SARS-CoV-2 infection of human-induced pluripotent stem cells-derived lung lineage cells evokes inflammatory and chemosensory responses by targeting mitochondrial pathways.

The COVID-19 disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects the lung, particularly the proximal airway and distal alveolar cells. NKX2.1+ primordial lung progenitors of the foregut (anterior) endoderm are the developmental precursors to all adult lung epithelial lineages and are postulated to play an important role in viral tropism. Here, we show that SARS-CoV-2 readily infected and replicated in human-induced pluripotent stem cell-derived proximal airway cells, distal alveolar cells, and lung progenitors. In addition to the upregulation of antiviral defense and immune responses, transcriptomics data uncovered a robust epithelial cell-specific response, including perturbation of metabolic processes and disruption in the alveolar maturation program. We also identified spatiotemporal dysregulation of mitochondrial heme oxygenase 1 (HMOX1), which is associated with defense against antioxidant-induced lung injury. Cytokines, such as TNF-α, INF-γ, IL-6, and IL-13, were upregulated in infected cells sparking mitochondrial ROS production and change in electron transport chain complexes. Increased mitochondrial ROS then activated additional proinflammatory cytokines leading to an aberrant cell cycle resulting in apoptosis. Notably, we are the first to report a chemosensory response resulting from SARS-CoV-2 infection similar to that seen in COVID-19 patients. Some of our key findings were validated using COVID-19-affected postmortem lung tissue sections. These results suggest that our in vitro system could serve as a suitable model to investigate the pathogenetic mechanisms of SARS-CoV-2 infection and to discover and test therapeutic drugs against COVID-19 or its consequences.

Pulmonary Rehabilitation in the Management of Chronic Obstructive Pulmonary Disease among Asian Indians- Current Status and Moving Forward.

Chronic Obstructive Pulmonary Disease (COPD) is a significant public health concern in India with high prevalence and associated disability, morbidity, mortality. The progression of COPD is not confined to the lungs but includes extrapulmonary involvement that reduces the functional capacity and quality of life. Pulmonary Rehabilitation (PR) is an evidence-based intervention, targeting multiple domains of pulmonary and extrapulmonary manifestations, and therefore, is recommended as an integral part of COPD management. The practical implementation of PR in India is poor. In this review, we have summarized the latest pieces of evidence in support of PR and highlight the challenges and potential solutions for PR implementation in India.

A simple x-ray scoring system for the diagnosis of chronic pulmonary aspergillosis.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) is a severe form of post-tuberculosis lung disease (PTBLD). Considering the high burden of TB in India, it can be concluded that the prevalence of CPA is also high. Chest x-ray though most feasible, interpretation is subjective. Therefore, decision on evaluation for CPA cannot be based on x-ray alone. OBJECTIVE: Present study evaluated an x-ray score as a marker for extent of lung damage in patients with PTBLD presenting with haemoptysis and its utility to predict Aspergillus serum IgG levels. METHODS: We used a modified scoring system developed by Anna Ralph et al X-ray score cut-offs of >71 and 40, with or without history of massive haemoptysis, were compared with serum IgG levels. RESULTS: With a chest x-ray score cut-off of 71, specificity was 88%. With an x-ray score of >71 combined with history of massive haemoptysis, 86% cases were found to be IgG positive. The specificity of this combination was 96%. CONCLUSION: This study concluded that a simple chest x-ray scoring system in addition to the symptom of massive haemoptysis helped in the decision on further evaluation of the subject for CPA, especially in resource constrained settings.

Ultrasonographic assessment of skeletal muscle mass and diaphragm function in patients with chronic obstructive pulmonary disease: A case-control study.

