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Sublingual immunotherapy in pediatric allergic rhinitis and asthma: Efficacy, safety, and practical considerations

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Abstract

Specific allergen immunotherapy (SIT) is the only disease-modifying treatment for allergic rhinitis and asthma. Subcutaneous immunotherapy (SCIT) is the only method with a US Food and Drug Administration (FDA)-approved formulation, but safety concerns limit administration to medical facilities. Sublingual immunotherapy (SLIT), under investigation in the United States, appears to have a more favorable safety profile, which may expand its use to populations generally not treated with SIT (eg, young children). This paper reviews SLIT studies that were specifically limited to the pediatric population. Most demonstrated evidence of clinical efficacy, but approximately 29% failed to demonstrate efficacy in symptom and medication scores in the first treatment year. Efficacy was seen in a broad range of allergen doses, but optimal dose range has not been established. SLIT appeared to be well tolerated in children as young as 2 years, but serious adverse reactions, including anaphylaxis, were reported. SLIT is a promising immunotherapy that may expand the population receiving SIT because of the convenience of home administration due to its favorable safety profile. However, questions remain unanswered, including optimal therapeutic dose.

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References and Recommended Reading

  1. Durham SR, Walker SM, Varga EM, et al.: Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med 1999, 341:468–475.

    Article  PubMed  CAS  Google Scholar 

  2. The Childhood Asthma Management Program Research Group: Long-term effects of budesonide or nedocromil in children with asthma. N Engl J Med 2000, 343:1054–1063.

    Article  Google Scholar 

  3. Guilbert TW, Morgan WJ, Zeiger RS, et al.: Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med 2006, 354:1985–1997.

    Article  PubMed  CAS  Google Scholar 

  4. Ariano R, Berto P, Tracci D, et al.: Pharmacoeconomics of allergen immunotherapy compared with symptomatic drug treatment in patients with allergic rhinitis and asthma. Allergy Asthma Proc 2006, 27:159–163.

    PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  6. Moller C, Dreborg S, Ferdousi HA, et al.: Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). J Allergy Clin Immunol 2002, 109:251–256.

    Article  PubMed  Google Scholar 

  7. Niggemann B, Jacobsen L, Dreborg S, et al.: Five-year follow-up on the PAT study: specific immunotherapy and long-term prevention of asthma in children. Allergy 2006, 61:855–859.

    Article  PubMed  CAS  Google Scholar 

  8. Des Roches A, Paradis L, Menardo JL, et al.: Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. VI. Specific immunotherapy prevents the onset of new sensitizations in children. J Allergy Clin Immunol 1997, 99:450–453.

    Article  PubMed  Google Scholar 

  9. Pajno GB, Barberio G, De Luca F, et al.: 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, 31:1392–1397.

    Article  PubMed  CAS  Google Scholar 

  10. Greisner WA 3rd, Settipane RJ, Settipane GA: Natural history of hay fever: a 23-year follow-up of college students. Allergy Asthma Proc 1998, 19:271–275.

    Article  PubMed  Google Scholar 

  11. Hankin CS, Cox L, Wang Z, Bronstone A: Allergy immunotherapy practice patterns and associated outcomes of care [abstract]. J Allergy Clin Immunol 2007, 119:S344.

    Article  Google Scholar 

  12. Bernstein JA: Pharmacoeconomic considerations for allergen immunotherapy. Clin Allergy Immunol 2004, 18:151–164.

    PubMed  Google Scholar 

  13. Subcutaneous immunotherapy. Allergy 2006, 61(Suppl 82):5–13.

  14. Cox L, Li J, Nelson H, Lockey R: Allergen immunotherapy: a practice parameter second update. J Allergy Clin Immunol 2007, 120:S25–S85.

    Article  Google Scholar 

  15. Di Rienzo V, Pagani A, Parmiani S, et al.: Post-marketing surveillance study on the safety of sublingual immunotherapy in pediatric patients. Allergy 1999, 54:1110–1113.

