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Allergen Immunotherapy for the Prevention of Allergic Asthma

  • Allergic Asthma (D Larenas-Linnemann de Martínez, Section Editor)
  • Published:
Current Treatment Options in Allergy Aims and scope Submit manuscript

Abstract

Purpose of review:

Children with allergic rhinitis (AR) have a high risk of developing asthma. An effect beyond end of allergen immunotherapy (AIT) has been demonstrated, and moreover a preventive effect on the development of asthma in children with AR is suggested. The aim of this review is to discuss the evidence for the asthma preventive capacity of AIT.

Recent findings:

According to the recently published systematic review and clinical practice AIT guideline from The European Academy of Allergy and Clinical Immunology (EAACI), there is sufficient evidence to recommend a 3-year course of AIT for children and adolescents with moderate to severe AR and grass/birch pollen allergy, for the prevention of asthma for up to 2 years post-AIT. Further, a recent high-quality trial demonstrated a preventive effect of a 3-year course of AIT with a sublingual grass tablet on asthma symptoms and medication 2 years post-AIT in children with AR and grass pollen allergy.

Summary:

AIT has a disease-modifying and asthma preventive effect, which may influence the indication for AIT in the future.

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Abbreviations

AD:

Atopic dermatitis/eczema

AIT:

Allergen immunotherapy

AR:

Allergic rhinitis/Allergic rhino conjunctivitis

CBA:

Non-randomized Controlled Before and After studies

HDM:

House dust mite

RCT:

Randomized controlled trial

SCIT:

Subcutaneous immunotherapy

SLIT:

Sublingual immunotherapy

SR:

Systematic Review

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Christiansen ES, Kjaer HF, Eller E, Bindslev-Jensen C, Host A, Mortz CG, et al. The prevalence of atopic diseases and the patterns of sensitization in adolescence. Pediatr Allergy Immunol. 2016;27:847–53.

    Article  Google Scholar 

  2. Henriksen L, Simonsen J, Haerskjold A, Linder M, Kieler H, Thomsen SF, et al. Incidence rates of atopic dermatitis, asthma, and allergic rhinoconjunctivitis in Danish and Swedish children. J Allergy Clin Immunol. 2015;136:360–6.

    Article  Google Scholar 

  3. Tejedor Alonso MA, Moro MM, Mugica Garcia MV. Epidemiology of anaphylaxis. Clin Exp Allergy. 2015;45:1027–39.

    Article  CAS  Google Scholar 

  4. Patil VK, Kurukulaaratchy RJ, Venter C, Grundy J, Roberts G, Dean T, et al. Changing prevalence of wheeze, rhinitis and allergic sensitisation in late childhood: findings from 2 Isle of Wight birth cohorts 12 years apart. Clin Exp Allergy. 2015;45:1430–8.

    Article  CAS  Google Scholar 

  5. Muraro A, Dubois AE, DunnGalvin A, Hourihane JO, de Jong NW, Meyer R, et al. EAACI Food Allergy and Anaphylaxis Guidelines. Food allergy health-related quality of life measures. Allergy. 2014;69:845–53.

    Article  CAS  Google Scholar 

  6. Burgess JA, Walters EH, Byrnes GB, Matheson MC, Jenkins MA, Wharton CL, et al. Childhood allergic rhinitis predicts asthma incidence and persistence to middle age: a longitudinal study. J Allergy Clin Immunol. 2007;120:863–9.

    Article  Google Scholar 

  7. Guerra S, Sherrill DL, Martinez FD, Barbee RA. Rhinitis as an independent risk factor for adult-onset asthma. J Allergy Clin Immunol. 2002;109:419–25.

    Article  Google Scholar 

  8. Ferdousi HA, Dreborg S. Asthma, bronchial hyperreactivity and mediator release in children with birch pollinosis. ECP and EPX levels are not related to bronchial hyperreactivity. Clin Exp Allergy. 1997;27:530–9.

    Article  CAS  Google Scholar 

  9. Ferdousi HA, Zetterstrom O, Dreborg S. Bronchial hyper-responsiveness predicts the development of mild clinical asthma within 2 yr in school children with hay-fever. Pediatr Allergy Immunol. 2005;16:478–86.

    Article  Google Scholar 

  10. Rochat MK, Illi S, Ege MJ, Lau S, Keil T, Wahn U, et al. Allergic rhinitis as a predictor for wheezing onset in school-aged children. J Allergy Clin Immunol. 2010;126:1170–5.

    Article  Google Scholar 

  11. Jacobsen L, Niggemann B, Dreborg S, Ferdousi HA, Halken S, Host A, et al. Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study. Allergy. 2007;62:943–8.

