Portal de Periódicos da CAPES

Sublingual immunotherapy: A comprehensive review

2006; Elsevier BV; Volume: 117; Issue: 5 Linguagem: Inglês

10.1016/j.jaci.2006.02.040

1097-6825

Linda Cox, Désirée Larenas‐Linnemann, Hendrik Nolte, David Weldon, Ira Finegold, Harold S. Nelson,

Dermatology and Skin Diseases

Sublingual immunotherapy (SLIT) has been used with increasing frequency in Europe and is viewed with increasing interest by allergists in the United States. To address this interest, a Joint Task Force of the American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and Immunology's Immunotherapy and Allergy Diagnostic Committees reviewed the available literature on SLIT and prepared this report. The task force concluded that despite clear evidence that SLIT is an effective treatment, many questions remained unanswered, including effective dose, treatment schedules, and overall duration of treatment. Until these have been determined, an assessment of the cost/benefit ratio of the treatment cannot be made. SLIT does appear to be associated with few serious side effects, but it has not been administered in high-risk asthmatic patients, nor in the studies reviewed has it been administered as a mixture of non–cross-reacting allergens. Furthermore, there is currently no allergy extract approved for this use in the United States, nor is there a Current Procedural Terminology code for billing purposes. All of these factors should be given careful consideration by anyone contemplating initiating SLIT treatment for their allergic patients. Sublingual immunotherapy (SLIT) has been used with increasing frequency in Europe and is viewed with increasing interest by allergists in the United States. To address this interest, a Joint Task Force of the American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and Immunology's Immunotherapy and Allergy Diagnostic Committees reviewed the available literature on SLIT and prepared this report. The task force concluded that despite clear evidence that SLIT is an effective treatment, many questions remained unanswered, including effective dose, treatment schedules, and overall duration of treatment. Until these have been determined, an assessment of the cost/benefit ratio of the treatment cannot be made. SLIT does appear to be associated with few serious side effects, but it has not been administered in high-risk asthmatic patients, nor in the studies reviewed has it been administered as a mixture of non–cross-reacting allergens. Furthermore, there is currently no allergy extract approved for this use in the United States, nor is there a Current Procedural Terminology code for billing purposes. All of these factors should be given careful consideration by anyone contemplating initiating SLIT treatment for their allergic patients. Sublingual immunotherapy (SLIT) has been used with increasing frequency in Europe and is being viewed with increased interest by US allergists. In Medline, Embase, and Biosis there were 21 SLIT citations in English in 1999 and 58 in 2004. From 1999 through 2005, there were 258. At the 2005 World Allergy Organization congress, there were 25 abstracts on SLIT. In light of this increasing interest, the American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and Immunology's (AAAAI) Immunotherapy and Allergy Diagnostics Committees formed a joint task force with the purpose of providing a comprehensive, updated report on SLIT for the North American allergy community. A reference list was compiled from articles known to task force members, references from review articles,1Andre C. Vatrinet C. Galvain S. Carat F. Sicard H. Safety of sublingual-swallow immunotherapy in children and adults.Int Arch Allergy Immunol. 2000; 121: 229-234Crossref PubMed Scopus (178) Google Scholar, 2Canonica G.W. Compalati E. Fumagalli F. Passalacqua G. Sublingual and oral immunotherapy.Immunol Allergy Clin North Am. 2004; 24: 685-704Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar, 3Canonica W. Passalacqua G. Noninjection routes for immunotherapy.J Allergy Clin Immunol. 