Current Clinical Guidelines for the Management of Patients with Allergic Rhinitis

The article presents modern approaches to the diagnosis and therapy of patients with allergic rhinitis. The document was developed by the professional association of pediatric specialists — the Union of Pediatricians of Russia — together with leading specialists of the Russian Association of Allergologists and Clinical Immunologists, the National Medical Association of Otorhinolaryngologists and is regularly updated taking into account the latest data on the effectiveness and safety of various medical interventions. The article provides information about the epidemiology of allergic rhinitis, provides characteristic diagnostic signs of the disease, allowing for establishment as timely as possible of a correct diagnosis and, taking into account a personalized approach, prescribe effective therapy.

1. Allergologiya i immunologiya: National guidelines. Khaitov RM, Il’ina NI, eds. Moscow: GEOTAR-Media; 2009. 656 p. (In Russ).

2. Astafieva NG, Baranov AA, Vishneva EA, et al. Allergic rhinitis. Russian Journal of Allergy. 2022;19(1): 100–141. (In Russ). doi: https://doi.org/10.36691/RJA1524

3. Khaitov MR, Namazova-Baranova LS, Chuchalin AG, et al. ARIA 2016: Integrated care pathways for predictive medicine across the life cycle. Russian Journal of Allergy. 2017;14(3):46–54. (In Russ).

4. Brozek JL, Bousquet J, Baena-Cagnani CE, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2016 revision. J Allergy Clin Immunol. 2017;140(4):950–958. doi: https://doi.org/10/1016/j/jaci.2017.03.050

5. 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, GA2LEN and AllerGen). Allergy. 2008;63(Suppl):8–160. doi: https://doi.org/10.1111/j.1398-9995.2007.01620.x

6. Khaitov M, Namazova-Baranova L, Ilyina N, et al. 2019 ARIA: care pathways for allergic rhinitis in Russia. Russian Journal of Allergy. 2020;17(1):7–22. (In Russ). doi: https://doi.org/10.36691/RAJ.2020.17.1.001

7. Wise SK, Lin SY, Toskala E, et al. International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis. Int Forum Allergy Rhinol. 2018;8(2):108–352. doi: https://doi.org/10.1002/alr.22073

8. Global atlas of allergy. Akdis CA, Agache I, eds. European Academy of Allergy and Clinical Immunology; 2014. 388 p.

9. Gushchin IS. Allergicheskoe vospalenie i ego farmakologicheskii kontrol’. Moscow: Farmarus Print; 1998. 250 p. (In Russ).

10. Il’ina NI, Kurbacheva OM, Pavlova KS, Il’ina EV. Skriningovoe epidemiologicheskoe issledovanie (GA2LEN) po vyyavleniyu allergicheskikh zabolevanii i zabolevanii organov dykhaniya v Rossii. Russian Journal of Allergy. 2009;(3):1. (In Russ).

11. Ilyina NI, Luss LV, Kurbacheva OM, et al. The influence of climatic factors on the spectrum and structure of allergic diseases in the case of the Moscow region. Russian Journal of Allergy. 2014;11(2): 25–31. (In Russ).]

12. Khaitov RM, Ilina NI, Kurbacheva OM, Pavlova KS. Traditions, success and innovations in modern allergology. Physiology and Pathology of Immune System. 2010;14(1):3–14. (In Russ).

13. Asher MI, Weiland SK. The International Study of Asthma and Allergies in Childhood (ISAAC). ISAAC Streering Committee. Clin Exp Allergy. 1998;28(Suppl 5):52–66; discussion 90–91. doi: https://doi.org/10.1046/j.1365-2222.1998.028s5052.x

14. Bauchau V, Durham SR. Prevalence and rate of diagnosis of allergic rhinitis in Europe. Eur Respir J. 2004;24(5):758–764. doi: https://doi.org/10.1183/09031936.04.00013904

15. Van Cauwenberge PB, Ciprandi G, Vermeiren J. Epidemiology of allergic rhinitis: Monograph. Brussel: UCB Institute of Allergy; 2001. 27 p.

16. White Book on Allergy. Pawankar R, Canonica GW, Holgate ST, et al., eds. The World Allergy Organization; 2013. 248 p.

17. Ant K, Pearce N, Anderson HR, et al. Global map of the prevalence of symptoms of rhinoconjunctivitis in children: The international Study of Asthma and Allergies in Childhood ISAAC Phase Three. Allergy. 2009;64(1):123–148. doi: https://doi.org/10.1111/j.1398-9995.2008.01884.x

18. Tomilova AYu, Namazova-Baranova LS, Torshkhoeva RM, et al. Prevalence of allergic rhinitis in Russian adolescents. European Respiratory Journal. 2011;38(S55):4286.

19. Namazova-Baranova LS, Alekseeva AA, Altunin VV, et al. Allergiya u detei: ot teorii — k praktike. Moscow: Pediatr; 2011. 668 p. (Sovremennaya pediatriya: ot teorii — k praktike). (In Russ).

