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Introduction Lung transplant (LTx) is a potential treatment option for all patients with chronic, end-stage respiratory disease, who are refractory to optimal medical therapy or where no medical therapy exists. In India, LTx is still in its evolving stages and published literature is sparse. The current study was carried out to study the selection criteria for lung transplant and to evaluate the clinical and socio-economic profile of patients referred for the same at a tertiary health care facility. Methods The study was a descriptive, prospective, observational study. All adults referred for lung transplant were evaluated for clinical and laboratory profiles. All enrolled patients were assessed for presence of referral criteria, listing criteria, contraindications, and willingness for lung transplant. These patients were followed up for 2 years for transplant-free survival, and the Cox proportional hazards model was used to determine independent predictors of all-cause mortality. Results A total of 103 were included in study. The most common diagnosis was interstitial lung disease (57.2%), followed by bronchiectasis (17.5%) and COPD (13.6%). Most patients were referred for LTx at an advanced stage as 90% met listing criteria. Fifty-four (52.4%) patients had an absolute or relative contraindication to transplant; however, the majority of those contraindications were modifiable. Patients with a lower socio-economic status were less likely to be willing for LTx. The median survival was 757 days. A 6-minute walk distance (6MWD) lesser than 250 m was found to be an independent predictor of mortality. Conclusion Making patients aware about lung transplant early in their treatment may give them sufficient time to come to terms with their disease and understand the risk and benefits associated. Efforts should be focused on screening and early treatment of reversible contraindications for the eligible patients. Patients with 6MWD < 250 m are at increased risk of mortality.

Background Sarcoidosis and tuberculosis (TB) are the two most common causes of granulomatous mediastinal lymphadenopathy. These often exhibit overlapping clinical and radiological characteristics, rendering accurate diagnosis difficult. MicroRNA (miRNA) analysis is increasingly utilised as a potential biomarker for various diseases. Exhaled breath condensate (EBC) is a noninvasive technique for biomarker evaluation in different respiratory conditions. We attempted to identify differentially expressed miRNAs in the EBC of sarcoidosis and mediastinal TB patients. Methods EBC was obtained from subjects with a definitive diagnosis of sarcoidosis and mediastinal TB. EBC was also obtained from age- and sex-matched control subjects. From EBC, miRNA isolation, cDNA preparation and qPCR array were performed. Differentially expressed miRNAs were shortlisted. Further validation was conducted in the EBC of a new subset. Results Subjects with a definitive diagnosis of sarcoidosis (50) and TB (50), and control subjects (50) were included. qPCR array from EBC (20 subjects from each group) shortlisted eight differentially expressed miRNAs (miR-126, miR-132, miR-139-3p, miR-139-5p, miR-181c, miR-454, miR-512-3p and miR-362-5p). In the validation set (EBC of 30 subjects from each group), miR-126 and miR-132 were differentially expressed significantly. The miR-126 and miR-132 expression ratio could differentiate sarcoidosis from mediastinal TB with an AUC of 0.618 (82% specificity and 41% sensitivity). Conclusion While EBC miRNA expression is significantly and differently altered in sarcoidosis and mediastinal TB, a simple ratiometric approach failed to provide clinically useful signatures for differentiating between the two in patients with mediastinal lymphadenopathy.

Introduction Tuberculosis (TB) continues to be one of the deadliest infectious diseases over the centuries, killing more people worldwide than any other single infectious disease. There is an urgent need for additional strategies which can expedite efforts to combat TB including a preventive vaccine. In this endeavour, we have developed a protocol for a multisite, double-blind, placebo-controlled clinical trial in India that aims to evaluate the efficacy and safety of two TB vaccines; namely, VPM1002 and Immuvac (M.w) (Mycobacterium Indicus Pranii) (MIP) among healthy household contacts (HHCs) of sputum smear-positive pulmonary TB (PTB) patients.Methods and analysis In the three-arm randomised double-blind placebo-controlled trial study protocol, a total of 12 000 HHCs (aged 6−99 years) of sputum smear-positive PTB patients will be randomised to receive either of the two vaccine candidates VPM1002 and MIP or placebo. The primary efficacy endpoint is the prevention of microbiologically confirmed TB. Secondary endpoints will include (1) prevention against Latent TB infection, (2) incidence of adverse events and serious adverse events in study participants, (3) efficacy of vaccine in prevention of PTB/extra PTB in different age groups (6–18 years, 19–35 years, 36–60 years and above 60 years) and (4) immunogenicity of VPM1002 and MIP at month 2 and month 6 after first vaccination in terms of flow cytometric analysis of M.Tb specific CD4+ and CD8+ T cells secreting cytokines and Luminex assays for the presence of different cytokines in the sera and supernatants of peripheral blood mononuclear cells cultures stimulated with whole cell lysates of M.Tb and subsequently similar analysis for the cases who develop TB postvaccination during the follow-up period.Ethics and dissemination Ethics committees’ approvals have been granted by the Institutional Human Ethics Committees of all participating centres in this study and the names of the ethics committees and approvals are as follows: (1) National Institute for Research in Tuberculosis (NIRT)-Chennai (including subsites): ECR/135/Inst/TN/2013/RR-19, Approval No. 390/NIRT-Institutional Ethics Committee (IEC)/2018 dated 5 December 2018 (NIRT-Madurai-ECR/1365/Inst/TN/2020; approval dated 8 June 2020; NIRT, Vellore: ECR/1215/Inst/TN/2019; approval dated 26 September 2020); (2) All India Institute of Medical Sciences (AIIMS), Delhi (including subsites)-Institute Ethics Committee, ECR/547/Inst/DL/2014/RR-17 ECR/538/Inst/DL/2014/RR-20; approval No.IEC-385/06-07-2018, approval OP-28/05.04.2019 and SFH- ECR/593/Inst/DL/2014/RR-20 IEC/VMMC/SJH/project/2019-05/25 ; 23 May 2019; (3) National Institute of Tuberculosis and Respiratory Diseases (NITRD), Delhi: ECR/315/Inst/DL/2013/RR-19; approval IEC-No-NITRD/EC/2019/9004; 8 January 2019; (4) Pune-National AIDS Research Institute (NARI) and subsite-ECR/23/Inst/MH/2013/RR-19; IEC-NARI/EC/approval/2018/196; 29 May 2018; (5) Regional Medical Research Centre-Bhubaneshwar-ECR/911/Inst/OR-2017/RR-21; approval, dated 25 April 2018; Subsites- AIIMS, Bhubaneshwar ECR/534/Inst/OD/2014/RR-17 and 20 approval No. T/EMF/Pulm. Med/19/01 dated 13 May 2019; SCB, Cuttack No. No.ECR/84/Inst/OR/2013/RR-20; approval no.186 dated 7 February 2020; (6) NTI-Bengaluru: Ethics Committee-No-ECR/1819/Inst/KA/2019; approval No NTI-IEC/1.2019/principal investigator, dated 31 January 2019; (7) BMMRC, Hyderabad- ECR/450/Inst/AP/2013/RR-16 approval No. 779/BMMRC/2018/IEC, dated 11 June 2018 (Subsite Share India- Mediciti Ethics Committee-ECR/283/Inst/AP/2013/RR-20; Approval no. EC/11/VII/2K20(1) dated 11 July 2020) and (8) SJMC-Bengaluru: ECR/238/Inst/KA/2013/RR-19; approval IEC/1/491/2020; 7 August 2020.The trial findings will be published in accordance with the Consolidated Standards of Reporting Trials guidance. The results of this clinical trial will be presented at scientific conferences and disseminated through publications in peer-reviewed journals, conference presentations and shared with Ministry of Health and Family Welfare, policy-makers and other stakeholders.Trial registration number CTRI/2019/01/017026.

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]

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.

