Experts' Opinion on diagnosis and management of Severe Asthma, an Indian/Low and middle-income countries (LMIC) Perspective.

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. 5 relevant papers 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.Conclusion 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.

A multicentre, double-blind, placebo-controlled randomized trial of Mycobacterium w in critically ill patients with COVID-19 (ARMY-2).

BACKGROUND: Mycobacterium w (Mw), an immunomodulator, resulted in better clinical status in severe coronavirus infectious disease 19 (COVID-19) but no survival benefit in a previous study. Herein, we investigate whether Mw could improve clinical outcomes and survival in COVID-19. MATERIALS AND METHODS: In a multicentric, randomized, double-blind, parallel-group, placebo-controlled trial, we randomized hospitalized subjects with severe COVID-19 to receive either 0.3 mL/day of Mw intradermally or a matching placebo for three consecutive days. The primary outcome was 28-day mortality. The co-primary outcome was the distribution of clinical status assessed on a seven-point ordinal scale ranging from discharged (category 1) to death (category 7) on study days 14, 21, and 28. The key secondary outcomes were the change in sequential organ failure assessment (SOFA) score on days 7 and 14 compared to the baseline, treatment-emergent adverse events, and others. RESULTS: We included 273 subjects (136 Mw, 137 placebo). The use of Mw did not improve 28-day survival (Mw vs. placebo, 18 [13.2%] vs. 12 [8.8%], P = 0.259) or the clinical status on days 14 (odds ratio [OR], 1.33; 95% confidence intervals [CI], 0.79-2.3), 21 (OR, 1.49; 95% CI, 0.83-2.7) or 28 (OR, 1.49; 95% CI, 0.79-2.8) between the two study arms. There was no difference in the delta SOFA score or other secondary outcomes between the two groups. We observed higher injection site reactions with Mw. CONCLUSION: Mw did not reduce 28-day mortality or improve clinical status on days 14, 21 and 28 compared to placebo in patients with severe COVID-19. [Trial identifier: CTRI/2020/04/024846].

NCCP-ICS joint consensus-based clinical practice guidelines on medical thoracoscopy.

ABSTRACT: Medical Thoracoscopy (MT) is commonly performed by respiratory physicians for diagnostic as well as therapeutic purposes. The aim of the study was to provide evidence-based information regarding all aspects of MT, both as a diagnostic tool and therapeutic aid for pulmonologists across India. The consensus-based guidelines were formulated based on a multistep process using a set of 31 questions. A systematic search of published randomized controlled clinical trials, open labelled studies, case reports and guidelines from electronic databases, like PubMed, EmBase and Cochrane, was performed. The modified grade system was used (1, 2, 3 or usual practice point) to classify the quality of available evidence. Then, a multitude of factors were taken into account, such as volume of evidence, applicability and practicality for implementation to the target population and then strength of recommendation was finalized. MT helps to improve diagnosis and patient management, with reduced risk of post procedure complications. Trainees should perform at least 20 medical thoracoscopy procedures. The diagnostic yield of both rigid and semirigid techniques is comparable. Sterile-graded talc is the ideal agent for chemical pleurodesis. The consensus statement will help pulmonologists to adopt best evidence-based practices during MT for diagnostic and therapeutic purposes.

Diagnosis of extra pulmonary tuberculosis: An update on novel diagnostic approaches.

