Allergy, Asthma & Respiratory Disease

The Korean Academy of Asthma, Allergy and Clinical Immunology (대한천식알레르기학회)
권호 표지
DOI QR코드

DOI QR Code

The Korean Academy of Asthma Allergy and Clinical Immunology guidelines for allergen immunotherapy

대한천식알레르기학회 알레르기 면역요법 진료지침

  • Hwa Young Lee (Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Sung-Yoon Kang (Division of Pulmonology and Allergy, Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine) ;
  • Kyunghoon Kim (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Ju Hee Kim (Department of Pediatrics, Kyung Hee University Medical Center) ;
  • Gwanghui Ryu (Department of Otorhinolaryngology-Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Jin-Young Min (Department of Otorhinolaryngology-Head & Neck Surgery, Kyung Hee University Hospital, Kyung Hee University College of Medicine) ;
  • Kyung Hee Park (Department of Internal Medicine, Yonsei University College of Medicine) ;
  • So-Young Park (Department of Internal Medicine, Chung-Ang University College of Medicine) ;
  • Myongsoon Sung (Department of Pediatrics, Soonchunhyang University Gumi Hospital) ;
  • Youngsoo Lee (Department of Allergy and Clinical Immunology, Ajou University School of Medicine) ;
  • Eun-Ae Yang (Department of Pediatrics, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Hye Mi Jee (Department of Pediatrics, CHA Bundang Medical Center, CHA University School of Medicine) ;
  • Eun Kyo Ha (Department of Pediatrics, Kangnam Sacred Heart Hospital, Hallym University College of Medicine) ;
  • Yoo Seob Shin (Department of Allergy and Clinical Immunology, Ajou University School of Medicine) ;
  • Sang Min Lee (Division of Pulmonology and Allergy, Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine) ;
  • Eun Hee Chung (Department of Pediatrics, Chungnam National University School of Medicine) ;
  • Sun Hee Choi (Department of Pediatrics, Kyung Hee University Hospital at Gangdong) ;
  • Young-Il Koh (Department of Allergy and Clinical Immunology, Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Seon Tae Kim (Department of Otolaryngology-Head & Neck Surgery, Gachon University Gil Medical Center, Gachon University College of Medicine) ;
  • Dong-Ho Nahm (Department of Allergy and Clinical Immunology, Ajou University School of Medicine) ;
  • Jung Won Park (Department of Internal Medicine, Yonsei University College of Medicine) ;
  • Jung Yeon Shim (Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine) ;
  • Young Min An (Jang's Pediatrics) ;
  • Doo Hee Han (Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine) ;
  • Man Yong Han (Department of Pediatrics, CHA Bundang Medical Center, CHA University School of Medicine) ;
  • Yong Won Lee (Division of Allergy & Clinical Immunology, Department of Internal Medicine, Center for Health Policy Research, Catholic Kwandong University College of Medicine, International St. Mary's Hospital) ;
  • Jeong-Hee Choi (Department of Pulmonology and Allergy, Hallym University Dongtan Sacred Heart Hospital) ;
  • Korean Academy of Asthma Allergy and Clinical Immunology (KAAACI) Allergen Immunotherapy and Allergen Working Group ( Korean Academy of Asthma Allergy and Clinical Immunology (KAAACI) )
  • 이화영 (가톨릭대학교 의과대학 서울성모병원 내과) ;
  • 강성윤 (가천대길병원 호흡기알레르기내과) ;
  • 김경훈 (서울대학교 의과대학 소아과학교실) ;
  • 김주희 (경희대학교 의과대학 소아청소년과학교실) ;
  • 류광희 (성균관대학교 의과대학 삼성서울병원 이비인후과) ;
  • 민진영 (경희대학교 의과대학 이비인후과학교실) ;
  • 박경희 (연세대학교 의과대학 내과학교실) ;
  • 박소영 (중앙대학교 의과대학 내과학교실) ;
  • 성명순 (순천향대학교 구미병원 소아청소년과) ;
  • 이영수 (아주대학교 의과대학 알레르기내과학교실) ;
  • 양은애 (가톨릭대학교 의과대학 대전성모병원 소아청소년과) ;
  • 지혜미 (차의과학대학교 분당차병원 소아청소년과) ;
  • 하은교 (한림대학교 의과대학 강남성심병원 소아청소년과) ;
  • 신유섭 (아주대학교 의과대학 알레르기내과학교실) ;
  • 이상민 (가천대길병원 호흡기알레르기내과) ;
  • 정은희 (충남대학교 의과대학 소아청소년과학교실) ;
  • 최선희 (경희대학교 강동병원 소아청소년과) ;
  • 고영일 (전남대학교 의과대학 알레르기내과학교실) ;
  • 김선태 (가천대학교 의과대학 길병원 이비인후과학) ;
  • 남동호 (아주대학교 의과대학 알레르기내과학교실) ;
  • 박중원 (연세대학교 의과대학 내과학교실) ;
  • 심정연 (성균관대학교 의과대학 강북삼성병원 소아청소년과) ;
  • 안영민 (장스 소아과) ;
  • 한두희 (서울대학교 의과대학 이비인후과학교실) ;
  • 한만용 (차의과학대학교 분당차병원 소아청소년과) ;
  • 이용원 (가톨릭관동대학교 의과대학 국제성모병원 알레르기내과/의학산업연구센터) ;
  • 최정희 (한림대학교동탄성심병원 호흡기알레르기내과) ;
  • 대한천식알레르기학회 면역요법/알레르겐연구팀 (대한천식알레르기학회)
  • Received : 2023.09.25
  • Accepted : 2023.12.06
  • Published : 2024.07.30
Download PDF
⟨ Previous Next ⟩

Abstract

Allergen immunotherapy (AIT) is a causative treatment of allergic diseases in which allergen extracts are regularly administered in a gradually escalated doses, leading to immune tolerance and consequent alleviation of allergic diseases. The need for uniform practice guidelines in AIT is continuously growing as the number of potential candidates for AIT increases and new therapeutic approaches are tried. This updated version of the Korean Academy of Asthma Allergy and Clinical Immunology recommendations for AIT, published in 2010, proposes an expert opinion by specialists in allergy, pediatrics, and otorhinolaryngology. This guideline deals with the basic knowledge of AIT, including mechanisms, clinical efficacy, allergen standardization, important allergens in Korea, and special consideration in pediatrics. The article also covers the methodological aspects of AIT, including patient selection, allergen selection, schedule and doses, follow-up care, efficacy measurements, and management of adverse reactions. Although this guideline suggests the optimal dosing schedule, an individualized approach and modifications are recommended considering the situation for each patient and clinic.

