Pleural effusion guidelines from ICS and NCCP Section 1: Basic principles, laboratory tests and pleural procedures.

Pleural effusion is a common problem in our country, and most of these patients need invasive tests as they can't be evaluated by blood tests alone. The simplest of them is diagnostic pleural aspiration, and diagnostic techniques such as medical thoracoscopy are being performed more frequently than ever before. However, most physicians in India treat pleural effusion empirically, leading to delays in diagnosis, misdiagnosis and complications from wrong treatments. This situation must change, and the adoption of evidence-based protocols is urgently needed. Furthermore, the spectrum of pleural disease in India is different from that in the West, and yet Western guidelines and algorithms are used by Indian physicians. Therefore, India-specific consensus guidelines are needed. To fulfil this need, the Indian Chest Society and the National College of Chest Physicians; the premier societies for pulmonary physicians came together to create this National guideline. This document aims to provide evidence based recommendations on basic principles, initial assessment, diagnostic modalities and management of pleural effusions.

Circulating HLA-DR+CD4+ effector memory T cells resistant to CCR5 and PD-L1 mediated suppression compromise regulatory T cell function in tuberculosis.

Chronic T cell activation is a hallmark of pulmonary tuberculosis (PTB). The mechanisms underpinning this important phenomenon are however, poorly elucidated, though known to rely on control of T effector cells (Teff) by regulatory T cells (Treg). Our studies show that circulating natural Treg cells in adults with PTB preserve their suppressive potential but Teff cells from such subjects are resistant to Treg-mediated suppression. We found this to be due to expansion of an activated Teff subset identified by Human Leukocyte Antigen (HLA)-DR expression. Sensitivity to suppression was restored to control levels by depletion of this subset. Comparative transcriptome analysis of Teff cells that contain HLA-DR+ cells versus the fraction depleted of this population identified putative resistance mechanisms linked to IFNG, IL17A, IL22, PD-L1 and ß-chemokines CCL3L3, CCL4 expression. Antibody blocking experiments confirmed HLA-DR+ Teff cells, but not the fraction depleted of HLA-DR+ effectors, to be resistant to Treg suppression mediated via CCR5 and PD-L1 associated pathways. In the presence of HLA-DR+ Teff cells, activation of NFκB downstream of CCR5 and PD-L1 was perturbed. In addition, HLA-DR+ Teff cells expressed significantly higher levels of Th1/Th17 cytokines that may regulate Treg function through a reciprocal counter-balancing relationship. Taken together, our study provides novel insight on how activated HLA-DR+CD4+ T cells may contribute to disease associated inflammation by compromising Treg-mediated suppression in PTB.

Circulating Mycobacterium tuberculosis DosR latency antigen-specific, polyfunctional, regulatory IL10+ Th17 CD4 T-cells differentiate latent from active tuberculosis.

The functional heterogeneity of T cell responses to diverse antigens expressed at different stages of Mycobacterium tuberculosis (Mtb) infection, in particular early secreted versus dormancy related latency antigens expressed later, that distinguish subjects with latent (LTBI), pulmonary (PTB) or extrapulmonary (EPTB) tuberculosis remains unclear. Here we show blood central memory CD4 T-cell responses specific to Mtb dormancy related (DosR) latency, but not classical immunodominant secretory antigens, to clearly differentiate LTBI from EPTB and PTB. The polyfunctionality score integrating up to 31 DosR-specific CD4 T-cell functional profiles was significantly higher in LTBI than EPTB or PTB subjects. Further analysis of 256 DosR-specific T-cell functional profiles identified regulatory IL10 + Th17 cells (IL10+IL17A+IL17F+IL22+) to be significantly enriched in LTBI; in contrast to pro-inflammatory Th17 cells (IFNγ+IL17A+/IL10-) in the blood and lung of EPTB and PTB subjects respectively. A blood polyfunctional, Mtb DosR latency antigen specific, regulatory, central memory response is therefore a novel functional component of T-cell immunity in latent TB and potential correlate of protection.

Insulin resistance in moderate to severe obstructive sleep apnea in nondiabetics and its response to continuous positive airway pressure treatment.

BACKGROUND: The effects of nasal continuous positive airway pressure (CPAP) on insulin resistance (IR) in obstructive sleep apnea (OSA) are still under discussion especially in nondiabetics. Trials have found conflicting results in this regard. AIMS: The study was to measure IR in nondiabetic patients with moderate to severe OSA and to evaluate the effect of nasal CPAP on IR in these patients. MATERIALS AND METHODS: A total of 30 consecutively newly diagnosed patients with moderate to severe OSA was enrolled in the study. OSA was diagnosed by doing an overnight polysomnography. Plasma glucose and insulin levels were measured at baseline and after 1 month of CPAP treatment. IR was calculated by homeostasis model assessment (HOMA) method. RESULTS: Of 30 OSA patients, 21 were males, and 9 were females. The mean age of the subjects was 49.9 years, and mean body mass index (BMI) was 29.33. All 30 patients had moderate to severe OSA with a mean apnea and hypopnea index (AHI) of 80.46/h. The Epworth sleepiness score (ESS) showed a significant change with 1 month of treatment with CPAP from baseline of 13 to 9.7 (P ≤ 0.0001). There was a significant reduction in fasting insulin levels from 21.75 to 19.39 (P = 0.009). There was a small fall in fasting glucose, but it was not significant. The HOMA IR also reduced from 5.78 to 4.82 which was significant (P = 0.024) without any significant change in BMI (P = 0.916). The HOMA IR did not showed any positive correlation with different variables of OSA severity, ESS (r = 0.156) (P = 0.410), AHI (r = 0.177) (P = 0.349), and percentage of test time <90% saturation (r = -0.296) (P = 0.112). CONCLUSION: Moderate to severe OSA is associated with an increase in IR and effective treatment with CPAP rapidly improves the insulin sensitivity in nondiabetic patients with OSA without any change in BMI.