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Do Allergy Drops have any Research Behind Them?

This is a list of the research regarding the use of sublingual immunotherapy (allergy drops). Occasionally when our patients ask other ‘knowledgeable’ individuals about allergy drop therapy they get the response, “That is still experimental and unproven.” When someone makes a comment like that, the question is raised: Is that individual too convinced there is only one right way to treat allergies (arrogant), or does that individual not know the science (ignorant), or does that individual have another motive (i.e. insurance company not wanting to pay benefits, or drug company not wanting to loose sales)? Examine the evidence and decide for yourself….

The current understanding of clinical efficacy, safety, mechanisms and indications for the use of sublingual-swallow immunotherapy (SLIT) in the treatment of allergies is embodied in the studies, papers and publications referenced in this document. Over 300 citations are contained in this bibliography, including over 90 peer-reviewed studies published since 1995.

Internationally, SLIT is used widely (50% in some European countries), with full regulatory and government backing. U.S. allergy leaders are writing in support of SLIT. (See section 1) The World Health Organization indicated its use in its 1998 position paper. In 2007, for the second time (originally in 2001), an international workgroup, including U.S. allergists, published the ARIA (Allergy Rhinitis and its Impact on Asthma) guidelines, indicating SLIT as a viable treatment approach. The ARIA paper indicates that not only is there more modern research on SLIT compared to SCIT, but it is also of higher quality in terms of the WHO guidelines for research studies. A Cochrane Review, the most trusted, independent, evidence-based, meta-analysis organization in the world, released their analysis in 2003 and determined SLIT both safe and effective (see section 1).

Two additional pivotal studies to note are the “10 year study…” showing the long lasting effect of SLIT (see section 1), and the 2004 head-to-head study of SLIT to injection in a double-blind, double-dummy approach (see section 2). Few studies have shown that SLIT was not effective, and those results are equivocal or dated.

Additional research efforts are underway in the U.S. and internationally; this document is updated periodically to include further publications. Last updated 03/15/2010

Scientific research and related publications

The following pages are a comprehensive bibliography of studies divided into six categories, with citations presented in chronological order:

1) Recent Major Texts, Guidelines, Reviews, Papers and Editorials

1. Theodoropoulos, D., Morris, M., Morris, D. Emerging concepts of sublingual immunotherapy for allergy. Drugs of Today 2009, 45(10); 737-750

2. Thompson JC, Morris MS. Case reports by Cochard and Eigenmann. J Allergy Clin Immunol 2010; 125:277.

3. Canonica, G.W., Bousquet, J., Casale, T., Lockey, R., Baena-Cagnani, C., Pawankar, R., et.al. Sub-Lingual Immunotherapy World Allergy Organization Position Paper 2009. WAO Journal-Nov 2009

4. Incorvaia C. Mauro M. Do indications to sublingual immunotherapy need to be revised? J Allergy Clin Immunol 2010; 125:277.

5. Marseglia, G., Incorvaia, C., LaRosa, M., Frati, F., Marcucci, F. Sublingual immunotherapy in children: facts and needs. Italian Journal of Pediatrics 2009; 35:31

6. Milgrom, H., Tran, Z.V. Sublingual immunotherapy, meta-analysis, and knowledge in the age of information. Journal of Allergy and Clinical Immunology 2009; 124:162-3.

7. Nieto, A., Mazon, A., Pamies, R., Bruno, L., Navarro, M., Montanes, A. Sublingual immunotherapy for allergic respiratory diseases: An evaluation of meta-analyses. Journal of Allergy and Clinical Immunology 2009.

8. Canonica, G., Passalacqua, G., Villa, E., Baena-Cagnani, C., Compalati,E. Sublingual immunotherapy (SLIT) for House Dust Mites (HDM) in respiratory allergy: update of metanalysis results. Journal of Allergy and Clinical Immunology 2009; 123 (2).

9. Emanuel, I., Parker, M., Traub, O. Undertreatment of allergy: Exploring the utility of sublingual immunotherapy. Otolaryngology – Head and Neck Surgery 2009; 140:615-621.

10. Krouse, J. Sublingual immunotherapy for inhalant allergy: Cautious optimism. Otolaryngology – Head and Neck Surgery. 2009; 140: 622-624.

11. Larenas-Linnemann, D. Sublingual immunotherapy in children: complete and updated review supporting evidence of effect. Current Opinion in Allergy and Clinical Immunology 2009; 9:168-176.

12. Passalacqua, G., Pawankar, R., Baena-Cagnani, C., Canonica, G. Sublingual immunotherapy: where do we stand? Present and future. Current Opinion in Allergy and Clinical Immunology. 2009; 9:1-3.

13. Berto, P., Frati, F., Incorvaia, C. Economic studies of immunotherapy: a review. Current Opinion in Allergy and Clinical Immunology. 2008; 8:585-589.

14. Durham, S. Sublingual immunotherapy: what have we learnt from the ‘big trials’? Current Opinion in Allergy and Clinical Immunology. 2008; 8: 577-584.

15. Gerth van Wijk, R. When to initiate immunotherapy in children with allergic disease? Lessons from the paediatric studies. Current Opinion in Allergy and Clinical Immunology. 2008; 8:565-570.

16. Rodriguez-Perez, N., Penagos, M., Portnoy, J. M., New Types of Immunotherapy in Children. Current Allergy and Asthma Reports. 2008; 8:484-492.

17. Cox, L. Sublingual Immunotherapy and Allergic Rhinitis. Current Allergy and Asthma Reports. 2008; 8:102-110.

18. Mondello, W. Hope for the food allergic: New research may lead to a cure. Living Without, editorial. 2008; Oct-Nov Issue: 22-28.

19. Morogna, M. Preventitive effects of sublingual immunotherapy in childhood: An open randomized controlled study. Annals of Allergy, Asthma, and Immunotherapy. 2008; 101: 206-211.

20. Larenas-Linnemann, D. Sublingual immunotherapy: Dosing in relation to clinical and immunological efficacy. Allergy and Asthma Proceedings. 2008; 29(2):130-138.

21. Canonica, W., Passalacqua, G. Is Sublingual Immunotherapy the Final Answer? Implications for the Allergist. WAO Journal. April 2008: 70-72.

22. Bousquet, J., Khaltaev, N., Cruz, A., Denburg, J., Fokkens, J., Togias, T., et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 Update (in collaboration with the World Health Organization, GA2 LEN* and AllerGen**). Allergy. 2008; 63(86): 8-160.

23. Penagos, M., Passalacqua, G., Compalati, E., Baena-Cagnani, C., 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: 599-609.

24. Cox, L. Sublingual Immunotherapy in Pediatric Allergic Rhinitis and Asthma: Efficacy, Safety, and Practical Considerations. Pediatric Allergy and Immunology. 2007; 7: 410-420.

25. Didier, A., et al. Optimal dose, efficacy, and safety of once-daily sublingual immunotherapy with a 5-grass pollen tablet for seasonal allergic rhinitis. American Academy of Allergy, Asthma & Immunology. October 2007: 1-8.

26. Pondrom, S. Sublingual Immunotherapy (SLIT) Quality of Life Outcomes. COSM 2007: American Rhinologic Society. 2007; 2(8): 24-25.

27. Cox, L. Sublingual immunotherapy, part 2: Safety and practical considerations. The Journal of Respiratory Disease. June 2007; 6: 237-243.

28. Tahamiler, R. Gkioukixel, S., Canakcioglu, S. Long-Term Efficacy of Sublingual Immunotherapy in Patients With Perennial Rhinitis. The Laryngoscope. 2007; 117:965-969.

29. Bachert, C., Vestenbaek, U., Christensen, J., Griffiths, U.K., Poulsen, P.B. Cost-effectiveness of grass allergen tablet (Grazax©) for the prevention of seasonal grass pollen induced rhinoconjunctivitis – a Northern European perspective. Clinical and Experimental Allergy. 2007; 37: 772-779.

30. Pham-Thi, N, et al. Assessment of sublingual immunotherapy efficacy in children with house dust mite-induced allergic asthma optimally controlled by pharmacologic treatment and mite-avoidance measures. Pediatric Allergy and Immunology. 2007; 18: 47-57.

31. Bonds, R. S. et al. Allergic Disorders: When Should You Consider Immunotherapy? Consultant. 2007; 47( 4): 405-412.

32. Cox, L. Sublingual immunotherapy, part 1: Review of Clinical Efficacy. The Journal of Respiratory Diseases. 2007; 28(4): 162-168.

33. Nelson, H. S. Allergen immunotherapy: Where is it now? Journal of Allergy and Clinical Immunology. 2007; 119( 4): 769-779.