    Article  PubMed  Google Scholar 

  16. Lombardi C, Gargioni S, Melchiorre A, et al.: Safety of sublingual immunotherapy with monomeric allergoid in adults: multicenter post-marketing surveillance study. Allergy 2001, 56:989–992.

    Article  PubMed  CAS  Google Scholar 

  17. Cox LS, Linnemann DL, Nolte H, et al.: Sublingual immunotherapy: a comprehensive review. J Allergy Clin Immunol 2006, 117:1021–1035.

    Article  PubMed  Google Scholar 

  18. Jacobsen L, Niggemann B, Dreborg S, et al.: Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study. Allergy 2007, 62:943–948.

    Article  PubMed  CAS  Google Scholar 

  19. 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, 55:1142–1147.

    Article  PubMed  CAS  Google Scholar 

  20. Pajno GB, Vita D, Parmiani S, et al.: Impact of sublingual immunotherapy on seasonal asthma and skin reactivity in children allergic to Parietaria pollen treated with inhaled fluticasone propionate. Clin Exp Allergy 2003, 33:1641–1647.

    Article  PubMed  CAS  Google Scholar 

  21. Rolinck-Werninghaus C, Wolf H, Liebke C, et al.: A prospective, randomized, double-blind, placebo-controlled multi-centre study on the efficacy and safety of sublingual immunotherapy (SLIT) in children with seasonal allergic rhinoconjunctivitis to grass pollen. Allergy 2004, 59:1285–1293.

    Article  PubMed  CAS  Google Scholar 

  22. Wuthrich B, Bucher C, Jorg W, et al.: Double-blind, placebo-controlled study with sublingual immunotherapy in children with seasonal allergic rhinitis to grass pollen. J Investig Allergol Clin Immunol 2003, 13:145–8.

    PubMed  CAS  Google Scholar 

  23. Yuksel H, Tanac R, Gousseinov A, Demir E: Sublingual immunotherapy and influence on urinary leukotrienes in seasonal pediatric allergy. J Investig Allergol Clin Immunol 1999, 9:305–313.

    PubMed  CAS  Google Scholar 

  24. Lue KH, Lin YH, Sun HL, et al.: Clinical and immunologic effects of sublingual immunotherapy in asthmatic children sensitized to mites: a double-blind, randomized, placebo-controlled study. Pediatr Allergy Immunol 2006, 17:408–415.

    Article  PubMed  Google Scholar 

  25. Niu CK, Chen WY, Huang JL, et al.: Efficacy of sublingual immunotherapy with high-dose mite extracts in asthma: A multi-center, double-blind, randomized, and placebo-controlled study in Taiwan. Respir Med 2006, 100:1374–1383.

    Article  PubMed  Google Scholar 

  26. Savolainen J, Jacobsen L, Valovirta E: Sublingual immunotherapy in children modulates allergen-induced in vitro expression of cytokine mRNA in PBMC. Allergy 2006, 61:1184–1190.

    Article  PubMed  CAS  Google Scholar 

  27. Valovirta E, Jacobsen L, Ljorring C, et al.: Clinical efficacy and safety of sublingual immunotherapy with tree pollen extract in children. Allergy 2006, 61:1177–1183.

    Article  PubMed  CAS  Google Scholar 

  28. Bufe A, Ziegler-Kirbach E, Stoeckmann E, et al.: Efficacy of sublingual swallow immunotherapy in children with severe grass pollen allergic symptoms: a double-blind placebo-controlled study. Allergy 2004, 59:498–504.

    Article  PubMed  CAS  Google Scholar 

  29. Hirsch T, Sahn M, Leupold W: Double-blind placebo-controlled study of sublingual immunotherapy with house dust mite extract (D.pt.) in children. Pediatr Allergy Immunol 1997, 8:21–27.

