Pathomorphological and immunohistochemical features of the esophageal mucosa in children with asthma combined with reflux esophagitis

Authors

  • T. D. Zadorozhna State Institution “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine https://orcid.org/0000-0001-8819-8901
  • Yu. H. Antypkin State Institution “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine https://orcid.org/0000-0002-8018-4393
  • T. R. Umanets State Institution “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine https://orcid.org/0000-0001-9058-7383
  • A. A. Buratynska State Institution “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine https://orcid.org/0000-0003-3790-0419
  • T. M. Archakova State Institution “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine https://orcid.org/0000-0001-5271-5479
  • M. I. Kiurdzhiieva State Institution “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine https://orcid.org/0000-0001-8140-029X
  • S. M. Kylykhevych State Institution “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine https://orcid.org/0000-0002-9312-7785

DOI:

https://doi.org/10.14739/2310-1237.2021.2.237538

Keywords:

pathology, immunohistochemistry, children, asthma, reflux esophagitis

Abstract

The most common comorbid pathology in children with asthma is gastroesophageal reflux disease (GERD) associated with reflux esophagitis (RE), which ranges from 32 % to 80 %. Histological changes of the esophageal mucosa in RE have been described in adults and children, but there are only isolated studies that describe the morphological features of the esophageal mucosa in combined pathology, taking into account the severity of asthma.

The aim is to study the histological and immunohistochemical features of the esophageal mucosa in children with asthma combined with reflux esophagitis.

Materials and methods. In 43 children aged 6–17 years with RE and severe asthma (group 1), with mild/moderate asthma (group 2) and without asthma (group 3), mucosal biopsies from the distal and proximal esophagus were examined by histolo­gical and immunohistochemical methods. Immunohistochemical research was performed in serial paraffin sections according to standard protocols using monoclonal antibodies to Ki-67, MMP-9, VEGF, BCL-2, IgE and CD68.

Results. In children with asthma combined with RE, the structural changes of the esophageal mucosa differed depending on the severity of asthma. Severe basal epithelial hyperplasia was registered in 92.31 % of children in group 1, and its frequency was significantly different from children in groups 2 and 3. A characteristic feature of children with asthma and reflux eso­phagitis was dyschronosis, which was characterized by foci of hypo- and hypertrophy of basal layer cells (92.31 % of children in group 1 and 37.50 % of children in group 2). Severe elongation of the “papillae” was found only in 38.46 % of children in group 1. Immunohistochemical features of the esophageal mucosa of children with asthma and reflux esophagitis revealed the expression of Ki-67 antigen, IgE and a weak macrophage response (CD68), the severity of which differed from children with reflux esophagitis without asthma.

Conclusions. Morphological changes in the esophageal mucosa of children with reflux esophagitis and asthma differ from children with reflux esophagitis without asthma in the presence of severe epithelial damage, dyschronosis of changes, severe elongation of the “papillae”, pronounced cell proliferation (Ki-67) and local IgE expression.

Author Biographies

T. D. Zadorozhna, State Institution “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Academy of Medical Sciences of Ukraine”, Kyiv

MD, PhD, DSc, Professor, Corresponding Member of NAMS of Ukraine, Head of the Laboratory of Pathomorphology

Yu. H. Antypkin, State Institution “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Academy of Medical Sciences of Ukraine”, Kyiv

MD, PhD, DSc, Academician of the National Academy of Medical Sciences of Ukraine, Director, Head of the Department

T. R. Umanets, State Institution “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Academy of Medical Sciences of Ukraine”, Kyiv

MD, PhD, DSc, Chief Researcher

A. A. Buratynska, State Institution “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Academy of Medical Sciences of Ukraine”, Kyiv

PhD student, Junior Researcher

T. M. Archakova, State Institution “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Academy of Medical Sciences of Ukraine”, Kyiv

MD, PhD, Senior Researcher, Laboratory of Pathomorphology

M. I. Kiurdzhiieva, State Institution “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Academy of Medical Sciences of Ukraine”, Kyiv

Pathologist, Laboratory of Pathomorphology

S. M. Kylykhevych, State Institution “Institute of Pediatrics, Obstetrics and Gynecology named after Academician O. M. Lukyanova of National Academy of Medical Sciences of Ukraine”, Kyiv