Keywords

Acknowledgement

이 면역치료 진료지침은 대한천식알레르기학회의 연구비 지원을 받아서 제작되었습니다. 지침 제작에 참여하신 대한천식알레르기학회 면역요법/알레르겐연구팀의 모든 선생님들께 감사를 드립니다. 이 논문은 Allergy Asthma Immunol Res (AAIR) 잡지에 1차 출판된 논문(https://doi.org/10.4168/aair.2023.15.6.725)으로 AAIR/AARD 잡지 편집장과 저자들의 2차출판허가를 받았습니다.

References

  1. Jutel M, Agache I, Bonini S, Burks AW, Calderon M, Canonica W, et al. International consensus on allergy immunotherapy. J Allergy Clin Immunol 2015;136:556-68. 
  2. Noon L. Prophylactic inoculation against hay fever. Lancet 1911;177:1572-3. 
  3. Freeman J. Further observations on the treatment of hay fever by hypodermic inoculations of pollen vaccine. Historical document. Ann Allergy 1960;18:427-34. 
  4. Hur GY, Kim TB, Kim ST, Han MY, Nahm DH, Lee YW, et al. Allergy immunotherapy. Korean J Asthma Allergy Clin Immunol 2010;30:153-83. 
  5. Balshem H, Helfand M, Schunemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol 2011;64:401-6. 
  6. Shamji MH, Sharif H, Layhadi JA, Zhu R, Kishore U, Renz H. Diverse immune mechanisms of allergen immunotherapy for allergic rhinitis with and without asthma. J Allergy Clin Immunol 2022;149:791-801. 
  7. Gardner LM, Thien FC, Douglass JA, Rolland JM, O'Hehir RE. Induction of T 'regulatory' cells by standardized house dust mite immunotherapy: an increase in CD4+ CD25+ interleukin-10+ T cells expressing peripheral tissue trafficking markers. Clin Exp Allergy 2004;34:1209-19. 
  8. Varona R, Ramos T, Escribese MM, Jimeno L, Galan A, Wurtzen PA, et al. Persistent regulatory T-cell response 2 years after 3 years of grass tablet SLIT: links to reduced eosinophil counts, sIgE levels, and clinical benefit. Allergy 2019;74:349-60. 
  9. Pavon-Romero GF, Parra-Vargas MI, Ramirez-Jimenez F, Melgoza-Ruiz E, Serrano-Perez NH, Teran LM. Allergen immunotherapy: current and future trends. Cells 2022;11:212. 
  10. Akdis CA, Akdis M. Mechanisms of allergen-specific immunotherapy. J Allergy Clin Immunol 2011;127:18-27; quiz 28-9. 
  11. Zimmer A, Bouley J, Le Mignon M, Pliquet E, Horiot S, Turfkruyer M, et al. A regulatory dendritic cell signature correlates with the clinical efficacy of allergen-specific sublingual immunotherapy. J Allergy Clin Immunol 2012;129:1020-30. 
  12. Shamji MH, Durham SR. Mechanisms of allergen immunotherapy for inhaled allergens and predictive biomarkers. J Allergy Clin Immunol 2017;140:1485-98. 
  13. Schandene L, Alonso-Vega C, Willems F, Gerard C, Delvaux A, Velu T, et al. B7/CD28-dependent IL-5 production by human resting T cells is inhibited by IL-10. J Immunol 1994;152:4368-74. 
  14. van de Veen W, Stanic B, Wirz OF, Jansen K, Globinska A, Akdis M. Role of regulatory B cells in immune tolerance to allergens and beyond. J Allergy Clin Immunol 2016;138:654-65. 
  15. Golden DB, Meyers DA, Kagey-Sobotka A, Valentine MD, Lichtenstein LM. Clinical relevance of the venom-specific immunoglobulin G antibody level during immunotherapy. J Allergy Clin Immunol 1982;69:489-93. 
  16. Muller U, Helbling A, Bischof M. Predictive value of venom-specific IgE, IgG and IgG subclass antibodies in patients on immunotherapy with honey bee venom. Allergy 1989;44:412-8. 
  17. Wachholz PA, Soni NK, Till SJ, Durham SR. Inhibition of allergen-IgE binding to B cells by IgG antibodies after grass pollen immunotherapy. J Allergy Clin Immunol 2003;112:915-22. 
  18. Mitthamsiri W, Pradubpongsa P, Sangasapaviliya A, Boonpiyathad T. Decreased CRTH2 expression and response to allergen re-stimulation on innate lymphoid cells in patients with allergen-specific immunotherapy. Allergy Asthma Immunol Res 2018;10:662-74. 
  19. Eljaszewicz A, Ruchti F, Radzikowska U, Globinska A, Boonpiyathad T, Gschwend A, et al. Trained immunity and tolerance in innate lymphoid cells, monocytes, and dendritic cells during allergen-specific immunotherapy. J Allergy Clin Immunol 2021;147:1865-77. 
  20. Bohle B, Kinaciyan T, Gerstmayr M, Radakovics A, Jahn-Schmid B, Ebner C. Sublingual immunotherapy induces IL-10-producing T regulatory cells, allergen-specific T-cell tolerance, and immune deviation. J Allergy Clin Immunol 2007;120:707-13. 
  21. Heeringa JJ, McKenzie CI, Varese N, Hew M, Bakx A, Aui PM, et al. Induction of IgG(2) and IgG(4) B-cell memory following sublingual immunotherapy for ryegrass pollen allergy. Allergy 2020;75:1121-32. 
  22. Couroux P, Ipsen H, Stage BS, Damkjaer JT, Steffensen MA, Salapatek AM, et al. A birch sublingual allergy immunotherapy tablet reduces rhinoconjunctivitis symptoms when exposed to birch and oak and induces IgG(4) to allergens from all trees in the birch homologous group. Allergy 2019;74:361-9. 
  23. James C, Bernstein DI. Allergen immunotherapy: an updated review of safety. Curr Opin Allergy Clin Immunol 2017;17:55-9. 
  24. Sturm GJ, Varga EM, Roberts G, Mosbech H, Bilo MB, Akdis CA, et al. EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy. Allergy 2018;73:744-64. 
  25. Golden DB, Demain J, Freeman T, Graft D, Tankersley M, Tracy J, et al. Stinging insect hypersensitivity: a practice parameter update 2016. Ann Allergy Asthma Immunol 2017;118:28-54. 
