A Delphi consensus on diagnosis, management, and treatment with allergen immunotherapy of polysensitized children in Spain: CAPP study, Part 1
Main Article Content
Keywords
consensus, delphi method, polysensitisation, children, allergen immunotherapy, diagnosis
Abstract
Background: The study aimed to evaluate the level of agreement between specialists in pediatric allergology regarding the diagnosis and indications for pollen allergen immunotherapy (AIT) of polysensitized children in Spain.
Materials and Methods: A Delphi study was performed using an online survey designed by a committee of pediatric AIT experts: 46 and 44 panelists participated in rounds 1 and 2, respectively. In round 1, 204 statements on 8 dimensions were evaluated (Diagnosis; Therapeutic management; Pollens – Part I; Mites; Moulds; Animals; Hymenoptera venom; and Mixtures - Part II). A total of 148 statements were finally accepted after round 2. Panel members rated their level of agreement with assessments on a 9-point Likert scale based on acceptance by ≥ 66.7% of them.
Results: According to the results, the polysensitization determination in allergic patients is confirmed by clinical history, skin prick test, total and specific IgE, and molecular diagnostics. Clinical assessments are recommended for the AIT effectiveness evaluation. Follow-ups should be performed 6 months after AIT initiation. According to experts, pollens are the most representative allergens in allergic rhinitis but AIT is more effective in bronchial asthma treatment. The IgE levels are positively related to the intensity of the symptomatology and the efficacy of Grass AIT. In pollen mixtures, a maximum mixture of three AIT allergens is established between Grass, Olive, and Cupressaceae. Mixing pollen from Platanus acerifolia and Parietaria is not recommended.
Conclusions: This study provides, where evidence is lacking, current expert-based opinions on clinical decision-making for managing pollen AIT in polysensitized children.
References
1. 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. 10.1186/s13223-015-0109-6
2. Arbes SJ, Jr., Gergen PJ, Elliott L, Zeldin DC. Prevalences of positive skin test responses to 10 common allergens in the US population: Results from the third National Health and Nutrition Examination Survey. J Allergy Clin Immunol. 2005;116(2):377–83. 10.1016/j.jaci.2005.05.017
3. 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(11):797–803. 10.1016/j.annepidem.2010.05.012
4. Migueres M, Fontaine JF, Haddad T, Grosclaude M, Saint-Martin F, Bem David D, et al. Characteristics of patients with respiratory allergy in France and factors influencing immunotherapy prescription: A prospective observational study (REALIS). Int J Immunopathol Pharmacol. 2011;24(2):387–400. 10.1177/039463201102400212
5. Salo PM, Arbes SJ, Jr., Jaramillo R, Calatroni A, Weir CH, Sever ML, et al. Prevalence of allergic sensitization in the United States: Results from the National Health and Nutrition Examination Survey (NHANES) 2005–2006. J Allergy Clin Immunol. 2014;134(2):350–9. 10.1016/j.jaci.2013.12.1071
6. Ojeda P, Sastre J, Olaguibel JM, Chivato T. Alergológica 2015: A national survey on allergic diseases in the adult Spanish population. J Investig Allergol Clin Immunol. 2018;28(3):151–64. 10.18176/jiaci.0264
7. Valero A, Pereira C, Loureiro C, Martínez-Cócera C, Murio C, Rico P, et al. Interrelationship between skin sensitization, rhinitis, and asthma in patients with allergic rhinitis: A study of Spain and Portugal. J Investig Allergol Clin Immunol. 2009;19(3):167–72.
