Undernourished Household Contacts Are at Increased Risk of Tuberculosis (TB) Disease, but not TB Infection- a Multicenter Prospective Cohort Analysis.

Undernutrition is the leading risk factor for tuberculosis (TB) globally and in India. This multicenter prospective cohort analysis from India suggests that undernutrition is associated with increased risk of TB disease but not TB infection among household contacts of persons with TB.

Expert opinion on diagnosis and management of Severe Asthma in low and middle income countries (LMIC) with focus on India.

OBJECTIVE: In this document, 9 Indian experts have evaluated the factors specific to LMICs when it came to Severe Asthma (SA) diagnosis, evaluation, biologic selection, non-biologic treatment options, and follow-up. DATA SOURCES: A search was performed using 50 keywords, focusing on the Indian/LMICs perspective, in PubMed, Cochrane Library, and Google Scholar. The key areas of the search were focused on diagnosis, phenoendotyping, non-biological therapies, selecting a biologic, assessment of treatment response, and management of exacerbation. STUDY SELECTIONS: The initial search revealed 1826 articles, from these case reports, observational studies, cohort studies, non-English language papers, etc., were excluded and we short-listed 20 articles for each area. Five relevant articles were selected by the experts for review. RESULTS: In LMICs, SA patients may be referred to the specialist for evaluation a little late for Phenoendotyping of SA. While biologic therapy is now a standard of care, pulmonologists in LMICs may not have access to all the investigations to phenoendotype SA patients like fractional exhaled nitric oxide (FeNO), skin prick test (SPT), etc., but phenotyping of SA patients can also be done with simple blood investigations, eosinophil count and serum immunoglobulin E (IgE). Choosing a biologic in the overlapping phenotype of SA and ACO patients is also a challenge in the LMICs. CONCLUSIONS: Given the limitations of LMIC, it is important to select the right patient and explain the potential benefits of biological therapy. Non-biologic add-on therapies can be attempted in a resource-limited setting where biological therapy is not available/feasible for patients.

Pharmacokinetics of rifampicin, isoniazid & pyrazinamide during daily & intermittent dosing: A preliminary study.

Background & objectives: The National Tuberculosis (TB) Control Programme has transitioned from thrice-weekly to daily drug treatment regimens in India. This preliminary study was conceived to compare the pharmacokinetics of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) in TB patients being treated with daily and thrice weekly anti-TB treatment (ATT). Methods: This prospective observational study was undertaken in 49 newly diagnosed adult TB patients receiving either daily ATT (n=22) or thrice-weekly ATT (n=27). Plasma RMP, INH and PZA were estimated by high-performance liquid chromatography. Results: The peak concentration (Cmax) of RMP was significantly higher (RMP: 8.5 µg/ml vs. 5.5 µg/ml; P=0.003) and Cmax of INH was significantly lower (INH: 4.8 µg/ml vs. 10.9 µg/ml; P<0.001) in case of daily dosing compared to thrice-weekly ATT. Cmax of drugs and doses was significantly correlated. A higher proportion of patients had subtherapeutic RMP Cmax (8.0 µg/ml) during thrice-weekly compared to daily ATT (78% vs. 36%; P=0.004). Multiple linear regression analysis showed that Cmax of RMP was significantly influenced by the dosing rhythm, pulmonary TB and Cmax of INH and PZA by the mg/kg doses. Interpretation & conclusions: RMP concentrations were higher and INH concentrations were lower during daily ATT, suggesting that INH doses may need to be increased in case of a daily regimen. Larger studies are, however, required using higher INH doses when monitoring for adverse drug reactions and treatment outcomes.

Expert Recommendations on Optimizing the Diagnosis and Management of Gastroesophageal Reflux Disease Associated with Comorbidities in the Indian Population.