20. Corren J. The impact of allergic rhinitis on bronchial asthma. J Allergy Clin Immunol. 1998;101(2 Pt 2):S352–S356. doi: https://doi.org/10.1016/s0091-6749(98)70218-0

21. Gergen PJ, Turkeltaub PC. The association of individual allergen reactivity with respiratory disease in a national sample: data from the second National Health and Nutrition Examination Survey, 1976- 80 (NHANES II). J Allergy Clin Immunol. 1992;90(4 Pt 1):579–588. doi: https://doi.org/10.1016/0091-6749(92)90130-t

22. Greisner WA 3rd, Settipane RJ, Settipane GA. Co-existence of asthma and allergic rhinitis: a 23-year follow-up study of college students. Allergy Asthma Proc. 1998;19(4):185–188. doi: https://doi.org/10.2500/108854198778557836

23. Guerra S, Sherrill DL, Martinez FD, Barbee RA. Rhinitis as an independent risk factor for adult-onset asthma. J Allergy Clin Immunol. 2002;109(3):419–425. doi: https://doi.org/10.1067/mai.2002.121701

24. Tohidinik HR, Mallah N, Takkouche B. History of allergic rhinitis and risk of asthma; a systematic review and meta-analysis. World Allergy Organ J. 2019;12(10):100069. doi: https://doi.org/10.1016/j.waojou.2019.100069

25. Vignola AM, Chanez P, Godard P, Bousquet J. Relationships between rhinitis and asthma. Allergy. 1998;53(9):833–839. doi: https://doi.org/10.1111/j.1398-9995.1998.tb03988.x

26. Rondón C, Campo P, Togias A, et al. Local allergic rhinitis: concept, pathophysiology, and management. J Allergy Clin Immunol. 2012;129(6):1460–1467. doi: https://doi.org/10.1016/j.jaci.2012.02.032

27. Kurbacheva OM, Pavlova KS. Allergic rhinitis and allergic conjunctivitis: one disease — two clinical forms. Russian Journal of Allergy. 2015;12(3):22–29. (In Russ). doi: https://doi.org/10.36691/RJA441

28. Thomas M. Allergic rhinitis: evidence for impact on asthma. BMC Pulm Med. 2006;6(Suppl 1):S4. doi: https://doi.org/10.1186/1471-2466-6-S1-S4

29. Poorey VK, Soni S, Thakur P, Gupta A. Effect of Nasal Allergy Over Spirometric Parameters: A Prospective Study. Indian J Otolaryngol Head Neck Surg. 2016;68(1):6–10. doi: https://doi.org/10.1007/s12070-015-0876-x

30. Togias A. Unique mechanistic features of allergic rhinitis. J Allergy Clin Immunol. 2000;105(6 Pt 2):S599–S604. doi: https://doi.org/10.1067/mai.2000.106885

31. Kurbacheva OM, Pavlova KS, Galitzkaya MA. Allergen-specific immunotherapy. Analytic review of current international and Russian federal position papers. Russian Journal of Allergy. 2017;14(1):24–32. (In Russ). doi: https://doi.org/10.36691/RJA333

32. Calderón MA, Casale TB, Togias A, et al. Allergen-specific immunotherapy for respiratory allergies: from meta-analysis to registration and beyond. J Allergy Clin Immunol. 2011;127(1): 30–38. doi: https://doi.org/10.1016/j.jaci.2010.08.024

33. Jacobsen L, Niggemann B, Dreborg S, et al. Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10 year follow-up on the PAT study. Allergy. 2007;62(8):943–948. doi: https://doi.org/10.1111/j.1398-9995.2007.01451.x

34. Jutel M, Agache I, Bonini S, et al. Internetional consensus on allergy immunotherapy. J Allergy Clin Immunol. 2015;136(3): 556–568. doi: https://doi.org/10.1016/j.jaci.2015.04.047

35. Moller C, Dreborg S, Ferdousi HA, et al. Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). J Allergy Clin Immunol. 2002; 109(2):251–256. doi: https://doi.org/10.1067/mai.2002.121317

36. Niggemann B, Jacobsen L, Dreborg S, et al. Five-year follow-up on the PAT study: specific immunotherapy and long-term prevention of asthma in children. Allergy. 2006;61(7):855–859. doi: https://doi.org/10.1111/j.1398-9995.2006.01068.x

37. Papadopoulos NG, Arakawa H, Carlsen KH, et al. International consensus on (ICON) pediatric asthma. Allergy. 2012;67(8):976–997. doi: https://doi.org/10.1111/j.1398-9995.2012.02865.x

38. 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(1):165–177. doi: https://doi.org/10.1111/all.13213

39. Bousquet PJ, Combescure C, Neukirch F, et al. Visual analog scales can assess the severity of rhinitis graded according to ARIA guidelines. Allergy. 2007;62(4):367–372. doi: https://doi.org/10.1111/j.1398-9995.2006.01276.x

40. Bousquet J, Schunemann HJ, Hellings PW, et al. MACVIA clinical decision algorithm in adolescents and adults with allergic rhinitis. J Allergy Clin Immunol. 2016;138(2):367–374.e2. doi: https://doi.org/10.1016/j.jaci.2016.03.025

41. Courbis AL, Murray RB, Arnavielhe S, et al. Electronic Clinical Decision Support System for allergic rhinitis management: MASK e-CDSS. Clin Exp Allergy. 2018;48(12):1640–1653. doi: https://doi.org/10.1111/cea.13230

42. Tyufilin DS, Deev IA, Kobyakova OS, et al. Allergic rhinitis control: contemporary approaches to evaluation. Bulletin of Siberian Medicine. 2019;18(2):262–273. (In Russ). doi: https://doi.org/10.20538/1682-0363-2019-2-262-273

43. Papadopoulos NG, Bernstein JA, Demoly P, et al. Phenotypes and endotypes of rhinitis and their impact on management: a PRACTALL report. Allergy. 2015;70(5):474–494. doi: https://doi.org/10.1111/all.12573

44. Kurbacheva OM, Pavlova KS. Federal’nye klinicheskie rekomendatsii. Allergen-spetsificheskaia immunoterapiia. Russian Journal of Allergy. 2006;(4-5):55–61. (In Russ).

