Progression Of Pulmonary Tuberculosis Research Articles

Spatial bacterial subpopulations of a human lung lobe and their potential impact on the progression of pulmonary tuberculosis

Better understanding the spatial variation in resident pulmonary bacteria can help to link the disease severity of pulmonary tuberculosis (TB) with lung bacteriomes. This study aimed to investigate bacterial compositions in subniches of a lung lobe from pulmonary TB patient with two separate visible lesions. There were no significant differences between the bacterial compositions in normal tissue and TB lesions, but the bacterial compositions of the two TB lesions differed significantly (P = 0.009). Interestingly, 52 OTUs (relative abundance >1%) that specifically inhabiting certain lung niches were observed and they were affiliated with five phyla. Specific OTUs affiliated with Firmicutes mainly inhabited normal tissues. The dominant phylum in the lung subniches was Proteobacteria, with a relative abundance between 67.03% and 99.99%. Ralstonia, Achromobacter, and Pseudomonas were the most abundant genera, collectively accounting for 34.02% of total bacterial species. A total of 667 of the 700 bacterial connections in a co-correlation network of 145 OTUs (Operational Taxonomic Unit) were positive, indicating a cooperative relationship between bacterial members. Using PICRUSt tool, we do predict bacterial MetaCyc functions responsible for lipid synthesis and heme biosynthesis across the lung lobe that are essential for generation of caseous necrosis and TB disease pathology. MetaCyc pathways responsible for the degradation of aromatic biogenic amines, sulfur oxidation, and denitrification were all related to M.tb growth status, and they were significantly enriched in the lesion with necrosis than that with inflammation. These results open a new insight for us to comprehend the spatial profile of bacteriomes in a pulmonary TB human lung lobe, and shed light on the design of future diagnosis and treatment for pulmonary TB disease.

Association Between Genetic Polymorphisms of lncRNA NEAT1 and Pulmonary Tuberculosis Risk, Clinical Manifestations in a Chinese Population.

BackgroundRecent studies have shown that abnormal expression of lncRNA NEAT1 is associated with the progression of pulmonary tuberculosis (PTB). The aim of our study was to analyze the relationship between single nucleotide polymorphisms (SNPs) of NEAT1 gene and susceptibility to PTB.MethodsFour SNPs (rs2239895, rs3741384, rs3825071, rs512715) in NEAT1 gene were genotyped in 479 patients with PTB and 476 controls by improved multiple ligase detection reaction (iMLDR) in a Chinese population.ResultsWe found no significant differences in allele and genotype frequencies of NEAT1 gene rs2239895, rs3741384, rs3825071, rs512715 between PTB patients and controls (all P > 0.05). There was no statistically significant association between genotype frequency distribution of dominant model, as well as recessive model, and genetic susceptibility to PTB patients (all P > 0.05). The TT genotype, T allele frequencies of rs3825071 were significantly increased in sputum smear-positive PTB patients when compared to sputum smear-negative PTB patients (P = 0.010, P = 0.003, respectively). Haplotype analysis shown that NEAT1 haplotype frequency was not associated with PTB susceptibility.ConclusionNEAT1 gene polymorphisms were not associated with the risk of PTB in Chinese population, and rs3825071 polymorphism might be related to sputum smear-positive in PTB patients.

Inflammation responses in patients with pulmonary tuberculosis in an intensive care unit.

Pulmonary tuberculosis caused by Mycobacterium tuberculosis remains a global problem. Inflammatory responses are the primary characteristics of patients with pulmonary tuberculosis in intensive care units (ICU). The aim of the present study was to investigate the clinical importance of inflammatory cells and factors for patients with pulmonary tuberculosis in ICU. A total of 124 patients with pulmonary tuberculosis in ICU were recruited for the present study. The inflammatory responses in patients with pulmonary tuberculosis in ICU were examined by changes in inflammatory cells and factors in the serum. The results indicated that serum levels of lymphocytes, plasma cells, granulocytes and monocytes were increased in patients with pulmonary tuberculosis in ICU compared with healthy controls. The serum levels of inflammatory factors interleukin (IL)-1, IL-6, IL-10, IL-12, and IL-4 were upregulated in patients with pulmonary tuberculosis in ICU. Lower plasma concentrations of IL-2, IL-15 and interferon-γ were detected in patients with pulmonary tuberculosis compared with healthy controls. It was demonstrated that high mobility group box-1 protein expression levels were higher in the serum of patients with pulmonary tuberculosis compared with healthy controls. Notably, an imbalance of T-helper cell (Th)1/Th2 cytokines was observed in patients with pulmonary tuberculosis. Pulmonary tuberculosis caused by M. tuberculosis also upregulated expression of matrix metalloproteinase (MMP)-1 and MMP-9 in hPMCs. In conclusion, these outcomes demonstrated that inflammatory responses and inflammatory factors are associated with the progression of pulmonary tuberculosis, suggesting that inhibition of inflammatory responses and inflammatory factors may be beneficial for the treatment of patients with pulmonary tuberculosis in ICU.

