Use of Thiols in the Treatment of COVID-19: Current Evidence.

There is a possible role for oxidative stress, a state characterized by an altered balance between the production of free radicals or reactive oxygen species (ROS) and antioxidant defences, in coronavirus disease 2019 (COVID-19), the genesis of which is quite complex. Excessive oxidative stress could be responsible for the alveolar damage, thrombosis, and red blood cell dysregulation observed in COVID-19. Apparently, deficiency of glutathione (GSH), a low-molecular-weight thiol that is the most important non-enzymatic antioxidant molecule and has the potential to keep the cytokine storm in check, is a plausible explanation for the severe manifestations and death in COVID-19 patients. Thiol drugs, which are considered mucolytic, also possess potent antioxidant and anti-inflammatory properties. They exhibit antibacterial activity against a variety of medically important bacteria and may be an effective strategy against influenza virus infection. The importance of oxidative stress during COVID-19 and the various pharmacological characteristics of thiol-based drugs suggest a possible role of thiols in the treatment of COVID-19. Oral and intravenous GSH, as well as GSH precursors such as N-acetylcysteine (NAC), or drugs containing the thiol moiety (erdosteine) may represent a novel therapeutic approach to block NF-kB and address the cytokine storm syndrome and respiratory distress observed in COVID-19 pneumonia patients.

Prevalence, risk factors and clinical correlates of COPD in a rural setting in Tanzania.

Chronic obstructive pulmonary disease (COPD) causes substantial burden of disease in developed countries, but there are limited data from Africa. We aimed to estimate the prevalence of COPD in Tanzania and identify the risk factors associated with it.This was a cross-sectional descriptive survey involving adults aged ≥35 years. We collected data on symptoms and risk factors using the Burden of Obstructive Lung Diseases questionnaire. Spirometry was performed and COPD diagnosed based on post-bronchodilator forced expiratory volume in 1 s/forced vital capacity <70%. We also measured indoor and outdoor carbon monoxide (CO) levels.A total of 869 participants (49.1% females) completed the questionnaires. Of these, 57.1% completed post-bronchodilator spirometry. Of the 25.2% ever-smokers, only 5.4% were current smokers. COPD prevalence was estimated at 17.5% (21.7% in males and 12.9% in females). COPD was associated with a history of cough, phlegm production and wheezing. 51.7% of COPD patients reported cough and 85% had mild to moderate airway limitation. Females had a higher rate of exacerbation. Pulmonary tuberculosis (TB) was reported in 10% of patients. Only 1.7% of patients who were diagnosed as COPD had ever received any medication, with only one female COPD patient having received an inhaler. 99.5% of the population used biomass fuels for cooking. The majority of households had CO levels up to 20 ppm.The prevalence of COPD in Tanzania is high, with a peak at a relatively young age and a preponderance in males. A history of TB, cigarette smoking and male sex are important risk factors. Indoor air pollution coupled with use of biomass fuel for cooking and heating may be an important risk factor for developing COPD in rural Tanzania. However, these factors need to be studied further.

Association between air pollution, body mass index, respiratory symptoms, and asthma among adolescent school children living in Delhi, India.

