Összefoglaló. Az allergiás betegségekben szenvedő emberek száma világszerte, köztük Magyarországon is növekszik. Az egészségügyi ellátórendszerek azon dolgoznak, hogy minél hatékonyabban tudják felhasználni a rendelkezésre álló forrásokat. Az Allergic Rhinitis and its Impact on Asthma (ARIA) szervezet célja az allergiás náthában szenvedő betegek ellátásának javítása, szakmai ajánlások készítése, aktualizálása. Ennek egyik módja integrált betegellátási utak kidolgozása. Célunk ezek hazai elérhetővé tétele, az ajánlások széles körű elterjesztése az Európai Unió (EU) többi tagállamához hasonlóan Magyarországon is. Az ARIA más nemzetközi innovatív szervezetek bevonásával olyan integrált betegellátási utakat fejlesztett ki, amelyek allergiás nátha, esetleg társbetegsége, az asztma esetén támogatják a kezelést. Ezeket újgenerációs irányelvek kidolgozása útján alkották, amelyekhez felhasználták a mobiltechnológiából és pollenkamra-vizsgálatokból származó valós evidenciákat is. A gyógyszeres terápia optimalizálásához a vizuális analóg skálán alapuló, úgynevezett Mobil Légúti Figyelő Hálózat algoritmusát digitalizálták, és valós evidenciák felhasználásával tovább finomították. Allergén immunterápiára az ARIA a világon elsőként dolgozott ki integrált betegellátási utakat 2019-ben. A kezelési irányelvekhez való adherenciaszint alacsony, a betegek a tüneteik erőssége alapján módosítják a kezelést. A flutikazon-propionát–azelasztin kombináció hatása erősebb az intranasalis kortikoszteroidokénál, míg az utóbbi hatásosabb az oralis H1-antihisztaminoknál. A mobiltelefonokban tárolt elektronikus napló vagy más ’mobile health’ (mHealth) eszközök használata segíti a betegek kiválasztását allergén immunterápiára. Az ARIA által javasolt algoritmus megfelelőnek mutatkozott az allergiás rhinitis kezelésére, ezért ezek az irányelvek bekerülnek integrált betegellátási utakba, és részét fogják képezni az EU Egészségügyi és Élelmiszer-biztonsági Főigazgatósága digitalizált, személyközpontú gondozási anyagainak. Az allergén immunterápia hatékony az inhalatív allergének által okozott allergiás betegségekben, alkalmazását azonban korlátozni kell gondosan válogatott betegekre. Orv Hetil. 2020; 161(49): 2059–2071.
Summary. The number of allergic patients is increasing all over the world, also in Hungary. Delivering effective and cost-effective health care is essential for all health care systems. ARIA (Allergic Rhinitis and its Impact on Asthma) aims to improve the care of patients who suffer from allergic rhinitis by setting up guidelines and updating them. Development of ICPs (integrated care pathways) can play an essential role in attaining this goal. Our aim is to make ICP-s developed by ARIA available also in Hungary, as is already the case in other countries of the European Union (EU). Together with other international initiatives, ARIA has worked out digitally-enabled ICPs to support care in allergic rhinitis and comorbid asthma. ICPs are based on new-generation guidelines using RWE (real-world evidence) from chamber studies and mobile technology. The MASK (Mobile Airways Sentinel NetworK) algorithm – based on visual analogue scale – was digitalized to support pharmacotherapy, and was refined by using RWE. ARIA was the first to develop ICPs for allergen immunotherapy (AIT) in 2019. Based on MASK data, patients did not follow guidelines and their adherence to treatment was poor. Patients would modify their treatments, depending on the disease control. The effect of fluticasone propionate–azelastine combination is superior to intranasal corticosteroids which are superior to oral H1-antihistamines. Electronic diaries obtained from cell phones and other ’mobile health’ (mHealth) devices help select patients for AIT. The ARIA algorithm for AR was found appropriate and no change is necessary. These guidelines will inform ICPs and will be included in the DG Santé digitally-enabled, person-centred care system. AIT is an effective treatment for allergic diseases caused by inhaled allergens. Its use should, however, be restricted to carefully selected patients. Orv Hetil. 2020; 161(49): 2059–2071.
Bousquet J, Hellings PW, Agache I, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018): Change management in allergic rhinitis and asthma multimorbidity using mobile technology. J Allergy Clin Immunol. 2019; 143: 864–879.
Bousquet JJ, Schünemann HJ, Togias A, et al. Next-generation ARIA care pathways for rhinitis and asthma: a model for multimorbid chronic diseases. Clin Transl Allergy 2019; 9: 44.
Bousquet J, Arnavielhe S, Bedbrook A, et al. MASK 2017: ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma multimorbidity using real-world-evidence. Clin Transl Allergy 2018; 8: 45.