2003; 111: 437-448Abstract Full Text Full Text PDF PubMed Scopus (301) Google Scholar, 4Olaguibel J.M. Alvarez Puebla M.J. Efficacy of sublingual allergen vaccination for respiratory vaccination for respiratory allergy in children. Conclusions from one meta-analysis.J Investig Allergol Clin Immunol. 2005; 15: 9-16PubMed Google Scholar, 5Passalacqua G. Guerra L. Pasquali M. Lombardi C. Canonica G.W. Efficacy and safety of sublingual immunotherapy.Ann Allergy Asthma Immunol. 2004; 93 (103): 3-13Abstract Full Text PDF PubMed Google Scholar, 6Passalacqua G. Fumagalli F. Guerra L. et al.Safety of allergen-specific sublingual immunotherapy and nasal immunotherapy.Chem Immunol Allergy. 2003; 82: 109-118Crossref PubMed Scopus (12) Google Scholar, 7Rakoski J. Wessner D. A short assessment of sublingual immunotherapy.Int Arch Allergy Immunol. 2001; 126: 185-187Crossref PubMed Scopus (9) Google Scholar, 8The European Academy of Allergology and Clinical Immunology (EAACI) Position Paper Consensus statement on the treatment of allergic rhinitis.Allergy. 2000; 55: 116-134Crossref PubMed Scopus (605) Google Scholar, 9Wilson D.R. Torres Lima M. Durham S.R. Sublingual immunotherapy for allergic rhinitis [review].The Cochrane Collaboration. 2005; (Issue 1)Google Scholar, 10Frew A.J. Smith H.E. Sublingual immunotherapy.J Allergy Clin Immunol. 2001; 107: 441-444Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar, 11Malling H.J. Is sublingual immunotherapy clinically effective?.Curr Opin Allergy Clin Immunol. 2002; 2: 523-531Crossref PubMed Scopus (52) Google Scholar, 12Malling H.J. Comparison of the clinical efficacy if subcutaneous and safety of subcutaneous and sublingual immunotherapy: methodological approaches and experimental results.Curr Opin Allergy Clin Immunol. 2004; 4: 539-542Crossref PubMed Scopus (20) Google Scholar, 13Gidaro G.B. Marcucci F. Sensi L. et al.The safety of sublingual-swallow immunotherapy: analysis of published studies.Clin Exp Allergy. 2005; 35: 565-571Crossref PubMed Scopus (156) Google Scholar, 14Baena-Cagnani C. Passalacqua G. Baena-Cagnani R. Sublingual immunotherapy in pediatric patients: beyond clinical efficacy.Curr Opin Allergy Clin Immunol. 2005; 5: 173-177Crossref PubMed Scopus (18) Google Scholar and PubMed (referenced through October 2005). One hundred four articles in English, French, and German were reviewed.1Andre C. Vatrinet C. Galvain S. Carat F. Sicard H. Safety of sublingual-swallow immunotherapy in children and adults.Int Arch Allergy Immunol. 2000; 121: 229-234Crossref PubMed Scopus (178) Google Scholar, 2Canonica G.W. Compalati E. Fumagalli F. Passalacqua G. Sublingual and oral immunotherapy.Immunol Allergy Clin North Am. 2004; 24: 685-704Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar, 3Canonica W. Passalacqua G. Noninjection routes for immunotherapy.J Allergy Clin Immunol. 2003; 111: 437-448Abstract Full Text Full Text PDF PubMed Scopus (301) Google Scholar, 4Olaguibel J.M. Alvarez Puebla M.J. Efficacy of sublingual allergen vaccination for respiratory vaccination for respiratory allergy in children. Conclusions from one meta-analysis.J Investig Allergol Clin Immunol. 2005; 15: 9-16PubMed Google Scholar, 5Passalacqua G. Guerra L. Pasquali M. Lombardi C. Canonica G.W. Efficacy and safety of sublingual immunotherapy.Ann Allergy Asthma Immunol. 2004; 93 (103): 3-13Abstract Full Text PDF PubMed Google Scholar, 6Passalacqua G. Fumagalli F. Guerra L. et al.Safety of allergen-specific sublingual immunotherapy and nasal immunotherapy.Chem Immunol Allergy. 2003; 82: 109-118Crossref PubMed Scopus (12) Google Scholar, 7Rakoski J. Wessner D. A short assessment of sublingual immunotherapy.Int Arch Allergy Immunol. 2001; 126: 185-187Crossref PubMed Scopus (9) Google Scholar, 8The European Academy of Allergology and Clinical Immunology (EAACI) Position Paper Consensus statement on the treatment of allergic rhinitis.Allergy. 