Relationship between nitric oxide levels and the activity of fibrogenic cytokine TGF-β1 and their role in diagnostics of the development of irreversible morphofunctional changes in bronchi of smoking adolescents

Authors

DOI:

https://doi.org/10.14739/2310-1237.2021.2.225193

Keywords:

exhaled nitric oxide (FeNO), TGF-β1, adolescent, smokers

Abstract

The aim is to study the relationship between the level of exhaled nitric oxide (FeNO) and the activity of the fibrogenic cytokine TGF-β1 in blood serum and brush biopsy samples of bronchial mucosa in order to determine their role in the development of irreversible morphological and functional changes in smoking adolescents.

Materials and methods. 20 adolescent smokers with chronic bronchitis (CB) (average age – 17.5 ± 0.2 years) were exa­mined. The comparison group consisted of 37 adolescent smokers without respiratory symptoms (average age – 15.9 ± 0.2 years) and 15 healthy adolescents, who never smoked (average age – 15.9 ± 0.4 years). In adolescent smokers the tobacco smoking status was assessed. To confirm active smoking, the nicotine metabolite cotinine was determined in urine. Instrumental methods included spirometry, chest X-ray, tracheobronchoscopy. The FeNO level was measured using a Niox Mino. TGF-β1 level was determined in the blood serum and brush biopsy samples of the bronchial mucosa.

Results. The FeNO levels were significantly lower in adolescent smokers with CB in comparison with adolescent smokers without respiratory symptoms (6.1 ± 0.3 ppb versus 8.8 ± 0.6 ppb, P < 0.05). The relationship between the FeNO levels and indicators of the tobacco smoking status has been established in patients with CB and in asymptomatic smokers. There was a significant increase in the TGF-β1 levels in the blood serum in patients with CB compared with asymptomatic smokers (478.7 ± 57.9 pg/ml versus 231.5 ± 23.5 pg/ml, P < 0.05). In smoking adolescents a relationship between a FeNO level and an increased activity of the fibrogenic cytokine TGF-β (r = -0.63; P < 0.05) has been established. In one third of patients the TGF-β1 factor was identified in the bronchial endothelium. The presence of this factor in the bronchial endothelium is a serious prognostic criterion for the risk of developing “inadequate” pneumofibrosis, which can lead to irreversible remodeling processes in the bronchi.

Conclusions. Determination of FeNO levels and TGF-β1 in the blood serum in smoking adolescents has a reliable diagnostic value for determining the risk group for the development of irreversible morphological and functional changes in the bronchi and can improve the efficiency of early diagnosis of chronic respiratory pathology.

Author Biographies

S. I. Ilchenko, Dnipro State Medical University, Ukraine

MD, PhD, DSc, Professor of the Department of Propedeutics of Pediatric Diseases

A. O. Fialkovska, Dnipro State Medical University, Ukraine

MD, PhD, Associate Professor of the Department of Propedeutics of Pediatric Diseases

K. V. Skriabina, Dnipro State Medical University, Ukraine

Assistant of the Department of Propedeutics of Pediatric Diseases

References

Antypkin, J. G., Chumachenko, N. G., Umanets, T. R., & Lapshin, V. F. (2016). Dynamika zakhvoriuvanosti ta poshyrenosti bronkholehenevoi patolohii u ditei. [The aspects of respiratory organs pathological conditions dynamics among child population]. Sovremennaya pediatriya, (2), 73-77. [in Ukrainian]. https://doi.org/10.15574/SP.2016.74.73.

Іlchenko, S. І., & Fialkovska, А. О. (2018). Diahnoz "khronichnyi bronkhit" v dytiachii pulmonolohii: "za" ta "proty". [Diagnosis "chronic bronchitis" in children's pulmonology: "pro" and "contra"]. Ukrainskyi pulmonolohichnyi zhurnal, (4), 32-34. [in Ukrainian].

Ilchenko, S. I., Fialkovskaya, A. O. (2017). Prohnozuvannia ryzyku rozvytku khronichnoho bronkhitu u pidlitkiv-kurtsiv [Predicting the risk of chronic bronchitis in teenage smokers]. Zdorov'e rebenka, (4), 29-33. [in Ukrainian]. https://doi.org/10.22141/2224-0551.12.4.2017.107624

Fischer, B. M., Voynow, J. A., Ghio, A. J. (2015). COPD: balancing oxidants and antioxidants. International journal of chronic obstructive pulmonary disease, 10, 261-276. https://doi.org/10.2147/COPD.S42414

Tsyplenkova, S. E., & Mizernitskiy, Yu. L. (2015). Sovremennye vozmozhnosti funktsional'noi diagnostiki vneshnego dykhaniya u detei [Current possibilities of functional diagnosis of external respiration in children]. Rossiyskiy Vestnik Perinatologii i Pediatrii, 60(5), 14-20. [In Russian].

