Advertisement

Allergen immunotherapy for allergic asthma – The future seems bright

  • Zuzana Diamant
    Correspondence
    Corresponding author. Department of Microbiology Immunology & Transplantation, KU Leuven, Catholic University of Leuven, Leuven, Belgium.
    Affiliations
    Dept of Microbiology Immunology & Transplantation, KU Leuven, Catholic University of Leuven, Belgium

    Dept of Respiratory Medicine & Allergology, Institute for Clinical Science, Skane University Hospital, Lund University, Lund, Sweden

    Department of Respiratory Medicine, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic

    Dept Clin Pharm & Pharmacol, Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands
    Search for articles by this author
  • Maurits van Maaren
    Affiliations
    Department of Internal Medicine, Allergy and Clinical Immunology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
    Search for articles by this author
  • Antonella Muraro
    Affiliations
    Food Allergy Referral Centre, Padua University Hospital, Padua, Italy
    Search for articles by this author
  • Milos Jesenak
    Affiliations
    Department of Pediatrics, Department of Pulmonology and Phthisiology, Department of Allergology and Clinical Immunology, Jessenius Faculty of Medicine, Comenius University in Bratislava, University Teaching Hospital in Martin, Martin, Slovakia
    Search for articles by this author
  • Ilja Striz
    Correspondence
    Corresponding author.
    Affiliations
    Department of Clinical and Transplant Immunology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
    Search for articles by this author
Published:January 23, 2023DOI:https://doi.org/10.1016/j.rmed.2023.107125

      Highlights

      • Allergen immunotherapy (AIT) is so far the only causal treatment of allergic diseases including asthma which has also been proven to be cost-effective.
      • The key benefits of AIT consist of disease modifying effects as well as protective (preventive) properties against the allergic march in allergic diseases including asthma.
      • Recently, real-life data underscored long-term effectiveness (disease remission/modification) of HDM-AIT across 9–10 years of follow-up in a large cohort of >14,000 patients with HDM-driven asthma.
      • Promising clinical benefits have previously also been achieved with pollen allergen extracts (both SCIT and SLIT), but more real-life data over longer periods of time including larger numbers of patients (including asthma) are of utmost interest to confirm the persistence of clinical effectiveness of pollen AIT.
      • Predictive biomarkers identifying responders to AIT represent an unmet need while research is ongoing.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Respiratory Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Durham S.T.
        • Shamji M.H.
        Allergen immunotherapy: past, present and future.
        Nat. Rev. Immunol. 2022 Oct 17; : 1-12https://doi.org/10.1038/s41577-022-00786-1
        • Noon L.
        Prophylactic inoculation against hay fever.
        Lancet. 1911; 177: 1572-1573https://doi.org/10.1016/S0140-6736(00)78276-6
        • Fritzsching B.
        • Contoli M.
        • Porsbjerg C.
        • Buchs S.
        • Larsen J.R.
        • Elliott L.
        • Rodriguez M.R.
        • Freemantle N.
        Long-term real-world effectiveness of allergy immunotherapy in patients with allergic rhinitis and asthma: results from the REACT study, a retrospective cohort study.
        Lancet Reg. Health. Eur. 2021; 13100275https://doi.org/10.1016/j.lanepe.2021.100275
        • Diamant Z.
        • Boot J.D.
        • Mantzouranis E.
        • Flohr R.
        • Sterk P.J.
        • Gerth van Wijk R.
        Biomarkers in asthma and allergic rhinitis.
        Pulm. Pharmacol. Ther. 2010; 23: 468-481https://doi.org/10.1016/j.pupt.2010.06.006
        • Diamant Z.
        • Gauvreau G.M.
        • Cockcroft D.W.
        • Boulet L.P.
        • de Jongh F.H.
        • Sterk P.J.
        • Dahlén B.
        • O'Byrne P.M.
        Inhaled allergen bronchoprovocation tests.
        J. Allergy Clin. Immunol. 2013; 132: 1045-1055.e6https://doi.org/10.1016/j.jaci.2013.08.023
        • Gauvreau G.M.
        • Davis B.E.
        • Scadding G.
        • Boulet L.P.
        • Bjermer L.
