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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.
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BACKGROUND: Modalities to improve tissue acquisition during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) have been investigated. Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy (EBUS-TMC) is a modality to obtain larger histological samples by inserting a cryoprobe into the mediastinal lesion. We aimed to study the diagnostic yield and safety of EBUS-TMC. METHODS: We performed a systematic search of the PubMed and Embase databases to extract the relevant studies. We then performed a meta-analysis to calculate the diagnostic yield of EBUS-TMC and compare it with EBUS-TBNA. RESULTS: Following a systematic search, we identified 14 relevant studies (869 patients undergoing EBUS-TMC and EBUS-TBNA). We then performed a meta-analysis of the diagnostic yield of EBUS-TMC and EBUS-TBNA from studies wherein both procedures were performed. The pooled diagnostic yield of EBUS-TMC was 92% (95% confidence interval [CI], 89%-95%). The pooled diagnostic yield of EBUS-TBNA was 81% (95% CI, 77%-85%). The risk difference in yield was 11% (95% CI, 6%-15%, I2 = 0%) when EBUS-TMC and EBUS-TBNA were compared. The only complication reported commonly with EBUS-TMC was minor bleeding. The complication rate was comparable with EBUS-TBNA. CONCLUSION: EBUS-TMC provides a greater diagnostic yield with a similar risk of adverse events compared to EBUS-TBNA. Future studies are required to clearly establish which patients are most likely to benefit from this modality.
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Objectives: This systematic review and meta-analysis aimed at summarizing the evidence of efficacy and safety of rituximab in rheumatoid arthritis-related interstitial lung disease (RA-ILD). Materials and methods: PubMed and Embase databases were searched until June 22, 2022, to identify studies on RA-ILD treated with rituximab, confined to predefined inclusion and exclusion criteria. A systematic review and meta-analysis were performed on the included studies to assess the overall stabilization or improvement in ILD, changes in percent-predicted (%-predicted) forced vital capacity (FVC), and %-predicted diffusion capacity of lungs for carbon monoxide (DLCO) following rituximab therapy. Results: A total of 15 studies (4 prospective and 11 retrospective studies) were included, with a total of 314 patients. There were 105 (60.7%) females out of 173 subjects for whom sex details were available from seven studies. The overall pooled proportion of patients with stabilization or improvement in ILD was 0.88 [95% confidence interval (CI): 0.76-0.96, p=0.02]. Rituximab improved FVC from baseline by 7.50% (95% CI: 1.35-13.65; p=0.02, fixed effect). Similarly, rituximab improved DLCO by 6.39% (95% CI: 1.366-14.43; p=0.12, random-effect). Two retrospective studies reported reduced mortality with rituximab therapy compared to tumor necrosis factor-alpha inhibitors. Conclusion: Treatment with rituximab in RA-ILD was associated with a significant improvement in %-predicted FVC, as well as stabilization or improvement in ILD after one year of treatment.
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PURPOSE: Obstructive sleep apnea (OSA) is a common clinical problem that is associated with adverse cardiovascular outcomes attributed to the oxidative stress due to sympathetic overstimulation. Treatment approaches targeting oxidative stress have been tried by multiple investigators. This systematic review and meta-analysis evaluated the efficacy and safety of such approaches. METHODS: Pubmed and Embase databases were searched for human studies evaluating the utility of antioxidant therapies in patients with OSA. RESULTS: A total of six studies (five randomized trials and one case-control study) were included, including 160 patients with OSA using N-acetyl cysteine, vitamin C, carbocysteine, superoxide dismutase, vitamin E, allopurinol, and their combinations. There was a significant improvement in flow-mediated dilatation (FMD) following antioxidants, with the pooled effect being 2.16 % (95% CI 1.65-2.67) using the random-effects model (I2 = 0% and p<0.001). It was also associated with a significant reduction in malondialdehyde levels and an increase in reduced glutathione (GSH) levels. There was also a significant improvement in the Epworth sleepiness scale, oxygen desaturation index, and minimum oxygen saturation during sleep without any significant adverse effects. CONCLUSION: Antioxidant therapy in patients with OSA is associated with improved endothelial function, reduced oxidative stress, and improved sleep parameters. These results call for future multicentre studies with longer follow-ups to assess the utility of antioxidant therapy in patients with OSA.