MD, PhD, Senior Researcher, Laboratory of Pathomorphology

References

  1. Anis, K., Chandnani, A., Ahmed, M. U., & Shaukat, F. (2019). Retrospective Analysis of Eosinophilic Esophagitis in Patients with Refractory Gastroesophageal Reflux Disease. Cureus, 11(7), e5252. https://doi.org/10.7759/cureus.5252
  2. Baruah, B., Kumar, T., Das, P., Thakur, B., Sreenivas, V., Ahuja, V., Gupta, S. D., & Makharia, G. K. (2017). Prevalence of eosinophilic esophagitis in patients with gastroesophageal reflux symptoms: A cross-sectional study from a tertiary care hospital in North India. Indian journal of gastroenterology, 36(5), 353-360. https://doi.org/10.1007/s12664-017-0789-6
  3. Bongiovanni, A., Parisi, G. F., Scuderi, M. G., Licari, A., Brambilla, I., Marseglia, G. L., & Leonardi, S. (2019). Gastroesophageal reflux and respiratory diseases: does a real link exist?. Minerva pediatrica, 71(6), 515-523. https://doi.org/10.23736/S0026-4946.19.05531-2
  4. Chistiakov, D. A., Killingsworth, M. C., Myasoedova, V. A., Orekhov, A. N., & Bobryshev, Y. V. (2017). CD68/macrosialin: not just a histochemical marker. Laboratory investigation, 97(1), 4-13. https://doi.org/10.1038/labinvest.2016.116
  5. Dobronravov, V. A., Mukhametdinova, A. O., Khrabrova, M. S., Nabokow, A., Gröne, H.-J., & Kliem, V. (2018). The prognostic significance of CD3+, CD68+, CD20+ interstitial cells in patients with kidney allograft glomerulitis. Nephrology (Saint-Petersburg), 22(6), 47-55. [in Russian]. https://doi.org/10.24884/1561-6274-2018-22-6-47-55
  6. Drazdauskaitė, G., Layhadi, J. A., & Shamji, M. H. (2020). Mechanisms of Allergen Immunotherapy in Allergic Rhinitis. Current allergy and asthma reports, 21(1), 2. https://doi.org/10.1007/s11882-020-00977-7
  7. Dunbar, K. B., Agoston, A. T., Odze, R. D., Huo, X., Pham, T. H., Cipher, D. J., Castell, D. O., Genta, R. M., Souza, R. F., & Spechler, S. J. (2016). Association of Acute Gastroesophageal Reflux Disease With Esophageal Histologic Changes. JAMA, 315(19), 2104-2112. https://doi.org/10.1001/jama.2016.5657
  8. Fang, L., Sun, Q., & Roth, M. (2020). Immunologic and Non-Immunologic Mechanisms Leading to Airway Remodeling in Asthma. International journal of molecular sciences, 21(3), 757. https://doi.org/10.3390/ijms21030757
  9. Global Initiative for Asthma. (2021). 2021 GINA Report, Global Strategy for Asthma Management and Prevention. www.ginasthma.org.
  10. Godwin, B., Wilkins, B., & Muir, A. B. (2020). EoE disease monitoring: Where we are and where we are going. Annals of allergy, asthma & immunology, 124(3), 240-247. https://doi.org/10.1016/j.anai.2019.12.004
  11. Grossi, L., Ciccaglione, A. F., & Marzio, L. (2017). Esophagitis and its causes: Who is "guilty" when acid is found "not guilty"?. World journal of gastroenterology, 23(17), 3011-3016. https://doi.org/10.3748/wjg.v23.i17.3011
  12. Huang H. (2018). Matrix Metalloproteinase-9 (MMP-9) as a Cancer Biomarker and MMP-9 Biosensors: Recent Advances. Sensors (Basel, Switzerland), 18(10), 3249. https://doi.org/10.3390/s18103249
  13. Hunt, R., Armstrong, D., Katelaris, P., Afihene, M., Bane, A., Bhatia, S., Chen, M. H., Choi, M. G., Melo, A. C., Fock, K. M., Ford, A., Hongo, M., Khan, A., Lazebnik, L., Lindberg, G., Lizarzabal, M., Myint, T., Moraes-Filho, J. P., Salis, G., Lin, J. T., … Review Team: (2017). World Gastroenterology Organisation Global Guidelines: GERD Global Perspective on Gastroesophageal Reflux Disease. Journal of clinical gastroenterology, 51(6), 467-478. https://doi.org/10.1097/MCG.0000000000000854
  14. Kia, L., Pandolfino, J. E., & Kahrilas, P. J. (2016). Biomarkers of Reflux Disease. Clinical Gastroenterology and Hepatology, 14(6), 790-797. https://doi.org/10.1016/j.cgh.2015.09.014
  15. Kim J. H. (2017). Serum vascular endothelial growth factor as a marker of asthma exacerbation. The Korean journal of internal medicine, 32(2), 258-260. https://doi.org/10.3904/kjim.2017.066
  16. Liu, L. L., Zhang, Y., Zhang, X. F., & Li, F. H. (2018). Influence of rutin on the effects of neonatal cigarette smoke exposure-induced exacerbated MMP-9 expression, Th17 cytokines and NF-κB/iNOS-mediated inflammatory responses in asthmatic mice model. The Korean journal of physiology & pharmacology, 22(5), 481-491. https://doi.org/10.4196/kjpp.2018.22.5.481