A study of various chest radiological manifestations of pulmonary tuberculosis in both human immunodeficiency virus-positive and human immunodeficiency virus-negative patients in south Indian population

Context: The chest radiography is an essential diagnostic tool in assessing the pattern and progression of pulmonary tuberculosis (PTB), which helps in taking suitable clinical decisions. Aims: The aim of this study is to bring out any specific radiologic pattern in PTB among human immunodeficiency virus (HIV) infected and noninfected and make an attempt to systemize reporting and recording radiographic findings. Settings and Design: Patients of all age groups with sputum positivity were included in the study and divided into groups based on gender, age and HIV-infected and noninfected patients. Chest radiographs were taken and assessed for findings. Materials and Methods: Data for the study were taken from sputum acid-fast bacilli positive patient's referred to the Department of Radiodiagnosis for chest X-ray and were evaluated with standard posterior-anterior chest radiograph. Statistical Analysis Used: Documented observations were compiled using SPSS-16.5 software (IBM). Univariate analysis was carried out for data interpretation. Findings/Results: Chest radiographic pattern change between HIV and noninfected cases. Lymphadenopathy was more common in patients with low CD4 count, predominantly involving the right hilar and mediastinal nodes. Large opacities with mid zone predilection, smaller opacities involving both upper zones, and bilateral lung involvement in patients with HIV coinfection was indicative of low CD4 count. Conclusions: In the present study, it was observed that major chest radiographic pattern change between patients with HIV and noninfected cases were increase in large opacities, decrease in cavity formation, increase in pleural effusion, no apical cap, and no volume loss. Lymphadenopathy was more common in patients with low CD4+ count (<200 cells/dl).

MiRNA-155 and miRNA-132 as potential diagnostic biomarkers for pulmonary tuberculosis: A preliminary study

In our study, we aimed to profile a panel microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary tuberculosis (PTB) and to illuminate the molecular mechanisms in the development of PTB. Firstly, gene expression profile of E-GEOD-49951 was downloaded from ArrayExpress database, and quantile-adjusted conditional maximum likelihood method was utilized to identify statistical difference between miRNAs of Mycobacterium tuberculosis (MTB)-infected individuals and healthy subjects. Furthermore, in order to assess the performance of our methodology, random forest (RF) classification model was utilized to identify the top 10 miRNAs with better Area Under The Curve (AUC) using 10-fold cross-validation method. Additionally, Monte Carlo Cross-Validation was repeated 50 times to explore the best miRNAs. In order to learn more about the differentially-expressed miRNAs, the target genes of differentially-expressed miRNAs were retrieved from TargetScan database and Ingenuity Pathways Analysis (IPA) was used to screen out biological pathways where target genes were involved. After normalization, a total of 478 miRNAs with higher than 0.25-fold quantile average across all samples were required. Based on the differential expression analysis, 38 differentially expressed miRNAs were identified when the significance was set as false discovery rate (FDR) < 0.01. Among the top 10 differentially expressed miRNAs, miRNA-155 obtained a highest AUC value 0.976, showing a good performance between PTB and control groups. Similarly, miRNA-449a, miRNA-212 and miRNA-132 revealed also a good performance with AUC values 0.947, 0.931 and 0.930, respectively. Moreover, miRNA-155, miRNA-449a, miRNA-29b-1* and miRNA-132 appeared in 50, 49, 49 and 48 bootstraps. Thus, miRNA-155 and miRNA-132 might be important in the progression of PTB and thereby, might present potential signatures for diagnosis of PTB.

Clinical Case of Using Intravenous Forms of Anti-Tuberculosis Drugs to Improve the Treatment Efficiency of Tuberculosis in Patients with Malabsorption Syndrome

Clinical case of progression of pulmonary tuberculosis on a background of therapy with oral antimycobacterial drugs is presented for your information. Malabsorption of oral formulations was confirmed during treatment, allowing to change the treatment strategy and to cure the patient.

Phospholipase C, proteinase and hemolytic activities of Candida spp. isolated from pulmonary tuberculosis patients

