Dynamics of Clinical, Radiological and Laboratory Parameters in Patients with an Infiltrative Form of Firstly Diagnosed Pulmonary Tuberculosis

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Maryna Kochuieva
Vasyl Kushnir
Ivan Hrek
Anton Rohozhyn
Olena Klimova
Yuliya Kalashnykova

Abstract

According to the World Health Organization, each year 10 million people are diagnosed with tuberculosis for the first time and 1.5 million people die from it. The death rate from this disease has increased in the world for the first time in more than ten years. Unfortunately, Ukraine is in the TOP-10 countries with the largest number of tuberculosis cases among population. Only in December 2021, 1,229 cases of tuberculosis were registered in Ukraine.


To date, the course of the tuberculosis process has undergone significant changes. The infiltrative form (IF) of pulmonary tuberculosis accounts for the majority of new cases. Standardized treatment (60 doses in the intensive phase and 120 doses in the continuation phase) is not always sufficient for effective recovery and requires prolongation. That is why it is necessary to study the predictors that maximally reflect the need in therapy prolongation.


The objective: to analyze the dynamics of clinical, laboratory and radiological parameters in patients with IF of newly diagnosed pulmonary tuberculosis (NDPT) under conditions of varying treatment effectiveness.


Materials and methods. 120 men of working age with IF NDPT were examined in KNP of the Kharkiv Regional Council “Regional TB Dispancer N1” during 2019–2021. Patients were divided into two groups: Group 1 (n=89) included patients with positive clinical and radiological dynamics of the tuberculosis process, and as a result of treatment clearing of Mycobacterium tuberculosis (MBT) from the sputum; Group 2 included patients (n=31) with weak positive dynamics, as a result of which IF was extended to 90 doses.


Comparison of clinical, laboratory and radiological data at the beginning and end of IF treatment in patients with different therapy efficiency was performed. The study was conducted in accordance with the requirements of good clinical practice, the Declaration of Helsinki of the World Medical Association, and was approved by the local ethic committee of the Kharkiv Medical Academy of Postgraduate Education.


Results. An analysis of the dynamics of clinical, radiological and laboratory data showed that the decrease of immuno-inflammatory indicators levels (C-reactive protein, IL-4, IL-10, circulating immune complexes; CD4/CD8 ratio) was more pronounced in the group of patients who did not need treatment prolongation. At the same time this group was also characterized by significant increase in the level of IFN-γ by the end of the IF treatment, which could indicate activation of cellular immunity together with decrease in the levels of IL-4 and IL-10 which indicated the suppression of humoral immunity. Due to the predominance of cellular immunity over humoral, macrophage activation and their phagocytic activity were accelerated, as a result of which the process of MBT elimination was much faster and more efficient in Group 1 patients.


Changes in cytokine levels were observed in patients of Group 1, who showed positive dynamics after IF treatment, but not in patients of Group 2, who demonstrated signs of cytokine dysregulation due to continuing specific inflammatory process.


Conclusions. Tuberculosis remains one of the global health problems. The general trend in the spread of tuberculosis and mortality from it throughout the world requires urgent efforts to the detection and treatment of this disease. In patients with IF pulmonary TB standard treatment was less effective in case of slow insufficient decrease in the levels of CRP, IL-10, γ-INF, and the CD4/CD8 ratio which was associated with slow cavities healing, continuing spreading of the infiltrative process. These patients needed prolonged treatment regimen.

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How to Cite
Kochuieva, M., Kushnir, V., Hrek, I., Rohozhyn, A., Klimova, O., & Kalashnykova, Y. (2021). Dynamics of Clinical, Radiological and Laboratory Parameters in Patients with an Infiltrative Form of Firstly Diagnosed Pulmonary Tuberculosis. Family Medicine, (5-6), 58–66. https://doi.org/10.30841/2307-5112.5-6.2021.253008
Section
Pulmonology
Author Biographies

Maryna Kochuieva, V. N. Karazin Kharkiv National University

Maryna M. Kochuieva,

Department of Internal Medicine No 2

Vasyl Kushnir, Kharkiv Medical Academy of Postgraduate Education, V. N. Karazin Kharkiv National University

Vasyl В. Kushnir,

Department of Phthisiology, Pulmonology and Family Medicine at the  Kharkiv Medical Academy of Postgraduate Education,

Department of General and Clinical Immunology and Allergology at the V. N. Karazin Kharkiv National University

Ivan Hrek, Kharkiv Medical Academy of Postgraduate Education, V. N. Karazin Kharkiv National University

Ivan I. Hrek,

Department of Phthisiology, Pulmonology and Family Medicine at the  Kharkiv Medical Academy of Postgraduate Education,

Department of General and Clinical Immunology and Allergology at the V. N. Karazin Kharkiv National University