    Article  PubMed  CAS  Google Scholar 

  30. Ippoliti F, De Santis W, Volterrani A, et al.: Immunomodulation during sublingual therapy in allergic children. Pediatr Allergy Immunol 2003, 14:216–221.

    Article  PubMed  Google Scholar 

  31. La Rosa M, Ranno C, Andre C, et al.: Double-blind placebo-controlled evaluation of sublingual-swallow immunotherapy with standardized Parietaria judaica extract in children with allergic rhinoconjunctivitis. J Allergy Clin Immunol 1999, 104:425–432.

    Article  PubMed  Google Scholar 

  32. Marcucci F, Sensi L, Di Cara G, et al.: Dose dependence of immunological response to sublingual immunotherapy. Allergy 2005, 60:952–956.

    Article  PubMed  CAS  Google Scholar 

  33. Novembre E, Galli E, Landi F, et al.: Coseasonal sublingual immunotherapy reduces the development of asthma in children with allergic rhinoconjunctivitis. J Allergy Clin Immunol 2004, 114:851–857.

    Article  PubMed  CAS  Google Scholar 

  34. Pajno GB, Morabito L, Barberio G, Parmiani S: Clinical and immunologic effects of long-term sublingual immunotherapy in asthmatic children sensitized to mites: a double-blind, placebo-controlled study. Allergy, 2000:842–849.

  35. Vourdas D, Syrigou E, Potamianou P, et al.: Double-blind, placebo-controlled evaluation of sublingual immunotherapy with standardized olive pollen extract in pediatric patients with allergic rhinoconjunctivitis and mild asthma due to olive pollen sensitization. Allergy 1998, 53:662–672.

    Article  PubMed  CAS  Google Scholar 

  36. Bahceciler NN, Isik U, Barlan IB, Basaran MM: Efficacy of sublingual immunotherapy in children with asthma and rhinitis: a double-blind, placebo-controlled study. Pediatr Pulmonol 2001, 32:49–55.

    Article  PubMed  CAS  Google Scholar 

  37. Tari MG, Mancino M, Monti G: Efficacy of sublingual immunotherapy in patients with rhinitis and asthma due to house dust mite. A double-blind study. Allergol Immunopathol (Madr) 1990, 18:277–284.

    CAS  Google Scholar 

  38. Roder E, Berger MY, Hop WC, et al.: Sublingual immunotherapy with grass pollen is not effective in symptomatic youngsters in primary care. J Allergy Clin Immunol 2007, 119:892–898.

    Article  PubMed  CAS  Google Scholar 

  39. Ippoliti F, De Santis W, Volterrani A, et al.: Psychological stress affects response to sublingual immunotherapy in asthmatic children allergic to house dust mite. Pediatr Allergy Immunol 2006, 17:337–345.

    Article  PubMed  Google Scholar 

  40. Arikan C, Bahceciler NN, Deniz G, et al.: Bacillus Calmette-Guerin-induced interleukin-12 did not additionally improve clinical and immunologic parameters in asthmatic children treated with sublingual immunotherapy. Clin Exp Allergy 2004, 34:398–405.

    Article  PubMed  CAS  Google Scholar 

  41. Bahceciler NN, Arikan C, Taylor A, et al.: Impact of sublingual immunotherapy on specific antibody levels in asthmatic children allergic to house dust mites. Int Arch Allergy Immunol 2005, 136:287–294.

    Article  PubMed  Google Scholar 

  42. Di Rienzo V, Marcucci F, Puccinelli P, 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, 33:206–210.

    Article  PubMed  Google Scholar 

  43. Frew AJ, Powell RJ, Corrigan CJ, Durham SR: Efficacy and safety of specific immunotherapy with SQ allergen extract in treatment-resistant seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006, 117:319–325.

    Article  PubMed  CAS  Google Scholar 

  44. Horst M, Hejjaoui A, Horst V, et al.: Double-blind, placebo-controlled rush immunotherapy with a standardized Alternaria extract. J Allergy Clin Immunol 1990, 85:460–472.