45. Droste JH, Kerhof M, de Monchy JG, et al. Association of skin test reactivity, specific IgE, total IgE, and eosinophils with nasal symptoms in a community-based population study. The Dutch ECRHS Group. J Allergy Clin Immunol. 1996;97(4):922–932. doi: https://doi.org/10.1016/s0091-6749(96)80066-2

46. Di Lorenzo G, Pacor ML, Amodio E, et al. Differences and similarities between allergic and nonallergic rhinitis in a large sample of adult patients with rhinitis symptoms. Int Arch Allergy Immunol. 2011;155(3):263–270. doi: https://doi.org/10.1159/000320050

47. Gelardi M, Passalacqua G, Fiorella ML, Quaranta N. Assessment of biofilm by nasal cytology in different forms of rhinitis and its functional correlations. Eur Ann Allergy Clin Immunol. 2013;45(1):25–29.

48. Gelardi M, Peroni DG, Incorvaia C, et al. Seasonal changes in nasal cytology in mite-allergic patients. J Inflamm Res. 2014;7: 39–44. doi: https://doi.org/10.2147/JIR.S54581

49. Park SC, Kim JH, Lee KH, et al. Association of serum eosinophilia and total immunoglobulin E concentration with the risk of allergic symptoms and allergic sensitization, respectively: A 2-year followup study. Int J Pediatr Otorhinolaryngol. 2016;86:167–171. doi: https://doi.org/10.1016/j.ijporl.2016.05.005

50. Tay TR, Bosco J, Aumann H, et al. Elevated total serum immunoglobulin E (≥1000 IU/mL): implications? Intern Med J. 2016;46(7):846–849. doi: https://doi.org/10.1111/imj.13073

51. Satwani H, Rehman A, Ashraf S, Hassan A. Is serum total IgE levels a good predictor of allergies in children? J Pak Med Assoc. 2009;59(10):698–702.

52. Tu YL, Chang SW, Tsai HJ, et al. Total serum IgE in a populationbased study of Asian children in Taiwan: reference value and significance in the diagnosis of allergy. PLoS One. 2013;8(11):e80996. doi: https://doi.org/10.1371/journal.pone.0080996

53. Casale TB, Bernstein IL, Busse WW, et al. Use of an antiIgE humanized monoclonal antibody in ragweed-induced allergic rhinitis. J Allergy Clin Immunol. 1997;100(1):110–121. doi: https://doi.org/10.1016/S0091-6749(97)70202-1

54. Okubo K, Okano M, Sato N, et al. Efficacy of Omalizumab for Severe Allergic Rhinitis Induced By Japanese Cedar Pollen in Patients Treated with Combination Oral Antihistamines and Nasal Corticosteroids. J Allergy Clin Immunol. 2019;143(2):AB424. doi: https://doi.org/10.1016/j.jaci.2018.12.955

55. Tsabouri S, Tseretopoulou X, Priftis K, Ntzani EE. Omalizumab for the treatment of inadequately controlled allergic rhinitis: a systematic review and meta-analysis of randomized clinical trials. J Allergy Clin Immunol Pract. 2014;2(3):332–340. doi: https://doi. org/10.1016/j.jaip.2014.02.001

56. Pavlova KS, Kulichenko DS, Kurbacheva OM, et al. Omalizumab in the severe exacerbations of seasonal allergic rhinitis. Russian Journal of Allergy. 2022;19(2):164–174. (In Russ). doi: https://doi.org/10.36691/RJA1539

57. Chervinsky P, Casale T, Townley R, et al. Omalizumab, an anti-IgE antibody, in the treatment of adults and adolescents with perennial allergic rhinitis. Ann Allergy Asthma Immunol. 2003;91(2):160–167. doi: https://doi.org/10.1016/S1081-1206(10)62171-0

58. Ameli F, Brocchetti F, Tosca MA, et al. Nasal endoscopy in children with suspected allergic rhinitis. Laryngoscope. 2011;121(10): 2055–2059. doi: https://doi.org/10.1002/lary.22156

59. Eren E, Aktas A, Arslanoglu S, et al. Diagnosis of allergic rhinitis: inter-rater reliability and predictive value of nasal endoscopic examination: a prospective observational study. Clin Otolaryngol. 2013;38(6):481–486. doi: https://doi.org/10.1111/coa.12171

60. Jareoncharsri P, Thitadilok V, Bunnag C, et al. Nasal endoscopic findings in patients with perennial allergic rhinitis. Asian Pac J Allergy Immunol. 1999;17(4):261–267.

61. Brunner JP, Jawad BA, McCoul ED. Polypoid change of the middle turbinate and paranasal sinus polyposis are distinct entities. Otolaryngol Head Neck Surg. 2017;157(3):519–523. doi: https:// doi.org/10.1177/0194599817711887

62. Roll A, Hofbauer G, Ballmer-Weber BK, Schmid-Grendelmeier P. Safety of specific immunotherapy using a four-hour ultra-rush induction scheme in bee and wasp allergy. J Investig Allergol Clin Immunol. 2006;16(2):79–85.