Anton Rohozhyn, Kharkiv Medical Academy of Postgraduate Education, V. N. Karazin Kharkiv National University

Anton V. Rohozhyn,

Department of Phthisiology, Pulmonology and Family Medicine at the  Kharkiv Medical Academy of Postgraduate Education,

Department of General and Clinical Immunology and Allergology at the V. N. Karazin Kharkiv National University

Olena Klimova, V. T. Zaycev Institute of General and Emergency Surgery of the National Academy of Medical Sciences of Ukraine

Olena M. Klimova,

Diagnostic Laboratory with Enzyme Immunoassay and Immunofluorescence Analysis

Yuliya Kalashnykova, V. T. Zaycev Institute of General and Emergency Surgery of the National Academy of Medical Sciences of Ukraine

Yuliya V. Kalashnykova,

Diagnostic Laboratory with Enzyme Immunoassay and Immunofluorescence Analysis

References

World Health Organization (2019) global tuberculosis report 2019. World Health Organization, Geneva. – references – scientific research publishing. [cited 2021 Nov 11]. Available from: https://www.scirp.org/reference/referencespapers.aspx?referenceid=2776592

Harding E. Who global progress report on tuberculosis elimination. The Lancet Respiratory Medicine. 2020;8(1):19. doi:10.1016/s2213-2600(19)30418-7.

Kolkailah AA, Fugar S, Rey-Mendoza J, Campagnoli T, Fakhran S. Revisiting the evolution of tuberculosis therapy: Historical reflections in the modern era. Oxford Medical Case Reports. 2018;2018(9). doi:10.1093/omcr/omy055.

Mathur M, Badhan RK, Kumari S, Kaur N, Gupta S. Radiological manifestations of pulmonary tuberculosis – a comparative study between immunocompromised and immunocompetent patients. Journal of Clinical and Diagnostic Research. 2017;11(9):TC06-TC09. doi: 10.7860/JCDR/2017/28183.10535.

Raznatovskaya EN. Efficiency of antimycobacterial chemotherapy in the registered cases of chemoresistance tuberculosis of lungs in Zaporizhzhia region. Likarska sprava. 2019;(1-2):69-74. doi:10.31640/JVD.1-2.2019(10).

Platonova ІL, Sahelashvili MІ, Lapovets NE, Tkach ОА, Schurko GV. Influence of violations of non-specific and systemic cell response to the efficiency of the chemotherapy of pulmonary multidrug-resistant tuberculosis. Tuberculosis, Lung Diseases, HIV Infection. 2019;(3):14-9. doi: 10.30978/TB2019-3-14.

Chen X, Wu R, Xu J, Wang J, Gao M, Chen Y, et al. Prevalence and associated factors of psychological distress in tuberculosis patients in Northeast China: A cross-sectional study. BMC Infectious Diseases. 2021;21(1). doi:10.1186/s12879-021-06284-4.

Chai Q, Wang L, Liu CH, Ge B. New insights into the evasion of host innate immunity by mycobacterium tuberculosis. Cellular & Molecular Immunology. 2020;17(9):901-13. doi: 10.1038/s41423-020-0502-z.

Li H, Javid B. Antibodies and tuberculosis: Finally coming of age? Nature Reviews Immunology. 2018;18(9):591-6. doi:10.1038/s41577-018-0028-0.

North RJ, Jung Y-J. Immunity to tuberculosis. Annual Review of Immunology. 2004;22(1):599-623. doi:10.1146/annurev.immunol.22.012703.104635.

Berrington WR, Hawn TR. Mycobacterium tuberculosis, macrophages, and the innate immune response: Does common variation matter? Immunological Reviews. 2007;219(1):167-86. doi:10.1111/j.1600-065X.2007.00545.x.

Maglione PJ, Xu J, Chan J. B cells moderate inflammatory progression and enhance bacterial containment upon pulmonary challenge with mycobacterium tuberculosis. The Journal of Immunology. 2007;178(11):7222-34. doi:10.4049/jimmunol.178.11.7222

Liskina IV, Rekalova EM. Heterogeneity of local immune cell reactions at pulmonary tuberculosis from the positions of immunomorphology (review of literature and own research). Sciences of Europe. 2019;38-2(38):43-54.

de Martino M, Lodi L, Galli L, Chiappini E. Immune response to mycobacterium tuberculosis: A narrative review. Frontiers in Pediatrics. 2019;7. doi: 10.3389/fped.2019.00350.

Lowe DM, Demaret J, Bangani N, Nakiwala JK, Goliath R, Wilkinson KA, et al. Differential effect of viable versus necrotic neutrophils on mycobacterium tuberculosis growth and cytokine induction in whole blood. Frontiers in Immunology. 2018;9(903) doi:10.3389/fimmu.2018.00903.