  17. Martin, L. J., He, H., Collins, M. H., Abonia, J. P., Biagini Myers, J. M., Eby, M., Johansson, H., Kottyan, L. C., Khurana Hershey, G. K., & Rothenberg, M. E. (2018). Eosinophilic esophagitis (EoE) genetic susceptibility is mediated by synergistic interactions between EoE-specific and general atopic disease loci. The Journal of allergy and clinical immunology, 141(5), 1690-1698. https://doi.org/10.1016/j.jaci.2017.09.046
  18. Mastracci, L., Grillo, F., Parente, P., Unti, E., Battista, S., Spaggiari, P., Campora, M., Scaglione, G., Fassan, M., & Fiocca, R. (2020). Gastro-esophageal reflux disease and Barrett's esophagus: an overview with an histologic diagnostic approach. Pathologica, 112(3), 117-127. https://doi.org/10.32074/1591-951X-162
  19. Matviychuk, B. O., Makara, V. Z., & Stasyshyn, A. R. (2018). Histolohichne doslidzhennia slyzovoi obolonky stravokhodu pry u skladnenii hastroezofahealnii refliuksnii khvorobi [Histological examination of the esophageal mucosa in complicated gastroesophageal reflux disease]. Art of medicine, 4(8), 121-123. [in Ukrainian].
  20. Montiel-Jarquín, Á. J., Lara-Cisneros, L., López-Colombo, A., Solís-Mendoza, H. A., Palmer-Márquez, M. L., & Romero-Figueroa, M. S. (2019). Expression of metalloproteinase-9 in patients with mild and severe forms of gastroesophageal reflux disease. Expresión de la metaloproteinasa-9 en pacientes con formas leves y graves de enfermedad por reflujo gastroesofágico. Cirugia y cirujanos, 87(4), 436-442. https://doi.org/10.24875/CIRU.18000691
  21. Ministry of Health of Ukraine. (October 8, 2013). Unifikovanyi klinichnyi protokol pervynnoi, vtorynnoi (spetsializovanoi) medychnoi dopomohy. Bronkhialna astma [Unified clinical protocol of primary, secondary (specialized) medical care. Bronchial asthma (No. 868)]. https://www.dec.gov.ua/wp-content/uploads/2019/11/2013_868_ykpmd_ba_dor.pdf
  22. Gupta, S., Lodha, R., & Kabra, S. K. (2018). Asthma, GERD and Obesity: Triangle of Inflammation. Indian journal of pediatrics, 85(10), 887-892. https://doi.org/10.1007/s12098-017-2484-0
  23. Souza, R. F., Bayeh, L., Spechler, S. J., Tambar, U. K., & Bruick, R. K. (2017). A new paradigm for GERD pathogenesis. Not acid injury, but cytokine-mediated inflammation driven by HIF-2α: a potential role for targeting HIF-2α to prevent and treat reflux esophagitis. Current opinion in pharmacology, 37, 93-99. https://doi.org/10.1016/j.coph.2017.10.004
  24. Sami, S. S., & Ragunath, K. (2013). The Los Angeles Classification of Gastroesophageal Reflux Disease. Video Journal and Encyclopedia of GI Endoscopy, 1(1), 103-104. https://doi.org/10.1016/S2212-0971(13)70046-3
  25. Ministry of Health of Ukraine. (October 8, 2013). Unifikovanyi klinichnyi protokol pervynnoi, vtorynnoi (spetsializovanoi) medychnoi dopomohy "Bronkhialna astma u ditei" [Unified clinical protocol of primary, secondary (specialized) medical care "Asthma in children" (No. 868)]. Klinichna immunolohiia. Alerholohiia. Infektolohiia, (1), 36-46. [in Ukrainian].
  26. Vieth, M., Mastracci, L., Vakil, N., Dent, J., Wernersson, B., Baldycheva, I., Wissmar, J., Ruth, M., & Fiocca, R. (2016). Epithelial Thickness is a Marker of Gastroesophageal Reflux Disease. Clinical gastroenterology and hepatology, 14(11), 1544-1551.e1. https://doi.org/10.1016/j.cgh.2016.06.018
  27. Wang, C. C., Chiu, Y. C., Chen, W. L., Yang, T. W., Tsai, M. C., & Tseng, M. H. (2021). A Deep Learning Model for Classification of Endoscopic Gastroesophageal Reflux Disease. International journal of environmental research and public health, 18(5), 2428. https://doi.org/10.3390/ijerph18052428

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Published

2021-08-20

How to Cite

1.
Zadorozhna TD, Antypkin YH, Umanets TR, Buratynska AA, Archakova TM, Kiurdzhiieva MI, Kylykhevych SM. Pathomorphological and immunohistochemical features of the esophageal mucosa in children with asthma combined with reflux esophagitis. Pathologia [Internet]. 2021Aug.20 [cited 2026May16];18(2):159-66. Available from: https://pat.zsmu.edu.ua/article/view/237538

Issue

Vol. 18 No. 2 (2021)

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Original research

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