Aim: Globally, the incidence of lung cancer amongst women appears to be increasing. We aimed to compare the socio-epidemiological and clinical characteristics of lung cancer amongst men and women from a large cohort at a tertiary care hospital in Northern India. Methods: Records of patients diagnosed with lung cancer between January 2008 and March 2020 were reviewed. Baseline epidemiological data, clinical characteristics, histologic profiles, treatment administered, and survival were compared between males and females. Results: A total of 2054 male and 438 female patients were included in analysis. Compared to males, female patients were younger [median age, 56 vs. 60 years, P < 0.001)], less likely to be working, less educated beyond secondary level and less likely to be smokers (29.1% vs. 84.9%, P < 0.0001). No difference in baseline performance status was observed. Females were more frequently diagnosed with adenocarcinoma (54.2% vs. 30.2%, P =

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.

Abstract Background Several methodological tests are available to detect SARS-CoV-2 antibody. Tests are mostly used in the aid of diagnosis or for serological assessment. No tests are fully confirmatory and have variable level of diagnostic ability. We aimed at assessing agreement with three serological tests: quantitative anti receptor binding domain ELISA (Q-RBD), qualitative ELISA (WANTAI SARS-CoV-2 Ab) and qualitative chemiluminescence assay (CLIA). Methods This study was a part of a large population based sero-epidemiological cohort study. Participants aged 1 year or older were included from 25 randomly selected clusters each in Delhi urban (urban resettlement colony of South Delhi district) and Delhi rural (villages in Faridabad district, Haryana). Three type of tests were applied to all the baseline blood samples. Result of the three tests were evaluated by estimating the total agreement and kappa value. Results Total 3491 blood samples collected from March to September, 2021, out of which 1700 (48.7%) from urban and 1791 (51.3%) from rural. Overall 44.1% of participants were male. The proportion of sero-positivity were 78.1%, 75.2% and 31.8% by Wantai, QRBD and CLIA tests respectively. The total agreement between Wantai and QRBD was 94.5%, 53.1% between Wantai and CLIA, and 56.8% between QRBD and CLIA. The kappa value between these three tests were 0.84 (95% CI 0.80–0.87), 0.22 (95% CI 0.19–0.24) and 0.26 (95% CI 0.23–0.28). Conclusions There was strong concordance between Wantai and QRBD test. Agreement between CLIA with other two tests was low. Wantai and QRBD tests measuring the antibody to same S protein can be used with high agreement based on the relevant scenario.

Objectives: India introduced BBV152/Covaxin and AZD1222/Covishield vaccines in January 2021. We estimated the effectiveness of these vaccines against severe COVID-19 among individuals aged ≥45 years. Methods: We did a multi-centric, hospital-based, case-control study between May and July 2021. Cases were severe COVID-19 patients, and controls were COVID-19 negative individuals from 11 hospitals. Vaccine effectiveness (VE) was estimated for complete (2 doses ≥ 14 days) and partial (1 dose ≥ 21 days) vaccination; interval between two vaccine doses and vaccination against the Delta variant. We used the random effects logistic regression model to calculate the adjusted odds ratios (aOR) with a 95% confidence interval (CI) after adjusting for relevant known confounders. Results: We enrolled 1143 cases and 2541 control patients. The VE of complete vaccination was 85% (95% CI: 79-89%) with AZD1222/Covishield and 71% (95% CI: 57-81%) with BBV152/Covaxin. The VE was highest for 6-8 weeks between two doses of AZD1222/Covishield (94%, 95% CI: 86-97%) and BBV152/Covaxin (93%, 95% CI: 34-99%). The VE estimates were similar against the Delta strain and sub-lineages. Conclusion: BBV152/Covaxin and AZD1222/Covishield were effective against severe COVID-19 among the Indian population during the period of dominance of the highly transmissible Delta variant in the second wave of the pandemic. An escalation of two-dose coverage with COVID-19 vaccines is critical to reduce severe COVID-19 and further mitigate the pandemic in the country.

Abstract Background Statins and aspirin have been proposed for treatment of COVID-19 because of their anti-inflammatory and anti-thrombotic properties. Several observational studies have shown favourable results. There is a need for a randomised controlled trial. Methods In this single-center, open-label, randomised controlled trial, 900 RT-PCR positive COVID-19 patients requiring hospitalisation, were randomly assigned to receive either atorvastatin 40 mg (Group A, n = 224), aspirin 75 mg (Group B, n = 225), or both (Group C, n = 225) in addition to standard of care for 10 days or until discharge whichever was earlier or only standard of care (Group D, n = 226). The primary outcome variable was clinical deterioration to WHO Ordinal Scale for Clinical Improvement ≥ 6. The secondary outcome was change in serum C-reactive protein, interleukin-6, and troponin I. Results The primary outcome occurred in 25 (2.8%) patients: 7 (3.2%) in Group A, 3 (1.4%) in Group B, 8 (3.6%) in Group C, and 7 (3.2%) in Group D. There was no difference in primary outcome across the study groups (P = 0.463). Comparison of all patients who received atorvastatin or aspirin with the control group (Group D) also did not show any benefit [Atorvastatin: HR 1.0 (95% CI 0.41–2.46) P = 0.99; Aspirin: HR 0.7 (95% CI 0.27–1.81) P = 0.46]. The secondary outcomes revealed lower serum interleukin-6 levels among patients in Groups B and C. There was no excess of adverse events. Conclusions Among patients admitted with mild to moderate COVID-19 infection, additional treatment with aspirin, atorvastatin, or a combination of the two does not prevent clinical deterioration. Trial Registry Number CTRI/2020/07/026791 ( http://ctri.nic.in ; registered on 25/07/2020)

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.

Tuberculosis (TB) remains a major infectious disease across the globe. With increasing TB infections and a rise in multi-drug resistance, rapid diagnostic modalities are required to achieve TB control. Radiological investigations and microbiological tests (microscopic examination, cartridge-based nucleic acid amplification tests, and cultures) are most commonly used to diagnose TB. Histopathological/cytopathological examinations are also required for an accurate diagnosis in many patients.The causative agent, Mycobacterium tuberculosis (Mtb), is known to circumvent the host's immune system. Circulating microRNAs (miRNAs) play a crucial role in biological pathways and can be used as a potential biomarker to detect tuberculosis. miRNAs are small non-coding RNAs and negatively regulate gene expression during post-transcriptional regulation. The differential expression of miRNAs in multiple clinical samples in tuberculosis patients may be helpful as potential disease biomarkers. This review summarizes the literature on miRNAs in various clinical samples as biomarkers for TB diagnosis.

Background: Indian data on treatment outcomes and survival in advanced non-small cell lung cancer (NSCLC) remain scarce. Materials and Methods: A retrospective review of 537 advanced NSCLC patients treated at a tertiary care facility in North India from January 2008 to March 2018 was done to assess treatment response and survival in terms of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: Median age of enrolled patients was 60 years (range: 26–89 years). The majority were males (78.2%) and smokers (66.5%). Adenocarcinoma (51.2%) was the most common pathological type. Most patients had good performance status (PS) (the Eastern Cooperative Oncology Group [ECOG] 0 or 1 in 55.7%) and received conventional chemotherapy (86.6%). ORR and DCR after 3–4 months of first-line treatment were 55.2% and 71.75%, respectively (n = 223). Never smokers had better ORR as well as DCR compared to chronic smokers whereas treatment with tyrosine kinase inhibitors achieved significantly better ORR, and patients with good PS had better DCR compared to those with poor PS. Median PFS (n = 455) was 7.0 months (95% confidence interval [CI]: 3.7–14.0) and median OS was 11.7 months (95% CI: 5.5–29.9 months). Good PS and nonsmoking status were independent predictors of better PFS on multivariate analysis. For OS, good PS, nonsmoking behavior, and treatment with epidermal growth factor receptor inhibitors were independent predictors. Conclusion: In advanced NSCLC, never-smokers, and patients with good baseline ECOG have favorable treatment and survival outcomes. Treatment with targeted therapy results in better ORR and OS but did not affect PFS.

