Humoral and cellular immunity to SARS-CoV-2 following vaccination with non-mRNA vaccines in adolescent/young adults with cancer: A prospective cohort study.

BACKGROUND: Data on SARS-CoV-2 vaccine responsiveness in adolescent/young adult (AYA) cancer patients are sparse. The present study assessed humoral and cellular immune responses post-vaccination in this population. METHODS: In this prospective study, patients aged 12-30 years undergoing cancer therapy ("on therapy") and survivors ("off therapy") were recruited. Anti-receptor binding domain (RBD) protein IgG levels were measured at baseline, four weeks post-first vaccine dose (T1), and six weeks post-second dose (T2). Cellular immunity was assessed using activation-induced markers and intracellular cytokine staining in a patient subset. The primary outcome was to quantify humoral responses in both cohorts at T2 compared to baseline. Clinical predictors of log antibody titres at T2 were identified. RESULTS: Between April-December 2022, 118 patients were recruited of median age 15.4 years. Among them, 77 (65.2 %) were in the "on therapy" group, and 77 (65.2 %) had received the BBV152 vaccine. At baseline, 108 (91.5 %) patients were seropositive for anti-RBD antibody. The log anti-RBD titre rose from baseline to T2 (p-value = 0.001) in the whole cohort; this rise was significant from baseline-T1 (p-value < 0.001), but not from T1 to T2 (p-value = 0.842). A similar pattern was seen in the "on therapy" cohort. BECOV-2 vaccine was independently associated with higher log anti-RBD titres than BBV152 (regression coefficient: 0.41; 95 % CI: 0.10-0.73; p = 0.011). Cellular immune responses were similar in the "on-" and "off therapy" groups at the three time points. CONCLUSION: Among AYA cancer patients, a single non-mRNA vaccine dose confers robust hybrid humoral immunity with limited benefit from a second dose.

Association of Leukocyte Subpopulations Identified by Flow Cytometry with Outcomes of Sepsis in a Respiratory Intensive Care Unit: An Observational Study.

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 48 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 48 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.

Prevalence of chronic obstructive pulmonary disease in Indian nonsmokers: a systematic review & meta-analysis.

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 26.6 %. 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 3 % (95 % CI, 2-3 %; I2=50.52 %, p=0.11). The pooled prevalence of COPD among biomass fuel-exposed individuals was 10 % (95 % CI, 2-18 %; I2=98.8 %, 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.

Systematic review and meta-analysis of the prevalence of obstructive sleep apnea in Indian adults.

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.

Guidelines for endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA): Joint Indian Chest Society (ICS)/Indian Association for Bronchology (IAB) recommendations.

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.

Air Pollution and Lung Cancer: A Review by International Association for the Study of Lung Cancer Early Detection and Screening Committee.

INTRODUCTION: The second leading cause of lung cancer is air pollution. Air pollution and smoking are synergistic. Air pollution can worsen lung cancer survival. METHODS: The Early Detection and Screening Committee of the International Association for the Study of Lung Cancer formed a working group to better understand issues in air pollution and lung cancer. These included identification of air pollutants, their measurement, and proposed mechanisms of carcinogenesis. The burden of disease and the underlying epidemiologic evidence linking air pollution to lung cancer in individuals who never and ever smoked were summarized to quantify the problem, assess risk prediction models, and develop recommended actions. RESULTS: The number of estimated attributable lung cancer deaths has increased by nearly 30% since 2007 as smoking has decreased and air pollution has increased. In 2013, the International Agency for Research on Cancer classified outdoor air pollution and particulate matter with aerodynamic diameter less than 2.5 microns in outdoor air pollution as carcinogenic to humans (International Agency for Research on Cancer group 1) and as a cause of lung cancer. Lung cancer risk models reviewed do not include air pollution. Estimation of cumulative exposure to air pollution exposure is complex which poses major challenges with accurately collecting long-term exposure to ambient air pollution for incorporation into risk prediction models in clinical practice. CONCLUSIONS: Worldwide air pollution levels vary widely, and the exposed populations also differ. Advocacy to lower sources of exposure is important. Health care can lower its environmental footprint, becoming more sustainable and resilient. The International Association for the Study of Lung Cancer community can engage broadly on this topic.

