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Chronic obstructive pulmonary disease (COPD) is India's second largest cause of death and is largely caused by smoking. Asymptomatic smokers develop COPD due to genetic, environmental, and molecular variables, making early screening crucial. Data-independent acquisition mass spectrometry (DIA-MS) based-proteomics offers an unbiased method to analyze proteomic profiles. This study is the first to use DIA-based proteomics to analyze individual serum samples from three distinct male cohorts: healthy individuals ( n = 10), asymptomatic smokers ( n = 10), and COPD patients ( n = 10). This comprehensive approach identified 667 proteins with a 1% false discovery rate. Differentially expressed proteins included 40 in the normal versus asymptomatic comparison, 88 in the COPD versus normal comparison, and 40 in the COPD versus asymptomatic comparison. Among them, protein-associated genes such as PRDX6 , ELANE , PRKCSH , PRTN3 , and MNDA could help differentiate COPD from asymptomatic smokers, while ELANE , H3-3A , IGHE , SLC4A1 , and SERPINA11 could differentiate COPD from healthy subjects. Pathway enrichment and protein-protein interaction analyses revealed significant alterations in hemostasis, immune system functions, fibrin clot formation, and post-translational protein modifications. Key proteins were validated using a parallel reaction monitoring assay. DIA data are available via ProteomeXchange with identifier PXD055242. Our findings reveal key protein classifiers in COPD patients, asymptomatic smokers, and healthy individuals, helping clinicians understand disease pathobiology and improve disease management and quality of life.

Background: The incidence and mortality of gynaecological cancers can significantly impact women's quality of life and increase the health care burden for organisations globally. The objective of this study was to evaluate global inequalities in the incidence and mortality of gynaecological cancers in 2022, based on The Global Cancer Observatory (GLOBOCAN) 2022 estimates. The future burden of gynaecological cancers (GCs) in 2050 was also projected., Methods: Data regarding to the total cases and deaths related to gynaecological cancer, as well as cases and deaths pertaining to different subtypes of GCs, gathered from the GLOBOCAN database for the year 2022. Predictions for the number of cases and deaths in the year 2050 were derived from global demographic projections, categorised by world region and Human Development Index (HDI)., Results: In 2022, there were 1 473 427 new cases of GCs and 680 372 deaths. The incidence of gynecological cancer reached 30.3 per 100 000, and the mortality rate hit 13.2 per 100 000. The age-standardised incidence of GCs in Eastern Africa is higher than 50 per 100 000, whereas the age-standardised incidence in Northern Africa is 17.1 per 100 000. The highest mortality rates were found in East Africa (ASMR (age-standardised mortality rates) of 35.3 per 100 000) and the lowest in Australia and New Zealand (ASMR of 8.1 per 100 000). These are related to the endemic areas of HIV and HPV. Very High HDI countries had the highest incidence of GCs, with ASIR (age-standardised incidence rates) of 34.8 per 100 000, and low HDI countries had the second highest incidence rate, with an ASIR of 33.0 per 100 000. Eswatini had the highest incidence and mortality (105.4 per 100 000; 71.1 per 100 000) and Yemen the lowest (5.8 per 100 000; 4.4 per 100 000). If the current trends in morbidity and mortality are maintained, number of new cases and deaths from female reproductive tract tumours is projected to increase over the next two decades., Conclusions: In 2022, gynaecological cancers accounted for 1 473 427 new cases and 680 372 deaths globally, with significant regional disparities in incidence and mortality rates. The highest rates were observed in Eastern Africa and countries with very high and low HDI, with Eswatini recording the most severe statistics. If current trends continue, the number of new cases and deaths from gynaecological cancers is expected to rise over the next two decades, highlighting the urgent need for effective interventions., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Social determinants of health (SDHs) have a substantial impact on patient care and outcomes globally, both in low- to middle-income countries and in high-income countries. In the clinic, lack of availability of diagnostic tools, inequities in access to care, and challenges obtaining and adhering to prescribed treatment plans may further compound these issues. This article addresses a case of rhinitis in the context of SDHs and inequities in care that may affect various communities and populations around the world. SDHs may include various aspects of one's financial means, education, access to medical care, environment and living situation, and community factors, each of which could play a role in the rhinitis disease manifestations, diagnosis, and management. Allergic and nonallergic rhinitis are considered from this perspective. Rhinitis epidemiology, disease burden, and risk factors are broadly addressed. Patient evaluation, diagnostic tests, and management options are also reviewed, and issues related to SDHs are noted. Finally, inequities in care, knowledge gaps, and unmet needs are highlighted. It is critical to consider SDHs and care inequities when evaluating and treating patients for rhinitis and other allergic conditions., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition., Methods: We analysed cross-sectional data from 33,983 adults (≥40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random-effects meta-analysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors., Findings: The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job., Interpretation: Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors., Funding: Wellcome Trust., Competing Interests: Fatima Rodrigues declares grants and personal fees from A. Menarini, Boehringer Ingelheim, Teva Pharma, Novartis, GlaxoSmithKline, AstraZeneca, VitalAire and Nippon Gases outside the submitted work. Wan C. Tan received grants from the Canadian Institute of Heath Research (CIHR/Rx&D Collaborative Research Program Operating Grants- 93,326) with industry partners Astra Zeneca Canada Ltd., Boehringer-Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Merck, Novartis Pharma Canada Inc., Nycomed Canada Inc., Pfizer Canada Ltd. for conducting the longitudinal population-based Canadian Cohort of Obstructive Lung Disease (CanCOLD) study on COPD. David Mannino is a consultant to GSK, AstraZeneca, Regeneron, Genentech, COPD Foundation, and expert witness on behalf of people suing Tobacco Industry (Schlesinger Law Firm). Sonia Buist is Chair of the Data Safety & Monitoring Board for the RELIANCE Clinical Trial. Frits Franssen declares personal fees from AstraZeneca, Chiesi, GlaxoSmithKline, MSD, Pieris, and Verona Pharma. Robab Breyer-Kohansal declares consulting fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Menarini, Novartis Pharma, and Sanofi, and participation on advisory boards for AstraZeneca, Menarini, and Sanofi. Thorarinn Gislason received a grant from the Icelandic Research Fund. Kevin Mortimer declares participation on advisory boards for AstraZeneca and GlaxoSmithKline. Sylvia Hartl declares grants from GSK, Chiesi Farma, Menarini Pharma, and AstraZeneca, and participation on advisory boards for Menarini Pharma and GSK. AFSA declares a grant from the COLT Foundation (CF/01/21)., (© 2024 The Author(s).)