    Article  CAS  Google Scholar 

  12. Martin PE, Matheson MC, Gurrin L, Burgess JA, Osborne N, Lowe AJ, et al. Childhood eczema and rhinitis predict atopic but not nonatopic adult asthma: a prospective cohort study over 4 decades. J Allergy Clin Immunol. 2011;127:1473–9.

    Article  Google Scholar 

  13. Dhami S, Nurmatov U, Arasi S, Khan T, Asaria M, Zaman H, et al. Allergen immunotherapy for allergic rhinoconjunctivitis: a systematic review and meta-analysis. Allergy 2017;72:1597–1631.

    Article  CAS  Google Scholar 

  14. Dhami S, Kakourou A, Asamoah F, Agache I, Lau S, Jutel M, et al. Allergen immunotherapy for allergic asthma: a systematic review and meta-analysis. Allergy 2017;72:1825–48.

    Article  CAS  Google Scholar 

  15. Dhami S, Zaman H, Varga EM, Sturm GJ, Muraro A, Akdis CA, et al. Allergen immunotherapy for insect venom allergy: a systematic review and meta-analysis. Allergy. 2017;72:342–65.

    Article  CAS  Google Scholar 

  16. Bousquet J, Lockey R, Malling HJ. Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. J Allergy Clin Immunol. 1998;102:558–62.

    Article  CAS  Google Scholar 

  17. Jutel M, Agache I, Bonini S, Burks AW, Calderon M, Canonica W, et al. International consensus on allergen immunotherapy II: mechanisms, standardization, and pharmacoeconomics. J Allergy Clin Immunol. 2016;137:358–68.

    Article  Google Scholar 

  18. Jutel M, Agache I, Bonini S, Burks AW, Calderon M, Canonica W, et al. International consensus on allergy immunotherapy. J Allergy Clin Immunol. 2015;136:556–68.

    Article  Google Scholar 

  19. Pfaar O, Bachert C, Bufe A, Buhl R, Ebner C, Eng P, et al. Guideline on allergen-specific immunotherapy in IgE-mediated allergic diseases: S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Society for Pediatric Allergy and Environmental Medicine (GPA), the Medical Association of German Allergologists (AeDA), the Austrian Society for Allergy and Immunology (OGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Dermatology (DDG), the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), the German Society of Pediatrics and Adolescent Medicine (DGKJ), the Society for Pediatric Pneumology (GPP), the German Respiratory Society (DGP), the German Association of ENT Surgeons (BV-HNO), the Professional Federation of Paediatricians and Youth Doctors (BVKJ), the Federal Association of Pulmonologists (BDP) and the German Dermatologists Association (BVDD). Allergo J Int. 2014;23:282–319.

    Article  Google Scholar 

  20. Jacobsen L, Nuchel PB, Wihl JA, Lowenstein H. Ipsen H. Immunotherapy with partially purified and standardized tree pollen extracts. IV. Results from long-term (6-year) follow-up. Allergy. 1997;52:914–20.

    Article  CAS  Google Scholar 

  21. Nieto A, Wahn U, Bufe A, Eigenmann P, Halken S, Hedlin G, et al. Allergy and asthma prevention 2014. Pediatr Allergy Immunol. 2014;25:516–33.

    Article  Google Scholar 

  22. Eng PA, Borer-Reinhold M, Heijnen IA, Gnehm HP. Twelve-year follow-up after discontinuation of preseasonal grass pollen immunotherapy in childhood. Allergy. 2006;61:198–201.

    Article  CAS  Google Scholar 

  23. Eng PA, Reinhold M, Gnehm HP. Long-term efficacy of preseasonal grass pollen immunotherapy in children. Allergy. 2002;57:306–12.

    Article  CAS  Google Scholar 

  24. Kristiansen M, Dhami S, Netuveli G, Halken S, Muraro A, Roberts G, et al. Allergen immunotherapy for the prevention of allergy: a systematic review and meta-analysis. Pediatr Allergy Immunol. 2017;28:18–29.

    Article  Google Scholar 

  25. •• Halken S, Larenas-Linnemann D, Roberts G, Calderon MA, Angier E, Pfaar O, et al. EAACI guidelines on allergen immunotherapy: prevention of allergy. Pediatr Allergy Immunol. 2017;28:728–45 A comprehensive guideline based on AGREE and including gaps in the evidence of the preventive capacity of AIT.