Gastroesophageal reflux disease (GERD) is among the most prevalent gastrointestinal (GI) disorders. It is known to often coexist with other chronic diseases such as asthma, chronic obstructive pulmonary disease (COPD), obesity, diabetes mellitus (DM), and hypertension. Upper endoscopy, esophageal manometry, and impedance-pH monitoring are a few invasive diagnostic options that are reserved for selected GERD patients. Symptom assessment by using questionnaires, such as the frequency scale for the symptoms of GERD (FSSG), is simple, convenient, noninvasive, and inexpensive. These questionnaires are widely used to facilitate diagnosis and appropriate treatment. Early diagnosis of GERD and timely management may improve clinical outcomes in patients. Proton pump inhibitors (PPIs) are the preferred therapy for GERD. However, evidence indicates that excessive and extended use of PPIs is linked to adverse events. An overview of the diagnosis and management of GERD, as well as an evidence-based overview of the relationship between GERD and asthma, COPD, obesity, DM, and hypertension, is presented in this review. Expert opinions and recommendations for diagnosing GERD using invasive tests and validated questionnaires have also been mentioned.

Prevalence of Airflow Obstruction as Measured by Spirometry, in Rural Southern Indian Adults.

Rural population-based estimates of airflow obstruction based on spirometry are unavailable from southern India. This study assessed the prevalence of spirometry-defined airflow obstruction in Vellore, Tamil Nadu.A cross sectional survey was done in nine villages, among adults aged ≥30 years, where previous cardiovascular surveys had been conducted (1994, 2011). Population proportional to size sampling was used to select 20 clusters, with sampling from all streets proportional to the number of households. One person randomly selected per household was interviewed for symptoms and risk factors. A respiratory therapist performed pre and post bronchodilator spirometry on all, following American Thoracic Society criteria. Airflow obstruction was defined as pre-bronchodilator Forced Expiratory Volume 1 s/Forced Vital Capacity (FEV1/FVC) < Lower Limit of Normal (LLN, derived from local prediction equations) and compared to other criteria.Of 1015 participants, 787 completed technically acceptable spirometry. The prevalence of airflow obstruction was 9.0% (95% CI: 5.8%-9.6%, 71). Fixed obstruction (post bronchodilator FEV1/FVC < LLN) was 4.6% (95% CI: 3.1%-6.1%, 36), and 4.1% (95% CI: 2.7%-5.5%, 32) using post bronchodilator FEV1/FVC < 70%. The GOLD criteria missed 56% (40) of those with airflow obstruction, of which 87.5% were females. Although 63.4% with airflow obstruction had moderate to severe disease, 82.2% were not on treatment and only 48.9% reported symptoms in the previous year.This study estimates prevalence of airflow obstruction based on spirometry in rural southern India. Despite significant impairment on spirometry, majority were undiagnosed, and half did not report symptoms.

Correlation of quantitative and qualitative parameters of high-resolution computed tomography with pulmonary function test for diagnosing and assessing the severity of obstructive pulmonary disease.

PURPOSE: The aim of the study was to evaluate the role of high-resolution computed tomography (HRCT) in the prediction of presence and severity of chronic obstructive pulmonary disease (COPD), based on the pulmonary function test (PFT), to correlate the various quantitative and qualitative indices of COPD in HRCT with PFT values, and to derive at the threshold values for various quantitative HRCT indices of COPD. MATERIAL AND METHODS: A one-year retrospective and prospective evaluation of the HRCTs of 90 cases and 38 controls was performed. Quantitative and qualitative parameters of COPD were assessed in HRCT and were correlated with PFT. RESULTS: Among the qualitative parameters, significant correlation with spirometry was found with the qualitative scoring for emphysema and presence and inhomogeneous attenuation. Among the quantitative indices, anterior junction line length, thoracic cage ratio at both aortic arch and inferior pulmonary vein level, thoracic cross-sectional area/[height]² at the aortic arch were found to have good correlation with spirometry. There was significant strong correlation of anterior junction line length and tracheal index with residual volume/total lung capacity (RV/TLC). The threshold values of chest X-ray and HRCT quantitative parameters were calculated and were found to be lower than those of the western population. CONCLUSION: HRCT has a definite role in the diagnosis of COPD and can be used to predict the severity of emphysema.

Thoracoscopic pleural biopsy improves yield of Xpert MTB/RIF for diagnosis of pleural tuberculosis.