BACKGROUND: The aim of these clinical standards is to aid the diagnosis and management of asthma in low-resource settings in low- and middle-income countries (LMICs). METHODS: A panel of 52 experts in the field of asthma in LMICs participated in a two-stage Delphi process to establish and reach a consensus on the clinical standards. RESULTS: Eighteen clinical standards were defined: Standard 1, Every individual with symptoms and signs compatible with asthma should undergo a clinical assessment; Standard 2, In individuals (>6 years) with a clinical assessment supportive of a diagnosis of asthma, a hand-held spirometry measurement should be used to confirm variable expiratory airflow limitation by demonstrating an acute response to a bronchodilator; Standard 3, Pre- and post-bronchodilator spirometry should be performed in individuals (>6 years) to support diagnosis before treatment is commenced if there is diagnostic uncertainty; Standard 4, Individuals with an acute exacerbation of asthma and clinical signs of hypoxaemia or increased work of breathing should be given supplementary oxygen to maintain saturation at 94-98%; Standard 5, Inhaled short-acting beta-2 agonists (SABAs) should be used as an emergency reliever in individuals with asthma via an appropriate spacer device for metered-dose inhalers; Standard 6, Short-course oral corticosteroids should be administered in appropriate doses to individuals having moderate to severe acute asthma exacerbations (minimum 3-5 days); Standard 7, Individuals having a severe asthma exacerbation should receive emergency care, including oxygen therapy, systemic corticosteroids, inhaled bronchodilators (e.g., salbutamol with or without ipratropium bromide) and a single dose of intravenous magnesium sulphate should be considered; Standard 8, All individuals with asthma should receive education about asthma and a personalised action plan; Standard 9, Inhaled medications (excluding dry-powder devices) should be administered via an appropriate spacer device in both adults and children. Children aged 0-3 years will require the spacer to be coupled to a face mask; Standard 10, Children aged <5 years with asthma should receive a SABA as-needed at step 1 and an inhaled corticosteroid (ICS) to cover periods of wheezing due to respiratory viral infections, and SABA as-needed and daily ICS from step 2 upwards; Standard 11, Children aged 6-11 years with asthma should receive an ICS taken whenever an inhaled SABA is used; Standard 12, All adolescents aged 12-18 years and adults with asthma should receive a combination inhaler (ICS and rapid onset of action long-acting beta-agonist [LABA] such as budesonide-formoterol), where available, to be used either as-needed (for mild asthma) or as both maintenance and reliever therapy, for moderate to severe asthma; Standard 13, Inhaled SABA alone for the management of patients aged >12 years is not recommended as it is associated with increased risk of morbidity and mortality. It should only be used where there is no access to ICS.The following standards (14-18) are for settings where there is no access to inhaled medicines. Standard 14, Patients without access to corticosteroids should be provided with a single short course of emergency oral prednisolone; Standard 15, Oral SABA for symptomatic relief should be used only if no inhaled SABA is available. Adjust to the individual's lowest beneficial dose to minimise adverse effects; Standard 16, Oral leukotriene receptor antagonists (LTRA) can be used as a preventive medication and is preferable to the use of long-term oral systemic corticosteroids; Standard 17, In exceptional circumstances, when there is a high risk of mortality from exacerbations, low-dose oral prednisolone daily or on alternate days may be considered on a case-by-case basis; Standard 18. Oral theophylline should be restricted for use in situations where it is the only bronchodilator treatment option available. CONCLUSION: These first consensus-based clinical standards for asthma management in LMICs are intended to help clinicians provide the most effective care for people in resource-limited settings.

