Interferon gamma levels in pleural fluid for the diagnosis of tuberculosis

PURPOSE: To assess the utility of interferon gamma levels, including identification of the best cutoff for the diagnosis of tuberculosis. METHODS: We prospectively studied consecutive patients in a tertiary care, university-affiliated hospital who had pleural effusions. Interferon gamma levels were measured blindly by radioimmunoassay. The diagnosis of tuberculosis was established using prespecified standard criteria. RESULTS: Of the 595 patients with pleural effusions, 82 patients (14%) had tuberculosis. The area under the receiver operating characteristic (ROC) curve for elevated interferon gamma levels in the diagnosis of tuberculosis was 0.99 (95% confidence interval [CI]: 0.97 to 1.00). A cutoff of 3.7 IU/mL yielded a sensitivity of 0.98 (95% CI: 0.91 to 1.00) and a specificity of 0.98 (95% CI: 0.96 to 0.99). The areas under the ROC curves, and the test's sensitivity and specificity, were similar among patients of different ages and by percentage of lymphocytes in the pleural fluid. In 5 of the 28 patients with hematologic malignancies, interferon gamma levels were slightly above the cutoff; no patient with vasculitis or granulomatous diseases had levels higher than 3.7 IU/mL. The 14 immunocompromised patients and the 3 transplantation patients with tuberculosis had interferon gamma levels greater than the cutoff. CONCLUSION: Elevated pleural interferon gamma levels (>3.7 IU/mL) are very valuable in diagnosing pleural tuberculosis. Patients with pleural effusion due to hematologic neoplasms occasionally have levels slightly above the cutoff.     

Malnutrition and the severity of lung disease in adults with pulmonary tuberculosis in Malawi.

SETTING: Zomba Central Hospital, Zomba, Malawi. OBJECTIVE: To examine the relationship between malnutrition and the severity of lung disease in human immunodeficiency virus (HIV) positive and negative adults with pulmonary tuberculosis (PTB). DESIGN: Cross-sectional study. METHODS: Chest radiographs and anthropometric measurements were obtained and bioelectrical impedance analysis was conducted in sputum-positive patients with pulmonary tuberculosis. Lung disease in chest radiographs was graded as normal, minimal, moderately advanced and far advanced according to a conventional classification system. RESULTS: Among 319 adults with PTB with or without HIV co-infection, body mass index (BMI), fat mass and phase angle were independently associated with increasing severity of lung disease. Multiple logistic regression analyses showed that BMI, fat mass and phase angle were associated with increasing severity of lung disease among 236 HIV-positive adults, when adjusted for sex, age, and plasma HIV load. CONCLUSION: The severity of lung disease in adults with PTB is associated with the extent of malnutrition, as reflected by BMI and body composition studies using bioelectrical impedance analysis.     

肺结核和肺外结核患者外周血淋巴细胞亚群的检测意义探讨

目的探讨肺结核与肺外结核患者外周血淋巴细胞亚群的检测意义。方法选择72例结核病患者,其中肺结核患者41例(A组),肺外结核患者31例(B组),同期选择32例健康体检者作为对照组(C组),应用流式细胞术即(FCM)进行检测。结果三组外周血淋巴细胞亚群的表达率比较,有统计学意义(P0.05),三组在CD+3CD+4/CD+3CD+8比值比较,差异无统计学意义(P0.05)。结论肺结核与肺外结核患者行外周血淋巴细胞亚群的检测对分析免疫状态有重要意义。     

肺结核患者血清SAMD9L基因表达水平与病情严重程度及预后的关系

目的?探究无菌α基序域9样蛋白（sterile alpha motif domain containing 9-like, SAMD9L）基因在肺结核患者血清中的表达水平与患者病情严重程度及预后的关系。方法?选取2019年2月20日─2020年6月23日期间我院收治的232例肺结核患者作为研究对象,根据患者病情严重程度分为轻症组（129例）和中重症组（103例）,收集并分析2组患者的一般资料。采用实时荧光定量PCR法检测血清中SAMD9L基因表达水平,比较2组间差异。采用ROC曲线分析血清SAMD9L mRNA表达水平对肺结核患者病情严重程度及预后的评估价值。结果?中重症组血清SAMD9L mRNA表达水平显著高于轻症组（P＜0.05）;中重症组预后不良的患者中有吸烟史人数及血清SAMD9L mRNA表达水平显著高于预后良好的患者（P＜0.05）。血清SAMD9L mRNA评估肺结核患者病情严重程度的AUC为0.783（95% CI：0.724～0.834）,敏感度和特异性度分别为68.93%和77.52%,最优截断值为1.22;血清SAMD9L mRNA评估肺结核患者预后不良的AUC为0.691（95%CI：0.627～0.750）,敏感度和特异度分别为64.00%和66.88%,最优截断值为1.25。结论?肺结核患者血清SAMD9L mRNA表达水平与病情严重程度及预后密切相关,病情越严重,血清SAMD9L mRNA表达水平越高,可为肺结核的早期诊断提供参考依据。     

