther. 2012;36:607–618.PubMedCrossRefGoogle Scholar
  33. 33.
    Tjellstrom B, Stenhammar L, Hogberg L, et al. Gut microflora associated characteristics in children with celiac disease. Am J Gastroenterol. 2005;100:2784–2788.PubMedCrossRefGoogle Scholar
  34. 34.
    Decker E, Engelmann G, Findeisen A, et al. Cesarean delivery is associated with celiac disease but not inflammatory bowel disease in children. Pediatrics. 2010;125:e1433–e1440.PubMedCrossRefGoogle Scholar
  35. 35.
    Marild K, Ye W, Lebwohl B, et al. Antibiotic exposure and the development of coeliac disease: a nationwide case-control study. BMC Gastroenterol. 2013;13:109.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Margoni D, Chouliaras G, Duscas G, et al. Bone health in children with celiac disease assessed by dual x-ray absorptiometry: effect of gluten-free diet and predictive value of serum biochemical indices. J Pediatr Gastroenterol Nutr. 2012;54:680–684.PubMedCrossRefGoogle Scholar
  37. 37.
    Roth DE, Shah R, Black RE, Baqui AH. Vitamin D status and acute lower respiratory infection in early childhood in Sylhet. Bangladesh Acta Paediatr. 2010;99:389–393.CrossRefGoogle Scholar
  38. 38.
    McNally JD, Leis K, Matheson LA, Karuananyake C, Sankaran K, Rosenberg AM. Vitamin D deficiency in young children with severe acute lower respiratory infection. Pediatr Pulmonol. 2009;44:981–988.PubMedCrossRefGoogle Scholar
  39. 39.
    Belderbos ME, Houben ML, Wilbrink B, et al. Cord blood vitamin D deficiency is associated with respiratory syncytial virus bronchiolitis. Pediatrics. 2011;127:e1513–e1520.PubMedCrossRefGoogle Scholar
  40. 40.
    Ferrara F, Quaglia S, Caputo I, et al. Anti-transglutaminase antibodies in non-coeliac children suffering from infectious diseases. Clin Exp Immunol. 2010;159:217–223.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Anna Röckert Tjernberg
    • 1
    Email author
  • Jonas F. Ludvigsson
    • 2
    • 3
  1. 1.Department of PediatricsKalmar County HospitalKalmarSweden
  2. 2.Department of PediatricsÖrebro University HospitalÖrebroSweden
  3. 3.Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetStockholmSweden

Personalised recommendations