BACKGROUND: Delhi is one of the most polluted cities in the world with annual average ambient PM10 and PM2.5 levels exceeding the World Health Organization standards by over 15 fold. We aimed to study the prevalence of respiratory and allergic symptoms and asthma among adolescent children living in Delhi (D) and compare it with children living in lesser polluted cities of Kottayam (K) and Mysore (M) located in Southern India. METHODS: 4361 boys and girls between the age group of 13-14 and 16-17 years from 12 randomly selected private schools from D, K, and M were invited to participate. Modified and expanded International Study for Asthma and Allergies in Children (ISAAC) questionnaires (Q) were filled by the students who also performed spirometry using the ultrasonic flow-sensor-based nDD Spirometer. RESULTS: 3157 students (50.4% boys) completed the Q and performed good quality spirometry. The prevalence of asthma and airflow obstruction among children living in Delhi was 21.7% using the ISAAC Q and 29.4% on spirometry, respectively. This was accompanied by significantly higher rates of self-reported cough, shortness of breath, chest tightness, sneezing, itchy and watery eyes, itchy skin, and eczema among Delhi children (vs. K-M, all P < 0.05). Delhi children were more overweight and obese (39.8% vs. 16.4%, P < 0.0001), and this was the only risk factor that was strongly associated with asthma (odds ratio [OR]: 1.79; confidence interval: 1.49-2.14), with a more pronounced effect in Delhi children (P = 0.04). Forced expiratory volume1 and Forced vital capacity values were significantly higher in Delhi children (vs. K-M P < 0.0001). Preserved ratio impaired spirometry was more common in K-M children (P < 0.0001). CONCLUSION: Adolescent children living in the polluted city of Delhi had a high prevalence of asthma, respiratory symptoms, allergic rhinitis, and eczema that was strongly associated with a high body mass index (BMI). Our study suggests an association between air pollution, high BMI, and asthma/allergic diseases, which needs to be explored further.

COPD awareness in the urban slums and rural areas around Pune city in India.

COPD is the second leading cause of death and disability adjusted life years (DALYs) in India, yet, it remains poorly recognized. We aimed to study the level of awareness of COPD in urban slums of Pune city in India and its neighboring rural areas. All male and female subjects above the age of 30 years residing in 13 randomly selected slums of Pune city (total population of 3000) and 7 randomly selected neighboring rural villages (total population of 3000) were invited to participate in this cross-sectional community survey. After obtaining written informed consent, 13 trained community health workers (CHWs) administered a questionnaire that captured their level of awareness of COPD. Of the 6000 subjects approached, 5420 residents (mean age ± SD = 48.0 ± 13.5 years; 38% males) consented and answered all questions. The number of people who had ever heard the word COPD was 49/5420 [0.9% (0.6-1.1%); 0.7% (0.5-1.3%) of the urban slum dwellers and 1.15% (0.5-1.3%) of rural residents]. Among those who had never heard the word COPD (n = 5371), when asked what was the name of the disease caused by long-term tobacco smoking, 38% said cancer, 16.7% said asthma, and 4.4% said TB. Among those who had heard the word COPD (n = 49), 6.1% said it was a disease of the heart, and 61% attributed COPD to smoke and dust pollution and 20% to tobacco smoking. The level of awareness of COPD in the Indian community is extremely low, highlighting the need to have nationwide mass awareness programs in India.

Particulate matter and markers of glycemic control and insulin resistance in type 2 diabetic patients: result from Wellcome Trust Genetic study.

There is growing evidence that air pollution is associated with increased risk of type 2 diabetes (T2DM). However, information related to whether particulate matter (PM) contributing to worsened metabolic control in T2DM patients is inconsistent. We examined the association of PM10 exposure with glucose-function parameters in young-onset T2DM patients. We investigated the association between a year ambient concentration of PM10 at residential places, using AERMOD dispersion model, with fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), 2 h post meal plasma glucose (2hPG), homeostasis model assessment of insulin resistance (HOMA-IR), ß-cell function (HOMA-ß) and disposition index (DI) in 1213 diabetic patients from the Wellcome Trust Genetic study at the Diabetes Unit, KEM Hospital Research Center, Pune, India. We used linear regression models and adjusted for a variety of individual and environmental confounding variables. Possible effect modification by age, gender, waist-to-hip ratio (WHR) and smoking status were investigated. Sensitivity analysis assessed the impact of relative humidity (RH) and temperature a day before examination and anti-diabetic and HHR medication (Hydralazine, Hydrochlorothiazide and Reserpine). We found that 1 SD increment in background concentration of PM10 at residential places (43.83 µg/m3) was significantly associated with 2.25 mmol/mol and 0.38 mmol/l increase in arithmetic means of HbA1c and 2hPG, respectively. A similar increase in PM10 was also associated with 4.89% increase in geometric mean of HOMA-IR. The associations remained significant after adjustment to RH and temperature, and WHR and smoking enhanced the size of the effect. Our study suggests that long-term exposure to PM10 is associated with higher glycaemia and insulin resistance. In context of our previous demonstration of association of SO2 and NO x and plasma C-reactive protein, we suggest that air pollution could influence progression of diabetes complications. Prospective studies and interventions are required to define mechanism and confirm causality.