    Article  PubMed  CAS  Google Scholar 

  45. Kohno Y, Minoguchi K, Oda N, et al.: Effect of rush immunotherapy on airway inflammation and airway hyperresponsiveness after bronchoprovocation with allergen in asthma. J Allergy Clin Immunol 1998, 102:927–934.

    Article  PubMed  CAS  Google Scholar 

  46. Varney VA, Gaga M, Frew AJ, et al.: Usefulness of immunotherapy in patients with severe summer hay fever uncontrolled by antiallergic drugs. Bmj 1991, 302:265–269.

    Article  PubMed  CAS  Google Scholar 

  47. Lent AM, Harbeck R, Strand M, et al.: Immunological response to administration of standardized dog allergen extract at differing doses. J Allergy Clin Immunol 2006, 118:1249–1256.

    Article  PubMed  CAS  Google Scholar 

  48. Nanda A, O’Connor M, Anand M, et al.: Dose dependence and time course of the immunologic response to administration of standardized cat allergen extract. J Allergy Clin Immunol 2004, 114:1339–1344.

    Article  PubMed  CAS  Google Scholar 

  49. Ewbank PA, Murray J, Sanders K, et al.: A double-blind placebo-controlled immunotherapy dose-response study with standardized cat extract. J Allergy Clin Immunol 2003, 111:155–161.

    Article  PubMed  CAS  Google Scholar 

  50. Creticos PS, Adkinson NF Jr, Kagey-Sobotka A, et al.: Nasal challenge with ragweed pollen in hay fever patients: effect of immunotherapy. J Clin Invest 1985, 76:2247–2253.

    Article  PubMed  CAS  Google Scholar 

  51. Haugaard L, Dahl R, Jacobsen L: A controlled dose-response study of immunotherapy with standardized, partially purified extract of house dust mite: clinical efficacy and side effects. J Allergy Clin Immunol 1993, 91:709–722.

    Article  PubMed  CAS  Google Scholar 

  52. Bousquet J, Hejjaoui A, Soussana M, Michel FB: Double-blind placebo-controlled immunotherapy grass-pollen allergoids. IV. Comparison of the safety and efficacy of two doses of a high-molecular-weight allergoid. J Allergy Clin Immunol 1990, 85:490–497.

    Article  PubMed  CAS  Google Scholar 

  53. Frew AJ, Powell RJ, Corrigan CJ, et al.: Efficacy and safety of specific immunotherapy with SQ allergen extract in treatment-resistant seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006, 117:319–325.

    Article  PubMed  CAS  Google Scholar 

  54. Durham SR, Yang WH, Pedersen MR, et al.: Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006, 117:802–809.

    Article  PubMed  CAS  Google Scholar 

  55. Purello-D’Ambrosio F, Gangemi S, Merendino RA, et al.: Prevention of new sensitizations in monosensitized subjects submitted to specific immunotherapy or not. A retrospective study. Clin Exp Allergy 2001, 31:1295–1302.

    Article  PubMed  CAS  Google Scholar 

  56. Polosa R, Al-Delaimy WK, Russo C, et al.: Greater risk of incident asthma cases in adults with allergic rhinitis and effect of allergen immunotherapy: a retrospective cohort study. Respir Res 2005 6:153.

    Article  PubMed  Google Scholar 

  57. Polosa R, Li Gotti F, Mangano G, et al.: Effect of immunotherapy on asthma progression, BHR and sputum eosinophils in allergic rhinitis. Allergy 2004, 59:1224–1228.

    Article  PubMed  CAS  Google Scholar 

  58. Stewart GE 2nd, Lockey RF: Systemic reactions from allergen immunotherapy. J Allergy Clin Immunol 1992, 90:567–578.

    Article  PubMed  Google Scholar 

  59. Tripodi S, Di Rienzo Businco A, Benincori N, et al.: Safety and tolerability of ultra-rush induction, less than one hour, of sublingual immunotherapy in children. Int Arch Allergy Immunol 2006, 139:149–152.