34. Durham, S. Tradition and innovation: Finding the right balance. Journal of Allergy and Clinical Immunology. 2007; 119( l4): 792-795.

35. Pajno, G. Sublingual immunotherapy: The optimism and the issues. Journal of Allergy and Clinical Immunology. 2007; 119( 4): 796-801.

36. Nelson, H. S. Advances in upper airway diseases and allergen immunotherapy. Journal of Allergy and Clinical Immunology. 2007; 119(4): 872-880.

37. Passalacqua, G . et al. Allergic Rhinitis and its Impact on Asthma update: Allergen immunotherapy. Journal of Allergy and Clinical Immunology. 2007; 119(4): 881-891.

38. Leatherman, B. et al. Sublingual Immunotherapy: Past, present, paradigm for the future? A review of the literature. Otolaryngology-Head and Neck Surgery. 2007; 136: S1-S20.

39. Marogna, M. et al. Effects of sublingual immunotherapy for multiple or single allergens in polysensitized patients. Annals of Allergy, Asthma & Immunology. 2007; 98: 274-280.

40. Finegold, I. Allergen immunotherapy; Present and future. Asthma and Allergy Proceedings. 2007; 28(1): 44-49.

41. Bellanti, J., Settipane, R. Sublingual immunotherapy: A procedure whose time has come? Asthma and Allergy Proceedings. 2007; 28(1), pages 1-2, January-February 2007.

42. Marogna M. et al . 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. International Archives of Allergy & Immunology. 2006; 142(1): 70-78.

43. Passalacqua G., Canonica, G.W. Sublingual immunotherapy: update 2006. Current Opinion in Allergy and Clinical Immunology. 2006; 6: 449-454.

44. Werner-Klein, M. Sublingual immunotherapy of allergic diseases. Expert Opinion in.Drug Delivery. 2006; 3(5): 599-612.

45. Calamita, Z., Saconato, H., Pela, A.B., Atallah, A.N. Efficacy of sublingual immunotherapy in asthma: systematic review of randomized-clinical trials using the Cochrane Collaboration method. Allergy. 2006; 61(10): 1162-72.

46. Berto, P. 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. Annals of Allergy, Asthma and Immunology. 2006; 97: 615-621.

47. Passalacqua, G., et al. New Insights in Sublingual Immunotherapy. Current Allergy and Asthma Reports. 2006; 6: 407-412.

48. McEldowney, S. J. et al. Pollen Immunotherapy: Selection, Prevention, and Future Directions. Current Allergy and Asthma Reports. 2006; 4: 420-426.

49. Bousquet, J. Sublingual Immunotherapy: Validated! Allergy. 2006; 61( S81): 5.

50. Burastero, S. E. Sublingual immunotherapy for allergic rhinitis: an update. Current Opinion in Otolaryngology & Head and Neck Surgery. 2006; 14: 197-201.

51. Didier, A. Future developments in sublingual immunotherapy. Allergy. 2006; 61(Suppl. 81): 29-31.

52. Malling, H-J. “Sublingual immunotherapy: efficacy – methodology and outcome of clinical trials. Allergy. 2006; 61(Suppl. 81): 24-28.

53. Moingeon, P. Sublingual immunotherapy: from biological extracts to recombinant allergens. Allergy. 2006; 61(Suppl. 81): 15-19.

54. Passalacqua, G. et al. Randomized double-blind controlled study with sublingual carbamylated allergoid immunotherapy in mild rhinitis due to mites. Allergy. 2006; 61: 849-854.

55. Canonica, G.W., Passalacqua G. Sublingual Immunotherapy in the Treatment of Adult Allergic Rhinitis Patients. Allergy. 2006; 61: 20.

56. Pham-Thi, N. et al. Sublingual immunotherapy in the treatment of children. Allergy. 2006; 61 (Suppl. 81): 7-10.

57. Ortolani, C. et al. Practice parameters for sublingual immunotherapy. Monaldi Archives for Chest Disease. 2006; 65(1): 44-6.

58. Guerra, L. et al. Randomized open comparison of the safety of SLIT in a no-updosing and traditional updosing schedule in patients with Parietaria allergy. Allergologia et immunopathologia. 2006; 34(02): 82-83.

59. Mascarell, L., et al. Novel Ways for Immune Intervention in Immunotherapy: Mucosal Allergy Vaccines. Immunology and Allergy Clinics of North America. 2006; 26: 283-306.

60. Cox, L. et al. Sublingual immunotherapy: A comprehensive review. Journal of Allergy and Clinical Immunology. 2006; 117(5): 1021-1035.

61. Nelson, H. Advances in upper airway diseases and allergen immunotherapy. Journal of Allergy and Clinical Immunology. 2006; 117(5): 1047-1053.

62. Durham, S. et al. Sublingual immunotherapy with once-daily grass allergen tablets: A randomized controlled trial in seasonal allergic rhinoconjunctivitis. Journal of Allergy and Clinical Immunology. 2006; 117(4): 802-809.

63. Passalacqua, G. e. al. Non-Injection Routes for Allergen Immunotherapy: Focus on Sublingual Immunotherapy. Inflammation & Allergy – Drug Targets. 2006; 5: 43-51.

64. Passalacqua, G. et al. Quantitative assessment of the compliance with once-daily sublingual immunotherapy regimen in real life (EASY Project: Evaluation of A novel SLIT formulation during a Year”). Journal of Allergy and Clinical Immunology. 2006; 117(4).

65. Potter, P, Update on sublingual immunotherapy. Annals of Allergy, Asthma and Immunology. 2006; 96(Suppl 1): S22-S25.

66. Bieber, T. Allergen-specific sublingual immunotherapy: less mystic, more scientific. Allergy. 2006; 61: 149-150.

67. Dahl R. et al. Specific immunotherapy with SQ standardized grass allergen tablets in asthmatics with rhinoconjunctivitis. Allergy. 2006; 61: 185-190.

68. Cingi, C. et al. Efficacy of long-term sublingual-oral immunotherapy in allergic rhinitis. ACTA Otorhinolaryngol Ital. 2005; 25: 214-219.

69. Marogna, M. et al. Clinical, functional, and immunologic effects of sublingual immunotherapy in birch pollinosis: A 3-year randomized controlled study. Journal of Allergy and Clinical Immunology. 2005; 115(6): 1184-1188.

70. Gidaro, G.B., et al. The safety of sublingual-swallow immunotherapy: an analysis of published studies. Clinical & Experimental Allergy. 2005; 35: 565-571.

71. Pajno, G. Allergen immunotherapy in early childhood: between Scylla and Charybdis Clinical & Experimental Allergy. 2005; 35: 551-553.

72. Courtney, A.U, et al. Childhood Asthma: Treatment Update. American Family Physician. 2005; 71(10): 1959-1968.

73. Parks, K. Advances in Immunotherapy: Current Considerations and Beyond. The Allergy and Immunology Report. 2005; 1(2).

74. Bousquet, J. Sublingual immunotherapy: from proven prevention to putative rapid relief of allergic symptoms. Allergy. 2005; 60: 1-3.

75. Lambrecht, B.N. Dendritic cells in the pathogenesis of asthma. Clinical and Experimental Allergy. 2004; 4: 123-128

76. Nelson, H. Advances in upper airway diseases and allergen immunotherapy. Journal of Allergy and Clinical Immunology. 2004; 113(4):635-42.

77. Passalacqua, G. et al. Efficacy and safety of sublingual immunotherapy. Annals of Allergy, Asthma, and Immunology. 2004; 93(1): 3-12.

78. Portnoy J. Allergen Immunotherapy in the Prevention of Asthma. Current Opinion Allergy Clinical Immunology. 2004; 4(2): 131-136.

79. Passalacqua, G, Canonica, G.W. Sublingual or injection immunotherapy: the final answer? Allergy. 2004; 59: 37-38.

80. Malling, H.J. Comparison of the clinical efficacy and safety of subcutaneous and sublingual immunotherapy: methodological approaches and experimental results. Current Opinion in Allergy and Clinical Immunology. 2004; 4: 539-542.

81. Mosages, R. The role of hyposensitization: do we need to start rethinking? Clinical Opinion in Allergy and Clinical Immunology. 2004; 4: 155-157.

82. Norman, P. S. Immunotherapy: 1999-2004. Journal of Allergy and Clinical Immunology. 2004; 113(6): 1013-1023.

83. Passalacqua G., Lombardi C., Canonica G.W. Sublingual Immunotherapy: An Update. Current Opinion in Allergy and Clinical Immunology. 2004; 4(1).