Tuberculosis (TB) remains a major global public health problem worldwide. Though Pulmonary TB (PTB) is mostly discussed, one in five cases of TB present are extrapulmonary TB (EPTB) that manifests conspicuous diagnostic and management challenges with respect to the site of infection. The diagnosis of EPTB is often delayed or even missed due to insidious clinical presentation, pauci-bacillary nature of the disease, and lack of laboratory facilities in the resource limited settings. Culture, the classical gold standard for the diagnosis of tuberculosis, suffers from increased technical and logistical constraints in EPTB cases. Other than culture, several other tests are available but their feasibility and effciacy for the detection of EPTB is still the matter of interest. We need more specific and precise test/s for the various forms of EPTB diagnosis which can easily be applied in the routine TB control program is required. A test that can contribute remarkably towards improving EPTB case detection reducing the morbidity and mortality is the utmost requirement. In this review we described the scenario of molecular and other noval methods available for laboratory diagnosis of EPTB, and also discussed the challenges linked with each diagnostic method. This review will make the readers aware of new emerging diagnostic techniques in the field of EPTB diagnosis. They can make an informed decision to choose the appropriate one according to the test availability, their clinical settings and financial considerations.

Long-Term Kinetics of SARS-CoV-2 Neutralizing and Anti-Receptor Binding Domain Antibodies among Laboratory-Confirmed COVID-19 Cases in Delhi National Capital Region, India: A Prospective, One-Year Follow-Up Study.

Background: This study was conducted with the objective of measuring the neutralizing and anti-receptor binding domain antibody levels against SARS-CoV-2 among laboratory-confirmed COVID-19 cases and exploring its long-term kinetics over a period of 1 year. Methods: One hundred laboratory-confirmed COVID-19 cases were recruited. Serum samples of the participants were collected within three months from the date of the positive COVID-19 report. The participants were prospectively followed up every three months for symptoms and the collection of blood samples for three additional rounds. The presence of anti-SARS-CoV-2 antibodies (IgA, IgG, and IgM antibodies), anti-receptor binding domain antibodies (anti-RBD), and neutralizing antibodies were measured. Findings: Median plaque reduction neutralization test (PRNT) titers showed a rising trend in the first three rounds of follow-up. The quantitative anti-receptor binding domain ELISA (QRBD) values showed a declining trend in the initial three rounds. However, both the PRNT titers and QRBD values showed significantly higher values for the fourth round of follow-up. Total antibody (WANTAI) levels showed an increasing trend in the initial three rounds (statistically significant). Interpretation: Neutralizing antibodies showed an increasing trend. The anti-receptor binding domain antibodies showed a decreasing trend. Neutralizing antibodies and anti-RBD antibodies persisted in the majority.

Association of Leukocyte Subpopulations Identified by Flow Cytometry with Outcomes of Sepsis in a Respiratory Intensive Care Unit: An Observational Study.

INTRODUCTION: The dysregulated host immune response in sepsis is orchestrated by peripheral blood leukocytes. This study explored the associations of the peripheral blood leukocyte subpopulations with early clinical deterioration and mortality in sepsis. METHODS: We performed a prospective observational single-center study enrolling adult subjects with sepsis within 48 h of hospital admission. Peripheral blood flow cytometry was performed for the patients at enrolment and after 5 days. The primary outcome was to explore the association between various leukocyte subpopulations at enrolment and early clinical deterioration [defined as an increase in the sequential organ failure assessment (SOFA) score between enrolment and day 5, or death before day 5]. Other pre-specified outcomes explored associations of leukocyte subpopulations at enrolment and on day 5 with in-hospital mortality. RESULTS: A total of 100 patients, including 47 with septic shock were enrolled. The mean (SD) age of the patients was 53.99 (14.93) years. Among them, 26 patients had early clinical deterioration, whereas 41 died during hospitalization. There was no significant association between the leukocyte subpopulations at enrolment and early clinical deterioration on day 5. On multivariate logistic regression, a reduced percentage of CD8 + CD25+ T-cells at enrolment was associated with in-hospital mortality [odds ratio (OR), 0.82 (0.70-0.97); p-value = 0.02]. A reduced lymphocyte percentage on day 5 was associated with in-hospital mortality [OR, 0.28 (0.11-0.69); p-value = 0.01]. In a post-hoc analysis, patients with "very early" deterioration within 48 h had an increased granulocyte CD64 median fluorescent intensity (MFI) [OR, 1.07 (1.01-1.14); p-value = 0.02] and a reduced granulocyte CD16 MFI [OR, 0.97 (0.95-1.00); p-value = 0.04] at enrolment. CONCLUSIONS: None of the leukocyte subpopulations showed an association with early clinical deterioration at day 5. Impaired lymphocyte activation and lymphocytopenia indicative of adaptive immune dysfunction may be associated with in-hospital mortality.

