OBJECTIVE: Cigarette smoking exacerbates the progression of pulmonary tuberculosis (TB). The role of tertiary lymphoid structures (TLS) in chronic lung diseases has gained attention; however, it remains unclear whether smoking-exacerbated lung damage in TB is associated with TLS. This study aimed to analyze the characteristics of pulmonary TLS in smokers with TB and to explore the possible role of TLS in smoking-related lung injury in TB. METHODS: Lung tissues from 36 male patients (18 smokers and 18 non-smokers) who underwent surgical resection for pulmonary TB were included in this study. Pathological and immunohistological analyses were conducted to evaluate the quantity of TLS, and chest computed tomography (CT) was used to assess the severity of lung lesions. The correlation between the TLS quantity and TB lesion severity scores was analyzed. The immune cells and chemokines involved in TLS formation were also evaluated and compared between smokers and non-smokers. RESULTS: Smoker patients with TB had significantly higher TLS than non-smokers ( P < 0.001). The TLS quantity in both the lung parenchyma and peribronchial regions correlated with TB lesion severity on chest CT (parenchyma: r = 0.5767; peribronchial: r = 0.7373; both P < 0.001). Immunohistochemical analysis showed increased B cells, T cells, and C-X-C motif chemokine ligand 13 (CXCL13) expression in smoker patients with TB ( P < 0.001). CONCLUSION Smoker TB patients exhibited increased pulmonary TLS, which was associated with exacerbated lung lesions on chest CT, suggesting that cigarette smoking may exacerbate lung damage by promoting TLS formation.
Humans ; Male ; Tuberculosis, Pulmonary/immunology* ; Middle Aged ; Tertiary Lymphoid Structures/pathology* ; Adult ; Lung/pathology* ; Smoking/adverse effects* ; Smokers ; Aged ; Tomography, X-Ray Computed

OBJECTIVE: To study the clinical value of detecting carcinoembryonic antigen levels in pleural effusion (PCEA) and serum (SCEA) and their ratio (P/S) in the differential diagnosis of pleural effusions resulting from tuberculosis and lung cancer. METHODS: This retrospectively study was conducted among 82 patients with pleural effusion caused by pulmonary tuberculous (TB; control group) and 120 patients with pleural effusion resulting from lung cancer in our hospital between April, 2016 and March, 2018. PCEA, SCEA and P/S were compared between the two groups and among the subgroups of lung cancer patients with squamous cell carcinoma (SqCa), adenocarcinoma (ACA), small cell carcinoma (SCLC). The receiveroperating characteristic curve (ROC) analysis was used to confirm the optimal critical value to evaluate the diagnostic efficiency of different combinations of PCEA, SCEA and P/S. RESULTS: PCEA, SCEA and P/S were significantly higher in the overall cancer patients and in all the 3 subgroups of cancer patients than in the patients with TB ( < 0.05). The areas under the ROC curve of PCEA, SCEA and P/S were 0.925, 0.866 and 0.796, respectively; PCEA had the highest diagnostic value, whose diagnostic sensitivity, specificity, accurate rate, and diagnostic threshold were 83.33%, 96.34, 88.61%, and 3.26 ng/ml, respectively; SCEA had the lowest diagnostic performance; the diagnostic performance of P/S was between that of SCEA and PCEA, but its combination with SCEA greatly improved the diagnostic performance and reduced the rates of misdiagnosis and missed diagnosis. Parallel tests showed that the 3 indexes combined had significantly higher diagnostic sensitivity than each or any two of the single indexes ( < 0.05), but the diagnostic specificity did not differ significantly. The area under the ROC curve of combined detections of the 3 indexes was 0.941 for diagnosis of lung cancer-related pleural effusion, higher than those of any other combinations of the indexes. CONCLUSIONS The combined detection of PCEA, SCEA and P/S has a high sensitivity for diagnosis of lung cancer-related pleural effusion and provides important information for rapid and accurate diagnosis of suspected cases.
Carcinoembryonic Antigen ; analysis ; blood ; Case-Control Studies ; Diagnosis, Differential ; Humans ; Lung Neoplasms ; blood ; complications ; Pleural Effusion ; blood ; diagnosis ; immunology ; Pleural Effusion, Malignant ; blood ; chemistry ; diagnosis ; ROC Curve ; Retrospective Studies ; Sensitivity and Specificity ; Tuberculosis, Pulmonary ; complications