84. Markert, U.R. and Elsner P. Local Immunotherapy in Allergy. Chemical Immunology and Allergy. (Lead chapter by D. Morris, et al). 2003; Vol. 82, Karger, Basel, Switzerland.

85. Wilson, D.R., Torres, L.M., Durham, S.R. Sublingual immunotherapy for allergic rhinitis. (Cochrane Review), The Cochrane Library, Issue 2. 2003.

86. Canonica, G. W. and Passalacqua, G. Non-injection routes for immunotherapy. Journal of Allergy and Clinical Immunology. 2003; 111(3): 437-448.

87. Nelson, H. S. Advances in upper airway diseases and allergen immunotherapy. Journal of Allergy and Clinical Immunology. 2003; 111(3): S793-798.

88. Di Rienzo, V., Canonica, G.W., and Passalacqua G. Long-lasting effect of sublingual immunotherapy in children with asthma due to house dust mite: a 10 year prospective study. Clinical and Experimental Allergy. 2003; 33: 206-210.

89. Bielory L., Heimall. Review of complementary and alternative medicine in treatment of ocular allergies. Current Opinion in Allergy and Clinical Immunology. 2003; 3: 395-399.

90. Passalacqua, G, Baena-Cagnani, C., Berardi, M., Canonica, G.W. Oral and sublingual immunotherapy in pediatric patients. Current Opinion in Allergy and Clinical Immunology. 2003; 3(2): 139-145.

91. Li, J. et al. Allergen immunotherapy: a practice parameter. Journal of Allergy and Clinical Immunology. 2003; 90: 27.

92. Kagi M.K., Wuthrich, B. Different methods of local allergen-specific immunotherapy. Allergy. 2002; 57: 379-388.

93. Reiber, M.E. Sublingual Administration of Allergen Desensitization. Tennessee Medicine. 2002: 465-467.

94. Douglass, J., O’Hehir, R. Specific allergen immunotherapy: time for alternatives? Clinical and Experimental Allergy. 2002; 32: 1-3.

95. Bousquet, J. The new ARIA guidelines: putting science into practice, Clinical and Experimental Allergy Review. 2002; 2:38-43.

96. Volpe, A. Della, et al. Sublingual Allergen-Specific Immunotherapy in Allergic Rhinitis and Related Pathologies: Efficacy in a Pediatric Population. International Journal of Immunopathology and Pharmacology. 2002; 15(1): 35-40.

97. Malling, H. Is Sublingual Immunotherapy Clinically Effective? Current Opinion Allergy and Clinical Immunology. 2002; 2(6): 523-532.

98. Allergic Rhinitis and its impact on Asthma (ARIA) Workshop Report. Journal of Allergy and Clinical Immunology. 2001; 108(5).

99. Bousquet, J. ARIA Workshop Group Guidelines. Journal of Allergy and Clinical Immunology. 2001: S242-S245.

100. Passalacqua G., Canonica, G.W. Allergen-Specific Sublingual Immunotherapy for Respiratory Allergy. BioDrugs. 2001; 15(8): 509-519.

101. Morris, D.L. Current use of sublingual-swallow immunotherapy. Current Opinion in Otolaryngology & Head and Neck Surgery. 2001; 9(3):179-180.

102. Marogna, M. et al. Clinical Practice Improvement Program for Immunotherapy of Respiratory Allergic Diseases. International Journal of Immunopathology and Pharmacology. 2001;14(2): 93-101.

103. Theodorpoulos, D., Lockey, R. Allergen Immunotherapy: Guidelines, Update and Recommendations of the World Health Organization. Allergy and Asthma Proceedings. 2000; 21(3): 159-66.

104. Frew, A. et al. Sublingual Immunotherapy. Journal of Allergy Clinical Immunology. 2001: 441-444.

105. Brown, J.L., Frew, A..J. The efficacy of oromucosal immunotherapy in respiratory allergy. Clinical & Experimental Allergy. 2001; 21(1): 8-10.

106. Rakoski, J., Wessner, D. A Short Assessment of Sublingual Immunotherapy. International Archives of Allergy and Immunology. 2001; 126: 185-187.

107. Pineda-Algorta, J. et al. Study of the efficacy of sublingual immunotherapy in patients with grass pollen sensitization: Mini Symposium 3 Sublingual Immunotherapy. Allergy. 2000; 63(55): 24.

108. Ano-Garcia, M. et al. Efficacy and safety of sublingual immunotherapy in patients with sensitization to Dermtophagoides pteronyssinus: Mini Symposium 3 Sublingual Immunotherapy. Allergy. 2000; 55(63): 24.

109. Khinchi, M.S. et al. Clinical efficacy of sublingual-swallow and subcutaneous immunotherapy in patients with allergic rhinoconjunctivitis due to birch pollen: Mini Symposium 3 Sublingual Immunotherapy. Allergy. 2000; 63(55): 24.

110. Donato, R.M. Patients with allergic rhinitis from Argentine treated with SLIT (sublingual immunotherapy) a non-injective route. Abstract presented October 2000 IACAI Conf.

111. Malling, H.J. Allergen-specific immunotherapy. Present state and directions for the future. Allergy. 1999; 54: 30-33.

112. Passalacqua, G. et al. Oral and Sublingual Immunotherapy: General Aspects and Critical Considerations. WMW Themenheft: Hyposensibilsierung. 1999: 433-437.

113. Donahue, J.G. et al. Utilization and cost of immunotherapy for allergic asthma and rhinitis. Annals of Allergy, Asthma and Immunology. 1999; 82: 339-347.

114. Bousquet J., Lockey R., Malling H.J. Allergen immunotherapy: therapeutic vaccines for allergic diseases. World Health Organization Position Paper Allergy. 1998; 53(44): 1-29.

115. Malling, H.J. Sublingual Immunotherapy. Clinical Experimental Allergy. 1996; 26: 1228-1231.

116. Passalacqua G., G.W. Canonica. Alternative routes for allergen-specific immunotherapy. Journal of Investigational Allergology and Clinical Immunology. 1996; 6(2): 81-87.

117. Creticos, P.S. A review of oral specific immunotherapy: Expressions on allergen specific immunotherapy. Stallergenes S.A. 1995: 1. (US Based DBPC Study)

2) Studies/Abstracts

11. Incorvaia, C., Rapetti, A., Scurati, S., Puccinelli, P, Capecce, M., Frati, F. Importance of patient’s education in favoring compliance with sublingual immunotherapy. Allergy2010 DOI: 10.1111

2. Skoner, D., Gentile, D., Bush, R., Fasano, M., McLaughlin, A., Esch, R., Sublingual immunotherapy in patients with allergic rhinoconjunctivitis caused by ragweed pollen. Journal of Allergy and Clinical Immunology 2010.

3. Durham, S., Emminger, W., Kapp, A., Colombo, G., de Monchy, J., Rak, S., et. al. Long-term clinical efficacy in grass pollen-induced rhinoconjunctivitis after treatment with SQ-standardized grass allergy immunotherapy tablet. Journal of allergy and Clinical Immunology 2010;125:131

4. Ariano, R., Berto, P., Incorvaia, C., Di Cara, G., Boccardo, R.,LaGrutta, S., et al. Economic evaluation of sublingual immunotherapy vs symptomatic treatment in allergic asthma. Ann Allergy, Asthma Immunol; 2009; 103:254-259.

5. Patriarca, G., Nucera, E., Roncallo, C., Aruanno, A., Lombardo, C., Decinti, M., et. al. Sublingual immunotherapy with venom for patients with Hymenoptera venom allergy. Journal of Allergy and Clinical Immunology 2009.

6. Reshamwala, N., Song, S., Yu, G.P., Swamy, R., Berquist, W., Nguyen, T., et. al. Study of Sublingual Immunotherapy in Subjects with Dermatophagoides Farniae and Timothy Grass Allergy. Journal of Allergy and Clinical Immunology 2008; 123 (2).

7. Emminger, W., Durham, S., Riis, B., Maloney, J., Nolte, H. The efficacy of Single-grass-allergen-immunotherapy-tablet Treatment in Mono- and Multi-sensitized Allergic Rhinitis Patients: Findings from a Post Hoc Analysis. Journal of Allergy and Clinical Immunology 2008; 123 (2)

8. Seidenberg, J., Wahn, U., Emeryk, A., Lheritier-Barrand, M., Gall, M. Evaluation of a Five Grass-pollen Sublingual Immunotherapy Tablets (SLIT) in a Pediatric Population at Peak Pollen Season and Immunological Outcomes. Journal of Allergy and Clinical Immunology 2008; 123 (2).