8. González-Mancebo E, Domínguez-Ortega J, Blanco-Bermejo S, González-Seco E, Trujillo MJ, de la Torre F. Comparison of two diagnostic techniques, skin-prick test and component resolved diagnosis in the follow-up of a cohort of paediatric patients with pollinosis. Multicentre pilot study in a highly exposed allergenic area. Allergol Immunopathol. 2017;45(2):121–6. 10.1016/j.aller.2016.04.005
9. Vidal C, Enrique E, Gonzalo A, Moreno C, Tabar AI. Diagnosis and allergen immunotherapy treatment of polysensitised patients with respiratory allergy in Spain: An Allergists’ Consensus. Clin Transl Allergy. 2014;4:36. 10.1186/2045-7022-4-36
10. Ha EK, Baek JH, Lee S-Y, Park YM, Kim WK, Sheen YH, et al. Association of polysensitization, allergic multimorbidity, and allergy severity: A cross-sectional study of school children. Int Arch Allergy Immunol. 2017;171(3–4):251–60. 10.1159/000453034
11. Migueres M, Dávila I, Frati F, Azpeitia A, Jeanpetit Y, Lhéritier-Barrand M, et al. Types of sensitization to aeroallergens: Definitions, prevalences and impact on the diagnosis and treatment of allergic respiratory disease. Clin Transl Allergy. 2014;4:16. 10.1186/2045-7022-4-16
12. Sastre J, Sastre-Ibañez M. Molecular diagnosis and immunotherapy. Curr Opin Allergy Clin Immunol. 2016;16(6):565–70. 10.1097/ACI.0000000000000318
13. Del-Río Camacho G, Montes Arjona AM, Fernández-Cantalejo Padial J, Rodríguez Catalán J. How molecular diagnosis may modify immunotherapy prescription in multi-sensitized pollen-allergic children. Allergol Immunopathol. 2018;46(6):552–6. 10.1016/j.aller.2018.03.002
14. 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. 10.1111/j.1398-9995.2007.01620.x
15. Custovic A, Wijk RG. The effectiveness of measures to change the indoor environment in the treatment of allergic rhinitis and asthma: ARIA update (in collaboration with GA(2)LEN). Allergy. 2005;60(9):1112–5. 10.1111/j.1398-9995.2005.00934.x
16. 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(4):765–98. 10.1111/all.13317
17. Ciprandi G, Incorvaia C, Puccinelli P, Dell’Albani I, Frati F. What should drive the choice of allergen for immunotherapy in polysensitized patients? Ann Allergy Asthma Immunol. 2012;109(2):148–9. 10.1016/j.anai.2012.06.007
18. Calderón 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(4):929–34. 10.1016/j.jaci.2011.11.019
19. Diamond IR, Grant RC, Feldman BM, Pencharz PB, Ling SC, Moore AM, et al. Defining consensus: A systematic review recommends methodologic criteria for reporting of Delphi studies. J Clin Epidemiol. 2014;67(4):401–9. 10.1016/j.jclinepi.2013.12.002
20. Nasa P, Jain R, Juneja D. Delphi methodology in healthcare research: How to decide its appropriateness. World J Methodol. 2021;11(4):116–29. 10.5662/wjm.v11.i4.116
21. Yeh JS, Van Hoof TJ, Fischer MA. Key features of academic detailing: Development of an expert consensus using the Delphi method. Am Health Drug Benefits. 2016;9(1):42–50.
22. Hasson F, Keeney S, McKenna H. Research guidelines for the Delphi survey technique. J Adv Nurs. 2000;32(4):1008–15.
23. James D, Warren-Forward H. Research methods for formal consensus development. Nurse Res. 2015;22(3):35–40. 10.7748/nr.22.3.35.e1297
24. Keeney S, Hasson F, McKenna H. Consulting the oracle: Ten lessons from using the Delphi technique in nursing research. J Adv Nurs. 2006;53(2):205–12. 10.1111/j.1365-2648.2006.03716.x
25. Niederberger M, Spranger J. Delphi technique in health sciences: A map. Front Public Health. 2020;8:457. 10.3389/fpubh.2020.00457
26. Veugelers R, Gaakeer MI, Patka P, Huijsman R. Improving design choices in Delphi studies in medicine: The case of an exemplary physician multi-round panel study with 100% response. BMC Med Res Methodol. 2020;20(1):156. 10.1186/s12874-020-01029-4
27. EMEA. Guideline on allergen products: Production and quality issues (EMEA/CHMP/BWP/304831/2007). 2008.
28. Bousquet J, Pfaar O, Togias A, Schünemann HJ, Ansotegui I, Papadopoulos NG, et al. 2019 ARIA Care pathways for allergen immunotherapy. Allergy. 2019;74(11):2087–102. 10.1111/all.13805
29. Brożek JL, Bousquet J, Agache I, Agarwal A, Bachert C, Bosnic-Anticevich S, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines-2016 revision. J Allergy Clin Immunol. 2017;140(4):950–8. 10.1016/j.jaci.2017.03.050
30. Zuberbier T, Bachert C, Bousquet PJ, Passalacqua G, Walter Canonica G, Merk H, et al. GA2 LEN/EAACI pocket guide for allergen-specific immunotherapy for allergic rhinitis and asthma. Allergy. 2010;65(12):1525–30. 10.1111/j.1398-9995.2010.02474.x
31. Martínez-Cañavate Burgos A, Torres-Borrego J, Molina Terán AB, Corzo JL, García BE, Rodríguez Pacheco R, et al. Molecular sensitization patterns and influence of molecular diagnosis in immunotherapy prescription in children sensitized to both grass and olive pollen. Pediatr Allergy Immunol. 2018;29(4):369–74. 10.1111/pai.12866
32. 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 25:1–101. 10.1111/pai.13189
33. Malm L, Gerth van Wijk R, Bachert C. Guidelines for nasal provocations with aspects on nasal patency, airflow, and airflow resistance. International Committee on Objective Assessment of the Nasal Airways, International Rhinologic Society. Rhinology. 2000;38(1):1–6.