  26. Canonica GW, Cox L, Pawankar R, Baena-Cagnani CE, Blaiss M, Bonini S, et al. Sublingual immunotherapy: World Allergy Organization position paper 2013 update. World Allergy Organ J 2014;7:6. 
  27. Malling HJ, Bousquet J. Subcutaneous immunotherapy for allergic rhinoconjunctivitis, allergic asthma, and prevention of allergic diseases. Clin Allergy Immunol 2008;21:343-58. 
  28. Brozek JL, Bousquet J, Baena-Cagnani CE, Bonini S, Canonica GW, Casale TB, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol 2010;126:466-76. 
  29. Ariano R, Kroon AM, Augeri G, Canonica GW, Passalacqua G. Long-term treatment with allergoid immunotherapy with Parietaria. Clinical and immunologic effects in a randomized, controlled trial. Allergy 1999;54:313-9. 
  30. Malling HJ, Stahl Skov P. Diagnosis and immunotherapy of mould allergy. VIII. Qualitative and quantitative estimation of IgE in Cladosporium immunotherapy. Allergy 1988;43:228-38. 
  31. Alvarez-Cuesta E, Cuesta-Herranz J, Puyana-Ruiz J, Cuesta-Herranz C, Blanco-Quiros A. Monoclonal antibody-standardized cat extract immunotherapy: risk-benefit effects from a double-blind placebo study. J Allergy Clin Immunol 1994;93:556-66. 
  32. Aas K. Hyposensitization in house dust allergy asthma. A double-blind controlled study with evaluation of the effect on bronchial sensitivity to house dust. Acta Paediatr Scand 1971;60:264-8. 
  33. Roberts G, Pfaar O, Akdis CA, Ansotegui IJ, Durham SR, Gerth van Wijk R, et al. EAACI Guidelines on Allergen Immunotherapy: allergic rhinoconjunctivitis. Allergy 2018;73:765-98. 
  34. Abramson MJ, Puy RM, Weiner JM. Injection allergen immunotherapy for asthma. Cochrane Database Syst Rev 2010;(8):CD001186. 
  35. Erekosima N, Suarez-Cuervo C, Ramanathan M, Kim JM, Chelladurai Y, Segal JB, et al. Effectiveness of subcutaneous immunotherapy for allergic rhinoconjunctivitis and asthma: a systematic review. Laryngoscope 2014;124:616-27. 
  36. Lin SY, Erekosima N, Kim JM, Ramanathan M, Suarez-Cuervo C, Chelladurai Y, et al. Sublingual immunotherapy for the treatment of allergic rhinoconjunctivitis and asthma: a systematic review. JAMA 2013;309:1278-88. 
  37. Mosbech H, Deckelmann R, de Blay F, Pastorello EA, Trebas-Pietras E, Andres LP, et al. Standardized quality (SQ) house dust mite sublingual immunotherapy tablet (ALK) reduces inhaled corticosteroid use while maintaining asthma control: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol 2014;134:568-75.e7. 
  38. de Blay F, Kuna P, Prieto L, Ginko T, Seitzberg D, Riis B, et al. SQ HDM SLIT-tablet (ALK) in treatment of asthma--post hoc results from a randomised trial. Respir Med 2014;108:1430-7. 
  39. Passalacqua G, Guerra L, Compalati E, Canonica GW. The safety of allergen specific sublingual immunotherapy. Curr Drug Saf 2007;2:117-23. 
  40. Penagos M, Passalacqua G, Compalati E, Baena-Cagnani CE, Orozco S, Pedroza A, et al. Metaanalysis of the efficacy of sublingual immunotherapy in the treatment of allergic asthma in pediatric patients, 3 to 18 years of age. Chest 2008;133:599-609. 
  41. Khinchi MS, Poulsen LK, Carat F, Andre C, Hansen AB, Malling HJ. Clinical efficacy of sublingual and subcutaneous birch pollen allergenspecific immunotherapy: a randomized, placebo-controlled, doubleblind, double-dummy study. Allergy 2004;59:45-53. 
  42. Hansen KS, Khinchi MS, Skov PS, Bindslev-Jensen C, Poulsen LK, Malling HJ. Food allergy to apple and specific immunotherapy with birch pollen. Mol Nutr Food Res 2004;48:441-8. 
  43. Kinaciyan T, Jahn-Schmid B, Radakovics A, Zwolfer B, Schreiber C, Francis JN, 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. J Allergy Clin Immunol 2007;119:937-43. 
  44. Sampson HA, Aceves S, Bock SA, James J, Jones S, Lang D, et al. Food allergy: a practice parameter update-2014. J Allergy Clin Immunol 2014;134:1016-25.e43. 
  45. Muraro A, Werfel T, Hoffmann-Sommergruber K, Roberts G, Beyer K, Bindslev-Jensen C, et al. EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy. Allergy 2014;69:1008-25. 
  46. Skypala IJ, Hunter H, Krishna MT, Rey-Garcia H, Till SJ, du Toit G, et al. BSACI guideline for the diagnosis and management of pollen food syndrome in the UK. Clin Exp Allergy 2022;52:1018-34. 
  47. Biedermann T, Kuna P, Panzner P, Valovirta E, Andersson M, de Blay F, et al. The SQ tree SLIT-tablet is highly effective and well tolerated: results from a randomized, double-blind, placebo-controlled phase III trial. J Allergy Clin Immunol 2019;143:1058-66.e6. 
  48. Till SJ, Stage BS, Skypala I, Biedermann T. Potential treatment effect of the SQ tree SLIT-tablet on pollen food syndrome caused by apple. Allergy 2020;75:2059-61. 
  49. Werfel T, Breuer K, Rueff F, Przybilla B, Worm M, Grewe M, et al. Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi-centre, randomized, dose-response study. Allergy 2006;61:202-5. 
  50. Nahm DH, Lee ES, Park HJ, Kim HA, Choi GS, Jeon SY. Treatment of atopic dermatitis with a combination of allergen-specific immunotherapy and a histamine-immunoglobulin complex. Int Arch Allergy Immunol 2008;146:235-40. 
  51. Yepes-Nunez JJ, Guyatt GH, Gomez-Escobar LG, Perez-Herrera LC, Chu AWL, Ceccaci R, et al. Allergen immunotherapy for atopic dermatitis: systematic review and meta-analysis of benefits and harms. J Allergy Clin Immunol 2023;151:147-58. 
  52. Bae JM, Choi YY, Park CO, Chung KY, Lee KH. Efficacy of allergen-specific immunotherapy for atopic dermatitis: a systematic review and meta-analysis of randomized controlled trials. J Allergy Clin Immunol 2013;132:110-7. 