2000; 55: 116-134Crossref PubMed Scopus (605) Google Scholar, 9Wilson D.R. Torres Lima M. Durham S.R. Sublingual immunotherapy for allergic rhinitis [review].The Cochrane Collaboration. 2005; (Issue 1)Google Scholar, 10Frew A.J. Smith H.E. Sublingual immunotherapy.J Allergy Clin Immunol. 2001; 107: 441-444Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar, 11Malling H.J. Is sublingual immunotherapy clinically effective?.Curr Opin Allergy Clin Immunol. 2002; 2: 523-531Crossref PubMed Scopus (52) Google Scholar, 12Malling H.J. Comparison of the clinical efficacy if subcutaneous and safety of subcutaneous and sublingual immunotherapy: methodological approaches and experimental results.Curr Opin Allergy Clin Immunol. 2004; 4: 539-542Crossref PubMed Scopus (20) Google Scholar, 13Gidaro G.B. Marcucci F. Sensi L. et al.The safety of sublingual-swallow immunotherapy: analysis of published studies.Clin Exp Allergy. 2005; 35: 565-571Crossref PubMed Scopus (156) Google Scholar, 14Baena-Cagnani C. Passalacqua G. Baena-Cagnani R. Sublingual immunotherapy in pediatric patients: beyond clinical efficacy.Curr Opin Allergy Clin Immunol. 2005; 5: 173-177Crossref PubMed Scopus (18) Google Scholar, 15Passalacqua G. Villa G. Altrinetti P. Sublingual swallow or spit?.Allergy. 2001; 56: 578Crossref PubMed Scopus (46) Google Scholar, 16Sanchez Palacios A. Schamann F. Garcia J.A. Sublingual immunotherapy with cat epithelial extract. Personal experience.Allergol Immunopathol (Madr). 2001; 29: 60-65Crossref PubMed Scopus (22) Google Scholar, 17Bowen T. Greenbaum J. Charbonneau et al.Canadian trial of sublingual swallow immunotherapy for ragweed rhinoconjunctivitis.Ann Allergy Asthma Immunol. 2004; 93: 425-430Abstract Full Text PDF PubMed Scopus (68) Google Scholar, 18Marcucci F. Sensi L. DiCara G. et al.Dose dependence of immunological response to sublingual immunotherapy.Allergy. 2005; 60: 952-956Crossref PubMed Scopus (59) Google Scholar, 19Durham S.R. Yang W.H. Pedersen M.R. Johansen N. Rak S. Sublingual immunotherapy with once-daily grass allergen tablets: A randomized controlled trial in seasonal allergic rhinoconjunctivitis.J Allergy Clin Immunol. 2006; 117: 802-809Abstract Full Text Full Text PDF PubMed Scopus (481) Google Scholar, 20Bordignon V. Parmiani S. Variation of the skin end-point in patients treated with sublingual specific immunotherapy.J Investig Allergol Clin Immunol. 2003; 13: 170-176PubMed Google Scholar, 21Bufe 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: 498-504Crossref PubMed Scopus (140) Google Scholar, 22Casanovas M. Guerra F. Moreno C. et al.Double-blind, placebo-controlled clinical trial of preseasonal treatment with allergenic extracts of Olea europaea pollen administered sublingually.J Investig Allergol Clin Immunol. 1994; 4: 305-314PubMed Google Scholar, 23Clavel R. Bousquet J. Andre C. Clinical efficacy of sublingual-swallow immunotherapy: a double-blind, placebo-controlled trial of a standardized five-grass-pollen extract in rhinitis.Allergy. 1998; 53: 493-498Crossref PubMed Scopus (203) Google Scholar, 24Lima M. Wilson D. Pitkin L. et al.Grass pollen sublingual immunotherapy for seasonal rhinoconjunctivitis: a randomized controlled trial.Clin Exp Allergy. 2002; 32: 507-514Crossref PubMed Scopus (164) Google Scholar, 25Nelson H. Oppenheimer J. Vatsia G.A. Buchmeier A. A double blind, placebo-controlled evaluation of sublingual immunotherapy with standardized cat extract.J Allergy Clin Immunol. 1993; 92: 229-236Abstract Full Text PDF PubMed Scopus (116) Google Scholar, 26Passalacqua G. Albano M. Riccio A. et al.Clinical and immunologic effects of a rush sublingual immunotherapy to Parietaria species: a double-blind, placebo-controlled trial.J Allergy Clin Immunol. 1999; 104: 964-968Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar, 27Sambugaro R. Puccinelli P. Burastero S.E. et al.The efficacy of sublingual immunotherapy for respiratory allergy is not affected by different dosage regimens in the induction phase.Allergol Immunopathol (Madr). 