Association of pulmonary black carbon accumulation with cardiac fibrosis in residents of Sao Paulo, Brazil.

Evidence suggests that myocardial interstitial fibrosis, resulting from cardiac remodeling, may possibly be influenced by mechanisms activated through the inhalation of airborne pollutants. However, limited studies have explored the relationship between lifetime exposure to carbon-based particles and cardiac fibrosis, specially using post-mortem samples. This study examined whether long-term exposure to air pollution (estimated by black carbon accumulated in the lungs) is associated with myocardial fibrosis in urban dwellers of megacity of Sao Paulo. Data collection included epidemiological and autopsy-based approaches. Information was obtained by interviewing the next of kin and through the pathologist's report. The individual index of exposure to carbon-based particles, which we designed as the fraction of black carbon (FBC), was estimated through quantification of particles on the macroscopic lung surface. Myocardium samples were collected for histopathological analysis to evaluate the fraction of cardiac fibrosis. The association between cardiac fibrosis and FBC, age, sex, smoking status and hypertension was assessed by means of multiple linear regression models. Our study demonstrated that the association of FBC with cardiac fibrosis is influenced by smoking status and hypertension. Among hypertensive individuals, the cardiac fibrosis fraction tended to increase with the increase of the FBC in both groups of smokers and non-smokers. In non-hypertensive individuals, the association between cardiac fibrosis fraction and FBC was observed primarily in smokers. Long-term exposure to tobacco smoke and environmental particles may contribute to the cardiac remodeling response in individuals with pre-existing hypertension. This highlights the importance of considering hypertension as an additional risk factor for the health effects of air pollution on the cardiovascular system. Moreover, the study endorses the role of autopsy to investigate the effects of urban environment and personal habits in determining human disease.

Validation of physician certified verbal autopsy using conventional autopsy: a large study of adult non-external causes of death in a metropolitan area in Brazil.

BACKGROUND: Reliable mortality data are essential for the development of public health policies. In Brazil, although there is a well-consolidated universal system for mortality data, the quality of information on causes of death (CoD) is not even among Brazilian regions, with a high proportion of ill-defined CoD. