European Journal of Epidemiology

, Volume 27, Issue 4, pp 281–286 | Cite as

Analyzing atopic and non-atopic asthma

  • Juha Pekkanen
  • Jussi Lampi
  • Jon Genuneit
  • Anna-Liisa Hartikainen
  • Marjo-Riitta Järvelin


There is a need to better define phenotypes of asthma. However, many studies have data available only on asthma and atopy, so they are often used to define ‘atopic’ and ‘non-atopic’ asthma. We discuss and illustrate the problems of analyzing such outcomes. We used the 31 year follow-up of the Northern Finland Birth Cohort 1966 (n = 5,429). ‘Atopic asthma’ and ‘non-atopic asthma’ were defined based on presence or absence of atopy (any skin prick test ≥3 mm) at age 31. Gender and ownership of cat in childhood were used as risk factors. Simple calculations on hypothetical datasets were used to support the conclusions. ‘Atopic asthma’ and ‘non-atopic asthma’, are not well separated disease entities. The association of a risk factor with ‘atopic asthma’ and ‘non-atopic asthma’ is determined both by its association with asthma and with atopy. E.g. if a risk factor is not associated with asthma, but is protective for atopy, this will produce a protective association with ‘atopic asthma’, but an opposite association with ‘non-atopic asthma’. This is the result from the typical analysis, which uses all non-asthmatics as the comparison group. Valid results, unconfounded by atopy, can be gained by comparing asthmatics to non-asthmatics separately among atopics and non-atopics, i.e. by doing the analysis stratified by atopy. If data only on asthma and atopy are available, asthma and atopy should be analyzed at first as separate outcomes. If atopic and non-atopic asthma are used as additional outcomes, valid results can be gained by stratifying the analysis by atopy.


Asthma Atopy Epidemiology Methods Phenotype 

Supplementary material

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Supplementary material 1 (DOC 61 kb)