        • Chaker A.
        • Cockcroft D.W.
        • Dahlén B.
        • Fokkens W.
        • Hellings P.
        • Lazarinis N.
        • O'Byrne P.M.
        • Tufvesson E.
        • Quirce S.
        • Van Maaren M.
        • de Jongh F.H.
        • Diamant Z.
        Allergen Provocation Tests in Respiratory Research: Building on 50 Years of Experience. 60. 2022 Aug 252102782https://doi.org/10.1183/13993003.02782-2021 (2)
        • Shamji M.H.
        • Sharif H.
        • Layhadi J.A.
        • 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
        • Striz I.
        • Brabcova E.
        • Kolesar L.
        • Sekerkova A.
        Cytokine networking of innate immunity cells: a potential target of therapy.
        Clin. Sci. 2014; 126: 593-612
        • Chan R.
        • Stewart K.
        • Misirovs R.
        • Lipworth B.J.
        Targeting downstream type 2 cytokines or upstream epithelial alarmins for severe asthma.
        J. Allergy Clin. Immunol. Pract. 2022 Jun; 10: 1497-1505https://doi.org/10.1016/j.jaip.2022.01.040
        • Colas A. Magnan, S. Brouard
        Immunoglobulin E response in health and disease beyond allergic disorders.
        Allergy. 2022; 77: 1700-1718
        • Diamant Z.
        • Sampson A.P.
        Anti-inflammatory mechanisms of leukotriene modulators.
        Editorial. Clin. Exp. Allergy. 1999 Nov; 29: 1449-1453https://doi.org/10.1046/j.1365-2222.1999.00711.x
        • Diamant Z.
        • Hiltermann J.T.
        • van Rensen E.L.
        • Callenbach P.M.
        • Veselic-Charvat M.
        • van der Veen H.
        • Sont J.K.
        • Sterk P.J.
        The effect of inhaled leukotriene D4 and methacholine on sputum cell differentials in asthma.
        Am. J. Respir. Crit. Care Med. 1997; 155: 1247-1253https://doi.org/10.1164/ajrccm.155.4.9105062
        • Cockcroft D.W.
        • Davies B.E.
        Mechanisms of airway hyperresponsiveness.
        J. Allergy Clin. Immunol. 2006; 118: 551-559
        • Kirmaz C.
        • Ozenturk Kirgiz O.
        • Bayrak P.
        • Yilmaz O.
        • Vatansever S.
        • Ozbilgin K.
        • Onur E.
        • Celik O.
        • Sogut A.
        • Ay G.
        • Yuksel H.
        Effects of allergen-specific immunotherapy on functions of helper and regulatory T cells in patients with seasonal allergic rhinitis.
        Eur. Cytokine Netw. 2011; 22: 15-23
        • Keles S.
        • Karakoc-Aydiner E.
        • Ozen A.
        • Izgi A.G.
        • Tevetoglu A.
        • Akkoc T.
        • Bahceciler N.N.
        • Barlan I.
        A novel approach in allergen-specific immunotherapy: combination of sublingual and subcutaneous routes.
        J. Allergy Clin. Immunol. 2011 Oct; 128: 808-815.e7https://doi.org/10.1016/j.jaci.2011.04.033
        • Welsh R.A.
        • Song N.
        • Sadegh-Nasseri S.
        How does B cell antigen presentation affect memory CD4 T cell differentiation and longevity?.
        Front. Immunol. 2021; 10677036https://doi.org/10.3389/fimmu.2021.677036
        • Cox L.S.
        • Murphey A.
        • Hankin C.
        The cost-effectiveness of allergen immunotherapy compared with pharmacotherapy for treatment of allergic rhinitis and asthma, Immuno.l allergy clin.
        . North Am. 2020 Feb; 40: 69-85https://doi.org/10.1016/j.iac.2019.09.003
        • Viswanathan R.K.
        • Busse W.W.
        Allergen immunotherapy in allergic respiratory diseases: from mechanisms to meta-analyses.
        Chest. 2012 May; 141: 1303-1314https://doi.org/10.1378/chest.11-2800
        • Cox L.
        • Nelson H.
        • Lockey R.
        • Calabria C.
        • Chacko T.