Anti-SARS-CoV-2 antibody kinetics up to 6 months of follow-up: Result from a nation-wide population-based, age stratified sero-epidemiological prospective cohort study in India.

Repeated serological testing tells about the change in the overall infection in a community. This study aimed to evaluate changes in antibody prevalence and kinetics in a closed cohort over six months in different sub-populations in India. The study included 10,000 participants from rural and urban areas in five states and measured SARS-CoV-2 antibodies in serum in three follow-up rounds. The overall seroprevalence increased from 73.9% in round one to 90.7% in round two and 92.9% in round three. Among seropositive rural participants in round one, 98.2% remained positive in round two, and this percentage remained stable in urban and tribal areas in round three. The results showed high antibody prevalence that increased over time and was not different based on area, age group, or sex. Vaccinated individuals had higher antibody prevalence, and nearly all participants had antibody positivity for up to six months.

Cell-Mediated Immunity (CMI) for SARS-CoV-2 Infection Among the General Population of North India: A Cross-Sectional Analysis From a Sub-sample of a Large Sero-Epidemiological Study.

Background Cell-mediated immunity (CMI), or specifically T-cell-mediated immunity, is proven to remain largely preserved against the variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including Omicron. The persistence of cell-mediated immune response in individuals longitudinally followed up for an extended period remains largely unelucidated. To address this, the current study was planned to study whether the effect of cell-mediated immunity persists after an extended period of convalescence or vaccination. Methods Whole blood specimens of 150 selected participants were collected and tested for Anti-SARS-CoV-2 Interferon-gamma (IFN-γ) response. Ex vivo SARS-CoV-2-specific interferon-gamma Enzyme-linked Immunospot (IFN-γ ELISpot) assay was carried out to determine the levels of virus-specific IFN-γ producing cells in individual samples. Findings Out of all the samples tested for anti-SARS-CoV-2 T-cell-mediated IFN-γ response, 78.4% of samples were positive. The median (interquartile range) spots forming units (SFU) per million levels of SARS-CoV-2-specific IFN-γ producing cells of the vaccinated and diagnosed participants was 336 (138-474) while those who were vaccinated but did not have the disease diagnosis was 18 (0-102); the difference between the groups was statistically significant. Since almost all the participants were vaccinated, a similar pattern of significance was observed when the diagnosed and the never-diagnosed participants were compared, irrespective of their vaccination status. Interpretations Cell-mediated immunity against SARS-CoV-2 persisted, irrespective of age and sex of the participant, for more than six months of previous exposure. Participants who had a history of diagnosed COVID-19 infection had better T-cell response compared to those who had never been diagnosed, in spite of being vaccinated.

MiR-326-mediated overexpression of NFIB offsets TGF-ß induced epithelial to mesenchymal transition and reverses lung fibrosis.