Bousquet J, Bedbrook A, Czarlewski W, et al. Guidance to 2018 good practice: ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma. Clin Transl Allergy 2019; 9: 16.
Bousquet J, Anto JM, Annesi-Maesano I, et al. POLLAR: Impact of air POLLution on Asthma and Rhinitis; a European Institute of Innovation and Technology Health (EIT Health) project. Clin Transl Allergy 2018; 8: 36.
Bousquet J, Addis A, Adcock I, et al. Integrated care pathways for airway diseases (AIRWAYS-ICPs). Eur Respir J. 2014; 44: 304–323.
Bosnic-Anticevich S, Costa E, Menditto E, et al. ARIA pharmacy 2018 “Allergic rhinitis care pathways for community pharmacy”: AIRWAYS ICPs initiative (European Innovation Partnership on Active and Healthy Ageing, DG CONNECT and DG Santé) POLLAR (Impact of Air POLLution on Asthma and Rhinitis) GARD Demonstration project. Allergy 2019; 74: 1219–1236.
Bousquet J, Pfaar O, Togias A, et al. 2019 ARIA Care pathways for allergen immunotherapy. Allergy 2019; 74: 2087–2102.
Bousquet J, Schünemann HJ, Togias A, 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 real-world evidence. J Allergy Clin Immunol. 2020; 145: 70–80.e3.
Bousquet J, Pham-Thi N, Bedbrook A, et al. Next-generation care pathways for allergic rhinitis and asthma multimorbidity: a model for multimorbid non-communicable diseases – Meeting Report (Part 1). J Thorac Dis. 2019; 11: 3633–3642.
Márk Zs, Bikov A, Gálffy G. Prevalence of respiratory allergic diseases caused by ragweed in Hungary. [A parlagfű okozta légzőszervi allergiás megbetegedések előfordulása Magyarországon.] Orv Hetil. 2016; 157: 1989–1993. [Hungarian]
Sultész M, Balogh I, Katona G, et al. Trends in prevalence and risk factors of allergic rhinitis symptoms in primary schoolchildren 6 years apart in Budapest. Allergol Immunopathol (Madr). 2017; 45: 487–495.
Sultész M, Balogh I, Katona G, et al. Changes in Prevalence and Risk Factors of Allergic Rhinitis Symptoms in Primary Schoolchildren in Budapest between 2007 and 2013. [Az allergiás nátha prevalenciájának és rizikótényezőinek változása 2007 és 2013 között budapesti általános iskolások körében.] Fül-orr-gégegyógyászat 2019; 65: 91–97. [Hungarian]
Hidvégi P. (ed.) Healthy way of life. [Az egészséges életmód.] Eszterházy Károly Főiskola, Líceum Kiadó, Eger, 2015. [Hungarian]
Kadocsa E, Hirschberg A, Vóna I, et al. Professional guideline of the Hungarian Ministry of Human Resources for the treatment of allergic rhinitis. [Az Emberi Erőforrások Minisztériuma szakmai irányelve az allergiás rhinitis ellátásáról.] Eü Közlöny 2015; 65(19): 2616–2626. [Hungarian]
Meltzer EO, Wallace D, Dykewicz M, et al. Minimal clinically important difference (MCID) in allergic rhinitis: Agency for Healthcare Research and Quality or anchor-based thresholds? J Allergy Clin Immunol Pract. 2016; 4: 682–688.e6.
Brożek JL, Bousquet J, Baena-Cagnani CE, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol. 2010; 126: 466–476.
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: 950–958.
Dykewicz MS, Wallace DV, Baroody F, et al. Treatment of seasonal allergic rhinitis: an evidence-based focused 2017 guideline update. Ann Allergy Asthma Immunol. 2017; 119: 489–511.e41.
Bousquet J, Devillier P, Anto JM, et al. Daily allergic multimorbidity in rhinitis using mobile technology: a novel concept of the MASK study. Allergy 2018; 73: 1622–1631.
Bousquet J, Devillier P, Arnavielhe S, et al. Treatment of allergic rhinitis using mobile technology with real-world data: the MASK observational pilot study. Allergy 2018; 73: 1763–1774.
Bousquet J, Schünemann HJ, Hellings PW, et al. MACVIA clinical decision algorithm in adolescents and adults with allergic rhinitis. J Allergy Clin Immunol. 2016; 138: 367–374.e2.
Hampel FC, Ratner PH, Van Bavel J, et al. Double-blind, placebo-controlled study of azelastine and fluticasone in a single nasal spray delivery device. Ann Allergy Asthma Immunol. 2010; 105: 168–173.
Kaszuba SM, Baroody FM, deTineo M, et al. Superiority of an intranasal corticosteroid compared with an oral antihistamine in the as-needed treatment of seasonal allergic rhinitis. Arch Intern Med. 2001; 161: 2581–2587.