BACKGROUND AND OBJECTIVE: Extrapulmonary tuberculosis (EPTB) accounts for ~15% of all TB patients, and TB pleural effusion is the second most common site of EPTB. The diagnosis of pleural TB is challenging due to the pauci-bacillary nature of the disease. Histopathology of thoracoscopically obtained pleural biopsy provides the highest diagnostic yield. The Xpert MTB/RIF assay (Xpert) is a PCR test that can identify both Mycobacterium tuberculosis (MTB) and rifampicin resistance. Currently, there is a lack of clarity regarding the value of Xpert on pleural tissue. We report our experience of using Xpert on thoracoscopic pleural biopsy samples. METHODS: We retrospectively reviewed the records of patients who underwent thoracoscopy in our institution over a 1-year period. Relevant clinical details; indications; and results of tests on pleural tissue and fluid, including histopathology, mycobacterial cultures and Xpert, were extracted. RESULTS: Of the 156 patients who underwent thoracoscopy, 73 (47%) had TB, 66 (42%) malignancy and 17 (11%) other conditions. Histopathology was diagnostic in all the 73 TB patients (100%). The yields of the microbiological tests against histopathology on thoracoscopic biopsy sample and pleural fluid were: pleural tissue Xpert 45%, pleural tissue culture 39%, pleural fluid culture 17% and pleural fluid Xpert 14%. Pleural tissue provided higher yields than fluid in both Xpert and culture (P < 0.05). Pleural tissue Xpert provided a higher yield than culture and substantially improved yield compared with closed pleural biopsy as we previously reported. CONCLUSION: Thoracoscopic pleural biopsy results in increased sensitivity on Xpert testing.

RePORT International: Advancing Tuberculosis Biomarker Research Through Global Collaboration.

Progress in tuberculosis clinical research is hampered by a lack of reliable biomarkers that predict progression from latent to active tuberculosis, and subsequent cure, relapse, or failure. Regional Prospective Observational Research in Tuberculosis (RePORT) International represents a consortium of regional cohorts (RePORT India, RePORT Brazil, and RePORT Indonesia) that are linked through the implementation of a Common Protocol for data and specimen collection, and are poised to address this critical research need. Each RePORT network is designed to support local, in-country tuberculosis-specific data and specimen biorepositories, and associated research. Taken together, the expected results include greater global clinical research capacity in high-burden settings, and increased local access to quality data and specimens for members of each network and their domestic and international collaborators. Additional networks are expected to be added, helping to spur tuberculosis treatment and prevention research around the world.

Tuberculin test using Indian indigenous purified-protein derivative (PPD) shows only moderate agreement with international standard PPD.

Background: In India, the prevalence of Latent TB infection (LTBI) is estimated to be around 40%. Various formulations of PPD(Purified protein derivative) are available, for diagnosis of LTBI, which may give variable responses. The commercially available PPD in India is by Arkray Healthcare (TST-Arkray). It is unclear if this product may have a similar sensitivity compared to other internationally accepted tuberculins (TST-Tubersol). Objectives: To assess the performance of the two TSTs compared to Quantiferon-Gold Plus (QFT-Plus). Methodology: A blood sample was collected for the QFT-Plus test. Both the TSTs were placed in the right and the left volar aspect of the forearms and 48 hrs later, the subjects came back to the study site for reading. Results: Among the 512 participants who were recruited, 326 subjects were healthcare professionals and 186 subjects were household contacts of patients with tuberculosis. They were tested with both TST-Tubersol and TST-Arkray, 139(27 %) participants tested positive for TST-Tubersol (≥10 mm), whereas 203 participants (40.1 %)tested positive for TST-Arkray. There was moderate agreement between the two tests with k = 0.58. Also, there was only poor agreement between both the TSTs with QFT Plus(kappa = 0.19 for Tubersol and 0.17 for Arkray). With QFT-Plus as gold standard, the sensitivity, specificity, PPV and NPV of TST-Tubersol, ast an induration cut-off of 10 mm was 46.8 %,76.3 %,31.8 % and 85.8 %. respectively and TST- Arkray; 60.6 %, 64 %, 28.5 % and 87.2 % respectively. Conclusion: The Indian TST (Arkray Diagnostics) has shown moderate agreement with the internationally accepted Tubersol. Additionally, there was poor agreement between the TSTs and QFT plus test.