63. Malling HJ, Corren J, Creticos PS. Allergen-specific immunotherapy. In: Allergy: Expert Consult Online and Print. Elsevier; 2011. pp. 171–180. 64. Pitsios C, Petalas K, Dimitriou A, et al. Workup and Clinical Assessment for Allergen Immunotherapy Candidates. Cells. 2022;11(4):653. doi: https://doi.org/10.3390/cells11040653

64. Tschopp JM, Sistek D, Schindler C, et al. Current allergic asthma and rhinitis: diagnostic efficiency of three commonly used atopic markers (IgE, skin prick tests, and Phadiatop). Results from 8329 randomized adults from the SAPALDIA Study. Swiss Study on Air Pollution and Lung Diseases in Adults. Allergy. 1998;53(6):608– 613. doi: https://doi.org/10.1111/j.1398-9995.1998.tb03937.x

65. Nevis IF, Binkley K, Kabali C. Diagnostic accuracy of skinprick testing for allergic rhinitis: a systematic review and metaanalysis. Allergy Asthma Clin Immunol. 2016;12:20. doi: https://doi.org/10.1186/s13223-016-0126-0

66. Health Quality Ontario. Skin Testing for Allergic Rhinitis: A Health Technology Assessment. Ont Health Technol Assess Ser. 2016;16(10):1–45.

67. Liu CY, Zhang Y, Han DM, Zhang L. Evaluation of serum specific IgE for the diagnosis of allergic rhinitis with multi-allergens. Chin Med J (Engl). 2010;123(20):2836–2841.

68. Jiang XD, Li GY, Dong Z, Zhu DD. Correlation analysis of two serum-specific immunoglobulin E test systems and skin-prick test in allergic rhinitis patients from northeast China. Am J Rhinol Allergy. 2011;25(2):116–119. doi: https://doi.org/10.2500/ajra.2011.25.3572

69. Cox L. Overview of serological-specific IgE antibody testing in children. Curr Allergy Asthma Rep. 2011;11(6):447–453. doi: https://doi.org/10.1007/s11882-011-0226-3

70. Hamilton RG, Oppenheimer J. Serological IgE Analyses in the Diagnostic Algorithm for Allergic Disease. J Allergy Clin Immunol Pract. 2015;3(6):833–840; quiz 841–842. doi: https://doi. org/10.1016/j.jaip.2015.08.016

71. Steering Committee Authors; Review Panel Members. A WAO — ARIA — GA2LEN consensus document on molecularbased allergy diagnosis (PAMD@): Update 2020. World Allergy Organ J. 2020;13(2):100091. doi: https://doi.org/10.1016/j.waojou.2019.100091

72. Ferrer M, Sanz ML, Sastre J, et al. Molecular diagnosis in Allergology: application of the microarray technique. J Investig Allergol Clin Immunol. 2009;19(1):19–24.

73. Akdis CA, Jutel M, Akdis M. Regulatory effects of histamine and histamine receptor expression in human allergic immune responses. Chem Immunol Allergy. 2008;94:67–82. doi: https:// doi.org/10.1159/000154858

74. Allocco FT, Votypka V, De Tineo M, et al. Effects of fexofenadine on the early response to nasal allergen challenge. Ann Allergy Asthma Immunol. 2002;89(6):578–584. doi: https://doi.org/10.1016/S1081-1206(10)62105-9

75. Benninger M, Farrar JR, Blaiss M, et al. Evaluating approved medications to treat allergic rhinitis in the United States: an evidence-based review of efficacy for nasal symptoms by class. Ann Allergy Asthma Immunol. 2010;104(1):13–29. doi: https://doi.org/10.1016/j.anai.2009.11.020

76. Berger WE, Lumry WR, Meltzer EO, Pearlman DS. Efficacy of desloratadine, 5 mg, compared with fexofenadine, 180 mg, in patients with symptomatic seasonal allergic rhinitis. Allergy Asthma Proc. 2006;27(3):214–223. doi: https://doi.org/10.2500/aap.2006.27.2851

77. Bocsan CI, Bujor AI, Miron N, et al. In vivo anti-inflammatory effect of H1 antihistamines in allergic rhinitis: a randomized clinical trial. Balkan Med J. 2015:32(4):352–358. doi: https://doi.org/10.5152/balkanmedj.2015.15884

78. Bousquet J, Bachert C, Canonica GW, et al. ACCEPT-1 Study Group. Efficacy of desloratadine in intermittent allergic rhinitis: a GA2LEN study. Allergy. 2009;64(10):1516–1523. doi: https://doi.org/10.1111/j.1398-9995.2009.02115.x

79. Canonica GW, Tarantini F, Compalati E, Penagos M. Efficacy of desloratadine in the treatment of allergic rhinitis: a metaanalysis of randomized, double-blind, controlled trials. Allergy. 2007;62(4):359–366. doi: https://doi.org/10.1111/j.1398-9995.2006.01277.x

80. De Blic J, Wahn U, Billard E, et al. Levocetirizine in children: evidenced efficacy and safety in a 6-week randomized seasonal allergic rhinitis trial. Pediatr Allergy Immunol. 2005;16(3):267–275. doi: https://doi.org/10.1111/j.1399-3038.2005.00216.x

81. 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(6):489–511.e41. doi: https://doi.org/10.1016/j.anai.2017.08.012

82. Farré M, Pérez-Mañá C, Papaseit E, et al. Bilastine vs. hydroxyzine: occupation of brain histamine H1-receptors evaluated by positron emission tomography in healthy volunteers. Br J Clin Pharmacol. 2014;78(5):970–980. doi: https://doi.org/10.1111/bcp.12421

83. Gillman S, Gillard M, Strolin Benedetti M. The concept of receptor occupancy to predict clinical efficacy: a comparison of second generation H1 antihistamines. Allergy Asthma Proc. 2009;30(4): 366–376. doi: https://doi.org/10.2500/aap.2009.30.3226

84. Leurs R, Church MK, Taglialatela M. H1-antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects. Clin Exp Allergy. 2002;32(4):489–498. doi: https://doi.org/10.1046/j.0954-7894.2002.01314.x

85. Lukat K, Rivas P, Roger A, et al. A direct comparison of efficacy between desloratadine and rupatadine in seasonal allergic rhinoconjunctivitis: a randomized, double-blind, placebocontrolled study. J Asthma Allergy. 2013;6:31–39. doi: https://doi. org/10.2147/JAA.S39496

86. Mösges R, König V, Köberlein J. The effectiveness of modern antihistamines for treatment of allergic rhinitis — an IPD metaanalysis of 140,853 patients. Allergol Int. 2013;62(2):215–222. doi: https://doi.org/10.2332/allergolint.12-OA-0486

87. Muntean A, Bocsan I, Deleanu DM. The effect of H1-antihistamines on allergic inflammation in patients with allergic rhinitis. Human and Veterinary Medicine. 2016;8(4):161–165.