9. Bufe, A., Henmar, H., Gronager, P., Durham, S. Sublingual Immunotherapy with Fast-Dissolving Grass Tablets Induces Comparable IgF4 Antibody and IgE-blocking Responses in Children and Adults. Journal of Allergy and Clinical Immunology 2009; 123 (2).

10. 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. Annals of Allergy, Asthma & Immunology. 2009; 102:69-75.

11. Omnes, L. F., Bousquet, J., Scheinmann, P., Neukirch, F., Jasso-Mosqueda, G., Chicoye, A., et al. Pharmacoeconomic assessment of specific immunotherapy versus current symptomatic treatment for allergic rhinitis and asthma in France. European Annals of Allergy and Clinical Immunology. 2007; 39(5): 148-156.

12. Severino, M., Cortellini, G., Bonadonna, P., Francescato, E., Panzini, I., Macchia, D., et al. Sublingual immunotherapy for large local reactions caused by honeybee sting: A double-blind placebo-controlled trial. American Academy of Allergy, Asthma & Immunology. 2008: 1-5.

13. Alvarez-Cuesta, E., Berges-Gimeno, P., Mancebo, E.G., Fernandez-Caldas, E., Cuesta-Herranz, J., Casnovas, M. Sublingual immunotherapy with a standardized cat dander extract: Evaluation of efficacy in a double blind placebo controlled study. Allergy: European Journal of Allergy and Clinical Immunology. 2007; 62(7): 810-817.

14. Esch, R. Sublingual immunotherapy. Current Opinion in Otolaryngology & Head and Neck Surgery 2008; 16: 260-264.

15. Esch, R., Bush, R., Peden, D., Lockey, R. Sublingual-oral administration of standardized allergenic extracts: Phase one safety and dosing results. Annals of Allergy, Asthma and Immunology. 2008; 100(5): 475-481.

16. Horiguchi, S., Okamoto, Y., Yonekura, S., Okawa, T., Yamamoto, H., Kunni, N., et al. A randomized controlled trial of sublingual immunotherapy for Japanese cedar pollinosis. International Archives of Allergy & Immunology. 2008; 146: 76-84.

17. Berto, P., Frati, F., Incorvaia, C., Cadario, G., Contiguglia, R., Di Gioacchino, M., et al. Comparison of costs of sublingual immunotherapy and drug treatment in grass-pollen induced allergy: Results from the SIMAP database study. Current Medical Research and Opinion. 2008; 24(1): 261-266.

18. Jacobsen, L., Valovirta, E., How strong is the evidence that immunotherapy in children prevents the progression of allergy and asthma. Current Opinion in Allergy & Clinical Immunology. 2007; 7(6): 556-560.

19. Nuhoglu, Y., Ozumut, SS., Ozdemir, C., Ozdemir, M., Nuhoglu, C., Erguven, M. Sublingual immunotherapy to house dust mite in pediatric patients with allergic rhinitis and asthma: A retrospective analysis of clinical course over a 3-year follow-up period. Journal of Investigational Allergology and Clinical Immunology. 2007; 17(6): 375-378.

20. De Blay, F., Barnig, C., Kanny, G. et al. Sublingual-swallow immunotherapy with standardized 3-grass pollen extract: a double-blind, placebo-controlled study. Annals of Allergy, Asthma, and Immunology. 2007; 99: 453-461.

21. Penagos, M. et al. Meta-analysis of the efficacy of sublingual immunotherapy in the treatment of allergic asthma in pediatric patients, 3 to 18 years of age. Chest. 2007.

22. Cadario, G. Sublingual immunotherapy efficacy in patients with atopic dermatitis and house dust mites sensitivity: a prospective pilot study. Current Medical Research and Opinion. 2007; 23(100): 2503-6.

23. Durham, SR., Riis, B. Grass allergen tablet immunotherapy relieves individual seasonal eye and nasal symptoms, including nasal blockage. Allergy. 2007; 62(8): 954-7.

24. Grier, T., et al. Stability of standardized grass, dust mite, cat, and short ragweed allergens after mixing with mold or cockroach extracts. Annals of Allergy, Asthma, and Immunology. 2007; 99: 151-160.

25. Ozdemir C., et al. Efficacy of long-term sublingual immunotherapy as an adjunct to pharmacotherapy in house dust mire-allergic children with asthma. Pediatric Allergy and Immunology. 2007; 18: 508-515.

26. Roder, E., et al. Sublingual immunotherapy with grass pollen is not effective in symptomatic youngsters in primary care. Journal of Allergy and Clinical Immunology. 2007; 119(4): 892-898.

27. Kinaciyan, T., et al. Successful sublingual immunotherapy with birch pollen has limited effects on concomitant food allergy to apple and the immune response to the Bet v 1 homolog Mal d 1. Journal of Allergy and Clinical Immunology. 2007; 119(4): 937-943.

28. Penagos, M., et al. Efficacy of sublingual immunotherapy in the treatment of allergic rhinitis in pediatric patients 3 to 18 years of age: A meta-analysis of randomized, placebo-controlled, double-blind trials. Annals of Allergy Asthma and Immunology. 2006; 97(2): 141-8.

29. Bordignon, V., Samuele, E.B. Multiple daily administrations of low-dose sublingual immunotherapy in allergic rhinoconjunctivitis. Annals of Allergy, Asthma & Immunology. 2006; 97: 158-163.

30. Dahl, R., et al. Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis. Journal of Allergy and Clinical Immunology. 2006; 118(2): 434-440.

31. Valovirta, E., et al. Clinical efficacy and safety of sublingual immunotherapy with tree pollen extract in children. Allergy. 2006; 61: 1177-1183.

32. Calamita, Z. et al. Efficacy of sublingual immunotherapy in asthma: systematic review of randomized-clinical trials using the Cochrane Collaboration method. Allergy. 2006; 61: 1162-1172.

33. Bernardini, R., et al. Sublingual immunotherapy with a latex extract in paediatric patients: a double blind, placebo-controlled study. Current Medical Research and Opinions. 2006; 22(8): 1515-1522.

34. Niu, C., 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. Respiratory Medicine. 2006: 1-10.

35. Olaguibel, J., Alvarez Puebla, M. Efficacy of sublingual allergen vaccination for respiratory allergy in children. Conclusions from one meta-analysis. Journal of Investigational Allergology and Clinical Immunonlogy. 2005; 15(1): 9-16.

36. Di Rienzo, V., et al. Post-marketing survey on the safety of sublingual immunotherapy in children below the age of 5 years. Clinical and Experimental Allergy. 2005; 35(5): 560.

37. Fiocchi, A., et al. A prospective study on safety of sublingual immunotherapy in children aged 3 to 6 years. Journal of Allergy and Clinical Immunology. 2005; 115(2): S265.

38. Tesse, R., et al. Effects of oral bacterial immunotherapy in children with atopic eczema/dermatitis syndrome. Journal of Allergy and Clinical Immunology. 2005; 115(2): S266.

39. Bahceciler N., et al. Impact of sublingual immunotherapy on specific antibody levels in children allergic to house dust mites. International Archives of Allergy and Immunology. 2005; 136(3): 287-294.

40. Wilson, D., et al. Sublingual immunotherapy for allergic rhinitis: systematic review and meta-analysis. Allergy. 2005; 60(1): page 4.

41. Marogna, M., et al. Randomized controlled open study of sublingual immunotherapy for respiratory allergy in real-life: Clinical efficacy and more. Allergy. 2004; 59(11): 1205-1210.

42. Novembre, E., et al. Coseasonal sublingual immunotherapy reduces the development of
asthma in children with allergic rhinoconjunctivitis. Journal Allergy and Clinical
Immunology. 2004; 114(4): 851-857.

43. Smith, H., et al. Randomized controlled trial of high-dose sublingual immunotherapy to treat allergic rhinitis. Journal Allergy and Clinical Immunology. 2004; 114(4): 831- 837.
44. Savi, E., et al. A latex-containing hepatitis-B vaccine administered in a severely latex allergic paediatric patient after specific sublingual immunotherapy: A case report. Allergy. 2004; 59(9): 1014-1015.

45. Drachenberg, K., et al. Sublingual specific immunotherapy for adults and children: A post marketing surveillance study. Journal of Investigational Allergology and Clinical Immunology. 2004; 32(2): 76-81.

46. Mastrandrea F. The potential role of allergen-specific sublingual immunotherapy in atopic dermatitis. American Journal of Clinical Dermatology. 2004; 5(5): 281-294.

47. Cistero, B., et al. Tolerance and effects on skin reactivity to latex of sublingual rush immunotherapy with a latex extract. Journal of Investigational Allergology and Clinical Immunology. 2004; 14(1): 17-25.

