Download PDF
Semin Respir Crit Care Med 2022; 43(05): 709-719
DOI: 10.1055/s-0042-1749454
Review Article

Immunotherapy for Asthma

Jelena Eremija
1   Section of Allergy and Immunology, Department of Medicine, Asthma, and Airway Disease Research Center, University of Arizona, Tucson, Arizona
,
Tara F. Carr
1   Section of Allergy and Immunology, Department of Medicine, Asthma, and Airway Disease Research Center, University of Arizona, Tucson, Arizona
› Author Affiliations
› Further Information
    Permissions and Reprints

Abstract

Asthma represents one of the biggest global health concerns with increasing prevalence and influence on global health. Several distinct asthma phenotypes have been identified with one of the most common, earliest recognized, and described being the allergic asthma phenotype, in which allergens trigger asthma through mechanisms involving allergen-specific immunoglobulin E (IgE). Allergen-specific immunotherapy (AIT), in the forms of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), has been used for many decades as a tool for reducing IgE-mediated sensitization and controlling symptoms of allergic disease, most commonly for allergic rhinitis, and it remains the only currently available disease modifying therapy in atopic patients. AIT has been studied for use in mild to moderate allergic asthma. While the data are often inconsistent, and utilize a multitude of different methods, antigens, and outcome measures, in general, AIT may have several beneficial effects on asthma disease control, quality of life, and requirement for medication. These benefits are notable when immunotherapy is used as an adjunct to pharmacologic treatment in carefully selected and monitored patients with mild to moderate persistent asthma. Patients with severe asthma are excluded from these trials. Importantly, patients with asthma, and in particular severe asthma, may have a higher rate of systemic adverse reactions to SCIT, including anaphylaxis; however, these events are overall rare. Future research in the area is needed to definitively assess the benefit of SCIT and SLIT for patients with asthma, comparing outcomes with different methods, addressing the role of AIT in severe asthma, significance of multiallergen AIT in allergic asthma, and safety concerns in asthma.

Keywords

asthma - allergic asthma - asthma management - allergen-specific immunotherapy - subcutaneous immunotherapy - sublingual immunotherapy