Idiopathic Pulmonary Fibrosis (IPF) is a progressively fatal and incurable disease characterized by the loss of alveolar structures, increased epithelial-mesenchymal transition (EMT), and aberrant tissue repair. In this study, we investigated the role of Nuclear Factor I-B (NFIB), a transcription factor critical for lung development and maturation, in IPF. Using both human lung tissue samples from patients with IPF, and a mouse model of lung fibrosis induced by bleomycin, we showed that there was a significant reduction of NFIB both in the lungs of patients and mice with IPF. Furthermore, our in vitro experiments using cultured human lung cells demonstrated that the loss of NFIB was associated with the induction of EMT by transforming growth factor beta (TGF-ß). Knockdown of NFIB promoted EMT, while overexpression of NFIB suppressed EMT and attenuated the severity of bleomycin-induced lung fibrosis in mice. Mechanistically, we identified post-translational regulation of NFIB by miR-326, a miRNA with anti-fibrotic effects that is diminished in IPF. Specifically, we showed that miR-326 stabilized and increased the expression of NFIB through its 3'UTR target sites for Human antigen R (HuR). Moreover, treatment of mice with either NFIB plasmid or miR-326 reversed airway collagen deposition and fibrosis. In conclusion, our study emphasizes the critical role of NFIB in lung development and maturation, and its reduction in IPF leading to EMT and loss of alveolar structures. Our study highlights the potential of miR-326 as a therapeutic intervention for IPF. The schema shows the role of NFIB in maintaining the normal epithelial cell characteristics in the lungs and how its reduction leads to a shift towards mesenchymal cell-like features and pulmonary fibrosis. A In normal lungs, NFIB is expressed abundantly in the epithelial cells, which helps in maintaining their shape, cell polarity and adhesion molecules. However, when the lungs are exposed to factors that induce pulmonary fibrosis, such as bleomycin, or TGF-ß, the epithelial cells undergo epithelial to mesenchymal transition (EMT), which leads to a decrease in NFIB. B The mesenchymal cells that arise from EMT appear as spindle-shaped with loss of cell junctions, increased cell migration, loss of polarity and expression of markers associated with mesenchymal cells/fibroblasts. C We designed a therapeutic approach that involves exogenous administration of NFIB in the form of overexpression plasmid or microRNA-326. This therapeutic approach decreases the mesenchymal cell phenotype and restores the epithelial cell phenotype, thus preventing the development or progression of pulmonary fibrosis.

Transoesophageal bronchoscopic ultrasound-guided fine-needle aspiration (EUS-B-FNA) for left adrenal gland (LAG) sampling: A report of three cases with a review of the literature.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a standard-of-care modality for evaluating mediastinal lymph nodes and masses. The EBUS bronchoscope may also be introduced through the oesophageal route to perform sampling of accessible lesions, a technique described as transoesophageal bronchoscopic ultrasound-guided fine-needle aspiration (EUS-B-FNA). Because of the central oesophageal approach, EUS-B-FNA provides easy access to the left para-tracheal, subcarinal and para-oesophageal lymph nodes. In addition, the left adrenal gland (LAG) can also be imaged and sampled during the EUS-B-FNA procedure. In patients with suspected lung cancer, accurate staging is essential. Adrenal metastasis is relatively common and may often be a solitary metastatic site. We describe three cases where EUS-B-FNA was performed to safely sample the enlarged LAG in suspected lung cancer. We also review the literature on the performance characteristics of EUS-B-FNA for LAG aspiration.

Effect of Metformin on Plasma Exposure of Rifampicin, Isoniazid, and Pyrazinamide in Patients on Treatment for Pulmonary Tuberculosis.

BACKGROUND: To evaluate the effect of metformin on the plasma levels of rifampicin, isoniazid, and pyrazinamide in patients with drug-sensitive pulmonary tuberculosis being treated with first-line antituberculosis treatment (ATT) and to assess the influence of gene polymorphisms on the metabolic pathway of metformin and plasma levels of antitubercular drugs. METHODS: Nondiabetic adults aged 18-60 years with pulmonary tuberculosis were randomized to either the standard ATT (ATT group) or ATT plus metformin (METRIF group) groups in a phase IIB clinical trial. An intensive pharmacokinetic study with blood collection at 0 hour (predosing), followed by 1, 2, 4, 6, 8, and 12 hours after dosing was conducted during the first month of treatment in a subset of 60 study participants after a minimum of 14 doses. Plasma concentrations of rifampicin, isoniazid, pyrazinamide, and metformin were measured by high-performance liquid chromatography using validated methods, and pharmacokinetic parameters and OCT1 and MATE1 gene polymorphisms were compared between the groups. RESULTS: Significant increases in the clearance of rifampicin, isoniazid, and pyrazinamide were observed in patients in the METRIF group (n = 29) compared with those in the ATT group (n = 31). The AA genotypes of the single-nucleotide polymorphism of rs2289669 (MATE1) in the METRIF group showed a significantly decreased area under the concentration-time curve to the last observation point and increased clearance of rifampicin. CONCLUSIONS: Metformin altered rifampicin and isoniazid plasma concentrations in patients receiving antituberculosis treatment for pulmonary tuberculosis with little effect on sputum conversion at the end of treatment. Studies with larger sample sizes are needed to understand host drug-drug interactions.