Background: Estimating seroepidemiolgical prevalence of SARS-CoV-2 antibody is an essential public health strategy. There is insufficient evidence of prevalence among those belonging to young age population in India. Objective: To compare the SARS-CoV-2 seropositivity rate between children and adults in selected sites from India. Materials and Methods: This was a multicentric population-based seroepidemiological study conducted in selected urban and rural areas of five sites selected from four states (Delhi, Odisha, Uttar Pradesh, Tripura) of India. Participants aged ≥1 year were included from different clusters of each area. Total serum antibody against SARS-CoV-2 virus was assessed qualitatively by using a standard enzyme-linked immunosorbent assay (ELISA) kit.Results: Data collection period was from 15 March 2021 to 10 June 2021. Total available data was of 4509 participants, of whom 700 were

Background: Hypoxia in patients with COVID-19 is one of the strongest predictors of mortality. Silent hypoxia is characterised by the presence of hypoxia without dyspnoea. Silent hypoxia has been shown to affect the outcome in previous studies. Methods: This was a retrospective study of a cohort of patients with SARS-CoV-2 infection who were hypoxic at presentation. Clinical, laboratory and treatment parameters in patients with silent hypoxia and dyspnoeic hypoxia were compared. Multivariate logistic regression models were fitted to identify the factors predicting mortality. Results: Among 2080 patients with COVID-19 admitted to our hospital, 811 patients were hypoxic with SpO2

Background: There is a lack of data on the prevalent practices of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in India. Aim: To study the current practices of EBUS-TBNA in India. Methods: This survey was an online questionnaire designed on the Google forms interface. The survey included various questions related to demographics, sedation, analgesia and anesthesia, technical aspects, and infection control related to the procedure of EBUS-TBNA. Results: Data from 134 respondents (mean age: 42.2 years) were analyzed. Most (97.8%) were pulmonologists or physicians, and a majority (94.8%) practicing in either a private multi-specialty setting or medical college. 40.3% had received procedure training at a formal training program. Mild/moderate sedation was the most common strategy (70.1%). Midazolam (76.7%), Fentanyl (76.0%), followed by propofol (46.5%), were the most frequent drugs, and 82.8% preferred combination sedation. 26.1% used cricothyroid lignocaine injection, and the use of 1% or 2% lignocaine for spray-as-you-go administration was similar. The oral route was preferred, while the laryngeal mask airway was the most common airway conduit under general anesthesia. Suspected granulomatous mediastinal lymphadenopathy (TB/sarcoidosis) (67.2%), followed by lung cancer (32.8%), were the most common indications of EBUS-TBNA. 81.3% performed EBUS-TBNA for lung cancer staging. 21 G needle was preferred (64.9%), and vacuum suction was common (80.6%). 55.2% routinely performed ROSE. Alcohol fixed glass slide smears were the most common method (93.1%) for cytological preparation. 49.3% also performed EUS-B-FNA. 76.9% routinely obtained endo bronchial biopsy and transbronchial lung biopsy in patients with suspected sarcoidosis. Elastography was infrequently used. Nearly three-fourths (77.6%) reused EBUS needles. Conclusion: There is practice variability in the multiple aspects related technical performance of EBUS-TBNA. Evidence-based guidelines addressing the multiple technical aspects are required to standardize the practice of EBUS-TBNA.

Background: Hydroxychloroquine (HCQ) had generated considerable interest for coronavirus disease 2019 (COVID-19) prophylaxis. We conducted a prospective observational study at a tertiary care hospital in India, with dedicated COVID-19 care facilities. Objectives: Primary objective was incidence of adverse effects, secondary objective being efficacy in preventing COVID-19. Methods: Healthcare workers were recruited and grouped based on voluntary HCQ prophylaxis as per national guidelines. Side effects in HCQ group were graded in accordance with national cancer institute-common terminology criteria for adverse events (NCI-CTCAE) version 5.0. At 3–7-week follow-up, groups were compared for COVID-19 exposure, symptoms development and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR results. Results: Among 358 participants recruited, 216 (60.3%) were males and mean age was 31.2 ± 6.6 years. Chemoprophylaxis was initiated by 258 (72%) participants. After loading dose, 7 (2.7%) reported grade 2 and 1 (0.4%) grade 3 adverse effects. Discontinuation of HCQ due to side effects was reported in 11 (4.3%) participants. Electrocardiogram was done by 50 (19.4%) participants on HCQ; no abnormalities were noted. A total of 106 (41%) among those taking and 63 (63%) among those not taking HCQ were tested for SARS-CoV-2 due to influenza-like illness or significant exposure. Among all participants, 25 (6.9%, 95% confidence interval [CI] 4.3–9.6) developed COVID-19 during the study period. In the group taking HCQ, 10 (3.9%) tested positive compared to 15 (15%) in the group not taking HCQ (P < 0.001). Odds ratio with HCQ intake was 0.34 (95% CI 0.13–0.83, P = 0.01) and the number needed to treat was 12. Conclusion: HCQ is safe at the recommended dose for pre-exposure prophylaxis of COVID-19.

Introduction: Elastography is a non-invasive tool that may allow differentiation between benign and malignant lymph nodes during endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA). In tuberculosis (TB) endemic areas, clinicoradiological features of mediastinal TB and sarcoidosis often overlap, rendering an accurate diagnosis challenging. There is interest in the identification of modalities to aid in this differentiation. There are currently no published data on the utility of EBUS-elastography in differentiating between TB and sarcoidosis. Methods: Subjects undergoing EBUS-TBNA were prospectively enrolled, and elastography features were observed. Subjects with definitive diagnosis of TB or sarcoidosis were enrolled. The elastography features recorded included the three-colour classification patterns and strain ratio. Results: We enrolled 96 subjects with a definitive diagnosis (53 with TB and 43 with sarcoidosis). Of the 27 patients in whom the lymph nodes were classified as type 1 on endobronchial ultrasound elastography colour pattern, 17 had a diagnosis of TB (62.9%), while 10 were sarcoidosis (37%). For type 2 lymph nodes, 20/45 (44.4%) were TB and 25/45 (55.6%) were sarcoidosis. Type 3 lymph nodes were TB in 16/24 (66.7%) and sarcoidosis in 8/24 (33.3%). In classifying type 1 as 'sarcoidosis' and Type 3 as 'tubercular', the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were 48.5%, 55.6%, 66.7%, 37%, and 0.51, respectively. The strain ratio (Median [IQR]) was 1.29 (0.37–5.98) in TB and 2.10 (0.83–4.52) in sarcoidosis group (P = 0.48). Conclusion: Ultrasound elastographic lymph node characteristics have a poor diagnostic utility to differentiate between TB and sarcoidosis during EBUS-TBNA.

Weight gain is an independent risk factor for decline in cardiometabolic and overall health-related quality of life in midlife women. The AIIMS-DST initiative aims to develop and validate stepwise recommendations specific for weight management in midlife women. The key clinical questions specific to weight management in midlife women were finalized with the help of a multidisciplinary team of experts in the guideline development group. Phase I including a systematic and/or narrative review, grading of evidence, and expert opinion was sought to develop clinical practice recommendations for each clinical question. Phase II focused on validation of clinical practice recommendations using the peer-review, Delphi method, and GRADE approach. The guidelines provide clinical practice points to address challenges encountered by midlife women in their attempts to manage obesity via lifestyle modification techniques. The initiation of discussion would help the health-care provider to identify the weight management needs of the women, educate women on different modalities of weight management, and empower them to incorporate corrective lifestyle behaviors. Before initiating the management, a comprehensive assessment of clinical and lifestyle-related parameters should be completed. A personalized behavioral lifestyle modification program addressing the midlife-specific barriers for optimal metabolic, musculoskeletal, and mental health should be planned. A consistent follow-up is required for maintenance of corrective eating and activity habits by addressing midlife-specific barriers for sustenance of healthy weight. These recommendations will be useful in opportunistic screening and management of obesity in midlife women across health-care settings.