Glacy J, Putnam K, Godfrey S, et al. Treatments for seasonal allergic rhinitis. [Internet] Agency for Healthcare Research and Quality, Rockville, MD, 2013 Jul. Report No. 13-EHC098-EF.
Allergic rhinitis: developing drug products for treatment. Guidance for industry. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), February 2016, Clinical/Medical Revision 1. Available from: https://www.fdanews.com/ext/resources/files/2016/02/02-12-16-AllergicRhinitisGuidance.pdf?1520761249 [accessed: May 23, 2020].
Katial RK, Salapatek AM, Patel P. Establishing the onset of action of intranasal corticosteroids: is there an ideal study design? Allergy Asthma Proc. 2009; 30: 595–604.
Bousquet J, Meltzer EO, Couroux P, et al. Onset of action of the fixed combination intranasal azelastine–fluticasone propionate in an allergen exposure chamber. J Allergy Clin Immunol Pract. 2018; 6: 1726–1732.e6.
Patel P, Roland PS, Marple BF, et al. An assessment of the onset and duration of action of olopatadine nasal spray. Otolaryngol Head Neck Surg. 2007; 137: 918–924.
Horak F, Zieglmayer UP, Zieglmayer R, et al. Azelastine nasal spray and desloratadine tablets in pollen-induced seasonal allergic rhinitis: a pharmacodynamic study of onset of action and efficacy. Curr Med Res Opin. 2006; 22: 151–157.
Zieglmayer P, Zieglmayer R, Bareille P, et al. Fluticasone furoate versus placebo in symptoms of grass-pollen allergic rhinitis induced by exposure in the Vienna Challenge Chamber. Curr Med Res Opin. 2008; 24: 1833–1840.
Murdoch RD, Bareille P, Ignar D, et al. The improved efficacy of a fixed-dose combination of fluticasone furoate and levocabastine relative to the individual components in the treatment of allergic rhinitis. Clin Exp Allergy 2015; 45: 1346–1355.
Pizzulli A, Perna S, Florack J, et al. The impact of telemonitoring on adherence to nasal corticosteroid treatment in children with seasonal allergic rhinoconjunctivitis. Clin Exp Allergy 2014; 44: 1246–1254.
Price D, Scadding G, Ryan D, et al. The hidden burden of adult allergic rhinitis: UK healthcare resource utilisation survey. Clin Transl Allergy 2015; 5: 39.
Bousquet J, Murray R, Price D, et al. The allergic allergist behaves like a patient. Ann Allergy Asthma Immunol. 2018; 121: 741–742.
Bédard A, Basagaña X, Anto JM, et al. Mobile technology offers novel insights into the control and treatment of allergic rhinitis: the MASK study. J Allergy Clin Immunol. 2019; 144: 135–143.e6.
Scadding GK, Kariyawasam HH, Scadding G, et al. BSACI guideline for the diagnosis and management of allergic and non-allergic rhinitis. (Revised Edition 2017; First edition 2007.) Clin Exp Allergy 2017; 47: 856–889.
Bachert C, Bousquet J, Hellings P. Rapid onset of action and reduced nasal hyperreactivity: new targets in allergic rhinitis management. Clin Transl Allergy 2018; 8: 25.
Church MK, Maurer M, Simons FE, et al. Risk of first-generation H1-antihistamines: a GA2LEN position paper. Allergy 2010; 65: 459–466.
Halken S, Larenas-Linnemann D, Roberts G, et al. EAACI guidelines on allergen immunotherapy: prevention of allergy. Pediatr Allergy Immunol. 2017; 28: 728–745.
Bonertz A, Roberts G, Slater JE, et al. Allergen manufacturing and quality aspects for allergen immunotherapy in Europe and the United States: an analysis from the EAACI AIT Guidelines Project. Allergy 2018; 73: 816–826.
Roberts G, Pfaar O, Akdis CA, et al. EAACI guidelines on allergen immunotherapy: allergic rhinoconjunctivitis. Allergy 2018; 73: 765–798.
Ryan D, Gerth van Wijk R, Angier E, et al. Challenges in the implementation of the EAACI AIT guidelines: a situational analysis of current provision of allergen immunotherapy. Allergy 2018; 73: 827–836.
Pfaar O, Bachert C, Bufe A, 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: 282–319.
Muraro A, Roberts G, Halken S, et al. EAACI guidelines on allergen immunotherapy: executive statement. Allergy 2018; 73: 739–743.
Zielen S, Devillier P, Heinrich J, et al. Sublingual immunotherapy provides long-term relief in allergic rhinitis and reduces the risk of asthma: a retrospective, real-world database analysis. Allergy 2018; 73: 165–177.
Meadows A, Kaambwa B, Novielli N, et al. A systematic review and economic evaluation of subcutaneous and sublingual allergen immunotherapy in adults and children with seasonal allergic rhinitis. Health Technol Assess. 2013; 17: 1–322.
