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Vol. 161, No. 2, 2013
Issue release date: May 2013
Int Arch Allergy Immunol 2013;161:163–173

Asthmatic Response to Milk Ingestion Challenge in Adults: A Comparison of the Open and Double-Blind Challenges

Pelikan Z.
Allergy Research Foundation, Breda, The Netherlands

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Background: Cow’s milk allergy can participate in pathophysiological mechanisms underlying bronchial asthma in some adult patients. This role should ultimately be confirmed by means of a milk ingestion challenge. In this study, the diagnostic value of the open food ingestion challenge (OFICH) and the double-blind placebo-controlled food challenge (DBPCFC) techniques with milk were compared in adult patients suffering from bronchial asthma with suspected milk allergy. Methods: In 87 asthmatics with a suspected history and positive skin tests for milk, the 87 OFICHs and DBPCFCs were performed in combination with spirometry and followed up to 72 h after the challenge. Results: Of 87 patients, 74 (85%) developed a positive asthmatic response (AR) (20 immediate, 33 late, 6 dual late and 15 delayed; p < 0.01) and 13 (15%) developed a negative AR (p > 0.1) to OFICH. Seventy-five (86%) developed a positive AR (17 immediate, 35 late, 8 dual late and 15 delayed; p < 0.01) and 12 (14%) developed a negative AR (p > 0.05) to DBPCFC. The correlation between the OFICH and DBPCFC was statistically significant (p < 0.01). All placebo control challenges were negative (p > 0.2). Conclusions: In some adults with bronchial asthma, involvement of an allergy to cow’s milk results in the appearance of various AR types (immediate, late, dual late or delayed). The milk allergy can be confirmed by open or double-blind techniques, combined with spirometry. No significant differences were found between the OFICH and DBPCFC results. OFICH with natural milk combined with spirometry seems, therefore, to be an adequate technique for the detection of milk allergy in asthmatics. The DBPCFC can be performed as an additional check, if necessary.

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  1. Sampson HA, Burks AW: Adverse reactions to foods; in Adkinson NF, Bochner BS, Busse WW, Holgate ST, Lemanske RF, Simons FE (eds): Middleton’s Allergy – Principles & Practice, ed 7. Philadelphia, Mosby-Elsevier, 2009, pp 1139–1167.
  2. Ayres JG, Baker JC: Food-induced asthma; in Brostoff J, Challacombe SJ (eds): Food Allergy and Intolerance, ed 2. London, Saunders/Elsevier, 2002, pp 529–540.
  3. Sicherer SH, Sampson HA: Food allergy. J Allergy Clin Immunol 2010;125:S116–S125.
  4. Bock SA: Diagnostic evaluation. Pediatrics 2003;111:1638–1644.

    External Resources

  5. Liu AH, Renee J, Sicherer SH, Wood RA, Bock SA, Burks AW, Massing M, Cohn RD, Zeldin DC: National prevalence and risk factors for food allergy and relationship to asthma: results from the National Health and Nutrition Examination Survey 2005–2006. J Allergy Clin Immunol 2010;126:798–806.
  6. Fiocchi A, Schünemann HJ, Brozek J, Restani P, Beyer K, Troncone R, Martelli A, Terracciano L, Bahna SL, Rance F, Ebisawa M, Heine RG, Assa’ad A, Sampson H, Verduci E, Bouygue GR, Baena-Cagnani C, Canonica W, Lockey RF: Diagnosis and rationale for action against cow’s milk allergy (DRACMA): a summary report. J Allergy Clin Immunol 2010;126:1119–1128.
  7. Burks AW, Tang M, Sicherer S, Muraro A, Eigenmann PA, Ebisawa M, Fiocchi A, Chiang W, Beyer K, Wood R, Hourihane J, Jones SM, Lack G, Sampson HA: ICON: food allergy. J Allergy Clin Immunol 2012;129:906–920.
  8. Boyce JA, Assa’ad A, Burks AW, Jones SM, Sampson HA, Wood RA, Plaut M, Cooper SF, Fenton MJ: Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel. J Allergy Clin Immunol 2010;126:S1–S58.
  9. Vickery BP, Chin S, Burks AW: Pathophysiology of food allergy. Pediatr Clin North Am 2011;58:363–376.
  10. Dupont Ch: Food allergy: recent advances in pathophysiology and diagnosis. Ann Nutr Metab 2011;59(suppl 1):8–18.
  11. Mansoor DK, Sharma HP: Clinical presentations of food allergy. Pediatr Clin North Am 2011;58:315–326.
  12. Perez-Machado MA, Ashwood P, Torrente F, Salvestrini C, Sim R, Thompson MA, Walker-Smith JA, Murch SH: Spontaneous TH1 cytokine production by intraepithelial but not circulating T cells in infants with or without food allergies. Allergy 2004;59:346–353.
  13. Paajanen L, Vaarala O, Karttunen R, Tuure T, Korpela R, Kokkonen J: Increased IFN-γ secretion from duodenal biopsy samples in delayed-type cow’s milk allergy. Pediatr Allergy Immunol 2005;16:439–444.
  14. Scott-Taylor TH, Hourihane JOB, Strobel S: Correlation of allergen-specific IgG subclass antibodies and T lymphocyte cytokine responses in children with multiple food allergies. Pediatr Allergy Immunol 2010;21:935–944.
  15. Veres G, Westrholm-Ormio M, Kokkonen J, Arato A, Savilahti E: Cytokines and adhesion molecules in duodenal mucosa of children with delayed-type food allergy. J Pediatr Gastroenterol Nutr 2003;37:27–34.
  16. Osterlund P, Suomalainen H: Low frequency of CD4+, but not CD8+, T cells expressing interferon-gamma is related to cow’s milk allergy in infancy. Pediatr Allergy Immunol 2002;13:262–268.
  17. Sabra A, Bellanti JA, Reis MJ, Castro HJ, de Inocencio JM, Sabra S: IgE and non-IgE food allergy. Ann Allergy Asthma Immunol 2003;90(suppl 3):71–76.

