Current Allergy and Asthma Reports

, Volume 13, Issue 6, pp 571–579 | Cite as

Will Sublingual Immunotherapy Offer Benefit for Asthma?

  • Carlos E. Baena-Cagnani
  • Désirée Larenas-Linnemann
  • Alvaro Teijeiro
  • Giorgio Walter Canonica
  • Giovanni Passalacqua
Hot Topic

Abstract

Evidence shows that sublingual immunotherapy (SLIT) is indicated in patients with allergic rhinitis (AR). In this article we discuss whether SLIT could offer benefit for children and adults with asthma. We reviewed individual trials on SLIT in asthmatic patients, but also asthma data reported in some SLIT trials conducted in AR patients. Findings were complemented with data from systematic reviews and meta-analysis on the subject since 2000 and some guidelines that mention immunotherapy for asthma treatment. In AR patients with concomitant persistent asthma, SLIT reduces medication needs while maintaining symptom control. This holds especially true for house dust mite SLIT. Data on pollen SLIT and lung symptom improvement with SLIT, however, are less convincing. Therefore, we suggest SLIT should be added as an optional add-on therapy for patients with asthma whenever a causative allergen has been demonstrated and AR is associated with asthma. For the future, SLIT should be studied in specifically designed asthma studies in allergic asthmatics without AR.

Keywords

Asthma Immunotherapy Sublingual Children Adults SLIT Pollen SLIT House dust mite SLIT 