48. Khinich, M. Clinical efficacy of sublingual and subcutaneous birch pollen allergen-specific immunotherapy: A randomized, placebo-controlled, double-blind, double-dummy study. Allergy. 2004; 59: 45-53.

49. Tonnel, A. et al. Allergic rhinitis due to house dust mites: evaluation of the efficacy of specific sublingual immunotherapy. Allergy. 2004; 59: 491-197.

50. Bufe, A. et al. Efficacy of sublingual swallow immunotherapy in children with severe grass pollen allergic symptoms: A double-blind placebo-controlled study. Allergy. 2004; 59(5): 498-504.

51. Pajno, G., et al. Sublingual immunotherapy abrogates seasonal bronchial hyperresponsiveness in children with Parietaria-induced respiratory allergy: A randomized controlled trial dagger. Allergy. 2004; 59(8): 883-887.

52. Pajno, G., et al. Comparisons between injection and sublingual immunotherapy for rhinitis and asthma in allergic children to house dust mite or parietaria pollen. A case controlled study. Journal of Allergy and Clinical Immunology. 2004; 113(2): (abs.).

53. Niu, C., et al. Efficacy and safety of sublingual immunotherapy with high dose house dust mite extract in asthmatic children – a multicenter randomized double-blind, and placebo-controlled study. Journal of Investigational Allergology and Clinical Immunology. 2004; 113(2): (abs.).

54. Mauro, M., et al. Efficacy and safety of subcutaneous and sublingual immunotherapy in birch pollinosis. Journal of Allergy and Clinical Immunology. 2004; 113(2).

55. Melranci, C., Matteoli M., Efficacy of allergoid sublingual immunotherapy in children with asthma and/or allergic rhinoconjunctivitis: Comparison study with drugs. Journal of Allergy and Clinical Immunology. 2004; 113(2): (abs.).

56. Bassi M., et al. High dose sublingual immunotherapy: Economic evaluation from an Italian observational data base study. Journal of Allergy and Clinical Immunology. 2004; 113(2): (abs.).

57. Pajno, G. Efficacy of sublingual immunotherapy in asthma and eczema. Chemical Immunology and Allergy. 2003; 82: 77-88.

58. Wuthrich, B., et al. Double-blind, placebo-controlled study with sublingual immunotherapy in children with seasonal allergic rhinitis to grass pollen. Journal of Investigational Allergology and Clinical Immunology. 2003; 13(3): 145-148.

59. Andre, et al. A double-blind placebo-controlled evaluation of sublingual immunotherapy with a standardized ragweed extract in patients with seasonal rhinitis. International Archives of Allergy and Immunology. 2003; 131: 111-118.

60. Ippoliti, F., et al. Immunomodulation during sublingual therapy in allergic children. Pediatric Allergy and Immunology. 2003; 14: 216-221.

61. Pajno, G., et al. Parietaria pollen sublingual immunotherapy for asthmatic children: Seasonal behavior in methacholine PC20. Journal of Allergy and Clinical Immunology. 2003: (abs).

62. Mortemousque, B., et al. House-dust mite sublingual –swallow immunotherapy in perennial conjunctivitis: A double-blind, placebo-controlled study. Clinical and Experimental Allergy. 2003; 33: 464-469.

63. Gonzalez, E., et al. Efficacy and safety of a standardized sublingual therapeutic vaccine of cat epithelia extract. Journal of Allergy and Clinical Immunology. 2003: S200(abs).

64. Cirla, A., et al. A pre-seasonal birch/hazel sublingual immunotherapy can improve the outcome of grass pollen injective treatment in bisensitized individuals. A case-referent, two year controlled study. Allergol et Immunopath. 2003; 31(1): 31-43.

65. Madonini, F., et al. Long-term and preventive effects of sublingual allergen specific immunotherapy: A retrospective, multicentric study. International Journal of Immunopathology and Pharmacology. 2003; 16(1): 73-79.

66. Bordignon, V., Parmiani, S. Variation of the skin end-point in patients treated with sublingual specific immunotherapy. Journal of Investigative Allergology and Clinical Immunology. 2003; 13(3): 170-176.

67. Torres Lima, M. et al. Grass pollen sublingual immunotherapy for seasonal rhinoconjunctivitis: A randomized controlled trial. Clinical and Experimental Allergy. 2002; 32: 507-514.

68. Silvestri, M., et al. Changes in inflammatory and clinical parameters and in bronchial hyperreactivity in asthmatic children sensitized to house dust mites following sublingual immunotherapy. Journal of Investigative Allergology and Clinical Immunology. 2002; 12(1): 6-7 (abs).

69. Velarde-Domiquez, T., et al. Clinical effectiveness and security of sublingual immunotherapy as a treatment for allergy asthma secondary to Dermaphgoides in pediatric population. Rev Sanid Milit Mex. 2002; 56(1): 10-14 (abs).

70. Molina, A., Criado, J., et al. Inmunoterapia con un extracto oral de Alternaria en el asma infanil. Eficacia clinica, seguridad, repercusiones sobre parametros in vivo e in vitro. Allergol et Immunpathol. 2002; 30(6): 319-330.

71. Olaguibel, J., et al. Adherence to and safety of a high dose sublingual immunotherapy regimen with a standardized grass pollen extract. Journal of Allergy and Clinical Immunology. 2002; 109(1): S201.

72. Pajno, G., et al. Impact of sublingual immunotherapy on seasonal asthma of allergic children to parietaria pollen treated with inhaled fluticasone propionate. Journal of Allergy and Clinical Immunology. 2002; 109(1): S200.

73. Ariano, R., et al. Efficacy of sublingual specific immunotherapy in Cupressaceae allergy using an extract of Cupressus arizonica. A double blind study. Allergol Immunopathol. 2001; 29(6): 238-244.

74. Bahceciler, N., et al. Efficacy of sublingual immunotherapy in children with asthma and rhinitis: A double-blind, placebo-controlled study. Pediatric Pulmonology. 2001; 32: 49-55.

75. Caffarelli, C., et al. Preseasonal local allergoid immunotherapy to grass pollen in children. Allergy. 2000; 55: 1142-1147.

76. Kinchi, m., Poulsen, L., Malling, D., Dieierlaurent, Berjout, A. Course of Birch, Bat V1 and Bat V2, IgE Levels following Sublingual-Swallow and Parenteral Birch Immunotherapy. 2000

77. Valle, C., et al. Effects of sublingual immunotherapy in patients sensitized to Ambrosia. An open controlled study. Allergol et Immunopathol. 2000; 28(6): 311-317.

78. Mastrandrea, F., et al. Specific sublingual immunotherapy in atopic dermatitis. Results of a 6-year follow-up of 35 consecutive patients. Allergol et Immunopathol. 2000; 28(2): 54-62.

79. Pajno, G., et al. Clinical and immunological effects of long-term sublingual immunotherapy in asthmatic children sensitized to mites: A double-blind placebo controlled study. Allergy. 2000; 55: 842-849.

80. Guez, S., et al. House dust mite SLIT in perennial rhinitis: A double blind placebo controlled study. Allergy. 2000; 55: 369-375.

81. Pradalier, A., et al. Sublingual-swallow immunotherapy (SLIT) with a standardized five-grass-pollen extract (drops and sublingual tablets) versus placebo in seasonal rhinitis. Allergy. 1999; 54: 819-828.

82. Bousquet, J., et al. Sublingual-swallow immunotherapy (SLIT) in patients with asthma due to house-dust mites: A double blind, placebo-controlled study. Allergy. 1999; 54(3): 249-260.

83. Purello-D’Ambrosio, F., et al. Sublingual immunotherapy: A double blind placebo controlled trial with Parietaria judaica extract standardized in mass units in patients with rhinoconjunctivitis, asthma or both. Allergy. 1999; 54: 968-973.

84. La Rosa, M., et al. Double-blind placebo-controlled evaluation of sublingual-swallow immunotherapy with standardized Parietaria judaica extract in children with allergic rhinoconjunctivitis. Journal of Allergy and Clinical Immunology. 1999: 425-432.

85. Passalacqua, G., et al. Clinical and immunologic effects of a rush sublingual immunotherapy to Parietaria species: A double-blind, placebo-controlled trial. Journal of Allergy and Clinical Immunology. 1999: 964-968.

86. Di Rienzo, V., et al. Grass pollen specific sublingual/swallow immunotherapy in children: Open-controlled comparison among different treatment protocols. Allergol et Immunopathol. 1999; 27(3): 145-151.

87. Vourdas, D., 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.

88. Clavel, R., Bousquet, J., et al. Clinical efficacy of sublingual-swallow immunotherapy: A double-blind, placebo-controlled trial of standardized five-grass-pollen extract in rhinitis. Allergy. 1998; 53: 493-498.

