The role of leukotriene receptor blockers in the treatment of allergic rhinitis in combination with chronic rhinosinusitis with nasal polyps

Background. Leukotrienes play an important role in the pathogenesis of allergic rhinitis (AR) and eosinophilic type of chronic rhinosinusitis with nasal polyps (CRSwNP). There is a phenotype of CRSwNP in combination with AR, which has specifics of local inflammation.

The aim of our study was to investigate the efficacy of using an antileukotriene drug in the treatment of AR in combination with CRSwNP.

Materials and methods. 63 patients with AR and bilateral CRSwNP after endoscopic bilateral polypotomy were randomly divided into 2 groups. In the 1st group 32 people (age 50.28 ± 1.37 years) were prescribed a basic therapy with nasal spray of mometasone furoate at a daily dose of 400 µg in combination with montelukast 1 tab. 10 mg at night, in the 2^nd group 31 people (age 50.31 ± 1, 16 years old) received only mometasone furoate monotherapy. Endoscopic examination of the nasal cavity was performed once every 3 months. The follow-up period was 1 year.

Results. After 3 months in the 1^st group of patients there was a recurrence of polyp growth was observed in 25% of cases, in the 2^nd group in 35.5% of patients (p < 0.05). After 6 months, the number of relapses of CRSwNP decreased to 15.6% of cases in group 1 and to 22.6% in group 2 (p < 0.05). After 9 months in group 1 recurrence of NP was recorded in 12.5% of patients and nasal polyps were completely absent during endoscopic examination in 9.4% of cases, in the 2^nd group, relapse was detected in 19.35% of patients (p < 0.05). 1 year after surgery, in group 1, relapse of NP was found in 12.5% of patients with AR and in 12.5% of cases was remission of the pathological process with cancellation of basic therapy. In group 2, recurrence of NP was in 16.1% of cases, there were no reasons for withdraw treatment of intranasal glucocorticosteroids in this group.

Discussion. The clinical effectiveness of the addition of Montelukast to basic therapy has been reflected in a reduction in the growth rate of polyposic vegetation, the number of repeated operations and the stabilization of the flow of chronic inflammatory process.

Conclusions. In the case of the clinical phenotype of AR with CRSwNP, the addition of a leukotriene receptor blocker montelukast to the basic therapy of intranasal glucocorticosteroids made it possible to improve drug control of both diseases and reduce the frequency of CRSwNP relapses.

1. Papadopoulos N.G., Bernstein J.A., Demoly P., Dykewicz M., Fokkens W., Hellings P.W. et al. Phenotypes and endotypes of rhinitis and their impact on management: a PRACTALL report. Allergy. 2015;70(5):474–494. https://doi.org/10.1111/all.12573.

2. Klimek L., Bachert C., Pfaar O., Becker S., Bieber T., Brehler R. et al. ARIA guideline 2019: treatment of allergic rhinitis in the German health system. Allergologie Select. 2019;3(1):22–50. https://doi.org/10.5414/alx02120e.

3. Brożek J.L., Bousquet J., Agache I., Agarwal A., Bachert C., Bosnic-A nticevich S. et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines – 2016 revision. J Aller and Clin Immunol. 2017;140(4):950–958. https://doi.org/10.1016/j.jaci.2017.03.050.

4. Pezato R., Lobato Gregório L., Pérez-N ovo C., Ferreira T., Bezerra P., Kosugi E.M. Montelukast Has no Impact on the Systemic Production of TGFβ-1 in Patients with Nasal Polyposis Associated with Aspirin Intolerance. Int Arch Otorhinolaryngol. 2021;25(1):88–91. https://doi.org/10.1055/s-0040-1702972.

5. Okamura T., Sumitomo S., Morita K., Iwasaki Y., Inoue M., Nakachi S. et al. TGFβ3-expressing CD4+CD25(-)LAG3+ regulatory T cells control humoral immune responses. Nat Commun. 2015;6:6329. https://doi.org/10.1038/ncomms7329.

6. Kountakis S.E., Arango P., Bradley D., Wade Z.K., Borish L. Molecular and cellular staging for the severity of chronic rhinosinusitis. Laryngoscope. 2004;114(11):1895–1905. https://doi.org/10.1097/01.mlg.0000147917.43615.c0.

7. London N.R., Ramanathan M. The Role of the Sinonasal Epithelium in Allergic Rhinitis. Otolaryngol Clin North Amer. 2017;50(6):1043–1050. https://doi.org/10.1016/j.otc.2017.08.002.

8. Peters-Golden M., Gleason M., Togias A. Cysteinyl leukotrienes: multi- functional mediators in allergic rhinitis. Clin and Exp Aller. 2006;36(6):689. https://doi.org/10.1111/J.1365-2222.2006.02498.X.

9. Cingi C., Muluk N.B., Ipci K., Şahin E. Antileukotrienes in Upper Airway Inflammatory Diseases. Cur Aller and Ast Rep. 2015;15(11):64. https://doi.org/10.1007/s11882-015-0564-7.

10. Rasp G. Is there a role for leukotriene antagonists in the prevention of recurrent nasal polyps? Curr Opin Allergy Clin Immunol. 2010;10(3):200–205. https://doi.org/10.1097/ACI.0b013e328339117f.