  1. 1.
    Sears MR, Greene JM, Willan AR, Wiecek EM, Taylor DR, Flannery EM, Cowan JO, Herbison GP, Silva PA, Poulton R. A longitudinal, population-based, cohort study of childhood asthma followed to adulthood. N Engl J Med. 2003;349(15):1414–22.PubMedCrossRefGoogle Scholar
  2. 2.
    Vonk JM, Boezen HM. Predicting adult asthma in childhood. Curr Opin Pulm Med. 2006;12(1):42–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Ronmark E, Jonsson E, Platts-Mills T, et al. Different pattern of risk factors for atopic and nonatopic asthma among childred: report from the obstructive lung disease in Northern Sweden Study. Allergy. 1999;54:926–35.PubMedCrossRefGoogle Scholar
  4. 4.
    Kurukulaaratchy RJ, Fenn M, Matthews S, Arshad SH. Characterisation of atopic and non-atopic wheeze in 10 year old children. Thorax. 2004;59(7):563–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Moncayo AL, Vaca M, Oviedo G, Erazo S, Quinzo I, Fiaccone RL, Chico ME, Barreto ML, Cooper PJ. Risk factors for atopic and non-atopic asthma in a rural area of Ecuador. Thorax. 2010;65(5):409–16.PubMedCrossRefGoogle Scholar
  6. 6.
    Martin PE, Matheson MC, Gurrin L, Burgess JA, Osborne N, Lowe AJ, Morrison S, Mészáros D, Giles GG, Abramson MJ, Walters EH, Allen KJ, Dharmage SC. Childhood eczema and rhinitis predict atopic but not nonatopic adult asthma: a prospective cohort study over 4 decades. J Allergy Clin Immunol. 2011;127(6):1473–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Munthe-Kaas MC, Carlsen KH, Håland G, Devulapalli CS, Gervin K, Egeland T, Carlsen KL, Undlien D. T cell-specific T-box transcription factor haplotype is associated with allergic asthma in children. J Allergy Clin Immunol. 2008;121(1):51–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Chatterjee R, Batra J, Das S, Sharma SK, Ghosh B. Genetic association of acidic mammalian chitinase with atopic asthma and serum total IgE levels. J Allergy Clin Immunol. 2008;122(1):202–8. (208.e1-7).PubMedCrossRefGoogle Scholar
  9. 9.
    Nguyen KD, Vanichsarn C, Nadeau KC. Impaired IL-10-dependent induction of tolerogenic dendritic cells by CD4+ CD25hiCD127lo/- natural regulatory T cells in human allergic asthma. Am J Respir Crit Care Med. 2009;180((9):823–33. (Epub 2009 Aug 13).PubMedCrossRefGoogle Scholar
  10. 10.
    Lötvall J, Akdis CA, Bacharier LB, Bjermer L, Casale TB, Custovic A, Lemanske RF Jr, Wardlaw AJ, Wenzel SE, Greenberger PA. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol. 2011;127(2):355–60.PubMedCrossRefGoogle Scholar
  11. 11.
    Wenzel SE. Asthma: defining of the persistent adult phenotypes. Lancet. 2006;368(9537):804–13.PubMedCrossRefGoogle Scholar
  12. 12.
    Global Initiative for asthma. The global strategy for asthma management and prevention (updated 2007).
  13. 13.
    Pearce N, Pekkanen J, Beasley R. How much asthma is really attributable to atopy? Thorax. 1999;54(3):268–72.PubMedCrossRefGoogle Scholar
  14. 14.
    Ronchetti R, Jesenak M, Rennerova Z, Barreto M, Ronchetti F, Villa MP. Relationship between atopic asthma and the population prevalence rates for asthma or atopy in children: atopic and nonatopic asthma in epidemiology. Allergy Asthma Proc. 2009;30(1):55–63.PubMedCrossRefGoogle Scholar
  15. 15.
    Eder W, Ege MJ, von Mutius E. The asthma epidemic. N Engl J Med. 2006;355(21):2226–35.PubMedCrossRefGoogle Scholar
  16. 16.
    Pekkanen J, Lampi J, Hartikainen AL, Järvelin MR. Comparing risk factors of atopic and non-atopic asthma may lead to misleading conclusions. Epidemiology. 2009;20(6):S40.CrossRefGoogle Scholar
  17. 17.
    Lampi J, Canoy D, Jarvis D, Hartikainen AL, Keski-Nisula L, Järvelin MR, Pekkanen J. Farming environment and prevalence of atopy at age 31: prospective birth cohort study in Finland. Clin Exp Allergy. 2011;41(7):987–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Brand PL, Baraldi E, Bisgaard H, Boner AL, Castro-Rodriguez JA, Custovic A, de Blic J, de Jongste JC, Eber E, Everard ML, Frey U, Gappa M, Garcia-Marcos L, Grigg J, Lenney W, Le Souëf P, McKenzie S, Merkus PJ, Midulla F, Paton JY, Piacentini G, Pohunek P, Rossi GA, Seddon P, Silverman M, Sly PD, Stick S, Valiulis A, van Aalderen WM, Wildhaber JH, Wennergren G, Wilson N, Zivkovic Z, Bush A. Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach. Eur Respir J. 2008;32(4):1096–110.PubMedCrossRefGoogle Scholar
  19. 19.
    Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first 6 years of life. The group health medical associates. N Engl J Med. 1995;332:133–8.PubMedCrossRefGoogle Scholar
  20. 20.
    Henderson J, Granell R, Heron J, Sherriff A, Simpson A, Woodcock A, Strachan DP, Shaheen SO, Sterne JA. Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood. Thorax. 2008;63(11):974–80.PubMedCrossRefGoogle Scholar
  21. 21.
    Pekkanen J, Sunyer J, Anto JM. European community respiratory health study. operational definitions of asthma in studies on its aetiology. Eur Respir J. 2005;26(1):28–35.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Juha Pekkanen
    • 1
    • 2
  • Jussi Lampi
    • 1
    • 2
  • Jon Genuneit
    • 3
  • Anna-Liisa Hartikainen
    • 4
  • Marjo-Riitta Järvelin
    • 5
    • 6
    • 7
  1. 1.Department of Environmental HealthNational Institute for Health and WelfareKuopioFinland
  2. 2.Public Health and Clinical NutritionUniversity of Eastern FinlandKuopioFinland
  3. 3.Institute of Epidemiology and Medical BiometryUlm UniversityUlmGermany
  4. 4.Department of Clinical Sciences/Obstetrics and GynecologyUniversity of OuluOuluFinland
  5. 5.Department of Biostatistics and EpidemiologySchool of Public Health, Imperial CollegeLondonUK
  6. 6.Child and Adolescent HealthNational Institute for Health and WelfareOuluFinland
  7. 7.Institute of Health Sciences and Biocenter OuluUniversity of OuluOuluFinland

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