Factors of chemoresistant pulmonary tuberculosis progression in patients receiving palliative treatment

Materials and methods. 81 CRPTB patients were examined and divided into two groups: the main group consisted of 52 patients receiving palliative treatment and the control group consisted of 29 patients receiving antimycobacterial therapy by category 4 according to drug resistance. The MOS SF-36 questionnaire was used to evaluate the quality of life. Studies of serum TNF-α level were determined by enzyme-linked immunosorbent assay using immunoenzymometric reader Sirio S and a set “Bender MedSystems GmbH” (Austria), (pg/ml). Body mass index was calculated with the help of calculator New BMI (New Body Mass Index), (kg/m2). Results of this study were processed using the modern methods of analysis with the help of a personal computer and the statistical package of the licensed software program Statistica® for Windows 6.0 (StatSoft Inc., No AXXR712 D833214FAN5).

Results. CRPTB patients receiving palliative treatment have simultaneously a high activity of inflammatory specific process, predominant body mass deficit and low quality of life (both its physical and mental component). And along with this in patients receiving CRPTB treatment, activity of specific inflammatory process is 2.2 times lower, normal level of body weight predominate and quality of life is satisfactory (with satisfactory levels of both its components). Assessment of correlation relationships gave an opportunity to find out that in CRPTB patients, receiving palliative treatment, absence of the specific process antimycobacterial therapy leads to an increase in blood serum TNFα which in its turn promotes development of body mass deficit and as a consequence quality of life is decreased through decrease of all its components. In patients receiving etiotropic treatment activity of specific inflammatory process promotes decrease of body mass and quality of life but these changes are not so expressed as in case with patients receiving palliative treatment.
Conclusions. Factors of CRPTB progression in patients receiving palliative treatment include increase of TNFα level in the blood serum (≥180 pg/ml), deficit in body mass (≤18.1 kg/m 2 ), decrease in quality of life index (≤50 relative units).
Along with the problem of chemoresistant pulmonary tuberculosis (CRPTB) treatment efficacy improvement, currently there is another urgent issue in the world, including Ukraine. And this issue is the tactics of disease management in CRTB patients receiving palliative treatment [8]. It is often that in case with long standing tuberculosis patients develop resistance to many antimycobacterial drugs (AMBD) that complicates tuberculosis course and could lead to impossibility of antimycobacterial therapy (AMBT) and transition to palliative treatment of tuberculosis.
The World Health Organization (WHO) recommended assessing status of patients receiving palliative treatment by means of quality of life questionnaires (QL) which are integral indicators of person's general wellbeing [1,2].
According to literature data application of the Russian version of questionnaire Medical Outcomes Study-Short Form (MOS) SF-36, developed by J. E. Ware in 1992 [9] and translated by researchers of the Multinational Center of Quality of Life Research (MCQLR, Saint Petersburg) in 1998 [3], can be used not only for QL population-based researches of healthy persons but also for researches in case of various diseases, including tuberculosis [4][5][6]10,11].
Cachexia-related cardiac failure is one of causes of patients' death in case of CRPTB. This cardiac failure is a frequent catabolic syndrome in case of a chronic specific process. That is why it is essential to improve QL of CRPTB patients receiving palliative treatment. And this is of particular importance for patients with the end stage of disease when catabolic processes are progressive and significantly worsen their general condition.
Hong-Min F. A. N. et al. (2010) [12] have revealed a synergistic interaction between the genotype of Tumor Necrosis Factor (TNF)-α-308 GG and Body Mass Index. In addition to that data an interaction between TNF-α-238 GG genotype and the risk of pulmonary tuberculosis development has been indicated by their researches: multiple correlation coefficients for TNF-α-238 GG and TNF-α-308 GA genotypes were 1,98 (95% confidence interval (CI) 1.06-3.71) concerning the risk of pulmonary tuberculosis development. А Moges B. et al. (2012) [13] have revealed correlation between the prevalence of tuberculosis among prisoners in Ethiopia and body mass deficit (BMD).
After literature data analysis we defined that the urgent matter consists in a complex study of catabolic processes and QL of CRPTB patients receiving palliative treatment for the purpose of cachexia prevention.

