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Performance of T-SPOT.TB™ (TS-TB) and QuantiFERON TB Gold- In tube (QFT-IT) assays was evaluated for detection of M. tuberculosis (Mtb) infection in patients with suspected extra-pulmonary or smear-negative pulmonary tuberculosis (TB) in a low prevalence country. Twenty-one out of 35 patients were affected by active TB. Mtb culture isolation was achieved in 76% of cases. Tuberculin skin testing (TST), TS-TB, and QFT-IT yielded a positive result in 67%, 95% and 81% of cases, respectively. Agreement of interferon-γ release assays and TST was 70% (κ=0.18 for TS-TB; κ=0.46 for QFT-IT). Increased sensitivity of blood assays (>80%) improved diagnostic evaluation of difficult TB cases.

Background: Bioelectrical impedance analysis (BIA) is a valuable method for estimating fat-free mass and fat mass in patients with COPD by using specific predictive equations. In addition, raw BIA variables such as high- to low-frequency impedance ratios (IRs) and phase angle, most likely as a result of providing information on muscle quality, have been related to disease severity and mortality in patients with several diseases but never in COPD. The aim of this study was to investigate the predictive role of raw BIA variables on 2-year survival in COPD., Methods: Impedance (Z) at 5-10-50-100-250 kHz and phase angle at 50 kHz were determined in 210 patients with COPD. Three IRs were calculated: Z at 50 kHz/Z at 5 kHz (50/5 IR), Z at 100 kHz/Z at 5 kHz (100/5 IR), and Z at 250 kHz/Z at 5 kHz (250/5 IR). Demographic, respiratory, and body composition data at baseline were recorded. All-cause mortality was assessed during 2 years of follow-up., Results: After the follow-up period, all-cause mortality was 13.8%. Statistically significant differences between nonsurvivors and survivors emerged in terms of age, weight, BMI, FEV 1, inspiratory capacity, and modified Medical Research Council dyspnea score. With respect to nutritional variables, nonsurvivors had lower fat-free mass (P = .031), lower fat mass (P = .015), higher IRs (P < .001 for all the ratios), and lower phase angle (P < .001) compared with survivors. After adjustment for confounding factors, each unit increase of IRs and each unit decrease of phase angle were associated with a higher risk of death., Conclusions: IRs and phase angle, as raw BIA variables, are independent and powerful predictors of all-cause mortality in COPD and should be considered, together with inspiratory capacity and 6-min walk distance, as significant prognostic factors in the short- to middle-term., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Various criteria have been used so far for the diagnosis of malnutrition or sarcopenia in patients suffering from chronic obstructive pulmonary disease (COPD)., Objective: To determine the prevalence of malnutrition and sarcopenia in COPD, as defined by international diagnostic criteria, and determine their relationships with raw BIA variables., Methods: Two-hundred and sixty-three COPD patients (185 males and 78 females) underwent both clinical examination and respiratory, anthropometric, bioelectrical impedance analysis (BIA raw variables: phase angle and impedance ratio), handgrip strength (HGS), 4 m gait speed and biochemical measurements. Malnutrition and sarcopenia were diagnosed based on European Society for Clinical Nutrition and Metabolism (ESPEN) criteria and European Working Group on Sarcopenia in Older People (EWGSOP) criteria, respectively., Results: The overall prevalence of malnutrition and sarcopenia was 19.8% and 24.0% respectively, increasing with disease severity. The prevalence of sarcopenia was significantly higher in patients with malnutrition (71.2% vs 12.3%; p < 0.001), especially in those with systemic inflammation (cachectic patients) (85.7% vs 61.3%; p < 0.001). Malnourished patients with sarcopenia had a significant reduction in BMI, fat-free mass and HGS compared to non-sarcopenic patients. Finally, impedance ratio significantly increased and phase angle decreased in patients with severe sarcopenia and in cachectic patients., Conclusion: A relatively high prevalence of malnutrition and sarcopenia was found in COPD patients applying international standard criteria, with some discrepancy between the two diagnoses. In addition, clear-cut changes in raw BIA variables were observed in malnourished patients with systemic inflammation and sarcopenic patients., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Diagnosing pleural tuberculosis (plTB) might be difficult due to limited sensitivity of conventional microbiology tools. As M. tuberculosis (MTB)-specific T cells are recruited into pleural space in plTB, their detection may provide useful clinical information. To this aim, in addition to standard diagnostic tests, we used the QuantiFERON-TB Gold In-Tube (QFT-IT) test in blood and pleural effusion (PE) samples from 48 patients with clinical suspicion of plTB, 18 (37.5%) of whom had confirmed plTB. Four of them (22.2%) tested positive with a nucleic acid amplification test for MTB. The tuberculin skin test was positive in most confirmed plTB cases (88.9%). Positive QFT-IT tests were significantly more frequent in patients with confirmed plTB, as compared to patients with an alternative diagnosis, both in blood (77.7 vs 36.6%, p=0.006) and in PE samples (83.3% vs 46.6%, p=0.02). In addition, both blood and PE MTB-stimulated IFN-gamma levels were significantly higher in plTB patients (p=0.03 and p=0.0049 vs non-plTB, respectively). In blood samples, QFT-IT had 77.8% sensitivity and 63.3% specificity, resulting in 56.0% positive (PPV) and 82.6% negative (NPV) predictive values. On PE, QFT-IT sensitivity was 83.3% and specificity 53.3% (PPV 51.7% and NPV 84.2%). The optimal AUC-derived cut-off for MTB-stimulated pleural IFN-gamma level was 3.01 IU/mL (77.8% sensitivity, 80% specificity, PPV 68.4% and NPV 82.8%). These data suggest that QFT-IT might have a role in ruling out plTB in clinical practice.

