Chronic obstructive pulmonary disease (COPD) in women due to indoor biomass burning: a meta analysis.

Chronic Obstructive Pulmonary Disease (COPD) is attributable to household air pollution and is known to increase the Disability Adjusted Life Years (DALYs), morbidity and mortality and women are most susceptible groups for the exposure. In order to understand the global risk among women with COPD due to exposure of household air pollutants, an evidence-based systematic review and meta-analysis was conducted. Meta regression analysis was carried out to identify potential sources of heterogeneity. The summary estimates of the included studies showed higher prevalence of COPD due to biomass fuel exposure in women. Clinical diagnosis has shown more risk of COPD prevalence compared to diagnosis based on spirometer test alone. However, the data between included studies for both clinical and spirometry-based studies showed higher heterogeneity. The present meta-data analysis has shown that household air pollutants may be a factor associated with increased risk of COPD in women.

A non-viral nano-delivery system targeting epigenetic methyltransferase EZH2 for precise acute myeloid leukemia therapy.

Acute myeloid leukemia (AML), which is common in the elderly population, accounts for poor long-term survival with a high possibility of relapse. The associated lack of currently developed therapeutics is directing the search for new therapeutic targets relating to AML. EZH2 (Enhancer of Zeste Homolog 2) is a histone methyltransferase member of the polycomb-group (PcG) family, and its significant overexpression in AML means it has emerged as a potential epigenetic target. Here, we propose the human serum albumin (HSA) nanoparticle based delivery of small interfering RNA (siRNA), which can target EZH2-expressing genes in AML. EZH2 specific siRNA loaded in a polyethyleneimine (PEI) conjugated HSA nanocarrier can overcome the systemic instability of siRNA and precisely target the AML cell population for increased EZH2 gene silencing. A stable nanosized complex (HSANPs-PEI@EZH2siRNA), achieved via the electrostatic interaction of PEI and EZH2 siRNA, shows increased systemic stability and hemocompatibility, and enhanced EZH2 gene silencing activity in vitro, compared to conventional transfection reagents. HSANPs-PEI@EZH2siRNA-treated AML cells showed downregulated EZH2, which is associated with a reduced level of Bmi-1 protein, and H3K27me3 and H2AK119ub modification. The ubiquitin-mediated proteasomal degradation pathway plays a critical role in the downregulation of associated proteins following HSANPs-PEI@EZH2siRNA exposure to AML cells. c-Myb is the AML-responsive transcription factor that directly binds on the EZH2 promoter and was downregulated in HSANPs-PEI@EZH2siRNA-treated AML cells. The systemic exposure to HSANPs-PEI@EZH2siRNA of AML engrafted immunodeficient nude mice displayed efficient EZH2 gene silencing and a reduced AML cell population in peripheral blood and bone marrow. The present study demonstrates a non-viral siRNA delivery system for epigenetic targeting based superior anti-leukemic therapy.

Hypoxia-mediated alteration in cholesterol oxidation and raft dynamics regulates BDNF signalling and neurodegeneration in hippocampus.

Brain-derived neurotrophic factor (BDNF) which is primarily associated with neuronal survivability, differentiation and synaptic plasticity has been reported to mediate neurodegeneration in hypoxia through its p75 Neurotrophin receptors (p75NTR). The molecular events promoting BDNF-mediated pro-death signalling in hypoxia, however, still remain an enigma. This study attempts towards deciphering the signalling cascades involved in alteration of BDNF isoforms and its cognate receptor subtypes leading to neurodegeneration in hypoxia. Adult Sprague-Dawley rats were exposed to global hypobaric hypoxia simulating an altitude of 7620 m at standard temperature and humidity. Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology. Our findings reveal enriched expression of p75NTR in lipid rafts and higher expression of tyrosine receptor kinase ß (Trkß) in non-raft regions following hypoxic exposure. Further investigations on membrane properties revealed decline in membrane fluidity along with increased cholesterol oxidation resulting in reduced translocation of Trkß from non-raft to raft regions. Supplementation of vitamin E during hypoxic exposure on the other hand reduced cholesterol oxidation and increased translocation of Trkß from non-raft to raft regions and promoted neuronal survival. Hence, our findings suggest a novel mechanism of cholesterol oxidation-induced alteration in raft dynamics which is promotes p75 receptor-mediated death signalling in hippocampal neurons during chronic hypoxia.

Assessing hazardous risks of indoor airborne polycyclic aromatic hydrocarbons in the kitchen and its association with lung functions and urinary PAH metabolites in kitchen workers.