Solicited Cough Sound Analysis for Tuberculosis Triage Testing: The CODA TB DREAM Challenge Dataset.

Cough is a common and commonly ignored symptom of lung disease. Cough is often perceived as difficult to quantify, frequently self-limiting, and non-specific. However, cough has a central role in the clinical detection of many lung diseases including tuberculosis (TB), which remains the leading infectious disease killer worldwide. TB screening currently relies on self-reported cough which fails to meet the World Health Organization (WHO) accuracy targets for a TB triage test. Artificial intelligence (AI) models based on cough sound have been developed for several respiratory conditions, with limited work being done in TB. To support the development of an accurate, point-of-care cough-based triage tool for TB, we have compiled a large multi-country database of cough sounds from individuals being evaluated for TB. The dataset includes more than 700,000 cough sounds from 2,143 individuals with detailed demographic, clinical and microbiologic diagnostic information. We aim to empower researchers in the development of cough sound analysis models to improve TB diagnosis, where innovative approaches are critically needed to end this long-standing pandemic.

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.

Evaluation of humoral immune deficiency in Indian patients with bilateral bronchiectasis with no apparent aetiology.

Background: Infections continue to be the leading aetiology of bronchiectasis in developing countries like India. Among non-infectious cases, the majority will have no identifiable cause despite extensive evaluation. Recently, immunodeficiency has been recognized as an important aetiology, but data on its prevalence remain rather sparse. Objectives: The objective of this study is to evaluate the prevalence of humoral immunodeficiency in a cohort of adults with bilateral bronchiectasis with no apparent aetiology. Methods: This is the single-site study from Christian Medical College (Vellore, India) of adults with HRCT-proven non-infectious bronchiectasis. Humoral immunity was assessed through quantitative analysis of immunoglobulins and IgG subclass levels. Results: Among 158 cases, immunoglobulin deficiency was found in 15%. Low IgM was the most predominate finding (7%), followed by common variable immunodeficiency (3%) and low IgA (2.5%). In addition, IgG subclass deficiency was found in 5%. In 53% of cases, no specific aetiology could be identified. Conclusion: Humoral immune deficiency is present in a significant proportion of patients with non-infectious bronchiectasis. Routine measurement of serum immunoglobulins should therefore be considered as part of the evaluation.

Rural South Indian spirometry values show wide variation compared to existing prediction equations.

Background and Objective: India, a highly heterogeneous country, has no common reference standards for predicting spirometry values, with very few recent studies from south India. This study aimed to create reference equations for rural south Indian adults, based on a population-based survey in Vellore, south India and compare it with other equations from India. Methods: The data from 583 non-smoking, asymptomatic participants (30 years and older) from a spirometry-based survey for airflow obstruction (rural Vellore, 2018), were used to develop equations for FEV1, FEV1/FVC, and FVC. The dataset was divided for development (70%) and validation (30%), by gender. Differences between observed and predicted values were assessed using the new equations and comparisons made with other equations from India. Results: Predictions with Vellore rural equations were closest to the previous south Indian equations from urban Bangalore. However, the Bangalore equations led to overestimation of FVC values in males, and of both FEV1 and FVC values in females. Using the rural Vellore equations also led to a higher percent of males being classified as having airflow obstruction, compared to the Bangalore equations which underestimated airflow obstruction in this rural population. Comparison with previously derived Indian equations from other parts of the country showed pronounced variations. Conclusions: Our study reiterates the need for representative rural and urban studies of adults from various parts of India, to obtain region specific reference equations, given the wide variations in spirometry values in "normal" individuals, due to social heterogeneities of the Indian population and resulting complexities in defining normal.

Guidelines for endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA): Joint Indian Chest Society (ICS)/Indian Association for Bronchology (IAB) recommendations.

