Clinical characteristics of non-sleepy obstructive sleep apnea patients: a study in a tertiary care sleep clinic in India.

Obstructive sleep apnea (OSA) encompasses a diverse population, manifesting with or without symptoms of excessive daytime sleepiness. There is contention surrounding the significance of non-sleepy OSA within clinical contexts and whether routine treatment is warranted. This study aims to evaluate epidemiological and clinical distinctions between sleepy and non-sleepy OSA patients. A retrospective analysis was conducted on consecutive patients undergoing polysomnography for OSA assessment at tertiary care hospitals between 2018 and 2023. For 176 of 250 patients, complete polysomnography records with OSA diagnoses were available. Non-sleepy OSA was defined when a patient had an Epworth sleepiness scale score <10 and polysomnography demonstrated an apnea hypopnea index ≥5/hour. Non-sleepy OSA patients were matched with sleepy OSA patients in terms of age and gender distribution (mean age 51.24±13.25 years versus 50.9±10.87 years, male 70.4% versus 73.3%). The sensitivity of STOP-BANG≥3 for the non-sleepy OSA group was 87.7%, 89.3%, and 95.2% for any OSA severity, moderate to severe OSA, and severe OSA, respectively, while the corresponding sensitivity for the sleepy OSA group was 96.5%, 98.6%, and 100% for any OSA severity, moderate to severe OSA, and severe OSA, respectively. A novel symptom scoring tool, HASSUN (hypertension, nocturnal apneas, snoring, sleep disturbance, unrefreshing sleep, and nocturia), demonstrated a sensitivity of over 90% for all severity categories of OSA in both non-sleepy and sleepy OSA groups. The prevalence of cardiovascular and metabolic comorbidities did not significantly differ between non-sleepy and sleepy OSA patients. The physiological parameters, including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC ratio, arterial partial pressure of oxygen, and bicarbonate at baseline, were comparable between the two groups. To conclude, non-sleepy OSA patients are less obese, exhibit fewer symptoms, and have less severe OSA in comparison to sleepy OSA. Non-sleepy OSA patients display a similar likelihood of cardiovascular and metabolic comorbidities compared to sleepy OSA patients. Further investigations are warranted to elucidate the mechanisms underlying cardiovascular metabolic comorbidities in non-sleepy OSA patients. The proposed HASSUN scoring tool for non-sleepy OSA screening necessitates validation in future studies.

Radial Endobronchial Ultrasound to Diagnose a Case of Non-Hodgkin's Lymphoma in the Lung: A Case Report and Literature Review.

Non-Hodgkin's lymphomas (NHLs) are a heterogeneous group of lymphoproliferative malignancies that are very rarely seen in the lung. Although they generally have a favorable prognosis, the clinical symptoms and most efficient methods of diagnosis have not yet been clearly defined. This report highlights an interesting case wherein a 75-year-old male who presented with complaints of fever, cough, and generalized weakness for three weeks was diagnosed and treated as a case of pneumonia. He did not respond to conventional treatment with antibiotics and antipyretics. Hence, computed tomography of the thorax was done which showed consolidation in the right lower lobe along with a few enlarged right hilar nodes. To evaluate this unresolved pneumonia, he was further evaluated with a radial endobronchial ultrasound (EBUS) and biopsy, which helped in arriving at a diagnosis of NHL. This case illustrates the significance of advanced interventions such as radial EBUS to identify the exact etiology of the lesions. This is the first case to document the ultrasound images of NHL in the lung, obtained using a radial EBUS.

Author Response.

How to cite this article: Ramaswamy A, Kumar R, Ish P, Gupta N. Author Response. Indian J Crit Care Med 2024;28(4):405.

HAT and HDAC: Enzyme with Contradictory Action in Neurodegenerative Diseases.