Temporal evolution of diaphragm thickness and diaphragm excursion among subjects hospitalized with COVID-19: A prospective observational study.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has an affinity for the angiotensin-converting enzyme 2 (ACE2) receptors, which are present abundantly on the diaphragm. This study aims to describe temporal changes in diaphragmatic thickness and excursion using ultrasonography in subjects with acute COVID-19. METHODS: This prospective observational study included adults hospitalized with COVID-19 in the past 48 hours. The diaphragm thickness at end-expiration (DTE), diaphragm thickening fraction (DTF), and diaphragm excursion during tidal breathing (DE) and maximal inspiration (DEmax) were measured using ultrasonography daily for 5 days. The changes in DTE, DTF, DE, and Demax from day 1 to day 5 were assessed. RESULTS: This study included 64 adults (62.5% male) with a mean (SD) age of 50.2 (17.5) years. A majority (91%) of the participants had mild or moderate illness. The median (IQR) DTE, DTF (%), DE and Demax on day 1 were 2.2 (1.9, 3.0) mm, 21.5% (14.2, 31.0), 19.2 (16.5, 24.0) mm, and 26.7 (22.0, 30.2) mm, respectively. On day 5, there was a significant reduction in the DTE (p=0.002) with a median (IQR) percentage change of -15.7% (-21.0, 0.0). The DTF significantly increased on day 5 with a median (IQR) percentage change of 25.0% (-19.2, 98.4), p=0.03. There was no significant change in DE and Demax from day 1 to day 5, with a median (IQR) percentage change of 3.6% (-5.2, 15) and 0% (-6.7, 5.9), respectively. CONCLUSIONS: Non-intubated patients with COVID-19 exhibited a temporal decline in diaphragm thickness with increase in thickening fraction over 5 days of hospital admission. Further research is warranted to assess the impact of COVID-19 pneumonia on diaphragmatic function.

A Delphi consensus statement for the management of post-COVID interstitial lung disease.

INTRODUCTION: As millions of people worldwide recover from COVID-19, a substantial proportion continue to have persistent symptoms, pulmonary function abnormalities, and radiological findings suggestive of post-COVID interstitial lung disease (ILD). To date, there is limited scientific evidence on the management of post-COVID ILD, necessitating a consensus-based approach. AREAS COVERED: A panel of experts in pulmonology and thoracic radiology was constituted. Key questions regarding the management of post-COVID ILD were identified. A search was performed on PubMed and EMBASE and updated till 1 March 2022. The relevant literature regarding the epidemiology, pathophysiology, diagnosis and treatment of post-COVID ILD was summarized. Subsequently, suggestions regarding the management of these patients were framed, and a consensus was obtained using the Delphi approach. Those suggestions which were approved by over 80% of the panelists were accepted. The final document was approved by all panel members. EXPERT OPINION: Dedicated facilities should be established for the care of patients with post-COVID ILD. Symptom screening, pulmonary function testing, and thoracic imaging have a role in the diagnosis. The pharmacologic and non-pharmacologic options for the management of post-COVID ILD are discussed. Further research into the pathophysiology and management of post-COVID ILD will improve our understanding of this condition.

Clinical profile and in-hospital outcomes of COVID-19 among adolescents at a tertiary care hospital in India.

Introduction: We aimed to describe the clinical profile and risk factors for severe disease in adolescents hospitalised with coronavirus disease 2019 (COVID-19). Methods: A retrospective analysis of an admitted cohort of COVID-19 patients was performed at a tertiary hospital in North India. Adolescents aged 12-18 years who were hospitalised during the first wave (March-December, 2020) and the second wave (March-June, 2021) were included. Data on the demographic details, clinical presentation, laboratory parameters, disease severity at admission, treatments received, and in-hospital outcomes were retrieved. Results: The study included 197 adolescents with a median [inter-quartile range (IQR)] age of 15 (13-17) years, of whom 117 (59.4%) were male. Among these, 170 (86.3%) were admitted during the first wave. Underlying co-morbidities were present in nine (4.6%) patients. A total of 60 (30.9%) patients were asymptomatic. In the severity grading, 148 (84.6%) had mild, 16 (9.1%) had moderate, and 11 (6.3%) had severe disease. Fever (14.9%) and cough (14.9%) were the most commonly encountered symptoms. The median (IQR) duration of hospital stay was 10 (8-13) days, and six (3.1%) patients died in the hospital. Conclusion: Adolescents admitted with COVID-19 had predominantly asymptomatic or mild disease, and the mortality rate was 3.1%.

A multicenter study on the safety and efficacy of bronchial thermoplasty in adults with severe asthma.