Publication History

Article published online:
17 June 2022

© 2022. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Expert panel report 3: Guidelines for the diagnosis and management of asthma. Accessed November 15, 2021 at: www.nhlbi.nih.gov/guidelines/asthma/epr3/index.htm
    PubMedGoogle Scholar
  • 2 World Health Organization. Global surveillance, prevention and control of chronic respiratory diseases: a comprehensive approach. 2007 . Accessed November 15, 2021 at: http://www.who.int/gard/publications/GARD%20Book%202007
    PubMedGoogle Scholar
  • 3 Control CfD. Most Recent National Asthma Data. 2021 . Accessed November 15, 2021 at: https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm
    PubMedGoogle Scholar
  • 4 Centers for Disease Control and Prevention (CDC). Vital signs: asthma prevalence, disease characteristics, and self-management education: United States, 2001–2009. MMWR Morb Mortal Wkly Rep 2011; 60 (17) 547-552
    PubMedGoogle Scholar
  • 5 Haldar P, Pavord ID, Shaw DE. et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med 2008; 178 (03) 218-224
    Google Scholar
  • 6 Carr TF, Zeki AA, Kraft M. Eosinophilic and noneosinophilic asthma. Am J Respir Crit Care Med 2018; 197 (01) 22-37
    CrossrefPubMedGoogle Scholar
  • 7 Lotvall J, Akdis CA, Bacharier LB. et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol 2011; 127 (02) 355-360
    CrossrefPubMedGoogle Scholar
  • 8 Johansson SG, Hourihane JO, Bousquet J. et al; EAACI (the European Academy of Allergology and Cinical Immunology) nomenclature task force. A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force. Allergy 2001; 56 (09) 813-824
    CrossrefPubMedGoogle Scholar
  • 9 Buckley RD, Carr TF. Association of aeroallergen sensitization and atopic disease in the Sonoran Desert. Allergy Asthma Proc 2017; 38 (05) 370-375
    CrossrefPubMedGoogle Scholar
  • 10 Gough H, Grabenhenrich L, Reich A. et al; MAS study group. Allergic multimorbidity of asthma, rhinitis and eczema over 20 years in the German birth cohort MAS. Pediatr Allergy Immunol 2015; 26 (05) 431-437
    CrossrefPubMedGoogle Scholar
  • 11 Castro-Rodríguez JA, Holberg CJ, Wright AL, Martinez FD. A clinical index to define risk of asthma in young children with recurrent wheezing. Am J Respir Crit Care Med 2000; 162 (4 Pt 1): 1403-1406
    CrossrefPubMedGoogle Scholar
  • 12 Miranda C, Busacker A, Balzar S, Trudeau J, Wenzel SE. Distinguishing severe asthma phenotypes: role of age at onset and eosinophilic inflammation. J Allergy Clin Immunol 2004; 113 (01) 101-108
    CrossrefPubMedGoogle Scholar
  • 13 Agache I, Akdis C, Jutel M, Virchow JC. Untangling asthma phenotypes and endotypes. Allergy 2012; 67 (07) 835-846
    CrossrefPubMedGoogle Scholar
  • 14 Israel E, Reddel HK. Severe and difficult-to-treat asthma in adults. N Engl J Med 2017; 377 (10) 965-976
    CrossrefPubMedGoogle Scholar
  • 15 Morgan WJ, Crain EF, Gruchalla RS. et al; Inner-City Asthma Study Group. Results of a home-based environmental intervention among urban children with asthma. N Engl J Med 2004; 351 (11) 1068-1080
    CrossrefPubMedGoogle Scholar
  • 16 Murray CS, Foden P, Sumner H, Shepley E, Custovic A, Simpson A. Preventing severe asthma exacerbations in children. A randomized trial of mite-impermeable bedcovers. Am J Respir Crit Care Med 2017; 196 (02) 150-158
    CrossrefPubMedGoogle Scholar
  • 17 Akar-Ghibril N, Casale T, Custovic A, Phipatanakul W. Allergic endotypes and phenotypes of asthma. J Allergy Clin Immunol Pract 2020; 8 (02) 429-440
    CrossrefPubMedGoogle Scholar
  • 18 Carr TF, Kraft M. Management of severe asthma before referral to the severe asthma specialist. J Allergy Clin Immunol Pract 2017; 5 (04) 877-886
    CrossrefPubMedGoogle Scholar
  • 19 Burks AW, Calderon MA, Casale T. et al. Update on allergy immunotherapy: American Academy of Allergy, Asthma & Immunology/European Academy of Allergy and Clinical Immunology/PRACTALL consensus report. J Allergy Clin Immunol 2013; 131 (05) 1288-96.e3
    CrossrefPubMedGoogle Scholar
  • 20 Cox L, Nelson H, Lockey R. et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol 2011; 127 (Suppl. 01) S1-S55
    CrossrefPubMedGoogle Scholar
  • 21 Zhang W, Lin C, Sampath V, Nadeau K. Impact of allergen immunotherapy in allergic asthma. Immunotherapy 2018; 10 (07) 579-593