In view of the increasing risk of neurodegenerative diseases, epigenetics plays a fundamental role in the field of neuroscience. Several modifications have been studied including DNA methylation, histone acetylation, histone phosphorylation, etc. Histone acetylation and deacetylation regulate gene expression, and the regular activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs) provides regulatory stages for gene expression and cell cycle. Imbalanced homeostasis in these enzymes causes a detrimental effect on neurophysiological function. Intriguingly, epigenetic remodelling via histone acetylation in certain brain areas has been found to play a key role in the neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. It has been demonstrated that a number of HATs have a role in crucial brain processes such regulating neuronal plasticity and memory formation. The most recent therapeutic methods involve the use of small molecules known as histone deacetylase (HDAC) inhibitors that antagonize HDAC activity thereby increase acetylation levels in order to prevent the loss of HAT function in neurodegenerative disorders. The target specificity of the HDAC inhibitors now in use raises concerns about their applicability, despite the fact that this strategy has demonstrated promising therapeutic outcomes. The aim of this review is to summarize the cross-linking between histone modification and its regulation in the pathogenesis of neurological disorders. Furthermore, these findings also support the notion of new pharmacotherapies that target particular areas of the brain using histone deacetylase inhibitors.

Thoracoscopic blood patch instillation for persistent air leak in pneumothorax: a case series and systematic review.

Persistent air leaks in patients with pneumothorax can lead to significant morbidity. If a patient with persistent air leak is medically unfit for thoracic surgery, medical pleurodesis via chest tube or thoracoscopy is either an option. Thoracoscopy offers the advantage of visualizing the site of the air leak and enabling direct instillation of the pleurodesis agent or glue at that location. Autologous blood patch instillation via chest tube has been reported to be a cheap and very effective technique for the management of persistent air leaks. However, thoracoscopic blood patch instillation has not been reported in the literature. We report two cases of secondary spontaneous pneumothorax in which patients had persistent air leaks for more than seven days and were subjected to thoracoscopy to locate the site of the leak. In the same sitting, 50 mL of autologous blood patch was instilled directly at the leak site. Post-procedure, the air leak subsided in both patients, and the chest tube was removed with complete lung expansion. We also conducted a systematic review of the use of medical thoracoscopic interventions for treating persistent air leaks.

Cryodebulking to Relieve Critical Airway Narrowing Due to a Central Airway Tumor at the Carina: A Case Report and Literature Review.

Central airway tumors presenting as critical airway stenosis is a medical emergency. Employing a cryoprobe, we successfully debulked a central airway tumor, providing rapid relief to a patient who came to the emergency room with severe breathlessness, hemoptysis, and respiratory failure. The current report underscores the efficacy of cryodebulking as an immediate and minimally invasive technique and a compelling alternative to conventional heat-based therapies.

Correlation of severity & clinical outcomes of COVID-19 with virus variants: A prospective, multicentre hospital network study.

BACKGROUND OBJECTIVES: The clinical course of COVID-19 and its prognosis are influenced by both viral and host factors. The objectives of this study were to develop a nationwide platform to investigate the molecular epidemiology of SARS-CoV-2 (Severe acute respiratory syndrome Corona virus 2) and correlate the severity and clinical outcomes of COVID-19 with virus variants. METHODS: A nationwide, longitudinal, prospective cohort study was conducted from September 2021 to December 2022 at 14 hospitals across the country that were linked to a viral sequencing laboratory under the Indian SARS-CoV-2 Genomics Consortium. All participants (18 yr and above) who attended the hospital with a suspicion of SARS-CoV-2 infection and tested positive by the reverse transcription-PCR method were included. The participant population consisted of both hospitalized as well as outpatients. Their clinical course and outcomes were studied prospectively. Nasopharyngeal samples collected were subjected to whole genome sequencing to detect SARS-CoV-2 variants. RESULTS: Of the 4972 participants enrolled, 3397 provided samples for viral sequencing and 2723 samples were successfully sequenced. From this, the evolution of virus variants of concern including Omicron subvariants which emerged over time was observed and the same reported here. The mean age of the study participants was 41 yr and overall 49.3 per cent were female. The common symptoms were fever and cough and 32.5 per cent had comorbidities. Infection with the Delta variant evidently increased the risk of severe COVID-19 (adjusted odds ratio: 2.53, 95% confidence interval: 1.52, 4.2), while Omicron was milder independent of vaccination status. The independent risk factors for mortality were age >65 yr, presence of comorbidities and no vaccination. INTERPRETATION CONCLUSIONS: The authors believe that this is a first-of-its-kind study in the country that provides real-time data of virus evolution from a pan-India network of hospitals closely linked to the genome sequencing laboratories. The severity of COVID-19 could be correlated with virus variants with Omicron being the milder variant.