2003; 31: 329-337PubMed Google Scholar, 28Tonnel A.B. Scherpereel A. Douay B. et al.Allergic rhinitis due to house dust mites: evaluation of the efficacy of specific sublingual immunotherapy.Allergy. 2004; 59: 491-497Crossref PubMed Scopus (90) Google Scholar, 29Vourdas 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: 662-672Crossref PubMed Scopus (193) Google Scholar, 30Pradalier A. Basset D. Claudel 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: 819-828Crossref PubMed Scopus (146) Google Scholar, 31Lombardi C. Gargioni S. Venturi S. et al.Controlled study of preseasonal immunotherapy with grass pollen extract in tablets: effect on bronchial hyperreactivity.J Investig Allergol Clin Immunol. 2001; 11: 41-45PubMed Google Scholar, 32DiRienzo 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: 206-210Crossref PubMed Scopus (346) Google Scholar, 33Pajno G.B. 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: 1641-1647Crossref PubMed Scopus (101) Google Scholar, 34Pajno G.B. 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; 55: 842-849Crossref PubMed Scopus (224) Google Scholar, 35Marogna M. Spadolinii I. Massolo A. et al.Clinical, functional and immunologic effects of sublingual immunotherapy I birch pollinosis: a 3-year randomized controlled study.J Allergy Clin Immunol. 2005; 115: 1184-1188Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar, 36Marogna M. Spadolini I. Massalo A. et al.Randomized controlled open study of sublingual immunotherapy for respiratory allergy in real life: clinical efficacy and more.Allergy. 2004; 59: 1205-1210Crossref PubMed Scopus (168) Google Scholar, 37Wuthrich B. Bucher C.H. 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: 145-148PubMed Google Scholar, 38Rolinck-Werninghaus C. Wolf H. Liebke C. et al.A prospective, randomized, double-blind, placebo-controlled multicentre study on the efficacy and safety of sublingual immunotherapy (SLIT) in children with seasonal allergic rhinoconjunctivitis to grass pollen.Allergy. 2004; 59: 1285-1294Crossref PubMed Scopus (115) Google Scholar, 39Tari M.G. 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: 277-284PubMed Google Scholar, 40Tari M.G. Mancino M. Madonna F. et al.Immunologic evaluation of 24 month course of sublingual immunotherapy.Allergol Immunopathol (Madr). 1994; 22: 209-216PubMed Google Scholar, 41Silvestri M. Spallarossa D. Battistini E. et al.Changes in inflammatory and clinical parameters and in bronchial hyperreactivity asthmatic children sensitized to house dust mites following sublingual immunotherapy.J Investig Allergol Clin Immunol. 2002; 12: 52-59PubMed Google Scholar, 42Bousquet J. Scheinmann P. Guinnepain M.T. et al.Sublingual-swallow immunotherapy (SLIT) in patients with asthma due to house-dust mites: a double-blind, placebo-controlled study.Allergy. 1999; 54: 249-260Crossref PubMed Scopus (238) Google Scholar, 43DiRienzo V. Pagani A. Parmiani S. et al.Post-marketing surveillance study on the safety of sublingual immunotherapy in pediatric patients.Allergy. 1999; 54: 1110-1113Crossref PubMed Scopus (157) Google Scholar, 44Madonini E. Agostinis F. Barra R. et al.Safety and efficacy of sublingual allergen-specific immunotherapy. A retrospective, multicenter study.Int J Immunopathol Pharmacol. 2000; 13: 77-81PubMed Google Scholar, 45Kinchi M.S. Poulsen L.K. Carat F. et al.Clinical efficacy of sublingual and subcutaneous birch pollen allergen-specific immunotherapy: a randomized placebo-controlled, double blind, double dummy study.Allergy. 2004; 59: 45-53Crossref Scopus (325) Google Scholar, 46La 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: 425-432Abstract Full Text Full Text PDF PubMed Scopus (226) Google Scholar, 47Mortemousque B. Bertel F. De Casamayor J. et al.House-dust mite sublingual-swallow immunotherapy in perennial conjunctivitis: a double-blind, placebo-controlled study.Clin Exp Allergy. 