34. Agache I, Bilò M, Braunstahl GJ, Delgado L, Demoly P, Eigenmann P, et al. In vivo diagnosis of allergic diseases—Allergen provocation tests. Allergy. 2015;70(4):355–65. 10.1111/all.12586
35. Augé J, Vent J, Agache I, Airaksinen L, Campo Mozo P, Chaker A, et al. EAACI Position paper on the standardization of nasal allergen challenges. Allergy. 2018;73(8):1597–608. 10.1111/all.13416
36. Eguiluz-Gracia I, Testera-Montes A, González M, Pérez-Sánchez N, Ariza A, Salas M, et al. Safety and reproducibility of nasal allergen challenge. Allergy. 2019;74(6):1125–34. 10.1111/all.13728
37. Eifan AO, Shamji MH, Durham SR. Long-term clinical and immunological effects of allergen immunotherapy. Curr Opin Allergy Clin Immunol. 2011;11(6):586–93. 10.1097/ACI.0b013e32834cb994
38. Zielen S, Kardos P, Madonini E. Steroid-sparing effects with allergen-specific immunotherapy in children with asthma: A randomized controlled trial. J Allergy Clin Immunol. 2010;126:942–9. 10.1016/j.jaci.2010.06.002
39. Abramson MJ, Puy RM, Weiner JM. Injection allergen immunotherapy for asthma. Cochrane Database Syst Rev. 2010; 8:CD001186. 10.1002/14651858.CD001186.pub2
40. Kappen J, Diamant Z, Agache I, Bonini M, Bousquet J, Canonica GW, et al. Standardization of clinical outcomes used in allergen immunotherapy in allergic asthma: An EAACI position paper. Allergy. 2023;78(11):2835–50. 10.1111/all.15817
41. 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 (ÖGAI), 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(8):282–319. 10.1007/s40629-014-0032-2
42. Nelson H, Kleine-Tebbe J, Nolte H, Riis B, Durham S, Bernstein D. P438 Efficacy of SQ SLIT-tablets in mono-and poly-sensitized HDM, grass, and ragweed allergic subjects. Ann Allergy Asthma Immunol. 2017;119:S91. 10.1016/j.anai.2017.09.034
43. Ciprandi G, Incorvaia C, Puccinelli P, Scurati S, Masieri S, Frati F. The Polismail lesson: Sublingual immunotherapy may be prescribed also in polysensitized patients. Int J Immunopathol Pharmacol. 2010;23(2):637–40. 10.1177/039463201002300227
44. Emminger W, Durham SR, 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. J Allergy Clin Immunol. 2009;123(2):S75. Doi : 10.1016/j.jaci.2008.12.257
45. Nelson H, Blaiss M, Nolte H, Würtz SØ, Andersen JS, Durham SR. Efficacy and safety of the SQ-standardized grass allergy immunotherapy tablet in mono-and polysensitized subjects. Allergy. 2013;68(2):252–5. 10.1111/all.12074
46. Kim JY, Jang MJ, Kim DY, Park SW, Han DH. Efficacy of subcutaneous and sublingual immunotherapy for house dust mite allergy: A network meta-analysis-based comparison. J Allergy Clin Immunol Pract. 2021;9(2):4450–4458.e6. 10.1016/j.jaip.2021.08.018
47. Liu W, Zeng Q, He C, Chen R, Tang Y, Yan S, et al. Compliance, efficacy, and safety of subcutaneous and sublingual immunotherapy in children with allergic rhinitis. Pediatr Allergy Immunol. 2021;32(1):86–91. 10.1111/pai.13332
48. Nolte H, Maloney J, Nelson HS, Bernstein DI, Lu S, Li Z, et al. Onset and dose-related efficacy of house dust mite sublingual immunotherapy tablets in an environmental exposure chamber. J Allergy Clin Immunol. 2015;135(6):1494–501.e6. 10.1016/j.jaci.2014.12.1911
49. Calderón MA, Larenas D, Kleine-Tebbe J, Jacobsen L, Passalacqua G, Eng PA, et al. European Academy of Allergy and Clinical Immunology task force report on “dose–response relationship in allergen-specific immunotherapy.” Allergy. 2011;66(10):1345–59. 10.1111/j.1398-9995.2011.02669.x
50. Calderon MA, Casale TB, Nelson HS, Bacharier LB, Bansal P, Bernstein DI, et al. Extrapolating evidence-based medicine of AIT into clinical practice in the United States. J Allergy Clin Immunol Pract. 2023;11(4):1100–15. 10.1016/j.jaip.2022.10.033
51. Sastre J, Landivar ME, Ruiz-García M, Andregnette-Rosigno MV, Mahillo I. How molecular diagnosis can change allergen-specific immunotherapy prescription in a complex pollen area. Allergy. 2012;67(5):709–11. 10.1111/j.1398-9995.2012.02808.x