Comparative yield of transbronchial cryo-nodal biopsy, transbronchial intra-nodal forceps biopsy, and transbronchial needle aspiration for mediastinal lesions at a tertiary care center in India (COLD-FORCEPS study).

Endobronchial ultrasound (EBUS) guided mediastinal cryobiopsy, and intranodal forceps biopsy are newer modalities for sampling mediastinal lymph nodes. The data regarding the diagnostic yield of both modalities is scarce. Patients were recruited retrospectively from our existing database. Patients who had undergone both an EBUS guided mediastinal cryobiopsy and an intranodal forceps biopsy were enrolled in the study. The final diagnosis was made with a clinical-pathological-radiological assessment and clinico-radiological follow-up after one month. A total of 34 patients were enrolled in the study who had undergone both EBUS guided mediastinal cryobiopsy and intranodal forceps biopsy and had complete data available, including 1-month follow-up data. The sample adequacy rate of EBUS-transbronchial needle aspiration (EBUS-TBNA), EBUS-TBNA with mediastinal cryobiopsy, and EBUS-TBNA with intranodal forceps biopsy was 94.11%, 97.05%, and 94.11%, respectively (p=0.56). The diagnostic yield achieved in EBUS-TBNA, EBUS-TBNA with mediastinal cryobiopsy, and EBUS-TBNA with intranodal forceps biopsy was 73.52%, 82.35%, and 79.41%, respectively (p=0.38). No major complications were seen in any patient. To conclude, adding EBUS guided mediastinal cryobiopsy and intranodal forceps biopsy to EBUS-TBNA may not be superior to routine EBUS-TBNA.

Clinical utility of intrabronchial antifungal instillation in a complicated case of chronic pulmonary aspergillosis: case report and systematic review of literature.

Chronic pulmonary aspergillosis (CPA) is a progressive, debilitating clinical condition associated with significant morbidity. Surgery is the mainstay of treatment for life-threatening hemoptysis in symptomatic patients with simple aspergillomas. However, in patients with chronic cavitary pulmonary aspergillosis, surgical removal of aspergillomas is fraught with difficulty due to debilitating nature of the illness. Here we present a case showcasing the utility of intrabronchial voriconazole instillation in controlling hemoptysis in a patient unfit for surgery followed by systematic review of literature involving 11 clinical studies after screening a total of 5572 studies from PubMed and Google Scholar database. Data gathered from these studies addresses the concerns regarding the efficacy, safety of the procedure as well as draws attention regarding several lacunae in our existing knowledge. A 53-year-old male with chronic pulmonary aspergillosis who had recurrent episodes of hemoptysis despite bronchial artery embolization and was unfit for surgery due to limited lung reserve, patient underwent single session of intrabronchial voriconazole instillation which resulted in dramatic symptomatic and radiological improvement. Intrabronchial antifungal instillation may be a safe and effective option for hemoptysis control in patients with chronic pulmonary aspergillosis.

Prediction of Weaning Outcome from Mechanical Ventilation Using Ultrasound Assessment of Parasternal Intercostal Muscle Thickness.