2003; 33: 464-469Crossref PubMed Scopus (72) Google Scholar, 48Passalacqua G. Albano M. Fregonese L. et al.Randomized controlled trial of local allergoid immunotherapy on allergic inflammation in mite-induced rhinoconjunctivitis.Lancet. 1998; 351: 629-632Abstract Full Text Full Text PDF PubMed Scopus (267) Google Scholar, 49Guez S. Vatrinet C. Fadel R. Andre C. House-dust mite sublingual-swallow immunotherapy (SLIT) in perennial rhinitis: a double-blind, placebo-controlled study.Allergy. 2000; 55: 369-375Crossref PubMed Scopus (138) Google Scholar, 50Lombardi C. Gergoni S. Melchiorre A. et al.Safety of sublingual immunotherapy with monomeric allergoid in adults: multicenter post-marketing surveillance study.Allergy. 2001; 56: 989-992Crossref PubMed Scopus (72) Google Scholar, 51Bernardis P. Agnoletto M. Puccinelli P. et al.Injective versus sublingual immunotherapy in Alternaria tenuis allergic patients.J Investig Allergol Clin Immunol. 1996; 6: 55-62PubMed Google Scholar, 52Mastrandrea F. Coradduza G. Serio G. et al.T-cell receptor V-beta repertoire in mite-allergic subjects after sublingual immunotherapy.J Investig Allergol Clin Immunol. 2000; 10: 142-148PubMed Google Scholar, 53Agostinis F. Tellarini L. Canonica G.W. et al.Safety of sublingual immunotherapy with a monomeric allergoid in very young children.Allergy. 2005; 60: 133Crossref PubMed Scopus (100) Google Scholar, 54Pajno G.B. Peroni D.G. Vita D. et al.Safety of sublingual immunotherapy in children with asthma.Pediatr Drugs. 2003; 5: 777-781Crossref PubMed Scopus (60) Google Scholar, 55Mastrandrea F. Serio G. Minelli M. et al.Specific sublingual immunotherapy in atopic dermatitis. Results of a 6 year follow-up of 35 consecutive patients.Allergol Immunopathol (Madr). 2000; 28: 54-62PubMed Google Scholar, 56DiRienzo V. Puccinelli P. Frati F. Parmiani S. Grass pollen specific sublingual/swallow immunotherapy in children: open-controlled comparison among different treatment protocols.Allergol Immunopathol (Madr). 1999; 27: 145-151PubMed Google Scholar, 57Bahceciler N.N. 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: 287-294Crossref PubMed Scopus (120) Google Scholar, 58Feliziani V. Marfisi R.M. Parmiani S. Rush immunotherapy with sublingual administration of grass allergen extract.Allergol Immunopathol (Madr). 1993; 21: 173-178PubMed Google Scholar, 59Andre C. Perrin-Fayolle M. Grosclaude M. et al.A double-blind placebo-controlled evaluation of sublingual immunotherapy with a standardized ragweed extract in patients with seasonal rhinitis. Evidence for a dose-response relationship.Int Arch Allergy Immunol. 2003; 131: 111-118Crossref PubMed Scopus (114) Google Scholar, 60Ariano R. Spadolini I. Panzani R.C. Efficacy of sublingual specific immunotherapy in cupressaceae allergy using an extract of Cupressus arizonica. A double blind study.Allergol Immunopathol (Madr). 2001; 29: 238-244Crossref PubMed Scopus (60) Google Scholar, 61Bahceciler N.N. Isik U. Barlan I.B. Basaran M.M. Efficacy of sublingual immunotherapy in children with asthma and rhinitis: a double-blind, placebo-controlled study.Pediatr Pulmonol. 2001; 32: 49-55Crossref PubMed Scopus (161) Google Scholar, 62D'Ambrosio F.P. Sublingual immunotherapy: a double-blind, placebo-controlled trial with Parietaria judaica extract standardised in mass units in patients with rhinoconjunctivitis, asthma, or both.Allergy. 1999; 54: 968-973Crossref PubMed Scopus (112) Google Scholar, 63Drachenberg K.J. Pfeiffer P. Urban E. Sublingual immunotherapy—results from a multi-centre, randomised, double-blind, placebo-controlled study with a standardised birch and grass/rye pollen extract.Allergologie. 2001; 24: 525-534Google Scholar, 64Drachenberg K.J. Urban E. Proll S. Woroniecki S.R. Sublingual specific immunotherapy for adults and children: a post-marketing surveillance study.Allergol Immunopathol (Madr). 2004; 32: 76-81Crossref PubMed Google Scholar, 65Feliziani V. Lattuada G. Parmiani S. Dal'Aglio P.P. Safety and efficacy of sublingual rush immunotherapy with grass allergen extracts. A double blind study.Allergol Immunopathol (Madr). 