52. Sastre J. Molecular diagnosis in allergy. Clin Exp Allergy. 2010;40(10):1442–60. 10.1111/j.1365-2222.2010.03585.x.
53. Asero R, Tripodi S, Dondi A, Di Rienzo Businco A, Sfika I, Bianchi A, et al. Prevalence and clinical relevance of IgE sensitization to profilin in childhood: A multicenter study. Int Arch Allergy Immunol. 2015;168(1):25–31. 10.1159/000441222
54. Almeida E, Caeiro E, Todo-Bom A, Duarte A, Gazarini L. Sensitization to grass allergens: Phl p1, Phl p5 and Phl p7 Phl p12 in adult and children patients in Beja (Southern Portugal). Allergol Immunopathol (Madr). 2019;47(6):579–84. 10.1016/j.aller.2019.04.006
55. Sekerkova A, Polackova M, Striz I. Detection of Phl p 1, Phl p 5, Phl p 7 and Phl p 12 specific IgE antibodies in the sera of children and adult patients allergic to Phleum pollen. Allergol Int. 2012;61(2):339–46. 10.2332/allergolint.11-OA-0372
56. Cipriani F, Mastrorilli C, Tripodi S, Ricci G, Perna S, Panetta V, et al. Diagnostic relevance of IgE sensitization profiles to eight recombinant Phleum pratense molecules. Allergy. 2018;73(3):673–82. 10.1111/all.13338
57. Sastre J, Rodríguez F, Campo P, Laffond E, Marín A, Alonso MD. Adverse reactions to immunotherapy are associated with different patterns of sensitization to grass allergens. Allergy. 2015;70(5):598–600. 10.1111/all.12575
58. 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(5):1103–10, 10.e1–4. 10.1016/j.jaci.2009.02.012
59. 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(3):210–7. 10.1159/000365630
60. Berge M, Bertilsson L, Hultgren O, Hugosson S, Saber A. Pre-treatment allergen-specific IgE analysis and outcomes of allergen immunotherapy. Eur Ann Allergy Clin Immunol. 2022;54(5):218–28. 10.23822/EurAnnACI.1764-1489.199
61. Walker SM, Durham SR, Till SJ, Roberts G, Corrigan CJ, Leech SC, et al. Immunotherapy for allergic rhinitis. Clin Exp Allergy. 2011;41(9):1177–200. 10.1111/j.1365-2222.2011.03794.x
62. GINA. Global strategy for asthma management and prevention. (2023 update). Available from: https://ginasthma.org/2024-report/
63. Radulovic S, Calderon MA, Wilson D, Durham S. Sublingual immunotherapy for allergic rhinitis. Cochrane Database Syst Rev. 2010;2010(12):Cd002893. 10.1002/14651858.CD002893.pub2
64. Ciprandi G, Cadario G, Di Gioacchino M, Gangemi S, Minelli M, Ridolo E, et al. Sublingual immunotherapy in polysensitized allergic patients with rhinitis and/or asthma: Allergist choices and treatment efficacy. J Biol Regul Homeost Agents. 2009;23(3):165–71.
65. Ciprandi G, Cadario G, Valle C, Ridolo E, Verini M, Di Gioacchino M, et al. Sublingual immunotherapy in polysensitized patients: Effect on quality of life. J Investig Allergol Clin Immunol. 2010;20(4):274–9.
