European Journal of Epidemiology

, Volume 34, Issue 5, pp 509–520 | Cite as

Can environment or allergy explain international variation in prevalence of wheeze in childhood?

  • Gudrun WeinmayrEmail author
  • Andrea Jaensch
  • Ann-Kathrin Ruelius
  • Francesco Forastiere
  • David P. Strachan
  • the ISAAC Phase Two Study Group


Asthma prevalence in children varies substantially around the world, but the contribution of known risk factors to this international variation is uncertain. The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two studied 8–12 year old children in 30 centres worldwide with parent-completed symptom and risk factor questionnaires and aeroallergen skin prick testing. We used multilevel logistic regression modelling to investigate the effect of adjustment for individual and ecological risk factors on the between-centre variation in prevalence of recent wheeze. Adjustment for single individual-level risk factors changed the centre-level variation from a reduction of up to 8.4% (and 8.5% for atopy) to an increase of up to 6.8%. Modelling the 11 most influential environmental factors among all children simultaneously, the centre-level variation changed little overall (2.4% increase). Modelling only factors that decreased the variance, the 6 most influential factors (synthetic and feather quilt, mother’s smoking, heating stoves, dampness and foam pillows) in combination resulted in a 21% reduction in variance. Ecological (centre-level) risk factors generally explained higher proportions of the variation than did individual risk factors. Single environmental factors and aeroallergen sensitisation measured at the individual (child) level did not explain much of the between-centre variation in wheeze prevalence.


Asthma Child Hypersensitivity Environmental risk factors International variation 



We wish to thank all children, parents, teachers, field workers and lab workers for their enormous contributions to this collaborative study.

Financial support

This work was supported by the German Research Foundation (DFG) (Grant No. WE 4306/3-1).

Supplementary material

10654_2018_463_MOESM1_ESM.pdf (380 kb)
Supplementary material 1 (PDF 379 kb)


  1. 1.
    Weinmayr G, Weiland SK, Björkstén B, Brunekreef B, Büchele G, Cookson WOC, et al. Atopic sensitization and the international variation of asthma symptom prevalence in children. Am J Respir Crit Care Med. 2007;176:565–74.CrossRefPubMedGoogle Scholar
  2. 2.
    ISAAC Steering Committee I, Beasley R, Keil U, Von Mutius E, Pearce N. Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. Lancet. 1998;351:1225–32.CrossRefGoogle Scholar
  3. 3.
    Weiland SK, Björkstén B, Brunekreef B, Cookson WOC, von Mutius E, Strachan DP. Phase II of the International Study of Asthma and Allergies in Childhood (ISAAC II): rationale and methods. Eur Respir J. 2004;24:406–12.CrossRefPubMedGoogle Scholar
  4. 4.
    von Mutius E, Martinez FD, Fritzsch C, Nicolai T, Roell G, Thiemann HH. Prevalence of asthma and atopy in two areas of West and East Germany. Am J Respir Crit Care Med. 1994;149:358–64.CrossRefGoogle Scholar
  5. 5.
    Wong GWK, Ko FWS, Hui DSC, Fok TF, Carr D, von Mutius E, et al. Factors associated with difference in prevalence of asthma in children from three cities in China: multicentre epidemiological survey. BMJ. 2004;329:486.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    ISAAC Steering Comittee. ISAAC Phase Two. Updated 5 Apr 2017. Accessed: 11 Oct 2017.
  7. 7.
    Weinmayr G, Dreyhaupt J, Jaensch A, Forastiere F, Strachan DP. Multilevel regression modelling to investigate variation in disease prevalence across locations. Int J Epidemiol. 2017;46:336–47.PubMedGoogle Scholar
  8. 8.
    Bauer DJ. A note on comparing the estimates of models for cluster-correlated or longitudinal data with binary or ordinal outcomes. Psychometrika. 2008;74:97–105.CrossRefGoogle Scholar
  9. 9.
    Richardson DB, Rzehak P, Klenk J, Weiland SK. Analyses of case-control data for additional outcomes. Epidemiology. 2007;18:441–5.CrossRefPubMedGoogle Scholar
  10. 10.
    Weinmayr G, Gehring U, Genuneit J, Büchele G, Kleiner A, Siebers R, et al. Dampness and moulds in relation to respiratory and allergic symptoms in children: results from Phase Two of the International Study of Asthma and Allergies in Childhood (ISAAC Phase Two). Clin Exp Allergy. 2013;43:762–74.CrossRefPubMedGoogle Scholar
  11. 11.
    Weinmayr G, Forastiere F, Büchele G, Jaensch A, Strachan DP, Nagel G. Overweight/obesity and respiratory and allergic disease in children: International Study of Asthma and Allergies in Childhood (ISAAC) phase two. PLoS ONE. 2014;9:e113996.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    García-Marcos L, Castro-Rodríguez JA, Suarez-Varela MM, Garrido JB, Hernandez GG, Gimeno AM, et al. A different pattern of risk factors for atopic and non-atopic wheezing in 9–12-year-old children. Pediatr Allergy Immunol. 2005;16:471–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Yemaneberhan H, Bekele Z, Venn A, Lewis S, Parry E, Britton J. Prevalence of wheeze and asthma and relation to atopy in urban and rural Ethiopia. Lancet. 1997;350:85–90.CrossRefPubMedGoogle Scholar
  14. 14.
    Basagaña X, Sunyer J, Kogevinas M, Zock J-P, Duran-Tauleria E, Jarvis D, et al. Socioeconomic status and asthma prevalence in young adults: the European Community Respiratory Health Survey. Am J Epidemiol. 2004;160:178–88.CrossRefPubMedGoogle Scholar
  15. 15.
    Heinrich J, Bedada GB, Zock J-P, Chinn S, Norbäck D, Olivieri M, et al. Cat allergen level: its determinants and relationship to specific IgE to cat across European centers. J Allergy Clin Immunol. 2006;118:674–81.CrossRefPubMedGoogle Scholar
  16. 16.
    Douwes J, Pearce N. Asthma and the westernization “package”. Int J Epidemiol. 2002;31:1098–102.CrossRefPubMedGoogle Scholar
  17. 17.
    Ivert AK, Levander MT, Merlo J. Adolescents’ utilisation of psychiatric care, neighbourhoods and neighbourhood socioeconomic deprivation: a multilevel analysis. PLoS ONE. 2013;8:e81127.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Gupta RS, Zhang X, Sharp LK, Shannon JJ, Weiss KB. The protective effect of community factors on childhood asthma. J Allergy Clin Immunol. 2009;123(1297–1304):e2.Google Scholar
  19. 19.
    Kogan MD, Singh GK, Dee DL, Belanoff C, Grummer-Strawn LM. Multivariate analysis of state variation in breastfeeding rates in the United States. Am J Public Health. 2008;98:1872–80.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Merlo J, Ostergren PO, Broms K, Bjorck-Linné A, Liedholm H. Survival after initial hospitalisation for heart failure: a multilevel analysis of patients in Swedish acute care hospitals. J Epidemiol Community Health. 2001;55:323–9.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Institute of Epidemiology and Medical BiometryUlm UniversityUlmGermany
  2. 2.Department of EpidemiologyLazio Regional Health ServiceRomeItaly
  3. 3.Population Health Research InstituteSt George’s, University of LondonLondonUK

Personalised recommendations