Introduction: The small cell variant is a relatively uncommon but aggressive form of lung cancer. The present study aims to analyse the clinical characteristics, treatment outcomes and prognostic factors of an ambispectively enrolled large cohort of small cell lung cancer (SCLC) in the Indian population over a decade-long period. Materials and Methods: All patients diagnosed with SCLC between 2008 and 2020 at a tertiary care lung cancer clinic were included. The clinical details, demographics, details of investigations, treatment and survival outcomes were recorded and analysed. Results: A total of 361 patients were included. The majority were males (86.4%) with a mean (SD) age of 57.3 (12.3) years. Further, 34.9% were current smokers, with the median smoking index being 520 (interquartile range [IQR]: 260–1000). The majority had good performance status, that is, the Eastern Cooperative Oncology Group scale (ECOG) 0 or 1 (65%), and Karnofsky Performance Scale (KPS) ≥70 (85.9%). Also, 73.3% had extensive stage disease. The median time from symptom onset to definitive diagnosis was 91 days. Treatment details were available for 179 patients: chemotherapy only (n = 128), combined chemo-radiotherapy (n = 41) and radiotherapy only (n = 10). The median (IQR) progression-free survival (PFS) was 182 (94 to 306) days and the median (IQR) overall survival (OS) was 205 (94 to 429) days. On univariate analysis, factors that significantly affected survival included smoking index and performance status. However, on multivariate analysis, only the performance status significantly affected PFS, whereas none of these factors were significant for OS. Conclusions: SCLC predominantly affects males with a heavy smoking index. The diagnosis is usually made late; survival remains poor and is predominantly affected by the performance status.

Background: While long-term studies on the correlates of protection, vaccine effectiveness, and enhanced surveillance are awaited for SARS-CoV-2 vaccine, studies on breakthrough infections help understand the nature and course of this illness among vaccinated individuals and guide in public health preparedness. This study aims to compare the differences in the hospitalization outcomes SARS-CoV-2 infection of fully vaccinated individuals with with those of unvaccinated and partially vaccinated individuals. Materials and Methods: Single institution observational cohort study. This study compared the differences in clinical, biochemical parameters and the hospitalization outcomes of 53 fully vaccinated individuals with those of unvaccinated (1464) and partially vaccinated (231) individuals, among a cohort of 2,080 individuals hospitalized with SARS-CoV-2 infection. Descriptive statistics and propensity-score weighted multivariate logistic regression analysis adjusting for clinical and laboratory parameters were used to compare the differences and to identify factors associated with outcomes. Results: Completing the course of vaccination protected individuals from developing severe COVID-19 as evidenced by lower proportions of those with hypoxia, abnormal levels of inflammatory markers, requiring ventilatory support, and death compared to unvaccinated and partially vaccinated individuals. There were no differences in these outcomes among patients who received either vaccine type approved in India. Conclusions: Efforts should be made to improve the vaccination rates as a timely measure to prepare for the upcoming waves of this highly transmissible pandemic. Vaccination rates of the communities may also guide in the planning of the health needs and appropriate use of medical resources.

Introduction: Quantitation of microRNAs secreted by lung cells can provide valuable information regarding lung health. Exhaled breath condensate (EBC) offers a non-invasive way to sample the secreted microRNAs, and could be used as diagnostic tools for lung cancer. Materials & Methods: EBC samples from twenty treatment-naïve patients with pathologically confirmed lung cancer and twenty healthy subjects were profiled for miRNAs expression. Selected microRNAs were further validated, using quantitative-PCR, in an independent set of 10 subjects from both groups. Results: A total of 78 miRNAs were found to be significantly upregulated in the EBC of lung cancer patients compared to the control group. Six of these 78 miRNAs were shortlisted for validation. Of these, miR-31–3p, let7i, and miR-449c were significantly upregulated, exhibited good discriminatory power. Discussion: Differential expression of miRNAs secreted by lung cells could be quantitated in EBC samples, and could be used as a potential non-invasive tool for early diagnosis of lung cancer.

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.

ABSTRACT The epidemiology of Mycoplasma pneumoniae (Mp) is poorly understood in India. The present study was conducted to identify the prevalence of Mp in a large set of patients with acute respiratory tract infections (ARI) in an Indian tertiary hospital. During 2015–2020, we tested throat swab specimens from patients with the clinical diagnosis of ARI (n = 1,098) by a real-time PCR and compared the demographic, clinical, laboratory, and outcome data of Mp-positive and Mp-negative patients. During the study period, 5% (55/1,098) of the tested samples were positive for Mp by PCR. School-aged children and young adults represented 36% (20/55) of the cases and 47.3% (26/55) of the cases were registered during the summer and monsoon. Among the Mp-positive patients, 61.8% (34/55) had underlying conditions; the most common were malignancy (n = 12; 21.8%) and hypertension (n = 6; 10.9%). Fever (98.2% versus 84.9%; P = 0.006), and pharyngitis (27.3% versus 16.3%; P = 0.034) were significantly common in the Mp-positive group than Mp-negative group. Among the Mp-positive group, 20% (11/55) of patients were admitted to an intensive care unit and a total of 7/55 (12.7%) patients received ventilatory support. The mortality in the Mp-positive cohort was 13.3%. The study provides baseline data regarding Mp prevalence and clinical characteristics. The application of molecular assays for diagnosing this pathogen among hospitalized patients with ARI could reduce inappropriate empirical antibiotic treatment and improve patient outcomes. Further large-scale studies are required to avoid the underdiagnosis of Mp infections in India and such studies should address some research gaps, such as macrolide resistance and molecular typing. IMPORTANCE M. pneumoniae (Mp) is a significant pathogen causing atypical pneumonia but by far these infections are underreported clinical entities in India. In the present study, we report the prevalence of Mp and describe the demographic and baseline clinical data of Mp-positive cases in an Indian tertiary care hospital. Our study may improve the clinician’s awareness of this important agent of respiratory infection therefore timely and accurate diagnostic tools can be applied for patient management decisions and outcomes.

Background: Novel coronavirus (SARS-CoV-2) infection is associated with hypoxemic respiratory failure. Mechanical ventilation (MV) is reported to have high mortality in SARS-CoV-2 acute respiratory distress syndrome. We aimed to investigate whether awake prone positioning (PP) can improve oxygenation and prevent intubation when employed early. Methods: This prospective interventional study included proven coronavirus disease 2019 (COVID-19) patients with room air saturation 93% or less. The primary outcome was the rate of intubation between the two groups. The secondary outcomes included ROX index (SpO2/FiO2%/respiratory rate, breaths/min) at 30 min following the intervention, ROX index at 12 h, time to recovery of hypoxemia, and mortality. Results: A total of 45 subjects were included (30 cases and 15 controls) with a mean (standard deviation [SD]) age of 53.1 (11.0) years. The age, comorbidities, and baseline ROX index were similar between the two groups. The median duration of PP achieved was 7.5 h on the 1st day. The need for MV was higher in the control group (5/15; 33.3%) versus prone group (2/30; 6.7%). At 30 min, there was a statistically significant improvement in the mean (SD) ROX index of cases compared with that of the controls (10.7 [3.8] vs. 6.7 [2.6], P < 0.001). No significant adverse effects related to intervention were noted. Conclusion: Awake PP is associated with significant improvement in oxygenation and may reduce the need for MV in subjects with COVID-19.

