Non-atopic Asthma: A Continuing Enigma

  • Chris Corrigan
Part of the Allergy Frontiers book series (ALLERGY, volume 3)

Despite large inroads into understanding the comparative pathology of atopic and non-atopic asthma in the past decade, and appreciation that the airways mucosa is a key site of IgE synthesis, and that such synthesis may not always be detectable peripherally and not always directed against conventional “aeroallergens”, non-atopic asthma remains an enigma. A working hypothesis of mechanisms of intrinsic asthma, built around the possible roles of IgE is presented in Fig. 1. In terms of the bronchial mucosal cellular infiltrate and local expression of cytokines and chemokines that are thought to be important in disease pathogenesis, atopic and non-atopic asthma are very similar diseases.


Allergy Clin Immunol Bronchial Hyperresponsiveness Bronchial Mucosa Respiratory Mucosa Asthma Pathogenesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Rackeman FM (1947) A working classification of asthma. Am J Med 33:601–606CrossRefGoogle Scholar
  2. 2.
    Rackeman FM, Burrage WS, Irwin JW (1950) Intrinsic asthma. Postgrad Med 8:134–140Google Scholar
  3. 3.
    Johansson SGO, Hourihane JO'B, Bousquet J (2001) A revised nomenclature for allergy: an EAACI position statement from the EAACI nomenclature task force [position paper]. Allergy 56:813–824PubMedCrossRefGoogle Scholar
  4. 4.
    Mungan D, Bavbek S, Peksari V (2001) Trichophyton sensitivity in allergic and nonallergic asthma. Allergy 108:21–28Google Scholar
  5. 5.
    Kauffmann F, Dizier M-H (1995) EGEA (Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy) – design issues. Clin Exp Allergy 25:19–22PubMedCrossRefGoogle Scholar
  6. 6.
    Romanet-Manent S, Charpin D, Magnan A, Lanteaume A, Vervloet D (2002) Allergic vs. nonallergic asthma: what makes the difference? Allergy 57:607–613PubMedCrossRefGoogle Scholar
  7. 7.
    Kroegel C, Jager L, Walker C (1997) Is there a place for intrinsic asthma as a distinct immuno-pathological entity? Eur Respir J 10:513–515PubMedCrossRefGoogle Scholar
  8. 8.
    Sporik R, Holgate ST, Platts-Mills T (1990) Exposure to house dust mite allergen (Der p1) and the development of asthma in childhood. N Engl J Med 323:502–507PubMedGoogle Scholar
  9. 9.
    Peat JK, Salome CM, Woolcock AJ (1990) Longitudinal changes in atopy during a 4-year period: relation to bronchial hyperresponsiveness and respiratory symptoms in a population sample of Australian schoolchildren. J Allergy Clin Immunol 85:65–74PubMedCrossRefGoogle Scholar
  10. 10.
    Gotzsche PC, Johansen HK, Hammarquist C (2001) House dust mite control measures for asthma [Cochrane review]. The Cochrane Library, issue 3. Oxford Update Software.Google Scholar
  11. 11.
    Barbee RA, Hallon M, Kaltenborn W (1987) A longitudinal study of serum IgE in a community cohort: correlations with age, sex, smoking and atopic status. J Allergy Clin Immunol 79:919–927PubMedCrossRefGoogle Scholar
  12. 12.
    Burrows B, Martinez FD, Halonen M, Barbee RA, Cline MG (1989) Association of asthma with serum IgE levels and skin-test reactivity to allergens. N Engl J Med 320:271–277PubMedGoogle Scholar
  13. 13.
    Beeh KM, Ksoll M, Buhl R (2000) Elevation of total serum immunoglobulin E is associated with asthma in nonallergic individuals. Eur Respir J 16:609–614PubMedCrossRefGoogle Scholar
  14. 14.
    Van Eerdewegh P, Little RD, Dupuis J (2002) Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness. Nature 418:426–430PubMedCrossRefGoogle Scholar
