Atopic and Nonatopic Asthma in Children: Two Different Diseases?

Natalya V. Kukhtinova, PhD¹*, Elena G. Kondyurina, PhD, ScD¹, Michael J. Lentze, PhD²

¹Novosibirsk State Medical University, Novosibirsk, Russian Federation

²University Child Hospital, Bonn, Germany

*Corresponding author: Natalya V. Kukhtinova, PhD, Department of Pediatrics, Novosibirsk State Medical University, 52, Krasny ave., 630091 Novosibirsk, Russian Federation. Tel/Fax: 7-383-2291082. E-mail: n_kukhtinova@ngs.ru natalya_kuhtinov@mail.ru

Abstract: 

The majority of the studies in the field of childhood asthma lie within the scope of allergy/atopic asthma; however, airway hyperresponsiveness is considered a marker of asthma, independent of the atopic status and should be regarded as a parallel pathological process that can lead to subsequent symptoms and clinical evidence of asthma in children, without the evidence of atopy. The aim of this study is to estimate the possible differences in clinical and lung functions, and the immunological status of children with atopic and nonatopic asthma phenotypes. In a prospective study design, 54 children (age 3-18 years) in Germany were monitored via active surveillance, by twice-a-week phone calls. All the children were divided into two groups, based on their atopic status, clinical date and lung function tests. The first 27 patients had atopic asthma (AA), whereas the second set of 27 patients had nonatopic asthma (NA). All patients underwent IgE and RAST tests for the most common inhalant allergens, and a quantitative measurement of Eosinophil Cationic Protein (ECP) by CAP-radioallergosorbent test-fluorescence enzyme immunoassay (UniCAP, Pharmacia Diagnostics, Germany). Further, the IgA, IgM, IgG subclasses, IL-6 and CRP levels in the serum were tested. The resultant data showed significant differences in the prevailing IgE level 317.5±58 g/l in AA versus 83±21 in NA. However, there was no significant distinction either in the ECP serum level in children with atopic and nonatopic asthma or in the IL-6 serum level. An unexpected result was the significant drop in the level of serum CRP in group NA - 0.68±0.37 g/l; while in group AA this result was 1.5±0.38 g/l. No significant differences were noted between the mean values of the IgM and IgG levels in patients of all groups; however, the IgG levels increased only in the children with nonatopic asthma. Our study did not reveal any type of immunoglobulin deficiency. The IgA level was relatively decreased in children with nonatopic asthma compared with those with the atopic form. Patients from group NA had significantly higher IgG4 subclass levels than patients from group AA. The results of our study show that both atopic and nonatopic asthma are diseases, with similar inflammatory changes, however having probably different pathogenetic immunological mechanisms.

Keywords: 
asthma; allergy; pulmonary function; eosinophyl cation protein.
References: 

1. Nieminen MM, Kaprio J, Koskenvou M. A population based study of bronchial asthma in adult twins. Am Rev Respirate Dis 1990; 142:1351-1358.

2. Holloway JW, Jongepier H, Beghe B, Koppelman G, Holgate S, Postma DS. The genetics of asthma. In: Asthma Edit. by Chang F, Fabrri LM. Eurespir Mon, 2003. p 27-45.

3. Rasmussen F, Taylor DR, Flannery EM, Cowan OJ, Grenn JM, Herbison GP, Sears MR. Outcome in Adulthood of asymptomatic airway hyperresponsiveness in childhood: a longitudinal population study. Pediatr Pulmonol 2002; 34:164-171.

4. Stein RT, Sherrill D, Morgan WJ. Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet 1999; 354:541-545.

5. Ball TM, Castro-Podriguez JA, Griffith KA, Holberg CJ, Martinez FD, Wright Al. Siblings, day-care attendance, and the risk of asthma and wheezing during childhood. The New England Journal of Medicine 2000; August 24:538-544.

6. Oymar K, Havnene J, Halvorsen T, Bierkness R. Eosinophil counts and urinary eosinophil protein X in children hospitalized for wheezing during the first year of life: prediction of recurrent wheezing. Acta Pediatr 2001; 90: 843-9.

7. Just J, Segala C, Sahroui F, Grimfeld A, Neukirchl F. Short-term health effects of particulate and photochemical air pollution in asthmatic children. Eur Resp J 2002; 20:899-906.

