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Background & objectivesAcute respiratory distress syndrome (ARDS) is a common disorder in critically ill patients and is associated with high mortality. There is a paucity of literature on this condition from developing countries. This prospective observational study was designed to find out the aetiology, outcomes and predictors of mortality in ARDS.MethodsSixty four consecutive patients who satisfied American-European Consensus Conference (AECC) definition of ARDS from medical Intensive Care Unit (ICU) of a tertiary care centre in New Delhi, India, were enrolled in the study. Demographic, biochemical and ventilatory variables were recorded for each patient. Baseline measurements of serum interleukin (IL)-1β, IL-6, tumour necrosis factor-alpha (TNF-α), procalcitonin (PCT) and high sensitivity C-reactive protein (hsCRP) were performed.ResultsCommon causes of ARDS included pneumonia [44/64 (68.7%)], malaria [9/64 (14.1%)] and sepsis [8/64 (12.5%]. Eight of the 64 (12.5%) patients had ARDS due to viral pneumonia. The 28-day mortality was 36/64 (56.2%).Independent predictors of mortality included non-pulmonary organ failure, [Hazard ratio (HR) 7.65; 95% CI 0.98-59.7, P=0.05], Simplified Acute Physiology Score (SAPS-II) [HR 2.36; 95% CI 1.14-4.85, P=0.02] and peak pressure (P peak ) [HR 1.13; 95% CI 1.00-1.30, P = 0.04] at admission.Interpretation & conclusionsBacterial and viral pneumonia, malaria and tuberculosis resulted in ARDS in a considerable number of patients. Independent predictors of mortality included non-pulmonary organ failure, SAPS II score and P peak at baseline. Elevated levels of biomarkers such as TNF-α, PCT and hsCRP at admission might help in identifying patients at a higher risk of mortality.

Background: Several genetic variants are associated with the risk of idiopathic pulmonary fibrosis (IPF). These have not been systematically reviewed., Methods: We searched the PubMed, Embase and GWAS Catalog databases for studies indexed between inception and 15 January 2024 describing genetic variants associated with IPF susceptibility. We included studies describing common associated single nucleotide polymorphisms (SNPs). We excluded studies describing rare variants, non-SNP variants and those without an allelic model analysis. We recorded study type, participant characteristics, genotyping methods, IPF diagnostic criteria, the SNPs and the respective genes, odds ratios, and other details. We also searched databases for functions of the identified genes., Results: The primary search retrieved 2697 publications; we included 42 studies. There were nine genome-wide association/linkage studies, while 27 were candidate gene studies. The studies included 22-11 160 IPF subjects. 88 SNPs in 58 genes or loci were found associated with IPF susceptibility. MUC5B rs35705950 was the most studied SNP. Most (n=51) SNPs were in the intronic or intergenic regions; only 11 were coding sequence variants. The SNPs had odds ratios ranging from 0.27 to 7.82 for an association with IPF. Only 22 SNPs had moderate-large effects (OR >1.5 or <0.67). Only 49.1% of the associated genes have a known functional role in IPF; the role of G protein-related signalling and transcriptional regulation (zinc-finger proteins) remain unexplored., Conclusion: Several common SNPs in over 50 genes have been found associated with IPF susceptibility. These variants may inform gene panels for future studies (PROSPERO CRD42023408912)., Competing Interests: Conflict of interest: All authors have nothing to disclose., (Copyright ©The authors 2024.)

Background and Objective: There is a need for simple functional test to assess treatment response in chronic pulmonary aspergillosis (CPA) in resource-constrained settings. The one-minute-sit-to-stand test (1-min-STS) is one such test. However, the minimal important difference (MID) for 1-min-STS in subjects with CPA remains unknown. Herein, we estimate the MID for 1-min-STS for CPA subjects., Materials and Methods: We retrospectively reviewed the clinical details of CPA subjects treated with oral azoles for 6 months. We included only subjects who completed the 1-min-STS test at baseline and 6 months. We used the change in VAS (visual analogue scale, for overall improvement) as an external anchor. We used the anchor and the distribution (standard deviation-based) methods to determine the MID estimates. We used the anchor-based method only if there was correlation of 0.3 with the 1-min-STS test., Results: One hundred-eight subjects completed the 1-min-STS test at baseline and 6 months. We did not find significant correlation between the change in VAS for overall improvement (r2 = 0.024, P value = 0.809) and the 1-min-STS test. The MID for the 1-min-STS test was 2 repetitions (range, 1.5-2.8 repetitions)., Conclusion: The MID for the 1-min-STS test in subjects with CPA was 2 repetitions. Future studies using a global rating of change scale as an anchor must confirm our findings., (Copyright © 2024 Copyright: © 2024 Indian Chest Society.)