  15. 15.
    Humbert M, Grant JA, Taborda-Barata L (1996) High-affinity IgE receptor (FcepsilonRI)-bearing cells in bronchial biopsies from atopic and nonatopic asthma. Am J Respir Crit Care Med 153:1931–1937PubMedGoogle Scholar
  16. 16.
    Ying S, Humbert M, Meng Q (2001) Local expression of epsilon germline gene transcripts and RNA for the epsilon heavy chain of IgE in the bronchial mucosa in atopic and nonatopic asthma. J Allergy Clin Immunol 107:686–692PubMedCrossRefGoogle Scholar
  17. 17.
    Takhar P, Corrigan CJ, Smurthwaite L, O'Connor BJ, Durham SR, Lee TH, Gould HJ (2007) Class switch recombination to IgE in the bronchial mucosa of atopic and nonatopic patients with asthma. J Allergy Clin Immunol 119:213–218PubMedCrossRefGoogle Scholar
  18. 18.
    Gould HJ, Takhar P, Harries HE, Durham SR, Corrigan CJ (2006) Germinal-centre reactions in allergic inflammation. Trends Immunol 27:446–445PubMedCrossRefGoogle Scholar
  19. 19.
    Takhar P, Smurthwaite L, Coker CA, Fear DJ, Banfield GK, Carr VA, Durham SR, Gould HJ (2005) Allergen drives class switching to IgE in the nasal mucosa in allergic rhinitis. J Immunol 174:5024–5032PubMedGoogle Scholar
  20. 20.
    Smurthwaite L, Walker SN, Wilson DR, Birch DS, Merrett TG, Durham SR, Gould HJ (2001) Persistent IgE synthesis in the nasal mucosa of hay fever patients. Eur J Immunol 31:3422–3431PubMedCrossRefGoogle Scholar
  21. 21.
    Gould HJ, Takhar P, Harries HE, Chevretton E, Sutton BJ (2007) The allergic march from Staphylococcus aureus superantigens to immunoglobulin E. Chem Immunol Allergy 93:106–136PubMedCrossRefGoogle Scholar
  22. 22.
    Riechelmann H, Essig A, Duetschle T, Rau A, Rothermel B, Weschta M (2005) Nasal carriage of Staphylococcus aureus in house dust mite allergic patients and healthy controls. Allergy 60:1418–1423PubMedCrossRefGoogle Scholar
  23. 23.
    Bachert C, Gevaert P, Howarth P, Holtappels G, van Cauwenberge P, Johansson SGO (2003) IgE to Staphylococcus aureus enterotoxins in serum is related to severity of asthma. J Allergy Clin Immunol 111:1131–1132PubMedCrossRefGoogle Scholar
  24. 24.
    Berger WE (2002) Monoclonal anti-IgE antibody: a novel therapy for allergic airways disease. Ann Allergy Asthma Immunol 88:152–160PubMedCrossRefGoogle Scholar
  25. 25.
    Novembre E, Cianferoni A, Lombardi E (2001) Natural history of “intrinsic” atopic dermatitis. Allergy 56:452–453PubMedCrossRefGoogle Scholar
  26. 26.
    Kerschenlohr K, Decard S, Darsow U (2003) Clinical and immunologic reactivity to aero-allergens in “intrinsic” atopic dermatitis patients. J Allergy Clin Immunol 111:195–197PubMedCrossRefGoogle Scholar
  27. 27.
    Bentley AM, Menz G, Storz C (1992) Identification of T lymphocytes, macrophages and activated eosinophils in the bronchial mucosa in intrinsic asthma: relationship to symptoms and bronchial responsiveness. Am Rev Respir Dis 146:500–506PubMedGoogle Scholar
  28. 28.
    Bentley AM, Durham SR, Kay AB (1994) Comparison of the immunopathology of extrinsic, intrinsic and occupational asthma. J Invest Allergol Clin Immunol 4:222–232Google Scholar
  29. 29.
    Humbert M, Durham SR, Ying S (1996) IL-4 and IL-5 mRNA and protein in bronchial biopsies from patients with atopic and nonatopic asthma: evidence against “intrinsic” asthma being a distinct immunopathologic entity. Am J Respir Crit Care Med 154:1497–1504PubMedGoogle Scholar
  30. 30.