Background: Guidelines for flexible bronchoscopy in adults recommend both Cricothyroid and Spray-as-you-go method as the acceptable techniques for lignocaine administration. No studies have compared these two methods for topical anesthesia during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Objectives: Co-primary outcomes were the comparison of cough count and operator-rated overall procedure satisfaction on a Visual Analog Scale (VAS) between the groups. The secondary outcomes were cumulative lignocaine dose, time from bronchoscope introduction to crossing the vocal cords, procedure duration, and complications between the groups. Methods: Consecutive participants (age >18 years) undergoing EBUS-TBNA were randomized (1:1) to either cricothyroid or spray-as-you-go methods for lignocaine administration. Results: Three hundred and sixty-five participants were randomized (183: Cricothyroid and 182: Spray-as-you-go). Cough count till reaching carina (median [interquartile range]) was significantly lower (cricothyroid, 1 [0–2] vs. spray-as-you-go, 4 [2–6], P < 0.001) and operator rated overall procedure satisfaction, on VAS (mean ± standard deviation) (cricothyroid, 7.96 ± 1.48 vs. spray-as-you-go, 7.29 ± 1.48, P < 0.001) significantly greater in the cricothyroid group. Cumulative lignocaine dose (163.28 ± 31.50 mg vs. 177.0 ± 30.12 mg, P < 0.0001) and time from bronchoscope introduction to crossing the vocal cords (20.80 ± 11.21 s vs. 38.08 ± 15.26 s, P < 0.001) was significantly lower in the cricothyroid group. Procedure duration was similar in both the groups. Minor complications occurred in three patients in cricothyroid and six patients in the spray-as-you-go group (P = 0.31). Conclusions: Cricothyroid lignocaine administration is associated with less cough and superior operator-rated procedure satisfaction during EBUS-TBNA, at a lower cumulative lignocaine dose administered. Trial Registration: www.clinicaltrials.gov NCT02981264

Background: Lignocaine can be administered during bronchoscopy using either a direct injection through the cricothyroid membrane (the cricothyroid method) or a spray of lignocaine solution through the bronchoscope working channel (the spray-as-you-go method). In this meta-analysis of randomized controlled trials (RCTs), we compared the efficacy of these two methods for topical anesthesia during flexible bronchoscopy. Methods: We performed a systematic search to extract the relevant RCTs comparing the two techniques. Results: Five RCTs meeting the inclusion criteria (747 subjects) were identified. The cricothyroid method was associated with significantly less cough (standardized mean difference [SMD] = −1.18, 95% confidence interval [CI] [−1.75, −0.62], P < 0.001, significant heterogeneity I2 = 86%, P < 0.001). On analysis of secondary outcomes, the cricothyroid method was associated with a greater operator-rated procedure satisfaction (SMD = 1.00, 95% CI [0.74, 1.25], P < 0.001), less time for upper airway negotiation (mean difference, MD = −0.99, 95% CI [−1.37, −0.6], P < 0.001), and a significantly less cumulative dose of lignocaine administered (MD = −68.12, 95% CI [−130.18, −6.06], P = 0.03). The overall procedure duration (MD = 0.08, 95% CI [−0.09, 0.24], P = 0.36) and patient discomfort (MD = −0.08, 95% CI [−0.38, 0.22], P = 0.59) were not different between the two methods. There was no significant publication bias (P = 0.94). Conclusions: The cricothyroid method is associated with less cough during flexible bronchoscopy. Other advantages are a greater operator-rated procedure satisfaction at a less cumulative lignocaine dose. These findings highlight the superior performance characteristics of the cricothyroid method for lignocaine administration for flexible bronchoscopy.

Background and Objectives: Chronic obstructive pulmonary disease (COPD) is a common airway disease that is frequently associated with comorbidities. In this study, we assessed the co-existence of obstructive sleep apnea (OSA) among patients with stable COPD. Methodology: This cross-sectional study included patients with stable COPD who were screened with Epworth's Sleepiness Scale (ESS). Those with ESS score of >10 were subjected to in-lab polysomnography (PSG). PSG was manually analyzed and reported. Patients with apnea–hypopnea index of >5/h were diagnosed as OSA. Results: This study included 301 patients (78.1% male, 76.4% smokers, age 59.6 ± 10 years) with stable COPD. ESS score of >10 was observed in 47 (15.6%) patients. Among patients with ESS score of >10, OSA was observed in 34 (72.3%) patients. The overall prevalence of OSA among patients with COPD was 10.9%. Patients with co-existing OSA were older and had thicker neck and higher body mass index (BMI) as compared to COPD alone. In addition, patients with associated OSA had worse health-related quality of life (QOL) as shown by higher St. George's Respiratory Questionnaire score (42.42 ± 7.22 vs. 25.22 ± 8.66;P < 0.001). Conclusions: Co-existing OSA is common among patients with COPD and has a significant adverse effect on the QOL. Among COPD patients, older age, thick neck, and high BMI may predict co-existing OSA and require PSG for the confirmation.

Background: Medical thoracoscopy (MT) is a useful diagnostic and therapeutic procedure for a variety of pleural conditions. There is a lack of literature on prevalent practices of MT in India. Aims and Objectives: The objective of the study was to study the prevalent practices of MT in India. Materials and Methods: A structured online survey on various aspects of thoracoscopy was designed on the “Google Forms” web software. Results: One hundred and eight responses were received, of which 100 respondents performed MT. The majority were pulmonologists, and most had started performing thoracoscopy within the last 5 years. Rigid thoracoscope was the most commonly used instrument. The common indications of procedure included undiagnosed pleural effusion, talc pleurodesis, and adhesiolysis. Local anesthesia with conscious sedation was the preferred anesthetic modality. Midazolam, along with fentanyl, was the most widely used sedation combination. 2% lignocaine was the most commonly used concentration for local infiltrative anesthesia. Nearly two-thirds of the respondents reported having encountered any complication of thoracoscopy. Significant reported complications included empyema, incision/port-site infection, re-expansion pulmonary edema, and procedure-related mortality. Conclusion: MT is a rapidly evolving interventional pulmonology procedure in India. There is, however, a significant variation in practice and variable adherence to available international guidelines on thoracoscopy. Formal training programs within India and national guidelines for pleuroscopy considering the local resources are required to improve the safety and yield of this useful modality.

The coronavirus disease 2019 (COVID-19) has affected different countries in a differential manner. The host susceptibility and host factors are important parameters for this variability. This study aimed to assess the effect of tuberculosis (TB) endemicity and Bacille Calmette-Guerin (BCG) coverage on COVID-19. Available data regarding TB incidence, BCG coverage (as per the World Health Organization), and COVID-19 incidence of 168 countries as of 19th September 2021. Countries were divided into four cohorts based upon annual TB incidence and BCG coverage and COVID-19 incidence and case fatality rates were compared using the Kruskal-Wallis test. Countries with low TB incidence and low BCG coverage had the highest COVID-19 incidence per lac population. However, no significant difference was seen in COVID-19 cases fatality rate. Higher TB incidence and BCG coverage were associated with lesser incidence of COVID-19. This result paves the way for research into pathogenesis and host immune response in COVID-19.

To elucidate the molecular mechanisms that manifest lung abnormalities during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, we performed whole-transcriptome sequencing of lung autopsies from 31 patients with severe COVID-19 and ten uninfected controls. Using metatranscriptomics, we identified the existence of two distinct molecular signatures of lethal COVID-19. The dominant ‘classical’ signature (n=23) showed upregulation of the unfolded protein response, steroid biosynthesis and complement activation, supported by massive metabolic reprogramming leading to characteristic lung damage. The rarer signature (n=8) that potentially represents ‘cytokine release syndrome’ (CRS) showed upregulation of cytokines such as IL1 and CCL19, but absence of complement activation. We found that a majority of patients cleared SARS-CoV-2 infection, but they suffered from acute dysbiosis with characteristic enrichment of opportunistic pathogens such as Staphylococcus cohnii in ‘classical’ patients and Pasteurella multocida in CRS patients. Our results suggest two distinct models of lung pathology in severe COVID-19 patients, which can be identified through complement activation, presence of specific cytokines and characteristic microbiome. These findings can be used to design personalized therapy using in silico identified drug molecules or in mitigating specific secondary infections.