References

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

  1. 1.
    b. Global strategy on asthma management and prevention. 2012 [cited 2013 11th May]; Available from: http://www.ginasthma.org/local/uploads/files/GINA_Report_2012Feb13.pdf.
  2. 2.
    • Lazic N, Roberts G, Custovic A, Belgrave D, Bishop CM, Winn J, et al. Multiple atopy phenotypes and their associations with asthma: similar findings from two birth cohorts. Allergy. 2013. Epub 2013/04/30. Importance of the different asthma phenotypes; those linked to allergy will probably best benefit from allergen-specific immunotherapy.Google Scholar
  3. 3.
    Custovic A, Lazic N, Simpson A. Pediatric asthma and development of atopy. Curr Opin Allergy Clin Immunol. 2013;13(2):173–80. Epub 2013/02/07.PubMedCrossRefGoogle Scholar
  4. 4.
    2008 EcG. Global strategy for the diagnosis and management of asthma in children 5 years and younger. 2009 [cited 11 May 2013]; Available from: http://www.ginasthma.org/local/uploads/files/GINA_Under5.
  5. 5.
    Wahn U, Bergmann R, Kulig M, Forster J, Bauer CP. The natural course of sensitisation and atopic disease in infancy and childhood. Pediatr Allergy Immunol. 1997;8(10 Suppl):16–20. Epub 1997/01/01.PubMedGoogle Scholar
  6. 6.
    Huss K, Naumann PL, Mason PJ, Nanda JP, Huss RW, Smith CM, et al. Asthma severity, atopic status, allergen exposure and quality of life in elderly persons. Ann Allergy Asthma Immunol. 2001;86(5):524–30. Epub 2001/05/31.PubMedCrossRefGoogle Scholar
  7. 7.
    Sporik R, Holgate ST, Platts-Mills TA, Cogswell JJ. Exposure to house-dust mite allergen (Der p I) and the development of asthma in childhood. A prospective study. N Engl J Med. 1990;323(8):502–7. Epub 1990/08/23.PubMedCrossRefGoogle Scholar
  8. 8.
    Holt PG, Rowe J, Kusel M, Parsons F, Hollams EM, Bosco A, et al. Toward improved prediction of risk for atopy and asthma among preschoolers: a prospective cohort study. J Allergy Clin Immunol. 2010;125(3):653–9, 9 e1–9 e7. Epub 2010/03/17.Google Scholar
  9. 9.
    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(4):450–3. Epub 1997/04/01.PubMedCrossRefGoogle Scholar
  10. 10.
    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(2):85–91. Epub 2007/04/28.PubMedGoogle Scholar
  11. 11.
    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(1):7–13. Epub 2010/06/10.PubMedGoogle Scholar
  12. 12.
    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(2):251–6. Epub 2002/02/14.PubMedCrossRefGoogle Scholar
  13. 13.
    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(8):943–8. Epub 2007/07/11.PubMedCrossRefGoogle Scholar
  14. 14.
    Valovirta E. Effect of AIT in children including potential to prevent the development of asthma. Allergy. 2011;66 Suppl 95:53–4. Epub 2011/06/28.PubMedCrossRefGoogle Scholar
  15. 15.
    •• 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(10):1537–46. Epub 2011/10/18. Design of one of the most interesting studies to come out in the area of preventive effect of SLIT. If the preventive effect can be shown, this might mark a change in conduct and a widening of the indication for SLIT in the future. PubMedCrossRefGoogle Scholar
  16. 16.
    Abramson MJ, Puy RM, Weiner JM. Injection allergen immunotherapy for asthma. Cochrane Database Syst Rev. 2010;8, CD001186. Epub 2010/08/06.PubMedGoogle Scholar
  17. 17.
    Larenas-Linnemann DE, Pietropaolo-Cienfuegos DR, Calderon MA. Evidence of effect of subcutaneous immunotherapy in children: complete and updated review from 2006 onward. Ann Allergy Asthma Immunol. 2011;107(5):407–16 e11. Epub 2011/10/25.PubMedCrossRefGoogle Scholar
  18. 18.
    Penagos M, Passalacqua G, Compalati E, Baena-Cagnani CE, Orozco S, Pedroza A, et al. Metaanalysis of the efficacy of sublingual immunotherapy in the treatment of allergic asthma in pediatric patients, 3 to 18 years of age. Chest. 2008;133(3):599–609. Epub 2007/10/24.PubMedCrossRefGoogle Scholar
  19. 19.
    Compalati E, Passalacqua G, Bonini M, Canonica GW. The efficacy of sublingual immunotherapy for house dust mites respiratory allergy: results of a GA2LEN meta-analysis. Allergy. 2009;64(11):1570–9. Epub 2009/10/03.PubMedCrossRefGoogle Scholar