Bousquet J, Khaltaev N, Cruz AA, 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.
Bonertz A, Roberts GC, Hoefnagel M, et al. Challenges in the implementation of EAACI guidelines on allergen immunotherapy: a global perspective on the regulation of allergen products. Allergy 2018; 73: 64–76.
Committee for Medicinal Products for Human Use (CPMP). Guideline on allergen products: production and quality issues. EMEA/CHMP/BWP/304831/2007. London, 20 November 2008.
Wheatley L, Wood R, Nadeau K, et al. Mind the gaps: clinical trial concepts to address unanswered questions in aeroallergen immunotherapy. An NIAID/AHRQ workshop. J Allergy Clin Immunol. 2019; 143: 1711–1726.
Bousquet J, Lockey R, Malling HJ, 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: 401–405.
Didier A, Malling HJ, Worm M, et al. Optimal dose, efficacy, and safety of once-daily sublingual immunotherapy with a 5-grass pollen tablet for seasonal allergic rhinitis. J Allergy Clin Immunol. 2007; 120: 1338–1345.
Durham SR, Emminger W, Kapp A, et al. SQ-standardized sublingual grass immunotherapy: confirmation of disease modification 2 years after 3 years of treatment in a randomized trial. J Allergy Clin Immunol. 2012; 129: 717–725.e5.
Passalacqua G, Baena-Cagnani CE, Bousquet J, et al. Grading local side effects of sublingual immunotherapy for respiratory allergy: speaking the same language. J Allergy Clin Immunol. 2013; 132: 93–98.
Nam YH, Lee SK. Physician’s recommendation and explanation is important in the initiation and maintenance of allergen immunotherapy. Patient Prefer Adherence 2017; 11: 381–387.
Chivato T, Álvarez-Calderón P, Panizo C, et al. Clinical management, expectations, and satisfaction of patients with moderate to severe allergic rhinoconjunctivitis treated with SQ-standardized grass-allergen tablet under routine clinical practice conditions in Spain. Clin Mol Allergy 2017; 15: 1.
Pitsios C, Dietis N. Ways to increase adherence to allergen immunotherapy. Curr Med Res Opin. 2019; 35: 1027–1031.
Bender BG, Lockey RF. Solving the problem of nonadherence to immunotherapy. Immunol Allergy Clin North Am. 2016; 36: 205–213.
Jutel M, Papadopoulos NG, Gronlund H, et al. Recommendations for the allergy management in the primary care. Allergy 2014; 69: 708–718.
Pinnock H, Thomas M, Tsiligianni I, et al. The International Primary Care Respiratory Group (IPCRG) Research Needs Statement 2010. Prim Care Respir J. 2010; 19(Suppl 1): S1–S20.
Canonica GW, Bachert C, Hellings P, et al. Allergen immunotherapy (AIT): a prototype of precision medicine. World Allergy Organ J. 2015; 8: 31.
O’Hehir RE, Varese NP, Deckert K, et al. Epidemic thunderstorm asthma protection with five-grass pollen tablet sublingual immunotherapy: a clinical trial. Am J Respir Crit Care Med. 2018; 198: 126–128.
Global Initiative for Asthma. Global strategy for asthma management and prevention (2018 update). Available from: https://ginasthma.org/wp-content/uploads/2019/01/2018-GINA.pdf [accessed: May 23, 2020].
Summary of product characteristics. Acarizax 12 SQ-HDM oral lyophilisate. European Medicines Agency. Available from: https://mri.cts-mrp.eu/Human/Downloads/DE_H_1947_001_FinalPI.pdf [accessed: May 23, 2020].
Masuyama K, Okamoto Y, Okamiya K, et al. Efficacy and safety of SQ house dust mite sublingual immunotherapy-tablet in Japanese children. Allergy 2018; 73: 2352–2363.
Valovirta E, Petersen TH, Piotrowska T, et al. Results from the 5-year SQ grass sublingual immunotherapy tablet asthma prevention (GAP) trial in children with grass pollen allergy. J Allergy Clin Immunol. 2018; 141: 529–538.e13.
Kristiansen M, Dhami S, Netuveli G, et al. Allergen immunotherapy for the prevention of allergy: a systematic review and meta-analysis. Pediatr Allergy Immunol. 2017; 28: 18–29.
Bousquet J, Arnavielhe S, Bedbrook A, et al. The Allergic Rhinitis and its Impact on Asthma (ARIA) score of allergic rhinitis using mobile technology correlates with quality of life: the MASK study. Allergy 2018; 73: 505–510.
Pfaar O, Demoly P, Gerth van Wijk R, et al. Recommendations for the standardization of clinical outcomes used in allergen immunotherapy trials for allergic rhinoconjunctivitis: an EAACI position paper. Allergy 2014; 69: 854–867.