Aim: There is limited data on prognostic value of baseline plasma cell free DNA (cfDNA) in advanced squamous non-small cell lung cancer (sq-NSCLC). This prospective observational study aimed to assess change in plasma cfDNA levels in locally-advanced/metastatic sq-NSCLC with chemotherapy and its correlation with symptom-scores and radiological-responses., Methods: Chemotherapy-naive patients with stages-IIIB/IIIC/IV sq-NSCLC ( n = 59), smokers with chronic obstructive pulmonary disease [COPD, COPD-controls (CC); n = 27] and healthy-controls ( n = 25) were enrolled. Respiratory symptom burden (RSB) and total symptom burden (TSB) were calculated from mean visual-analog-scores (VAS) of dyspnoea, cough, chest pain, hemoptysis RSB, anorexia and fatigue (all six for TSB). cfDNA was isolated from peripheral blood. All patients received platinum-doublet chemotherapy. RSB/TSB/cfDNA assessment and contrast-enhanced computed tomography (CECT)-thorax scans were done at baseline and post-chemotherapy., Results: At baseline, 13/59 (22%) sq-NSCLC, 3/27 (11%) CC and none (0%) healthy-controls had detectable cfDNA. All three CC were heavy smokers with no evidence of malignancy and undetectable cfDNA levels on repeat testing. In sq-NSCLC group, majority were males (95%), current-smokers (88%), heavy-smokers (70%), had metastatic disease (59%) with median age of 65 years. Eastern Co-operative Oncology Group (ECOG) performance status (PS) was 0-1 (56%) and 2 (42%). Median RSB- and TSB-scores were 9 [interquartile range (IQR) = 5-14] and 16 (IQR = 9-23), respectively. Of the 59 patients, 54 received ≥ 1 cycle while 27 underwent post-C4 evaluation with detectable cfDNA levels in 18/27 (66.7%). No baseline characteristic correlated with cfDNA detectability. Median overall survival (OS) and progression-free survival (PFS) were 262 days and 167 days, respectively. ECOG PS ≥ 2, RSB-score > 9 and TSB-score > 16 were all associated with worse OS and PFS as was cfDNA detectability [median OS = 97 days vs. 298 days and median PFS = 97 days vs. 197 days; P = 0.025; hazard ratio (HR) = 2.17]., Conclusions: Baseline cfDNA detectability is independently associated with poor OS and PFS in patients with advanced sq-NSCLC on chemotherapy., Competing Interests: The authors declare that they have no conflicts of interest., (© The Author(s) 2024.)

Background: Brain metastases (BM) are common in metastatic nonsmall cell lung cancer (NSCLC). However, routine neuroimaging in asymptomatic patients with metastatic NSCLC is controversial as there is no conclusive evidence of benefit from the detection and treatment of asymptomatic BM. Herein, we evaluated the prevalence of asymptomatic BM and its treatment implications in a resource-limited setting., Methods: Consecutive patients with newly diagnosed, treatment-naïve, metastatic, nonsquamous NSCLC (NS-NSCLC) were included. Subjects who already had clinical or radiological features suggestive of BM were excluded from the study. All eligible subjects underwent contrast-enhanced magnetic resonance imaging (MRI) of the brain. Management of the detected BM was at the discretion of the treating clinicians., Results: Among 809 subjects who were screened, 100 (12.4%) were included in the study and underwent MRI. BM was present in 30 (30%) of the subjects and absent in the remaining 70 subjects. A majority of BM were multiple (70%), involved the frontal lobe commonly (73.3%), and had a mean (standard deviation) size of 13.2 (7.3) mm. Detection of BM resulted in a treatment alteration in 17 (17%) of the study subjects (brain irradiation, n = 17, change in targeted therapy, n = 3) with BM. There was no difference in survival of patients who underwent treatment alteration for management of BM compared to those who did not ( P = 0.132)., Conclusions: About one-third of patients with metastatic NS-NSCLC had BM in MRI despite the absence of symptoms. Despite treatment of the majority of the patients with BM with brain irradiation, there was no demonstrable survival benefit. Hence, we conclude that although routine neuroimaging of asymptomatic patients with newly diagnosed metastatic NSCLC may result in treatment alteration (primarily brain irradiation) in a small proportion of patients, it may not influence outcomes in resource-constrained settings., (Copyright © 2023 Copyright: © 2023 Indian Journal of Cancer.)

Background: The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in Indian asthmatic patients remains unknown. We systematically reviewed the literature for estimating the prevalence of Aspergillus sensitization (AS) and ABPA in Indian subjects with bronchial asthma., Methods: We searched the PubMed and Embase databases for studies from India reporting the prevalence of AS or ABPA in at least 50 asthmatics. The primary outcome of our study was to assess the prevalence of ABPA. The secondary outcomes were to evaluate the prevalence of AS in asthma and ABPA in Aspergillus-sensitized asthma. We pooled the prevalence estimates using a random effects model and examined the factors influencing the prevalence using multivariate meta-regression., Results: Of the 8,383 records retrieved, 34 studies with 14,580 asthmatics met the inclusion criteria. All the studies were from tertiary centers. The pooled prevalence of ABPA in asthmatics (26 studies; 5,554 asthmatics) was 16.2% [95% confidence interval (CI), 12.5-20.4]. The pooled prevalence of AS in asthma (29 studies; 13,405 asthmatics) was 30.9% (95% CI, 25.3-36.6), while the prevalence of ABPA in AS (20 studies; 1,493 asthmatics) was 48.2% (95% CI, 39.6-56.8). Meta-regression identified studies published after 2009 (OR 1.14; 95% CI, 1.02-1.28) and studies with severe asthmatics (OR 1.12; 95% CI, 1.00-1.26) as the only factors associated with higher ABPA prevalence., Conclusions: There is a high prevalence of ABPA in Indian asthmatic subjects at tertiary centers, underscoring the need for screening all asthmatic subjects in special asthma and chest clinics for ABPA.