  20. 20.
    Larenas-Linnemann D. Sublingual immunotherapy in children: complete and updated review supporting evidence of effect. Curr Opin Allergy Clin Immunol. 2009;9(2):168–76. Epub 2009/03/28.PubMedCrossRefGoogle Scholar
  21. 21.
    •• Larenas Linnemann D, Blaiss M, Van Beever H, Compalati E, Baena-Cagnani C. Pediatric sublingual immunotherapy efficacy: evidence analysis, 2009–2012 Ann Allergy Asthma Immunol. 2013;110. Epub 18 april 2013. Recent complete review of published trials on SLIT in pediatric allergy. Each article is also analyzed on quality of evidence according to GRADE. Clinical and immunological outcomes are presented.Google Scholar
  22. 22.
    • Lin SY, Erekosima N, Kim JM, et al. Sublingual immunotherapy for the treatment of allergic rhinoconjunctivitis and asthma: a systematic review. JAMA. 2013;309(12):1278–88. Evidence for SLIT in respiratory allergy.Google Scholar
  23. 23.
    •• Radulovic S, Wilson D, Calderon M, Durham S. Systematic reviews of sublingual immunotherapy (SLIT). Allergy. 2011;66(6):740–52. Epub 2011/03/30. Second Cochrane meta-analysis of SLIT for respiratory allergy. PubMedCrossRefGoogle Scholar
  24. 24.
    Frati F, Scurati S, Puccinelli P, Justicia JL, Adamec T, Sieber HJ, et al. Development of an allergen extract for sublingual immunotherapy—evaluation of Staloral. Expert Opin Biol Ther. 2009;9(9):1207–15. Epub 2009/07/16.PubMedCrossRefGoogle Scholar
  25. 25.
    Dahl R, Stender A, Rak S. Specific immunotherapy with SQ standardized grass allergen tablets in asthmatics with rhinoconjunctivitis. Allergy. 2006;61(2):185–90. Epub 2006/01/18.PubMedCrossRefGoogle Scholar
  26. 26.
    Marogna M, Spadolini I, Massolo A, Berra D, Zanon P, Chiodini E, et al. Long-term comparison of sublingual immunotherapy vs inhaled budesonide in patients with mild persistent asthma due to grass pollen. Ann Allergy Asthma Immunol. 2009;102(1):69–75. Epub 2009/02/12.PubMedCrossRefGoogle Scholar
  27. 27.
    • Marogna M, Colombo F, Spadolini I, Massolo A, Berra D, Zanon P, et al. Randomized open comparison of montelukast and sublingual immunotherapy as add-on treatment in moderate persistent asthma due to birch pollen. J Investig Allergol Clin Immunol. 2010;20(2):146–52. Epub 2010/05/14. SLIT versus montelukast as add-on treatment in patients with moderate persistent asthma, showing greater benefit for SLIT as it also reduces nasal symptoms.PubMedGoogle Scholar
  28. 28.
    Ott H, Sieber J, Brehler R, Folster-Holst R, Kapp A, Klimek L, et al. Efficacy of grass pollen sublingual immunotherapy for three consecutive seasons and after cessation of treatment: the ECRIT study. Allergy. 2009;64(9):1394–401. Epub 2009/09/22.PubMedCrossRefGoogle Scholar
  29. 29.
    • Nelson HS, Nolte H, Creticos P, Maloney J, Wu J, Bernstein DI. Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults. J Allergy Clin Immunol. 2011;127(1):72–80. e1-2. Epub 2011/01/08. The first big grass tablet SLIT trial in the US.PubMedCrossRefGoogle Scholar
  30. 30.
    •• Durham SR, Emminger W, Kapp A, de Monchy JG, Rak S, Scadding GK, et al. SQ-standardized sublingual grass immunotherapy: confirmation of disease modification 2 years after 3 years of treatment in a randomized trial. J Allergy Clin Immunol. 2012;129(3):717–25 e5. Epub 2012/01/31. Long-term effect of grass tablet SLIT for allergic rhinitis, 2 years after discontinuation of a 3 years’ treatment.PubMedCrossRefGoogle Scholar
  31. 31.
    Milani M, Pecora S, Rainbow Study Investigator G. Clinical relevance of non-grass pollens respiratory allergies in Italy and effects of specific sublingual immunotherapy: The Rainbow Trial, a multicentre 3-year prospective observational study. Eur Ann Allergy Clin Immunol. 2011;43(4):111–6.PubMedGoogle Scholar
  32. 32.
    Migueres M, Fontaine JF, Haddad T, Grosclaude M, Saint-Martin F, Bem David D, et al. Characteristics of patients with respiratory allergy in France and factors influencing immunotherapy prescription: a prospective observational study (REALIS). Int J Immunopathol Pharmacol. 2011;24(2):387–400. Epub 2011/06/11.PubMedGoogle Scholar