        • Finegold I.
        • Nelson M.
        • Weber R.
        • Bernstein D.I.
        • Blessing-Moore J.
        • Khan D.A.
        • Lang D.M.
        • Nicklas R.A.
        • Oppenheimer J.
        • Portnoy J.M.
        • Randolph C.
        • Schullet D.E.
        • Spector S.L.
        • Tilles S.
        • Wallace D.
        Allergen immunotherapy: a practice parameter third update.
        J. Allergy Clin. Immunol. 2011; 127: S1-S5
        • Greenhawt M.
        • Oppenheimer J.
        • Nelson M.
        • Nelson H.
        • Lockey R.
        • Lieberman P.
        • Nowak-Wegrzyn A.
        • Peters A.
        • Collins C.
        • Bernstein D.I.
        • Blessing-Moore L.
        • Khan D.
        • Nicklas R.A.
        • Portnoy J.M.
        • Randolph C.R.
        • Schuller D.E.
        • Spector S.L.
        • Tilles S.A.
        • Wallace D.
        Sublingual immunotherapy: a focused allergen immunotherapy practice parameter update.
        Ann. Allergy Asthma Immunol. 2017; 118: 276-282.e2
        • Nelson H.S.
        2020 updated asthma guidelines: allergen immunotherapy.
        J. Allergy Clin. Immunol. 2020; 146: 1286-1287
        • Zissler U.M.
        • Schmidt-Weber C.B.
        Predicting success of allergen-specific immunotherapy.
        Front. Immunol. 2020 Aug 25; 11: 1826https://doi.org/10.3389/fimmu.2020.01826
        • Penagos M.
        • Durham S.R.
        Allergen immunotherapy for long-term tolerance and prevention.
        J. Allergy Clin. Immunol. 2022; 149: 802-811
        • Shamji M.H.
        • Layhadi J.A.
        • Sharif H.
        • Penagos M.
        • Durham S.R.
        Immunological responses and biomarkers for allergen-specific immunotherapy against inhaled allergens.
        J. Allergy Clin. Immunol. Pract. 2021 May; 9: 1769-1778https://doi.org/10.1016/j.jaip.2021.03.029
        • Tan T.J.
        • Delgado-Dolset M.I.
        • Escribese M.M.
        • Barber D.
        • Layhadi J.A.
        • Shamji M.H.
        Biomarkers of AIT: models of prediction of efficacy.
        Allergol Select. 2022; 6: 267-275https://doi.org/10.5414/ALX02333E
        • Muraro A.
        • Roberts G.
        • Halken S.
        • Agache I.
        • Angier E.
        • Fernandez-Rivas M.
        • Gerth van Wijk R.
        • Jutel M.
        • Lau S.
        • Pajno G.
        • Pfaar O.
        • Ryan D.
        • Sturm G.J.
        • van Ree R.
        • Varga E.M.
        • Bachert C.
        • Calderon M.
        • Canonica G.W.
        • Durham S.R.
        • Malling H.J.
        • Wahn U.
        • Sheikh A.
        EAACI guidelines on allergen immunotherapy: executive statement.
        Allergy. 2018; 73: 739-743
        • Virchow J.C.
        • Backer V.
        • Kuna P.
        • Prieto L.
        • Nolte H.
        • Villesen H.H.
        • Ljørring C.
        • Riis B.
        • de Blay F.
        Efficacy of a house dust mite sublingual allergen immunotherapy tablet in adults with allergic asthma: a randomized clinical trial.
        JAMA. 2016; 315: 1715-1725
        • GINA Report
        Global strategy for asthma management and prevention.
        • Kiel M.A.
        • Röder E.
        • Gerth van Wijk R.
        • Al M.J.
        • Hop W.C.
        • Rutten-van Mölken M.P.
        Real-life compliance and persistence among users of subcutaneous and sublingual allergen immunotherapy.
        J. Allergy Clin. Immunol. 2013; 132 (e2): 353-360https://doi.org/10.1016/j.jaci.2013.03.013
        • Hellings P.W.
        • Pugin B.
        • Mariën G.
        • Bachert C.
        • Breynaert C.
        • Bullens D.M.
        • Ceuppens J.L.