Cigarette smoking is the major cause of chronic inflammatory diseases such as chronic obstructive pulmonary disease (COPD). It is paramount to develop pharmacological interventions and delivery strategies against the cigarette smoke (CS) associated oxidative stress in COPD. This study in Wistar rats examined cysteamine in nanoemulsions to counteract the CS distressed microenvironment. In vivo , 28 days of CS and 15 days of cysteamine nanoemulsions treatment starting on 29th day consisting of oral and inhalation routes were established in Wistar rats. In addition, we conducted inflammatory and epithelial-to-mesenchymal transition (EMT) studies in vitro in human bronchial epithelial cell lines (BEAS2B) using 5% CS extract. Inflammatory and anti-inflammatory markers, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-1β, IL-8, IL-10, and IL-13, have been quantified in bronchoalveolar lavage fluid (BALF) to evaluate the effects of the cysteamine nanoemulsions in normalizing the diseased condition. Histopathological analysis of the alveoli and the trachea showed the distorted, lung parenchyma and ciliated epithelial barrier, respectively. To obtain mechanistic insights into the CS COPD rat model, "shotgun" proteomics of the lung tissues have been carried out using high-resolution mass spectrometry wherein genes such as ABI1 , PPP3CA , PSMA2 , FBLN5 , ACTG1 , CSNK2A1 , and ECM1 exhibited significant differences across all the groups. Pathway analysis showed autophagy, signaling by receptor tyrosine kinase, cytokine signaling in immune system, extracellular matrix organization, and hemostasis, as the major contributing pathways across all the studied groups. This work offers new preclinical findings on how cysteamine taken orally or inhaled can combat CS-induced oxidative stress.

The coronavirus (COVID-19) pandemic, along with its various strains, has emerged as a global health crisis that has severely affected humankind and posed a great challenge to the public health system of affected countries. The replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mainly depends on RNA-dependent RNA polymerase (RdRp), a key enzyme that is involved in RNA synthesis. In this regard, we designed, synthesized, and characterized hybrid thiouracil and coumarin conjugates (HTCAs) by ether linkage, which were found to have anti-SARS-CoV-2 properties. Our in vitro real-time quantitative reverse transcription PCR (RT-qPCR) results confirmed that compounds such as 5d , 5e , 5f , and 5i inhibited the replication of SARS-CoV-2 with EC 50 values of 14.3 ± 0.14, 6.59 ± 0.28, 86.3 ± 1.45, and 124 ± 2.38 μM, respectively. Also, compound 5d displayed significant antiviral activity against human coronavirus 229E (HCoV-229E). In addition, some of the HTCAs reduced the replication of SARS-CoV-2 variants such as D614G and B.617.2. In parallel, HTCAs in uninfected Vero CCL-81 cells indicated that no cytotoxicity was noticed. Furthermore, we compared the in silico interaction of lead compounds 5d and 5e toward the cocrystal structure of Suramin and RdRp polymerase with Remdesvir triphosphate, which showed that compounds 5d , 5e , and Remdesvir triphosphate (RTP) share a common catalytical site of RdRp but not Suramin. Additionally, the in silico ADMET properties predicted for the lead HTCAs and RTP showed that the maximum therapeutic doses recommended for compounds 5d and 5e were comparable to those of RTP. Concurrently, the pharmacokinetics of 5d was characterized in male Wistar Albino rats by administering a single oral gavage at a dose of 10 mg/kg, which gave a Cmax value of 0.22 μg/mL and a terminal elimination half-life period of 73.30 h. In conclusion, we established a new chemical entity that acts as a SARS-CoV-2 viral inhibitor with minimal or no toxicity to host cells in the rodent model, encouraging us to proceed with preclinical studies., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