11. Mashkova T.A., Maltsev A.B. Clinical and laboratory evaluation of nasal obstruction in patients with polypoid rhinosinusitis. Rossiiskaya Otorinolaringologiya. 2015;6(79):43–46. (In Russ.) https://doi.org/10.18692/1810-4800-2015-6-43-46.

12. Du J., Ba L., Zhou J., Yu L., Liu R., Zhang J. et al. The role of cysteinyl leukotrienes and their receptors in refractory nasal polyps. Prostaglandins Leukot Essent Fatty Acids. 2017;126:39–48. https://doi.org/10.1016/j.plefa.2017.09.009.

13. Bousquet J., Khaltaev N., Cruz A.A., Denburg J., Fokkens W.J., Togias A. et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2) LEN and AllerGen). Allergy. 2008;(86):8–160. https://doi.org/10.1111/j.1398-9995.2007.01620.x.

14. Mashkova T.A., Mal’tsev A.B., Nerovny A.I., Bakulina L.S. The role of a leukotriene receptor antagonist in the restoration of the nasal breathing in the patients presenting with polypous rhinosinusitis. Vestnik Oto-Rino-Laringologii. 2017;82(5):32–35. (In Russ.) https://doi.org/10.17116/otorino201782532-35.

15. Wentzel J.L., Soler Z.M., DeYoung K., Nguyen S.A., Lohia S., Schlosser R.J. Leukotriene antagonists in nasal polyposis: a meta-analysis and systematic review. Am J Rhinol Allergy. 2013;27(6):482–489. https://doi.org/10.2500/ajra.2013.27.3976.

16. Savlevich E.L., Zurochka A.V., Kurbacheva O.M., Egorov V.I., Gaganov L.E., Lyubimova E.V. Transforming growth factors TGF-β1, TGF-β2 and TGF-β3 in the tissue of nasal polyps in different phenotypes of chronic rhinosinusitis with nasal polyps. Medical Immunology (Russia). 2022;24(1):147–156. (In Russ.) https://doi.org/10.15789/1563-0625-TGF-2365.

17. Savlevich E.L., Kurbacheva O.M. Features of the course of polypous rhinosinusitis combined with allergic rhinitis. Meditsinskiy Sovet. 2019;(20):38–43. (In Russ.) https://doi.org/10.21518/2079-701X-2019-20-38-43.

18. Savlevich E.L., Dyneva M.E., Gaganov L.E., Egorov V.I., Gerasimov A.N., Kurbacheva O.M. Diagnostic and treatment algorithm for different phenotypes of chronic rhinosinusitis with nasal polyps. Rus J Aller. 2019;16(2):50–60. (In Russ.) https://doi.org/10.36691/RJA1198.

19. Savlevich E.L., Cherenkova V.A., Molodnitskaia A.Yu. Basic principles for the treatment of chronic rhinosinusitis with nasal polyps. Meditsinskiy Sovet. 2020;(16):73–78. (In Russ.) https://doi.org/10.21518/2079-701X-2020-16-73-78.

20. Fokkens W.J., Lund V.J., Mullol J., Bachert C., Alobid I., Baroody F. et al. European position paper on rhinosinusitis and nasal polyps 2012. Rhinol Suppl. 2012;50(23):1–298. https://doi:10.4193/Rhino50E2.

21. Chuchueva N.D., Savlevich E.L., Kozlov V.S., Doronina V.A. Evaluation of efficacy of the Olyfrin spray in treatment of patients with atrophic rhinitis using the Russian- language version of SNOT-25 questionnaire with Houser’s modifications. Rossiyskaya Otorinolaringologiya. 2020;19(4):102–112. (In Russ.) https://doi.org/10.18692/1810-4800-2020-4-102-112.

22. Hulse K.E., Stevens W.W., Tan B.K., Schleimer R.P. Pathogenesis of nasal polyposis. Clin Exp Allergy. 2015;45(2):328–346. https://doi.org/10.1111/cea.12472.

23. Holgate S.T., Peters-Golden M., Panettieri R.A., Henderson W.R. Jr. Roles of cysteinyl leukotrienes in airway inflammation, smooth muscle function, and remodeling. J Allergy Clin Immunol. 2003;111(1 Suppl.):18–34. https://doi.org/10.1067/mai.2003.25.

24. Vuralkan E., Saka C., Akin I., Hucumenoglu S., Unal B.U., Kuran G., Ocal B. Comparison of montelukast and mometasone furoate in the prevention of recurrent nasal polyps. Ther Adv Respir Dis. 2012;6(1):5–10. https://doi.org/10.1177/1753465811427577.

25. Savlevich E.L., Egorov V.I., Shachnev K.N., Tatarenko N.G. The analysis of polypous rhinosinusitis treatment regimens in the Russian Federation. Rossiyskaya Otorinolaringologiya. 2019;18(1):124–134. (In Russ.) https://doi.org/10.18692/1810-4800-2019-1-124-134.

26. Van Gerven L., Langdon C., Cordero A., Cardelús S., Mullol J., Alobid I. Lack of long-term add-on effect by montelukast in postoperative chronic rhinosinusitis patients with nasal polyps. Laryngoscope. 2018;128(8):1743–1751. https://doi.org/10.1002/lary.26989.