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Antioxidants , Oxidative Stress , Sleep Apnea, Obstructive , Sleep Apnea, Obstructive/drug therapy , Humans , Antioxidants/therapeutic use , Oxidative Stress/drug effects , Oxidative Stress/physiologyABSTRACT
Pleural effusion is a common problem in our country, and most of these patients need invasive tests as they can't be evaluated by blood tests alone. The simplest of them is diagnostic pleural aspiration, and diagnostic techniques such as medical thoracoscopy are being performed more frequently than ever before. However, most physicians in India treat pleural effusion empirically, leading to delays in diagnosis, misdiagnosis and complications from wrong treatments. This situation must change, and the adoption of evidence-based protocols is urgently needed. Furthermore, the spectrum of pleural disease in India is different from that in the West, and yet Western guidelines and algorithms are used by Indian physicians. Therefore, India-specific consensus guidelines are needed. To fulfil this need, the Indian Chest Society and the National College of Chest Physicians; the premier societies for pulmonary physicians came together to create this National guideline. This document aims to provide evidence based recommendations on basic principles, initial assessment, diagnostic modalities and management of pleural effusions.
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ABSTRACT: Medical Thoracoscopy (MT) is commonly performed by respiratory physicians for diagnostic as well as therapeutic purposes. The aim of the study was to provide evidence-based information regarding all aspects of MT, both as a diagnostic tool and therapeutic aid for pulmonologists across India. The consensus-based guidelines were formulated based on a multistep process using a set of 31 questions. A systematic search of published randomized controlled clinical trials, open labelled studies, case reports and guidelines from electronic databases, like PubMed, EmBase and Cochrane, was performed. The modified grade system was used (1, 2, 3 or usual practice point) to classify the quality of available evidence. Then, a multitude of factors were taken into account, such as volume of evidence, applicability and practicality for implementation to the target population and then strength of recommendation was finalized. MT helps to improve diagnosis and patient management, with reduced risk of post procedure complications. Trainees should perform at least 20 medical thoracoscopy procedures. The diagnostic yield of both rigid and semirigid techniques is comparable. Sterile-graded talc is the ideal agent for chemical pleurodesis. The consensus statement will help pulmonologists to adopt best evidence-based practices during MT for diagnostic and therapeutic purposes.
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BACKGROUND AND OBJECTIVES: The role of cell-free DNA (cfDNA) in operable nonsmall cell lung cancer (NSCLC) is unclear. This study was aimed to evaluate the feasibility for identification of cfDNA in pleural lavage fluid and its correlation with plasma in resectable NSCLCs. METHODS: Consecutively resected NSCLCs were evaluated for cfDNA levels in preoperative plasma (PLS1), intraoperative pleural-lavage (PLV) and postoperative (at 1 month) plasma sample (PLS2). CfDNA was isolated and measured quantitatively by qPCR in a TaqMan probe-detection approach using the human ß-actin gene as the amplifying target. RESULTS: All (n = 34) except one were negative for malignant cells in PLV cytology. CfDNA could be isolated from all the three samples (PLS1, PLV, and PLS2) successfully in each patient. The median cfDNA levels in PLS1, PLV and PLS2 were 118 ng/mL (IQR 61-158), 167 ng/mL (IQR 59.9-179.9) and 103 ng/mL (IQR 66.5-125.4) respectively. The median follow-up was 34.1 months (IQR 25.2-41.6). A significant overall-survival (OS) and disease-free survival (DFS) were recorded for patients with cfDNA level cut-offs at 125, 170, and 100 ng/mL, respectively for PLS1, PLV, and PLS2. Patients with raised cfDNA in PLS1 (>125 ng/mL) and PLV (>170 ng/mL) had significantly poorer 2-year OS, p = 0.005 and p = 0.012, respectively. The hazards (OS) were also higher for those with raised cfDNA in PLV (HR = 5.779, 95% CI = 1.162-28.745, p = 0.032). PLV (>170 ng/mL) had increased pleural recurrences (p = 0.021) and correlated significantly with poorer DFS at 2-years (p = 0.001) with increased hazards (HR = 9.767, 95% CI = 2.098-45.451, p = 0.004). Multivariable analysis suggested higher cfDNA in PLV as a poor prognostic factor for both OS and DFS. CONCLUSIONS: Among patients with operable NSCLC, it is feasible to identify cfDNA in pleural lavage and correlate PLV cfDNA with pleural recurrences and outcomes.