  33. 33.
    Caffarelli C, Sensi LG, Marcucci F, Cavagni G. Preseasonal local allergoid immunotherapy to grass pollen in children: a double-blind, placebo-controlled, randomized trial. Allergy. 2000;55(12):1142–7. Epub 2000/12/16.PubMedCrossRefGoogle Scholar
  34. 34.
    Bufe A, Eberle P, Franke-Beckmann E, Funck J, Kimmig M, Klimek L, et al. Safety and efficacy in children of an SQ-standardized grass allergen tablet for sublingual immunotherapy. J Allergy Clin Immunol. 2009;123(1):167–73 e7. Epub 2009/01/10.PubMedCrossRefGoogle Scholar
  35. 35.
    O'Hehir RE, Gardner LM, de Leon MP, Hales BJ, Biondo M, Douglass JA, et al. House dust mite sublingual immunotherapy: the role for transforming growth factor-beta and functional regulatory T cells. Am J Respir Crit Care Med. 2009;180(10):936–47. Epub 2009/08/22.PubMedCrossRefGoogle Scholar
  36. 36.
    Trebuchon F, David M, Demoly P. Medical management and sublingual immunotherapy practices in patients with house dust mite-induced respiratory allergy: a retrospective, observational study. Int J Immunopathol Pharmacol. 2012;25(1):193–206. Epub 2012/04/18.PubMedGoogle Scholar
  37. 37.
    Marogna M, Bruno M, Massolo A, Falagiani P. Long-lasting effects of sublingual immunotherapy for house dust mites in allergic rhinitis with bronchial hyperreactivity: a long-term (13-year) retrospective study in real life. Int Arch Allergy Immunol. 2007;142(1):70–8. Epub 2006/10/04.PubMedCrossRefGoogle Scholar
  38. 38.
    Ariano R, Berto P, Incorvaia C, Di Cara G, Boccardo R, La Grutta S, et al. Economic evaluation of sublingual immunotherapy vs. symptomatic treatment in allergic asthma. Ann Allergy Asthma Immunol. 2009;103(3):254–9. Epub 2009/10/01.PubMedCrossRefGoogle Scholar
  39. 39.
    • Mosbech H. Tolerability and efficacy of house dust mite AIT. Allergy. 2011;66 Suppl 95:55–6. Epub 2011/06/28. First data on house-dust mite tablet SLIT.PubMedCrossRefGoogle Scholar
  40. 40.
    • Marogna M, Massolo A, Colombo F, Isella P, Bruno M, Falagiani P. Children passive smoking jeopardises the efficacy of standard anti-allergic pharmacological therapy, while sublingual immunotherapy withstands. Allergol Immunopathol (Madr). 2011;39(2):60–7. Epub 2011/01/11. SLIT did reduce bronchial hyper-responsiveness and symptoms even in children with passive smoking and asthma symptoms as opposed to pharmacotherapy where hyperreactivity did not improve.CrossRefGoogle Scholar
  41. 41.
    Cortellini G, Spadolini I, Patella V, Fabbri E, Santucci A, Severino M, et al. Sublingual immunotherapy for Alternaria-induced allergic rhinitis: a randomized placebo-controlled trial. Ann Allergy Asthma Immunol. 2010;105(5):382–6. Epub 2010/11/09.PubMedCrossRefGoogle Scholar
  42. 42.
    Pozzan M, Milani M. Efficacy of sublingual specific immunotherapy in patients with respiratory allergy to Alternaria alternata: a randomised, assessor-blinded, patient-reported outcome, controlled 3-year trial. Curr Med Res Opin. 2010;26(12):2801–6. Epub 2010/11/06.PubMedCrossRefGoogle Scholar
  43. 43.
    Roger A, Justicia JL, Navarro LA, Eseverri JL, Ferres J, Malet A, et al. Observational study of the safety of an ultra-rush sublingual immunotherapy regimen to treat rhinitis due to house dust mites. Int Arch Allergy Immunol. 2011;154(1):69–75. Epub 2010/07/29.PubMedCrossRefGoogle Scholar
  44. 44.
    Mosges R, Graute V, Christ H, Sieber HJ, Wahn U, Niggemann B. Safety of ultra-rush titration of sublingual immunotherapy in asthmatic children with tree-pollen allergy. Pediatr Allergy Immunol. 2010;21(8):1135–8. Epub 2010/12/02.PubMedCrossRefGoogle Scholar
  45. 45.
    Stelmach I, Kaczmarek-Wozniak J, Majak P, Olszowiec-Chlebna M, Jerzynska J. Efficacy and safety of high-doses sublingual immunotherapy in ultra-rush scheme in children allergic to grass pollen. Clin Exp Allergy. 2009;39(3):401–8. Epub 2009/01/13.PubMedCrossRefGoogle Scholar
  46. 46.