(1) Introduction: COPD is a common and serious condition affecting a significant proportion of the population globally. Patients often suffer from exacerbations which lead to the worsening of their health status and respiratory function, and can often lead to death. Quick and cheap investigations are required that are capable of predicting mortality in patients with acute exacerbations that can be applied in low resource settings. (2) Materials and methods: This was a retrospective study carried out using hospital records of patients admitted for AECOPD from 1 January 2017 to 30 November 2022. Chi-square test (for sex) and Student's t -test were used to look for significant associations. Receiver Operating Characteristics (ROC) curves were plotted and Area Under Curve (AUC) values were calculated for various hematological parameters. Youden's J was used to identify the ideal cut-off with optimal sensitivity and specificity. Multivariate Cox regression was used to identify independent hematological predictors of mortality. Kaplan-Meir survival plots for neutrophil lymphocyte ratio (NLR) with the optimal cut-off were plotted. (3) Results: Amongst the 500 patients, 42 died while 458 survived, giving a mortality rate of 8.4%. NLR had the strongest association with mortality. The cut-off for various parameters were: NLR 14.83 (AUC 0.73), total leukocyte count (TLC) 13,640 cells/mm 3 (AUC 0.60), absolute neutrophil count (ANC) 12,556 cells/mm 3 (AUC 0.62), derived NLR (dNLR) 9.989 (AUC 0.73), hemoglobin 11.8 mg/dL (AUC 0.59), packed cell volume (PCV) 36.6% (AUC 0.60), and platelet lymphocyte ratio (PLR) 451.32 (AUC 0.55). (4) Conclusions: In patients with acute exacerbation of COPD, NLR was strongly associated with mortality, followed by dNLR. Cox regression identified NLR as an independent predictor of mortality.

The most recent recommendations from the 2020 National Asthma Education and Prevention Program Update and Global Initiative for Asthma 2021 guide evidence-based clinical decision making. However, given the present state of health disparities by age, income, and race, the equitable implementation and dissemination of these guidelines will be unlikely without further guidance. This work group report reviews the current state of the new asthma guideline implementation; presents updated evidence-based therapeutic options with attention to specific patient populations; and addresses barriers to the implementation of these guidelines in minoritized, historically marginalized, and underresourced communities. Allergists and immunologists can use practical ways to accomplish the goals of improved asthma care access and advanced asthma care across the life span, with specific considerations to historically marginalized populations. Modifiable barriers to guideline implementation include financial barriers, environmental factors, and allergy subspecialty access and care coordination. Various programs to improve access to guideline-based asthma care include community programs, school-based asthma programs, and digital health solutions, with an emphasis on reducing disparities by race., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Globally, data on the coronavirus disease (COVID-19) pandemic showed a higher risk of infection and complications in people with non-communicable diseases (NCDs). In India, the prevalence of NCDs and their risk factors vary significantly between states. Compared to other states, Kerala has the highest prevalence of non-communicable diseases in the country, along with the highest proportion of the elderly population. The study evaluates the disease management patterns and changes in healthcare behaviors among adults with NCDs in Kerala during the COVID-19 pandemic., Methods: A cross-sectional study was conducted among 410 adult NCD patients in rural Thiruvananthapuram district, Kerala. Using a semi-structured interview schedule, the present study gathered information on socio-demographic characteristics, disease patterns, healthcare utilization, and behavioral change during the pandemic., Results: Mean age of the participants was 62 years (range: 37-88; women: 64%). The most prevalent NCD was hypertension (74%) and diabetes (65%) followed by chronic respiratory disease (12%), cardiovascular disease (11%), and cancer (2%). Nearly 76% had difficulty in obtaining consultation/medical follow-up. Around 10% relied on telecommunication and 32% reported increased stress during the pandemic. Those with low socio-economic status and with a single NCD were more vulnerable to the challenges faced during the pandemic., Conclusion: A higher proportion of adults with NCDs faced difficulties in healthcare access and had negative healthcare behaviors during the pandemic. The findings highlight the need to ensure better healthcare for people living with NCDs during the times of pandemic., Competing Interests: None., (© 2023 The Authors.)

The prevalence of childhood asthma contributes to the global burden of the disease substantially. Air pollution in India has increased. In this study, we examine the associations among greenspaces, air pollution, and asthma prevalence in children and adolescents over a large, diverse population in India. We used state-wide global burden of disease data on asthma from age 0 to 19 years in 2005, 2011, and 2017. For greenspace, we used the normalized differential vegetation index (NDVI), which is the surface reflectance of light during photosynthetic activity. NDVI, air pollutants (PM 2.5 , PM 10 , SO 2 , NO 2 , and O 3 ), weather, and socio-demographic factors were included in generalized estimating equation (GEE) models to estimate their associations with childhood asthma prevalence over time. Novel data visualization illustrated the complex spatial distributions. NDVI was associated with asthma prevalence (β = 0.144; 95% CI = 0.10, 0.186; p < 0.0001) for high PM 2.5 , along with high levels of both gaseous air pollutants, SO 2 , and NO 2 ((β = 0.12; 95% CI = 0.08, 0.16; p < 0.0001) and (β = 0.09; 95% CI = 0.05, 0.13; p < 0.0001)). However, NDVI and high O 3 , had a strong negative association with asthma prevalence (β = -0.19; 95% CI = -0.26, -0.11; p < 0.0001). We observed additional effects of the interaction between the NDVI and high concentrations of PM 2.5 , PM 10 , NO 2 , and O 3 , assuming that these associations share a common pathway, and found interaction effects for asthma prevalence. Given the changing environmental conditions that interplay over geographical characteristics on the prevalence of asthma, further studies may elucidate a better understanding of these complex associations., Competing Interests: The authors declare no conflict of interest.