66. Barber D, Diaz-Perales A, Escribese MM, Kleine-Tebbe J, Matricardi PM, Ollert M, et al. Molecular allergology and its impact in specific allergy diagnosis and therapy. Allergy. 2021;76(12):3642–58. 10.1111/all.14969
67. 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(3):813–28. 10.1016/j.jaci.2019.01.024
68. Zimmer J, Bonertz A, Vieths S. Quality requirements for allergen extracts and allergoids for allergen immunotherapy. Allergol Immunopathol (Madr). 2017;45 Suppl 1:4–11. 10.1016/j.aller.2017.09.002
2. Arbes SJ, Jr., Gergen PJ, Elliott L, Zeldin DC. Prevalences of positive skin test responses to 10 common allergens in the US population: Results from the third National Health and Nutrition Examination Survey. J Allergy Clin Immunol. 2005;116(2):377–83. 10.1016/j.jaci.2005.05.017
3. 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(11):797–803. 10.1016/j.annepidem.2010.05.012
4. Migueres M, Fontaine JF, Haddad T, Grosclaude M, Saint-Martin F, Bem David D, et al. Characteristics of patients with respiratory allergy in France and factors influencing immunotherapy prescription: A prospective observational study (REALIS). Int J Immunopathol Pharmacol. 2011;24(2):387–400. 10.1177/039463201102400212
5. Salo PM, Arbes SJ, Jr., Jaramillo R, Calatroni A, Weir CH, Sever ML, et al. Prevalence of allergic sensitization in the United States: Results from the National Health and Nutrition Examination Survey (NHANES) 2005–2006. J Allergy Clin Immunol. 2014;134(2):350–9. 10.1016/j.jaci.2013.12.1071
6. Ojeda P, Sastre J, Olaguibel JM, Chivato T. Alergológica 2015: A national survey on allergic diseases in the adult Spanish population. J Investig Allergol Clin Immunol. 2018;28(3):151–64. 10.18176/jiaci.0264
7. Valero A, Pereira C, Loureiro C, Martínez-Cócera C, Murio C, Rico P, et al. Interrelationship between skin sensitization, rhinitis, and asthma in patients with allergic rhinitis: A study of Spain and Portugal. J Investig Allergol Clin Immunol. 2009;19(3):167–72.
8. González-Mancebo E, Domínguez-Ortega J, Blanco-Bermejo S, González-Seco E, Trujillo MJ, de la Torre F. Comparison of two diagnostic techniques, skin-prick test and component resolved diagnosis in the follow-up of a cohort of paediatric patients with pollinosis. Multicentre pilot study in a highly exposed allergenic area. Allergol Immunopathol. 2017;45(2):121–6. 10.1016/j.aller.2016.04.005
9. Vidal C, Enrique E, Gonzalo A, Moreno C, Tabar AI. Diagnosis and allergen immunotherapy treatment of polysensitised patients with respiratory allergy in Spain: An Allergists’ Consensus. Clin Transl Allergy. 2014;4:36. 10.1186/2045-7022-4-36
10. Ha EK, Baek JH, Lee S-Y, Park YM, Kim WK, Sheen YH, et al. Association of polysensitization, allergic multimorbidity, and allergy severity: A cross-sectional study of school children. Int Arch Allergy Immunol. 2017;171(3–4):251–60. 10.1159/000453034
11. Migueres M, Dávila I, Frati F, Azpeitia A, Jeanpetit Y, Lhéritier-Barrand M, et al. Types of sensitization to aeroallergens: Definitions, prevalences and impact on the diagnosis and treatment of allergic respiratory disease. Clin Transl Allergy. 2014;4:16. 10.1186/2045-7022-4-16
12. Sastre J, Sastre-Ibañez M. Molecular diagnosis and immunotherapy. Curr Opin Allergy Clin Immunol. 2016;16(6):565–70. 10.1097/ACI.0000000000000318
13. Del-Río Camacho G, Montes Arjona AM, Fernández-Cantalejo Padial J, Rodríguez Catalán J. How molecular diagnosis may modify immunotherapy prescription in multi-sensitized pollen-allergic children. Allergol Immunopathol. 2018;46(6):552–6. 10.1016/j.aller.2018.03.002
14. 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. 10.1111/j.1398-9995.2007.01620.x
15. Custovic A, Wijk RG. The effectiveness of measures to change the indoor environment in the treatment of allergic rhinitis and asthma: ARIA update (in collaboration with GA(2)LEN). Allergy. 2005;60(9):1112–5. 10.1111/j.1398-9995.2005.00934.x
16. 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(4):765–98. 10.1111/all.13317
17. Ciprandi G, Incorvaia C, Puccinelli P, Dell’Albani I, Frati F. What should drive the choice of allergen for immunotherapy in polysensitized patients? Ann Allergy Asthma Immunol. 2012;109(2):148–9. 10.1016/j.anai.2012.06.007
18. Calderón 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(4):929–34. 10.1016/j.jaci.2011.11.019
19. Diamond IR, Grant RC, Feldman BM, Pencharz PB, Ling SC, Moore AM, et al. Defining consensus: A systematic review recommends methodologic criteria for reporting of Delphi studies. J Clin Epidemiol. 2014;67(4):401–9. 10.1016/j.jclinepi.2013.12.002
20. Nasa P, Jain R, Juneja D. Delphi methodology in healthcare research: How to decide its appropriateness. World J Methodol. 2021;11(4):116–29. 10.5662/wjm.v11.i4.116
21. Yeh JS, Van Hoof TJ, Fischer MA. Key features of academic detailing: Development of an expert consensus using the Delphi method. Am Health Drug Benefits. 2016;9(1):42–50.