Background: The effect of application of fingernail polish on S pO 2 measurement remains unclear. We conducted this systematic review to ascertain the impact of fingernail polish on S pO 2 measurement., Methods: We queried PubMed, Embase, and CINAHL databases for publications indexed through December 2022. We included studies providing paired S pO 2 data from fingertips without and after nail polish application or reporting the number of subjects whose S pO 2 could not be measured due to fingernail polish. We used random effects modeling to summarize standardized mean differences (SMDs) and corresponding 95% CI for different nail polish colors from comparative studies., Results: We retrieved 122 studies and included 21 publications, mostly performed on healthy volunteers. Of these, 17 (81.0%) studies had a low risk of bias. We summarized mean SMD for 10 nail polish colors (black, blue, brown, green, orange, pink, purple, red, white, and yellow) from 25 paired data sets on S pO 2 across 20 studies. We found small (likely clinically insignificant) but statistically significant differences in mean S pO 2 when fingers were coated with black, blue, brown, or purple nail polish (SMD -0.57, -0.47, -0.33, and -0.25, respectively; 95% CI -0.86 to -0.29, -0.84 to -0.10, -0.59 to -0.07, and -0.48 to -0.02, respectively). Only one of 4 studies reported a high proportion of unsuccessful oximeter readings from fingers painted with black (88.0%) or brown (36.0%) nail polish., Conclusions: Although fingernail polish of some colors can marginally reduce S pO 2 reading or occasionally impede S pO 2 measurement, the variability is clinically insignificant., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2023 by Daedalus Enterprises.)

Background & Objectives: The risk factors for clinically significant diffuse parenchymal lung abnormalities (CS-DPLA) persisting after severe coronavirus disease 2019 (COVID-19) pneumonia remain unclear. The present study was conducted to assess whether COVID-19 severity and other parameters are associated with CS-DPLA., Methods: The study participants included patients who recovered after acute severe COVID-19 and presented with CS-DPLA at two or six month follow up and control group (without CS-DPLA). Adults volunteers without any acute illness, chronic respiratory illness and without a history of severe COVID-19 were included as healthy controls for the biomarker study. The CS-DPLA was identified as a multidimensional entity involving clinical, radiological and physiological pulmonary abnormalities. The primary exposure was the neutrophil-lymphocyte ratio (NLR). Recorded confounders included age, sex, peak lactate dehydrogenase (LDH), advanced respiratory support (ARS), length of hospital stay (LOS) and others; associations were analyzed using logistic regression. The baseline serum levels of surfactant protein D, cancer antigen 15-3 and transforming growth factor-β (TGF-β) were also compared among cases, controls and healthy volunteers., Results: We identified 91/160 (56.9%) and 42/144 (29.2%) participants with CS-DPLA at two and six months, respectively. Univariate analyses revealed associations of NLR, peak LDH, ARS and LOS with CS-DPLA at two months and of NLR and LOS at six months. The NLR was not independently associated with CS-DPLA at either visit. Only LOS independently predicted CS-DPLA at two months [adjusted odds ratios (aOR) (95% confidence interval [CI]), 1.16 (1.07-1.25); P<0.001] and six months [aOR (95% CI) and 1.07 (1.01-1.12); P=0.01]. Participants with CS-DPLA at six months had higher baseline serum TGF-β levels than healthy volunteers., Interpretation and Conclusions: Longer hospital stay was observed to be the only independent predictor of CS-DPLA six months after severe COVID-19. Serum TGF-β should be evaluated further as a biomarker., Competing Interests: None

Background: Interferon-gamma (IFN-γ) down-regulates plasma procalcitonin (PCT), marker of inflammation. Chronic pulmonary aspergillosis (CPA) is associated with low IFN-γ levels. Thus, plasma PCT may be elevated in CPA and could have a role in diagnosing and monitoring treatment response in CPA. Herein, we investigate the diagnostic performance of plasma PCT in CPA., Methods: We extracted the demographic, clinical, radiological, treatment outcomes, and plasma PCT levels of CPA subjects and controls (previously treated pulmonary tuberculosis with radiological abnormalities on CT chest [diseased controls] and treatment naïve active pulmonary tuberculosis [PTB]). We treated CPA subjects with six months of oral itraconazole. We took 0.25 ng/mL as a cut-off value for PCT. The study's primary objective was to ascertain the diagnostic performance of PCT in diagnosing CPA. The key secondary outcome was to study the change in the plasma PCT levels after itraconazole therapy., Results: We included 190 CPA cases and 40 controls (diseased controls [n = 20] and active PTB [n = 20]). PCT was elevated (≥0.25 ng/mL) in only 7 (3.7%) subjects with CPA. The sensitivity and specificity of PCT (≥0.25 ng/mL) were 3.7% (1.5-7.4%) and 100 (91.2-100%), respectively. The area under the curve for plasma PCT was 0.48 (95% confidence interval, 0.39-0.58). The plasma PCT values were available in 93 subjects at six months. There was a significant decline in the median plasma levels of PCT after treatment; however, the PCT levels either increased or remained the same in 45% of the subjects., Conclusion: Plasma procalcitonin has poor performance in diagnosing and following subjects with CPA., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Background : The prevalence of aspergillus sensitization (AS) and allergic bronchopulmonary aspergillosis (ABPA) in asthmatic children remains unclear. Objective : To systematically review the literature to estimate the prevalence of AS and ABPA in children with bronchial asthma. Methods : We searched the PubMed and Embase databases for studies reporting the prevalence of AS or ABPA in pediatric asthma. The primary outcome was to assess the prevalence of AS, while the secondary outcome was to evaluate the prevalence of ABPA. We pooled the prevalence estimates using a random effects model. We also calculated the heterogeneity and publication bias. Results : Of the 11,695 records retrieved, 16 studies with 2468 asthmatic children met the inclusion criteria. Most studies were published from tertiary centers. The pooled prevalence of AS in asthma (15 studies; 2361 subjects) was 16.1% (95% confidence intervals [CI], 9.3-24.3). The prevalence of AS was significantly higher in prospective studies, studies from India, and those from developing countries. The pooled prevalence of ABPA in asthma (5 studies; 505 children) was 9.9% (95% CI, 0.81-27.6). There was significant heterogeneity and publication bias for both outcomes. Conclusions : We found a high prevalence of AS and ABPA in asthmatic children. There is a need for community-based studies from different ethnicities using a standard methodology to ascertain the true prevalence of AS and ABPA in pediatric asthma.