BACKGROUND AND AIM: Bronchial thermoplasty (BT) is a treatment option for patients with severe asthma. BT involves controlled delivery of radiofrequency energy using a bronchoscopic catheter, thereby reducing bronchial hyperreactivity. Herein, we describe our experience on the safety and efficacy of BT in severe asthma. METHODS: This was a retrospective multicenter study of subjects who underwent BT at four centers across India. RESULTS: We included 36 subjects (mean ± standard deviation [SD] age, 50.9 ± 11.5 years, women [69.44%]) undergoing 105 BT treatment sessions. All the subjects met the American Thoracic Society/European Respiratory Society criteria for severe asthma, 22.2% were requiring oral maintenance glucocorticoids. The mean ± SD baseline %predicted forced expiratory volume in one second (FEV1) was 62.07 ± 18.54. The median interquartile range (IQR) annual asthma exacerbation rate in the year preceding BT was 3.5 (1-10). We encountered intraprocedural complications in 7 (6.7%) sessions. An exacerbation of asthma following BT occurred in 6 (5.7%) procedures. We observed a significant improvement in the asthma control test and the asthma control questionnaire scores following BT. The quality of life (asthma quality of life questionnaire) also significantly improved. We noted a significant reduction in the number of exacerbations following BT (median [IQR], 3 [1-10] per year pre-BT versus 0.5 [0-3] per year post-BT, P < 0.001). No significant change occurred in the %predicted FEV1 following BT. CONCLUSION: BT is a feasible treatment option in patients with severe asthma. More extensive studies are required to establish the efficacy of BT in real-life settings.

Single-dose oral ivermectin in mild and moderate COVID-19 (RIVET-COV): A single-centre randomized, placebo-controlled trial.

INTRODUCTION: Ivermectin is an antiparasitic drug which has in-vitro efficacy in reducing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load. Hence, Ivermectin is under investigation as a repurposed agent for treating COVID-19. METHODS: In this pilot, double blind, randomized controlled trial, hospitalized patients with mild-to-moderate COVID-19 were assigned to a single oral administration of an elixir formulation of Ivermectin at either 24 mg or 12 mg dose, or placebo in a 1:1:1 ratio. The co-primary outcomes were conversion of RT-PCR to negative result and the decline of viral load at day 5 of enrolment. Safety outcomes included total and serious adverse events. The primary outcomes were assessed in patients who had positive RT-PCR at enrolment (modified intention-to-treat population). Safety outcomes were assessed in all patients who received the intervention (intention-to-treat population). RESULTS: Among the 157 patients randomized, 125 were included in modified intention-to-treat analysis. 40 patients each were assigned to Ivermectin 24 mg and 12 mg, and 45 patients to placebo. The RT-PCR negativity at day 5 was higher in the two Ivermectin arms but failed to attain statistical significance (Ivermectin 24 mg, 47.5%; 12 mg arm, 35.0%; and placebo arm, 31.1%; p-value = 0.30). The decline of viral load at day 5 was similar in each arm. No serious adverse events occurred. CONCLUSIONS: In patients with mild and moderate COVID-19, a single oral administration of Ivermectin did not significantly increase either the negativity of RT-PCR or decline in viral load at day 5 of enrolment compared with placebo.

A review of therapies for the overlap syndrome of obstructive sleep apnea and chronic obstructive pulmonary disease.

Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) are common chronic diseases. These two noncommunicable diseases (NCDs) are prevalent among approximately 10% of the general population. Approximately 1% of the population is affected by the co-existence of both conditions, known as the overlap syndrome (OS). OS patients suffer from greater degrees of nocturnal oxygen desaturation and cardiovascular consequences than those with either condition in isolation. Besides OS, patients with COPD may suffer from a spectrum of sleep-related breathing disorders, including hypoventilation and central sleep apnea. The article provides an overview of the pathogenesis, associated risk factors, prevalence, and management of sleep-related breathing disorders in COPD. It examines respiratory changes during sleep caused by COPD and OSA. It elaborates upon the factors that link the two conditions together to lead to OS. It also discusses the clinical evaluation and diagnosis of these patients. Subsequently, it reviews the pathophysiological basis and the current evidence for three potential therapies: positive airway pressure therapy [including continuous positive airway pressure (CPAP) and bilevel positive airway pressure], oxygen therapy, and pharmacological therapy. It also proposes a phenotypic approach toward the diagnosis and treatment of OS and the entire spectrum of sleep-related breathing disorders in COPD. It concludes with the current evidence gaps and future areas of research in the management of OS.

Secretion management in patients with ineffective airway clearance with non-invasive mechanical ventilation use: Expert guidance for clinical practice.