  53. Nurmatov U, Dhami S, Arasi S, Pajno GB, Fernandez-Rivas M, Muraro A, et al. Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis. Allergy 2017;72:1133-47. 
  54. Pajno GB, Fernandez-Rivas M, Arasi S, Roberts G, Akdis CA, AlvaroLozano M, et al. EAACI Guidelines on allergen immunotherapy: IgEmediated food allergy. Allergy 2018;73:799-815. 
  55. Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy 2008;63 Suppl 86:8-160. 
  56. Dhami S, Nurmatov U, Arasi S, Khan T, Asaria M, Zaman H, et al. Allergen immunotherapy for allergic rhinoconjunctivitis: a systematic review and meta-analysis. Allergy 2017;72:1597-631. 
  57. Bousquet J, Lockey R, Malling HJ, Alvarez-Cuesta E, Canonica GW, Chapman MD, et al. Allergen immunotherapy: therapeutic vaccines for allergic diseases. World Health Organization. American academy of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol 1998;81:401-5. 
  58. Moote W, Kim H, Ellis AK. Allergen-specific immunotherapy. Allergy Asthma Clin Immunol 2018;14(Suppl 2):53. 
  59. Halken S, Larenas-Linnemann D, Roberts G, Calderon MA, Angier E, Pfaar O, et al. EAACI guidelines on allergen immunotherapy: prevention of allergy. Pediatr Allergy Immunol 2017;28:728-45. 
  60. Bachert C, Larche M, Bonini S, Canonica GW, Kundig T, Larenas-Linnemann D, et al. Allergen immunotherapy on the way to productbased evaluation-a WAO statement. World Allergy Organ J 2015;8:29. 
  61. Pfaar O, Bachert C, Bufe A, Buhl R, Ebner C, Eng P, et al. Guideline on allergen-specific immunotherapy in IgE-mediated allergic diseases: S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Society for Pediatric Allergy and Environmental Medicine (GPA), the Medical Association of German Allergologists (AeDA), the Austrian Society for Allergy and Immunology (OGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Dermatology (DDG), the German Society of Oto- Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), the German Society of Pediatrics and Adolescent Medicine (DGKJ), the Society for Pediatric Pneumology (GPP), the German Respiratory Society (DGP), the German Association of ENT Surgeons (BV-HNO), the Professional Federation of Paediatricians and Youth Doctors (BVKJ), the Federal Association of Pulmonologists (BDP) and the German Dermatologists Association (BVDD). Allergo J Int 2014;23:282-319. 
  62. Reisman RE, Mauriello PM, Davis GB, Georgitis JW, DeMasi JM. A double-blind study of the effectiveness of a high-efficiency particulate air (HEPA) filter in the treatment of patients with perennial allergic rhinitis and asthma. J Allergy Clin Immunol 1990;85:1050-7. 
  63. Terreehorst I, Hak E, Oosting AJ, Tempels-Pavlica Z, de Monchy JG, Bruijnzeel-Koomen CA, et al. Evaluation of impermeable covers for bedding in patients with allergic rhinitis. N Engl J Med 2003;349:237-46. 
  64. Jeon YH, Lee YJ, Sohn MH, Lee HR. Effects of vacuuming mattresses on allergic rhinitis symptoms in children. Allergy Asthma Immunol Res 2019;11:655-63. 
  65. Park KH, Sim DW, Lee SC, Moon S, Choe E, Shin H, et al. Effects of air purifiers on patients with allergic rhinitis: a multicenter, randomized, double-blind, and placebo-controlled study. Yonsei Med J 2020;61:689-97. 
  66. Stillerman A, Nachtsheim C, Li W, Albrecht M, Waldman J. Efficacy of a novel air filtration pillow for avoidance of perennial allergens in symptomatic adults. Ann Allergy Asthma Immunol 2010;104:440-9. 
  67. Wood RA, Johnson EF, Van Natta ML, Chen PH, Eggleston PA. A placebo-controlled trial of a HEPA air cleaner in the treatment of cat allergy. Am J Respir Crit Care Med 1998;158:115-20. 
  68. Bjornsdottir US, Jakobinudottir S, Runarsdottir V, Juliusson S. The effect of reducing levels of cat allergen (Fel d 1) on clinical symptoms in patients with cat allergy. Ann Allergy Asthma Immunol 2003;91:189-94. 
  69. Gherasim A, Jacob A, Schoettel F, Domis N, de Blay F. Efficacy of air cleaners in asthmatics allergic to cat in ALYATEC((R)) environmental exposure chamber. Clin Exp Allergy 2020;50:160-9. 
  70. Muller UR, Johansen N, Petersen AB, Fromberg-Nielsen J, Haeberli G. Hymenoptera venom allergy: analysis of double positivity to honey bee and Vespula venom by estimation of IgE antibodies to species-specific major allergens Api m1 and Ves v5. Allergy 2009;64:543-8. 
  71. Canonica GW, Bousquet J, Casale T, Lockey RF, Baena-Cagnani CE, Pawankar R, et al. Sub-lingual immunotherapy: World Allergy Organization Position Paper 2009. Allergy 2009;64 Suppl 91:1-59. 
  72. Wilson DR, Lima MT, Durham SR. Sublingual immunotherapy for allergic rhinitis: systematic review and meta-analysis. Allergy 2005;60:4-12. 
  73. Cox L, Nelson H, Lockey R, Calabria C, Chacko T, Finegold I, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol 2011;127(1 Suppl):S1-55. 
  74. Oykhman P, Kim HL, Ellis AK. Allergen immunotherapy in pregnancy. Allergy Asthma Clin Immunol 2015;11:31. 
  75. Henmar H, Lund G, Lund L, Petersen A, Wurtzen PA. Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy. Clin Exp Immunol 2008;153:316-23. 
  76. Park HS, Nahm DH, Chae BW. Allergen standardization of Dermatophagoides farinae (D. farinae) extracts. Korean J Allergy 1996;16:19-25. 
  77. Frew AJ, Powell RJ, Corrigan CJ, Durham SR; UK Immunotherapy Study Group. Efficacy and safety of specific immunotherapy with SQ allergen extract in treatment-resistant seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006;117:319-25. 
  78. Ewan PW, Alexander MM, Snape C, Ind PW, Agrell B, Dreborg S. Effective hyposensitization in allergic rhinitis using a potent partially purified extract of house dust mite. Clin Allergy 1988;18:501-8. 