    External Resources

  18. Bellanti JA, Zeligs BJ, Reis MJ, Sabra A: Abnormalities of Th1 function in non-IgE food allergy, celiac disease, and ileal lymphonodular hyperplasia: a new relationship? Ann Allergy Asthma Immunol 2003;90(suppl 3):84–89.

    External Resources

  19. Papadakis KA, Landers C, Prehn J, Kouroumalis EA, Moreno ST, Gutierrez-Ramos JC, Hodge MR, Targan SR: CC chemokine receptor 9 expression defines a subset of peripheral blood lymphocytes with mucosal T cell phenotype and Th1 or T-regulatory 1 cytokine profile. J Immunol 2003;171:159–165.
  20. Youngman KR, Lazarus NH, Butcher EC: Lymphocyte homing: Chemokines and adhesion molecules in T cell and IgA plasma cell localization in the mucosal immune system; in Mestecky J, Binnenstock J, Lamm M, Strober W, McGhee JR, Mayer L (eds): Mucosal Immunology, ed 3. Burlington, Elsevier-Academic Press, 2005, pp 667–680.
  21. Bienenstock J, Clancy RL: Bronchus-associated lymphoid tissue; in Mestecky J, Binnenstock J, Lamm M, Strober W, McGhee JR, Mayer L (eds): Mucosal Immunology, ed 3. Burlington, Elsevier-Academic Press 2005, pp 375–384.
  22. Fickling WE, Robertson DAF: Immunologically mediated damage of the gut; in Brostoff J, Challacombe SJ (eds): Food allergy and intolerance, ed 2. London, Saunders/Elsevier, 2002, pp 293–301.
  23. Berin MC, Sampson HA: Food allergy: Immunophysiology; in Mestecky J, Binnenstock J, Lamm M, Strober W, McGhee JR, Mayer L (eds): Mucosal immunology, ed 3. Burlington, Elsevier-Academic Press, 2005, pp 1335–1350.
  24. Jyonouchi H: Non-IgE mediated food allergy. Inflamm Allergy Drug Targets 2008;7:173–180.
  25. Novembre E, Martino de M, Vierucci A: Foods and respiratory allergy. J Allergy Clin Immunol 1988;81:1059–1065.
  26. Pelikan Z, Pelikan-Filipek M: Bronchial response to the food ingestion challenge. Ann Allergy 1987;58:164–172.
  27. Pelikan Z: Asthmatic response (AR) to the food ingestion challenge: a comparison of the double-blind placebo-controlled (DBPCC) and open placebo-controlled (OPCC) challenges. Allergy 2002;57(suppl 73):86(abstract 238).
  28. Pelikan Z: Rhinitis, secretory otitis media and sinus disease caused by food allergy; in Brostoff J, Challacombe SJ (eds): Food allergy and Intolerance, ed 2. London, Saunders/Elsevier, 2002, pp 499–528.
  29. Pelikan Z: The late nasal response, its clinical and immunologic features, possible mechanisms and pharmacologic modulation. Thesis. Amsterdam, Free University of Amsterdam, 1996.
  30. James JM: Respiratory manifestations of food allergy. Pediatrics 2003;111:1625–1630.
  31. Schäfer T, Böhler E, Ruhdorfer S, Weigl L, Wessner D, Filipiak B, Wichmann HE, Ring J: Epidemiology of food allergy/food intolerance in adults: association with other manifestations of atopy. Allergy 2001;56:1172–1179.
  32. Bindslev-Jensen C, Ballmer-Weber BK, Bengtsson U, Blanco C, Ebner C, Hourihane J, Knulst AC, Moneret-Vautrin DA, Nekam K, Niggemann B, Ring J, Osterballe M, Ortolani C, Schnopp C, Werfel T: Standardization of food challenges in patients with immediate reactions to foods-position paper from European Academy of Allergology and Clinical Immunology. Allergy 2004;59:690–697.
  33. Correa FF, Vieira MC, Yamamoto DR, Speridião Pda G, de Morais MB: Open challenge for the diagnosis of cow’s milk protein allergy. J Pediatr (Rio J) 2010;86:163–166.
  34. James JM, Eigenmann PA, Eggleston PA, Sampson HA: Airway reactivity changes in asthmatic patients undergoing blinded food challenges. Am J Respir Crit Care Med 1996;153:597–603.