Background: There is a paucity of data on biomarkers for the early deterioration and clinical instability of patients in community-acquired pneumonia (CAP), as treatment failure occurs in the first seven days in 90% of patients. Aim: To evaluate serum albumin and copeptin with CURB-65, PSI scoring and ATS/IDSA minor criteria for the prediction of early mortality or ICU-admission (7 days) and clinical instability after 72 h. Methods: In 100 consecutive hospitalized adult CAP patients, PSI-scores, CURB-65 scores, ATS/IDSA 2007 minor criteria, copeptin and albumin on admission were evaluated. Univariate and multivariate Cox regression analysis was performed to assess independent risk factors for early combined mortality or ICU admission. Predictive powers of albumin and copeptin were tested with ROC curves and ICU-free survival probability was tested using Kaplan−Meier analysis. Results: Albumin was lower and copeptin higher in patients with short-term adverse outcomes (p < 0.05). Cox regression analysis showed that albumin [HR (95% CI): 0.41 (0.18−0.94, p = 0.034)] and copeptin [HR (95% CI): 1.94 (1.03−3.67, p = 0.042)] were independent risk factors for early combined mortality or ICU admission (7 days). The Kaplan−Meier analysis observed that high copeptin (>27.12 ng/mL) and low albumin levels (<2.85 g/dL) had a lower (p < 0.001) survival probability. The diagnostic accuracy of albumin was better than copeptin. The inclusion of albumin and copeptin into ATS/IDSA minor criteria significantly improved their predictive power. Conclusions: Both biomarkers serum albumin and copeptin can predict early deterioration and clinical instability in hospitalized CAP patients and increase the prognostic power of the traditional clinical scoring systems.

Asthma and chronic obstructive pulmonary disease are considered unique diseases with distinct characteristics. Asthma-chronic obstructive pulmonary disease overlap is a disorder in which the clinical characteristics of asthma and chronic obstructive pulmonary disease coexist. Asthma-chronic obstructive pulmonary disease overlap is a heterogenous condition; patients can have varied clinical presentations. There are significant gender variations among different phenotypes overlap. Age of symptom onset is another important consideration. Severity of symptoms, spirometry findings, smoking history, and type of airway inflammation varies between the different phenotypes. Understanding disease pathophysiology and establishing phenotypic models will improve a precision approach., Competing Interests: Disclosure The authors declare no relevant disclosures pertinent to this article. No funding was received for the manuscript., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Several studies have proposed that the neutrophil−lymphocyte ratio (NLR) is one of the various biomarkers that can be useful in assessing COVID-19 disease-related outcomes. Our systematic review analyzes the relationship between on-admission NLR values and COVID-19 severity and mortality. Six different severity criteria were used. A search of the literature in various databases was conducted from 1 January 2020 to 1 May 2021. We calculated the pooled standardized mean difference (SMD) for the collected NLR values. A meta-regression analysis was performed, looking at the length of hospitalization and other probable confounders, such as age, gender, and comorbidities. A total of sixty-four studies were considered, which included a total of 15,683 patients. The meta-analysis showed an SMD of 3.12 (95% CI: 2.64−3.59) in NLR values between severe and non-severe patients. A difference of 3.93 (95% CI: 2.35−5.50) was found between survivors and non-survivors of the disease. Upon summary receiver operating characteristics analysis, NLR showed 80.2% (95% CI: 74.0−85.2%) sensitivity and 75.8% (95% CI: 71.3−79.9%) specificity for the prediction of severity and 78.8% (95% CI: 73.5−83.2%) sensitivity and 73.0% (95% CI: 68.4−77.1%) specificity for mortality, and was not influenced by age, gender, or co-morbid conditions. Conclusion: On admission, NLR predicts both severity and mortality in COVID-19 patients, and an NLR > 6.5 is associated with significantly greater the odds of mortality.