        • Clement G.
        • Cox T.
        • Ebo D.
        • Gevaert P.
        • Halewyck S.
        • Hox V.
        • Ladha K.
        • Jacobs R.
        • Rombaux P.
        • Schrijvers R.
        • Speleman K.
        • Van der Brempt X.
        • Van Gerven L.
        • Vanderveken O.
        • Verhaeghe B.
        • Vierstraete K.
        • Vlaminck S.
        • Watelet J.B.
        • Bousquet J.
        • Seys S.F.
        Stepwise approach towards adoption of allergen immunotherapy for allergic rhinitis and asthma patients in daily practice in Belgium: a BelSACI-Abeforcal-EUFOREA statement.
        Clin. Transl. Allergy. 2019 Feb 4; 9: 1https://doi.org/10.1186/s13601-019-0243-1
        • Woehlk C.
        • Von Bülow A.
        • Ghanizada M.
        • Søndergaard M.B.
        • Hansen S.
        • Porsbjerg C.
        Allergen immunotherapy effectively reduces the risk of exacerbations and lower respiratory tract infections in both seasonal and perennial allergic asthma: a nationwide epidemiological study.
        Eur. Respir. J. 2022 Nov 17; 602200446https://doi.org/10.1183/13993003.00446-2022
        • 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 Feb; 117: 263-268https://doi.org/10.1016/j.jaci.2005.09.054
        • Penagos M.
        • Passalacqua G.
        • Compalati E.
        • Baena-Cagnani C.E.
        • Orozco S.
        • Pedroza A.
        • Canonica G.W.
        Metaanalysis of the efficacy of sublingual immunotherapy in the treatment of allergic asthma in pediatric patients, 3 to 18 years of age.
        Chest. 2008 Mar; 133: 599-609https://doi.org/10.1378/chest.06-1425
        • Abramson M.J.
        • Puy R.M.
        • Weiner M.J.
        Injection allergen immunotherapy for asthma.
        Cochrane Database Syst. Rev. 2010 Aug 4; : CD001186https://doi.org/10.1002/14651858.CD001186.pub2
        • Dhami S.
        • Kakourou A.
        • Asamoah F.
        • Agache I.
        • Lau S.
        • Jutel M.
        • Muraro A.
        • Roberts G.
        • Akdis C.A.
        • Bonini M.
        • Cavkaytar O.
        • Flood B.
        • Gajdanowicz P.
        • Izuhara K.
        • Kalayci Ö.
        • Mosges R.
        • Palomares O.
        • Pfaar O.
        • Smolinska S.
        • Sokolowska M.
        • Asaria M.
        • Netuveli G.
        • Zaman H.
        • Akhlaq A.
        • Sheikh A.
        Allergen immunotherapy for allergic asthma: a systematic review and meta-analysis.
        Allergy. 2017 Dec; 72 (Allergy. 2017 Dec;72(12):1825-1848. doi: 10.1111/all.13208): 1825-1848https://doi.org/10.1111/all.13208
        • Möller C.
        • Dreborg S.
        • Ferdousi H.A.
        • Halken S.
        • Høst A.
        • Jacobsen L.
        • Koivikko A.
        • Koller D.Y.
        • Niggemann B.
        • Norberg L.A.
        • Urbanek R.
        • Valovirta E.
        • Wahn U.
        Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study).
        J. Allergy Clin. Immunol. 2002 Feb; 109: 251-256https://doi.org/10.1067/mai.2002.121317
        • Pajno G.B.
        • Vita D.
        • Parmiani S.
        • Caminiti L.
        • La Grutta S.
        • Barberio G.
        Impact of sublingual immunotherapy on seasonal asthma and skin reactivity in children allergic to Parietaria pollen treated with inhaled fluticasone propionate.
        Clin. Exp. Allergy. 2003 Dec; 33: 1641-1647https://doi.org/10.1111/j.1365-2222.2003.01809.x
        • Polosa R.
        • Li Gotti F.
        • Mangano G.
        • Paolino G.
        • Mastruzzo C.
        • Vancheri C.
        • Lisitano N.
        • Crimi N.
        Effect of immunotherapy on asthma progression, BHR and sputum eosinophils in allergic rhinitis.