BACKGROUND: Indoor air pollution is associated with decreased pulmonary function but the relative impact of pollution from kitchen sources on health risks in kitchen workers is not well-known or studied. A study was conducted to measure the kitchen indoor air quality including PAHs estimation and risk assessment based on reported PAHs in indoor air in a central kitchen at North India. METHODS: A cross sectional study was undertaken to assess the lung function status using spirometer and urinary PAH metabolite measurements using GC-MS/MS among 94 male kitchen workers and their corresponding controls. Assessment of the indoor air quality levels was evaluated using standard methods. RESULTS: All the indoor air pollutants were within the recommended guidelines except CO, TVOC and PAH emission in the kitchen. Incremental life time cancer risk (ICLR) based on indoor air PAH measurements indicates potential for carcinogenic risk. Significant lung function decline was observed among kitchen workers as compared to controls after adjusting for smoking habits. Urinary PAH metabolites were detected in kitchen workers and measured concentrations were comparatively higher than control subjects. CONCLUSION: The decline in lung functions after adjustment for confounders and detection of urinary PAH metabolites in kitchen workers can be associated with higher concentrations of PAHs, CO and TVOCs in kitchen indoor air.

Alterations in Lung Functions Based on BMI and Body Fat % Among Obese Indian Population at National Capital Region.

BACKGROUND: In India, non-asthmatic hospital admission case study has been conducted to find out the relationship between obesity and lung functions. The main objective of the present study was to find out the alterations in lung functions due to obesity among Indian population living at National Capital Region (NCR). MATERIALS AND METHODS: We examined 609 non obese and 211 obese subjects in a cross sectional study from National Capital Region, India with age group ranges between 18-70 years. BMI and body fat % was determined using body fat analyzer. Obese and non-obese subjects were classified based on criteria for BMI and Body fat %. Lung function test viz., FEV1 and PEFR were conducted using portable spirometer (PIKO-1). RESULTS: A significant correlation (p<0.05) was observed between BMI and PEFR among non-obese male and female subjects. Decline in PEFR and FEV1 values for corresponding increase in body fat % was observed among study subjects. A significant (p<0.01) decline in mean FEV1 and PEFR was observed among non-obese and obese subjects, compared to their Indian reference standards for lung functions. A significant negative correlation (p<0.01) was observed between body fat % and lung functions (FEV1, PEFR). CONCLUSION: It is concluded that obese subjects are at a risk of lung function impairment, based on the criteria followed for BMI and body fat %. The study also demonstrate that body fat% classification as a better index for determination of obese subjects compared to BMI classification, with respect to lung function impairments.

Meta-analysis approach to study the prevalence of chronic obstructive pulmonary disease among current, former and non-smokers.

Comparative risk assessment for Chronic Obstructive Pulmonary Disease (COPD) among current, former and non-smokers categories remains controversial and not studied in detail. We conducted a meta-analysis to summarize all the relevant published studies on this topic and to update the association between smoking and prevalence of COPD in current, former and non-smokers. Identification, screening, eligibility and inclusion of articles for the study were conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Quality assessment of included studies was undertaken using a scoring sheet. Meta-analysis after the final synthesis of the selected studies was performed using the STATA and Comprehensive Meta-Analysis (CMA) software. Estimates from forty two independent studies reporting 547,391 individuals were identified. Twenty two studies were conducted in Europe, nine in America and ten in Asia and one from New Zealand. The meta-analysis showed that the prevalence of COPD was significantly higher in current smokers compared with former and non-smokers. However, owing to large heterogeneity among the estimates obtained from the studies, stratification was done with respect to continent, diagnostic criteria of COPD and study design which also showed similar results. The stratified analysis also revealed similar trend of results with prevalence of COPD being higher in current smokers as compared to former and non-smokers. The present meta-analysis highlights the positive association between smoking and COPD prevalence. There is an urgent need to implement more effective policies towards the restriction of tobacco use, to reduce the burden of COPD.

Gender Disparity in Lung Function Abnormalities among a Population Exposed to Particulate Matter Concentration in Ambient Air in the National Capital Region, India.