Background: Monitoring the function of parasternal intercostal muscles provides information on respiratory load and capacity and thus can be a weaning monitoring tool. Objective: The goal was to study the diagnostic accuracy of parasternal intercostal muscle thickness fraction (PICTF%) as a predictor of weaning. Materials and methods: A prospective observational study on consecutively admitted patients who were intubated and mechanically ventilated for a duration of at least 48 hours was carried out. When an SBT was planned by the treating physician, the study examiner performed the ultrasound measurements of parasternal intercostal muscle thickness (inspiration and expiration) and thickening fraction using M-mode ultrasonography (USG). The PICTF% was calculated as "(peak inspiratory thickness - end-expiratory thickness)/end-expiratory thickness) × 100." Weaning failure was defined if the patient had a failed spontaneous breathing trial (SBT) or the need for a reintubation within 48 hours following extubation. The SBT failure was defined as the need to connect the patient back to the ventilator prior to its completion due to any reason as decided by the clinician. Results: Of 81 screened patients, 60 patients met the inclusion criteria, of whom 49 patients had successful SBT, and 48 patients could be successfully extubated. The PMTF% cut-off value more than or equal to 15.38% was associated with the best sensitivity (75%) and specificity (87.8%) in predicting extubation failure. Conclusion: The PICTF% has a good diagnostic accuracy in predicting weaning failure. How to cite this article: Ramaswamy A, Kumar R, Arul M, Ish P, Madan M, Gupta NK, et al. Prediction of Weaning Outcome from Mechanical Ventilation Using Ultrasound Assessment of Parasternal Intercostal Muscle Thickness. Indian J Crit Care Med 2023;27(10):704-708.

Comparison of immediate withdrawal and stepwise reduction in duration of non-invasive ventilation in chronic obstructive pulmonary disease patients presenting with acute hypercapnic respiratory failure.

There is no universally acceptable protocol for the withdrawal of non-invasive ventilation (NIV) in chronic obstructive pulmonary disease (COPD) patients presenting with acute hypercapnic respiratory failure (AHcRF). This study was carried out to evaluate immediate against stepwise reduction in NIV. Sixty COPD patients with AHcRF who were managed with NIV were randomized into two groups - immediate NIV withdrawal (Group A), and stepwise reduction of NIV duration (Group B). The rate of successful NIV withdrawal, time to recurrence of hypercapnic respiratory failure, total duration of NIV use, and hospital length of stay (LOS), were compared among the 2 groups. NIV was successfully withdrawn in 51/60 (85%) patients. NIV was successfully withdrawn in 24/30 (80%) patients in Group A and 27/30 (90%) patients in Group B (p=0.472). The total duration of NIV use was significantly lower in Group A (38.97±17 hours) as compared to Group B (64.3±7.74 hours) (p<0.0001). The hospital LOS was significantly lower in group A (5.8±1.6 days) as compared to Group B (7.7±0.61 days) (p<0.0001). To conclude, immediate withdrawal of the NIV after recovery of respiratory failure among patients with exacerbation of COPD is feasible and does not increase the risk of weaning failure.

Pre-conference workshop on pulmonary rehabilitation and smoking cessation - NATCON 2022.

The 77th National Conference of Tuberculosis and Chest Diseases was held on 27th February 2023. The workshop on Pulmonary rehabilitation and smoking cessation was conducted as a part of the various pre-conference workshops being conducted on the occasion. It helped the participants to know regarding the role, efficacy and benefits of pulmonary rehabilitation and smoking cessation for the management of Chronic respiratory diseases.

Post-extubation high-flow nasal cannula oxygen therapy versus non-invasive ventilation in chronic obstructive pulmonary disease with hypercapnic respiratory failure.

The sequential use of non-invasive ventilation (NIV) for weaning in hypercapnic respiratory failure patients is a recommended practice. However, the effectiveness of weaning on High flow nasal cannula (HFNC) is unclear. Chronic obstructive pulmonary disease patients with hypercapnic respiratory failure who received invasive ventilation were screened for enrolment. This study was a single-centre, prospective, randomized comparative study. The primary outcome was treatment failure within 72 hours after extubation. Patients who were screened positive for extubation were enrolled in the study and randomized into the HFNC group and NIV group using a computer-generated simple randomization chart. The treatment failure was defined as a return to invasive mechanical ventilation, or a switch in respiratory support modality (i.e., changing from HFNC to NIV or from NIV to HFNC). Of 72 patients, 62 patients were included in the study. Treatment failure occurred in 8 patients (26.67 %) in HFNC group and 8 patients in NIV group (25%) (p=0.881). The mean duration of ICU stay in HFNC group was 5.47±2.26 days and 6.56±3.39 in NIV group (p=0.376). In the current study, HFNC was non-inferior to NIV in preventing post-extubation respiratory failure in COPD patients, while HFNC had better treatment tolerance.

Severity and mortality associated with COVID-19 among children hospitalised in tertiary care centres in India: a cohort study.