Objective: The diagnostic performance of pleural fluid interleukins as potential biomarkers for tuberculous pleural effusion (TPE) remains unclear. We assessed the diagnostic accuracy of various interleukins in the pleural fluid for TPE and evaluated their ability to differentiate TPE from other effusions., Methods: We queried the PubMed and Embase databases for studies indexed till October 2021. We included studies that (a) provided information regarding sensitivity and specificity of pleural fluid interleukins for diagnosing TPE, or (b) compared pleural fluid interleukin levels between TPE and malignant or parapneumonic effusions. We used hierarchical summary receiver operating characteristic plots to model summary sensitivity and specificity. Random effects modeling was employed to pool standardized mean differences (SMD) across descriptive studies comparing TPE and other effusions., Results: We included 80 publications in our review; most were small and of poor quality. All interleukins except interleukin-27 (interleukins 1-beta, 2, 4, 6, 8, 10, 12, 12p40, 13, 18, 33) showed poor diagnostic accuracy and inconsistent discrimination of TPE from other effusions. The summary estimates for sensitivity, specificity, and diagnostic odds ratio were 0.94 (95 % CI 0.85-0.98), 0.97 (95 % CI 0.93-0.99), and 507.13 (95 % CI 130.66-1968.34) respectively for pleural fluid interleukin-27. Mean pleural fluid interleukin-27 levels in TPE were significantly higher than malignant (summary SMD 3.72, 95 % CI 2.81-4.63) or parapneumonic (summary SMD 2.45, 95 % CI -1.80-3.09) effusions., Conclusion: Pleural fluid interleukins are poor diagnostic biomarkers for TPE. Only pleural fluid interleukin-27 exhibited good accuracy in diagnosing TPE and needs further evaluation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Advancements in the intensive care unit (ICU) have improved critically ill subjects' short-term outcomes. However, there is a need to understand the long-term outcomes of these subjects. Herein, we study the long-term outcomes and factors associated with poor outcomes in critically ill subjects with medical illnesses., Materials and Methods: All subjects (≥12 years) discharged after an ICU stay of at least 48 hours were included. We evaluated the subjects at 3 and 6 months after ICU discharge. At each visit, subjects were administered the World Health Organization Quality of Life Instrument (WHO-QOL-BREF) questionnaire. The primary outcome was mortality at 6 months after ICU discharge. The key secondary outcome was quality of life (QOL) at 6 months., Results: In total, 265 subjects were admitted to the ICU, of whom 53 subjects (20%) died in the ICU, and 54 were excluded. Finally, 158 subjects were included: 10 (6.3%) subjects were lost to follow-up. The mortality at 6 months was 17.7% (28/158). Most subjects [16.5% (26/158)] died within the initial 3 months after ICU discharge. Quality of life scores were low in all the domains of WHO-QOL-BREF. About 12% ( n = 14) of subjects could not perform the activity of daily living at 6 months. After adjusting for covariates, ICU-acquired weakness at the time of discharge (OR 15.12; 95% CI, 2.08-109.81, p <0.01) and requirement for home ventilation (OR 22; 95% CI, 3.1-155, p <0.01) were associated with mortality at 6 months., Conclusion: Intensive care unit survivors have a high risk of death and a poor QOL during the initial 6 months following discharge., How to Cite This Article: Kodati R, Muthu V, Agarwal R, Dhooria S, Aggarwal AN, Prasad KT, et al . Long-term Survival and Quality of Life among Survivors Discharged from a Respiratory ICU in North India: A Prospective Study. Indian J Crit Care Med 2022;26(10):1078-1085., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2022; Jaypee Brothers Medical Publishers (P) Ltd.)

Objective: Pleural fluid lysozyme (LP) and its ratio to serum lysozyme (LP/LS) have been proposed as potential biomarkers for diagnosing tuberculous pleural effusion (TPE). We assessed the diagnostic accuracy of LP and LP/LS for TPE and evaluated their ability to differentiate TPE from other effusions., Methods: We queried the PubMed and Embase databases for studies indexed until October 2021. We included studies that (a) provided information regarding the sensitivity and specificity of LP or LP/LS for the diagnosis of TPE, or (b) compared LP or LP/LS between TPE and malignant or parapneumonic effusions. We used hierarchical summary receiver operating characteristic plots to model summary sensitivity and specificity. Random effects modeling was employed to pool standardized mean differences (SMD) across descriptive studies comparing TPE and other effusions., Results: We included 11 publications in our review, most of which were small and of poor quality. The summary estimates for sensitivity, specificity, and diagnostic odds ratio (DOR) were 0.94 (95% confidence interval [CI] 0.53-1.00), 0.89 (95% CI 0.63-0.97), and 129.88 (95% CI 6.26-2695), and 0.98 (95% CI 0.58-1.00), 0.91 (95% CI 0.84-0.96), and 708.47 (95% CI 11.42-43946), respectively, for LP and LP/LS. Mean LP and LP/LS in TPE were significantly higher than in malignant effusions (summary SMD 1.51 [95% CI 1.04-1.98] and 1.77 [95% CI 1.31-2.22], respectively), and parapneumonic effusions (summary SMD 0.86 [95% CI 0.51-1.22] and 1.15 [95% CI 0.64-1.66], respectively)., Conclusion: There is low-quality evidence of good diagnostic accuracy for both LP and LP/LS in identifying TPE, the latter being marginally superior., Competing Interests: None