1995; 23: 224-230PubMed Google Scholar, 66Hirsch T. Sahn M. Loupold W. Double-blind placebo-controlled study of sublingual immunotherapy with house dust mite extract (D. pt.) in children.Pediatr Allergy Immunol. 1997; 8: 21-27Crossref PubMed Scopus (178) Google Scholar, 67Horak F. Stubner B. Berger U.E. Marks B. Toth J. Jager S. Immunotherapy with sublingual birch pollen extract. A short-term double blind placebo study.J Investig Allergol Clin Immunol. 1998; 8: 165-171PubMed Google Scholar, 68Hordijk G.J. Antvelink J.B. Luwema R.A. Sublingual immunotherapy with a standardised grass pollen extract: a double-blind placebo-controlled study.Allergol Immunopathol (Madr). 1998; 26: 234-240PubMed Google Scholar, 69Ippoliti F. De Santis W. Volterrani A. et al.Immunomodulation during sublingual therapy in allergic children.Pediatr Allergy Immunol. 2003; 14: 216-221Crossref PubMed Scopus (175) Google Scholar, 70Mungan D. Misirligil Z. Gurbuz L. Comparison of the efficacy of subcutaneous and sublingual immunotherapy in mite-sensitive patients with rhinitis and asthma—a placebo controlled study.Ann Allergy Asthma Immunol. 1999; 82: 485-490Abstract Full Text PDF PubMed Scopus (175) Google Scholar, 71Sabbah A. Hassoun S. Le Sellin J. et al.A double-blind, placebo-controlled trial by the sublingual route of immunotherapy with a standardized grass pollen extract.Allergy. 1994; 49: 309-313Crossref PubMed Scopus (185) Google Scholar, 72Smith H. White P. Annila I. et al.Randomized controlled trial of high-dose sublingual immunotherapy to treat seasonal allergic rhinitis.J Allergy Clin Immunol. 2004; 114: 831-837Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar, 73Troise C. Voltolini S. Canessa A. et al.Sublingual immunotherapy in Parietaria pollen-induced rhinitis: a double-blind study.J Investig Allergol Clin Immunol. 1995; 5: 25-30PubMed Google Scholar, 74Voltolini S. Modena P. Minale P. et al.Sublingual immunotherapy in tree pollen allergy. Double blind, placebo-controlled study with a biologically standardized extract of three pollens (alder, birch and hazel) administered by a rush schedule.Allergol Immunopathol (Madr). 2001; 29: 103-110Crossref PubMed Scopus (71) Google Scholar, 75Cirla A.M. Cirla P.E. Parmiani S. Pecora S. 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 Immunopathol (Madr). 2003; 31: 31-43PubMed Google Scholar, 76D'Ambrosio F.P. Ricciardi L. Isola S. et al.Rush sublingual immunotherapy in Parietaria allergic patients.Allergol Immunopathol (Madr). 1996; 21: 146-151Google Scholar, 77Gozalo F. Martin S. Rico P. et al.Clinical efficacy and tolerance of two year Lolium perenne sublingual immunotherapy.Allergol Immunopathol (Madr). 1997; 25: 219-227PubMed Google Scholar, 78Yuksel 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: 305-313PubMed Google Scholar, 79Novembre 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: 851-857Abstract Full Text Full Text PDF PubMed Scopus (440) Google Scholar, 80Valle C. Bazzi S. Berra D. et al.Effects of sublingual immunotherapy in patients sensitized to Ambrosia. An open controlled study.Allergol Immunopathol (Madr). 2000; 28: 311-317PubMed Google Scholar, 81Arikan C. Bahceciler N.N. Deniz G. et al.Bacillus Calmetter-Guerin-induced interleukin-12 did not additionally improve clinical and immunologic parameters in asthmatic children treated with sublingual immunotherapy.Clin Exp Allergy. 2004; 34: 398-416Crossref PubMed Scopus (58) Google Scholar, 82Quirino T. Iemoli E. Siciliani E. et al.Sublingual versus injective immunotherapy in grass pollen allergic patients: a double blind (double dummy) study.Clin Exp Allergy. 1996; 26: 1253-1261Crossref PubMed Scopus (183) Google Scholar, 83Malet A. Valero A. Lluch-Perez M. et al.Sublingual immunotherapy with a Dermatophagoides pteronyssinus extract in mass units: assessment of efficacy, safety and degree of compliance.Alergol Immunol Clin. 2000; 15: 145-150Google Scholar, 84Cafferelli C. Sensi L.G. Marcucci F. Cavagni G. Preseasonal local allergoid immunotherapy to grass pollen in children: a double-blind, placebo-controlled, randomized trial.Allergy. 