    CrossrefPubMedGoogle Scholar
  • 22 Nagata M, Nakagome K. Allergen immunotherapy in asthma: current status and future perspectives. Allergol Int 2010; 59 (01) 15-19
    CrossrefPubMedGoogle Scholar
  • 23 Passalacqua G, Canonica GW, Bagnasco D. Benefit of SLIT and SCIT for allergic rhinitis and asthma. Curr Allergy Asthma Rep 2016; 16 (12) 88
    CrossrefPubMedGoogle Scholar
  • 24 Tosca MA, Licari A, Olcese R, Marseglia G, Sacco O, Ciprandi G. Immunotherapy and asthma in children. Front Pediatr 2018; 6: 231
    CrossrefPubMedGoogle Scholar
  • 25 National Asthma Education and Prevention Program. Expert panel report 3 (EPR-3): guidelines for the diagnosis and management of asthma-Summary Report 2007. J Allergy Clin Immunol 2007; 120 (Suppl. 05) S94-S138
    PubMedGoogle Scholar
  • 26 Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention,. 2019 . Accessed July 31, 2019 at: www.ginasthma.org
    PubMedGoogle Scholar
  • 27 Brożek JL, Bousquet J, Agache I. et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines-2016 revision. J Allergy Clin Immunol 2017; 140 (04) 950-958
    Google Scholar
  • 28 Lin SY, Azar A, Suarez-Cuervo C. et al. The Role of Immunotherapy in the Treatment of Asthma. AHRQ Comparative Effectiveness Reviews. Rockville: MD; 2018
    Google Scholar
  • 29 Cloutier MM, Baptist AP, Blake KV. et al; Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC). 2020 focused updates to the asthma management guidelines: a report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol 2020; 146 (06) 1217-1270
    CrossrefPubMedGoogle Scholar
  • 30 Agache I, Lau S, Akdis CA. et al. EAACI guidelines on allergen immunotherapy: house dust mite-driven allergic asthma. Allergy 2019; 74 (05) 855-873
    CrossrefPubMedGoogle Scholar
  • 31 Dhami S, Kakourou A, Asamoah F. et al. Allergen immunotherapy for allergic asthma: a systematic review and meta-analysis. Allergy 2017; 72 (12) 1825-1848
    CrossrefPubMedGoogle Scholar
  • 32 Ameal A, Vega-Chicote JM, Fernández S. et al. Double-blind and placebo-controlled study to assess efficacy and safety of a modified allergen extract of Dermatophagoides pteronyssinus in allergic asthma. Allergy 2005; 60 (09) 1178-1183
    CrossrefPubMedGoogle Scholar
  • 33 García-Robaina JC, Sánchez I, de la Torre F, Fernández-Caldas E, Casanovas M. Successful management of mite-allergic asthma with modified extracts of Dermatophagoides pteronyssinus and Dermatophagoides farinae in a double-blind, placebo-controlled study. J Allergy Clin Immunol 2006; 118 (05) 1026-1032
    CrossrefPubMedGoogle Scholar
  • 34 Kuna P, Kaczmarek J, Kupczyk M. Efficacy and safety of immunotherapy for allergies to Alternaria alternata in children. J Allergy Clin Immunol 2011; 127 (02) 502-506
    CrossrefPubMedGoogle Scholar
  • 35 Kiliç M, Altintaş DU, Yilmaz M, Bingöl-Karakoç G, Burgut R, Güneşer-Kendirli S. Evaluation of efficacy of immunotherapy in children with asthma monosensitized to Alternaria. Turk J Pediatr 2011; 53 (03) 285-294
    PubMedGoogle Scholar
  • 36 Lozano J, Cruz MJ, Piquer M, Giner MT, Plaza AM. Assessing the efficacy of immunotherapy with a glutaraldehyde-modified house dust mite extract in children by monitoring changes in clinical parameters and inflammatory markers in exhaled breath. Int Arch Allergy Immunol 2014; 165 (02) 140-147
    CrossrefPubMedGoogle Scholar
  • 37 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 (08) 853-859
    CrossrefPubMedGoogle Scholar
  • 38 Baris S, Kiykim A, Ozen A, Tulunay A, Karakoc-Aydiner E, Barlan IB. Vitamin D as an adjunct to subcutaneous allergen immunotherapy in asthmatic children sensitized to house dust mite. Allergy 2014; 69 (02) 246-253
    CrossrefPubMedGoogle Scholar
  • 39 Adkinson Jr NF, Eggleston PA, Eney D. et al. A controlled trial of immunotherapy for asthma in allergic children. N Engl J Med 1997; 336 (05) 324-331
    CrossrefPubMedGoogle Scholar
  • 40 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 (05) 942-949
    CrossrefPubMedGoogle Scholar
  • 41 Pifferi M, Baldini G, Marrazzini G. et al. Benefits of immunotherapy with a standardized Dermatophagoides pteronyssinus extract in asthmatic children: a three-year prospective study. Allergy 2002; 57 (09) 785-790