BACKGROUND: Although muscle dysfunction is a major contributor to morbidity in chronic obstructive pulmonary disease (COPD), assessment of skeletal muscle, and diaphragm function is not routinely performed in COPD patients. OBJECTIVES: (1) The aim is to assess muscle dysfunction in COPD by measuring the zone of apposition of diaphragm, diaphragm excursion, thickness of diaphragm, and rectus femoris cross-sectional area (RFCSA) with ultrasonography.(2) To correlate the above assessments with spirometric parameters; notably forced expiratory volume in 1 s (FEV1). METHODS: Twenty-four consecutive stable COPD patients and 18 controls were included after obtaining written informed consent. Demographic and clinical data, spirometric values, 6-min walk distance, and sonographic parameters mentioned above were compiled for the analysis. RESULTS: All included participants were male with a mean age of 62.5 ± 8.4 years. The mean FEV1in cases was 1.12 ± 0.4 L versus 2.41 ± 0.5 L in controls. The diaphragm thickness (1.8 ± 0.5 mm vs. 2.2 ± 0.6 mm;P = 0.005) and RFCSA was significantly lower in COPD patients (4.8 ± 1.3 cm[2] vs. 6.12 ± 1.2 cm[2];P = 0.02). However, diaphragm excursion (5.35 ± 2.8 cm vs. 7 ± 2.6 cm) although lower in COPD patients, was not significantly different between the groups. Correlation between FEV1and ultrasound diaphragm measurements and RFCSA by Spearman's Rho correlation was poor (ρ= 0.2). CONCLUSION: Ultrasonographic assessment of the diaphragm and rectus femoris can be used as markers to assess skeletal muscle dysfunction in COPD as diaphragmatic function and RFCSA were lower in COPD patients.

Obstructive Sleep Apnea in a rural population in South India: Feasibility of health care workers to administer level III sleep study.

OBJECTIVES: To estimate the occurrence of obstructive sleep apnea (OSA) and its risk factors in a rural Indian population using screening questionnaire and Level III sleep study. To determine the feasibility to train community health workers to administer Level III sleep study in the high-risk population. MATERIALS AND METHODS: The study was conducted from seven villages with adult population of 2247, in Mugalur, near Bengaluru, from January to April 2014. Berlin questionnaire was used to screen 321 participants chosen by stratified random sampling. A total of 26 out of 321 patients underwent Level III sleep study at home, administered by the health workers, who were trained in three sessions to hook up the machine. Data were verified by a certified sleep physician. RESULTS: The mean age was 39.43 ± 15.6 years with the M:F ratio of 0.98:1. Prevalence of risk of OSA by Berlin questionnaire was 8.72% (95% confidence interval [CI] 5.63, 11.81) in the total population, 7.4% in males and 11.7% in females. Older age (odds ratio [OR] 3.97; CI 1.63, 9.6), hypertension (OR 11; CI 4.3, 28.2), obesity (OR 2.35; CI 1, 5.5), and higher Mallampati score (OR 3.78; CI 1.7, 8.4) were significantly associated with high risk of OSA (P = 0.0001-0.04). Twenty-six patients underwent Level III sleep study and OSA was diagnosed in 12 patients. The mean apnea-hypopnea index (AHI) of this group was 9.7/h. The prevalence of OSA by AHI criteria was 3.74%. CONCLUSIONS: OSA is underdiagnosed in rural populations, although risk factors are present. Training community health workers to administer Level III sleep study is a feasible and cost-effective strategy.

Undiagnosed Obstructive Sleep Apnea and Postoperative Outcomes: A Prospective Observational Study.

BACKGROUND: The prevalence of undiagnosed obstructive sleep apnea (OSA) during preoperative evaluation and the best method to screen OSA and its association with postoperative complications remain unclear. OBJECTIVES: To determine the prevalence of undiagnosed OSA in preoperative Indian patients undergoing noncardiac surgery, to compare the diagnostic accuracy of the STOP-BANG questionnaire to a preoperative level III sleep study, and to assess the association of OSA with postoperative complications. METHODS: A prospective cohort of 245 consecutive adults with ≥2 risk factors for OSA who underwent noncardiac surgery between July 2011 and February 2013 were studied. The STOP-BANG questionnaire was administered to all patients, and 182/245 (74.2%) patients underwent a preoperative level III sleep study. Patients were followed for postoperative complications in hospital and contacted at 30 days after surgery. RESULTS: 70/182 (38.5%) obtained a new diagnosis of OSA, including 11/182 (6%) with moderate to severe OSA (apnea-hypopnea index ≥15/h). On logistic regression analyses, the presence of OSA was independently associated with postoperative oxygen desaturation (OR 5.96, 95% CI 2.35-15.1, p < 0.01), a postoperative complication within 7 days (OR 3.63, 95% CI 1.77-7.45, p < 0.01) and within 30 days (OR 3.5, 95% CI 1.74-7.1, p < 0.01). The STOP-BANG questionnaire did not identify 12/70 (17%) of the patients diagnosed with OSA and classified 28% of the cohort as OSA when the level III sleep study was negative. CONCLUSIONS: Unrecognized OSA is common in preoperative patients and is independently associated with postoperative complications. The STOP-BANG questionnaire had a lower performance in the diagnosis of OSA in a South Indian population than the level III sleep study.