PURPOSE: Severe asthma and asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) are difficult to control and are often associated with poor clinical outcomes. However, much is not understood regarding the diagnosis and treatment of severe asthma and ACOS. To evaluate the current perceptions of severe asthma and COPD among asthma and COPD specialists, we designed an e-mail and internet-based questionnaire survey. METHODS: Subjects were selected based on clinical specialty from among the members of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Academy of Tuberculosis and Respiratory Diseases. Of 432 subjects who received an e-mail invitation to the survey, 95 subjects, including 58 allergists and 37 pulmonologists, responded and submitted their answers online. RESULTS: The specialists estimated that the percentage of severe cases among total asthma patients in their practice was 13.9%±11.0%. Asthma aggravation by stepping down treatment was the most common subtype, followed by frequent exacerbation, uncontrolled asthma despite higher treatment steps, and serious exacerbation. ACOS was estimated to account for 20.7% of asthma, 38.0% of severe asthma, and 30.1% of COPD cases. A history of smoking, persistently low forced expiratory volume in 1 second (FEV1), and low FEV1 variation were most frequently classified as the major criteria for the diagnosis of ACOS among asthma patients. Among COPD patients, the highly selected major criteria for ACOS were high FEV1 variation, positive bronchodilator response, a personal history of allergies and positive airway hyperresponsiveness. Allergists and pulmonologists showed different assessments and opinions on asthma phenotyping, percentage, and diagnostic criteria for ACOS. CONCLUSIONS: Specialists had diverse perceptions and clinical practices regarding severe asthma and ACOS patients. This heterogeneity must be considered in future studies and strategy development for severe asthma and ACOS.
Allergy and Immunology ; Asthma* ; Diagnosis ; Electronic Mail ; Forced Expiratory Volume ; Humans ; Hypersensitivity ; Lung Diseases, Obstructive ; Population Characteristics ; Pulmonary Disease, Chronic Obstructive ; Smoke ; Smoking ; Specialization* ; Tuberculosis

OBJECTIVETo detect the expression of Mycobacterium tuberculosis secreted protein Ag85B in paraffin-embedded tissues by immunohistochemistry (IHC), and to evaluate its application in the pathological diagnosis of tuberculosis.

METHODSOne hundred and five tuberculosis specimens (54 pulmonary tuberculosis, 51 lymph nodal tuberculosis) and 51 specimens of other diseases (8 lung cancer, 10 pulmonary abscess, 10 bronchiectasis, 7 lymphoma, 5 necrotizing lymphadenitis, 4 reactive hyperplasia lymphoid, and 7 sarcoidosis) were collected from January 2012 to July 2013 from Beijing Chest Hospital, Capital Medical University. One-step IHC was performed on paraffin-embedded tissues using antibody directed against Ag85B.

RESULTSIHC and Ziehl-Neelsen (ZN) acid-fast staining showed that distribution and intensity of Ag85B expression were concordant with the distribution and number of acid-fast bacilli. IHC showed significantly higher sensitivity than ZN staining (50.5%, 53/105 vs. 31.4%, 33/105; χ² = 7.877, P = 0.005). The combined sensitivity of IHC and ZN staining was 59.0%. Moreover, oil immersion was not necessary for IHC, allowing more rapid diagnosis.

CONCLUSIONIHC detection of Ag85B is a simple method with higher sensitivity than ZN staining, and demonstrated good value in the pathological diagnosis of tuberculosis.

Acyltransferases ; metabolism ; Antigens, Bacterial ; metabolism ; Biomarkers ; metabolism ; Bronchiectasis ; diagnosis ; immunology ; Humans ; Immunohistochemistry ; Lymphadenitis ; diagnosis ; immunology ; Mycobacterium tuberculosis ; immunology ; Sarcoidosis ; diagnosis ; Staining and Labeling ; Tuberculosis, Lymph Node ; diagnosis ; immunology ; Tuberculosis, Pulmonary ; diagnosis ; immunology

OBJECTIVETo verify efficacy of moxibustion apparatus on pulmonary tuberculosis (PT) and explore adjuvant treatment method for PT.

METHODSOne hundred cases of PT were randomly divided into a moxibustion group and a routine treatment group, 50 cases in each one. The regular antituberculous therapy (2HRZE/4HRE) was applied in both groups. In addition, the moxibustion apparatus was used at Bailao (EX-HN 15), Feishu (BL 13), Gaohuang (BL 43), Qihai (CV 6), Zhongfu (LU 1), Danzhong (CV 17), Guanyuan (CV 4), Zusanli (ST 36) and so on in the moxibustion group. The change of lesion area in chest radiography, degradation rate of bacte rium in the sputum, T-lymphocyte subsets and natural kill (NK) cells were observed before and after treatment in two groups.