89. Horak, F., et al. Immunotherapy with sublingual birch pollen extract. A short-term double blind placebo study. Journal of Investigative Allergology and Clinical Immunology. 1998; 8(3): 165-171.

90. Hordijk, G., et al. Sublingual immunotherapy with a standardised grass pollen extract: A double-blind placebo-controlled study. Allergol et Immunopathol. 26(5): 234-240.

91. Passalacqua, G., et al. Randomized controlled trial of local allergoid immunotherapy on allergic inflammation in mite-induced rhinoconjunctivitis. The Lancet. 1998; 351: 629-632.

92. Luwema, R., et al. Sublingual immunotherapy with a standardized grass pollen extract (Oralgen); A placebo controlled study. The Journal of Allergy and Clinical Immunology. 1997; 99(1): Part 2 (abs 282).

93. Passalacqua, G., et al. Clinical and immunological effects of a long-term sublingual-oral immunotherapy to mite: A double blind study. The Journal of Allergy and Clinical Immunology. 1997; 99(1): Part 2 (abs 1630).

94. Van Deusen, M., et al. Efficacy and safety of oral immunotherapy with short ragweed. Annals of Allergy, Asthma & Immunology. 1997; 78: 573-580.

95. Gozalo, F., et al. Clinical efficacy and tolerance of two year Lolium perenne sublingual immunotherapy. Allergol et Immunopathol. 1997; 25(5): 219-227.

96. Passalacqua, G. Sublingual immunotherapy: Accumulated experience. Journal of Investigative Allergology and Clinical Immunology. 1997; 7(5): 364-366.

97. Hirsh, T., et al. Double blind placebo controlled study of sublingual immunotherapy with house dust mites extracts in children. Pediatric Allergy & Immunology. 1997; 8: 21-27.

98. Purello-D’Ambrosio, F., et al. Rush sublingual immunotherapy in parietaria allergic patients. Allergol et Immunopathol. 1996; 21(4): 146-151.

99. Troise, C., et al. Sublingual immunotherapy in Parietaria pollen-induced rhinitis: A double-blind study. Journal of Investigational Allergology and Clinical Immunology. 1995; 5(1): 25-30.

100. Clavel, R., et al. Reduction of corticosteroid therapy by sublingual immunotherapy. Double blind study against placebo of Standardized 5 Grass Pollen Extract in Rhinitis. Allergy. 1995; 50(26): 279.

101. Giovane, A., et al. A three-year double-blind placebo-controlled study with specific oral immunotherapy to Dermatophagoides: Evidence of safety and efficacy in paediatric patients. Clinical and Experimental Allergy. 1994; 24: 53-59.

102. Sabbah, A., et al. A double-blind, placebo-controlled trial by the sublingual route of immunotherapy with a standardized grass pollen. Allergy. 1994; 49: 309-313.

103. Casanovas, M., et al. Double-blind, placebo-controlled clinical trial of preseasonal treatment with allergenic extracts of Olea europaea pollen administered sublingually. Journal of Investigational Allergology and Clinical Immunology. 1994; 4(6): 305-314.

104. Tari, M., et al. Immunologic evaluation of 24 month course of sublingual immunotherapy. Allergol et Immunopathol. 1994; 22(5): 209-216.

105. Tari, M., et al. Efficacy of sublingual immunotherapy in patients with rhinitis and asthma due to house dust mite-A double blind study. Allergol et Immunopathol. 1990; 18(5): 277-284.

106. Leng, X., et al. A double-blind trial of oral immunotherapy for Artemisia pollen asthma with evaluation of bronchial response to the pollen allergen and serum-specific IgE antibody. Annals of Allergy, Asthma & Immunology. 1990; 64: 27-31.

107. Taudorf, E., et al. Oral immunotherapy in birch pollen hayfever. Journal of Allergy and Clinical Immunology. 1987; 80(2): 153-161.

108. Van Nierkerk, C., De Wet, J. Efficacy of grass-maize pollen oral immunotherapy in patients with seasonal hay-fever; A double blind study. Clinical and Experimental Allergy. 1987; 17: 507-513.

109. Scadding, G., Brostoff, J. Low dose sublingual therapy in patients with allergic rhinitis due to house dust mite. Clinical and Experimental Allergy. 1986; 16: 483-491.

110. Morris, D. Treatment of respiratory disease with ultra-small doses of antigens. Annals of Allergy, Asthma & Immunology. 1970; 28(10): 494-500.

3) Comparison Studies of Sublingual and Subcutaneous Antigen Administration

1. Cochard, M., Eigenmann, P. Sublingual immunotherapy is not always a save alternative to subcutaneous immunotherapy. June 2009 retrieved from jacionline.

2. Larenas-Linnemann, D. Subcutaneous and Sublingual Immunotherapy in Children: Complete Update on controversies, Dosing and Efficacy. Current Allergy and Asthma Reports; 2008. 8:465-474.

3. Pokladnikova, J., Krcmova, I., Vlcek, J. Economic evaluation of sublingual vs. subcutaneous allergen immunotherapy. Annals of Allergy, Asthma and Immunology. 2008; 100(5): 482-489.

4. Townley, R. Is Sublingual Immunotherapy “Ready for Prime Time”? Chest. 2008; 133: 589-590.

5. Saporta, D., McDaniel, A. Efficacy comparison of multiple-antigen subcutaneous injection immunotherapy and multiple-antigen sublingual immunotherapy. ENT – Ear, Nose & Throat Journal. 2007; 86(8): 493-497.

6. Mauroa, M., Russelloa, M., Incorvaiab, C., Gazzolaa, G., Di Carac, G., Frati, F. Comparison of efficacy, safety and immunologic effects of subcutanious and sublingual immunotherapy in birch pollinosis: A randomized study. European Annals of Allergy and Clinical Immunology. 2007; 39: 119-122.

7. Khinichi, M.S., Poulsen, L.K., Carat, F., Andre, C., Hansen, A.B., Malling, H.J. Clinical efficacy of sublingual and subcutaneous birch pollen allergen-specific immunotherapy: A randomized, placebo-controlled, double-blind, double-dummy study. Allergy. 2004; 59: 45-53.

8. Mungan, D., et al. Comparison of the efficacy of subcutaneous and sublingual immunotherapy in mite-sensitive patients with rhinitis and asthma a placebo controlled study. Annals of Allergy, Asthma, and Immunology. 1999; 82: 485-490.

9. Quirino, T., et al. Sublingual versus injective immunotherapy in grass pollen allergic patients: a double blind (double dummy) study. Clinical and Experimental Allergy. 1996; 26: 1253-1261.

10. Bernardis, P., et al. Injective versus sublingual immunotherapy in Alternaria tenuis allergic patients. Journal of Investigational Allergology and Clinical Immunology. 1996; 6(1): 55-62.

4) Mechanisms of Sublingual Immunotherapy

1. Incorvaia, C., Frati, F., Puccinelli, P., Marcucci, F., Di Cara, G., Sensi, L., et al. Effects of sublingual immunotherapy on allergic inflammation. Inflammation & Allergy Drug Targets. 2008; 7: 167-172.

2. Burastero, S., et al. Effect of sublingual immunotherapy with grass monomeric allergoid on allergen-specific T-cell proliferation and interleukin 10 production. Annals of Allergy, Asthma & Immunology. 2008; 100: 343-349.

3. Bohle, B., Kinaciyan, T., Gersymayr, M., Radakovics, A., Jahn-Schmid, B., Ebner, C. Sublingual immunotherapy indusces IL-10-producing T regulatory cells, allergen-specific T-cell tolerance, and immune deviation. Journal of Allergy and Clinical Immunology. 2007; 120: 707-713.

4. Ciprandi, G., Cirillo, I., Tosca, M., Marseglia, G., Fenoglio, D. Sublingual immunotherapy-induced IL-10 production is associated with changed response to the decongestion test: Preliminary results. Allergy and Asthma Proceedings. 2007; 28(5): 574-577.

5. Akdis, M., Akdis, C. Mechanisms of allergen-specific immunotherapy. Journal of Allergy and Clinical Immunology. 2007; 119(4): 780-791.

6. Bahceciler, N., et al. Immunologic aspects of sublingual immunotherapy in the treatment of allergy and asthma. Current Medical Chemistry. 2007; 14: 265-269.

7. Ciprandi, G., et al. Sublingual immunotherapy: An update on immunologica and functional effects. Allergy and Asthma Proceedings. 2007; 28(1): 40-43.

8. Frati, F., et al. Mucosal immunization application to allergic disease: Sublingual immunotherapy. Allergy and Asthma Proceedings. 2007; 28(1): 35-39.