2000; 55: 1142-1147Crossref PubMed Scopus (111) Google Scholar, 85Madonini E. Agostinis F. Barra R. et al.Long-term and preventive effects of sublingual allergen-specific immunotherapy: a retrospective, multicentric study.J Immunopathol Pharmacol. 2003; 16: 73-79PubMed Google Scholar, 86Bagnasco M. Mariani G. Passalacqua G. et al.Absorption and distribution kinetics of the major Parietaria judaica allergen (Par j1) administered by noninjectable routes in healthy human beings.J Allergy Clin Immunol. 1997; 100: 122-129Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar, 87Marcucci F. Sensi L. Frati F. et al.Sublingual tryptase and ECP in children treated with grass pollen sublingual immunotherapy (SLIT): safety and immunologic implications.Allergy. 2001; 56: 1091-1095Crossref PubMed Scopus (59) Google Scholar, 88Reich M. Zwacka G. Markert U.R. Nonspecific plasma proteins during sublingual immunotherapy.Chem Immunol Allergy. 2003; 82: 99-108Crossref PubMed Scopus (5) Google Scholar, 89Ciprandi G. Fenoglio D.I. Cirillo I. et al.Induction of interleukin 10 by sublingual immunotherapy for house dust mites: a preliminary report.Ann Allergy Asthma Immunol. 2005; 95: 38-44Abstract Full Text PDF PubMed Scopus (120) Google Scholar, 90Fanta C. Bohle B. Hirt W. et al.Systemic immunological changes induced by administration of grass pollen allergens via the oral mucosa during sublingual immunotherapy.Int Arch Allergy Immunol. 1999; 120: 218-224Crossref PubMed Scopus (129) Google Scholar, 91Marcucci F. Sensi L. Frati F. et al.Effects on inflammation parameters of a double-blind, placebo controlled one-year course of SLIT in children monosensitized to mites.Allergy. 2003; 58: 657-662Crossref PubMed Scopus (60) Google Scholar, 92Pajno G.B. Paassalacqua G. Vita D. et al.Sublingual immunotherapy abrogates seasonal bronchial hyperresponsiveness in children with Parietaria-induced respiratory allergy: a randomized controlled trial.Allergy. 2004; 59: 883-887Crossref PubMed Scopus (73) Google Scholar, 93Jutel M. Akdis M. Budak F. et al.IL-10 and TGF-β cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy.Eur J Immunol. 2003; 33: 1205-1214Crossref PubMed Scopus (796) Google Scholar, 94Cistero Bahima A. Sastre J. Enrique E. et al.Tolerance and effects on skin reactivity to latex of sublingual rush immunotherapy with a latex extract.J Investig Allergol Clin Immunol. 2004; 14: 17-25PubMed Google Scholar, 95Gammeri E. Arena A. D'Anneo R. et al.Safety and tolerability of ultra-rush (20 minutes) sublingual immunotherapy in patients with allergic rhinitis and/or asthma.Allergol Immunopathol (Madr). 2005; 33: 142-144Crossref PubMed Scopus (15) Google Scholar, 96Rossi R.E. Monasterolo G. A pilot study of feasibility of ultra-rush (20-25 minutes) sublingual-swallow immunotherapy in 679 patients (699 sessions) with allergic rhinitis and/or asthma.Int J Immunopathol Pharmacol. 2005; 18: 277-285PubMed Google Scholar, 97Fiocchi 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: 254-258Abstract Full Text PDF PubMed Scopus (115) Google Scholar, 98DiRenzo V. Minelli M. Musarra A. et al.Post-marketing survey of sublingual immunotherapy in children below the age of 5 years.Clin Exp Allergy. 2005; 35: 560-564Crossref PubMed Scopus (141) Google Scholar, 99Lombardi C. Gani F. Landi M. et al.Quantitative assessment of the adherence to sublingual immunotherapy.J Allergy Clin Immunol. 2004; 113: 1219-1220Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar, 100Grosclaude M. Bouillot P. Alt R. et al.Safety of various dosage regimens during induction of sublingual immunotherapy. A preliminary study.Int Arch Allergy Immunol. 2002; 129: 248-253Crossref PubMed Scopus (76) Google Scholar, 101Mitsch A. Drachenberg K.J. Positive results in a primary mu