Background and Objective: The epidemiology of interstitial lung diseases (ILDs) in developing countries remains unknown. The objective of this study was to estimate the incidence, prevalence, and national burden of ILDs in India., Methods: Data of consecutive subjects (aged >12 years) with ILDs included in a registry between March 2015 and February 2020 were analyzed retrospectively. The proportion of each ILD subtype was determined. The crude annual incidence and prevalence of ILDs for our region were estimated. Subsequently, the primary estimates of the national annual incident and prevalent burden of ILD and its subtypes were calculated. Alternative estimates for each ILD subtype were calculated using the current and a large, previous Indian study (n = 1,084). Data were analyzed using SPSS version 22 and are presented descriptively., Results: A total of 2,005 subjects (mean age, 50.7 years; 47% men) were enrolled. Sarcoidosis (37.3%) was the most common ILD subtype followed by connective tissue disease (CTD)-related ILDs (19.3%), idiopathic pulmonary fibrosis (IPF, 17.0%), and hypersensitivity pneumonitis (HP, 14.4%). The crude annual incidence and prevalence of ILDs were 10.1-20.2 and 49.0-98.1, respectively per 100,000 population. The best primary estimates for the crude national burden of all ILDs, sarcoidosis, CTD-ILD, IPF, HP, and other ILDs (in thousands) were 433-867, 213-427, 75-150, 51-102, 54-109, and 39-78. The respective alternative estimates (in thousands) were sarcoidosis, 127-254; CTD-ILD, 81-162; IPF, 46-91; HP, 130-261; other ILDs, 49-98., Conclusion: In contrast to developed countries, sarcoidosis and HP are the ILDs with the highest burden in India., Competing Interests: The authors have declared that no competing interests exist.

Objective: We compared diagnostic accuracy of pleural fluid Xpert MTB/RIF (Xpert) and Xpert MTB/RIF Ultra (Ultra) assays for diagnosing tuberculous pleural effusion (TPE), through systematic review and comparative meta-analysis., Methods: We searched PubMed and Embase databases for publications reporting diagnostic accuracy of Xpert or Ultra for TPE. We used bivariate random-effects modeling to summarize diagnostic accuracy information from individual studies using either mycobacterial culture or composite criteria as reference standard. We performed meta-regression through hierarchical summary receiver operating characteristic (HSROC) modeling to evaluate comparative performance of the two tests from studies reporting diagnostic accuracy of both in the same study population., Results: We retrieved 1097 publications, and included 74 for review. Summary estimates for sensitivity and specificity for Xpert were 0.52 (95% CI 0.43-0.60, I2 82.1%) and 0.99 (95% CI 0.97-0.99, I2 85.1%), respectively, using culture-based reference standard; and 0.21 (95% CI 0.17-0.26, I2 81.5%) and 1.00 (95% CI 0.99-1.00, I2 37.6%), respectively, using composite reference standard. Summary estimates for sensitivity and specificity for Ultra were 0.68 (95% CI 0.55-0.79, I2 80.0%) and 0.97 (95% CI 0.97-0.99, I2 92.1%), respectively, using culture-based reference standard; and 0.47 (95% CI 0.40-0.55, I2 64.1%) and 0.98 (95% CI 0.95-0.99, I2 54.8%), respectively, using composite reference standard. HSROC meta-regression yielded relative diagnostic odds ratio of 1.28 (95% CI 0.65-2.50) and 1.80 (95% CI 0.41-7.84) respectively in favor of Ultra, using culture and composite criteria as reference standard., Conclusion: Ultra provides superior diagnostic accuracy over Xpert for diagnosing TPE, mainly because of its higher sensitivity., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: None

Background: Various molecular underpinnings of lung cancer have been noted in Asian populations, especially with targetable oncogenic drivers such as EGFR mutations and ALK rearrangements, although they have been lesser described in South Asian/Indian patients., Methods: Tumour molecular testing results from non-small cell lung cancer (NSCLC) patients with a name of South Asian origin and diagnosed from 2005 to 2019 at the Stanford Cancer Center in the United States were retrospectively reviewed and compared to the results of molecular testing from PGIMER in Chandigarh, India, from the patients diagnosed from 2011 to 2019., Results: We identified 72 patients of South Asian (largely Indian) origin, of whom 64 patients (51% female) had mutational testing at Stanford. Of the tested patients, 33% of cases harboured either an EGFR exon 19 deletion or exon 21 L858R mutation, and 12.5% had ALK rearrangements. At PGIMER, a larger sample of 1,264 patients was identified (33% female), with 22.5% of patients having two main EGFR activating mutations, and 9.5% harbouring an ALK rearrangement., Conclusions: South Asian, largely Indian, patients with NSCLC appear to have a higher chance of harbouring EGFR mutations and ALK translocation as compared to Caucasians. The percentage of South Asian patients with these molecular abnormalities was largely similar in two different geographical locations. These findings corroborate prior single-institution findings and emphasise the importance of molecular testing., Competing Interests: None