88. Naclerio RM. The effect of antihistamines on the immediate allergic response: a comparative review. Otolaryngol Head Neck Surg. 1993;108(6):723–730. doi: https://doi.org/10.1177/019459989310800615

89. Okubo K, Suzuki T, Tanaka A, Aoki H. Efficacy and safety of rupatadine in Japanese patients with seasonal allergic rhinitis: a double-blind, randomized, multicenter, placebo-controlled clinical trial. Allergol Int. 2019;68(2):207–215. doi: https://doi.org/10.1016/j.alit.2018.08.011

90. Valk P, Jetten A, Simons R. Effects of a single oral dose of bilastine 20 mg on flying ability in healthy volunteers under conditions of simulated cabin pressure. Soesterberg: TNO; 2015. 60 p.

91. Ilyina NI, Pavlova KS. Antihistamines, anti-inflammatory and anti-allergic properties of desloratadine. Consilium Medicum. 2015;17(3):79–83. (In Russ).

92. Church MK, Maurer M, Simons FE, et al. Risk of firstgeneration H(1)-antihistamines: a GA(2)LEN position paper. Allergy. 2010;65(4):459–466. doi: https://doi.org/10.1111/j.1398-9995.2009.02325.x

93. Simons FE. Advances in H1-antihistamines. N Engl J Med. 2004;351(21):2203–2217. doi: https://doi.org/10.1056/NEJMra033121

94. Castillo M, Scott NW, Mustafa MZ, et al. Topical antihistamines and mast cell stabilisers for treating seasonal and perennial allergic conjunctivitis. Cochrane Database Syst Rev. 2015;2015(6):CD009566. doi: https://doi.org/10.1002/14651858.CD009566.pub2

95. Lee TA, Pickard AS. Meta-analysis of azelastine nasal spray for the treatment of allergic rhinitis. Pharmacotherapy. 2007;27(6): 852–859. doi: https://doi.org/10.1592/phco.27.6.852

96. Al Sayyad JJ, Fedorowicz Z, Alhashimi D, Jamal A. Topical nasal steroids for intermittent and persistent allergic rhinitis in children. Cochrane Database Syst Rev. 2007;2007(1):CD003163. doi: https://doi.org/10.1002/14651858.CD003163.pub4

97. Dibildox J. Safety and efficacy of mometasone furoate aqueous nasal spray in children with allergic rhinitis: results of recent clinical trials. J Allergy Clin Immunol. 2001;108(1 Suppl):S54–S58. doi: https://doi.org/10.1067/mai.2001.115567

98. Herman H. Once-daily administration of intranasal corticosteroids for allergic rhinitis: a comparative review of efficacy, safety, patient preference, and cost. Am J Rhinol. 2007;21(1):70–79. doi: https://doi.org/10.2500/ajr.2007.21.2896

99. Penagos M, Compalati E, Tarantini F, et al. Efficacy of mometasone furoate nasal spray in the treatment of allergic rhinitis: meta-analysis of randomized, double-blind, placebocontrolled, clinical trials. Allergy. 2008;63(10):1280–1291. doi: https://doi.org/10.1111/j.1398-9995.2008.01808.x

100. Rodrigo GJ, Neffen H. Efficacy of fluticasone furoate nasal spray vs. placebo for the treatment of ocular and nasal symptoms of allergic rhinitis: a systematic review. Clin Exp Allergy. 2011;41(2):160–170. doi: https://doi.org/10.1111/j.1365-2222.2010.03654.x

101. Wu EL, Harris WC, Babcock CM, et al. Epistaxis Risk Associated with Intranasal Corticosteroid Sprays: A Systematic Review and Meta-analysis. Otolaryngol Head Neck Surg. 2019;161(1):18–27. doi: https://doi.org/10.1177/0194599819832277

102. Yanez A, Rodrigo GJ. Intranasal corticosteroids versus topical H1 receptor antagonists for the treatment of allergic rhinitis: a systematic review with meta-analysis. Ann Allergy Asthma Immunol. 2002;89(5):479–484. doi: https://doi.org/10.1016/S1081-1206(10)62085-6

103. 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(6):1833–1840. doi: https://doi.org/10.1185/03007990802155792

104. DeWester J, Philpot EE, Westlund RE, et al. The efficacy of intranasal fluticasone propionate in the relief of ocular symptoms associated with seasonal allergic rhinitis. Allergy Asthma Proc. 2003;24(5):331–337.