22. Hasson F, Keeney S, McKenna H. Research guidelines for the Delphi survey technique. J Adv Nurs. 2000;32(4):1008–15.
23. James D, Warren-Forward H. Research methods for formal consensus development. Nurse Res. 2015;22(3):35–40. 10.7748/nr.22.3.35.e1297
24. Keeney S, Hasson F, McKenna H. Consulting the oracle: Ten lessons from using the Delphi technique in nursing research. J Adv Nurs. 2006;53(2):205–12. 10.1111/j.1365-2648.2006.03716.x
25. Niederberger M, Spranger J. Delphi technique in health sciences: A map. Front Public Health. 2020;8:457. 10.3389/fpubh.2020.00457
26. Veugelers R, Gaakeer MI, Patka P, Huijsman R. Improving design choices in Delphi studies in medicine: The case of an exemplary physician multi-round panel study with 100% response. BMC Med Res Methodol. 2020;20(1):156. 10.1186/s12874-020-01029-4
27. EMEA. Guideline on allergen products: Production and quality issues (EMEA/CHMP/BWP/304831/2007). 2008.
28. Bousquet J, Pfaar O, Togias A, Schünemann HJ, Ansotegui I, Papadopoulos NG, et al. 2019 ARIA Care pathways for allergen immunotherapy. Allergy. 2019;74(11):2087–102. 10.1111/all.13805
29. Brożek JL, Bousquet J, Agache I, Agarwal A, Bachert C, Bosnic-Anticevich S, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines-2016 revision. J Allergy Clin Immunol. 2017;140(4):950–8. 10.1016/j.jaci.2017.03.050
30. Zuberbier T, Bachert C, Bousquet PJ, Passalacqua G, Walter Canonica G, Merk H, et al. GA2 LEN/EAACI pocket guide for allergen-specific immunotherapy for allergic rhinitis and asthma. Allergy. 2010;65(12):1525–30. 10.1111/j.1398-9995.2010.02474.x
31. Martínez-Cañavate Burgos A, Torres-Borrego J, Molina Terán AB, Corzo JL, García BE, Rodríguez Pacheco R, et al. Molecular sensitization patterns and influence of molecular diagnosis in immunotherapy prescription in children sensitized to both grass and olive pollen. Pediatr Allergy Immunol. 2018;29(4):369–74. 10.1111/pai.12866
32. 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 25:1–101. 10.1111/pai.13189
33. Malm L, Gerth van Wijk R, Bachert C. Guidelines for nasal provocations with aspects on nasal patency, airflow, and airflow resistance. International Committee on Objective Assessment of the Nasal Airways, International Rhinologic Society. Rhinology. 2000;38(1):1–6.