  79. Haugaard L, Dahl R, Jacobsen L. A controlled dose-response study of immunotherapy with standardized, partially purified extract of house dust mite: clinical efficacy and side effects. J Allergy Clin Immunol 1993;91:709-22. 
  80. Olsen OT, Larsen KR, Jacobsan L, Svendsen UG. A 1-year, placebo-controlled, double-blind house-dust-mite immunotherapy study in asthmatic adults. Allergy 1997;52:853-9. 
  81. Van Metre TE, Adkinson NF, Jr., Amodio FJ, Lichtenstein LM, Mardiney MR, Norman PS, et al. A comparative study of the effectiveness of the Rinkel method and the current standard method of immunotherapy for ragweed pollen hay fever. J Allergy Clin Immunol 1980;66:500-13. 
  82. Creticos PS, Adkinson NF, Jr., Kagey-Sobotka A, Proud D, Meier HL, Naclerio RM, et al. Nasal challenge with ragweed pollen in hay fever patients. Effect of immunotherapy. J Clin Invest 1985;76:2247-53. 
  83. Creticos PS, Marsh DG, Proud D, Kagey-Sobotka A, Adkinson NF, Jr., Friedhoff L, et al. Responses to ragweed-pollen nasal challenge before and after immunotherapy. J Allergy Clin Immunol 1989;84:197-205. 
  84. Furin MJ, Norman PS, Creticos PS, Proud D, Kagey-Sobotka A, Lichtenstein LM, et al. Immunotherapy decreases antigen-induced eosinophil cell migration into the nasal cavity. J Allergy Clin Immunol 1991;88:27-32. 
  85. Varney VA, Gaga M, Frew AJ, Aber VR, Kay AB, Durham SR. Usefulness of immunotherapy in patients with severe summer hay fever uncontrolled by antiallergic drugs. BMJ 1991;302:265-9. 
  86. Dolz I, Martinez-Cocera C, Bartolome JM, Cimarra M. A double-blind, placebo-controlled study of immunotherapy with grass-pollen extract Alutard SQ during a 3-year period with initial rush immunotherapy. Allergy 1996;51:489-500. 
  87. Walker SM, Pajno GB, Lima MT, Wilson DR, Durham SR. Grass pollen immunotherapy for seasonal rhinitis and asthma: a randomized, controlled trial. J Allergy Clin Immunol 2001;107:87-93. 
  88. Bodtger U, Poulsen LK, Jacobi HH, Malling HJ. The safety and efficacy of subcutaneous birch pollen immunotherapy - a one-year, randomised, double-blind, placebo-controlled study. Allergy 2002;57:297-305. 
  89. Hedlin G, Graff-Lonnevig V, Heilborn H, Lilja G, Norrlind K, Pegelow K, et al. Immunotherapy with cat- and dog-dander extracts. V. Effects of 3 years of treatment. J Allergy Clin Immunol 1991;87:955-64. 
  90. Varney VA, Edwards J, Tabbah K, Brewster H, Mavroleon G, Frew AJ. Clinical efficacy of specific immunotherapy to cat dander: a double-blind placebo-controlled trial. Clin Exp Allergy 1997;27:860-7. 
  91. Ewbank PA, Murray J, Sanders K, Curran-Everett D, Dreskin S, Nelson HS. A double-blind, placebo-controlled immunotherapy dose-response study with standardized cat extract. J Allergy Clin Immunol 2003;111:155-61. 
  92. Nanda A, O'Connor M, Anand M, Dreskin SC, Zhang L, Hines B, et al. Dose dependence and time course of the immunologic response to administration of standardized cat allergen extract. J Allergy Clin Immunol 2004;114:1339-44. 
  93. Lent AM, Harbeck R, Strand M, Sills M, Schmidt K, Efaw B, et al. Immunologic response to administration of standardized dog allergen extract at differing doses. J Allergy Clin Immunol 2006;118:1249-56. 
  94. Horst M, Hejjaoui A, Horst V, Michel FB, Bousquet J. Double-blind, placebo-controlled rush immunotherapy with a standardized Alternaria extract. J Allergy Clin Immunol 1990;85:460-72. 
  95. Kuna P, Kaczmarek J, Kupczyk M. Efficacy and safety of immunotherapy for allergies to Alternaria alternata in children. J Allergy Clin Immunol 2011;127:502-8 e1-6. 
  96. Abramson MJ, Puy RM, Weiner JM. Allergen immunotherapy for asthma. Cochrane Database Syst Rev 2000;(2):CD001186. 
  97. Agache I, Lau S, Akdis CA, Smolinska S, Bonini M, Cavkaytar O, et al. EAACI Guidelines on Allergen Immunotherapy: house dust mite-driven allergic asthma. Allergy 2019;74:855-73. 
  98. Aalberse RC, Acevedo N, Aglas L, Altmann F, Arruda KL, Asero R, et al. Molecular allergology user's guide 2.0. Zurich (Swiss): The European Academy of Allergy and Clinical Immunology (EAACI); 2022. 
  99. Arshad SH, Tariq SM, Matthews S, Hakim E. Sensitization to common allergens and its association with allergic disorders at age 4 years: a whole population birth cohort study. Pediatrics 2001;108:E33. 
  100. Bousquet PJ, Castelli C, Daures JP, Heinrich J, Hooper R, Sunyer J, et al. Assessment of allergen sensitization in a general population-based survey (European Community Respiratory Health Survey I). Ann Epidemiol 2010;20:797-803. 
  101. Calderon MA, Cox L, Casale TB, Moingeon P, Demoly P. Multiple-allergen and single-allergen immunotherapy strategies in polysensitized patients: looking at the published evidence. J Allergy Clin Immunol 2012;129:929-34. 
  102. Ciprandi G, Alesina R, Ariano R, Aurnia P, Borrelli P, Cadario G, et al. Characteristics of patients with allergic polysensitization: the POLIS-MAIL study. Eur Ann Allergy Clin Immunol 2008;40:77-83. 
  103. Demoly P, Passalacqua G, Pfaar O, Sastre J, Wahn U. Management of the polyallergic patient with allergy immunotherapy: a practice-based approach. Allergy Asthma Clin Immunol 2016;12:2. 
  104. Kim YJ, Lee MY, Yang AR, Sol IS, Kwak JH, Jung HL, et al. Trends of Sensitization to Inhalant Allergens in Korean Children Over the Last 10 Years. Yonsei Med J 2020;61:797-804. 
  105. Kim HY, Shin YH, Han MY. Determinants of sensitization to allergen in infants and young children. Korean J Pediatr 2014;57:205-10. 