Increased cortisol: cortisone ratio in acute pulmonary tuberculosis

To evaluate a possible role for altered cortisol metabolism in mediating the immunoparesis associated with progressive tuberculosis (TB), we have studied the hypothalamic-pituitary-adrenal axis, and the activities of the 11beta-hydroxysteroid dehydrogenases (11-HSDs) that interconvert active cortisol and inactive cortisone. In active pulmonary tuberculosis (PTB), the ratio of cortisol/cortisone metabolites in 24-h urine showed a shift towards active cortisol (ratio, 1.19 +/- 0.1, n = 16 versus 0. 89 +/- 0.05 in cured pulmonary tuberculosis (CTB), n = 13, p < 0. 01; and 0.78 +/- 0.04 healthy volunteers (HV), n = 11, p < 0.005). Conversion of cortisone (administered as 25 mg orally) to cortisol in peripheral plasma was higher in PTB (peak 1,157 +/- 55 nM, n = 14 versus 862 +/- 50 nM in CTB, n = 10, p < 0.005, and 882 +/- 73 nM in HV, n = 10; p < 0.005). Cortisol/cortisone ratio was increased in bronchoalveolar lavage fluid in PTB (7.73 +/- 1.48, mean +/- SE, n = 13) compared with HV (4.05 +/- 0.38, n = 11, p < 0.05) but was not different in plasma (PTB, 3.25 +/- 0.68; HV, 4.01 +/- 0.92). Responses of plasma cortisol to dexamethasone, CRH stimulation, and multidose ACTH stimulation were not different. These data suggest that in pulmonary tuberculosis, central control of glucocorticoid production is normal but that peripheral metabolism, in particular in the lung, is deviated in favor of the active metabolite cortisol. This offers a possible mechanism to explain the immunoparesis observed in progressive pulmonary tuberculosis.     

Markers of disease severity in chronic obstructive pulmonary disease

BACKGROUND AND OBJECTIVES: Diagnosis and assessment of treatment effect in chronic obstructive pulmonary disease (COPD) have relied primarily on the examination of a complex set of symptoms and the use of spirometry. However, these methods require long periods of assessment to determine whether patients show clinically relevant improvements after intervention. We therefore wanted to determine how existing clinical and laboratory measures change with COPD severity and identify disease markers that can serve as better endpoints for diagnosis and assessment of COPD progression and treatment effect. METHODS: Using standard COPD keywords and terms, we searched PubMed, ISI Web of Science, and Cochrane Review databases for retrospective and prospective clinical studies published since 1966. We identified 652 studies (n = 146,255) from 1978 to September 2003 based on the availability of spirometric and demographic data, investigation of possible markers, absence of acute exacerbations and co-morbidities, and the withdrawal of standard COPD medication. Central tendencies and dispersions of subject baseline measures were collected according to study sample size, smoking status, and mild, moderate and severe COPD stages. A fixed effect meta-analysis was then conducted on each measure at various disease stages. RESULTS: Arterial oxygen tension, sputum neutrophils and IL-8, and serum TNF-alpha and C-Reactive Protein showed a trend toward separation between COPD stages. Other measures such as pack-years and St George's Respiratory Questionnaire only distinguished between disease and disease-free states. CONCLUSIONS: We observed little separation between disease stages for many measures used in COPD diagnosis and clinical trials. This demonstrates the poor sensitivity of such endpoints to define a patient's clinical status and to quantify treatment effect. Therefore, we recommend that longitudinal studies and disease modelling be the primary methods for assessing whether potential markers of disease progression can be used for COPD diagnosis and clinical trials.     

Diabetes modifies the male:female ratio in pulmonary tuberculosis.

SETTING: Socio-cultural factors have been invoked to explain the male predominance among patients with pulmonary tuberculosis, but there is no conclusive evidence of their role. OBJECTIVE: To assess male predominance in a group of diabetics with pulmonary tuberculosis compared with patients with pulmonary tuberculosis alone. DESIGN: Clinical records of in-patients with pulmonary tuberculosis and with (TBDM group, n = 202) or without (TB group, n = 226) diabetes mellitus were reviewed, and the male percentages in each of six age groups (15-29, 30-39, 40-49, 50-59, 60-69, > or = 70 years) calculated. RESULTS: In the TB group, no gender difference (51% males) was found in the first age period, followed by a male predominance thereafter (71%, 68%, 75%, 63% and 58%). The TBDM group showed a similar pattern in the first two age groups (56% and 74%), followed by a steadily decline (r(S) = -0.90, P = 0.04) in male percentage (60%, 44%, 45%, 27%), leading to a female predominance after age 50. The association of age and gender was also corroborated by logistic regression in TBDM (P = 0.02), but not in TB (P = 0.19) patients. CONCLUSIONS: Diabetes was associated with a progressive shift of male predominance in pulmonary tuberculosis. Because diabetes is a disease that affects social activities similarly in men and women, our results suggest that factors other than socio-cultural ones are also important for determining the male predominance in pulmonary tuberculosis.     

Ace gene I/D polymorphism and sarcoidosis pulmonary disease severity.