    Article  Google Scholar 

  26. • Dhami S, Nurmatov U, Halken S, Calderon MA, Muraro A, Roberts G, et al. Allergen immunotherapy for the prevention of allergic disease: protocol for a systematic review. Pediatr Allergy Immunol. 2016;27:236–41 A comprehensive systematic review of the preventive capacity of AIT.

    Article  Google Scholar 

  27. Valovirta E, Berstad AK, de Blic J, Bufe A, Eng P, Halken S, et al. Design and recruitment for the GAP trial, investigating the preventive effect on asthma development of an SQ-standardized grass allergy immunotherapy tablet in children with grass pollen-induced allergic rhinoconjunctivitis. Clin Ther. 2011;33:1537–46.

    Article  CAS  Google Scholar 

  28. Holt PG, Sly PD, Sampson HA, Robinson P, Loh R, Lowenstein H, et al. Prophylactic use of sublingual allergen immunotherapy in high-risk children: a pilot study. J Allergy Clin Immunol. 2013;132:991–3.

    Article  CAS  Google Scholar 

  29. Zolkipli Z, Roberts G, Cornelius V, Clayton B, Pearson S, Michaelis L, et al. Randomized controlled trial of primary prevention of atopy using house dust mite allergen oral immunotherapy in early childhood. J Allergy Clin Immunol. 2015;136:1541–7.

    Article  Google Scholar 

  30. Crimi N, Li GF, Mangano G, Paolino G, Mastruzzo C, Vancheri C, et al. A randomized, controlled study of specific immunotherapy in monosensitized subjects with seasonal rhinitis: effect on bronchial hyperresponsiveness, sputum inflammatory markers and development of asthma symptoms. Ann Ital Med Int. 2004;19:98–108.

    PubMed  Google Scholar 

  31. Grembiale RD, Camporota L, Naty S, Tranfa CM, Djukanovic R, Marsico SA. Effects of specific immunotherapy in allergic rhinitic individuals with bronchial hyperresponsiveness. Am J Respir Crit Care Med. 2000;162:2048–52.

    Article  CAS  Google Scholar 

  32. Niggemann B, Jacobsen L, Dreborg S, Ferdousi HA, Halken S, Host A, et al. Five-year follow-up on the PAT study: specific immunotherapy and long-term prevention of asthma in children. Allergy. 2006;61:855–9.

    Article  CAS  Google Scholar 

  33. Moller C, Dreborg S, Ferdousi HA, Halken S, Host A, Jacobsen L, et al. Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). J Allergy Clin Immunol. 2002;109:251–6.

    Article  Google Scholar 

  34. Song W, Lin X, Chai R. Efficacy evaluation of standardized dust mite allergen specific immunotherapy to patients of allergic rhinitis. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2014;28:300–2.

    CAS  PubMed  Google Scholar 

  35. Moller C, Dreborg S, Lanner A, Bjorksten B. Oral immunotherapy of children with rhinoconjunctivitis due to birch pollen allergy. A double blind study. Allergy. 1986;41:271–9.

    Article  CAS  Google Scholar 

  36. Novembre E, Galli E, Landi F, Caffarelli C, Pifferi M, De ME, et al. Coseasonal sublingual immunotherapy reduces the development of asthma in children with allergic rhinoconjunctivitis. J Allergy Clin Immunol. 2004;114:851–7.

    Article  CAS  Google Scholar 

  37. Marogna M, Tomassetti D, Bernasconi A, Colombo F, Massolo A, Businco AD, et al. Preventive effects of sublingual immunotherapy in childhood: an open randomized controlled study. Ann Allergy Asthma Immunol. 2008;101:206–11.

    Article  Google Scholar 

  38. •• Valovirta E, Petersen TH, Piotrowska T, Laursen MK, Andersen JS, Sorensen HF, et al. Results from the 5-year SQ grass SLIT-tablet asthma prevention (GAP) trial in children with grass pollen allergy. J Allergy Clin Immunol. 2018;141:529–38. The first high quality RCT investigating the asthma preventive effect of grass tablet SLIT.

  39. Schmitt J, Schwarz K, Stadler E, Wustenberg EG. Allergy immunotherapy for allergic zrhinitis effectively prevents asthma: results from a large retrospective cohort study. J Allergy Clin Immunol. 2015;136:1511–6.

    Article  Google Scholar 

  40. Zielen S, Devillier P, Heinrich J, Richter H, Wahn U. Sublingual immunotherapy provides long-term relief in allergic rhinitis and reduces the risk of asthma: a retrospective, real-world database analysis. Allergy 2018;73:165–77.