  106. Hur GY, Kim TB, Han MY, Nahm DH, Park JW; Allergen and Immunotherapy Work Group of the Korean Academy of Asthma, Allergy and Clinical Immunology (KAAACI). A survey of the prescription patterns of allergen immunotherapy in Korea. Allergy Asthma Immunol Res 2013;5:277-82. 
  107. Burbach GJ, Heinzerling LM, Edenharter G, Bachert C, Bindslev-Jensen C, Bonini S, et al. GA(2)LEN skin test study II: clinical relevance of inhalant allergen sensitizations in Europe. Allergy 2009;64:1507-15. 
  108. Mahler V, Esch RE, Kleine-Tebbe J, Lavery WJ, Plunkett G, Vieths S, et al. Understanding differences in allergen immunotherapy products and practices in North America and Europe. J Allergy Clin Immunol 2019;143:813-28. 
  109. Kim TB, Kim KM, Kim SH, Kang HR, Chang YS, CW Kim, et al. Sensitization rates for inhalant allergens in Korea: a multicenter study. Korean J Asthma Allergy Clin Immnol 2007;23:283-93. 
  110. Adkinson NF Jr, Eggleston PA, Eney D, Goldstein EO, Schuberth KC, Bacon JR, et al. A controlled trial of immunotherapy for asthma in allergic children. N Engl J Med 1997;336:324-31. 
  111. Yang MS, Lee SP, Kwon YJ, Lee SM. Dog and cat allergies and allergen avoidance measures in Korean adult pet owners who participated in a pet exhibition. Allergy Asthma Immunol Res 2018;10:155-64. 
  112. Kang SY, Yang MS, Park SY, Kim JH, Won HK, Kwon OY, et al. The role of allergen-specific IgE in predicting allergic symptoms on dog and cat exposure among Korean pet exhibition participants. World Allergy Organ J 2020;13:100488. 
  113. Twaroch TE, Curin M, Valenta R, Swoboda I. Mold allergens in respiratory allergy: from structure to therapy. Allergy Asthma Immunol Res 2015;7:205-20. 
  114. Kordash TR, Amend MJ, Williamson SL, Jones JK, Plunkett GA. Effect of mixing allergenic extracts containing Helminthosporium, D. farinae, and cockroach with perennial ryegrass. Ann Allergy 1993;71:240-6. 
  115. Lee YW, Choi SY, Lee EK, Sohn JH, Park JW, Hong CS. Cross-allergenicity of pollens from the Compositae family: Artemisia vulgaris, Dendranthema grandiflorum, and Taraxacum officinale. Ann Allergy Asthma Immunol 2007;99:526-33. 
  116. Leavengood DC, Renard RL, Martin BG, Nelson HS. Cross allergenicity among grasses determined by tissue threshold changes. J Allergy Clin Immunol 1985;76:789-94. 
  117. Nelson HS, Ikle D, Buchmeier A. Studies of allergen extract stability: the effects of dilution and mixing. J Allergy Clin Immunol 1996;98:382-8. 
  118. Grier TJ, LeFevre DM, Duncan EA, Esch RE. Stability of standardized grass, dust mite, cat, and short ragweed allergens after mixing with mold or cockroach extracts. Ann Allergy Asthma Immunol 2007;99:151-60. 
  119. Anderson MC, Baer H. Antigenic and allergenic changes during storage of a pollen extract. J Allergy Clin Immunol 1982;69:3-10. 
  120. Sridhara S, Singh BP, Arora N, Verma J, Gangal SV. A study on antigenic and allergenic changes during storage in three different biological extracts. Asian Pac J Allergy Immunol 1992;10:33-8. 
  121. Alvarez-Cuesta E, Bousquet J, Canonica GW, Durham SR, Malling HJ, Valovirta E. Standards for practical allergen-specific immunotherapy. Allergy 2006;61 Suppl 82:1-20. 
  122. Allergen immunotherapy: a practice parameter second update. J Allergy Clin Immunol 2007;120:S25-85. 
  123. Tabar AI, Muro MD, Garcia BE, Alvarez MJ, Acero S, Rico P, et al. Dermatophagoides pteronyssinus cluster immunotherapy. A controlled trial of safety and clinical efficacy. J Investig Allergol Clin Immunol 1999;9:155-64. 
  124. Casanovas M, Martin R, Jimenez C, Caballero R, Fernandez-Caldas E. Safety of an ultra-rush immunotherapy build-up schedule with therapeutic vaccines containing depigmented and polymerized allergen extracts. Int Arch Allergy Immunol 2006;139:153-8. 
  125. Harvey SM, Laurie S, Hilton K, Khan DA. Safety of rush immunotherapy to multiple aeroallergens in an adult population. Ann Allergy Asthma Immunol 2004;92:414-9. 
  126. Kim ME, Kim JE, Sung JM, Lee JW, Choi GS, Nahm DH. Safety of accelerated schedules of subcutaneous allergen immunotherapy with house dust mite extract in patients with atopic dermatitis. J Korean Med Sci 2011;26:1159-64. 
  127. Lee SH, Kim ME, Shin YS, Ye YM, Park HS, Nahm DH. Safety of ultra-rush schedule of subcutaneous allergen immunotherapy with house dust mite extract conducted in an outpatient clinic in patients with atopic dermatitis and allergic rhinitis. Allergy Asthma Immunol Res 2019;11:846-55. 
  128. Nielsen L, Johnsen CR, Mosbech H, Poulsen LK, Malling HJ. Antihistamine premedication in specific cluster immunotherapy: a double-blind, placebo-controlled study. J Allergy Clin Immunol 1996;97:1207-13. 
  129. Wang L, Wang C, Lou H, Zhang L. Antihistamine premedication improves safety and efficacy of allergen immunotherapy. Ann Allergy Asthma Immunol 2021;127:363-71.e1. 
  130. Brockow K, Kiehn M, Riethmuller C, Vieluf D, Berger J, Ring J. Efficacy of antihistamine pretreatment in the prevention of adverse reactions to Hymenoptera immunotherapy: a prospective, randomized, placebo-controlled trial. J Allergy Clin Immunol 1997;100:458-63. 
  131. Tabar AI, Echechipia S, Garcia BE, Olaguibel JM, Lizaso MT, Gomez B, et al. Double-blind comparative study of cluster and conventional immunotherapy schedules with Dermatophagoides pteronyssinus. J Allergy Clin Immunol 2005;116:109-18. 