The effective treatment modalities for severe coronavirus disease 2019 (COVID-19) are needed. As the primary cause of mortality is a hyperinflammatory state, the interleukin-6 antagonist tocilizumab has been used in multiple clinical studies. We conducted this systematic review and meta-analysis to estimate the effectiveness of tocilizumab in reduction of mortality due to COVID-19. A systematic search of the Pubmed and Embase databases was performed to extract randomized controlled trials (RCTs) regarding the use of tocilizumab therapy for COVID-19. An overall pooled mortality analysis was performed, and odds ratios were reported. Cochrane risk of bias assessment tool was used to assess the risk of bias. Heterogeneity was assessed using the I2 statistic. Nine RCTs, including 6489 patients, were selected for meta-analysis. Seven trials reported 28-day mortality, and one trial each reported 21-day and 30-day mortality. There were 846 deaths among 3358 participants in the steroid group while 943 deaths among 3131 patients randomized to the control group (random-effects odds ratio 0.87, 95% confidence interval 0.73-1.03, p=0.11). There was some heterogeneity among the trials as the I2 value was 15%, with a p-value of 0.31. There was a reduction in the need for ICU admission in the tocilizumab group. A higher risk of secondary infections was noted in the tocilizumab group (fixed-effects odds ratio 0.72, 95% confidence interval 0.55-0.95, p=0.02). This meta-analysis of RCTs demonstrated that the use of tocilizumab was not associated with a reduction in all-cause mortality in patients with COVID-19 and had higher odds of secondary infections.

Background: Obstructive sleep apnea (OSA) is a common disorder in which breathing repeatedly stops during sleep. Leukocyte telomere length (LTL) and OSA are linked with an increased risk of oxidative stress and inflammation. The possible link between LTL and OSA in Asian Indians has not been evaluated. Thus, the present study aims to compare the link between LTL and OSA in Asian Indians.Methods: In this study, 300 subjects (120 obese with OSA, 110 obese without OSA, and 70 non-obese without OSA) were included after overnight polysomnography and a fasting blood sample. Clinical, anthropometry, metabolic markers, insulin, 25-hydroxyvitamin D [25(OH) D], and parathyroid hormones (PTH) levels were investigated. LTL was investigated by a QPCR. Univariate and stepwise multivariate linear regression analyses adjusting for age, gender, BMI, and % body fat were conducted while treating LTL as a dependent variable in relation to AHI and other covariates.Results: Obese subjects with OSA had significantly decreased 25(OH)D and increased PTH levels. The mean telomere length (T/S) ratio was significantly shorter in patients with OSA. The adjusted correlation analysis showed that shortening of telomere length correlated with increasing age, apnea-hypopnea index (AHI), oxygen desaturation index, and RDI. Univariate analysis showed that LTL revealed a trend toward a negative correlation with a mean age (β + SE, −0.015 + 0.0006; p = 0.01) and positive correlation with AHI [β +slandered error (SE), 0.042 + 0.017; p = 0.008]. In the multiple regression analysis, LTL was positively associated with AHI (β + SE, 0.281 + 0.04; p = 0.001) after adjusting for age, sex, BMI, and % body fat. Even when adjusted for confounding factors, 25(OH)D, and PTH levels, LTL still was related to AHI (β + SE, 0.446 + 0.02; p = 0.05).Conclusion: Our study indicates the presence of an association between LTL and OSA and a significant impact of OSA severity and telomeres shortening in Asian Indians.

Addressing oxygen requirements of rural India should aim at using a safe, low-cost, easily available, and replenishable source of oxygen of moderate purity. This may be possible with the provision of a self-sustaining oxygen concentrator (pressure swing adsorption with multiple molecular sieve technology) capable of delivering oxygen at high-flow rates, through a centralized distribution system to 100 or more bedded rural hospitals, with back up from an oxygen bank of 10 × 10 cylinders. This will provide a 24 × 7 supply of oxygen of acceptable purity (~93%) for the treatment of hypoxemic conditions and will enable hospitals to specifically provide for high-flow oxygen in at least 15% of the beds. It may also serve as a facility for a local refill of oxygen cylinders for emergency use within the hospital as well as to subsidiary primary health centers, subcenters, and ambulances, thereby nudging our health-care system toward self-sufficiency in oxygen generation and utilization.

Abstract Objectives To assess the impact of adding statin (atorvastatin) and/or aspirin on clinical deterioration in patients infected with SARS-CoV-2 who require hospitalisation. The safety of these drugs in COVID-19 patients will also be evaluated. Trial design This is a single-centre, prospective, four-arm parallel design, open-label, randomized control trial. Participants The study will be conducted at National Cancer Institute (NCI), Jhajjar, Haryana, which is a part of All India Institute of Medical Sciences (AIIMS), New Delhi, and has been converted into a dedicated COVID-19 management centre since the outbreak of the pandemic. All RT-PCR confirmed cases of SARS-CoV-2 infection with age ≥ 40 years and < 75 years requiring hospital admission (patients with WHO clinical improvement ordinal score 3 to 5) will be included in the trial. Written informed consent will be taken for all recruited patients. Patients with a critical illness (WHO clinical improvement ordinal score > 5), documented significant liver disease/dysfunction (aspartate transaminase [AST] / alanine aminotransferase [ALT] > 240), myopathy and rhabdomyolysis (creatine phosphokinase [CPK] > 5x normal), allergy or intolerance to statins or aspirin, prior statin or aspirin use within 30 days, history of active gastrointestinal bleeding in past three months, coagulopathy, thrombocytopenia (platelet count < 100000/ dl), pregnancy, active breastfeeding, or inability to take oral or nasogastric medications will be excluded. Patients refusing to give written consent and taking drugs that are known to have a significant drug interaction with statin or aspirin [including cyclosporine, HIV protease inhibitors, hepatitis C protease inhibitor, telaprevir, fibric acid derivatives (gemfibrozil), niacin, azole antifungals (itraconazole, ketoconazole), clarithromycin and colchicine] will also be excluded from the trial. Intervention and comparator In this study, the benefit and safety of atorvastatin (statin) and/or aspirin as adjuvant therapy will be compared with the control group receiving usual care for management of COVID-19. Atorvastatin will be prescribed as 40 mg oral tablets once daily for ten days or until discharge, whichever is earlier. The dose of aspirin will be 75 mg once daily for ten days or until discharge, whichever is earlier. All other therapies will be administered according to the institute’s COVID-19 treatment protocol and the treating physician’s clinical judgment. Main outcomes All study participants will be prospectively followed up for ten days or until hospital discharge, whichever is longer for outcomes. The primary outcome will be clinical deterioration characterized by progression to WHO clinical improvement ordinal score ≥ 6 (i.e., endotracheal intubation, non-invasive mechanical ventilation, pressor agents, renal replacement therapy, ECMO requirement, and mortality). The secondary outcomes will be change in serum inflammatory markers (C-reactive protein and Interleukin-6), Troponin I, and creatine phosphokinase (CPK) from time zero to 5th day of study enrolment or 7th day after symptom onset, whichever is later. Other clinical outcomes that will be assessed include progression to Acute Respiratory Distress Syndrome (ARDS), shock, ICU admission, length of ICU admission, length of hospital admission, and in-hospital mortality. Adverse drug effects like myalgia, myopathy, rhabdomyolysis, hepatotoxicity, and bleeding will also be examined in the trial to assess the safety of the interventions. Randomisation The study will use a four-arm parallel-group design. A computer-generated permuted block randomization with mixed block size will be used to randomize the participants in a 1:1:1:1 ratio to group A (atorvastatin with conventional therapy), group B (aspirin with conventional therapy), group C (aspirin + atorvastatin with conventional therapy), and group D (control; only conventional therapy). Blinding (masking) The study will be an open-label trial. Numbers to be randomised (sample size) As there is no existing study that has evaluated the role of aspirin and atorvastatin in COVID-19 patients, formal sample size calculation has not been done. Patients satisfying the inclusion and exclusion criteria will be recruited during six months of study period. Once the first 200 patients are included in each arm (i.e., total 800 patients), the final sample size calculation will be done on the basis of the interim analysis of the collected data. Trial Status The institutional ethical committee has approved the study protocol (Protocol version 3.0 [June 2020]). Participant recruitment starting date: 28th July 2020 Participant recruitment ending date: 27th January 2021 Trial duration: 6 months Trial registration The trial has been prospectively registered in Clinical Trial Registry – India (ICMR- NIMS): Reference no. CTRI/2020/07/026791 (registered on 25 July 2020)]. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Background: The optimal strategy for the withdrawal of noninvasive ventilation (NIV) remains unknown. This study was planned to compare three different strategies for the withdrawal of NIV among patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with hypercapnic respiratory failure (HcRF). Materials and Methods: Patients with AECOPD with HcRF who improved on NIV were randomized into three groups – immediate withdrawal (Group A), stepwise reduction of pressure support (Group B), and stepwise reduction of duration (Group C) of NIV. The probability of successful withdrawal was compared among the groups. Results: This study included 90 patients (males – 86.6%) with a mean (±standard deviation [SD]) age of 59.9 ± 8.3 years. The mean (±SD) pH and PaCO2 at admission were 7.23 ± 0.04 and 84.4 ± 12.0 mm Hg, respectively. The duration of NIV received before randomization was 31.6 ± 9.2 h with maximum inspiratory positive airway pressure and expiratory positive airway pressure of 17.6 ± 2.7 cm H2O and 7.4 ± 1.4 cm H2O, respectively. NIV was successfully withdrawn in 23/30 (76.6%) in Group A, 27/30 (90%) in Group B, and 26/30 (86.6%) in Group C (P = 0.31). The total duration of NIV use and length of hospital stay was lower in Group A and B as compared to Group C (P = 0.001). Conclusions: Immediate withdrawal of the NIV after recovery of respiratory failure among patients with exacerbation of COPD is feasible. Immediate withdrawal did not increase the risk of weaning failure from the NIV.