    Article  Google Scholar 

  41. Peng H, Li CW, Lin ZB, Li TY. Long-term efficacy of specific immunotherapy on house dust mite-induced allergic rhinitis in China. Otolaryngol Head Neck Surg. 2013;149:40–6.

    Article  Google Scholar 

  42. Pfaar O, Demoly P, van Gerth WR, Bonini S, Bousquet J, Canonica GW, et al. Recommendations for the standardization of clinical outcomes used in allergen immunotherapy trials for allergic rhinoconjunctivitis: an EAACI Position Paper. Allergy. 2014;69:854–67.

    Article  CAS  Google Scholar 

  43. Garcia BE, Gonzalez-Mancebo E, Barber D, Martin S, Tabar AI, Diaz de Durana AM, et al. Sublingual immunotherapy in peach allergy: monitoring molecular sensitizations and reactivity to apple fruit and Platanus pollen. J Investig Allergol Clin Immunol. 2010;20:514–20.

    CAS  PubMed  Google Scholar 

  44. Szepfalusi Z, Bannert C, Ronceray L, Mayer E, Hassler M, Wissmann E, et al. Preventive sublingual immunotherapy in preschool children: first evidence for safety and pro-tolerogenic effects. Pediatr Allergy Immunol. 2014;25:788–95.

    Article  Google Scholar 

  45. Pifferi M, Baldini G, Marrazzini G, Baldini M, Ragazzo V, Pietrobelli A, et al. Benefits of immunotherapy with a standardized Dermatophagoides pteronyssinus extract in asthmatic children: a three-year prospective study. Allergy. 2002;57:785–90.

    Article  CAS  Google Scholar 

  46. Marogna M, Spadolini I, Massolo A, Canonica GW, Passalacqua G. Randomized controlled open study of sublingual immunotherapy for respiratory allergy in real-life: clinical efficacy and more. Allergy. 2004;59:1205–10.

    Article  CAS  Google Scholar 

  47. Limb SL, Brown KC, Wood RA, Eggleston PA, Hamilton RG, Adkinson NF Jr. Long-term immunologic effects of broad-spectrum aeroallergen immunotherapy. Int Arch Allergy Immunol. 2006;140:245–51.

    Article  CAS  Google Scholar 

  48. Dominicus R. 3-Years’ long-term effect of subcutaneous immunotherapy (SCIT) with a high-dose hypoallergenic 6-grass pollen preparation in adults. Eur Ann Allergy Clin Immunol. 2012;44:135–40.

    CAS  PubMed  Google Scholar 

  49. Des Roches A, Paradis L, Menardo JL, Bouges S, Daures JP, Bousquet J. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. VI. Specific immunotherapy prevents the onset of new sensitizations in children. J Allergy Clin Immunol. 1997;99:450–3.

    Article  CAS  Google Scholar 

  50. Inal A, Altintas DU, Yilmaz M, Karakoc GB, Kendirli SG, Sertdemir Y. Prevention of new sensitizations by specific immunotherapy in children with rhinitis and/or asthma monosensitized to house dust mite. J Investig Allergol Clin Immunol. 2007;17:85–91.

    CAS  PubMed  Google Scholar 

  51. Reha CM, Ebru A. Specific immunotherapy is effective in the prevention of new sensitivities. Allergol Immunopathol (Madr). 2007;35:44–51.

    Article  CAS  Google Scholar 

  52. Asero R. Injection immunotherapy with different airborne allergens did not prevent de novo sensitization to ragweed and birch pollen north of Milan. Int Arch Allergy Immunol. 2004;133:49–54.

    Article  CAS  Google Scholar 

  53. Harmanci K, Razi CH, Toyran M, Kanmaz G, Cengizlier MR. Evaluation of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy. Asian Pac J Allergy Immunol. 2010;28:7–13.

    PubMed  Google Scholar 

  54. Tella R, Bartra J, San MM, Olona M, Bosque M, Gaig P, et al. Effects of specific immunotherapy on the development of new sensitisations in monosensitised patients. Allergol Immunopathol (Madr). 2003;31:221–5.

    Article  CAS  Google Scholar 

  55. Ohashi Y, Nakai Y. Immunotherapy for cure and prophylaxis of allergic rhinitis. Clin Exp Allergy Rev. 2009;9:6–10.

    Article  CAS  Google Scholar 

  56. Di Rienzo V, Marcucci F, Puccinelli P, Parmiani S, Frati F, Sensi L, et al. Long-lasting effect of sublingual immunotherapy in children with asthma due to house dust mite: a 10-year prospective study. Clin Exp Allergy. 2003;33:206–10.