Objective
To define factors of chemoresistant pulmonary tuberculosis progression in patients receiving palliative treatment by means of their QL, TNF-α levels and body mass index (BMI) complex assessment.

CRPTB patients receiving treatment in the Municipal
Institution "Zaporizhzhia Regional Hospital" and in specialized tuberculosis hospital of the State Institution "Sofia Correctional Facility No. 55" of the Ministry of Justice of Ukraine in Zaporizhzhia Region participated in the study. All patients (100%) were males. Their average age was 40.1 ± 12.1 years. The patients were divided into two groups: the main group consisted of 52 patients receiving palliative treatment and the control group consisted of 29 patients receiving AMBT by category 4 according to drug resistance in compliance with Unified Clinical Protocol of Medical Care "Tuberculosis" (Order by the Ministry of Health Care of Ukraine No. 620 of September 04, 2014) [7]. Comparison groups were comparable by age and gender. The blood serum TNF-α level was studied by means of enzyme-linked immunosorbent assay using immunoenzymometric reader Sirio S and a set "Bender MedSystems GmbH" (Austria), (pg/ml).
Body Mass Index (BMI) was calculated with a help of calculator New BMI (New Body Mass Index), (kg/m 2 ).
All patients signed patient's informed written consent for participation in this study.
Results of this study were processed using the modern methods of analysis with a help of a personal computer and the statistical package of the licensed software program Statistica ® for Windows 6.0 (StatSoft Inc., № AXXR712 D833214FAN5). Normality of quantitative indicators distribution was analyzed with a use of Shapiro-Wilks test. Descriptive statistics was presented in form of a median with interquartile range -Me [Q 25 ; Q 75 ], as far as the matter was about the parameter which differed from the normal one. Significance of differences between the compared values was defined with a help of Mann-Whitney test. All tests were two-sided. A р value <0.05 was considered statistically significant. Correlation analysis was performed with a use of Pearson correlation coefficient (r).

Results and discussion
After assessment of indexes included in this study it was determined that CRPTB patients receiving palliative treatment had reliable changes of all parameters as compared to the group of patients receiving AMBT (Table 1). So, the blood serum TNFα level was 2.2 times higher (180 (80; 620) pg/ml as compared to 80 (60; 120) pg/ml) and it indicated a high activity of inflammatory specific process in patients. Level of BMI was 14.9 % lower and its average value was 18.1 (16.8; 21.2) kg/m 2 . And this meant that body mass deficit (BMD) prevailed in patients with tuberculosis which is an unfavorable factor for cachexia development. Following the assessment of the correlation relationships between indexes of TNFα, BMI and QL in CRPTB patients depending on the type of treatment the resulting data were determined ( Table 2). CRPTB patients receiving palliative treatment had significant correlation relationships between all these indexes. So, when the blood serum TNFα level increased there was a decrease in BMI (r = -0.76; P = 0.001) and GI QL (r = -0.51; P = 0.001) through the significant reduction of its both general indexes MCS (r = -0.51; P = 0.001) and PCS (r = -0.49; P = 0.001). Decrease in BMI had a direct correlation relationship with decrease in GI QL (r = 0.50; P = 0.001) through reduction of its both general indexes MCS (r = 0.40; P = 0.004) and PCS (r = 0.49; P = 0.001). Decrease in GI QL was directly dependent on decline of MCS (r=0.89; р=0.001), as well as on decline of PCS (r = 0.92; P = 0.001).
In case with patients receiving treatment of CRPTB it was also that increase in blood serum TNFα level come against the background of BMI (r = -0.49; P = 0.01) and GI QL (r = -0.46; P = 0.01) reduction through significant lowering of both indexes MCS (r=-0.47; P = 0.01) and PCS (r = -0.40; P = 0.03). Increase of GI QL was directly dependent on increase in MCS (r = 0.94; P = 0.001), as well as on decline of PCS (r = 0.95; P = 0.001). Correlation relationships between BMI and QL indexes were not revealed.

Conclusions
1. CRPTB patients receiving palliative treatment have simultaneously a high activity of inflammatory specific process, predominant body mass deficit and low quality of life (its physical as well as mental component). And at