Introduction: The clinical and epidemiological presentations of patients with coronavirus disease 2019 (COVID-19) in India is still not well explored. We studied the epidemiological and clinical profile and outcomes of COVID-19 patients admitted to a tertiary care private hospital in Kerala, India., Methods: In this retrospective study, we analyzed data of 476 adult (≥18 years) COVID-19 patients admitted to a tertiary care hospital in Kerala from September 1, 2020 to March 31, 2021. The patients were categorized into mild, moderate, and severe cases and followed till discharge or death. Data were analyzed using Statistical Package for the Social Sciences (SPSS) version 23.0 with a significance set at P < 0.05., Results: The median age was 57 years (56% men). Mild, moderate, and severe cases accounted for 17%, 65%, and 18%, respectively. Around 75% had at least one comorbidity, and 51% had multiple comorbidities. The most common comorbidities were diabetes (45%), hypertension (44%), dyslipidemia (15%), and cardiac problems (12%). The elevated D-dimer values among patients in different categories were significantly different, with 74% in severe, 46% in moderate, and 19% in mild category patients. Serum ferritin, C-reactive protein, lactic acid dehydrogenase, and neutrophil to lymphocyte ratio values were significantly higher for severely ill patients. Thirty deaths (67% men) occurred during the study period, with a case fatality rate of 6.3%. Mortality mainly happened in the older age group (80%) and those with multimorbidity (90%)., Conclusion: Age and multimorbidity are the major contributing factors for death in hospitalized COVID-19 patients. Generalization of the findings necessitates well-designed large-scale studies., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Secretoglobin family 1A member 1 (SCGB1A1) alternatively known as club cell protein 16 is a protective pneumo-protein. Decreased serum levels of SCGB1A1 have been associated with tobacco smoke induced chronic obstructive pulmonary disease (TS-COPD). Exposure to biomass smoke (BMS) is an important COPD risk factor among women in low and lower-middle income countries. Therefore, in a cross-sectional study ( n = 50/group; total 200 subjects) we assessed serum SCGB1A1 levels in BMS-COPD subjects (11 male, 39 female) compared to TS-COPD (all male) along with TS-CONTROL (asymptomatic smokers, all male) and healthy controls (29 male, 21 female) in an Indian population. Normal and chronic bronchitis like bronchial mucosa models developed at the air-liquid interface using human primary bronchial epithelial cells (3 donors, and three replicates per donor) were exposed to cigarette smoke condensate (CSC; 0.25, 0.5, and 1%) to assess SCGB1A1 transcript expression and protein secretion. Significantly ( p < 0.0001) decreased serum SCGB1A1 concentrations (median, interquartile range, ng/mL) were detected in both BMS-COPD (1.6; 1.3-2.4) and TS-COPD (1.8; 1.4-2.5) subjects compared to TS-CONTROL (3.3; 2.9-3.5) and healthy controls (5.1; 4.5-7.2). The levels of SCGB1A1 were positively correlated ( r = 0.7-0.8; p < 0.0001) with forced expiratory volume in 1 s, forced vital capacity, their ratios, and exercise capacity. The findings are also consistent within the BMS-COPD sub-group as well. Significantly ( p < 0.03) decreased SCGB1A1 concentrations were detected with severity of COPD, dyspnea, quality of life, and mortality indicators. In vitro studies demonstrated significantly ( p < 0.05) decreased SCGB1A1 transcript and/or protein levels following CSC exposure. Circulating SCGB1A1 levels may therefore also be considered as a potent marker of BMS-COPD and warrant studies in larger independent cohorts.

Rationale: The Global Burden of Disease program identified smoking and ambient and household air pollution as the main drivers of death and disability from chronic obstructive pulmonary disease (COPD). Objectives: To estimate the attributable risk of chronic airflow obstruction (CAO), a quantifiable characteristic of COPD, due to several risk factors. Methods: The Burden of Obstructive Lung Disease study is a cross-sectional study of adults, aged ≥40, in a globally distributed sample of 41 urban and rural sites. Based on data from 28,459 participants, we estimated the prevalence of CAO, defined as a postbronchodilator FEV 1 -to-FVC ratio less than the lower limit of normal, and the relative risks associated with different risk factors. Local relative risks were estimated using a Bayesian hierarchical model borrowing information from across sites. From these relative risks and the prevalence of risk factors, we estimated local population attributable risks. Measurements and Main Results: The mean prevalence of CAO was 11.2% in men and 8.6% in women. The mean population attributable risk for smoking was 5.1% in men and 2.2% in women. The next most influential risk factors were poor education levels, working in a dusty job for ≥10 years, low body mass index, and a history of tuberculosis. The risk of CAO attributable to the different risk factors varied across sites. Conclusions: Although smoking remains the most important risk factor for CAO, in some areas, poor education, low body mass index, and passive smoking are of greater importance. Dusty occupations and tuberculosis are important risk factors at some sites.