Introduction: Over the past few years, the demographic profile of lung cancer has changed. However, most reports are limited by small numbers, short follow-up period, and show an inconsistent pattern. A comprehensive evaluation of changing trends over a long period has not been done. Materials and Methods: Consecutive lung cancer patients were studied over a 10-year period from January 2008 to March 2018 at the All India Institute of Medical Sciences, New Delhi, and relevant clinical information, and survival outcomes were analyzed. Results: A total of 1862 patients were evaluated, with mean (SD) age of 59 (11.1) years, and comprising 82.9% males. Majority were smokers (76.2%) with median smoking index of 500 (interquartile range [IQR]: 300–800). Adenocarcinoma (ADC) was the most common type (34%), followed by squamous cell carcinoma (SCC – 28.6%) and small cell lung cancer (SCLC) (16.1%). Over the 10-year period, ADC increased from 9.5% to 35.9%, SCC from 25.4% to 30.6%, and non-small cell lung cancer -not otherwise specified (NSCLC-NOS) decreased from 49.2% to 21.4%. The proportion of females with lung cancer increased although smoking rates remained similar. Majority of NSCLC (95%) continued to be diagnosed at an advanced stage (3 or 4). Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements were present in 25.3% and 11.5% ADC patients, respectively. The median overall survival was 8.8 months (IQR 3.7–19) for all patients and 12.57 (IQR 6.2–28.7) months among the 1013 patients who were initiated on specific treatment (chemotherapy, targeted therapy, radiotherapy, or surgery). Never-smokers were younger, more likely to be female and educated, had a higher prevalence of ADC and EGFR/ALK mutations, and had better survival. Conclusion: Among this large cohort, our center seems to follow the global trend with increasing incidence of ADC. EGFR mutation positivity was similar to existing reports, while higher ALK positivity was detected. A characteristic phenotype of never-smokers with lung cancer was elucidated which demonstrated better survival.

Introduction Sleep-related breathing disorders (SRBDs) including obstructive sleep apnea (OSA) and central sleep apnea (CSA) are quite common and are the leading causes of mortality in acromegaly. OSA in acromegaly is generally attributed to changes in oropharyngeal soft tissues. Data on OSA in Indian acromegaly are scant, especially cephalometric findings. The aim of this study is to evaluate the burden of SRBDs in acromegaly and its correlation to cephalometric parameters. Materials and Methods A total of 32 subjects (20 men and 12 women), diagnosed with acromegaly on the basis of standard clinical, biochemical, and hormonal measurements were recruited. In addition to the above parameters, polysomnography and magnetic resonance imaging (MRI) of the pharynx were performed in all subjects. Results The mean age of the subjects was 42.66 ± 11.13 years (range = 26–66) and mean duration of study after first presentation was 7.6 ± 6.3 years (range = 0.25–32). A total of 28 of 32 (93.3%) subjects had sellar MRI documented macroadenomas while 20 (62.5%) patients were treatment naive at the time of assessment. Twenty-nine (90.6%) patients had evidence of SRBD and all of them had OSA subtype. The Apnea–Hypopnea Index (AHI) indicating severity of OSA (mild 21.8%, moderate 34.4%, and severe 34.4%) correlated positively with tongue length, uvula length, and uvula thickness on MRI. However, AHI had no correlation with the severity of GH excess or disease activity or individual parameters such as weight, body mass index, blood pressure, hemoglobin A1c, serum human growth hormone, and insulin-like growth factor-1 level. Conclusion SRBD, the generally overlooked comorbidity, is highly prevalent in subjects with acromegaly and is almost always due to OSA, the severity of which correlates positively with tongue and uvula size. Well-designed, long-term follow-up study on a large cohort of acromegalic patients is required to improve our understanding on the subject.

Background: Central airway obstruction (CAO) is a potentially lethal condition that requires urgent endobronchial intervention and may occur due to several nonmalignant causes. The effect of these interventions on clinically relevant outcomes such as symptomatic and functional status over a period of time is, however, sparsely studied. Materials and Methods: Consecutive patients with CAO due to nonmalignant causes and undergoing various therapeutic bronchoscopy procedures were evaluated. Symptoms were assessed using the Visual Analog Scale (VAS) and Speiser score, and functional status was assessed using the 6-min walk test, spirometry, and St. George Respiratory Questionnaire (SGRQ) score at baseline and after 48 h, 4 weeks, and 12 weeks postprocedure. Results: Over 2 years, 31 patients with CAO due to nonmalignant etiology underwent 41 therapeutic bronchoscopic procedures. Majority of procedures (96.8%) were done using the rigid bronchoscope under general anesthesia. Postintubation tracheal stenosis was the most common indication (32.2%). The various procedures included, controlled radial expansion balloon dilatation of the stenotic airway (53.6%), deployment of silicone stents (19.5%), and mechanical debulking of airway tumors (16.1%). Significant improvement occurred in dyspnea and cough scores and in the Speiser score from baseline to 48 h postprocedure, and further improved at 4 weeks and 12 weeks. Similarly, the 6 min walk distance, forced expiratory volume in 1 s, and SGRQ scores progressively improved from baseline to 12 weeks. Complications occurred in 26.8% of total procedures, with no procedure-related mortality. Conclusion: Therapeutic bronchoscopy interventions provide rapid and sustained benefits in symptoms and functional status of participants with CAO of nonmalignant etiology, with an acceptable safety profile.

Background: Ongoing pandemic because of COVID-19 has spread across countries, with varied clinical features and severity. Awareness of clinical course among asymptomatic and symptomatology in symptomatic cases is essential for patients' management as well as optimal utilization of health services (in resource limited settings) based on clinical status and risk factors. This study aimed to describe the clinical characteristics and outcomes of patients admitted with COVID-19 illness in the initial phase of the pandemic in India. Methods: It was an observational study. Patients aged 18 years or more, with confirmed SARS-CoV-2 infection, asymptomatic or mildly ill, were included. Patients with moderate-severe disease at admission or incomplete clinical symptomatology records were excluded. Data regarding demography, comorbidities, clinical features and course, treatment, results of SARS-CoV-2 RT-PCR, chest radiographs, and laboratory parameters were obtained retrospectively from hospital records. The outcome was noted in terms of course, patients discharged, still admitted (at the time of the study), or death. Results: Out of 231 cases, most were males (78.3%) with a mean age of 39.8 years. Comorbidities were present in 21.2% of patients, diabetes mellitus and hypertension being the most common. The most common symptoms were dry cough (81, 35%), fever (64, 27.7%), sore throat (36, 15.6%); asymptomatic infection noted in 108 (46.8%) patients. The presence of comorbidities was an independent predictor of symptomatic disease (OR-2.66; 95%CI 1.08–6.53, P = 0·03). None of the patients progressed to moderate-severe COVID-19, and there were no deaths. Conclusions: A large proportion of patients remained asymptomatic whereas those with comorbidities were more likely to be symptomatic. Most with mild disease had a stable disease course, barring few complication in those with comorbidities. The pandemic continues to grow as large number of asymptomatic cases may go undiagnosed.