  35. Wang J, Liu AH: Food allergies and asthma. Curr Opin Allergy Clin Immunol 2011;11:249–254.
  36. Venter C, Pereira B, Voigt K, Grundy J, Clayton CB, Higgins B, Arshad SH, Dean T: Comparison of open and double-blind placebo-controlled food challenges in diagnosis of food hypersensitivity amongst children. J Hum Nutr Diet 2007;20:565–579.
  37. Nowak-Wegrzyn A, Assad AH, Bahna SL, Bock SA, Sicherer SH, Teuber SS: Work group report: oral food challenge testing. J Allergy Clin Immunol 2009;123:S365–S383.
  38. Roberts G, Lack G: Food allergy and asthma – what is the link? Pediatr Respir Rev 2003;4:205–212.
  39. Sicherer SH: Food allergy: when and how to perform oral food challenges. Pediatr Allergy Immunol 1999;10:226–234.
  40. Vlieg-Boerstra BJ, Heide van der S, Bijleveld CM, Kukler J, Duiverman EJ, Dubois AE: Placebo reactions in double-blind, placebo-controlled food challenges in children. Allergy 2007;62:905–912.
  41. Mankad VS, Williams LW, Lee LA, LaBelle GS, Anstrom KJ, Burks AW: Safety of open food challenges in the office setting. Ann Allergy Asthma Immunol 2008;100:469–474.
  42. Asero R, Fernandez-Rivas M, Knulst AC, Bruijnzeel-Koomen CA: Double-blind, placebo-controlled food challenges in adults in everyday clinical practice: a reappraisal of their limitations and real indications. Curr Opin Allergy Clin Immunol 2009;9:379–385.
  43. Wood RA: Oral food challenge testing; in Adkinson NF, Bochner BS, Busse WW, Holgate ST, Lemanske RF, Simons FE (eds): Middleton’s Allergy – Principles and Practice, ed 7. Philadelphia, Mosby-Elsevier, 2009, pp 1309–1317.
  44. Lieberman J, Sampson HA: Outpatient, open oral food challenges – a one year reprospective study. Ann Allergy Asthma Immunol 2010;105(suppl 1):A15 (abstract 46).
  45. Lieberman JA, Cox AL, Vitale M, Sampson HA: Outcomes of office-based, open food challenges in the management of food allergy. J Allergy Clin Immunol 2011;128:1120–1022.
  46. Bock SA, Cherrington L: Oral food challenges in a practice setting apart from hospitals and academic centers. J Allergy Clin Immunol 2012;129:1422.
  47. Pelikan Z, Pelikan M, Kruis M, Berger MPF: The immediate asthmatic response to allergen challenge. Ann Allergy 1986;56:252–260.
  48. Pelikan Z, Pelikan-Filipek M: The late asthmatic response to allergen challenge. Part I + II. Ann Allergy 1986;56:414–420, 421–435.
  49. Pelikan Z: Delayed type of asthmatic response to bronchial challenge with allergen. I. Clinical features. Ann Allergy Asthma Immunol 2010;104:394–404.
  50. Niggemann B, Beyer K: Pitfalls in double-blind, placebo-controlled oral food challenges. Allergy 2007;62:729–732.
  51. Williams LW: Skin testing and food challenges for the evaluation of food allergy. Curr Allergy Rep 2001;1:61–66.
  52. Melillo G, Bonini S, Cocco G, Davies RJ, de Monchy JG, Frølund L, Pelikan Z: Provocation tests with allergens. Allergy 1997;52(suppl 35):5–36.

    External Resources

  53. Sterk PJ, Fabbri LM, Quanjer PhH, Cockcroft DW, O’Byrne PM, Anderson SD, Juniper EF, Malo JL: Airway responsiveness – standardized challenge testing with pharmacological, physical and sensitizing stimuli in adults. Eur Respir J 1993;16(suppl): 53–83.
  54. Houd DJ, Taylor CC: Multivariate Analysis of Variance and Repeated Measures. London, Chapman and Hall, 1987.

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