Competing Interests: None

Background: SARSCoV-2, a coronavirus that causes COVID-19, is spreading rapidly. By the middle of August-2021, it has affected over 3 million confirmed cases in India. The main aim of this study was to examine the clinical profile of COVID-19 patients and their length of stay during treatment in a hospital., Materials and Methods: It was a hospital-based retrospective study conducted by using a total enumeration technique in July-August 2021 at Nehru Hospital, Postgraduate Institute of Medical Education and Research (PGIMER) in India. The present study was conducted on 72 COVID-19 patients who took treatment in 4C and 5C wards. Structured questionnaires were used to collect data, which included bio-demographic factors and questions about their treatment and length of stay., Results: The majority of the 72 COVID-19 positive patients were men (62%), belonged to the age group of 41-60 years (35%), had SpO 2 levels ranging from 91%-95% (45%), and received room air O 2 therapy (63%) during their treatment in the hospital. Female patients had a longer length of stay (7.33 days), patients under the age of 20 years had the longest hospital stay (11.5 days), patients with SpO 2 less than 70% had the longest hospital stay (8 days), and patients who received oxygen using a non-rebreathing mask had the longest hospital stay (11 days)., Conclusion: To avoid panic situations, regular admission and discharge of patients was essential due to the considerable increase in cases during the second wave. Patient length of stay was reduced as a consequence of collaboration and cooperation among all physicians, residents, staff nurses, and paramedics, with the goal of discharging the patient after a room air trial and follow up if needed., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Background: Venous thromboembolism (VTE) in cancer remains underdiagnosed. This prospective study aimed to evaluate the feasibility of screening for VTE in lung cancer (LC) patients. We assess the incidence of VTE, its risk factors, and effects on overall survival (OS)., Methods: Consecutive treatment-naive LC patients were screened for deep venous thrombosis (DVT) with compression ultrasonography and pulmonary thromboembolism (PTE) with computed tomography pulmonary angiography (CTPA) at diagnosis and after 3 months of treatment. The incidence rate of VTE (DVT and/or PTE) was calculated. Risk factors associated with VTE were assessed using logistic regression analysis. All participants were followed-up to 1 year after enrollment. OS was compared in LC subjects with and without VTE, using the Cox proportional hazard analysis., Results: Around 301 subjects with LC (stages IIIB-IV accounted for 83.1%) were enrolled, of which 16 had VTE (5.3%). The incidence rate of VTE was 90 per 1000 person-years (PY). PTE was asymptomatic in 27.3% of cases while all DVT episodes were symptomatic. The incidence rate of asymptomatic PTE identified during the screening was 17 per 1000 PY. The median duration from LC diagnosis to the VTE event was 96.5 days. Median OS was significantly less in VTE patients [161 versus 311 days; P = 0.007] and death was attributable to VTE in 50%. After adjusting for covariates, VTE (hazard ratio [HR] = 2.1), smoking (HR = 1.7), and Eastern cooperative oncology group performance status ≥2 (HR = 1.6) were independently associated with poor OS in LC., Conclusions: VTE occurs in approximately 1 in 20 newly-diagnosed patients with LC and is associated with decreased OS. Screening for PTE may be considered even in resource-limited settings., Competing Interests: None

Background: The modified International Society for Human and Animal Mycology (ISHAM) allergic bronchopulmonary aspergillosis (ABPA) working group (AWG) criteria lists up to five components for diagnosing ABPA in asthmatics. Whether eliminating specific components of the existing criteria would have the same diagnostic utility as the original remains unknown., Objective: To evaluate the performance of several simplified criteria for diagnosing ABPA., Methods: We compared the performance of seven new criteria (after excluding or modifying one or more of the components of the ISHAM-AWG criteria) with the modified ISHAM-AWG criteria in asthmatic subjects using latent class analysis (LCA). We also tested the performance of the newer criteria using accuracy measures against a multidisciplinary team (MDT) diagnosis of ABPA. We considered the diagnostic accuracy of the newer criteria to be acceptable if the correct classification and false-negative rates were >95% and <5%, respectively, on an MDT evaluation., Results: We analyzed data from 543 asthmatic subjects (58.8% women; mean age, 36.8 years). Using LCA, the sensitivity of the A.fumigatus -specific IgE-based criteria ranged from 92-99%, while the specificity varied between 92% and 100%. The MDT diagnosed ABPA in 106 (19.5%) subjects. Using MDT as the reference standard, the correct classification and false-negative rates were >95% for three of the seven and <5% for four of the seven newer criteria., Conclusions: We found several of the newly developed criteria to perform, like the modified ISHAM-AWG criteria, for diagnosing ABPA complicating asthma. A prospective study in current clinical algorithms is required for validating our observations., Competing Interests: RA has received grant support from Cipla, India on research in ABPA PS. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Agarwal, Saxena, Muthu, Sehgal, Dhooria, Prasad, Aggarwal and Chakrabarti.)

Muthu V, Sehgal IS, Dhooria S, Prasad KT, Aggarwal AN, Agarwal R. Corticosteroids for Non-severe COVID-19: Primum Non Nocere. Indian J Crit Care Med 2022;26(3):403-404., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2022; Jaypee Brothers Medical Publishers (P) Ltd.)