9. Rossi, R.E., Monasterolo, G., Coco, G., Silvestro, L., Operti, D. Evaluation of serum IgG4 antibodies specific to grass pollen allergen components in the follow up of allergic patients undergoing subcutaneous and sublingual immunotherapy. Vaccine. 2007; 25(5): 957-964.

10. Savolainen, J., et al. Sublingual immunotherapy in children modulates allergen-induced in vitro expression of cytokine mRNA in PBMC. Allergy. 2006; 61: 1184-1190.

11. Sun, J., et al. Sublingual tolerance induction with antigen conjugated to cholera toxin B subunit induces foxp3+CD25+CD4+ regulatory T cells and suppresses delayed-type hypersensitivity reactions. Scandinavian Journal of Immunology. 2006; 64: 251-259.

12. Akdis, C., et al. Immunological mechanisms of sublingual immunotherapy. Allergy. 2006; 61: 11.

13. Ciprandi, G., et al. Sublingual immunotherapy induces spirometric improvement associated with IL-10 production: Preliminary reports. International Immunopharmacology. 2006; 6: 1370-1373.

14. Jutel, M., et al. Mechanisms of allergen specific immunotherapy – T-cell tolerance and more. Allergy. 2006; 61: 796-807.

15. Malling, H., et al. Safety and immunological changes during sublingual immunotherapy with standarized quality grass allergen tablets. Journal of Investigative Allergology and Clinical Immunology. 2006; 16(3): 162-168.

16. Cosmi, L., et al. Sublingual immunotherapy with Dermatophagoides monomeric allergoid down-regulates allergen-specific immunoglobulin E and increases both interferon-y-and interleukin-10-production. Clinical and Experimental Allergy. 2006; 36: 261-272.

17. Ciprandi, G., et al. Allergen-specific immunotherapy: An update on immunological mechanisms of action. Monaldi Archives for Chest Disease. 2006; 65(1): 34-37.

18. Ciprani, G., et al. Sublingual immunotherapy and regulatory T-cells. Allergy. 2006; 61: 511-513.

19. Dehlink, E., et al. Absence of systemic immunologic changes during dose build-up phase and early maintenance period in effective specific sublingual immunotherapy in children. Clinical and Experimental Allergy. 2006; 36: 32-39.

20. Moingeon, P., et al. Immune mechanisms of allergen-specific sublingual immunotherapy. Allergy. 2006; 61: 151-165.

21. Ciprandi, G., et al. Induction of interleukin 10 by sublingual immunotherapy for house dust mites: A preliminary report. Annals of Allergy, Asthma & Immunology. 2005; 95.

22. Lambrecht, B. Dendritic cells in the pathogenesis of asthma. Clinical and Experimental Allergy. 2004; 4: 123-128.

23. Jan de Heer, H., et al. Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen. Journal of Experimental Medicine. 2004; 200(1): 89-98.

24. Arikan, C., et al. BCG-induced IL-12 did not improve parameters in asthmatic children treated w/sublingual immunotherapy. Clinical and Experimental Allergy. 2004; 34: 398-405.

25. Reich, M., et al. Nonspecific plasma proteins during sublingual immunotherapy. Local Immunotherapy in Allergy. Chemical Immunology. 2003; 82: 99-108.

26. Bagnasco, M., et al. Pharmacokinetics of an allergen and a monomeric allergoid for oromucosal immunotherapy in allergic volunteers. Clinical and Experimental Allergy. 2001; 31: 54-60.

27. Marcucci, F., et al. Sublingual tryptase and ECP in children treated with grass pollen sublingual immunotherapy (SLIT): Safety and immunologic implications. Allergy. 2001; 56: 1091-1095.

28. Markert, U.R. Preliminary analysis of clinical parameters, plasma proteins and T cell functions of allergic patients after up to 3 years sublingual immunotherapy- Abstract presented October 2000 0 IACAI conference.

29. Fanta, C., et al. Systemic immunological changes induced by administration of grass pollen allergens via the oral mucosa during sublingual immunotherapy. International Archives of Allergy and Immunology. 1999; 120: 218-224.

30. Yuksel, H., et al. Sublingual immunotherapy and influence on urinary leukotrienes in seasonal pediatric allergy. Journal of Investigative Allergology and Clinical Immunology. 1999; 9(5): 305-313.

31. Bagnasco, M., et al. Absorption and distribution kinetics of the major Parietaria allergen administered by noninjectable routes to healthy human beings. Journal of Allergy and Clinical Immunology. 1997; 100: 13-18.

32. Giannarini, L. Decrease of allergen-specific T cell response induced by local nasal immunotherapy. Clinical and Experimental Allergy. 1998; 28: 547-551.

5) Safety and Quality-of-Life Related Studies

1. Wise, S., Woody, J., Koepp, S., Schlosser, R. Quality of life outcomes with sublingual immunotherapy. American Journal of Otolaryngology. 2009;30:305-311

2. 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. Journal of Allergy and Clinical Immunology. 2009; 12 (1) 167-173.

3. Windom, H., Lockey, R. an update on the safety of specific immunotherapy. Current Opinion in Allergy and Clinical Immunology. 2008, 8:571-576

4. Rodriguez-Perez, N., Ambriz-Moreno, M. J., Canonica, G. W., Penagos, M. Frequency of acute systemic reactions in patients with allergic rhinitus and asthma treated with sublingual immunotherapy. Annals of Allergy, Asthma, & Immunology. 2008; 101: 304-310.

5. Blazowski, L. Anaphylactic shock because of sublingual immunotherapy overdose during third year of maintenance dose. Allergy Online. December 2007, retrieved from http://www.blackwell-synergy.com

6. Moreno-Ancillo, A., Moreno, C., Ojeda, P., Dominguez, C., Barasona, MJ., Garcia-Cubillana, A., Martin, S. Efficacy and quality of life with once-daily sublingual immunotherapy with grasses plus olive pollen extract without updosing. Journal of Investigational Allergology & Clinical Immunology. 2007; 17: 399-405.

7. Dunsky, E. et al. Anaphylaxis to sublingual immunotherapy. Allergy. 2006; 61: 1235-1244.

8. Antico, A., et al. Anaphylaxis by latex sublingual immunotherapy. Allergy. 2006; 61: 1236-1237.

9. Larsen, T., et al. Safety and tolerability of grass pollen tablets in sublingual immunotherapy – a phase-1 study. Allergy. 2006; 61: 1173-1176.

10. Frati, F., et al. Dose dependence of efficacy but not of safety in sublingual immunotherapy. Monaldi Archives of Chest Disease. 2006; 65(1): 38-40.

11. Kleine-Tebbe, J., et al. Safety of a SQ-standarized grass allergen tablet for sublingual immunotherapy: A randomized, placebo-controlled trial. Allergy. 2006; 61: 181-184.

12. Tripodi, S., et al. Safety and tolerability of ultra-rush induction, less than one hour, of sublingual immunotherapy in children. International Archives of Allergy and Immunology. 2006; 139: 149-152.

13. Di Rienzo, V., et al. Post-marketing survey on the safety of sublingual immunotherapy in children below the age of 5 years. Clinical and Experimental Allergy. 2005; 35: 560-564.

14. Scolozzi, R. Tolerability of the allergoid sublingual immunotherapy with a monomeric allergoid in patients with allergic rhinitis and/or asthma. Journal of Allergy and Clinical Immunology. 2004; 113(2): (abs).

15. Silvestris, A. Tolerability of sublingual immunotherapy with monomeric allergoid in allergic sensitizations to house dust mite, Parietaria and grass. Journal of Allergy and Clinical Immunology. 2004; 114(2): (abs).

16. Grosclaude, M., et al. Safety of various dosage regimens during induction of sublingual immunotherapy. International Archives of Allergy and Immunology. 2003; 129(3): 248-253.

17. Hasan, H., et al. Short report – evaluation of immunotherapy for seasonal and perennial allergic rhinitis using quality of life questionnaires. Current Allergy & Clinical Immunology. 2003; 16(1).

18. Lombardi, C., et al. Safety of sublingual immunotherapy with monomeric allergoid in adults: multicenter post-marketing surveillance study. Allergy. 2001; 56: 989-992.

19. Lombardi, C., et al. Sublingual immunotherapy is clinically safe in patients with oral allergy syndrome. Allergy. 2000.

20. Andre, C., et al. Safety of sublingual immunotherapy in children and adults. International Archives of Allergy and Immunology. 2000; 121: 229-234.