    CrossrefPubMedGoogle Scholar
  • 42 Wang H, Lin X, Hao C. et al. A double-blind, placebo-controlled study of house dust mite immunotherapy in Chinese asthmatic patients. Allergy 2006; 61 (02) 191-197
    CrossrefPubMedGoogle Scholar
  • 43 Tsai TC, Lu JH, Chen SJ, Tang RB. Clinical efficacy of house dust mite-specific immunotherapy in asthmatic children. Pediatr Neonatol 2010; 51 (01) 14-18
    CrossrefPubMedGoogle Scholar
  • 44 Creticos PS, Reed CE, Norman PS. et al. Ragweed immunotherapy in adult asthma. N Engl J Med 1996; 334 (08) 501-506
    CrossrefPubMedGoogle Scholar
  • 45 Roberts G, Hurley C, Turcanu V, Lack G. Grass pollen immunotherapy as an effective therapy for childhood seasonal allergic asthma. J Allergy Clin Immunol 2006; 117 (02) 263-268
    CrossrefPubMedGoogle Scholar
  • 46 Ohman Jr JL, Findlay SR, Leitermann KM. Immunotherapy in cat-induced asthma. Double-blind trial with evaluation of in vivo and in vitro responses. J Allergy Clin Immunol 1984; 74 (3 Pt 1): 230-239
    CrossrefPubMedGoogle Scholar
  • 47 Epstein TG, Murphy-Berendts K, Liss GM, Bernstein DI. Risk factors for fatal and nonfatal reactions to immunotherapy (2008-2018): post injection monitoring and severe asthma. Ann Allergy Asthma Immunol 2021; 127 (01) 64-69.e1
    CrossrefPubMedGoogle Scholar
  • 48 Soto-Quiros M, Avila L, Platts-Mills TA. et al. High titers of IgE antibody to dust mite allergen and risk for wheezing among asthmatic children infected with rhinovirus. J Allergy Clin Immunol 2012; 129 (06) 1499-1505.e5
    CrossrefPubMedGoogle Scholar
  • 49 Platts-Mills TA, Erwin EA, Heymann PW, Woodfolk JA. Pro: The evidence for a causal role of dust mites in asthma. Am J Respir Crit Care Med 2009; 180 (02) 109-113 , discussion 120–121
    CrossrefPubMedGoogle Scholar
  • 50 Sylvestre L, Jégu J, Metz-Favre C, Barnig C, Qi S, de Blay F. Component-based allergen-microarray: Der p 2 and Der f 2 dust mite sensitization is more common in patients with severe asthma. J Investig Allergol Clin Immunol 2016; 26 (02) 141-143
    CrossrefPubMedGoogle Scholar
  • 51 Miller RL, Peden DB. Environmental effects on immune responses in patients with atopy and asthma. J Allergy Clin Immunol 2014; 134 (05) 1001-1008
    CrossrefPubMedGoogle Scholar
  • 52 Posa D, Perna S, Resch Y. et al. Evolution and predictive value of IgE responses toward a comprehensive panel of house dust mite allergens during the first 2 decades of life. J Allergy Clin Immunol 2017; 139 (02) 541-549.e8
    CrossrefPubMedGoogle Scholar
  • 53 Posa D, Hofmaier S, Arasi S, Matricardi PM. Natural Evolution of IgE Responses to mite allergens and relationship to progression of allergic disease: a review. Curr Allergy Asthma Rep 2017; 17 (05) 28
    CrossrefPubMedGoogle Scholar
  • 54 Virchow JC, Backer V, Kuna P. et al. Efficacy of a house dust mite sublingual allergen immunotherapy tablet in adults with allergic asthma: a randomized clinical trial. JAMA 2016; 315 (16) 1715-1725
    Google Scholar
  • 55 de Blay F, Kuna P, Prieto L. et al. SQ HDM SLIT-tablet (ALK) in treatment of asthma—post hoc results from a randomised trial. Respir Med 2014; 108 (10) 1430-1437
    CrossrefPubMedGoogle Scholar
  • 56 Devillier P, Fadel R, de Beaumont O. House dust mite sublingual immunotherapy is safe in patients with mild-to-moderate, persistent asthma: a clinical trial. Allergy 2016; 71 (02) 249-257
    CrossrefPubMedGoogle Scholar
  • 57 Wang L, Yin J, Fadel R, Montagut A, de Beaumont O, Devillier P. House dust mite sublingual immunotherapy is safe and appears to be effective in moderate, persistent asthma. Allergy 2014; 69 (09) 1181-1188
    CrossrefPubMedGoogle Scholar
  • 58 Mosbech H, Deckelmann R, de Blay F. 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 (03) 568-575.e7
    Google Scholar
  • 59 Pham-Thi N, Scheinmann P, Fadel R, Combebias A, Andre C. Assessment of sublingual immunotherapy efficacy in children with house dust mite-induced allergic asthma optimally controlled by pharmacologic treatment and mite-avoidance measures. Pediatr Allergy Immunol 2007; 18 (01) 47-57
    CrossrefPubMedGoogle Scholar
  • 60 Marogna M, Braidi C, Bruno ME. et al. The contribution of sublingual immunotherapy to the achievement of control in birch-related mild persistent asthma: a real-life randomised trial. Allergol Immunopathol (Madr) 2013; 41 (04) 216-224