Summary Background Candida spp. are the most common opportunistic fungal pathogens in humans. Oral Candida infection has been reported to be increased with pulmonary tuberculosis patients. Extracellular hydrolytic enzymes seem to play an important role in candidal overgrowth. Objective To determine the enzymatic activity and to investigate the distribution of phospholipase C (PLC) gene among the Candida isolates from patients with pulmonary tuberculosis and non tuberculosis patients. Method The study involved a total of 62 isolates of Candida from patients with pulmonary tuberculosis (37) and non tuberculosis patients (25) of Aarupadaiveedu Medical College Hospital, Pudhucherry, India. After species identification, the isolates were analyzed for the production/activity of phospholipase C, proteinase, caseinase, lipase, gelatinase, hemolysin and hydrophobicity. In addition, the distribution of PLC gene was investigated to elucidate molecular mechanism of virulence. Results All the isolates were able to produce proteinase, caseinase and lipase. Phospholipase C, hemolytic activity and the hydrophobicity were observed as 72.9, 29.7 and 27% respectively for the isolates from the patients with pulmonary tuberculosis. The corresponding values for the isolates of non tuberculosis patients were 24, 24 and 16% respectively. Gelatinolytic activity was not observed in any of the isolates. The polymerase chain reaction (PCR) based analysis for the distribution of the PLC gene showed 94.5% for the isolates of pulmonary tuberculosis patients and 84% for the isolates of non tuberculosis patients. Appreciably, the expression of the phospholipase was observed high in Candida glabrata isolates of pulmonary tuberculosis patients over the C. glabrata strains of non tuberculosis individuals. Conclusion Candida isolates invariably showed high levels of phospholipase, proteinase, caseinase and lipase activities. Particularly, the phospholipase activity was relatively high among the isolates from pulmonary tuberculosis patients. This may be one of the virulence mechanisms of pathogenic Candida, which might get elicited during the progression of pulmonary tuberculosis. Based on the present findings, it could be envisaged that the extracellular virulence of Candida spp. might have significant functional role in the progression of secondary etiology. The PLC gene of C. glabrata was sequenced and deposited in NCBI (Accession No: EU 814636). The phylogenetic analysis of the sequences evidenced that the C. glabrata as a pathogenic strain of Candida spp.

The causes of death in patients with non-MDR pulmonary tuberculosis in our hospital

We studied the causes of death in 295 patients (mean (+/- SD) age 70.5 +/- 13.2 y.o.) with active non-MDR pulmonary tuberculosis who died in our hospital between 1991 and 1999. A hundred and twenty eight patients (43.4%, group A) died of tuberculosis, while 167 patients (56.6%) of other accompanying diseases. In 46 patients of the latter (15.6%, group B), pulmonary tuberculosis gave an unfavorable impact on their clinical course. In these patients the extent of pulmonary tuberculosis on chest roentgenograph was similar with the remaining 121 patients who also died of the accompanying diseases (41.0%, group C) and was less severe than those of the group A patients. Their nutritional conditions measured by serum albumin and choline-esterase level on admission, however, were as low as those of the group A patients and distinctly worse than those of the group C patients. Most patients of groups A and B died within 3 months after admission, while less than half patients of group C died during the same period. The age frequency distribution of the patients in groups B and C had a single peak in the age group 70 to 89, while that in group A showed two peaks, one similar peak as in groups B and C, and another peak in the age group 50 to 59. The numbers of homeless patients, of the patients with extensive cavitary lesions, and of the patients who died of ARDS (Adult Respiratory Distress Syndrome) or severe pneumothorax in group A were the most also in the age group 50 to 59, indicating that the patients' delay in admitting to hospitals was the major cause of high motality in this age group. As to detailed causes of death in group A, patients died of respiratory failure (32 cases), emaciation (28 cases), progression of pulmonary tuberculosis (20 cases), ARDS (15 cases), tuberculosis-related diseases such as pneumothorax, hemoptysis, and DIC (24 cases). In groups B and C patients died of organ failure (36 cases), infectious diseases (33 cases) and malignancy (30 cases). The total number of died patients has increased, and the proportion of cases dying of ARDS and infectious diseases has increased statistically significantly recently.

Clinical experience with ataractic therapy in tuberculous psychiatric patients.

When we learned of the efficacy of Rauwolfia serpentina products in managing psychoneurotic tension states and frank psychoses, we decided to try them on patients with both psychosis and tuberculosis. Practically, we hoped that the drugs would make the patients more cooperative in their treatment for tuberculosis. Theoretically, we thought that assuaging emotional turmoil might be a genetic attack against each of the two diseases we were trying to combat. Our approach was based on the long-standing assumption that psychogenic factors influence the development and progression of pulmonary tuberculosis. In some patients the disease may cause an outright depression, but in most it probably sets up a state of anxiety and tension. For the psychotic patient with tuberculosis, control of his agitated, manic, or schizophrenic state is even more imperative if successful antituberculosis therapy is really to be accomplished. In view of the often dramatic results reported from the use of the tranquilizing drugs, a study was set up to determine their possible value in a group of psychotic tuberculous patients. It was hoped that three things might be learned: (1) From a purely practical standpoint whether the drug makes the patients more cooperative toward accepting the treatment for tuberculosis. (2) Whether the tranquilizing drug would lessen the emotional turmoil. (3) Finally, what tranquilizing drug or what combination would be most efficacious. Although electroconvulsive therapy still has its place in the treatment of psychotic patients, there is frequently considerably hesitation about using it on active tuberculous psychotic patients, because of fear that convulsions may possibly activate or spread the disease. It was, therefore, thought that a less violent method of controlling disturbed behavior would be very advantageous.

Trauma as a factor in pulmonary tuberculosis

Summary 1. Trauma plays a definite rôle in the precipitation and progression of pulmonary tuberculosis. 2. Trauma may continue to exert its deleterious effect on an individual even after more or less complete recovery from the initial symptoms in had produced. 3. The influence of trauma causes a lowering of resistance of the body and thus predisposes for the development in tuberculosis. 4. Since tuberculosis is a disease to which all human beings are susceptible, the disease may light up at any time under the influence of trauma.