Rogachikov, A. I. Shakhanov, A. V., & Uryasev, О. М. (2015). Vydykhaemyi oksid azota kak dopolnitel'nyi diagnosticheskii instrument v ambulatornoi praktike [Exhaled nitric oxide as an additional diagnostic tool in ambulatory practice]. Zemskii vrach, (1), 32-36. [In Russian].

Chuchalin, A. G. (2018). Rol' oksida azota v sovremennoi klinicheskoi praktike: nauchnyi doklad na V Vserossiiskom kongresse "Legochnaya gipertenziya" (13 dekabrya 2017 g.) [A role of nitric oxide for the modern clinical practice: A scientific report at the 5th Pan-Russian Congress on pulmonary hypertension, December 13, 2017]. Pulmonologiya, 28(4), 503-511. [in Russian]. https://doi.org/10.18093/0869-0189-2018-28-4-503-511

Turner, S. W., Chang, A. B., & Yang, I. A. (2019). Clinical utility of exhaled nitric oxide fraction in the management of asthma and COPD. Breathe, 15(4), 306-316. https://doi.org/10.1183/20734735.0268-2019

Tsyplenkova, S. E., & Mizernitsky, Yu. L. (2014). Klinicheskoe znachenie fraktsionnogo opredeleniya oksida azota v vydykhaemom vozdukhe kak instrumenta diagnostiki i otsenki effektivnosti lecheniya khronicheskikh zabolevanii organov dykhaniya u detei [Clinical significance of expired air nitric oxide fractional determination as instrument of diagnosis and therapeutic efficiency assessment of pediatric chronic respiratory diseases]. Permskii meditsinskii zhurnal, 31(2), 56-61.

Kytikova, O. Yu., Gvozdenko, Т. A., Antonyuk, M. V., & Novgorodtseva, T. P. (2019). Rol' oksida azota v patofiziologii i lechenii hronicheskoj obstruktivnoj bolezni legkih [The role of nitric oxide in pathophysiology and treatment ofchronic obstructive pulmonary disease]. Byulleten' fiziologii i patologii dykhaniya, 1(71), 105-111. [in Russian]. https://doi.org/10.12737/article_5c89ab4f8523c5.66345570

Soodaeva, S. K., Klimanov, I. A., & Nikitina, L. Yu. (2017). Nitrozivnyi i oksidativnyi stress pri zabolevaniyakh organov dykhaniya [Nitrosative and oxidative stresses in respiratory diseases]. Pulmonologiya, 27(2), 262-273. [in Russian]. https://doi.org/10.18093/0869-0189-2017-27-2-262-273

Cameli, P., Bargagli, E., Bergantini, L., d'Alessandro, M., Pieroni, M., Fontana, G. A., Sestini, P., & Refini, R. M. (2020). Extended Exhaled Nitric Oxide Analysis in Interstitial Lung Diseases: A Systematic Review. International journal of molecular sciences, 21(17), 6187. https://doi.org/10.3390/ijms21176187

Verhamme, F. M., Bracke, K. R., Joos, G. F., & Brusselle, G. G. (2015). Transforming growth factor-β superfamily in obstructive lung diseases. more suspects than TGF-β alone. American journal of respiratory cell and molecular biology, 52(6), 653-662. https://doi.org/10.1165/rcmb.2014-0282RT

Ilchenko, S., Fialkovskaia, A. (2018). Personifikovanyi pidkhid do profilaktyky tiutiunokurinnia u pidlitkiv [A personalized approach to the prevention of smoking in adolescents]. ScienceRise: Medical Science, (1), 35-38. [in Ukrainian]. https://doi.org/10.15587/2519-4798.2018.121691

Abaturov, A. E., Volosovets, A. P., & Yulish, E. I. (2013). Rol' prooksidantnoi i antioksidantnoi sistem pri vospalitel'nykh zabolevaniyakh organov dykhaniya [The role of prooxidant and antioxidant systems in inflammatory diseases of the respiratory system]. Kharkov: Planeta-Print. [in Russian].

American Thoracic Society, & European Respiratory Society (2005). ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. American journal of respiratory and critical care medicine, 171(8), 912-930. https://doi.org/10.1164/rccm.200406-710ST

Noguchi, S., Yatera, K., Wang, K. Y., Oda, K., Akata, K., Yamasaki, K., Kawanami, T., Ishimoto, H., Toyohira, Y., Shimokawa, H., Yanagihara, N., Tsutsui, M., & Mukae, H. (2014). Nitric oxide exerts protective effects against bleomycin-induced pulmonary fibrosis in mice. Respiratory research, 15(1), 92. https://doi.org/10.1186/s12931-014-0092-3

Published

2021-08-20

How to Cite

1.
Ilchenko SI, Fialkovska AO, Skriabina KV. Relationship between nitric oxide levels and the activity of fibrogenic cytokine TGF-β1 and their role in diagnostics of the development of irreversible morphofunctional changes in bronchi of smoking adolescents. Pathologia [Internet]. 2021Aug.20 [cited 2024Apr.26];18(2):189-95. Available from: http://pat.zsmu.edu.ua/article/view/225193

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Original research