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disorder characterized by the accumulation of surfactant in the alveolar spaces resulting in hypoxemic respiratory failure. Whole lung lavage (WLL), the preferred treatment for PAP, physically removes the lipoproteinaceous material from the alveolar spaces. Since its initial description in 1963, the WLL procedure has undergone various modifications. However, the procedure has not been standardized yet. After securing a double lumen endotracheal tube, we perform WLL under general anesthesia. One lung is ventilated, while the other is lavaged using one-liter aliquots of pre-warmed saline. We use gravity-assisted drainage of the lavaged lung after each cycle till the milky white and opaque fluid becomes clear (usually 15-20 cycles). Herein, we describe the step-by-step procedure, precautions, and monitoring of WLL. We also provide videos demonstrating one-lung ventilation and bronchoscopic confirmation of lung isolation., Competing Interests: Each author declares that he or she has no commercial associations (e.g. consultancies, stock ownership, equity interest, patent/licensing arrangement etc.) that might pose a conflict of interest in connection with the submitted article.

Background: We conducted this systematic review to evaluate whether asthma increases the risk of severe disease and adverse outcomes among subjects with COVID-19., Methods: We queried the PubMed and Embase databases for studies indexed through December 2020. We included studies providing data on severe disease, hospitalization, ICU care, need for mechanical ventilation, or mortality among subjects with COVID-19 with and without asthma. We calculated the relative risk for each reported outcome of interest and used random effects modeling to summarize the data., Results: We retrieved 1,832 citations, and included 90 studies, in our review. Most publications reported data retrieved from electronic records of retrospective subject cohorts. Only 25 studies were judged to be of high quality. Subjects with asthma and COVID-19 had a marginally higher risk of hospitalization (summary relative risk 1.13, 95% CI 1.03-1.24) but not for severe disease (summary relative risk 1.17, 95% CI 0.62-2.20), ICU admission (summary relative risk 1.13, 95% CI 0.96-1.32), mechanical ventilation (summary relative risk 1.05, 95% CI 0.85-1.29), or mortality (summary relative risk 0.92, 95% CI 0.82-1.04) as compared to subjects with COVID-19 without asthma., Conclusions: Comorbid asthma increases risk of COVID-19-related hospitalization but not severe disease or other adverse outcomes in subjects with COVID-19., Competing Interests: The authors have no conflicts to disclose., (Copyright © 2021 by Daedalus Enterprises.)

Background: Data on the prevalence of programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) in non-small cell lung cancer (NSCLC) and their clinical significance in Indian patients are limited., Methods: Newly diagnosed NSCLC cases (adenocarcinoma or squamous cell carcinoma [SqCC] histology) were included in the present study. The TILs were evaluated based on morphology on hematoxylin and eosin-stained slides. PD-L1 expression in tumors was assessed using immunohistochemistry with rabbit monoclonal antibody (SP263) on the Ventana automated immunostainer. Tumors with PD-L1 expression > 50% on tumor cells were considered PD-L1-positive. Tumors in which TILs occupy > 25% of stroma were considered to have high TILs. The association of PD-L1 expression and TILs with various clinical parameters including overall survival (OS) was investigated., Results: The present study included 128 cases of NSCLC (67 adenocarcinoma, 61 SqCC). PD-L1 positivity was observed in 17.2% of the patients with NSCLC. Baseline characteristics of PD-L1-positive subjects were similar to PD-L1-negative subjects except for a higher prevalence of liver metastasis (18.2% vs. 2.8%; p = .018) and a higher probability of diagnosis from extrapulmonary biopsies. High TILs were observed in 26.6% of the subjects. However, PD-L1 expression and high TIL did not affect OS., Conclusions: PD-L1 positivity and high TILs were observed in 20% and 25% of the patients with NSCLC, respectively, however, neither were predictors of survival in SqCC.

Objective: The proportion of COVID-19 patients having active pulmonary tuberculosis, and its impact on COVID-19 related patient outcomes, is not clear. We conducted this systematic review to evaluate the proportion of patients with active pulmonary tuberculosis among COVID-19 patients, and to assess if comorbid pulmonary tuberculosis worsens clinical outcomes in these patients., Methods: We queried the PubMed and Embase databases for studies providing data on (a) proportion of COVID-19 patients with active pulmonary tuberculosis or (b) severe disease, hospitalization, or mortality among COVID-19 patients with and without active pulmonary tuberculosis. We calculated the proportion of tuberculosis patients, and the relative risk (RR) for each reported outcome of interest. We used random-effects models to summarize our data., Results: We retrieved 3,375 citations, and included 43 studies, in our review. The pooled estimate for proportion of active pulmonary tuberculosis was 1.07% (95% CI 0.81%-1.36%). COVID-19 patients with tuberculosis had a higher risk of mortality (summary RR 1.93, 95% CI 1.56-2.39, from 17 studies) and for severe COVID-19 disease (summary RR 1.46, 95% CI 1.05-2.02, from 20 studies), but not for hospitalization (summary RR 1.86, 95% CI 0.91-3.81, from four studies), as compared to COVID-19 patients without tuberculosis., Conclusion: Active pulmonary tuberculosis is relatively common among COVID-19 patients and increases the risk of severe COVID-19 and COVID-19-related mortality., Competing Interests: The authors have declared that no competing interests exist.