Mortality in Two Waves of COVID-19: A Comparative Analysis of a Tertiary Care Hospital in India.

Background COVID-19 has spread as two distinct surges of cases in many countries. Several countries have reported differences in disease severity and mortality in the two waves. Objective Compare the in-hospital mortality in the two COVID-19 waves at a tertiary care hospital in India. Methods We conducted a retrospective data collection. Distinct periods of surges in cases and admissions were defined as the first wave spanning from March 2020 to December 2020 and the second wave from April 2021 to June 21, 2021. The primary outcome of this study was to compare mortality rates in terms of total hospital mortality rate (TMR) and case fatality rate (CFR). Results Mortality rates of wave 2 were approximately 10 times that of wave 1 (TMR of 20.3% in wave 2 versus 2.4% in wave 1 and CFR of 1.5% versus 17.7% in wave 1 and 2, respectively). Mortalities in wave 2 had a larger proportion of severe disease at presentation, faster progression of symptoms to death, and more patients without any chronic comorbid condition dying due to the direct effect of COVID-19 acute respiratory distress syndrome (ARDS). Conclusion Our data matches the worldwide reported pooled hospital mortality figures and shows the comparative difference in disease severity between the two waves.

Phenotypic Profiling of Immune Cells and Their Mediators in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder and has been proposed to have an imbalance between pro-inflammatory and anti-inflammatory factors. METHODS: This study was conducted on 41 participants {18 COPD patients (smokers, COPD S (n = 9); reformed smokers, COPD RS (n = 9)) and 23 controls (non-smokers, CNS (n = 14); smokers, CS (n = 9))}. Flow cytometry was used to identify circulatory immune cells and correlated with serum cytokines. RESULTS: On comparison, significantly lower frequency of CD3+ T cells were observed in COPD S as compared to CNS (p < 0.01) and CS (p < 0.01); CD4+ T cells were lower in COPD S (p < 0.05), COPD RS (p < 0.05) and CNS (p < 0.01) as compared to CS. CD8+ T cells were elevated in COPD S as compared to CS (p < 0.05). Lower frequency of cDCs were observed in COPD S as compared to CS (p < 0.05) and COPD RS as compared to CNS (p < 0.01) and CS (p < 0.01). Lower frequency of pDCs were observed in COPD RS as compared to COPD S (p < 0.05), CNS (p < 0.05) and CS (p < 0.01). Lower frequency of Tregs was observed in COPD S as compared to CNS (p < 0.05) and CS (p < 0.05). CONCLUSIONS: Characteristic changes observed indicate a significant impact of immune cells in the progression of the disease.

T-cell signature cytokines distinguish pulmonary sarcoidosis from pulmonary tuberculosis.