Over the past decade, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has become an indispensable tool in the diagnostic armamentarium of the pulmonologist. As the expertise with EBUS-TBNA has evolved and several innovations have occurred, the indications for its use have expanded. However, several aspects of EBUS-TBNA are still not standardized. Hence, evidence-based guidelines are needed to optimize the diagnostic yield and safety of EBUS-TBNA. For this purpose, a working group of experts from India was constituted. A detailed and systematic search was performed to extract relevant literature pertaining to various aspects of EBUS-TBNA. The modified GRADE system was used for evaluating the level of evidence and assigning the strength of recommendations. The final recommendations were framed with the consensus of the working group after several rounds of online discussions and a two-day in-person meeting. These guidelines provide evidence-based recommendations encompassing indications of EBUS-TBNA, pre-procedure evaluation, sedation and anesthesia, technical and procedural aspects, sample processing, EBUS-TBNA in special situations, and training for EBUS-TBNA.

Anticoagulation Strategies in Non-Critically Ill Patients with Covid-19.

BACKGROUND: Optimal thromboprophylaxis for hospitalized patients with coronavirus disease 2019 (Covid-19) is uncertain. METHODS: In an open-label, adaptive platform trial, we randomly assigned hospitalized adults with Covid-19 to low-dose low-molecular-weight heparin thromboprophylaxis or intermediate-dose or low-dose plus aspirin. In response to external evidence, the aspirin intervention was discontinued and a therapeutic-dose arm added. The primary end point was death or the requirement for new organ support by day 28, analyzed with a Bayesian logistic model. Enrolment was closed as a result of operational constraints. RESULTS: Between February 2021 and March 2022, 1574 patients were randomly assigned. Among 1526 participants included in the analysis (India, n=1273; Australia and New Zealand, n=138; and Nepal, n=115), the primary outcome occurred in 35 (5.9%) of 596 in low-dose, 25 (4.2%) of 601 in intermediate-dose, 20 (7.2%) of 279 in low-dose plus aspirin, and 7 (14%) of 50 in therapeutic-dose anticoagulation. Compared with low-dose thromboprophylaxis, the median adjusted odds ratio for the primary outcome for intermediate-dose was 0.74 (95% credible interval [CrI], 0.43 to 1.27; posterior probability of effectiveness [adjusted odds ratio<1; Pr], 86%), for low-dose plus aspirin 0.88 (95% CrI, 0.47 to 1.64; Pr, 65%), and for therapeutic-dose anticoagulation 2.22 (95% CrI, 0.77 to 6.20; Pr, 7%). Overall thrombotic and bleeding rates were 0.8% and 0.4%, respectively. There were 10 serious adverse reactions related to anticoagulation strategy, of which nine were grade 1 or 2 across study interventions and one grade 4 episode of retroperitoneal hematoma in a patient receiving intermediate-dose anticoagulation. CONCLUSIONS: In hospitalized non­critically ill adults with Covid-19, compared with low-dose, there was an 86% posterior probability that intermediate-dose, 65% posterior probability that low-dose plus aspirin, and a 7% posterior probability that therapeutic-dose anticoagulation reduced the odds of death or requirement for organ support. No treatment strategy met prespecified stopping criteria before trial closure, precluding definitive conclusions. (Funded by Australian National Health and Medical Research Council or Medical Research Future Fund Investigator and Practitioner Grants and others; ClinicalTrials.gov number, NCT04483960.)

Semantic segmentation of bone structures in chest X-rays including unhealthy radiographs: A robust and accurate approach.