105. Bielory L, Chun Y, Bielory BP, Canonica GW. Impact of mometasone furoate nasal spray on individual ocular symptoms of allergic rhinitis: a meta-analysis. Allergy. 2011;66(5):686–693. doi: https://doi.org/10.1111/j.1398-9995.2010.02543.x

106. 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(5):1726–1732.e6. doi: https://doi.org/10.1016/j.jaip.2018.01.031

107. Debbaneh PM, Bareiss AK, Wise SK, McCoul ED. Intranasal Azelastine and Fluticasone as Combination Therapy for Allergic Rhinitis: Systematic Review and Meta-analysis. Otolaryngol Head Neck Surg. 2019;161(3):412–418. doi: https://doi.org/10.1177/0194599819841883

108. Hampel FC, Ratner PH, Van Bavel J, et al. Double-blind, placebocontrolled study of azelastine and fluticasone in a single nasal spray delivery device. Ann Allergy Asthma Immunol. 2010;105(2): 168–173. doi: https://doi.org/10.1016/j.anai.2010.06.008

109. Andrews CP, Mohar D, Salhi Y, et al. Efficacy and safety of twicedaily and once-daily olopatadine-mometasone combination nasal spray for seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2020;124(2):171–178.e2. doi: https://doi.org/10.1016/j.anai.2019.11.007

110. Gross GN, Berman G, Amar NJ, et al. Efficacy and safety of olopatadine-mometasone combination nasal spray for the treatment of seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2019;122(6):630–638.e3. doi: https://doi.org/10.1016/j. anai.2019.03.017

111. Hampel FC, Pedinoff AJ, Jacobs RL, et al. Olopatadinemometasone combination nasal spray: Evaluation of efficacy and safety in patients with seasonal allergic rhinitis. Allergy Asthma Proc. 2019;40(4):261–272. doi: https://doi.org/10.2500/aap.2019.40.4223

112. Patel P, Salapatek AM, Tantry SK. Effect of olopatadinemometasone combination nasal spray on seasonal allergic rhinitis symptoms in an environmental exposure chamber study. Ann Allergy Asthma Immunol. 2019;122(2):160–166.e1. doi: https://doi.org/10.1016/j.anai.2018.10.011

113. Patel P, Salapatek AM, Talluri RS, et al. Pharmacokinetics of intranasal mometasone in the fixed-dose combination GSP301 versus two monotherapy intranasal mometasone formulations. Allergy Asthma Proc. 2018;39(4):232–239. doi: https://doi.org/10.2500/aap.2018.39.4134

114. Prenner BM, Amar NJ, Hampel FC Jr, et al. Efficacy and safety of GSP301 nasal spray in children aged 6 to 11 years with seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2022;129(5): 618–626. doi: https://doi.org/10.1016/j.anai.2022.07.029

115. Segall N, Prenner B, Lumry W, et al. Long-term safety and efficacy of olopatadine-mometasone combination nasal spray in patients with perennial allergic rhinitis. Allergy Asthma Proc. 2019;40(5):301–310. doi: https://doi.org/10.2500/aap.2019.40.4233

116. Wei C. The efficacy and safety of H1-antihistamine versus Montelukast for allergic rhinitis: A systematic review and metaanalysis C. Biomed Pharmacother. 2016;83:989–997. doi: https://doi.org/10.1016/j.biopha.2016.08.003

117. Lu Y, Yin M, Cheng L. Meta-analysis of leukotriene receptor antagonist montelukast in the treatment of allergic rhinitis. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2014;49(8):659–667.

118. Modgill V, Badyal DK, Verghese A. Efficacy and safety of montelukast add-on therapy in allergic rhinitis. Methods Findings Exp Clin Pharmacol. 2010;32(9):669–674. doi: https://doi.org/10.1358/mf.2010.32.9.1533686

119. Ngamphaiboon J. Montelukast in general pediatric practices. J Med Assoc Thai. 2005;88(Suppl 4):S348–S351.

120. Seresirikachorn K, Chitsuthipakorn W, Kanjanawasee D, et al. Leukotriene Receptor Antagonist Addition to H1-Antihistamine Is Effective for Treating Allergic Rhinitis: A Systematic Review and Meta-analysis. Am J Rhinol Allergy. 2019;33(5):591–600. doi: https://doi.org/10.1177/1945892419844459

121. Xu Y, Zhang J, Wang J. The Efficacy and Safety of Selective H1-Antihistamine versus Leukotriene Receptor Antagonist for Seasonal Allergic Rhinitis: A Meta-Analysis. PLoS One. 2014;9(11):e112815. doi: https://doi.org/10.1371/journal.pone.0112815

122. Nayak A. A review of montelukast in the treatment of asthma and allergic rhinitis. Expert Opin Pharmacother. 2004;5:679–686. doi: https://doi.org/10.1517/14656566.5.3.679

123. Polos PG. Montelukast is an effective monotherapy for mild asthma and for asthma with co-morbid allergic rhinitis. Prim Care Respir J. 2006;15(5):310–311; author reply 311–312. doi: https://doi.org/10.1016/j.pcrj.2006.07.003

124. Watts K, Chavasse RJPG. Leukotriene receptor antagonists in addition to usual care for acute asthma in adults and children. Cochrane Database Syst Rev. 2012;2012(5):CD006100. doi: https://doi.org/10.1002/14651858.CD006100.pub2

125. Ciebiada M, Górska-Ciebiada M, DuBuske LM, Górski P. Montelukast with desloratadine or levocetirizine for the treatment of persistent allergic rhinitis. Ann Allergy Asthma Immunol. 2006;97(5):664–671. doi: https://doi.org/10.1016/S1081-1206(10)61098-8

126. Gupta V, Matreja PS. Efficacy of montelukast and levocetirizine as treatment for allergic rhinitis. J Allergy Ther. 2010;1:103. doi: https://doi.org/10.4172/2155-6121.1000103