        Allergy. 2004 Nov; 59: 1224-1228https://doi.org/10.1111/j.1398-9995.2004.00537.x
        • Jacobsen L.
        • Niggemann B.
        • Dreborg S.
        • Ferdousi H.A.
        • Halken S.
        • Høst A.
        • Koivikko A.
        • Norberg L.A.
        • Valovirta E.
        • Wahn U.
        • Möller C.
        The PAT investigator group). Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study.
        Allergy. 2007 Aug; 62: 943-948https://doi.org/10.1111/j.1398-9995.2007.01451.x
        • Valovirta E.
        • Petersen T.H.
        • Piotrowska T.
        • Laursen M.K.
        • Andersen J.S.
        • Sorensen H.F.
        • Klink R.
        GAP investigators, Results from the 5-year SQ grass sublignual immunotherapy tablet asthma prevention (GAP) trial in children with grass pollen allergy.
        J. Allergy Clin. Immunol. 2018; 141: 529-538.e13
        • Wahn U.
        • Bachert C.
        • Heinrich J.
        • Richter H.
        • Zielen S.
        Real-world benefits of allergen immunotherapy for birch pollen-associated allergic rhinitis and asthma.
        Allergy. 2019 Mar; 74: 594-604https://doi.org/10.1111/all.13598
        • Arshad S.H.
        Does allergen immunotherapy for allergic rhinitis prevent asthma?.
        Ann. Allergy Asthma Immunol. 2022 Sep; 129: 286-291https://doi.org/10.1016/j.anai.2022.04.028
        • Gradman J.
        • Halken S.
        Preventive effect of allergen immunotherapy on asthma and new sensitizations.
        J. Allergy Clin. Immunol. Pract. 2021 May; 9: 1813-1817https://doi.org/10.1016/j.jaip.2021.03.010
        • Schmitt J.
        • Schwarz K.
        • Stadler E.
        • Wüstenberg E.G.
        Allergy immunotherapy for allergic rhinitis effectively prevents asthma: results from a large retrospective cohort study.
        J. Allergy Clin. Immunol. 2015 Dec; 136: 1511-1516https://doi.org/10.1016/j.jaci.2015.07.038
        • Cardona V.
        • Luengo O.
        • Labrador-Horrillo M.
        Immunotherapy in allergic rhinitis and lower airway outcomes.
        Allergy. 2017 Jan; 72: 35-42https://doi.org/10.1111/all.12989
        • Pitsios C.
        • Demoly P.
        • Bilo M.B.
        • Gerth van Wijk R.
        • Pfaar O.
        • Sturm G.J.
        • Rodriguez del Rio P.
        • Tsoumani M.
        • Gawlik R.
        • Paraskevopoulos G.
        • Rueff F.
        • Valovirta E.
        • Papadopoulos N.G.
        • Calderon M.A.
        Clinical contraindications to allergen immunotherapy : an EAACI position paper.
        Allergy. 2015; 70: 897-909
        • Hankin C.S.
        • Lockey R.F.
        Patient characteristics associated with allergen immunotherapy initiation and adherence.
        J. Allergy Clin. Immunol. 2011; 127 (e1-3): 46-48
        • Pajno G.B.
        • Vita D.
        • Caminiti L.
        • Arrigo T.
        • Lombardo F.
        • Incorvaia C.
        • Barberio G.
        Children's compliance with allergen immunotherapy according to administration routes.
        J. Allergy Clin. Immunol. 2005; 116: 1380-1381
        • Incorvaia C.
        • Rapetti A.
        • Scurati S.
        • Puccinelli P.
        • Capecce M.
        • Frati F.
        Importance of patients' education in favouring compliance with sublingual immunotherapy.
        Allergy. 2010; 65: 1341-1342
        • Cavi E.
        • Peveri S.
        • Senna G.
        • Passalacqua G.
        Causes of SLIT discontinuation and strategies to improve the adherence: a pragmatic approach.
        Allergy. 2013; 68: 1193-1195
        • Vita D.
        • Caminiti L.
        • Ruggeri P.
        • Pajno G.B.
        Sublingual immunotherapy: adherence based on timing and monitoring control visits.