8. Juniper EF, Guyatt GH, Epstein RS, Ferrie PJ, Jaeschke R, Hiller TK. Evaluation of impairment of health related quality of life in asthma: development of a questionnaire for use in clinical trials. Thorax 1992; 47:76-83.

9. Quanjer PH, Tammeling GJ, Gotes JE, Pedersen OF, Peslin R, Yernault JC. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Resp J 1993; 6(Suppl.16):5-40.

10. Bibi H, Montgomery M, Pasterkamp H, Chernick V. Relationship between response to inhaled salbutamol and methaholine bronchial provocation in children with suspected asthma. Pediatr Pulmonol 1991; 10:244-248.

11. Rasmussen F, Taylor DR, Flannery EM, Cowan OJ, Grenn JM, Herbison GP, Sears MR. Outcome in Adulthood of Asymptomatic Airway Hyperresponsiveness in Childhood. Pediatric Pulmonology 2002; 34:164-171.

12. Celedon JC, Litonjua AA, Ryan L, Platts-Mills T, Weiss ST, Gold DR. Exposure to cat allergen, maternal history of asthma and wheezing in the first 5 years of life. Lancet 2002; 360(9335):781-2.

13. Strahan DP. Family size, infection and atopy. The first decade of the hygiene hypotheses. Thorax 2000; 55(Suppl 1):2-10.

14. Ball TM, Castro-Podriguez JA, Griffith KA, Holberg CJ, Martinez FD, Wright Al. Siblings, day-care attendance, and the risk of asthma and wheezing during childhood. The New England Journ of Med 2000; 343 (8):538-43.

15. Nolte H, Backer V, Porsbjerg C. Environmental factors as a cause for the increase in allergic diseases. Ann Allergy Asthma Immunol 2001; 87(6 Suppl 3):7-11.

16. GINA, update 2004. Available from www.ginasthma.org

17. Lau S, Illi S, Sommerfeld C, Völkel K, Madloch C, Grüber C, et al. Transient early wheeze is not associated with impaired lung function in 7-yr-old children. Eur Resp J 2003; 21:834-841.

18. Guerkan F, Davutoglu M, Bilici M. Pulmonary function test in atopic and nonatopic asthmatic children. Allergol et Immunopathol 2002; 30(2):70-73.

19. Joseph-Bowen J, de Klerk N, Holt PG, Sly PD. Relationship of asthma, atopy, and bronchial responsiveness to serum eosinophil cationic proteins in early childhood. J Allergy Clin Immunol 2004 Nov; 114(5):1040-5.

20. Yoo Y, Koh YY, Kang H, Yu J, Nah KM, Kim CK. Sputum eosinophil counts and eosinophil cationic protein levels in cough-variant asthma and in classic asthma, and their relationships to airway hypersensitivity or maximal airway response to methacholine. Allergy 2004 Oct; 59(10):1055-62.

21. Selnes A, Dotterud L. No association between serum eosinophil cationic protein and atopic dermatitis or allergic rhinitis in an unselected population of children. J Eur Acad Dermatol Venereol 2005 Jan; 19(1):61-5.

22. Stelmach I, Majak P, Grzelewski T, Jerzynska J, Juralowicz D, Stelmach W, Borzecka-Podsiadlowicz M, Korzeniewska A, Kuna P. The ECP/Eo count ratio in children with asthma. J Asthma 2004 Aug; 41(5):539-46.

23. Caksen H, Oner AF, Arslan S. Kan MC, Cesur Y, Uner A. Immunoglobulin sub groups in children with febrile seizures. Pediatr Int 2001 Feb; 43(1):58-60.

24. Karaman O, Uguz A, Uzuner N. IgG subclasses in wheezing children. Indian J Pediatr 1999 May-June; 66(3):345-9.

25. Kitz R, Ahrens P, Zielen S. Immunoglobulin levels in bronchoalveolar lavage fluid of children with chronic chest disease. Pediatr Pulmonol 2000 Jun; 29(6):443-451.

26. de Moraes Lui C, Oliveira LC, Diogo CL, Kirschfink M, Grumach AS. Pediatric Allergy and Immunology 2002 Jun; 13(3):195.

The fully formatted PDF version is available.

Download Article

Int J Biomed. 2012;2(3):214-221.© 2012 International Medical Research and Development Corporation. All rights reserved.