Air pollution and respiratory health among diabetic and non-diabetic subjects in Pune, India-results from the Wellcome Trust Genetic Study.

Diabetics may be more vulnerable to the harmful effects of ambient air pollutants than healthy individuals. But, the risk factors that lead to susceptibility to air pollution in diabetics have not yet been identified. We examined the effect of exposure to ambient PM10 on chronic symptoms and the pulmonary function tests (PFT) in diabetic and non-diabetic subjects. Also, to investigate possible determinants of susceptibility, we recruited 400 type 2 diabetic and 465 healthy subjects who were investigated for chronic respiratory symptoms (CRSs) and then underwent measurement of forced vital capacity (FVC) and forced expiratory volume 1 (FEV1) according to standard protocol. Percent predicted FEV1 and FVC (FEV1% and FVC%, respectively) for each subject were calculated. Particulate matter (PM10) concentrations at residence place of subjects were estimated using AERMOD dispersion model. The association between PM10 and CRSs was explored using logistic regression. We also used linear regression models controlling for potential confounders to study the association between chronic exposure to PM10 and FEV1% and FVC%. Prevalence of current wheezing, allergy symptom, chest tightness, FEV1/FVC <70%, and physician-diagnosed asthma and COPD was significantly higher among diabetic subjects than non-diabetics. There was no significant difference between percent predicted value of PFT among diabetic and non-diabetic subjects (P < 0.05). We estimated that 1 SD increase in PM10 concentration was associated with a greater risk of having dyspnea by 1.50-fold (95% CI, 1.12-2.01). Higher exposure to PM10 concentration was also significantly associated with lower FVC%. The size of effect for 1 SD µg/m3 (=98.38) increase in PM10 concentration was 3.71% (95% CI, 0.48-4.99) decrease in FVC%. In addition, we indicated that strength of these associations was higher in overweight, smoker, and aged persons. We demonstrated a possible contribution of air pollution to reduced lung function independent of diabetes status. This study suggests that decline in exposure may significantly reduce disease manifestation as dyspnea and impaired lung function. We conduct that higher BMI, smoking, and older age were associated with higher levels of air pollution effects.

Challenges in recruitment and retention of clinical trial subjects.

BACKGROUND: Successful recruitment of patients is known to be one of the most challenging aspects in conduct of randomized controlled trials. Inadequate patient retention during conduct of trial affects conclusive results. OBJECTIVE: To assess the level of challenges faced by Indian investigators in recruitment and retention of trial subjects. METHODS: We developed a survey questionnaire on challenges encountered by investigators in subject recruitment and retention which was hosted on a web portal. RESULTS: Seventy-three investigators from India participated in the survey. The frequently encountered challenges in subject recruitment were complexity of study protocol (38%), lack of awareness about clinical trials in patients (37%), and sociocultural issues related to trial participation (37%). About 63% of participants strongly agreed that creating a positive awareness about clinical trials among people through press and media, having a dedicated clinical research coordinator for trial (50.7%), and designing a recruitment strategy prior to study initiation (46.6%) would enhance recruitment. Almost 50.7% of participants agreed that interacting with medical community in vicinity of the study site and educating patients about clinical trials during routine outpatient department visits (46.6%) would enhance recruitment. Experiencing a serious adverse event, subject's fear for study procedures (47%) and side effects (44%) were thought to have a moderate effect on subject retention. CONCLUSION: Our survey has put forth factors related to negative publicity by media, lack of patient education about clinical trials; complex study designs are barriers to clinical trial recruitment in India. It is essential to devise innovative and effective strategies focusing on education of public and mass media about clinical research in India.