Sarcoidosis is a systemic inflammatory disorder characterized by tissue infiltration due to mononuclear phagocytes and lymphocytes and associated noncaseating granuloma formation. Pulmonary sarcoidosis (PS) shares a number of clinical, radiological, and histopathological characteristics with that of pulmonary tuberculosis (PTB). Due to this, clinicians face issues in differentiating between PS and PTB in a substantial number of cases. There is a lack of any specific biomarker that can diagnose PS distinctively from PTB. We compared T-cell-based signature cytokines in patients with PS and PTB. In this study, we proposed a serum biomarker panel consisting of cytokines from cells: T helper (Th) 1 [interferon-gamma (IFN-γ); tumor necrosis factor-alpha (TNF-α)], Th9 [interleukin (IL)-9], Th17 [IL-17], and T regulatory (Treg) [IL-10; transforming growth factor-beta (TGF-ß)]. We performed the principal component analysis that demonstrated that our serum cytokine panel has a significant predictive ability to differentiate PS from PTB. Our results could aid clinicians to improve the diagnostic workflow for patients with PS in TB endemic settings where the diagnosis between PS and PTB is often ambiguous.

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.

Phylogeny and evolution of SARS-CoV-2 during Delta and Omicron variant waves in India.

SARS-CoV-2 evolution has continued to generate variants, responsible for new pandemic waves locally and globally. Varying disease presentation and severity has been ascribed to inherent variant characteristics and vaccine immunity. This study analyzed genomic data from 305 whole genome sequences from SARS-CoV-2 patients before and through the third wave in India. Delta variant was reported in patients without comorbidity (97%), while Omicron BA.2 was reported in patients with comorbidity (77%). Tissue adaptation studies brought forth higher propensity of Omicron variants to bronchial tissue than lung, contrary to observation in Delta variants from Delhi. Study of codon usage pattern distinguished the prevalent variants, clustering them separately, Omicron BA.2 isolated in February grouped away from December strains, and all BA.2 after December acquired a new mutation S959P in ORF1b (44.3% of BA.2 in the study) indicating ongoing evolution. Loss of critical spike mutations in Omicron BA.2 and gain of immune evasion mutations including G142D, reported in Delta but absent in BA.1, and S371F instead of S371L in BA.1 could explain very brief period of BA.1 in December 2021, followed by complete replacement by BA.2. Higher propensity of Omicron variants to bronchial tissue, probably ensured increased transmission while Omicron BA.2 became the prevalent variant possibly due to evolutionary trade-off. Virus evolution continues to shape the epidemic and its culmination.Communicated by Ramaswamy H. Sarma.

Association of air pollution and coronavirus disease 2019 (COVID-19) in India.

The COVID-19 pandemic has affected the world, leading to significant morbidity and mortality. Various meteorological parameters are considered essential for the viability and transmission of the virus. Multiple reports from various parts of the world suggest a correlation between the disease spread and air pollution severity. This study was carried out to identify the relationship between meteorological parameters, air pollution, and COVID-19 in New Delhi, one of the worst-affected states in India. We studied air pollution and meteorological parameters in New Delhi, India. We obtained data about COVID-19 occurrence, meteorological parameters, and air pollution indicators from various sources from Apr 1, 2020, till Nov 12, 2020. We performed correlational analysis and employed autoregressive distributed lag models (ARDLM) for identifying the relationship between COVID-19 cases with air pollution and meteorological parameters. We found a significant impact of PM 2.5, PM 10, and meteorological parameters on COVID-19. There was a significant positive correlation between daily COVID-19 cases and COVID-19-related deaths with PM2.5 and PM10 levels. Increasing temperature and windspeed were associated with a reduction in the number of cases while increasing humidity was associated with increased cases. This study demonstrated a significant association of PM2.5 and PM10 with daily COVID-19 cases and COVID-19-related mortality. This knowledge will likely help us prepare well for the future and implement air pollution control measures for other airborne disease epidemics.

Clinical Profile and Quality of Life of Patients With Post-pulmonary Tuberculosis Sequelae Presenting to a Tertiary Care Hospital.