RESULTSAfter the treatment for 3 months, there were 45 cases (90.0%) in the moxibustion group with more than 45% of focal absorption in chest radiography, which was obviously higher than 72.0% (36/50) in the routine treatment group (P < 0.01). The degradation rate of bacterium in the sputum in the moxibustion group was higher than that in the routine treatment group [82.0% (41/50) vs 60.0% (30/50), P < 0.01]. The CD3+, CD4+/CD8+ ratio of T-lymphocyte subsets and NK cells in the moxibustion group were significantly higher than those in the routine treatment group (P < 0.05, P < 0.01).

CONCLUSIONOn the basis of regular antituberculous therapy, moxibustion apparatus could significantly improve clinical effect, promote focal absorption and boost immunity, which is considered as an adjuvant treatment for PT.

Adolescent ; Adult ; Female ; Humans ; Male ; Middle Aged ; Moxibustion ; T-Lymphocyte Subsets ; immunology ; Tuberculosis, Pulmonary ; immunology ; therapy ; Young Adult

BACKGROUNDFactors of cell-mediated immunity and allergy together play their roles in the pathogenesis of pulmonary tuberculosis (PTB) and its prognosis. The purpose of this study was to investigate the computed tomographic demonstrations of HIV seropositive PTB and the relationship between its pathogenesis and CD4(+) T-lymphocyte count.

METHODSThe documented CT images of a total of 44 patients with HIV seropositive PTB, definitely diagnosed by etiological or pathological examinations, their clinical data and their CD4(+) T-lymphocyte count were retrospectively reviewed.

RESULTSThere were 15 cases of miliary tuberculosis, accounting for 34.1% of the total cases; 15 cases of nodular tuberculosis, 34.1%; 6 cases of ground-glass opacity, 13.6%; 5 cases of cord-liked fiber shadows, 11.4%; 16 cases of flaky and flocculating shadows, 36.4%; 5 cases of cavitation, 11.4%; 5 cases of tumor shadows, 11.4%; 2 cases of pleural thickening, 4.5% and 11 cases of pleural effusion, 25.0%; 1 case of calcification, 2.3%; 16 cases of lymphadenectasis, 36.4%. The foci were located around the pulmonary hilum, anterior segment of superior lobe, basal segment of inferior lobe, medial lobe and lingual lobe. CD4(+) T-lymphocyte count was closely related to the imaging demonstrations of HIV seropositive PTB.

CONCLUSIONSCT scanning can demonstrate various signs of PTB. CD4(+) T-lymphocyte level determines the variety of imaging demonstrations of HIV seropositive PTB and its prognosis.

Adolescent ; Adult ; Aged ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes ; immunology ; Child ; Female ; HIV Seropositivity ; diagnostic imaging ; immunology ; Humans ; Male ; Middle Aged ; Pleural Effusion ; Radiography ; Tuberculosis, Pulmonary ; diagnostic imaging ; immunology ; Young Adult

OBJECTIVETo detect Mycobacterium tuberculosis RD1-encoded antigens-specific, interferon-gamma (INF-gamma)-secreting T cells in pleural effusions, ascites, and cerebrospinal fluid.

METHODThe early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) peptides-specific T cells in peripheral blood mononuclear cell (MC), ascites MC, pleural effusions MC, and cerebrospinal fluid MC were detected using enzyme-linked immunospot assay (ELISPOT) for INF-gamma.

RESULTSESAT-6 or CFP-10 peptides-specific, INF-gamma-secreting T cells were detected in peripheral blood, ascites, pleural effusions, and cerebrospinal fluid, which marked the presence of tuberculosis infection. Patients with positive ELISPOT results of INF-gamma-release assay were all diagnosed as active tuberculosis. Spot forming cells in ascites and pleural effusions were much higher than those in peripheral blood (up to 6.4 and 31.9 times).

CONCLUSIONDetection of RD1-encoded antigens-specific, INF-gamma-secreting T cells in pleural effusions, ascites, and cerebrospinal fluid provides a new way to diagnose tuberculosis infection.