Infection control in the pulmonary function test laboratory.

Pulmonary function testing plays a crucial role in the diagnostic evaluation of patients with lung diseases. Cases of cross infection acquired from the pulmonary function laboratory, although rare, have been reported from various countries. It is therefore imperative to identify the risks and potential organisms implicated in cross infections in a pulmonary function test (PFT) laboratory and implement better and more effective infection control procedures, which will help in preventing cross infections. The infrastructure, the daily patient flow, and the prevalent disinfection techniques used in a PFT laboratory, all play a significant role in transmission of infections. Simple measures to tackle the cross infection potential in a PFT laboratory can help reduce this risk to a bare minimum. Use of specialized techniques and equipment can also be of much use in a set up that has a high turnover of patients. This review aims at creating awareness about the possible pathogens and situations commonly encountered in a PFT laboratory. We have attempted to suggest some relevant and useful infection control measures with regard to disinfection, sterilization, and patient planning and segregation to help minimize the risk of cross infections in a PFT laboratory. The review also highlights the lacuna in the current scenario of PFT laboratories in India and the need to develop newer and better methods of infection control, which will be more user-friendly and cost effective. Further studies to study the possible pathogens in a PFT laboratory and evaluate the prevalent infection control strategies will be needed to enable us to draw more precious conclusions, which can lead to more relevant, contextual recommendations for cross infections control in PFT lab in India.

Enhancing indoor air quality -The air filter advantage.

Air pollution has become the world's single biggest environmental health risk, linked to around 7 million deaths in 2012 according to a recent World Health Organisation (WHO) report. The new data further reveals a stronger link between, indoor and outdoor air pollution exposure and cardiovascular diseases, such as strokes and ischemic heart disease, as well as between air pollution and cancer. The role of air pollution in the development of respiratory diseases, including acute respiratory infections and chronic obstructive pulmonary diseases, is well known. While both indoor and outdoor pollution affect health, recent statistics on the impact of household indoor pollutants (HAP) is alarming. The WHO factsheet on HAP and health states that 3.8 million premature deaths annually - including stroke, ischemic heart disease, chronic obstructive pulmonary disease (COPD) and lung cancer are attributed to exposure to household air pollution. Use of air cleaners and filters are one of the suggested strategies to improve indoor air quality. This review discusses the impact of air pollutants with special focus on indoor air pollutants and the benefits of air filters in improving indoor air quality.

Physical properties of intact proteins may predict allergenicity or lack thereof.

BACKGROUND: Predicting the allergenicity of proteins is challenging. We considered the possibility that the properties of the intact protein that may alter the likelihood of being taken up by antigen presenting cells, may be useful adjuncts in predicting allergens and non-allergens in silico. It has been shown that negatively charged acidic proteins are preferentially processed by dendritic cells. METHODOLOGY: Datasets (aeroallergen, food-allergen and non-allergen) for in-silico study were obtained from public databases. Isoelectric point (pI), net charge, and electrostatic potential (EP) were calculated from the protein sequence (for pI and net charge) or predicted structure (for EP). RESULT: Allergens and non allergens differed significantly in pI, net charge, and EP (p<0.0001). Cluster analysis based on these parameters resulted in well defined clusters. Non-allergens were characterized by neutral to basic pI (mean+/-SE, 7.6+/-0.16) and positive charge. In contrast allergens were acidic (5.7+/-0.15) and negatively charged. Surface electrostatic potentials calculated from predicted structures were mostly negative for allergens and mostly positive for non-allergens. The classification accuracy for non-allergens was superior to that for allergens. Thus neutral to basic pI, positive charge, and positive electrostatic potentials characterize non-allergens, and seem rare in allergens (p<0.0001). It may be possible to predict reduced likelihood of allergenicity in such proteins, but this needs to be prospectively validated.