Asthma associated with nasal polyps: clinical characteristics and analysis of local expression of IL37 gene

Abstract

Introduction. Asthma associated with chronic rhinosinusitis with nasal polyps (CRSwNP) is considered to be one of the most complex phenotypes of asthma, not sufficiently characterized in terms of etiopathogenesis. Conflicting data from numerous studies create difficulties in making recommendations for the diagnosis and treatment of this condition.

The aim of our study was to analyze the level of local expression of the IL37 gene and Th1-, Th2-, Th17-cytokines in patients with asthma associated with CRSwNP.

Material and methods. 48 volunteers were included and divided into 4 groups: «Healthy volunteers», «Atopic asthma + CRSwNP», «Not-atopic asthma + CRSwNP», «CRSwNP without asthma». All participants in the study underwent clinical, laboratory, instrumental, histological examination, assessment of local expression of IL37 gene, as well as IFNG, IL1B, IL4, IL5, IL13, IL17F in the obtained biopsy material (polypous tissue) using RT-PCR.

Results. Our results confirmed the mutual influence of asthma and CRSwNP, and according to the SNOT-22 and ACQ-7 questionnaires, a combination of these diseases led to a more severe and uncontrolled course of both asthma and CRSwNP. These results correlated with an increase in the absolute and relative number of eosinophils in peripheral blood (p = 0.05) and by eosinophilic cell infiltration of nasal polyp stroma in the not-atopic asthma associated CRSwNP. We also found that local dysregulation of the Th1-, Th2-, Th17-immune response underly the development of CRSwNP in patients with asthma. Moreover, the high expression of IL37 gene in patients with asthma associated with CRSwNP, and especially in patients with not-atopic asthma associated with CRSwNP, probably indicates the inclusion of the compensatory mechanism.

Conclusion. IL37 can be considered as the future molecular biomarker of the severity of inflammation in asthma and CRSwNP. Further study of the pathogenesis of asthma and CRSwNP will help to understand the mechanisms that bind these diseases and consider possible target molecules for biological therapy.

Keywords:IL37 gene; bronchial asthma; chronic rhinosinusitis with nasal polyps; cytokines; inflammation; gene expression

For citation: Khaitov M.R., Dyneva M.E., Savlevich E.L., Kudlay D.A., Gaysina A.R., Nikolsky А.А., Shilovsky I.P, Kurbacheva O.M. Asthma associated with nasal polyps: clinical characteristics and analysis of local expression of IL37 gene, Immunologiya. 2020; 41 (1): 54-63. DOI: 10.33029/0206-4952-2020-41-1-54-63 (in Russian)

Acknowledgements. Work was supported by the Russian Science Foundation grant No. 19-15-00272.

Conflict of interest. The authors declare no conflict of interests.



References

1. Chaaban M.R., Walsh E.M., Erika M., WoodworthB.A., et al. Epidemiology and differential diagnosis of nasal polyps. Am. J. Rhinol. Allergy. 2013; 27 (6): 473–8.

2. Linneberg A., Dam Petersen K., Hahn-Pedersen J., Hammerby E., et al. Burden of allergic respiratory disease: a systematic review. Clin. Mol. Allergy. 2016; 14 (1): 1–14.

3. Kurbacheva O.M., Pavlova K.S. Is it possible to improve control of asthma without increasing doses of glucocorticosteroids? Prakticheskaya pulmonologiya. 2017; 2: 14–21. (in Russian)

4. Chichkova N. Bronchial asthma and polyposis rhinosinusitis: features of the clinical course and management tactics of patients. Astma i allergiya. 2015; 1: 19–22. (in Russian)

5. Kowalski M.L., Asero R., Bavbek S., Blanca M., et al. Classification and practical approach to the diagnosis and management of hypersensitivity to nonsteroidal anti-inflammatory drugs. Allergy. 2013; 68 (10): 1219–32.