Background: It is critical to identify high-risk groups among children with COVID-19 from low-income and middle-income countries (LMICs) to facilitate the optimum use of health system resources. The study aims to describe the severity and mortality of different clinical phenotypes of COVID-19 in a large cohort of children admitted to tertiary care hospitals in India. Methods: Children aged 0-19 years with evidence of SARS-CoV-2 infection (real time polymerase chain reaction or rapid antigen test positive) or exposure (anti-SARS-CoV-2 antibody, or history of contact with SARS-CoV-2) were enrolled in the study, between January 2021 and March 2022 across five tertiary hospitals in India. All study participants enrolled prospectively and retrospectively were followed up for three months after discharge. COVID-19 was classified into severe (Multisystem Inflammatory Syndrome in Children (MIS-C), severe acute COVID-19, 'unclassified') or non-severe disease. The mortality rates were estimated in different phenotypes. Findings: Among 2468 eligible children enrolled, 2148 were hospitalised. Signs of illness were present in 1688 (79%) children with 1090 (65%) having severe disease. High mortality was reported in MIS-C (18.6%), severe acute COVID-19 (13.3%) and the unclassified severe COVID-19 disease (12.3%). Mortality remained high (17.5%) when modified MIS-C criteria was used. Non-severe COVID-19 disease had 14.1% mortality when associated with comorbidity. Interpretation: Our findings have important public health implications for low resource settings. The high mortality underscores the need for better preparedness for timely diagnosis and management of COVID-19. Children with associated comorbidity or coinfections are a vulnerable group and need special attention. MIS-C requires context specific diagnostic criteria for low resource settings. It is important to evaluate the clinical, epidemiological and health system-related risk factors associated with severe COVID-19 and mortality in children from LMICs. Funding: Department of Biotechnology, Govt of India and Department of Maternal, Child and Adolescent Health and Aging, WHO, Geneva, Switzerland.

Spatiotemporal evaluation of drought characteristics based on standard drought indices at various timescales over Uttar Pradesh, India.

Prolonged and repeated drought, as seen in India and other parts of South Asia, is a symptom of climate change, which is partially the result of human interventions. The performance of the widely used drought metrics Standardized Precipitation Index (SPI) and Standardized Precipitation Evapotranspiration Index (SPEI) are evaluated for 18 stations in Uttar Pradesh state for the period 1971 to 2018 in this study. Drought characteristics such as intensity, duration, and frequency of different categories are estimated and compared based on SPI and SPEI. In addition, station proportion is estimated at a different timescales, providing a better insight into temporal variability drought of a specific category. Spatiotemporal trend variability of SPEI and SPI was investigated at a significance level of 0.05 using the non-parametric Mann-Kendall (MK) test. SPEI adds the effect of temperature rise and deficit change on the drought occurrences of different classes. SPEI provides a better estimation of drought characteristics due to its consideration of temperature change in the drought severity. The more significant number of drying events accounted for a timescale of 3 months and 6 months, reflecting the higher variability of the seasonal fluctuation of water balance over the state. At 9-month and 12-month timescales, SPI and SPEI fluctuate gradually with considerable differences between the duration and severity of the drought event. This study reveals that there have been a substantial number of drought events over the state during the last two decades (2000 to 2018). The results conclude that the study area is at risk of erratic meteorological drought conditions where the western part of the study is worst affected compared to the eastern part of Uttar Pradesh (India).

A 33-Year-Old Woman With Breathing Difficulty, Inspiratory Wheeze, and Hemoptysis.

CASE PRESENTATION: A 33-year-old teacher from Ghana with no medical comorbidities and no relevant family history came to our pulmonology department with progressive difficulty in breathing, wheezing, and stridor for 6 months. Similar episodes had been treated previously as bronchial asthma. She was being treated with high-dose inhaled corticosteroids and bronchodilators but had no relief. The patient also described two episodes of large quantities of hemoptysis (> 150 mL) in the previous week. A general physical examination revealed a tachypneic young woman with an audible inspiratory wheeze. Her BP was 128/80 mm Hg; pulse, 90 beats/min; and respiratory rate, 32 breaths/min. There was a hard, minimally tender, nodular swelling of 3 × 3 cm in the midline neck felt just below the cricoid cartilage, moving with deglutition and protrusion of the tongue, with no retrosternal extension. There was no cervical or axillary lymphadenopathy. Laryngeal crepitus was present.

