Diagnosis of respiratory epithelial clearance abnormality in patients suffering from chemo-resistant pulmonary tuberculosis with comorbidity of bronchial mucosa

Materials and methods. The respiratory epithelial clearance state diagnosis was carried out among 133 patients with CRPTB at the beginning of the intensive phase of antimycobacterial therapy during fibrobronchoscopy, provided there is a concomitant specific pathology of the mucous membrane (including its combination with non-specific endobronchitis). Average age of patients was 36.5 ± 1.1 years old. There were 89 (66.9 %) men and 44 (33.1 %) women. The tracheobronchial tree diagnostic fibrobronchoscopy with further study of the respiratory epithelial clearance condition among patients suffering from CRPTB was carried out by V. M. Khlystun at Phthisiology and Pulmonology Department of Zaporizhzhia State Medical University in CI Zaporizhzhia Regional Antituberculous Clinical Dispensary. Criteria of patients including into the research: existence of resistance of tuberculosis mycobacteria to anti-mycobacterial drugs in patients with new and repeated cases of tuberculosis, existence of pathology of the mucosa of bronchi confirmed during fiberoptic bronchoscopy. Serious associated diseases (HIV infection/AIDS, diabetes mellitus, etc.) were criteria of exception. The condition of bronchial mucosa was studied under narcotic anaesthesia by fiberoptic bronchoscopes of Olympus (Japan). Pathology of a bronchial tree was described according to classification by M. V. Shesterina, A. N. Kalyuk (1975). Results of the research are processed by modern methods of the analysis using the personal computer with the statistical package Statistica® for Windows 6.0 license program (StatSoft Inc., No. AXXR712 D833214FAN5).

Выводы. Предложенный способ диагностики нарушений мукоцилиарного транспорта у больных ХРТБ легких с сопутствующей патологией слизистой оболочки бронхов позволяет диагностировать нарушения мукоцилиарного транспорта и установить зависимость мукоцилиарной недостаточности от характера патологии слизистой оболочки бронхов. One of the important parts of the local respiratory protection system is the mucociliary system [1,2]. It provides purification of the tracheobronchial system from damaging factors and infectious agents, the action of which is the direct cause of disturbance of the bronchi drainage function -respiratory epithelial clearance (REC) [3]. As far as it is known, one of the pathogenetic mechanisms of bronchopulmonary diseases, including pulmonary tuberculosis, is precisely the violation of the bronchi drainage function [4,7].
As of today, there are sufficient methods for diagnosis of REC disorders [5,6], but there are no data on the diagnosis of REC disorders in patients suffering from chemo-resistant pulmonary tuberculosis (CRPTB) with concomitant pathology of the bronchial mucosa, which led to the search for an adequate method that would be simple and fast in use, minimally safe for a patient, and which would not cause significant material costs or specially trained personnel.
Thus, REC timely and early disorder diagnosis in patients suffering from CRPTB concomitant pathology of the bronchial mucosa is an actual problem of modern phthisiology, the solution of which will allow the timely application of rational correction, which will increase the effectiveness of this category treatment among patients.

The purpose of the research
To investigate the nature and features of REC disorders among patients suffering from CRPTB with comorbidity of the bronchi mucous membrane by using the diagnosis developed method of these disorders.