Use of pleural fluid ceruloplasmin in the differentiation of exudative and transudative pleural effusion.

BACKGROUND: Differentiating into transudate or exudate is the first step in the evaluation of effusions. Light's criteria is the standard but a significant number of transudates may not be differentiated based on these criteria. Acute phase proteins (APP) are present in plasma, which increase or decrease by about 25% during an acute inflammatory response. Ceruloplasmin (CP) is a positive APP. Hence, this study was done to know the diagnostic value of pleural fluid (pf) CP and pf to serum ceruloplasmin ratio (CPr) to differentiate the pleural effusion (PE) into exudate and transudate as compared to Light's criteria. SETTING: Medical wards of St John's Medical College Hospital, Bangalore. DESIGN: Cross-sectional descriptive study. Patients with PE were divided into exudate and transudate by definitive diagnosis. pfCP, CPr and Light's criteria were compared with definitive diagnosis for the differentiation of pf into exudate and transudate. RESULTS: The mean value of the pfCP and CPr was found to be significantly different between exudates and transudates. Sensitivity and specificity of pfCP at ≥ 13.34 mg/dl is 89.7% and 83.3%, CPr at ≥ 0.37 is 91.4% and 83.3%, Light's criteria 94.82% and 83.3%, respectively. Light's criteria, pfCP and CPr have similar PPV (98%) with Light's criteria having higher NPV (62.5%) than pfCP (45%) and CPr (50%), respectively. CPr has higher NPV than pfCP. CONCLUSIONS: pfCP and CPr can differentiate pf into exudate and transudate with comparable PPV to Light's criteria.

Chylothorax in gastric adenocarcinoma: A case report and systematic review of the English literature.

BACKGROUND: Chylothorax is a rare complication of gastric adenocarcinoma and data on its identification, prevalence and outcomes are scant. OBJECTIVES: To enable identification of gastric carcinoma as a cause of chylothorax. METHODS: A case report and a systematic review were conducted of all reported cases of gastric adenocarcinoma with chylothorax as the presenting complaint in the English literature. RESULTS: Chylothorax is a rare presenting complaint of gastric adenocarcinoma. There are only 18 case reports in the world literature, of which six are in English. Chylothorax occurred variably in gastric adenocarcinoma, either as a presenting feature or as a complication of therapy. Here, we analyze the index case and six patients in whom gastric carcinoma presented with chylothorax as the initial symptom. Respiratory features of cough and dyspnea preempted any abdominal complaint. Bilateral chylothorax (66%) with associated chylous ascites (50%) was common. Four of the six patients had skin lymphedema also as a prominent feature. The chylothoraces have been treated by therapeutic pleurocentesis, intercoastal tube drainage and restriction of oral intake. Gastric adenocarcinoma was associated with high mortality (50%) and morbidity. CONCLUSIONS: Chylothorax can be the presenting feature of gastric adenocarcinoma. A thorough search for this life-threatening disease should be done before labeling the chylothorax as idiopathic.

Recurrent spontaneous pneumomediastinum in a young female: Hamman's crunch revisited(†).

Presence of free air in the mediastinum without any identifiable cause is defined as spontaneous pneumomediastinum (SPM). SPM is more common in young males. The common inciting event leading to SPM are retching, vomiting, acute asthma attack, intense sport activity, inhalation of drugs and weight loss as seen in anorexia nervosa. Analgesics and rest is the mainstay of treatment. Recurrence of SPM is rare. We present a case of recurrent SPM occurring in a young female within few months interval. We also present a brief literature review.

Study of spirometry and airway reactivity in patients on disulfirm for treatment of alcoholism.

The aim of our study was to examine the short term effect ofdisulfiram on pulmonary functions of alcohol dependent subjects, who were chronic smokers J/Ve compared FEV1 % values on spirometry and airway reactivity to histamine challenge in alcohol dependent subjects at baseline and after 2 weeks of treatment with disulfiram. Disulfiram did not significantly alter FEVI values and airway reactivity during the treatment period and can thus be used safely in alcohol dependent subjects who are current smokers.