127. Liu G, Zhou X, Chen J, Liu F. Oral antihistamines alone vs in combination with leukotriene receptor antagonists for allergic rhinitis: a meta-analysis. Otolaryngol Head Neck Surg. 2018;158(3): 450–458. doi: https://doi.org/10.1177/0194599817752624

128. Khattiyawittayakun L, Seresirikachorn K, Chitsuthipakorn W, et al. Effects of decongestant addition to intranasal corticosteroid for chronic rhinitis: a systematic review and meta-analysis. Int Forum Allergy Rhinol. 2018;8(12):1445–1453. doi: https://doi.org/10.1002/alr.22193

129. Yoo JK, Seikaly H, Calhoun KH. Extended use of topical nasal decongestants. Laryngoscope. 1997;107(1):40–43. doi: https://doi.org/10.1097/00005537-199701000-00010

130. Okano M. Efficacy and safety of omalizumab for severe Japanese cedar pollinosis in patients treated with combination oral antihistamines and nasal corticosteroids. Poster presented at The EAACI. Lisbon, June 1–6, 2019. Poster #TP1372.

131. Yu C, Wang K, Cui X, et al. Clinical Efficacy and Safety of Omalizumab in the Treatment of Allergic Rhinitis: A Systematic Review and Meta-analysis of Randomized Clinical Trials. Am J Rhinol Allergy. 2020;34(2):196–208. doi: https://doi.org/10.1177/1945892419884774

132. Kilburn SA, Lasserson TJ, McKean MC. Pet allergen control measures for allergic asthma in children and adults. Cochrane Database Syst Rev. 2001;2001(1):CD002989. doi: https://doi.org/10.1002/14651858.CD002989

133. Sheikh A, Hurwitz B, Nurmatov U, van Schayck CP. House dust mite avoidance measures for perennial allergic rhinitis. Cochrane Database Syst Rev. 2010;2010(7):CD001563. doi: https://doi.org/10.1002/14651858.CD001563.pub3

134. Head K, Snidvongs K, Glew S, et al. Saline irrigation for allergic rhinitis. Cochrane Database Syst Rev. 2018;2018(6):CD012597. doi: https://doi.org/10.1002/14651858.CD012597.pub2

135. Hermelingmeier KE, Weber RK, Hellmich M, et al. Nasal irrigation as an adjunctive treatment in allergic rhinitis: a systematic review and meta-analysis. Am J Rhinol Allergy. 2012;26(5):e119– e125. doi: https://doi.org/10.2500/ajra.2012.26.3787

136. Li CL, Lin HC, Lin CY, Hsu TF. Effectiveness of Hypertonic Saline Nasal Irrigation for Alleviating Allergic Rhinitis in Children: A Systematic Review and Meta-Analysis. J Clin Med. 2019;8(1):64. doi: https://doi.org/10.3390/jcm8010064

137. Valerieva A, Church MK, Staevska M, et al. Micronized cellulose powder as a means to enhance intranasal symptomsdriven treatment: patients” attitudes in a real life setting. Allergy. 2016;71(Suppl 102):13.

138. Des Roches A, Paradis L, Menardo JL, et al. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. VI. Specific immunotherapy prevents the onset of new sensitizations in children. J Allergy Clin Immunol. 1997;99(4):450–453. doi: https://doi.org/10.1016/s0091-6749(97)70069-1

139. Dhami S, Nurmatov U, Arasi S, et al. Allergen immunotherapy for allergic rhinoconjunctivitis: A systematic review and metaanalysis. Allergy. 2017;72(11):1597–1631. doi: https://doi.org/10.1111/all.13201

140. Feng B, Wu J, Chen B, et al. Efficacy and safety of sublingual immunotherapy for allergic rhinitis in pediatric patients: A meta-analysis of randomized controlled trials. Am J Rhinol Allergy. 2017;31(1):27–35. doi: https://doi.org/10.2500/ajra.2017.31.4382

141. Kim JM, Lin SY, Suarez-Cuervo C. Allergen-specific immunotherapy for pediatric asthma and rhinoconjunctivitis: a systematic review. Pediatrics. 2013;131(6):1155–1167. doi: https://doi.org/10.1542/peds.2013-0343

142. Li Y, Yu SY, Tang R, et al. Sublingual Immunotherapy Tablets Relieve Symptoms in Adults with Allergic Rhinitis: A Meta-analysis of Randomized Clinical Trials. Chin Med J (Engl). 2018;131(21): 2583–2588. doi: https://doi.org/10.4103/0366-6999.244108

143. Mösges R, Valero Santiago A, Allekotte S, et al. Subcutaneous immunotherapy with depigmented-polymerized allergen extracts: a systematic review and meta-analysis. Clin Transl Allergy. 2019:9;29. doi: https://doi.org/10.1186/s13601-019-0268-5

144. Purello-D’Ambrosio F, Gangemi S, Merendino RA, et al. Prevention of new sensitizations in monosensitized subjects submitted to specific immunotherapy or not. A retrospective study. Clin Exp Allergy. 2001;31(8):1295–1302. doi: https://doi.org/10.1046/j.1365-2222.2001.01027.x

145. Radulovic S, Calderon MA, Wilson D, Durham S. Sublingual immunotherapy for allergic rhinitis. Cochrane Database Syst Rev. 2010;2010(12):CD002893. doi: https://doi.org/10.1002/14651858.CD002893.pub2

146. Tahamiler R, Saritzali G, Canakcioglu S. Long-term efficacy of sublingual immunotherapy in patients with perennial rhinitis. Laryngoscope. 2007;117(6):965–969. doi: https://doi.org/10.1097/MLG.0b013e31804f8141