Background: Whether a combination of glucocorticoid and antifungal triazole is superior to glucocorticoid alone in reducing exacerbations in patients with allergic bronchopulmonary aspergillosis (ABPA) remains unknown. We aimed to compare the efficacy and safety of prednisolone-itraconazole combination versus prednisolone monotherapy in ABPA., Methods: We randomised subjects with treatment-naïve acute-stage ABPA complicating asthma to receive either prednisolone alone (4 months) or a combination of prednisolone and itraconazole (4 and 6 months, respectively). The primary outcomes were exacerbation rates at 12 months and glucocorticoid-dependent ABPA within 24 months of initiating treatment. The key secondary outcomes were response rates, percentage decline in serum total IgE at 6 weeks, time to first ABPA exacerbation and treatment-emergent adverse events (TEAEs)., Results: We randomised 191 subjects to receive either prednisolone (n=94) or prednisolone-itraconazole combination (n=97). The 1-year exacerbation rate was 33% and 20.6% in the prednisolone monotherapy and prednisolone-itraconazole combination arms, respectively (p=0.054). None of the participants progressed to glucocorticoid-dependent ABPA. All of the subjects experienced a composite response at 6 weeks, along with a decline in serum total IgE (mean decline 47.6% versus 45.5%). The mean time to first ABPA exacerbation (417 days) was not different between the groups. None of the participants required modification of therapy due to TEAEs., Conclusions: There was a trend towards a decline in ABPA exacerbations at 1 year with the prednisolone-itraconazole combination versus prednisolone monotherapy. A three-arm trial comparing itraconazole and prednisolone monotherapies with their combination, preferably in a multicentric design, is required to define the best treatment strategy for acute-stage ABPA., Competing Interests: Conflict of interest: R. Agarwal has received grant support for conducting research in ABPA from Cipla Pharmaceuticals, Mumbai, India, outside the submitted work. Conflict of interest: V. Muthu has nothing to disclose. Conflict of interest: I.S. Sehgal has nothing to disclose. Conflict of interest: S. Dhooria has nothing to disclose. Conflict of interest: K.T. Prasad has nothing to disclose. Conflict of interest: M. Garg has nothing to disclose. Conflict of interest: A.N. Aggarwal has nothing to disclose. Conflict of interest: A. Chakrabarti has nothing to disclose., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Objective: We compared diagnostic accuracy of pleural fluid adenosine deaminase (ADA) and interferon-gamma (IFN-γ) in diagnosing tuberculous pleural effusion (TPE) through systematic review and comparative meta-analysis., Methods: We queried PubMed and Embase databases to identify studies providing paired data for sensitivity and specificity of both pleural fluid ADA and IFN-γ for diagnosing TPE. We used hierarchical summary receiver operating characteristic (HSROC) plots and HSROC meta-regression to model individual and comparative diagnostic performance of the two tests., Results: We retrieved 376 citations and included 45 datasets from 44 publications (4974 patients) in our review. Summary estimates for sensitivity and specificity for ADA were 0.88 (95% CI 0.85-0.91) and 0.91 (95% CI 0.89-0.92), while for IFN-γ they were 0.91 (95% CI 0.89-0.94) and 0.96 (95% CI 0.94-0.97), respectively. HSROC plots showed consistently greater diagnostic accuracy for IFN-γ over ADA across the entire range of observations. HSROC meta-regression using test-type as covariate yielded a relative diagnostic odds ratio of 2.22 (95% CI 1.68-2.94) in favour of IFN-γ, along with better summary sensitivity and specificity figures. No prespecified subgroup variable significantly influenced the summary diagnostic accuracy estimates., Conclusion: Pleural fluid IFN-γ estimation has better diagnostic accuracy than ADA estimation for diagnosis of TPE., Competing Interests: The authors have declared that no competing interests exist.

Background: Whether age would impact the outcomes in subjects with acute respiratory distress syndrome (ARDS) remains unclear. Herein, we study the effect of age as a predictor of mortality in ARDS., Materials and Methods: We categorized consecutive subjects with ARDS as either ARDS elderly (age >65 years) or ARDSnon elderly (age ≤65 years) admitted to the respiratory intensive care unit (ICU) of a tertiary care hospital in North India between January 2007 and December 2019. We compared the baseline clinical and demographic characteristics, lung mechanics, and mortality between the two groups. We also analyzed the factors predicting ICU survival using multivariate logistic regression analysis., Results: We included 625 patients (ARDS elderly , 140 [22.4%] and ARDS nonelderly , 485 [77.6%]) with a mean (standard deviation) age (56.3% males) of 40.6 (17.8) years. The ARDS elderly were more likely ( p = 0.0001) to have the presence of any comorbid illness compared to ARDS nonelderly . The elderly subjects had significantly higher pulmonary ARDS than the younger group. The severity of ARDS was however, similarly distributed between the two study arms. There were 224 (35.8%) deaths, and the mortality was significantly higher ( p = 0.012) in the ARDS elderly than the to ARDS nonelderly (ARDS elderly vs ARDS nonelderly , 45 vs 33.2%). On multivariate logistic regression analysis, the baseline sequential organ failure assessment scores, presence of pulmonary ARDS, and the development of new organ dysfunction were the independent predictors of mortality., Conclusion: The outcomes in subjects with ARDS are dependent on the severity of illness at admission and the etiology of ARDS rather than the age alone., How to Cite This Article: Sehgal IS, Agarwal R, Dhooria S, Prasad KT, Muthu V, Aggarwal AN. Etiology and Outcomes of ARDS in the Elderly Population in an Intensive Care Unit in North India. Indian J Crit Care Med 2021;25(6):648-654., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2021; Jaypee Brothers Medical Publishers (P) Ltd.)