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Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung , Cell-Free Nucleic Acids , Lung Neoplasms , Therapeutic Irrigation , Humans , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/mortality , Lung Neoplasms/surgery , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Lung Neoplasms/mortality , Male , Female , Pilot Projects , Middle Aged , Aged , Biomarkers, Tumor/genetics , Biomarkers, Tumor/blood , Prognosis , Cell-Free Nucleic Acids/blood , Cell-Free Nucleic Acids/genetics , Therapeutic Irrigation/methods , Neoplasm Staging , Follow-Up Studies , Survival RateABSTRACT
INTRODUCTION: The dysregulated host immune response in sepsis is orchestrated by peripheral blood leukocytes. This study explored the associations of the peripheral blood leukocyte subpopulations with early clinical deterioration and mortality in sepsis. METHODS: We performed a prospective observational single-center study enrolling adult subjects with sepsis within 48â h of hospital admission. Peripheral blood flow cytometry was performed for the patients at enrolment and after 5 days. The primary outcome was to explore the association between various leukocyte subpopulations at enrolment and early clinical deterioration [defined as an increase in the sequential organ failure assessment (SOFA) score between enrolment and day 5, or death before day 5]. Other pre-specified outcomes explored associations of leukocyte subpopulations at enrolment and on day 5 with in-hospital mortality. RESULTS: A total of 100 patients, including 47 with septic shock were enrolled. The mean (SD) age of the patients was 53.99 (14.93) years. Among them, 26 patients had early clinical deterioration, whereas 41 died during hospitalization. There was no significant association between the leukocyte subpopulations at enrolment and early clinical deterioration on day 5. On multivariate logistic regression, a reduced percentage of CD8 + CD25+ T-cells at enrolment was associated with in-hospital mortality [odds ratio (OR), 0.82 (0.70-0.97); p-value = 0.02]. A reduced lymphocyte percentage on day 5 was associated with in-hospital mortality [OR, 0.28 (0.11-0.69); p-value = 0.01]. In a post-hoc analysis, patients with "very early" deterioration within 48â h had an increased granulocyte CD64 median fluorescent intensity (MFI) [OR, 1.07 (1.01-1.14); p-value = 0.02] and a reduced granulocyte CD16 MFI [OR, 0.97 (0.95-1.00); p-value = 0.04] at enrolment. CONCLUSIONS: None of the leukocyte subpopulations showed an association with early clinical deterioration at day 5. Impaired lymphocyte activation and lymphocytopenia indicative of adaptive immune dysfunction may be associated with in-hospital mortality.
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Clinical Deterioration , Sepsis , Adult , Humans , Middle Aged , Flow Cytometry , Prognosis , Leukocytes , Intensive Care Units , Retrospective StudiesABSTRACT
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a standard-of-care modality for evaluating mediastinal lymph nodes and masses. The EBUS bronchoscope may also be introduced through the oesophageal route to perform sampling of accessible lesions, a technique described as transoesophageal bronchoscopic ultrasound-guided fine-needle aspiration (EUS-B-FNA). Because of the central oesophageal approach, EUS-B-FNA provides easy access to the left para-tracheal, subcarinal and para-oesophageal lymph nodes. In addition, the left adrenal gland (LAG) can also be imaged and sampled during the EUS-B-FNA procedure. In patients with suspected lung cancer, accurate staging is essential. Adrenal metastasis is relatively common and may often be a solitary metastatic site. We describe three cases where EUS-B-FNA was performed to safely sample the enlarged LAG in suspected lung cancer. We also review the literature on the performance characteristics of EUS-B-FNA for LAG aspiration.