34. Agache I, Bilò M, Braunstahl GJ, Delgado L, Demoly P, Eigenmann P, et al. In vivo diagnosis of allergic diseases—Allergen provocation tests. Allergy. 2015;70(4):355–65. 10.1111/all.12586
35. Augé J, Vent J, Agache I, Airaksinen L, Campo Mozo P, Chaker A, et al. EAACI Position paper on the standardization of nasal allergen challenges. Allergy. 2018;73(8):1597–608. 10.1111/all.13416
36. Eguiluz-Gracia I, Testera-Montes A, González M, Pérez-Sánchez N, Ariza A, Salas M, et al. Safety and reproducibility of nasal allergen challenge. Allergy. 2019;74(6):1125–34. 10.1111/all.13728
37. Eifan AO, Shamji MH, Durham SR. Long-term clinical and immunological effects of allergen immunotherapy. Curr Opin Allergy Clin Immunol. 2011;11(6):586–93. 10.1097/ACI.0b013e32834cb994
38. Zielen S, Kardos P, Madonini E. Steroid-sparing effects with allergen-specific immunotherapy in children with asthma: A randomized controlled trial. J Allergy Clin Immunol. 2010;126:942–9. 10.1016/j.jaci.2010.06.002
39. Abramson MJ, Puy RM, Weiner JM. Injection allergen immunotherapy for asthma. Cochrane Database Syst Rev. 2010; 8:CD001186. 10.1002/14651858.CD001186.pub2
40. Kappen J, Diamant Z, Agache I, Bonini M, Bousquet J, Canonica GW, et al. Standardization of clinical outcomes used in allergen immunotherapy in allergic asthma: An EAACI position paper. Allergy. 2023;78(11):2835–50. 10.1111/all.15817
41. 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 (ÖGAI), 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(8):282–319. 10.1007/s40629-014-0032-2
42. Nelson H, Kleine-Tebbe J, Nolte H, Riis B, Durham S, Bernstein D. P438 Efficacy of SQ SLIT-tablets in mono-and poly-sensitized HDM, grass, and ragweed allergic subjects. Ann Allergy Asthma Immunol. 2017;119:S91. 10.1016/j.anai.2017.09.034
43. Ciprandi G, Incorvaia C, Puccinelli P, Scurati S, Masieri S, Frati F. The Polismail lesson: Sublingual immunotherapy may be prescribed also in polysensitized patients. Int J Immunopathol Pharmacol. 2010;23(2):637–40. 10.1177/039463201002300227
44. Emminger W, Durham SR, 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. J Allergy Clin Immunol. 2009;123(2):S75. Doi : 10.1016/j.jaci.2008.12.257
45. Nelson H, Blaiss M, Nolte H, Würtz SØ, Andersen JS, Durham SR. Efficacy and safety of the SQ-standardized grass allergy immunotherapy tablet in mono-and polysensitized subjects. Allergy. 2013;68(2):252–5. 10.1111/all.12074
46. Kim JY, Jang MJ, Kim DY, Park SW, Han DH. Efficacy of subcutaneous and sublingual immunotherapy for house dust mite allergy: A network meta-analysis-based comparison. J Allergy Clin Immunol Pract. 2021;9(2):4450–4458.e6. 10.1016/j.jaip.2021.08.018
47. Liu W, Zeng Q, He C, Chen R, Tang Y, Yan S, et al. Compliance, efficacy, and safety of subcutaneous and sublingual immunotherapy in children with allergic rhinitis. Pediatr Allergy Immunol. 2021;32(1):86–91. 10.1111/pai.13332
48. Nolte H, Maloney J, Nelson HS, Bernstein DI, Lu S, Li Z, et al. Onset and dose-related efficacy of house dust mite sublingual immunotherapy tablets in an environmental exposure chamber. J Allergy Clin Immunol. 2015;135(6):1494–501.e6. 10.1016/j.jaci.2014.12.1911
49. Calderón MA, Larenas D, Kleine-Tebbe J, Jacobsen L, Passalacqua G, Eng PA, et al. European Academy of Allergy and Clinical Immunology task force report on “dose–response relationship in allergen-specific immunotherapy.” Allergy. 2011;66(10):1345–59. 10.1111/j.1398-9995.2011.02669.x
50. Calderon MA, Casale TB, Nelson HS, Bacharier LB, Bansal P, Bernstein DI, et al. Extrapolating evidence-based medicine of AIT into clinical practice in the United States. J Allergy Clin Immunol Pract. 2023;11(4):1100–15. 10.1016/j.jaip.2022.10.033
51. Sastre J, Landivar ME, Ruiz-García M, Andregnette-Rosigno MV, Mahillo I. How molecular diagnosis can change allergen-specific immunotherapy prescription in a complex pollen area. Allergy. 2012;67(5):709–11. 10.1111/j.1398-9995.2012.02808.x