        Allergy. 2010; 65: 668-669
        • Verhoeven E.
        • Rouadi P.
        • Jaoude E.A.
        • Abouyakouk M.
        • Ansotegui I.
        • Al-Ahmad M.
        • Al-Nesf M.A.
        • Azar C.
        • Bahna S.
        • Cuervo-Pardo L.
        • Diamant Z.
        • Douagui H.
        • Gomez R.M.
        • Gonzalez Diaz S.
        • Han J.K.
        • Idriss S.
        • Irani C.
        • karam M.
        • Klimek L.
        • Nsouli T.
        • Scadding G.
        • Senior B.
        • Smith P.
        • Yanez A.
        • Zaitoun F.
        • Hellings P.W.
        Digital tolls in allergy and respiratory care.
        World Allergy Organ. J. 2022; 15100661
        • Valenta R.
        • Karaulov A.
        • Niederberger V.
        • Zhernov Y.
        • Elisyutina O.
        • Campana R.:
        • Focke-Tejkl M.
        • Curin M.
        • Namazova-Baranova L.
        • Wang L.Y.
        • Pawankar R.
        • Khaitov M.
        Allergen extracts for in vivo diagnosis and treatment of allergy: is there a future?.
        J. Allergy Clin. Immunol. Pract. 2018; 6: 1845-1855.e2
        • Jensen-Jarolim E.
        • Roth-Walter F.
        • Jordakieva G.
        • Pali-Scholl I.
        Allergens and adjuvants in allergen immunotherapy for immune activation, tolerance, and resilience.
        J. Allergy Clin. Immunol. Pract. 2021; 9: 1780-1789
        • Creticos P.S.
        • Schroeder J.T.
        • Hamilton R.G.
        • Balcer-Whaley S.L.
        • Khattignavong A.P.
        • Lidnblad R.
        • Li H.
        • Coffman R.
        • Seyfert V.
        • Eiden J.J.
        • Broide D.
        Immune Tolerance Network Group, Immunotherapy with a ragweed-toll-like receptor 9 agonist vaccine for allergic rhinitis.
        N. Engl. J. Med. 2006; 355: 1445-1455
        • James L.K.
        The cloning and expression of human monoclonal antibodies: implications for allergen immunotherapy.
        Curr. Allergy Asthma Rep. 2016; 16: 15
        • Corren J.
        • Castro M.
        • O'Riordan T.
        • Hanania N.A.
        • Pavord I.D.
        • Quirce S.
        • Chipps B.E.
        • Wenzel S.E.
        • Thangavelu K.
        • Rice M.S.
        • Harel S.
        • Jagerschmidt A.
        • Khan A.H.
        • Kamat S.
        • Maroni J.
        • Rowe P.
        • Lu Y.
        • Amin N.
        • Pirozzi G.
        • Ruddy M.
        • Graham N.M.H.
        • Teper A.
        Dupilumab efficacy in patients with uncontrolled, moderate-to-severe allergic asthma.
        J. Allergy Clin. Immunol. Pract. 2020; 8: 516-626
        • Pohlit H.
        • Bellinghausen I.
        • Frey H.
        • Saloga J.
        Recent advances in the use of nanoparticles for allergen-specific immunotherapy.
        Allergy. 2017; 72: 1461-1474
        • Senti G.
        • Freiburghaus A.U.
        • Larenas-Linnemann D.
        • Hoffmann H.J.
        • Patterson A.M.
        • Klimek L.
        • Di Bona D.
        • Pfaar O.
        • Ahlbeck L.
        • Akdis M.
        • Weinfeld D.
        • Contreras-Verduzco F.A.
        • Pedroza-Melendez A.
        • Skaarup S.H.
        • Lee S.M.
        • Cardell L.O.
        • Schmid J.M.
        • Westin U.
        • Dollner R.
        • Kundig T.M.
        Intralymphatic immunotherapy: update and unmet needs.
        Int. Arch. Allergy Immunol. 2019; 178: 141-149
        • Senti G.
        • Graf N.
        • Haug S.
        • Ruedi N.
        • von Moos S.
        • Sonderegger T.
        • Johansen P.
        • Kundig T.M.