Dendritic cells (DCs) play an unsettled role in chronic obstructive pulmonary disease (COPD) pathogenesis. Two main blood subsets, myeloid (m) and plasmacytoid (p) DCs, have been identified in humans. Phenotype and frequency of circulating DC subsets were assessed by multi-parametric flow cytometry in 28 COPD patients and 30 healthy controls (15 never smokers and 15 smokers). Proportion and absolute number of pDCs were significantly reduced in COPD patients in comparison with never smokers (p<0.001 and p<0.003) along with a marked increase of the mDC/pDC ratio (p<0.001). Analysis of peripheral lymphocyte subsets showed that the naive/memory T cell ratio was significantly reduced in COPD patients in comparison with never smokers (p<0.001). Similar perturbations in the distribution of DCs and T cells also occurred in control smokers. This study is the first report of an imbalance of blood DCs in COPD. Influence of smoking and clinical relevance of these findings are discussed., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Treatment with tumor necrosis factor-alpha (TNF-alpha) inhibitors increases the risk of tuberculosis (TB) due to reactivation of latent Mycobacterium tuberculosis infection (LTBI). Screening for LTBI is based mainly on the tuberculin skin test (TST), which has several limitations in any patient who is immunosuppressed due to drugs or autoimmune disease. T cell interferon-gamma release assays (IGRA) have been shown to be more specific than TST in immunocompetent patients and potentially represent a new approach for the management of patients taking TNF-alpha blockers. Even if there is no evidence-based literature of IGRA superiority versus TST in this specific clinical setting, some studies suggest blood assays may be helpful in clinical management of these patients, in addition to currently recommended clinical screening for risk factors for LTBI.

Tuberculosis (TB) is the most deadly infectious disease in the world. TB control relies on passive case findings and targeted treatment of latently infected individuals at high risk of disease progression. Tuberculin skin testing (TST) is conventionally used for detection of TB infection. Recently, blood assays measuring the release of IFN-gamma by TB-specific effector memory T cells have been developed to overcome TST limitations. Overall, IFN-gamma release assays are more specific than TST, more sensitive in detecting active TB and correlate better with TB exposure in immune-competent patients, at least in low-burden settings. There are three US FDA-approved assays commercially available: the ELISpot-based assay T-SPOT.TB (Oxford Immunotech, UK) and two ELISA-based formats, QuantiFERON TB Gold (QFT) and QFT-in tube (Cellestis, Australia). Recent international guidelines and consensus statements recommend the use of IFN-gamma release assays at different levels in TB management. However, conclusive evidence-based information targeting populations at high TB risk, including HIV-infected individuals, children and patient candidates for biotherapy with TNF-alpha blockers, are lacking. The aim of this review is to focus our attention on studies addressing the performance of commercial IFN-gamma release assays in clinical management of TB infection in these highly selected settings to provide a more comprehensive picture of the actual scenario and to identify areas to be investigated further.

The reactivation of latent tuberculosis (TB) is a major complication of tumor necrosis factor (TNF)-alpha inhibitors. Screening for TB infection is recommended before anti-TNF therapy is initiated; however, the use of tuberculin skin testing (TST) is controversial, due to the high rate of false-negative results in patients receiving immunosuppressive treatment. To compare the performance of two commercial interferon (IFN)-gamma release assays (IGRA), T-SPOT.TB (TS-TB) and QuantiFERON-TB Gold "In-tube" (QFT-GIT), with TST for the detection of TB infection in patients due to start anti-TNF therapy, 69 human immunodeficiency virus (HIV)-negative Italian patients (mean age: 45.2 +/- 12.6 years; male=39) were enrolled between September 2005 to August 2006. Patients affected by rheumatoid arthritis (n = 18), psoriatic arthritis (n = 26), ulcerous rectocolitis (n = 6), and Crohn's disease (n = 19) were tested simultaneously with TST, TS-TB, and QFT-GIT. Overall, 26% of patients were positive by TST, 30.4% by TS-TB, and 31.8% by QFT-GIT. Agreement with TST was similar (kappa = 0.21, p = 0.0002 and kappa = 0.26, p < 0.001, respectively). In 11 TST-negative cases, IFN-gamma release assays were positive. In addition, in seven Mantoux-positive cases with no TB risk factors, TST result agreement was achieved with at least one blood test. Indeterminate results were detected in 5.8% and 2.8% of cases, respectively, with TS-TB and with QFT-GIT (p = not significant [ns]). In conclusion, our results suggest that IGRAs may be helpful for screening purposes in patient candidates for anti-TNF therapy to confirm positive TST results and in selected cases when false-negative results are suspected. The utility of blood tests in patients with low or no TB risk remains to be assessed.