    CrossrefPubMedGoogle Scholar
  • 61 Marogna M, Spadolini I, Massolo A. et al. Long-term comparison of sublingual immunotherapy vs inhaled budesonide in patients with mild persistent asthma due to grass pollen. Ann Allergy Asthma Immunol 2009; 102 (01) 69-75
    CrossrefPubMedGoogle Scholar
  • 62 Marogna M, Colombo F, Spadolini I. et al. Randomized open comparison of montelukast and sublingual immunotherapy as add-on treatment in moderate persistent asthma due to birch pollen. J Investig Allergol Clin Immunol 2010; 20 (02) 146-152
    PubMedGoogle Scholar
  • 63 Gómez Vera J, Flores Sandoval G, Orea Solano M, López Tiro J, Jiménez Saab N. Safety and efficacy of specific sublingual immunotherapy in patients with asthma and allergy to Dermatophagoides pteronyssinus. Rev Alerg Mex 2005; 52 (06) 231-236
    PubMedGoogle Scholar
  • 64 Niu CK, Chen WY, Huang JL, Lue KH, Wang JY. Efficacy of sublingual immunotherapy with high-dose mite extracts in asthma: a multi-center, double-blind, randomized, and placebo-controlled study in Taiwan. Respir Med 2006; 100 (08) 1374-1383
    CrossrefPubMedGoogle Scholar
  • 65 Pajno GB, Morabito L, Barberio G, Parmiani S. Clinical and immunologic effects of long-term sublingual immunotherapy in asthmatic children sensitized to mites: a double-blind, placebo-controlled study. Allergy 2000; 55 (09) 842-849
    CrossrefPubMedGoogle Scholar
  • 66 Leng X, Fu YX, Ye ST, Duan SQ. A double-blind trial of oral immunotherapy for Artemisia pollen asthma with evaluation of bronchial response to the pollen allergen and serum-specific IgE antibody. Ann Allergy 1990; 64 (01) 27-31
    PubMedGoogle Scholar
  • 67 Stelmach I, Kaczmarek-Woźniak J, Majak P, Olszowiec-Chlebna M, Jerzynska J. Efficacy and safety of high-doses sublingual immunotherapy in ultra-rush scheme in children allergic to grass pollen. Clin Exp Allergy 2009; 39 (03) 401-408
    CrossrefPubMedGoogle Scholar
  • 68 La Grutta S, Arena A, D'Anneo WR. et al. Evaluation of the antiinflammatory and clinical effects of sublingual immunotherapy with carbamylated allergoid in allergic asthma with or without rhinitis. A 12-month perspective randomized, controlled, trial. Eur Ann Allergy Clin Immunol 2007; 39 (02) 40-44
    PubMedGoogle Scholar
  • 69 Calderón M, Essendrop M. Specific immunotherapy with high dose SO standardized grass allergen tablets was safe and well tolerated. J Investig Allergol Clin Immunol 2006; 16 (06) 338-344
    PubMedGoogle Scholar
  • 70 Lue KH, Lin YH, Sun HL, Lu KH, Hsieh JC, Chou MC. Clinical and immunologic effects of sublingual immunotherapy in asthmatic children sensitized to mites: a double-blind, randomized, placebo-controlled study. Pediatr Allergy Immunol 2006; 17 (06) 408-415
    CrossrefPubMedGoogle Scholar
  • 71 Ippoliti F, De Santis W, Volterrani A. et al. Immunomodulation during sublingual therapy in allergic children. Pediatr Allergy Immunol 2003; 14 (03) 216-221
    CrossrefPubMedGoogle Scholar
  • 72 Maloney J, Prenner BM, Bernstein DI. et al. Safety of house dust mite sublingual immunotherapy standardized quality tablet in children allergic to house dust mites. Ann Allergy Asthma Immunol 2016; 116 (01) 59-65
    CrossrefPubMedGoogle Scholar
  • 73 Mösges R, Graute V, Christ H, Sieber HJ, Wahn U, Niggemann B. Safety of ultra-rush titration of sublingual immunotherapy in asthmatic children with tree-pollen allergy. Pediatr Allergy Immunol 2010; 21 (08) 1135-1138
    CrossrefPubMedGoogle Scholar
  • 74 Shao J, Cui YX, Zheng YF. et al. Efficacy and safety of sublingual immunotherapy in children aged 3-13 years with allergic rhinitis. Am J Rhinol Allergy 2014; 28 (02) 131-139
    CrossrefPubMedGoogle Scholar
  • 75 Corzo JL, Carrillo T, Pedemonte C. et al. Tolerability during double-blind randomized phase I trials with the house dust mite allergy immunotherapy tablet in adults and children. J Investig Allergol Clin Immunol 2014; 24 (03) 154-161
    PubMedGoogle Scholar
  • 76 Bufe A, Eberle P, Franke-Beckmann E. et al. Safety and efficacy in children of an SQ-standardized grass allergen tablet for sublingual immunotherapy. J Allergy Clin Immunol 2009; 123 (01) 167-173.e7
    CrossrefPubMedGoogle Scholar