Nakaz MOZ Ukrayiny vid 25.02.2020 N 530 «Pro zatverdzhennya standartiv okhorony zdorovya pry tuberkulozi» [Order of the Ministry of Health of Ukraine dated 25.02.2020 N 530 «On approval of health care standards for tuberculosis»]. Available from: https://phc.org.ua/sites/default/files/users/user90/Nakaz_MOZ_vid_25.02.2020_530_Standarty_medopomogy_pry_TB.pdf.

Oleshchenko GP, Bondarenko LA, Oleshchenko VO, Hlynenko VV, Yurchenko OP, Hnidenko KP. Sociopsychological aspects of treatment of patients with tuberculosis at the inpatient stage. Tuberculosis, Lung Diseases, HIV Infection. 2019;(4):30-5. doi:10.30978/TB2019-4-30.

Koyanagi A, Vancampfort D, Carvalho AF, DeVylder JE, Haro JM, Pizzol D, et al. Depression comorbid with tuberculosis and its impact on health status: Cross-sectional analysis of community-based data from 48 low- and middle-income countries. BMC Medicine. 2017;15(1). doi:10.1186/s12916-017-0975-5.

Karelin A. Great encyclopedia of psychological tests. Moscow: Eksmo Publ, 2007. 411 p.

Duzhiy ID, Oleshchenko GP. Comparison of the effectiveness of treatment of patients with pulmonary tuberculosis in conditions of TB system restructuring. Tuberculosis, Lung Diseases, HIV Infection. 2020;(2):37-44. doi:10.30978/TB2020-2-37.

Filatova ОV. Condition and dynamics of indicators of immune and antioxidant systems in patients with first diagnosed chemical resistant lung tuberculosis. World of Medicine and Biology. 2019;15(68):141. doi:10.26724/2079-8334-2019-2-68-141-144.

Hovardovska O, Schevchenko O, Arseniev O. The prognosis model of treatment efficiency for pulmonary tuberculosis in intensive phase of antituberculosis therapy. Science-Rise: Medical Science. 2018;7(27):27-32. doi: 10.15587/2519-4798.2018.148744.

Platonova IL, Sakhelashvili MI, Tkach ОA, Lapovec’ NE, Shtybel GD, Omelyan OV, et al. Dynamics of immunity changes in patients with multi-resistant pulmonary tuberculosis during the intensive phase of treatment. Tuberculosis, Lung Diseases, HIV Infection. 2017;3(30):73-79.

Kumar A, Chawla K, Thakur R, Joshi M, Satyamoorthy K, Bisht D. Proteomic analysis of circulating immune complexes from tuberculosis patients. Journal of Pure and Applied Microbiology. 2019;13(2):1235-44. doi:10.22207/jpam.13.2.65.

Pilaczyńska-Cemel M, Gołda R, Dąbrowska A, Przybylski G. Analysis of the level of selected parameters of inflammation, circulating immune complexes, and related indicators (neutrophil/lymphocyte, Platelet/Lymphocyte, CRP/CIC) in patients with obstructive diseases. Central European Journal of Immunology. 2019;44(3):292-8. doi:10.5114/ceji.2019.87498.

Yin Y, Qin J, Dai Y, Zeng F, Pei H, Wang J. The CD4+/CD8+ Ratio in Pulmonary Tuberculosis: Systematic and Meta-Analysis Article. Iran J Public Health. 2015;44(2):185-193.

Hilda JN, Das S, Tripathy SP, Hanna LE. Role of neutrophils in tuberculosis: A bird’s eye view. Innate Immunity. 2019;26(4):240-7. doi: 10.1177/1753425919881176.

Jyothi PM, Rajashekar M, Sumanlatha G. Role of Immuno-Endocrine interactions in tuberculosis. Donnish Journal of Infectious Diseases and Immunity. 2015;1(1):001-009.

Nancy Hilda J, Das S. Neutrophil CD64, TLR2 and TLR4 expression increases but phagocytic potential decreases during tuberculosis. Tuberculosis. 2018;111:135-42. doi: 10.1016/j.tube.2018.06.010.

Romanova OA, Martinov AV, Pogorila MS. Immunotropic effect of bis-succinyllysin in tuberculosis-infected mices with induced immunodeficiency. In The 3rd International scientific and practical conference “Modern directions of scientific research development” BioScience Publisher, Chicago, USA. 2021. p. 81.

Hmama Z, Peña-Díaz S, Joseph S, Av-Gay Y. Immunoevasion and immunosuppression of the macrophage bymycobacterium tuberculosis. Immunological Reviews. 2015;264(1):220-32. doi:10.1111/imr.12268.