  132. Temino VM, Wu P, Konig J, Fahrenholz JM. Safety of multiple aeroallergen rush immunotherapy using a modified schedule. Allergy Asthma Proc 2013;34:255-60. 
  133. Rieker-Schwienbacher J, Nell MJ, Diamant Z, van Ree R, Distler A, Boot JD, et al. Open-label parallel dose tolerability study of three subcutaneous immunotherapy regimens in house dust mite allergic patients. Clin Transl Allergy 2013;3:16. 
  134. Kim JT, Kim H, Kim SH, Kim DJ, Shin Y, Kim JD, et al. Comparison of allergenic properties among commercially available house dust mite allergen extracts in Korea. Yonsei Med J 2021;62:86-90. 
  135. Amin HS, Liss GM, Bernstein DI. Evaluation of near-fatal reactions to allergen immunotherapy injections. J Allergy Clin Immunol 2006;117:169-75. 
  136. Tankersley MS, Butler KK, Butler WK, Goetz DW. Local reactions during allergen immunotherapy do not require dose adjustment. J Allergy Clin Immunol 2000;106:840-3. 
  137. Roy SR, Sigmon JR, Olivier J, Moffitt JE, Brown DA, Marshall GD. Increased frequency of large local reactions among systemic reactors during subcutaneous allergen immunotherapy. Ann Allergy Asthma Immunol 2007;99:82-6. 
  138. Malling HJ. Minimising the risks of allergen-specific injection immunotherapy. Drug Saf 2000;23:323-32. 
  139. Lockey RF, Nicoara-Kasti GL, Theodoropoulos DS, Bukantz SC. Systemic reactions and fatalities associated with allergen immunotherapy. Ann Allergy Asthma Immunol 2001;87:47-55. 
  140. Bernstein DI, Wanner M, Borish L, Liss GM; Immunotherapy Committee, American Academy of Allergy, Asthma and Immunology. Twelveyear survey of fatal reactions to allergen injections and skin testing: 1990-2001. J Allergy Clin Immunol 2004;113:1129-36. 
  141. Lang DM, Alpern MB, Visintainer PF, Smith ST. Elevated risk of anaphylactoid reaction from radiographic contrast media is associated with both beta-blocker exposure and cardiovascular disorders. Arch Intern Med 1993;153:2033-40. 
  142. Muller UR, Haeberli G. Use of beta-blockers during immunotherapy for Hymenoptera venom allergy. J Allergy Clin Immunol 2005;115:606-10. 
  143. Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. Allergen immunotherapy: a practice parameter second update. J Allergy Clin Immunol 2007;120(3 Suppl):S25-85. 
  144. Cox L, Larenas-Linnemann D, Lockey RF, Passalacqua G. Speaking the same language: the World Allergy Organization Subcutaneous Immunotherapy Systemic Reaction Grading System. J Allergy Clin Immunol 2010;125:569-74, 574.e1-574.e7. 
  145. Pumphrey RS. Lessons for management of anaphylaxis from a study of fatal reactions. Clin Exp Allergy 2000;30:1144-50. 
  146. Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. The diagnosis and management of anaphylaxis: an updated practice parameter. J Allergy Clin Immunol 2005;115(3 Suppl 2):S483-523. 
  147. Bousquet J, Schunemann HJ, Togias A, Bachert C, Erhola M, Hellings PW, et al. Next-generation Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines for allergic rhinitis based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) and realworld evidence. J Allergy Clin Immunol 2020;145:70-80.e3. 
  148. Bousquet PJ, Combescure C, Klossek JM, Daures JP, Bousquet J. Change in visual analog scale score in a pragmatic randomized cluster trial of allergic rhinitis. J Allergy Clin Immunol 2009;123:1349-54. 
  149. Corrigan CJ, Kettner J, Doemer C, Cromwell O, Narkus A, Study G. Efficacy and safety of preseasonal-specific immunotherapy with an aluminium-adsorbed six-grass pollen allergoid. Allergy 2005;60:801-7. 
  150. Moller C, Dreborg S, Ferdousi HA, Halken S, Host A, Jacobsen L, et al. Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). J Allergy Clin Immunol 2002;109:251-6. 
  151. Pfaar O, Demoly P, Gerth van Wijk R, Bonini S, Bousquet J, Canonica GW, et al. Recommendations for the standardization of clinical outcomes used in allergen immunotherapy trials for allergic rhinoconjunctivitis: an EAACI Position Paper. Allergy 2014;69:854-67. 
  152. Shamji MH, Kappen JH, Akdis M, Jensen-Jarolim E, Knol EF, KleineTebbe J, et al. Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma: an EAACI Position Paper. Allergy 2017;72:1156-73. 
  153. Di Lorenzo G, Mansueto P, Pacor ML, Rizzo M, Castello F, Martinelli N, et al. Evaluation of serum s-IgE/total IgE ratio in predicting clinical response to allergen-specific immunotherapy. J Allergy Clin Immunol 2009;123:1103-10, 1110.e1-4. 
  154. Li Q, Li M, Yue W, Zhou J, Li R, Lin J, et al. Predictive factors for clinical response to allergy immunotherapy in children with asthma and rhinitis. Int Arch Allergy Immunol 2014;164:210-7. 
  155. Reisinger J, Horak F, Pauli G, van Hage M, Cromwell O, Konig F, et al. Allergen-specific nasal IgG antibodies induced by vaccination with genetically modified allergens are associated with reduced nasal allergen sensitivity. J Allergy Clin Immunol 2005;116:347-54. 
  156. Lima MT, Wilson D, Pitkin L, Roberts A, Nouri-Aria K, Jacobson M, et al. Grass pollen sublingual immunotherapy for seasonal rhinoconjunctivitis: a randomized controlled trial. Clin Exp Allergy 2002;32:507-14. 
  157. Bousquet J, Calvayrac P, Guerin B, Hejjaoui A, Dhivert H, Hewitt B, et al. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. I. In vivo and in vitro parameters after a short course of treatment. J Allergy Clin Immunol 1985;76:734-44. 
  158. Francis JN, James LK, Paraskevopoulos G, Wong C, Calderon MA, Durham SR, et al. Grass pollen immunotherapy: IL-10 induction and suppression of late responses precedes IgG4 inhibitory antibody activity. J Allergy Clin Immunol 2008;121:1120-5.e2. 
  159. Des Roches A, Paradis L, Knani J, Hejjaoui A, Dhivert H, Chanez P, et al. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. V. Duration of the efficacy of immunotherapy after its cessation. Allergy 1996;51:430-3. 