6. Stevens W.W., Peters A.T., Suh L., Norton J.E., et al. A retrospective, cross-sectional study reveals that women with CRSwNP have more severe disease than men. Immun. Inflamm. Dis. 2015; 3 (1): 14–22.

7. Yacoub M.R., Trimarchi M., Cremona G., Dal Farra S., et al. Are atopy and eosinophilic bronchial inflammation associated with relapsing forms of chronic rhinosinusitis with nasal polyps? Clin. Mol. Allergy. 2015; 13 (1): 1–6.

8. Tan B.K., Chandra R.K., Pollak J., Kato A., et al. Incidence and associated premorbid diagnoses of patients with chronic rhinosinusitis. J. Allergy Clin. Immunol. 2013. 131 (5): 1350–60.

9. Charrad R., Berraïes A., Hamdi B., Ammar J., et al. Increased expression of thymic stromal lymphopoietin in induced sputum from asthmatic children. Immunobiology. 2016; 221 (2): 182–7.

10. Saidov M.Z., Davudova B. Kh., Osmanov A.O., Klimova S.V., et al. Expression of toll-receptors in nasal polyps and peripheral blood cells from patients with polypous rhinosinusitis. Immunologiya. 2009; 5: 272–8. (in Russian)

11. Raedler D., Ballenberger N., Klucker E., Böck A., et al. Identification of novel immune phenotypes for allergic and nonallergic childhood asthma. J. Allergy Clin. Immunol. 2015; 135 (1): 81–91.

12. Fokkens WJ., Lund VJ., Mullol J., Bachert C., et al. European position paper on rhinosinusitis and nasal polyps. Rhinol. Suppl. 2012; 23 (3): 1–298.

13. Pearlman A.N., Chandra R.K., Chang D., Conley D.B., et al. Relationships between severity of chronic rhinosinusitis and nasal polyposis, asthma, and atopy. Am. J. Rhinol. Allergy. 2009; 23 (2): 145–8.

14. Savlevich E.L., Khaydukov S.V., Kurbacheva O.М., Bondareva G.P., et al. Characteristics of cellular immune status in the patients with chronic rhinosinusitis with nasal polyps. Meditsinskaya immunologiya. 2017; 19 (6): 731–8. (in Russian)

15. Yeganeh C., Xia H., Movassagh C., Koziol-White Chang Y., et al. Emerging mediators of airway smooth muscle dysfunction in asthma. Pulm. Pharmacol. Ther. 2013; 26 (1): 105–11.

16. Cheng J., Ouyang H., Du J. Expression and regulation of interleukin-37 in pathogenesis of nasal polyps. Indian J. Otolaryngol. Head Neck Surg. 2014; 66 (4): 401–6.

17. Saidov M.Z., Davudova B.Kh., Klimova S.V., BudikhinaA.S., et al. Clinical significance of the relationship between parameters of systemic and local adaptive and congenital immunity exemplified by polypous rhinosinusitis. Immunologiya. 2010; 1: 101–7. (in Russian)

18. Khaitov M.R., Akimov V.S. Genetic predisposition to development of asthma and atopy, approaches to identifying new genes associated with the development of asthma and atopy. Rossiyskiy allergologicheskiy zhurnal. 2004; 3: 67–74. (in Russian)

19. Zheltikova T.M., Protasov P.G., Antropova A.B., Glushkova A.M., et al. Galactomannan in polyp tissue as a diagnostic marker of fungal component in chronic rhinosinusitis with nasal polyposis. Immunologiya. 2014; 35 (2): 73–6. (in Russian)

20. Milonski J., Zielinska-Blizniewska H., Majsterek I., Przybylowska-Sygut K. Expression of POSTIN, IL-4 and IL-13 in chronic rhinosinusitis with nasal polyps. DNACellBiol. 2015; 34 (5): 342–9.

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)


JOURNALS of «GEOTAR-Media»