Non-invasive ventilation (NIV) is a mainstay of management of chronic respiratory failure in many disorders which are known to cause abnormal airway secretion clearance. Currently, there is no guidance regarding either the secretion handling during NIV use or the role of NIV in secretion management in these patients. The aim of this document was to provide an overview of the various techniques available in the management of respiratory secretions and their use in conjunction with NIV. Literature search was performed using the keywords, "(secretion OR secretions) AND (noninvasive ventilation OR NIV)" on PubMed and EMBASE. The search yielded 1681 and 509 titles from PubMed and EMBASE, respectively. After screening, 19 articles were included in this review. Suggestions of the expert panel were formulated by mutual consensus after reviewing the relevant literature. The draft of the expert panel's suggestions was circulated among all authors via electronic mail for comments. Any conflicts were resolved by mutual discussion to achieve agreement. The final document was approved by all. This document by the International Network for Airway Secretions Management in NIV describes various airway secretion clearance techniques. It provides the expert panel's suggestions for the use of these techniques in conjunction with NIV for patients with muco-obstructive and neuromuscular disorders.

Clinical predictors of response to EGFR-tyrosine kinase inhibitors in EGFR-mutated non-small cell lung cancer: A real-world multicentric cohort analysis from India.

BACKGROUND: The development of various targeted therapies against Epidermal Growth Factor Receptor (EGFR) has been a major step in therapeutic advancements in lung cancer. However, the response to tyrosine kinase inhibitors (TKI) therapy in a real-world setting has not been well elucidated. METHODS: As part of a retrospective analysis, patients with EGFR mutated non-small cell lung cancer at 4 tertiary care Institutions in North India between December 2007 and August 2018 were evaluated. The overall response rate, disease control rate, progression-free survival (PFS) and factors affecting PFS were analyzed. RESULTS: A total of 483 patients were included, including 52.4% males, with mean (±SD) age of 56.7 (±12.4) years. Majority (63.8%) had good performance status (Eastern Cooperative Oncology Group 0 or 1) and 77.4% were nonsmokers. Among the EGFR mutations, exon 19 deletion was the most common mutation detected (68.1%), followed by L858R mutation in exon 21 (26.9%). Extra-thoracic metastasis was present in 69.5% patients and majority of them had ≤ 2 metastatic sites (85.1%). TKIs were used as the first-line therapy in 64.8% patients, and gefitinib was the most frequently used TKI (67.3%), followed by erlotinib (26.7%). The overall response rate and disease control rate were 65.9% and 90.7% respectively. The median PFS was 9.3 months and brain was the exclusive site of progression in 18.0% patients. On univariate analysis, the factors that significantly affected PFS were, the number of metastatic sites and the type of EGFR mutation. On multivariate analysis, the number of metastatic sites was the only factor that affected the PFS [HR (95% CI): 2.5 (1.7-3.6); Pvalue <0.001]. Skin toxicity was the most common adverse event (32.3%), followed by involvement of the gastro-intestinal tract (22.5%). CONCLUSION: In this one of the largest multicentric Indian study of treatment outcomes in EGFR-mutated non-small cell lung cancer in a real-world setting, we found that increased tumor burden (number of metastatic sites > 2) was the only significant factor associated with a worse PFS.

Covid-19: a comprehensive review of a formidable foe and the road ahead.

INTRODUCTION: The Coronavirus disease-19 (COVID-19) caused by the novel beta coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) started in late December 2019 in Wuhan, China. Within a short span, COVID-19 was declared a global public health emergency affecting 214 countries with 5,939,234 confirmed cases and 3,67,255 deaths as of 30 May 2020. With limited knowledge about SARS-CoV-2, no approved treatment or vaccine is available till date. AREAS COVERED: We performed a review of literature on PubMed on the SARS-CoV-2 virus and COVID-19 illness including trials of preventive and therapeutic measures. This review presents the basic biology of coronaviruses, epidemiology of COVID-19, clinical presentations, investigational therapies and vaccines, infection prevention and control measures and the lessons from the present pandemic. EXPERT OPINION: The scale of the outbreak has brought the governments, health-care professionals, and scientists around the world under tremendous pressure to devise control strategies and develop novel prevention measures. While availability of vaccine for COVID-19 may take time, the disease may be contained through hand hygiene, physical distancing, travel restriction, and aggressive steps such as 'lockdown.' Clinical trials at different phases are ongoing across different countries to expedite the development of effective drugs and vaccine to overcome the pandemic.

Bronchial thermoplasty for severe asthma: A position statement of the Indian chest society.

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