    Ying S, Humbert M, Barkans J (1997) Expression of IL-4 and IL-5 mRNA and protein product by CD4 + and CD8 + T cells, eosinophils, and mast cells in bronchial biopsies obtained from atopic and nonatopic (intrinsic) asthmatics. J Immunol 158:3539–3544PubMedGoogle Scholar
  31. 31.
    Humbert M, Durham SR, Kimmitt P (1997) Elevated expression of messenger ribonucleic acid encoding interleukin-13 in the bronchial mucosa of atopic and non-atopic asthma. J Allergy Clin Immunol 99:657–665PubMedCrossRefGoogle Scholar
  32. 32.
    Kotsimbos TC, Ghaffar O, Minshall EM (1998) Expression of the IL-4 receptor alpha- subunit is increased in bronchial biopsy specimens from atopic and nonatopic asthma subjects. J Allergy Clin Immunol 102:859–866PubMedCrossRefGoogle Scholar
  33. 33.
    Yasruel Z, Humbert M, Kotsimbos TC (1996) Membrane-bound and soluble alpha IL-5 receptor mRNA in the bronchial mucosa of atopic and nonatopic asthmatics. Am J Respir Crit Care Med 154:1497–1504Google Scholar
  34. 34.
    Humbert M, Ying S, Corrigan C (1997) Bronchial mucosal expression of the genes encoding chemokines RANTES and MCP-3 in symptomatic atopic and nonatopic asthmatics: relationship to the eosinophil-active cytokines interleukin (IL)-5, granulocyte macrophage-colony-stimulating factor, and IL-3. Am J Respir Cell Mol Biol 16:1–8PubMedGoogle Scholar
  35. 35.
    Ying S, Meng Q, Zeibecoglou K (1999) Eosinophil chemotactic chemokines (eotaxin, eotaxin-2, RANTES, monocyte chemoattractant protein-3 (MCP-3), and MCP-4), and C-C chemokine receptor 3 expression in bronchial biopsies from atopic and nonatopic (intrinsic) asthmatics. J Immunol 163:6321–6329PubMedGoogle Scholar
  36. 36.
    Novak N, Bieber T (2003) Allergic and nonallergic forms of atopic diseases. J Allergy Clin Immunol 112:252–262PubMedCrossRefGoogle Scholar
  37. 37.
    Kotsimbos AT, Humbert M, Minshall E (1997) Upregulation of alpha GM-CSF-receptor in nonatopic asthma but not in atopic asthma. J Allergy Clin Immunol 99:666–672PubMedCrossRefGoogle Scholar
  38. 38.
    Zeibecoglou K, Ying S, Meng Q (2000) Expression of eotaxin in induced sputum of atopic and non-atopic asthmatics. Allergy 55:1042–1048PubMedCrossRefGoogle Scholar
  39. 39.
    Folkard SG, Westwick J, Millar AB (1997) Production of interleukin-8, RANTES and MCP-1 in intrinsic and extrinsic asthmatics. Eur Respir J 10:2097–2104PubMedCrossRefGoogle Scholar
  40. 40.
    Walker C, Bode E, Boer E, Hansel TT, Blaser K, Virchow JC (1992) Allergic and non-allergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and BAL. Am Rev Respir Dis 146:109–115PubMedGoogle Scholar
  41. 41.
    Virchow JC, Walker C, Hafner D (1995) T cells and cytokines in bronchoalveolar lavage fluid after segmental allergen challenge in atopic asthma. Am J Respir Crit Care Med 151: 960–968PubMedGoogle Scholar
  42. 42.
    Christodoulopoulos P, Cameron L, Nakamura Y (2001) Th2 cytokine-associated transcription factors in atopic and nonatopic asthma: evidence for differential signal transducer and activator of transcription 6 expression. J Allergy Clin Immunol 107:586–591PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2009

Authors and Affiliations

  • Chris Corrigan
    • 1
  1. 1.Department of Asthma, Allergy Respiratory Science and MRC and Asthma UK Centre for Allergic Mechanisms of AsthmaProfessor of Asthma, Allergy and Respiratory Science, King's College London School of MedicineLondonUK

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