The chest X-ray is a widely used medical imaging technique for the diagnosis of several lung diseases. Some nodules or other pathologies present in the lungs are difficult to visualize on chest X-rays because they are obscured byoverlying boneshadows. Segmentation of bone structures and suppressing them assist medical professionals in reliable diagnosis and organ morphometry. But segmentation of bone structures is challenging due to fuzzy boundaries of organs and inconsistent shape and size of organs due to health issues, age, and gender. The existing bone segmentation methods do not report their performance on abnormal chest X-rays, where it is even more critical to segment the bones. This work presents a robust encoder-decoder network for semantic segmentation of bone structures on normal as well as abnormal chest X-rays. The novelty here lies in combining techniques from two existing networks (Deeplabv3+ and U-net) to achieve robust and superior performance. The fully connected layers of the pre-trained ResNet50 network have been replaced by an Atrous spatial pyramid pooling block for improving the quality of the embedding in the encoder module. The decoder module includes four times upsampling blocks to connect both low-level and high-level features information enabling us to retain both the edges and detail information of the objects. At each level, the up-sampled decoder features are concatenated with the encoder features at a similar level and further fine-tuned to refine the segmentation output. We construct a diverse chest X-ray dataset with ground truth binary masks of anterior ribs, posterior ribs, and clavicle bone for experimentation. The dataset includes 100 samples of chest X-rays belonging to healthy and confirmed patients of lung diseases to maintain the diversity and test the robustness of our method. We test our method using multiple standard metrics and experimental results indicate an excellent performance on both normal and abnormal chest X-rays.

A Delphi consensus statement for the management of post-COVID interstitial lung disease.

INTRODUCTION: As millions of people worldwide recover from COVID-19, a substantial proportion continue to have persistent symptoms, pulmonary function abnormalities, and radiological findings suggestive of post-COVID interstitial lung disease (ILD). To date, there is limited scientific evidence on the management of post-COVID ILD, necessitating a consensus-based approach. AREAS COVERED: A panel of experts in pulmonology and thoracic radiology was constituted. Key questions regarding the management of post-COVID ILD were identified. A search was performed on PubMed and EMBASE and updated till 1 March 2022. The relevant literature regarding the epidemiology, pathophysiology, diagnosis and treatment of post-COVID ILD was summarized. Subsequently, suggestions regarding the management of these patients were framed, and a consensus was obtained using the Delphi approach. Those suggestions which were approved by over 80% of the panelists were accepted. The final document was approved by all panel members. EXPERT OPINION: Dedicated facilities should be established for the care of patients with post-COVID ILD. Symptom screening, pulmonary function testing, and thoracic imaging have a role in the diagnosis. The pharmacologic and non-pharmacologic options for the management of post-COVID ILD are discussed. Further research into the pathophysiology and management of post-COVID ILD will improve our understanding of this condition.

Effect of home-based pulmonary rehabilitation on health-related quality of life, lung function, exercise tolerance, and dyspnea in chronic obstructive pulmonary disorder patients in a tertiary care center in South India.

CONTEXT: Home-based pulmonary rehabilitation (PR) can increase compliance in chronic obstructive pulmonary disorder (COPD). There is paucity of data on this in India. AIMS: To study the effectiveness of home-based PR on lung function, health-related quality of life, exercise tolerance and dyspnea among patients with COPD. SETTING: The Department of Pulmonary Medicine, Christian Medical College, Vellore. SUBJECTS AND METHODS: This was a quasi-experimental study which included COPD patients who found hospital-based PR impractical. Those willing for home-based PR constituted the intervention group and those unwilling, constituted the control group. Both groups received standard of care otherwise. At 6 weeks, forced expiratory volume in 1 sec (FEV1), St. George Respiratory Questionnaire (SGRQ), six-minute walk test distance (6MWD), COPD assessment test (CAT) score and modified Borg dyspnea scale were compared with their baseline values. STATISTICAL ANALYSIS: Student paired t-test. RESULTS: A total of 42 patients completed the study, 21 in each arm. The baseline characteristics were comparable. The improvement in FEV1 was 90 ml in the intervention group and 4 ml in the control group (P = 0.01). There was no significant difference in 6MWD change. SGRQ score, Borg scale and CAT score improved significantly by 10.4, 2.4, and 3.4, respectively, in the intervention group when compared to the control group (P = 0.01). CONCLUSIONS: Home-based PR effectively provides tangible benefits in FEV1, QOL, exercise tolerance and dyspnea. It should be offered to those who are unable to avail institution-based PR, especially in this era of COVID pandemic.