        Epicutaneous allergen administration as a novel method of allergen-specific immunotherapy.
        J. Allergy Clin. Immunol. 2009; 124: 997-1002
        • Esposito S.
        • Isidori C.
        • Pacitto A.
        • Salvatoru C.
        • Sensi L.
        • Frati F.
        • Di Cara G.
        • Marcucci F.
        Epicutaneous immunotherapy in rhino-conjunctivitis and food allergies: a review of the literature.
        J. Transl. Med. 2018; 16: 329
        • Pajno G.B.
        • Fernandez-Rivas M.
        • Arasi S.
        • Roberts G.
        • Akdis C.A.
        • Alvaro-Lozano M.
        • Beyer K.
        • Bindslev-Jensen C.
        • Burks W.
        • Ebisawa M.
        • Eigenmann P.
        • Knol E.
        • Nadeau K.C.
        • Poulsen L.K.
        • van Ree R.
        • Santos A.F.
        • du Toit G.
        • Dhami S.
        • Nurmatov U.
        • Boloh Y.
        • Makela M.
        • O'Mahony L.
        • Papadopoulos N.
        • Sackesen C.
        • Agache I.
        • Angier E.
        • Halken S.
        • Jutel M.
        • Lau S.
        • Pfaar O.
        • Ryan D.
        • Sturm G.
        • Varga E.M.
        • Gerth van Wijk R.
        • Sheikh A.
        • Muraro A.
        EAACI Allergen Immunotherapy Guidelines Group, EAACI guidelines on allergen immunotherapy: IgE-mediated food allergy.
        Allergy. 2018; 73: 799-815
        • Kasemsuk N.
        • Ngaotepprutaram P.
        • Kanjanawasse D.
        • Suwanwech T.
        • Durham S.R.
        • Canonica G.W.
        • Tantilipikorn P P.
        Local nasal immunotherapy for allergic rhinitis: a systematic review and meta-analysis.
        Int. Forum Allergy Rhinol. 2022; https://doi.org/10.1002/alr.23011
        • Walker S.M.
        • Durham S.R.
        • Till S.R.
        • Roberts G.
        • Corrigan C.J.
        • Leech S.C.
        • Krishna M.T.
        • Rajakulasingham R.K.
        • Williams A.
        • Chantrell J.
        • Dixon L.
        • Frew A.J.
        • Nasser S.M.
        British society for allergy and clinical immunology, immunotherapy for allergic rhinitis.
        Clin. Exp. Allergy. 2011; 41: 1177-1200
        • Mosbech H.
        • Deckelmann R.
        • de Blay F.
        • Pastorello E.A.
        • Trebas-Pietras E.
        • Prieto Andres L.
        • Malcus I.
        • Ljorring C.
        • Canonica G.W.
        Standardized quality (SQ) house dus tmite 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: 568-575.e7
        • Dierick B.J.H.
        • van der Molen T.
        • Flokstra-de Blok B.M.J.
        • Muraro A.
        • Postma M.J.
        • Kocks J.W.H.
        • van Boven J.F.M.
        Burden and socioeconomics of asthma, allergic rhinitis, atopic dermatitis and food allergy.
        Expert Rev. Pharmacoecon. Outcomes Res. 2020; 20: 437-453
        • Akdis C.A.
        • Akdis M.
        Mechanisms of allergen-specific immunotherapy.
        J. Allergy Clin. Immunol. 2011; 127: 18-27
        • Drazdauskaite G.
        • Layhadi J.A.
        • Shamji M.H.
        Mechanisms of allergen immunotherapy in allergic rhinitis.
        Curr. Allergy Asthma Rep. 2021; 21: 2
        • Hesse L.
        • Oude Olberink J.N.G.
        • van Oosterhout A.J.M.
        • Nawijn M.C.
        Allergen immunotherapy for allergic airway diseases: use lessons from the past to design a brighter future.
        Pharmacol. Ther. 2022; 237108115
        • Kucuksezer U.C.
        • Ozdemir C.
        • Cevhertas L.
        • Ogulur I.
        • Akdis M.
        • Akdis C.A.
        Mechanisms of allergen-specific immunotherapy and allergen tolerance.
        Allergol. Int. 2020; 69: 549-560