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INTRODUCTION: Nonsmokers with chronic obstructive pulmonary disease (COPD) are neglected despite constituting half of all cases in studies from the developed world. Herein, we systematically reviewed the prevalence of COPD among nonsmokers in India. CONTENT: We searched Embase, Scopus, and PubMed databases for studies examining the prevalence of COPD among nonsmokers in India. We used the Joanna Briggs Institute (JBI) checklist to assess included studies' quality. Meta-analysis was performed using random-effects model. SUMMARY: Seven studies comprising 6,903 subjects were included. The quality of the studies ranged from 5/9 to 8/9. The prevalence of COPD varied between 1.6 and 26.6â¯%. Studies differed considerably in demographics and biomass exposure profiles of subjects. Among the four studies that enrolled both middle-aged and elderly Indian nonsmokers not screened based on biomass fuel exposure, the pooled prevalence of COPD was 3â¯% (95â¯% CI, 2-3â¯%; I2=50.52â¯%, p=0.11). The pooled prevalence of COPD among biomass fuel-exposed individuals was 10â¯% (95â¯% CI, 2-18â¯%; I2=98.8â¯%, p<0.001). OUTLOOK: Limited evidence suggests a sizable burden of COPD among nonsmokers and biomass fuel-exposed individuals in India. More epidemiological studies of COPD in nonsmokers are needed from low and middle-income countries.
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Background & objectives: Current practice around transfusion trigger in critically ill sepsis patients is not clear. Moreover, any association of haemoglobin trigger and other transfusion parameters such as age of red blood cells (RBCs) at transfusion and number of units of RBCs transfused with mortality and other adverse outcomes need further assessment. Methods: In this prospective study, patients aged 18-70 yr and admitted to intensive care with a diagnosis of sepsis were included (n=108). Baseline demographic, clinical and laboratory parameters were noted and various transfusion data, i.e., haemoglobin trigger, number of units of RBCs and the age of RBCs were recorded. Following outcome data were collected: 28 and 90 day mortality, duration of mechanical ventilation, vasopressor therapy, intensive care unit (ICU) and hospital stay and requirement of renal replacement therapy. Results: Of the total 108 participants, 78 (72.2%) survived till 28 days and 66 (61.1%) survived till 90 days. Transfusion trigger was 6.9 (6.7-7.1) g/dl [median (interquartile range)]. On multivariable logistic regression analysis, acute physiology and chronic health evaluation (APACHE) II [adjusted odds ratio (aOR) (95% confidence interval {CI}): 0.86 (0.78, 0.96); P=0.005], cumulative fluid balance (CFB) [aOR (95% CI): 0.99 (0.99, 0.99); P=0.005] and admission platelet count [aOR (95% CI): 1.69 (1.01, 2.84); P=0.043] were the predictors of 28 day mortality [model area under the receiver operating characteristics (AUROC) 0.81]. APACHE II [aOR (95% CI): 0.88 (0.81, 0.97); P=0.013], CFB [a OR (95% CI): 0.99977 (0.99962, 0.99993); P=0.044] and transfusion trigger [aOR (95% CI): 3 (1.07, 8.34); P=0.035] were the predictors of 90 day mortality (model AUROC: 0.82). Interpretation & conclusions: In sepsis, patients admitted to the ICU, current practice suggests transfusion trigger is below 7 g/dl and it does not affect any adverse outcome including 28 day mortality.
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Sepsis , Shock, Septic , Humans , Shock, Septic/epidemiology , Shock, Septic/therapy , Prospective Studies , Critical Illness , Sepsis/therapy , Hemoglobins/analysis , Intensive Care Units , Retrospective StudiesABSTRACT
AIM: To evaluate the utility of ApneaGraph® AG 200 in diagnosing Obstructive Sleep Apnoea (OSA) as compared to Polysomnography, localization of the site of upper airway obstruction, and the success rate of surgery. METHODS: A prospective study was conducted including fifteen patients of OSA undergoing surgical treatment. All patients underwent sequential overnight ApneaGraph (AG) and Polysomnogram (PSG) before and after 3 months following surgery. The preoperative and post-operative Apnoea-Hypopnoea Index (AHI) values were compared between AG and PSG. The success of surgery was defined as mean reduction in AHI by ≥ 50% and post-operative AHI < 20. RESULTS: The mean preoperative AHI using PSG was 53.7 and using AG was 44.9 (r = 0.83, p = 0.0001). All patients underwent AG-directed site-specific surgery. The mean postoperative AHI using PSG was 15.3 and using AG was 13.8 (r = 0.67, p = 0.0062). There was significant improvement in AHI post-surgery (p < 0.05, AG & PSG). The surgical success was achieved in 93.3%. The median follow-up was 14 months. CONCLUSION: ApneaGraph is a reliable alternative to PSG to diagnose OSA with an added advantage to localize the site of obstruction, yielding good surgical outcomes.