Materials and methods of research
The REC diagnosis was carried out among 133 patients with CRPTB at the beginning of the intensive phase of antimycobacterial therapy during fibrobronchoscopy (FBS), provided there is a concomitant specific pathology of the mucous membrane (including its combination with non-specific endobronchitis). Average age of patients was 36.5 ± 1.1 years old. There were 89 (66.9 %) men and 44 (33.1 %) women.
The tracheobronchial tree diagnostic FBS with further study of the REC condition among patients suffering from CRPTB was carried out by V. M. Khlystun at Phthisiology and Pulmonology Department of Zaporizhzhia State Medical University in CI "Zaporizhzhia Regional Antituberculous Clinical Dispensary".
The criteria for the patient inclusion in the research: presence of resistance of mycobacterium tuberculosis to antimycobacterial drugs, the presence of pathology of the bronchi mucous membrane, confirmed in the FBS. The exclusion criteria were severe concomitant diseases (HIV/AIDS, diabetes, etc.).
The condition of the bronchi mucous membrane was studied under the anesthetic anesthesia with the use of fibrotic bronchoscope, produced by Olympus Firm (Japan). The bronchial tree pathology was described under the classification of M. V. Shesterina, A. N. Kalyuk (1975).
The diagnosis of REC disorders in patients suffering from CRPTB with comorbidity of the bronchi mucous membrane was carried out as follows. Withdraw 0.5 ml of heparin solution in 5000 units into a syringe, whereupon 4 ml of a patient's venous blood is withdrawn into the same syringe. At the end of FBS, the patient is given 3.5-4.0 ml of this heparinized blood in each bronchus. After 10-15 minutes after the FBS, the patient begins to collect sputum into the Falcon container for every 6 hours. The presence of hemoglobin (Hb) is determined in each portion of the sputum with the help of "Azopiroma Sample-600/6" as follows. The patient's sputum from the container is poured into a 5 × 5 cm gauze wipe, after which 4 drops of the reagent are applied to the sample to be examined. When a violet-lilac color appears in 1 minute, the test is considered to be positive, and in the absence of color, the test is considered to be negative, which indicates the absence of residual hidden blood. The research is completed after a qualitative response to the presence of Hb is not determined in the 3 subsequent sputum portions. At times of withdrawal, a conclusion is made on the state of REC. That is, the time for indicator full withdrawal in the normal time is 18 hours. The time for the indicator to be withdrawn is 36-48 hours in the 1 st stage of mucociliary inefficiency (MCI), 54-66 hours in the 2 nd stage of MCI, and 72-126 hours in the 3 rd stage.
The research results were processed by modern methods of analysis on a personal computer using statistical software package Statistica ® for Windows 6.0 (StatSoft Inc., AXXR712 D833214FAN5). The distribution of quantitative characteristics normality was analyzed using the Shapiro-Wilk test. The parameters were normally distributed. The comparison of the indicators in the groups was carried out by the Student's t-criterion.

Results and discussion
The condition study in patients suffering from CRPTB with comorbidity of the bronchi mucous membrane allowed to establish that the normal REC state at the beginning of the intensive phase of antimycobacterial therapy was determined in a small number of patients, namely 7 (5.3 %). The majority number of patients were diagnosed with REC with different degrees of severity -126 (94.7 %): 68 patients (51.1 %) were diagnosed with MCI in the 1 st stage, 50 (37.6 %) persons in the 2 nd stage of MCI took the second place. The 3 rd stage of MCI was diagnosed only in 8 persons (6 %).
133 patients suffering from CRPTB were diagnosed with bronchial tuberculosis, 94 patients (70.7 %) of which had it in combination with nonspecific purulent endobronchitis. Table 1 shows the dependence of MCI on the nature of the pathology of the bronchi mucous membrane. It was found that the incidence of REC among patients with concomitant bronchial tuberculosis, combined with nonspecific purulent endobronchitis, was 2.4 times higher than in bronchial tuberculosis -related patients: 94 (70.7 %) versus 39 (29.3 %) (P < 0,05). Furthermore, patients with only bronchial tuberculosis MCI had the 1 st and 2 nd stage (53.8 % and 30.8 %, respectively), and the 3 rd stage of severity (8.5 %) was diagnosed with concomitant bronchial tuberculosis, combined with nonspecific purulent endobronchitis, with the prevalence of MCI of the 1 st stage of severity (50.0 %) and the 2 nd stage (40.2%).
Analyzing nonspecific purulent endobronchitis by localization, the obtained data indicated that the 1 st stage MCI prevailed in the limited process, in comparison with the 2 nd and 3 rd stage (70.2 % versus 24.6 % and 3.5 %, respectively; P < 0.05) and by 3.7 times than in the 1 st stage, the diffusion process (70.2 % vs 18.9 %, P < 0.05). And the 2 nd stage MCI prevailed over the 1 st and 3 rd stages (64.9 % vs 18.9 % and 16.2 %; P < 0.05) and by 2.6 times than in the limited process (64.9 % vs 24.6 %, P < 0.05). Furthermore, the 3 rd stage MCI (16.2 % vs 3.5 %) was diagnosed 4.6 times more often in the diffuse endobronchitis, although not accurately.
Thus, a reliable dependence of MCI on the nature of the pathology of the bronchial mucosa among patients suffering from CRPTB at the beginning of intensive phase of antimycobacterial therapy, which manifested itself in the fact that the connection to the nonspecific purulent endobronchitis of concomitant bronchial tuberculosis leads to an increase of MCI stage severity due to its diffuse localization.