52. Sastre J. Molecular diagnosis in allergy. Clin Exp Allergy. 2010;40(10):1442–60. 10.1111/j.1365-2222.2010.03585.x.
53. Asero R, Tripodi S, Dondi A, Di Rienzo Businco A, Sfika I, Bianchi A, et al. Prevalence and clinical relevance of IgE sensitization to profilin in childhood: A multicenter study. Int Arch Allergy Immunol. 2015;168(1):25–31. 10.1159/000441222
54. Almeida E, Caeiro E, Todo-Bom A, Duarte A, Gazarini L. Sensitization to grass allergens: Phl p1, Phl p5 and Phl p7 Phl p12 in adult and children patients in Beja (Southern Portugal). Allergol Immunopathol (Madr). 2019;47(6):579–84. 10.1016/j.aller.2019.04.006
55. Sekerkova A, Polackova M, Striz I. Detection of Phl p 1, Phl p 5, Phl p 7 and Phl p 12 specific IgE antibodies in the sera of children and adult patients allergic to Phleum pollen. Allergol Int. 2012;61(2):339–46. 10.2332/allergolint.11-OA-0372
56. Cipriani F, Mastrorilli C, Tripodi S, Ricci G, Perna S, Panetta V, et al. Diagnostic relevance of IgE sensitization profiles to eight recombinant Phleum pratense molecules. Allergy. 2018;73(3):673–82. 10.1111/all.13338
57. Sastre J, Rodríguez F, Campo P, Laffond E, Marín A, Alonso MD. Adverse reactions to immunotherapy are associated with different patterns of sensitization to grass allergens. Allergy. 2015;70(5):598–600. 10.1111/all.12575
58. 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(5):1103–10, 10.e1–4. 10.1016/j.jaci.2009.02.012
59. 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(3):210–7. 10.1159/000365630
60. Berge M, Bertilsson L, Hultgren O, Hugosson S, Saber A. Pre-treatment allergen-specific IgE analysis and outcomes of allergen immunotherapy. Eur Ann Allergy Clin Immunol. 2022;54(5):218–28. 10.23822/EurAnnACI.1764-1489.199
61. Walker SM, Durham SR, Till SJ, Roberts G, Corrigan CJ, Leech SC, et al. Immunotherapy for allergic rhinitis. Clin Exp Allergy. 2011;41(9):1177–200. 10.1111/j.1365-2222.2011.03794.x
62. GINA. Global strategy for asthma management and prevention. (2023 update). Available from: https://ginasthma.org/2024-report/
63. Radulovic S, Calderon MA, Wilson D, Durham S. Sublingual immunotherapy for allergic rhinitis. Cochrane Database Syst Rev. 2010;2010(12):Cd002893. 10.1002/14651858.CD002893.pub2
64. Ciprandi G, Cadario G, Di Gioacchino M, Gangemi S, Minelli M, Ridolo E, et al. Sublingual immunotherapy in polysensitized allergic patients with rhinitis and/or asthma: Allergist choices and treatment efficacy. J Biol Regul Homeost Agents. 2009;23(3):165–71.
65. Ciprandi G, Cadario G, Valle C, Ridolo E, Verini M, Di Gioacchino M, et al. Sublingual immunotherapy in polysensitized patients: Effect on quality of life. J Investig Allergol Clin Immunol. 2010;20(4):274–9.
66. Barber D, Diaz-Perales A, Escribese MM, Kleine-Tebbe J, Matricardi PM, Ollert M, et al. Molecular allergology and its impact in specific allergy diagnosis and therapy. Allergy. 2021;76(12):3642–58. 10.1111/all.14969
67. 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(3):813–28. 10.1016/j.jaci.2019.01.024
68. Zimmer J, Bonertz A, Vieths S. Quality requirements for allergen extracts and allergoids for allergen immunotherapy. Allergol Immunopathol (Madr). 2017;45 Suppl 1:4–11. 10.1016/j.aller.2017.09.002
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Mar 1, 2025
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Mesa-del-Castillo, M., Canals Candela, F. J., Martínez-Cañavate, A., Rivas-Juesas, C., Larramona Cabrera, H., Tortajada-Girbés, M., Lucas Moreno, J. M., Mar Folqué, M. del, Morales-Tirado, A., & I. Tabar, A. (2025). A Delphi consensus on diagnosis, management, and treatment with allergen immunotherapy of polysensitized children in Spain: CAPP study, Part 1. Allergologia Et Immunopathologia, 53(2), 124-140. https://doi.org/10.15586/aei.v53i2.1220
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Mesa-del-Castillo, M., Canals Candela, F. J., Martínez-Cañavate, A., Rivas-Juesas, C., Larramona Cabrera, H., Tortajada-Girbés, M., Lucas Moreno, J. M., Mar Folqué, M. del, Morales-Tirado, A., & I. Tabar, A. (2025). A Delphi consensus on diagnosis, management, and treatment with allergen immunotherapy of polysensitized children in Spain: CAPP study, Part 1. Allergologia Et Immunopathologia, 53(2), 124-140. https://doi.org/10.15586/aei.v53i2.1220