    Article  Google Scholar 

  57. Purello-D’Ambrosio F, Gangemi S, Merendino RA, Isola S, Puccinelli P, Parmiani S, et al. Prevention of new sensitizations in monosensitized subjects submitted to specific immunotherapy or not. A retrospective study. Clin Exp Allergy. 2001;31:1295–302.

    Article  Google Scholar 

  58. Marogna M, Spadolini I, Massolo A, Canonica GW, Passalacqua G. Long-lasting effects of sublingual immunotherapy according to its duration: a 15-year prospective study. J Allergy Clin Immunol. 2010;126:969–75.

    Article  Google Scholar 

  59. Pajno GB, Barberio G, De Luca F, Morabito L, Parmiani S. Prevention of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy. A six-year follow-up study. Clin Exp Allergy. 2001;31:1392–7.

    Article  CAS  Google Scholar 

  60. Gulen F, Zeyrek D, Can D, Altinoz S, Koksoy H, Demir E, et al. Development of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy. Asian Pac J Allergy Immunol. 2007;25:7–11.

    PubMed  Google Scholar 

  61. Di BD, Plaia A, Leto-Barone MS, La PS, Macchia L, Di LG. Efficacy of allergen immunotherapy in reducing the likelihood of developing new allergen sensitizations: a systematic review. Allergy. 2017;72:691–704.

    Article  Google Scholar 

  62. Di LG, Leto-Barone MS, La PS, Plaia A, Di BD. The effect of allergen immunotherapy in the onset of new sensitizations: a meta-analysis. Int Forum Allergy Rhinol. 2017;7:660–9.

    Article  Google Scholar 

  63. Roberts G, Pfaar O, Akdis CA, Ansotegui IJ, Durham SR, van WR G, et al. EAACI guidelines on allergen immunotherapy: allergic rhinoconjunctivitis. Allergy. 2018;73:765–98.

    Article  CAS  Google Scholar 

  64. Di Bona D, Plaia A, Leto-Barone MS, La Piana S, Di Lorenzo G. Efficacy of grass pollen allergen sublingual immunotherapy tablets for seasonal allergic rhinoconjunctivitis: a systematic review and meta-analysis. JAMA Intern Med. 2015;175:1301–9.

    Article  Google Scholar 

  65. Calderon MA, Vidal C, Rodriguez Del RP, Just J, Pfaar O, Tabar AI, et al. European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI): a real-life clinical assessment. Allergy. 2017;72:462–72.

    Article  CAS  Google Scholar 

  66. Rodriguez Del RP, Vidal C, Just J, Tabar AI, Sanchez-Machin I, Eberle P, et al. The European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI): a paediatric assessment. Pediatr Allergy Immunol. 2017;28:60–70.

    Article  Google Scholar 

  67. Larenas-Linnemann DE, Mosges R. Dosing of European sublingual immunotherapy maintenance solutions relative to monthly recommended dosing of subcutaneous immunotherapy. Allergy Asthma Proc. 2016;37:50–6.

    Article  Google Scholar 

  68. Sander I, Fleischer C, Meurer U, Bruning T, Raulf-Heimsoth M. Allergen content of grass pollen preparations for skin prick testing and sublingual immunotherapy. Allergy. 2009;64:1486–92.

    Article  CAS  Google Scholar 

  69. Larenas-Linnemann D. Direct comparison of efficacy of sublingual immunotherapy tablets for rhinoconjunctivitis. Ann Allergy Asthma Immunol. 2016;116:274–86.

    Article  Google Scholar 

  70. Bachert C, Larche M, Bonini S, Canonica GW, Kundig T, Larenas-Linnemann D, et al. Allergen immunotherapy on the way to product-based evaluation—a WAO statement. World Allergy Organ J. 2015;8:29.

    Article  Google Scholar 

  71. Brozek JL, Bousquet J, Agache I, Agarwal A, Bachert C, Bosnic-Anticevich S, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines-2016 revision. J Allergy Clin Immunol. 2017;140:950–8.

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  1. Hans Christian Andersen Children’s Hospital, Odense University Hospital, Sdr Boulevard 29, 5000, Odense C, Denmark

    Susanne Halken MD, DMSci

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  1. Susanne Halken MD, DMSci
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S. Halken reports personal fees from different companies, e.g., MEDA, Stallergenes, Allergopharma, and ALK-Abelló, outside the submitted work.

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This article is part of the Topical Collection on Allergic Asthma

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Halken, S. Allergen Immunotherapy for the Prevention of Allergic Asthma. Curr Treat Options Allergy 5, 453–469 (2018). https://doi.org/10.1007/s40521-018-0179-z

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