21. Madonini, E., et al. Safety and efficacy evaluation of sublingual allergen-specific immunotherapy – a retrospective, multicenter study. International Journal of Immunopathology and Pharmacology. 2000; 13(2): 77-81.

22. Di Rienzo, V., et al. Post-marketing surveillance study on the safety of sublingual immunotherapy in children. Allergy. Vol. 54, pgs. 1110-1113, 1999.

23. Ariano, R., et al. Efficacy and safety of oral immunotherapy in respiratory allergy to Parietaria judaica pollen. A double-blind study. Journal of Investigative Allergology and Clinical Immunology. 1998; 8(3): 155-160.

24. Feliziani, V., et al. Safety and efficacy of sublingual rush immunotherapy with grass allergen extracts. A double blind study. Allergol et Immunopathol. 1995; 23(5): 224-230.

6) Other Indications for Treatment (Foods and Chemicals)

1. Buyukozturk, S., Gelincik, A., Ozseker, F., Colakoglu, B., Dal, M. Latex Sublingual Immunotherapy: Can its safety be predicted? Annals of Allergy, Asthma & Immunology on line 02 March 2010.

2. Pereira, C., Bartolome, B., Asturian, J., Ibarrola, I., Tavares, B., Loureiro, G., et.al. Specific sublingual immunotherapy with peach LTP (Pru p 3). One year treatment: a case report. Cases Journal 2009; 2:6553

3. Patriarca, G., Nucera, E., Roncallo, C., Aruanno, A., Lombardo, C., Decinti, M., et.al. Sublingual immunotherapy with venom for patients with Hymenoptera venom allergy. June 2009 retrieved from jacionline

4. Skripak, J., Wood, R. Mammalian milk allergy: avoidance strategies and oral desensitization. Current opinion in Allergy and Clinical Immunology 2009; 9:259-264.

5. Beyer, K., Wahn, U. Oral immunotherapy for food allergy in children. Current Opinion in Allergy and Clinical Immunology 2008; 8:553-556.

6. Skripak, J., et.al. A randomized, double blind, placebo-controlled study of milk oral immunotherapy for cow’s milk allergy. Journal of Allergy and Clinical Immunology. 2008; 09.030.

7. Nucera, E., Schiavino, D., Buomomo, A., Pollastrini, E., Altomonte, G., Pecora, V. et. al. Sublingual-Oral Rush Desensitization to Mixed Cow and Sheep Milk: A Case Report. Journal of Investigational Allergology and Clinical Immunology. 2008; 18(3): 219-222.

8. Burks, W., Laubach, S., Jones, S. Oral tolerance, food allergy, and immunotherapy: Implications for future treatment (Update Review). Journal of Allergy and Clinical Immunology. 2008: 1-7.

9. Passalacqua, G. et al. Sublingual Immunotherapy with Honeybee Venom is Effective in Patients with Large Local Reactions Due to Bee Sting: A Randomised, Double Blind Placebo Controlled Trial. Journal of Allergy and Clinical Immunology. 2008; 121(3): 793.

10. Longo, G., Barbi, E., Berti, I., Meneghetti, R., Pittalis, A., Ronfani, L., et al. Specific oral tolerance induction in children with very severe cow’s milk-induced reactions. Journal of Allergy and Clinical Immunology. January 2008, retrieved February 1, 2008 from www.jacionline.org.

11. Munoz-Lopez, F. Food allergy: oral tolerance or immunotherapy. Allergologia et Immunopathologia. 2007; 35(5): 165-168.

12. Nettis, E., Colanardi, M.C., Soccio, A.L., Marcandrea, M., Pinto, L., Ferrannini, A., et al. Double-blind, placebo-controlled study of sublingual immunotherapy in patients with latex-induced urticaria: a 12-month study. British Journal of Dermatology. 2007; 156: 674-681.

13. Pajno, G., Caminiti, L., Vita, D., Barberio, G., Salzanno, G., Lombardo, F. et al. Sublingual immunotherapy in mite-sensitized children with atopic dermatitis: A randomized double-blind, placebo-controlled study. Journal of Allergy and Clinical Immunology. 2007; 120: 164-170.

14. Patriarca, G. et al. Oral specific desensitization in food-allergic children. Digestive Diseases Sciences. 2007; 52(7): 1662-72.

15. Passalacqua G., et al. Quantitative assessment of the compliance with once-daily sublingual immunotherapy in children (EASY Project: Evaluation of A Novel SLIT formulation during a Year). Pediatric Allergy and Immunology. 2007; 18: 58-62.

16. Buchanan, A. et al. Egg oral immunotherapy in nonanaphylactis children with egg allergy. Journal of Allergy and Clinical Immunology. 2007; 119(1): 199-205.

17. Kinaciyan, T. et al. Successful sublingual immunotherapy with birch pollen has limited effects on concomitant food allergy to apple and the immune response to the Bet v 1 homolog Mal d 1. Journal of Allergy and Clinical Immunology, 2007.

18. Patriarca, G. et al. Oral Rush Desensitization in Peanut Allergy: A Case Report. Digestive Diseases and Sciences. 2006; 51(3): 471-473.

19. Sun, J-B, et al. Sublingual Tolerance Induction with Antigen Conjugated to Cholera Toxin B Subunit Induces Fox p3+CD25+CD4+ Regulatory T Cells and Suppresses Delayed-Type Hypersensitivity Reactions. Scandinavian Journal of Immunology. 2006; 64: 251-259.

20. de Boissieu, D., Dupont, C. Sublingual immunotherapy for cow’s milk protein allergy: a preliminary report. Allergy. 2006; 61: 1238-1239.

21. Kerzl, R. et al. Life-threatening anaphylaxis to kiwi fruit: Protective sublingual allergen immunotherapy effect persists even after discontinuation. Journal of Allergy and Clinical Immunology; 2006.

22. Enrique, E. et al. Sublingual immunotherapy for hazelnut food allergy: A randomized, double-blind, placebo-controlled study with a standardized hazelnut extract. Journal of Allergy and Clinical Immunology.2005; Vol. 116(5): 1073-1079.

23. Meglio, P., Bartone, E., Plantamura, M., Arabito, E., Giampietro, PG. A protocol for oral desensitization in children with IgE-mediated cow’s milk allergy. Allergy. 2004; 59(9): 980-7.

24. Bahima, A. Cistero “Tolerance and effects on skin reactivity to latex of sublingual rush immunotherapy with a latex extract. Journal of Investigational Allergology and Clinical Immunology. 2004; 14(1): 17-25.

25. Severe anaphylaxis to kiwi fruit: Immunologic changes related to successful sublingual allergen immunotherapy. Journal of Allergy and Clinical Immunology; 2003: 1406-09.

26. Patriarca, G. et al. Oral desensitizing treatment in food allergy: clinical and immunologic results. Ailmentary Pharmacology Therapy. 2003; 17: 459-465.

27. Patriarca, G. Sublingual Desensitization: A New Approach to Latex Allergy Problem. Anesthesia & Analgesia. 2002; 95: 956-960.

28. Nucera, E. Immunological Aspects of Oral Desensitization in Food Allergy. Digestive Diseases and Sciences. 2000; 45(3): 637-641.

29. Patriarca, G., et al. Food allergy in children: results of a standardized protocol for oral desensitization. Hepatogastroenterology. 1998; 45(19): 52-58.

30. Morris, D.L. Intradermal Testing and Sublingual Desensitization for Nickel. Cutis. 1998; 61(3): 129-132.

31. Panzani, R.C., et al. Oral hyposensitization to nickel allergy: preliminary clinical results. International Archives of Allergy and Immunology. 1995; 107(1-3): 251-254.

32. Di Rienzo, V., Pucci, S., D’Alo, S., Di Cara, G., Incorvania, C., Frati, F., Romano, A. Effects of high-dose sublingual immunotherapy on quality of life in patients with cypress-induced rhinitis: A placebo-controlled study. Clinical and Experimental Allergy Reviews. 2006; 6: 67-70.

33. Vervloet, D., Birnbaum, J., Laurent, P., Hugues, B., Fardeau, M., Massabie-Bouchat, Y., Aferiat-Derome, A., André, C. Safety and efficacy of juniperus ashei sublingual-swallow ultra-rush pollen immunotherapy in cypress rhinoconjunctivitis: A double-blind, placebo-controlled study. International Archives of Allergy and Immunology. 2007; 142: 239-246.

34. Morris, D. Use of sublingual antigen in diagnosis and treatment of food allergy. Annals of Allergy, Asthma, & Immunology. 1969; 27(6): 289-94.

Updated: March 15, 2010

 

© 2002-2010 Allergychoices, Inc., 201 Main Street, Suite 710, La Crosse, WI 54601 – Reproduced with permission.

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