Bronchial thermoplasty (BT) is an interventional bronchoscopic treatment for severe asthma. There is a need to define patient selection criteria to guide clinicians in offering the appropriate treatment options to patients with severe asthma. Methodology: An expert group formed this statement under the aegis of the Indian Chest Society. We performed a systematic search of the MEDLINE and EMBASE databases to extract evidence on patient selection and the technical performance of BT. Results: The experts agreed that the appropriate selection of patients is crucial and proposed identification of the asthma phenotype, a screening algorithm, and inclusion/exclusion criteria for BT. In the presence of atypical clinical or chest radiograph features, there should be a low threshold for obtaining a thoracic computed tomography scan before BT. The patient should not have had an asthma exacerbation in the preceding two weeks from the day of the procedure. A 5-day course of glucocorticoid should be administered, beginning three days before the procedure day, and continued until the day following the procedure. General Anesthesia (total intravenous anesthesia with a neuromuscular blocker) provides ideal conditions for performing BT. A thin bronchoscope with a 2.0 mm working channel is preferable. An attempt should be made to deliver the maximum radiofrequency activations. Middle lobe treatment is not recommended. Following the procedure, overnight observation in the hospital, and a follow-up visit, a week following each treatment session, is desirable. Conclusion: This position statement provides practical guidance regarding patient selection and the technical performance of BT for severe asthma.

Background: Interstitial lung disease (ILD) is a complex and heterogeneous group of acute and chronic lung diseases of several known and unknown causes. While clinical practice guidelines (CPG) for idiopathic pulmonary fibrosis (IPF) have been recently updated, CPG for ILD other than IPF are needed. Methods: A working group of multidisciplinary clinicians familiar with clinical management of ILD (pulmonologists, radiologist, pathologist, and rheumatologist) and three epidemiologists selected by the leaderships of Indian Chest Society and National College of Chest Physicians, India, posed questions to address the clinically relevant situation. A systematic search was performed on PubMed, Embase, and Cochrane databases. A modified GRADE approach was used to grade the evidence. The working group discussed the evidence and reached a consensus of opinions for each question following face-to-face discussions. Results: Statements have been made for each specific question and the grade of evidence has been provided after performing a systematic review of literature. For most of the questions addressed, the available evidence was insufficient and of low to very low quality. The consensus of the opinions of the working group has been presented as statements for the questions and not as an evidence-based CPG for the management of ILD. Conclusion: This document provides the guidelines made by consensus of opinions among experts following discussion of systematic review of evidence pertaining to the specific questions for management of ILD other than IPF. It is hoped that this document will help the clinician understand the accumulated evidence and help better management of idiopathic and nonidiopathic interstitial pneumonias.

ABSTRACT Emerging evidence indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals are at an increased risk for coinfections; therefore, physicians need to be cognizant about excluding other treatable respiratory pathogens. Here, we report coinfection with SARS-CoV-2 and other respiratory pathogens in patients admitted to the coronavirus disease (COVID) care facilities of an Indian tertiary care hospital. From June 2020 through January 2021, we tested 191 patients with SARS-CoV-2 for 33 other respiratory pathogens using an fast track diagnostics respiratory pathogen 33 (FTD-33) assay. Additionally, information regarding other relevant respiratory pathogens was collected by reviewing their laboratory data. Overall, 13 pathogens were identified among patients infected with SARS-CoV-2, and 46.6% (89/191) of patients had coinfection with one or more additional pathogens. Bacterial coinfections (41.4% [79/191]) were frequent, with Staphylococcus aureus being the most common, followed by Klebsiella pneumoniae. Coinfections with SARS-CoV-2 and Pneumocystis jirovecii or Legionella pneumophila were also identified. The viral coinfection rate was 7.3%, with human adenovirus and human rhinovirus being the most common. Five patients in our cohort had positive cultures for Acinetobacter baumannii and K. pneumoniae, and two patients had active Mycobacterium tuberculosis infection. In total, 47.1% (90/191) of patients with coinfections were identified. The higher proportion of patients with coinfections in our cohort supports the systemic use of antibiotics in patients with severe SARS-CoV-2 pneumonia with rapid de-escalation based on respiratory PCR/culture results. The timely and simultaneous identification of coinfections can contribute to improved health of COVID-19 patients and enhanced antibiotic stewardship during the pandemic. IMPORTANCE Coinfections in COVID-19 patients may worsen disease outcomes and need further investigation. We found that a higher proportion of patients with COVID-19 were coinfected with one or more additional pathogens. A better understanding of the prevalence of coinfection with other respiratory pathogens in COVID-19 patients and the profile of pathogens can contribute to effective patient management and antibiotic stewardship during the current pandemic.

Background: Year 2020 started with global health crisis known as COVID-19. In lack of established tools and management protocols, COVID-19 had become breeding ground for fear and confusion, leading to stigma toward affected individuals. Method: A cross-sectional study was conducted to estimate prevalence of stigma in discharged COVID-19 patients from a COVID hospital in India. Participants were approached telephonically using a semistructured questionnaire to record their experiences. Questions were asked regarding stigma at six major domains of daily life. Among total 1,673 discharged participants, 600 were conveniently selected and out of them 311 responded on telephonic interviews. Result: We found that 182 (58.52%) participants (95% CI: 53.04–64.00) have self-perceived stigma, 163 (52.41%) participants (95% CI: 46.86–57.96) experienced quarantine-related stigma, 222 (71.38%) participants (95% CI: 66.36–76.40) experienced neighborhood stigma, 214 (68.81%) participants (95% CI: 63.66–73.95) experienced stigma while going out in marketplaces, 180 (57.88%) participants (95% CI: 52.39–63.37) experienced stigma at their work place, and 207 (66.56%) participants (95% CI: 61.31–71.80) reported stigma experienced by their family members. With a total of 84.5% (95% CI: 80.06–88.39) participants experiencing stigma at some domain and about 42.8% of participants facing stigma at all six domains. The commonest noted cause of stigma was fear of getting infected, reported by 184 (59.2%) participants. Conclusion: This study shows high prevalence of stigma in COVID-19 patients suffering in their common domains of daily lives.

There is an urgent need for effective treatment modalities for coronavirus disease 2019 (COVID-19). Data for the use of steroids in COVID-19 is emerging. We conducted this systematic review and meta-analysis to estimate the effectiveness of steroid administration in mortality reduction due to COVID-19 compared to the control group. A systematic search of the Pubmed and Embase databases was performed to extract randomized controlled trials (RCTs) regarding the use of steroid therapy for COVID-19. An overall and subgroup (based upon the type of steroid) pooled mortality analysis was performed, and odds ratios were reported. Cochrane risk of bias assessment tool was used to assess the risk of bias. Heterogeneity was assessed using the I2 statistic. Six RCTs, including 7707 patients, were selected for review. Three trials reported 28-day mortality, and two trials reported 21-day mortality, and one trial reported in-hospital mortality. There were 730 deaths among 2837 participants in the steroid group while 1342 deaths among 4870 patients randomized to the control group (Odds ratio 0.76, 95% confidence interval 0.58-1.00, p=0.05). The effect was significant in patients on oxygen or mechanical ventilation. There was no difference in the various preparations and doses of the steroids. There was heterogeneity among the trials as the I2 value was 53%, with a p-value of 0.06. There was no indication of increased serious adverse events. This meta-analysis of RCTs demonstrated that the use of systemic corticosteroids is associated with a reduction in all-cause mortality in patients with COVID-19 on oxygen or mechanical ventilation.