Previous studies of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in sarcoidosis have revealed both ethnic heterogeneity of I/D frequencies and controversy surrounding the association between the polymorphism and severity of disease. The objective of this study was, therefore, to clarify the role of the ACE I/D polymorphism in (1) disease susceptibility, (2) pulmonary disease severity (with particular reference to pulmonary fibrosis), and (3) pulmonary disease progression, in two distinct European sarcoidosis populations. Standard chest radiographic staging was performed on 118 UK and 56 Czech white patients with sarcoidosis at 2 yr from presentation. Pulmonary function data were analyzed, and patients were then categorized according to disease severity. A PCR-SSP assay was used to determine the ACE I/D genotype of each patient studied. The I/D allele frequencies from these patients were compared with frequencies from ethnically matched UK (n = 386) and Czech (n = 179) control subjects using a chi-square contingency table. No significant differences were seen in the distribution of the ACE I/D genotypes, allele frequencies or phenotype frequencies. Furthermore, no association was found between the ACE I/D polymorphism and pulmonary disease severity, fibrosis, and progression. We conclude that the ACE I/D polymorphism has no role in sarcoidosis susceptibility in European whites and that it is not a regulatory variant in this disease.     

Interferon-gamma and interleukin-10 gene polymorphisms in pulmonary tuberculosis

Several genes coding for different cytokines may affect host susceptibility to tuberculosis. This study investigates the relationship of the single base change polymorphic variants identified in the first intron of interferon-gamma (+874 T/A) and in the promoter region of interleukin-10 gene (-1,082 G/A), with cytokine production by peripheral blood mononuclear cells and tuberculosis susceptibility. We studied a Spanish population of 113 patients with culture-proven pulmonary tuberculosis, 207 healthy close contacts (125 tuberculin reactive and 82 tuberculin negative), and 100 healthy tuberculin-negative control subjects. Multiple logistic regression analysis showed that individuals homozygous for the interferon-gamma (+874) A allele had a 3.75-fold increased risk of developing tuberculosis (95% confidence interval, 2.26-6.23, p = 0.0017). Stimulated production of interferon-gamma by peripheral mononuclear cells from patients with genotype AA was depressed compared with that of non-AA homozygotes at the time of diagnosis and after completion of therapy. Multivariate analysis showed that the presence of an AA genotype and the absolute number of lymphocytes were the only independent predictors of interferon-gamma production. In contrast, the different rates of interleukin-10 production associated with the interleukin-10 polymorphism did not affect susceptibility to tuberculosis. Thus, a genetic defect in the production of interferon-gamma in individuals homozygous for the (+874) A allele could contribute to their increased risk of developing tuberculosis.     

Clinical value of serum copper, zinc and copper/zinc ratio in the differentiation of sarcoidosis from pulmonary tuberculosis and pulmonary carcinoma

Serum Cu, SZn and SCu/Zn ratio were studied in 14 patients with sarcoidosis, 72 patients with pulmonary tuberculosis, 15 patients with pulmonary carcinoma and 50 healthy persons as control. The results were: no significant differences were found between control group and sarcoidosis group in SCu, SZn and SCu/Zn ratio. In tuberculosis group and carcinoma group SCu increased and SZn decreased. Therefore, the SCu/Zn ratio increased significantly. The results suggested that SCu less than 1.2 ppm (means + 2 s), SZn greater than 0.8 ppm (means - 2 s) and SCu/Zn ratio less than 1.5 were helpful for the differential diagnosis of sarcoidosis from pulmonary tuberculosis and pulmonary carcinoma.     

不稳定型心绞痛患者纤维蛋白原/白蛋白比值与冠状动脉病变程度的关系

目的探讨不稳定型心绞痛(UA)患者纤维蛋白原/白蛋白比值(FAR)与冠状动脉病变程度的关系。方法回顾性分析确诊为UA患者140例,根据受试者工作特征(ROC)曲线得出FAR值预测UA患者冠状动脉中重度病变(Gensini评分20分)的最佳临界值并分为两组。比较两组患者临床资料、实验室检查结果、冠状动脉病变情况等。多因素Logistic回归分析UA中重度冠状动脉病变的相关危险因素。结果 FAR值预测UA患者冠状动脉中重度病变的最佳临界值为0.068 8,此时曲线下面积为0.705(95%CI:0.613～0.797),敏感度为74.0%,特异度为60.0%。两组患者合并糖尿病及吸烟史差异有显著性(均P0.05);高FAR组患者白细胞计数、低密度脂蛋白胆固醇、总胆固醇、空腹血糖、纤维蛋白原水平均高于低FAR组,而高密度脂蛋白胆固醇、白蛋白水平均低于低FAR组(均P0.05);随着FAR比值的增高,单支血管病变逐渐降低,双支及三支血管病变及Gensini评分逐渐增加,差异均有统计学意义(均P0.05)。Spearman相关性分析提示FAR与Gensini评分呈正相关(r=0.606,P0.001)。多因素Logistic回归显示FAR≥0.068 8(OR=7.553,P=0.016)是UA患者冠状动脉中重度病变的独立危险因素。结论 UA患者FAR值≥0.068 8对预测冠状动脉病变严重程度具有一定价值。