Multimodal analysis of the COVID-19-associated mucormycosis outbreak in Delhi, India indicates the convergence of clinical and environmental risk factors.

BACKGROUND: The aetiology of the major outbreak of COVID-19-associated mucormycosis (CAM) in India in spring 2021 remains incompletely understood. Herein, we provide a multifaceted and multi-institutional analysis of clinical, pathogen-related, environmental and healthcare-related factors during CAM outbreak in the metropolitan New Delhi area. METHODS: We reviewed medical records of all patients diagnosed with biopsy-proven CAM (n = 50) at 7 hospitals in the New Delhi, and NCR area in April-June 2021. Two multivariate logistic regression models were used to compare clinical characteristics of CAM cases with COVID-19-hospitalised contemporary patients as controls (n = 69). Additionally, meteorological parameters and mould spore concentrations in outdoor air were analysed. Selected hospital fomites were cultured. Mucorales isolates from CAM patients were analysed by ITS sequencing and whole-genome sequencing (WGS). RESULTS: Independent risk factors for CAM identified by multivariate analysis were previously or newly diagnosed diabetes mellitus, active cancer and severe COVID-19 infection. Supplemental oxygen, remdesivir therapy and ICU admission for COVID-19 were associated with reduced CAM risk. The CAM incidence peak was preceded by an uptick in environmental spore concentrations in the preceding 3-4 weeks that correlated with increasing temperature, high evaporation and decreasing relative humidity. Rhizopus was the most common genus isolated, but we also identified two cases of the uncommon Mucorales, Lichtheimia ornata. WGS found no clonal population of patient isolates. No Mucorales were cultured from hospital fomites. CONCLUSIONS: An intersection of host and environmental factors contributed to the emergence of CAM. Surrogates of access to advanced COVID-19 treatment were associated with lower CAM risk.

Prediction of Weaning Outcome from Mechanical Ventilation Using Diaphragmatic Rapid Shallow Breathing Index.

Background: Diaphragmatic dysfunction has been increasingly documented to play a critical role to determine ventilator dependency and failure of weaning. Objective: The goal was to study the diagnostic accuracy of diaphragmatic rapid shallow breathing index (D-RSBI) as a predictor of weaning outcomes in comparison to RSBI. Materials and methods: A prospective observational study on consecutively admitted patients who were intubated and mechanically ventilated for a duration of at least 48 hours was carried out. The right hemidiaphragm displacement [diaphragm displacement (DD)] was calculated by M-mode ultrasonography, and respiratory rate (RR) and tidal volume (TV) were documented from the ventilator readings. Rapid shallow breathing index (RSBI) was measured as RR/TV (in liters); D-RSBI was calculated as RR/DD (in millimeters) and expressed as breath/minute/millimeter. Extubation failure was defined as the reinstitution of mechanical ventilation at the end of, or during the spontaneous breathing trial (SBT), re-intubation or the need of noninvasive ventilation (NIV) for the patient within 48 hours of extubation. Results: Of 101 screened patients, 50 patients met the inclusion criteria, of whom 45 patients had successful SBT, and finally, 41 patients could be successfully extubated. Hence, the overall rate of weaning failure in the study population was 18%. The areas under the receiver operator characteristic (ROC) curves for D-RSBI and RSBI were 0.97 and 0.70, respectively (p <0.0001). The Pearson's correlation among RSBI and D-RSBI was 0.81 (p-value <0.001). Conclusion: Diaphragmatic rapid shallow breathing index has a positive correlation and greater diagnostic accuracy than RSBI, the conventional weaning index. How to cite this article: Shamil PK, Gupta NK, Ish P, Sen MK, Kumar R, Chakrabarti S, et al. Prediction of Weaning Outcome from Mechanical Ventilation Using Diaphragmatic Rapid Shallow Breathing Index. Indian J Crit Care Med 2022;26(9):1000-1005.