BACKGROUND: The World Health Organization (WHO) global air quality study shows that 27 Indian cities, including New Delhi, are among the one hundred cities with the worst air quality globally. The scope of airway obstruction cases among residents in locations with critical air pollution levels like particulate matter (PM) pollutants PM2.5 and PM1 has not been addressed in the National Capital region, India. OBJECTIVES: The present cross-sectional study was undertaken to assess the forced expiratory volume in one second (FEV1) % predicted abnormalities among residents living in the National Capital Region, India with respect to their exposure to particulate matter pollutants (PM1, PM2.5) in ambient air. METHODS: Eight hundred and fifty-four residents, including 433 men and 421 women ranging in age from 18-70 years, living in the National Capital Region (NCR) of India participated in the study. Particulate matter concentrations in ambient air (PM2.5 and PM1) were monitored at 10 residential locations in the National Capital Region, India (New Okhla Industrial Development Authority (NOIDA) and Gurgaon). The lung function test (FEV1) was conducted using a spirometer. RESULTS: The Indian Air Quality Index showed either very poor or severe levels for PM2.5 at all study locations. A significant negative linear relationship was found between higher concentrations of PM1 and reduced FEV1% predicted values (r = -0.8, p < 0.05). The prevalence of airway obstruction cases (79.6%, odds ratio 1.96, confidence interval 1.42-2.71) was higher (p<0.001) among female subjects compared to their male counterparts. Even though there was a significant decline in FEV1% predicted among 80% of cases in women, only 19.24% cases were in the moderate category and 6.18% cases in the severe category. The severe category of FEV1% predicted cases showed greater respiratory symptoms than the other two categories, which denotes higher risk among those in the severe category. The present study shows that obstruction cases increased from 1.97 to 7.40% and 2.73 to 14.93% in women, with a corresponding increase in PM1 and PM2.5 from the minimum to maximum concentration. CONCLUSIONS: Since the women in this study were non-smokers, the PM in ambient air can be considered to be the major reason for the decline in lung function. The sources of PM pollutants in the study locations are large scale infrastructural development activities such as building and road construction activities. Narrowed lung airways can alter the airway caliber or resistance and flow rates proportional to the airway radius, especially in smaller airways. The present study suggests the need for policy makers and stake holders to take the necessary steps to identify PM sources and reduce the emissions of PM concentrations in ambient air.

Mathematically derived body volume and risk of musculoskeletal pain among housewives in North India.

BACKGROUND: Global Burden of Disease Study 2010 demonstrates the impact of musculoskeletal diseases as the second greatest cause of disability globally in all regions of the world. The study was conducted to determine the role of mathematically derived body volume (BV), body volume index (BVI), body mass index (BMI), body surface area (BSA) and body fat % (BF %) on musculoskeletal pain (MSP) among housewives in National Capital Region (NCR). METHODS: A cross sectional study was undertaken among 495 housewives from Gurgaon and New Okhla Industrial Development Area (NOIDA) in National Capital Region (NCR), New Delhi, India. The study includes questionnaire survey, clinical examination and body composition monitoring among housewives. RESULTS: A significantly higher BMI, BVI, BV and BSA were observed in subjects with MSP as compared to those who had no MSP. This was also true for subjects with pain in knee for BMI category for overweight. Subjects with pain in limbs had significantly high BMI and BVI as compared to subjects with no MSP. A significant positive correlation of age with BMI, BVI, BV and BSA was observed among subjects having no MSP denoting a direct relationship of age and these body factors. CONCLUSIONS: The prevalence of MSP among housewives is associated with increasing age, BMI and BVI. This can possibly be used for formulating a strategy for prevention of MSP.

Adverse respiratory health and hematological alterations among agricultural workers occupationally exposed to organophosphate pesticides: a cross-sectional study in North India.

BACKGROUND: Non-protective work practices followed by farm workers during spraying of pesticides lead to occupational exposure among them. OBJECTIVE: This study is designed to explore the respiratory health and hematological profile of agricultural workers occupationally exposed to OP pesticides. MATERIALS AND METHODS: A cross sectional study was undertaken among 166 pesticide sprayers working in mango orchards of Lucknow district in North India compared with 77 controls to assess the respiratory illness, lung functions, cholinesterase levels and hematological profile. A questionnaire based survey and clinical examination for respiratory health were conducted among study subjects. Lung function test was conducted among study subjects by using spirometer. Cholinesterase level as biomarker of OP pesticides and hematological profile of study subjects were investigated in the laboratory by following the standard protocols. RESULTS: Overall respiratory morbidity observed among exposed subjects was 36.75%. Symptoms for respiratory illness like dry cough, productive cough, wheezing, irritation of throat and blood stained sputum were found to be significantly more (p<0.05) among pesticide sprayers than controls. Lung function parameters viz. PEFR, FEV1, %PEFR predicted, %FEV1 predicted and FEV1/FVC were found to be significantly decreased (p<0.05) among pesticide sprayers as compared to controls. Exposure wise distribution of respiratory illness and lung functions among pesticide sprayers show that the exposure duration significantly elevates (p<0.05) the respiratory problems and significantly decreases (p<0.001) lung functions among pesticide sprayers. Activities of acetylcholinesterase and butyrylcholinesterase were found to be significantly depleted (p<0.001) among pesticide sprayers as compared to controls which show the exposure of OP pesticides among them. The hematological profile viz. RBC, WBC, monocytes, neutrophils, MCV, MCH, MCHC and platelet count were significantly altered (p<0.001) in pesticide sprayers than controls. CONCLUSION: This study shows that the unsafe occupational exposure of OP pesticides causes respiratory illness, decreased lung functions and hematological alterations among pesticide sprayers.