147. Wilson DR, Lima MT, Durham SR. Sublingual immunotherapy for allergic rhinitis: systematic review and meta-analysis. Allergy. 2005;60(1):4–12. doi: https://doi.org/10.1111/j.1398-9995.2005.00699.x

148. Pavlova KS, Kurbacheva OM, Galitskaya MA, Smirnov DS. Actual conception of allergen-specific immunotherapy mechanisms, potential biomarkers of efficacy and ways of enhancement. Russian Journal of Allergy. 2017;14(4-5): 5–17. (In Russ). doi: https://doi.org/10.36691/RJA290

149. Akdis M, Akdis CA. Mechanisms of allergen-specific immunotherapy: multiple suppressor factors at work in immune tolerance to allergens. J Allergy Clin Immunol. 2014;133(3): 621–631. doi: https://doi.org/10.1016/j.jaci.2013.12.1088

150. 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(7):854–867. doi: https://doi.org/10.1111/all.12383

151. Mishra A, Kawatra R, Gola M. Interventions for atrophic rhinitis. Cochrane Database Syst Rev. 2012;2012(2):CD008280. doi: https://doi.org/10.1002/14651858.CD008280.pub2

152. Jose J, Coatesworth AP. Inferior turbinate surgery for nasal obstruction in allergic rhinitis after failed medical treatment. Cochrane Database Syst Rev. 2010;2010(12):CD005235. doi: https://doi.org/10.1002/14651858.CD005235.pub2

153. Feng S, Han M, Fan Y, et al. Acupuncture for the treatment of allergic rhinitis: a systematic review and meta-analysis. Am J Rhinol Allergy. 2015;29(1):57–62. doi: https://doi.org/10.2500/ajra.2015.29.4116

154. Zhang J, Zhang Y, Huang X, et al. Different Acupuncture Therapies for Allergic Rhinitis: Overview of Systematic Reviews and Network Meta-Analysis. Evid Based Complement Alternat Med. 2020;2020:8363027. doi: https://doi.org/10.1155/2020/8363027

155. Maspero JF, Rosenblut A, Finn A Jr, et al. Safety and efficacy of fluticasone furoate in pediatric patients with perennial allergic rhinitis. Otolaryngol Head Neck Surg. 2008;138(1):30–37. doi: https://doi.org/10.1016/j.otohns.2007.10.023

156. Nasser M, Fedorowicz Z, Aljufairi H, McKerrow W. Antihistamines used in addition to topical nasal steroids for intermittent and persistent allergic rhinitis in children. Cochrane Database Syst Rev. 2010;2010(7):CD006989. doi: https://doi.org/10.1002/14651858.CD006989.pub2

157. Roberts G, Xatzipsalti M, Borrego LM, et al. Paediatric rhinitis: position paper of the European Academy of Allergy and Clinical Immunology. Allergy. 2013;68(9):1102–1116. doi: https://doi.org/10.1111/all.12235

158. RADAR. Allergicheskii rinit u detei: Recommendations and algorithm for childhood allergic rhinitis. 2nd edn., rev. and add. Moscow: Original-maket; 2017. 80 p. (In Russ).

159. Watts AM, Cripps AW, West NP, Cox AJ. Modulation of Allergic Inflammation in the Nasal Mucosa of Allergic Rhinitis Sufferers With Topical Pharmaceutical Agents. Front Pharmacol. 2019;10:294. doi: https://doi.org/10.3389/fphar.2019.00294

160. Blaiss MS. Safety update regarding intranasal corticosteroids for the treatment of allergic rhinitis. Allergy Asthma Proc. 2011;32(6): 413–418. doi: https://doi.org/10.2500/aap.2011.32.3473

161. Scadding GK, Smith PK, Blaiss M, et al. Allergic Rhinitis in Childhood and the New EUFOREA Algorithm. Front Allergy. 2021;2:706589. doi: https://doi.org/10.3389/falgy.2021.706589

162. Sigurdardottir ST, Jonasson K, Clausen M, et al. Prevalence and early-life risk factors of school-age allergic multimorbidity: The EuroPrevall-iFAAM birth cohort. Allergy. 2021;76(9):2855–2865. doi: https://doi.org/10.1111/all.14857

163. Lopatin AS. Diagnostika i lechenie rinita i rinosinusita u beremennykh. Russian Journal of Allergy. 2006;(1):12–18. (In Russ).

164. Gani F, Braida A, Lombardi C, et al. Rhinitis in pregnancy. Allerg Immunol (Paris). 2003;35(8):306–313.

165. Kurbacheva OM, Shvets SM. Allergicheskii rinit i beremennost’: vozmozhnosti sovremennoi terapii. Effektivnaya farmakoterapiya. 2013;(18): 74–80. (In Russ).

166. Gilbert C, Mazzotta P, Loebstein R, Koren G. Fetal safety of drugs used in the treatment of allergic rhinitis: a critical review. Drug Saf. 2005;28(8):707–719. doi: https://doi.org/10.2165/00002018-200528080-00005

167. Yawn B, Knudtson M. Treating asthma and comorbid allergic rhinitis in pregnancy. J Am Board Fam Pract. 2007;20(3):289–298. doi: https://doi.org/10.3122/jabfm.2007.03.060144

168. Cetirizine Pregnancy and Breastfeeding Warnings. Available online: https://www.drugs.com/pregnancy/cetirizine.html. Accessed on July 22, 2024.

169. Kallen B, Otterblad Olausson P. Use of anti-asthmatic drugs during pregnancy. 3. Congenital malformations in the infants. Eur J Clin Pharmacol. 2007;63(4):383–388. doi: https://doi.org/10.1007/s00228-006-0259-z