  160. Bousquet J, Hejjaoui A, Soussana M, Michel FB. Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. IV. Comparison of the safety and efficacy of two dosages of a high-molecular-weight allergoid. J Allergy Clin Immunol 1990;85:490-7. 
  161. Kim JK, Kang SI, Kim DW. Development of airway allergic diseases and immunotherapy in children. Korean J Otorhinolaryngol-Head Neck Surg 2019;62:261-9. 
  162. Rosenstreich DL, Eggleston P, Kattan M, Baker D, Slavin RG, Gergen P, et al. The role of cockroach allergy and exposure to cockroach allergen in causing morbidity among inner-city children with asthma. N Engl J Med 1997;336:1356-63. 
  163. Alvaro-Lozano M, Akdis CA, Akdis M, Alviani C, Angier E, Arasi S, et al. EAACI Allergen Immunotherapy User's Guide. Pediatr Allergy Immunol 2020;31 Suppl 25(Suppl 25):1-101. 
  164. Pfaar O, Bousquet J, Durham SR, Kleine-Tebbe J, Larche M, Roberts G, et al. One hundred and ten years of Allergen Immunotherapy: a journey from empiric observation to evidence. Allergy 2022;77:454-68.
  165. Yu N, Luo H, Liang D, Lu N. Sublingual immunotherapy in mite-sensitized patients with atopic dermatitis: a randomized controlled study. Postepy Dermatol Alergol 2021;38:69-74. 
  166. Kristiansen M, Dhami S, Netuveli G, Halken S, Muraro A, Roberts G, et al. Allergen immunotherapy for the prevention of allergy: a systematic review and meta-analysis. Pediatr Allergy Immunol 2017;28:18-29. 
  167. Davila I, Dominguez-Ortega J, Navarro-Pulido A, Alonso A, Antolin-Amerigo D, Gonzalez-Mancebo E, et al. Consensus document on dog and cat allergy. Allergy 2018;73:1206-22. 
  168. Larenas-Linnemann D, Baxi S, Phipatanakul W, Portnoy JM; Environmental Allergens Workgroup. Clinical evaluation and management of patients with suspected fungus sensitivity. J Allergy Clin Immunol Pract 2016;4:405-14. 
  169. Portnoy J, Chew GL, Phipatanakul W, Williams PB, Grimes C, Kennedy K, et al. Environmental assessment and exposure reduction of cockroaches: a practice parameter. J Allergy Clin Immunol 2013;132:802-8. e1-25. 
  170. Wahn U, Tabar A, Kuna P, Halken S, Montagut A, de Beaumont O, et al. Efficacy and safety of 5-grass-pollen sublingual immunotherapy tablets in pediatric allergic rhinoconjunctivitis. J Allergy Clin Immunol 2009;123:160-6.e3. 
  171. Bufe A, Eberle P, Franke-Beckmann E, Funck J, Kimmig M, Klimek L, et al. Safety and efficacy in children of an SQ-standardized grass allergen tablet for sublingual immunotherapy. J Allergy Clin Immunol 2009;123:167-73.e7. 
  172. Rienzo VD, Minelli M, Musarra A, Sambugaro R, Pecora S, Canonica WG, et al. Post-marketing survey on the safety of sublingual immunotherapy in children below the age of 5 years. Clin Exp Allergy 2005;35:560-4. 
  173. Fiocchi A, Pajno G, La Grutta S, Pezzuto F, Incorvaia C, Sensi L, et al. Safety of sublingual-swallow immunotherapy in children aged 3 to 7 years. Ann Allergy Asthma Immunol 2005;95:254-8. 
  174. Agostinis F, Tellarini L, Canonica GW, Falagiani P, Passalacqua G. Safety of sublingual immunotherapy with a monomeric allergoid in very young children. Allergy 2005;60:133. 
  175. Shao J, Cui YX, Zheng YF, Peng HF, Zheng ZL, Chen JY, et al. Efficacy and safety of sublingual immunotherapy in children aged 3-13 years with allergic rhinitis. Am J Rhinol Allergy 2014;28:131-9. 
  176. Pajno GB, Caminiti L, Crisafulli G, Barberi S, Landi M, Aversa T, et al. Adherence to sublingual immunotherapy in preschool children. Pediatr Allergy Immunol 2012;23:688-9. 
  177. Karakoc-Aydiner E, Eifan AO, Baris S, Gunay E, Akturk E, Akkoc T, et al. Long-Term effect of sublingual and subcutaneous immunotherapy in dust mite-allergic children with asthma/rhinitis: a 3-year prospective randomized controlled trial. J Investig Allergol Clin Immunol 2015;25:334-42. 
  178. Eifan AO, Akkoc T, Yildiz A, Keles S, Ozdemir C, Bahceciler NN, et al. Clinical efficacy and immunological mechanisms of sublingual and subcutaneous immunotherapy in asthmatic/rhinitis children sensitized to house dust mite: an open randomized controlled trial. Clin Exp Allergy 2010;40:922-32. 
  179. Yukselen A, Kendirli SG, Yilmaz M, Altintas DU, Karakoc GB. Effect of one-year subcutaneous and sublingual immunotherapy on clinical and laboratory parameters in children with rhinitis and asthma: a randomized, placebo-controlled, double-blind, double-dummy study. Int Arch Allergy Immunol 2012;157:288-98. 
  180. Keles S, Karakoc-Aydiner E, Ozen A, Izgi AG, Tevetoglu A, Akkoc T, et al. A novel approach in allergen-specific immunotherapy: combination of sublingual and subcutaneous routes. J Allergy Clin Immunol 2011;128:808-15.e7. 
  181. Dhami S, Kakourou A, Asamoah F, Agache I, Lau S, Jutel M, et al. Allergen immunotherapy for allergic asthma: a systematic review and metaanalysis. Allergy 2017;72:1825-48. 
  182. Pajno GB, Bernardini R, Peroni D, Arasi S, Martelli A, Landi M, et al. Clinical practice recommendations for allergen-specific immunotherapy in children: the Italian consensus report. Ital J Pediatr 2017;43:13. 
  183. Calderon MA, Gerth van Wijk R, Eichler I, Matricardi PM, Varga EM, Kopp MV, et al. Perspectives on allergen-specific immunotherapy in childhood: an EAACI position statement. Pediatr Allergy Immunol 2012;23:300-6. 
  184. Arasi S, Passalacqua G, Caminiti L, Crisafulli G, Fiamingo C, Pajno GB. Efficacy and safety of sublingual immunotherapy in children. Expert Rev Clin Immunol 2016;12:49-56.