    Article  PubMed  CAS  Google Scholar 

  60. Kleine-Tebbe J, Ribel M, Herold DA: Safety of a SQ-standardised grass allergen tablet for sublingual immunotherapy: a randomized, placebo-controlled trial. Allergy 2006, 61:181–184.

    Article  PubMed  CAS  Google Scholar 

  61. Antico A, Pagani M, Crema A: Anaphylaxis by latex sublingual immunotherapy. Allergy 2006, 61:1236–1237.

    Article  PubMed  CAS  Google Scholar 

  62. Eifan AO, Keles S, Bahceciler NN, Barlan IB: Anaphylaxis to multiple pollen allergen sublingual immunotherapy. Allergy 2007, 62:567–568.

    Article  PubMed  CAS  Google Scholar 

  63. Agostinis F, Tellarini L, Canonica GW, et al.: Safety of sublingual immunotherapy with a monomeric allergoid in very young children. Allergy 2005, 60:133.

    Article  PubMed  CAS  Google Scholar 

  64. Fiocchi A, Pajno G, La Grutta S, et al.: Safety of sublingual-swallow immunotherapy in children aged 3 to 7 years. Ann Allergy Asthma Immunol 2005, 95:254–258.

    PubMed  Google Scholar 

  65. Rienzo VD, Minelli M, Musarra A, et al.: Post-marketing survey on the safety of sublingual immunotherapy in children below the age of 5 years. Clin Exp Allergy 2005, 35:560–564.

    Article  PubMed  Google Scholar 

  66. Berto P, Bassi M, Incorvaia C, et al.: Cost effectiveness of sublingual immunotherapy in children with allergic rhinitis and asthma. Allerg Immunol (Paris) 2005, 37:303–308.

    CAS  Google Scholar 

  67. Berto P, Passalacqua G, Crimi N, et al.: Economic evaluation of sublingual immunotherapy vs symptomatic treatment in adults with pollen-induced respiratory allergy: the Sublingual Immunotherapy Pollen Allergy Italy (SPAI) study. Ann Allergy Asthma Immunol 2006, 97:615–621.

    Article  PubMed  Google Scholar 

  68. Lombardi C, Gani F, Landi M, et al.: Quantitative assessment of the adherence to sublingual immunotherapy. J Allergy Clin Immunol 2004, 113:1219–1220.

    Article  PubMed  Google Scholar 

  69. Marogna M, Spadolini I, Massolo A, et al.: Randomized controlled open study of sublingual immunotherapy for respiratory allergy in real-life: clinical efficacy and more. Allergy 2004, 59:1205–1210.

    Article  PubMed  CAS  Google Scholar 

  70. Passalacqua G, Musarra A, Pecora S, et al.: Quantitative assessment of the compliance with a once-daily sublingual immunotherapy regimen in real life (EASY project: evaluation of a novel SLIT formulation during a year). J Allergy Clin Immunol 2006, 117:946–948.

    Article  PubMed  Google Scholar 

  71. Pajno GB, Vita D, Caminiti L, et al.: Children’s compliance with allergen immunotherapy according to administration routes. J Allergy Clin Immunol 2005, 116:1380–1381.

    Article  PubMed  Google Scholar 

  72. Pajno GB, Passalacqua G, Vita D, et al.: Sublingual immunotherapy abrogates seasonal bronchial hyperresponsiveness in children with Parietaria-induced respiratory allergy: a randomized controlled trial. Allergy 2004, 59883–59887.

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Cox, L. Sublingual immunotherapy in pediatric allergic rhinitis and asthma: Efficacy, safety, and practical considerations. Curr Allergy Asthma Rep 7, 410–420 (2007). https://doi.org/10.1007/s11882-007-0063-6

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