Background and objective There is a dearth of studies on the clinical presentation of patients with post-pulmonary tuberculosis (PTB) sequelae and its impact on their quality of life (QoL). In light of this, we conducted this study to analyze the clinical profile and QoL in patients with post-PTB sequelae. Methods Patients with a history of treated PTB and evidence of radiological damage were enrolled prospectively from November 2018 till June 2020 to study their clinical profile and QoL as per the eligibility criteria. A detailed clinical history was taken along with posteroanterior-view chest X-rays and CT scans of the thorax with bronchial angiography in patients with hemoptysis. QoL was assessed using the Hindi version of St. George's Respiratory Questionnaire (SGRQ) for which permission was obtained from the St. George's University of London. SGRQ scores were calculated using score calculation algorithms (Microsoft Excel-based) and missing data imputation as recommended by its developer. Results A total of 174 patients were included in the analysis. The analyzed population was relatively younger (mean age: 44.27 years) with BMIs leaning toward the lower side of normal (median: 19.6 kg/m²); the majority of the patients were males (59%) and non-smokers (77%). PTB had been diagnosed clinico-radiologically in the majority (68%) of patients with non-compliance to antitubercular treatment (ATT) being reported by only 9% of patients. Multiple courses of ATT were received by about one-third of patients, mainly on a clinico-radiologic basis. Systemic hypertension (HTN) (11%) and diabetes mellitus (DM) (9%) were the most common comorbidities. The most common symptom complex found was cough, expectoration, and dyspnea (n=102, 59%). At least one incidence of massive hemoptysis was reported by 20% of patients. Bronchial artery embolization (BAE) was performed for moderate to massive hemoptysis in 26% of patients with a success rate of >90%. One-fifth of the study participants required hospitalization for exacerbation of respiratory symptoms with more than half of these (59%) requiring ventilatory support. Health-related QoL was significantly impaired as reflected by a median SGRQ total score of 45.53. The most affected domain of QoL was the activity domain (mean score: 45.47). Females had worse QoL as compared to males (p=0.0062), and so did underweight patients (p=0.048). The prolonged duration of the illness also significantly impaired the QoL (p<0.001, r=0.313). Conclusion The sequelae of PTB are under-recognized even among physicians and are frequently misdiagnosed as active PTB. The QoL is more severely affected due to residual damage. This study highlights the clinical profile of this patient population and underscores the need to recognize post-PTB sequelae as a separate entity. An important remedy to mitigate its long-term consequences is its inclusion and recognition in national and international TB guidelines to facilitate its early identification and promote further research to address its evidence-based management.

Small molecule bio-signature in childhood intra-thoracic tuberculosis identified by metabolomics.

The diagnosis of pediatric tuberculosis (TB) remains a major challenge, hence the evaluation of new tools for improved diagnostics is urgently required. We investigated the serum metabolic profile of children with culture-confirmed intra-thoracic TB (ITTB) (n = 23) and compared it with those of non-TB controls (NTCs) (n = 13) using proton NMR spectroscopy-based targeted and untargeted metabolomics approaches. In targeted metabolic profiling, five metabolites (histidine, glycerophosphocholine, creatine/phosphocreatine, acetate, and choline) differentiated TB children from NTCs. Additionally, seven discriminatory metabolites (N-α-acetyl-lysine, polyunsaturated fatty acids, phenylalanine, lysine, lipids, glutamate + glutamine, and dimethylglycine) were identified in untargeted metabolic profiling. The pathway analysis revealed alterations in six metabolic pathways. The altered metabolites were associated with impaired protein synthesis, hindered anti-inflammatory and cytoprotective mechanisms, abnormalities in energy generation processes and membrane metabolism, and deregulated fatty acid and lipid metabolisms in children with ITTB. The diagnostic significance of the classification models obtained from significantly distinguishing metabolites showed sensitivity, specificity, and area under the curve of 78.2%, 84.6%, and 0.86, respectively, in the targeted profiling and 92.3%, 100%, and 0.99, respectively, in the untargeted profiling. Our findings highlight detectable metabolic changes in childhood ITTB; however, further validation is warranted in a large cohort of the pediatric population.