Rationale: Exposure to biomass smoke ( BMS ) has been implicated in chronic obstructive pulmonary disease ( COPD ). About 3 billion people worldwide use biomass fuel for cooking and heating. Women in rural communities of low- and lower-middle-income countries are disproportionately exposed to massive amounts of BMS during active cooking hours (4-6 h/day). Therefore, BMS exposure is considered as a risk factor for COPD in the same order of magnitude as tobacco smoke. In rural India, due to cultural reasons, women are the primary cook of the family and are mostly nonsmokers. Thus, BMS-induced COPD is predominant among rural Indian women. However, BMS-COPD remains a relatively unexplored health problem globally. Therefore, we investigated the serum chemokine and cytokine signatures of BMS-COPD and tobacco smoke-induced COPD ( TS-COPD ) patients compared to their control in a rural South Indian population for this field study., Methods: Concentrations of 40 serum chemokines and cytokines were measured using a multiplexed immunoassay. The study cohort consisted of BMS-COPD (female; n = 29) and BMS-exposed subjects without COPD ( BMS-CONTROL ; female; n = 24). For comparison, data from TS-COPD patients (male, n = 23) and tobacco smokers without COPD ( TS-CONTROL ; male, n = 22) were investigated. Subjects were matched for age, sex, and biomass exposure. Tobacco consumption was slightly higher in TS-COPD subjects compared to TS-CONTROL. BMS-exposed and TS-exposed subjects (currently exposed) were from the same locality with similar dwelling habits and socioeconomic status. A validated structured questionnaire-based survey and spirometry was performed. An additional control group with no tobacco and BMS exposure ( TS-BMS-CONTROL ; n = 15) was included. Statistical significance was set at p ≤ 0.01., Results: Serum median concentrations (pg/ml) of CCL15 [8799.35; 5977.22], CCL27 [1409.14; 1024.99], and CXCL13 [37.14; 26.03] were significantly higher in BMS-CONTROL compared to BMS-COPD subjects. Nine analytes exhibited higher concentrations in TS-CONTROL compared to TS-COPD subjects. Comparison of chemokine and cytokine concentrations among BMS-COPD versus TS-COPD and BMS-CONTROL versus TS-CONTROL subjects also revealed distinct molecular signatures., Conclusion: Our data identifies CCL27 and CXCL13 as putative, plausibly homeostatic/protective biomarkers for BMS-COPD within the investigated population that warrants validation in larger and multiple cohorts. The findings further indicate exposure-specific systemic response of chemokines and cytokines.

Background: Chronic obstructive pulmonary disease (COPD) is a devastating condition with limited pharmacotherapeutic options and exceptionally high public-health burden globally as well as in India. Tobacco smoking is the primary cause for COPD among men in India. Systemic inflammation involving altered regulation of cytokines controlling the host defense mechanism is a hallmark of COPD pathogenesis. However, biomarker discovery studies are limited among Indian COPD patients., Methods: We assessed the serum concentrations [median (25th-75th percentile) pg/ml] of interleukin ( IL )-2,4,6,8,10, granulocyte macrophage colony stimulating factor ( GM-CSF ), interferon gamma ( IFN- γ ), and tumor necrosis factor alpha ( TNF- α ) using a multiplexed immunoassay. Our study cohort consisted of 30 tobacco smokers with COPD ( TS COPD ) and 20 tobacco smokers without COPD ( TS CONTROL ) from South India. The study population was matched for age, sex (male), and tobacco consumption (pack-years). COPD was diagnosed according to the global initiative for chronic obstructive lung disease (GOLD) criteria of persistent airflow obstruction determined by the ratio of postbronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV 1 /FVC) of <0.7. A validated structured questionnaire-based survey [Burden of Obstructive Lung Disease (BOLD) study] and spirometry were performed during house to house visit of the field study. Statistical analysis included nonparametric (two-tailed) Mann-Whitney U and Spearman rank test, as appropriate (significance: p<0.05)., Results: Serum GM-CSF [69.64 (46.67, 97.48); 36.78 (30.07, 53.88), p=0.014], IFN- γ [51.06 (17.00, 84.86); 11.70 (3.18, 32.81), p=0.017], IL-4 [9.09 (1.8, 19.9); 1.8 (1.8, 4.46); p=0.024], and TNF- α [20.68 (5.5, 29.26); 3.5 (3.5, 4.5); p<0.001] concentrations (pg/ml) were increased in TS COPD subjects compared to TS CONTROL. A weak correlation between lung function parameters and cytokine concentrations was detected., Conclusion: Our pilot study reveals GM-CSF, IFN- γ , IL-4, and TNF- α as plausible COPD susceptibility biomarkers within the investigated South Indian population that needs to be validated in a larger cohort.

Genetic analysis in haploids provides unconventional yet powerful advantages not available in diploid organisms. In Arabidopsis thaliana, haploids can be generated through seeds by crossing a wild-type strain to a transgenic strain with altered centromeres. Here we report the development of an improved haploid inducer (HI) strain, SeedGFP-HI, that aids selection of haploid seeds prior to germination. We also show that haploids can be used as a tool to accelerate a variety of genetic analyses, specifically pyramiding multiple mutant combinations, forward mutagenesis screens, scaling down a tetraploid to lower ploidy levels and swapping of nuclear and cytoplasmic genomes. Furthermore, the A. thaliana HI can be used to produce haploids from a related species A. suecica and generate homozygous mutant plants from strong maternal gametophyte lethal alleles, which is not possible via conventional diploid genetics. Taken together, our results demonstrate the utility and power of haploid genetics in A. thaliana.