    • Stelmach I, Kaluzinska-Parzyszek I, Jerzynska J, Stelmach P, Stelmach W, Majak P. Comparative effect of pre-coseasonal and continuous grass sublingual immunotherapy in children. Allergy. 2012;67(3):312–20. Epub 2011/12/07. Both pre-coseasonal and continuous treatments were more efficacious than placebo. Pre-coseasonal treatment was even a bit better than continuous treatment on the nose symptoms.PubMedCrossRefGoogle Scholar
  47. 47.
    • Eifan AO, Akkoc T, Yildiz A, Keles S, Ozdemir C, Bahceciler NN, et al. Clinical efficacy and immunological mechanisms of sublingual and subcutaneous immunotherapy in asthmatic/rhinitis children sensitized to house dust mite: an open randomized controlled trial. Clin Exp Allergy. 2010. Epub 2010/01/27. Both SLIT and SCIT demonstrated clinical improvement compared with pharmacotherapy in asthma/rhinitis children sensitized to HDM.Google Scholar
  48. 48.
    •• Keles S, Karakoc-Aydiner E, Ozen A, Izgi AG, Tevetoglu A, Akkoc T, et al. A novel approach in allergen-specific immunotherapy: combination of sublingual and subcutaneous routes. J Allergy Clin Immunol. 2011;128(4):808–15 e7. Epub 2011/06/07. Up-dosing with SCIT to speed up efficacy and then switching to maintenance treatment with SLIT gave the best results compared to SLIT alone or SCIT alone.PubMedCrossRefGoogle Scholar
  49. 49.
    • Yukselen A, Kendirli SG, Yilmaz M, Altintas DU, Karakoc GB. Effect of one-year subcutaneous and sublingual immunotherapy on clinical and laboratory parameters in children with rhinitis and asthma: a randomized, placebo-controlled, double-blind, double-dummy study. Int Arch Allergy Immunol. 2012;157(3):288–98. Epub 2011/11/02. At the end of 1-year immunotherapy, the clinical efficacy of SCIT on rhinitis and asthma symptoms was more evident than SLIT when compared with the placebo. However, the study was heavily underpowered. SLIT did show improvement, but not statistically significantly.PubMedCrossRefGoogle Scholar
  50. 50.
    Abramson MJ, Puy RM, Weiner JM. Allergen immunotherapy for asthma. Cochrane Database Syst Rev. 2003;4, CD001186. Epub 2003/10/30.PubMedGoogle Scholar
  51. 51.
    Roder E, Berger MY, de Groot H, van Wijk RG. Immunotherapy in children and adolescents with allergic rhinoconjunctivitis: a systematic review. Pediatr Allergy Immunol. 2008;19(3):197–207. Epub 2008/01/29.PubMedCrossRefGoogle Scholar
  52. 52.
    Canonica GW, Bousquet J, Casale T, Lockey RF, Baena-Cagnani CE, Pawankar R, et al. Sub-lingual immunotherapy: World Allergy Organization Position Paper 2009. Allergy. 2009;64 Suppl 91:1–59. Epub 2010/02/06.PubMedGoogle Scholar
  53. 53.
    Turner S, Paton J, Higgins B, Douglas G. British Guidelines on the Management of A. British guidelines on the management of asthma: what’s new for 2011? Thorax. 2011;66(12):1104–5.PubMedCrossRefGoogle Scholar
  54. 54.
    Levy ML, Thomas M, Small I, Pearce L, Pinnock H, Stephenson P. Summary of the 2008 BTS/SIGN British Guideline on the management of asthma. Prim Care Respir J: J Gen Pract Airways Group. 2009;18 Suppl 1:S1–16. Epub 2009/02/12.Google Scholar
  55. 55.
    Papadopoulos NG, Arakawa H, Carlsen KH, Custovic A, Gern J, Lemanske R, et al. International consensus on (ICON) pediatric asthma. Allergy. 2012;67(8):976–97. Epub 2012/06/19.PubMedCrossRefGoogle Scholar
  56. 56.•
    Sikora JM, Tankersley MS, Immunotherapy A, Diagnostics C. Perception and practice of sublingual immunotherapy among practicing allergists in the United States: a follow-up survey. Ann Allergy Asthma Immunol. 2013;110(3):194–7 e4. Epub 2013/04/04. US allergist perception of SLIT as found in a recent survey among ACAAI members. PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Carlos E. Baena-Cagnani
    • 1
    • 3
  • Désirée Larenas-Linnemann
    • 2
  • Alvaro Teijeiro
    • 1
  • Giorgio Walter Canonica
    • 3
  • Giovanni Passalacqua
    • 3
  1. 1.CIMER (Research Center for Respiratory Medicine) Catholic UniversityFundación LIBRACórdobaArgentina
  2. 2.Hospital Médica SurMexicoMexico
  3. 3.Allergy and Respiratory Diseases, Department of Internal MedicineUniversity of GenoaGenoaItaly

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