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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.
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BACKGROUND: Since their introduction, both linear and radial endobronchial ultrasound (EBUS) have become an integral component of the practice of Pulmonology and Thoracic Oncology. The quality of health care can be measured by comparing the performance of an individual or a health service with an ideal threshold or benchmark. The taskforce sought to evaluate quality indicators in EBUS bronchoscopy based on clinical relevance/importance and on the basis that observed significant variation in outcomes indicates potential for improvement in health care outcomes. METHODS: A comprehensive literature review informed the composition of a comprehensive list of candidate quality indicators in EBUS. A multiple-round modified Delphi consensus process was subsequently performed with the aim of reaching consensus over a final list of quality indicators and performance targets for these indicators. Standard reporting items were developed, with a strong preference for items where evidence demonstrates a relationship with quality indicator outcomes. RESULTS: Twelve quality Indicators are proposed, with performance targets supported by evidence from the literature. Standardized reporting items for both radial and linear EBUS are recommended, with evidence supporting their utility in assessing procedural outcomes presented. CONCLUSION: This statement is intended to provide a framework for individual proceduralists to assess the quality of EBUS they provide their patients through the identification of clinically relevant, feasible quality measures. Emphasis is placed on outcome measures, with a preference for consistent terminology to allow communication and benchmarking between centres.
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Pulmonary Medicine , Quality Indicators, Health Care , Humans , Bronchoscopy , Benchmarking , EndosonographyABSTRACT
Obstructive sleep apnea (OSA) is a common sleep disorder associated with considerable morbidity. However, there is an underrepresentation of data from India and other developing countries in global reviews of OSA prevalence. This systematic review and meta-analysis examined the prevalence of OSA in India. The MEDLINE, Embase, and Scopus databases were searched for articles that reported the prevalence of OSA in the general Indian adult population using sleep studies. Eight studies were included comprising 11,009 subjects with mean age ranging from 35.5 to 47.8 years. On the Joanna Briggs Institute (JBI) checklist for prevalence studies, the study quality ranged from 3/9 to 9/9. Meta-analysis was performed using the random-effects model. The pooled prevalence of OSA (AHI ≥5 events/hour) was 11% overall (95% CI: 7%-15%; I2 = 98.0%, p<0.001), 13% in males (95% CI: 7%-18%; I2 = 96.0%, p<0.001), and 5% in females (95% CI: 3%-7%; I2 = 73.3%, p = 0.01). The pooled prevalence of moderate-to-severe OSA (AHI ≥15 events/hour) was 5% (95% CI: 2%-8%, I2 = 95.3%; p = 0.01). Based on these findings, approximately 104 million Indians of working age suffer from OSA, of whom 47 million have moderate-to-severe OSA. This represents a major public health problem in India with important implications for the global burden of the disease.
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Sarcoidosis is a systemic inflammatory disorder characterized by tissue infiltration due to mononuclear phagocytes and lymphocytes and associated noncaseating granuloma formation. Pulmonary sarcoidosis (PS) shares a number of clinical, radiological, and histopathological characteristics with that of pulmonary tuberculosis (PTB). Due to this, clinicians face issues in differentiating between PS and PTB in a substantial number of cases. There is a lack of any specific biomarker that can diagnose PS distinctively from PTB. We compared T-cell-based signature cytokines in patients with PS and PTB. In this study, we proposed a serum biomarker panel consisting of cytokines from cells: T helper (Th) 1 [interferon-gamma (IFN-γ); tumor necrosis factor-alpha (TNF-α)], Th9 [interleukin (IL)-9], Th17 [IL-17], and T regulatory (Treg) [IL-10; transforming growth factor-beta (TGF-ß)]. We performed the principal component analysis that demonstrated that our serum cytokine panel has a significant predictive ability to differentiate PS from PTB. Our results could aid clinicians to improve the diagnostic workflow for patients with PS in TB endemic settings where the diagnosis between PS and PTB is often ambiguous.