Antigens, Bacterial ; genetics ; Ascites ; metabolism ; Bacterial Proteins ; Humans ; Interferon-gamma ; cerebrospinal fluid ; metabolism ; Leukocytes, Mononuclear ; Mycobacterium tuberculosis ; Peptides ; Pleural Effusion ; immunology ; Recombinant Proteins ; T-Lymphocytes ; metabolism ; Tuberculosis, Pulmonary ; diagnosis

Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that infects alveolar macrophages following aerosol transmission. Lung macrophages provide a critical intracellular niche that is required for Mtb to establish infection in the human host. This parasitic relationship is made possible by the capacity of Mtb to block phagosome maturation following entry into the host macrophage, creating an environment that supports bacillary replication. Apoptosis is increasingly understood to play a role in host defense against intracellular pathogens including viruses, fungi, protozoa and bacteria. In the last 15 years an understanding of the role that macrophage apoptosis plays in TB has begun to emerge. Here we review the history and current state of the art of this topic and we offer a model of the macrophage-pathogen interaction that takes into the account the complexities of programmed cell death and the relationship between various death signaling pathways and host defense in TB.
Animals ; Apoptosis/*immunology ; Humans ; Macrophages/*cytology/*microbiology ; Mycobacterium tuberculosis/*immunology ; Tuberculosis, Pulmonary/*immunology

OBJECTIVETo establish a recombinant plasmid of CFP32 of Mycobacterium tuberculosis in E. coli, and to analyze its antigenicity.

METHODSRv0577 gene was amplified by polymerase chain reaction from genome of Mycobacterium tuberculosis, and then cloned into vector pMD18-T followed by the subclone into the expression vector pET21a. Recombinant CFP32 was expressed and purified. The antigenicity of the recombinant protein was analyzed by using Western-blot. The purified recombinant CFP32 protein was used as an antigen to screen the sera of 7 pulmonary TB patients (n = 97), as well as the other pulmonary disease patients (n = 25), and the clinically healthy controls (n = 38) by ELISA.

RESULTSRecombinant plasmid of CFP32 was established, and be expressed efficiently in E. coli BL21 (DE3). The relative molecular mass of the protein was about 300,000 by SDS-PAGE analysis. The protein purified by Ni-NTA was in a purity over 90%, which was confirmed by Western-blot analysis. ELISA analysis showed its sensitivity and specificity were 63.9% (62/97) and 96.8% (2/63) respectively.

CONCLUSIONThe recombinant expression plasmid pET21a CFP32 has been constructed and CFP32 proteins has been successfully expressed and be purified in E. coli and, ELISA analysis has identified the recombinant CFP32 as a candidate antigen for TB serodiagnosis.

Antigens, Bacterial ; blood ; Bacterial Proteins ; genetics ; immunology ; Cloning, Molecular ; Escherichia coli ; Gene Expression ; Humans ; Mycobacterium tuberculosis ; genetics ; isolation & purification ; Plasmids ; Recombinant Proteins ; Serologic Tests ; Tuberculosis, Pulmonary ; diagnosis ; microbiology

OBJECTIVETo explore the characteristics of cellular immunity in drug abusers with pulmonary tuberculosis.

METHODSSixty drug abusers with pulmonary tuberculosis and 60 non-drug abusers with pulmonary tuberculosis (control) were enrolled in this study. Three days after establishment of a definite diagnosis, peripheral blood was taken from the patients for lymphocyte subgroup (CD3(+), CD3(+)/CD4(+), CD3(+)/CD8(+) T lymphocyte subgroups and NK cells) examination by flow cytometry, and the CD4(+)/CD8+(+) ratio was calculated. The difference of cellular immunity between the drug abusers and control group was analyzed statistically.

RESULTSCD3(+) and CD3(+)/CD4(+) T lymphocytes subgroups and NK cells of the drug abusers were significantly lower than those of the control patients (P=0.037, 0.028 and 0.015), and the former patients had also significantly lower CD4(+)/CD8(+) ratio (P=0.021). The pulmonary tuberculosis types and CD3(+)/CD8(+) T lymphocyte subgroup were not significant different between the two groups (P=0.053 and 0.85).

CONCLUSIONDrug abuse might depress cellular immunity in patients with pulmonary tuberculosis, which further complicate the treatment of this disease.

Adolescent ; Adult ; CD3 Complex ; metabolism ; CD4 Antigens ; metabolism ; Female ; Humans ; Immunity, Cellular ; Killer Cells, Natural ; immunology ; Male ; Middle Aged ; Substance-Related Disorders ; complications ; immunology ; T-Lymphocytes ; immunology ; metabolism ; Tuberculosis, Pulmonary ; complications ; immunology ; prevention & control ; therapy ; Young Adult