Objective: To find out prevalence of hypertension amongst Mumbai executives., Methods: Data of annual medical check-up of 1653 executives was evaluated. Blood pressure was measured as per JNC VI/WHO guidelines., Results: Overall prevalence of hypertension amongst Mumbai executives was 26.86%. 21.28% of executives who were hypertensive based on causal reading were later found to have normal or high normal blood pressure., Conclusion: For all epidemiological surveys, blood pressure must be recorded on at least two subsequent occasions after initial screening.

Lifestyle modifications are universally accepted, not only as the first step in the management of hypertension but also a way to prevent hypertension. The INTERSALT study of 52 communities worldwide showed that weight, among all measured characteristics except age, had the strongest, significant, most consistent and independent correlation with blood pressure. INTERSALT epidemiological data had demonstrated a positive association between sodium intake and level of blood pressure. A rigorous analysis of 23 randomly controlled trials showed that 100 mmol/day reduction in sodium intake was associated with a decline of 5-7 mm Hg (systolic)/2.7 mm Hg (diastolic) in hypertensive subjects. Excessive alcohol consumption is another important risk factor for hypertension and has been reported to account for 5-30% of all hypertension. Moderately intense exercise at 40 to 60% of maximum oxygen consumption e.g., 30 to 45 minutes of brisk walking on 4-5 days a week, can lower blood pressure. The incidence of stroke and coronary artery disease in hypertensive patients who smoke is 2-3 times greater than in non-smoking patients with comparable blood pressure and stopping smoking rapidly reduces this risk. There have been several studies showing the stress reduction with various behavioural procedures, such as yoga, relaxation biofeedback, transcedental mediation and psychotherapy benefit hypertensive patients by lowering their blood pressure.

In a large multicentre study of 918 hypertensive patients, 28% of subjects were found to be smokers. Smokers had a higher average weight and associated diseases like coronary artery disease and diabetes. It is suggested that higher incidence of coronary artery disease and diabetes in the hypertensive smokers carries a higher risk of further cardiovascular events.

Using half-life disappearance of intradermally injected radioiodine as a parameter for cutaneous blood flow, a study was made of the effects of labetalol and propranolol on the vasoconstrictor response to adrenaline at environmental temperatures of 22 degrees C and 32 degrees C in seven healthy volunteers. Iodine clearance was reduced at 22 degrees C, and at both temperatures by 16 pcg of adrenaline. Orally administered propranolol (20 mg) enhanced these effects at the lower temperature and that of adrenaline at both temperatures. This method unequivocally demonstrates the aggravation of adrenaline-induced cutaneous vasoconstriction caused by oral administration of propranolol and distinguishes it from that caused by labetalol.

Tests among 410 Indians not artificially immunised against tetanus showed that 80% had measurable antitoxin. Single doses (100 Lf or 250 Lf) of a potent tetanus toxoid were given to such individuals with naturally acquired antitoxin. The 100 Lf dose produced on average a ten-fold rise in antibody level, and the 250 Lf dose a twenty-fold rise. In adults who had been artificially immunised, a 5 Lf dose produced a four-fold to ten-fold rise in antibody level. In infants three doses of triple vaccine produced satisfactory antitoxin concentrations. The levels of antibody achieved after a single 250 Lf dose should protect for 5 years. Single-dose vaccination may be better than the conventional three-dose scheme for a population that is unlikely to comply with a three-dose regimen and in whom naturally acquired antitoxin is associated with partial tolerance to tetanus toxoid. Naturally acquired antitoxin in Indians is probably the result of chronic clostridial contamination of the small bowel. This contamination can induce immune tolerance in the gut and systemically and may be the reason for the poor responses to vaccination in all except infants.

We studied 1217 cases of myocardial infarction, admitted to Patna Medical College Hospital, Patna, during the period 1979 to 1983, and correlated the incidence of the disease with air-temperature, seasons and months. There was no monthly variation in the incidence of the disease. The seasons similarly had no influence on incidence. The frequency of myocardial infarction, however, was significantly higher when the minimum air-temperature was 16 degrees C or less (P less than 0.001). This study indicates that drop in atmospheric temperature below a certain level directly increases the incidence of myocardial infarction and suggests simple prevention measures against the adverse effect of cold.

The effects of labetalol and propranolol were compared in eight healthy human volunteers using pulse rate and blood pressure changes in response to low rates of adrenaline infusion. Propranolol not only blocked but reversed the positive chronotropic and vasodepressor effects of adrenaline. Labetalol appeared to block these effects only partially. The alpha blocking property of labetalol may have contributed to this difference and hence is unlikely to cause alpha receptor mediated side-effects of endogenously released adrenaline in stress. This model is able to differentiate with great sensitivity between pure beta blockers and alpha beta blocking agents.