Seasonal variations in cholinesterase activity, nerve conduction velocity and lung function among sprayers exposed to mixture of pesticides.

Pesticide spraying operation is associated with the increased risk of adverse health effects among sprayers who do not follow safe farm work practices. A study was conducted among pesticide sprayers in North India to evaluate the clinical and subclinical variations in their vital health parameters before and after the pesticide spraying season. Blood cholinesterase levels, pulmonary function test, nerve conduction velocity and self-reported symptoms were studied among 18 eligible and consenting male sprayers. Mean acetylcholinesterase activity was reduced by 55 % in the post-exposure assessment (P<0.001) as compared to pre-exposure levels. Mean forced expiratory volume in 1 s was 20 % lower in the post-exposure assessment as compared to the pre-exposure level (P<0.05). No significant change was observed in the motor and sensory nerve conduction velocity in the median nerve of sprayers before and after the spraying activity. Also, no significant variation was observed with respect to self-reported symptoms except weakness in arms and legs (P<0.05). The significant decline in lung function and acetylcholinesterase level after pesticide exposure reflects the strongly negative effect of exposure to pesticides during spraying activity. More longitudinal studies among pesticide sprayers must be undertaken to further substantiate the cause-effect relationship between pesticide exposure and its subclinical effects. There is a strong necessity to minimise the exposure through the use of personal protective equipment in pesticide sprayers.

Evaluating risks of acquired clinical vulnerability among subjects exposed to E-waste.

Acquired clinical vulnerability (ACV) results from insults that produce consequential pathophysiological changes and predispose exposed subjects to future disease. ACV comprises a complex biological process that is manifested by exposure to toxicants, generally over the course of many years, and results from subtle changes that occur at the cellular and molecular level. A large proportion of the world's population has already been, or will be, exposed to toxicants emanating from E-waste during the course of their lives. In countries where E-waste recycling is an important economic activity (China, India, among others), the challenge facing researchers is to devise suitable methods for identifying and objectively measuring ACV. Primary prevention can be achieved through legislation/awareness/monitoring and secondary prevention by developing innovative diagnostic tools and corrective measures. Studies in which attempts are made to define the health impact of multiple exposures, as routinely occurs in E-waste recycling, should include measures of as many of the following parameters as possible: (a) characterization of pollutant levels in air/water/soil at the residential or workplace, (b) periodical clinical examination of exposed subjects, (c) assessments of circulating toxicant loads in blood/urine/hair, (d) genomic variation and resultant susceptibility to complex biological responses, (viz, inflammation/dysplasia/immunosuppression/tissue regeneration) that derive from pathway modulation (viz., cytoskeleton/metabolism/cell adhesion/immune system/neuroactive ligand-receptor interaction/cytokine/signaling), (e) routine monitoring of altered gene expression from modulation of hematology or the above-mentioned pathways. E-waste exposure may also serve as a model for the types of multiple exposures that occur in other industrial or environmental exposures. Moreover, the approach used to study and address or alleviate E-waste exposure may also be useful in other environmental exposure situations. The studies necessary to address and alleviate E-waste hazards may eventually be cost-effective, since they are likely to result in manifold savings in reduced health costs, increased human productivity, and reduced indirect social costs.

Adverse health effects of pesticides in agrarian populations of developing countries.

Developing countries use only 20% of the world's agrochemicals, yet they suffer 99% of deaths from pesticide poisoning. Pesticide poisoning is a significant problem in developing countries primarily because of unsafe pesticide application and handling practices. Safety is further exacerbated by the illiteracy and poverty that prevails in most farming communities of developing countries. Pesticides classified as being extremely or highly hazardous by FAO and WHO, including those banned by other countries, continue to be used in developing countries. Many farmers in developing countries continue to be exposed to pesticides from either storing them in or near their residences, or from inadequate or unsafe application or handling practices. Farming populations exposed to pesticides suffer from several health problems, primarily neurological abnormalities, respiratory ailments, and reproductive, endocrinological, and dermal problems. In developing countries, the scientific literature (including the Indian Institute of Toxicology Research, India) have taken the initiative to monitor health problems resulting from pesticide exposure in agrarian communities. The welfare fund for agricultural laborers could institute a special program for pesticide applicators in developing countries. The primary need, currently, in such countries is creation and implementation of sound national policies to effectively articulate appropriate guidelines for managing farm pest control activities. Such policies should be aimed at both limiting pesticide exposure and usage, but doing so without damaging the yields of food production. If such steps are taken, it is fully expected that the incidence of adverse health consequences for agrarian populations from pesticide toxicity will decrease, and the health of farmers improve.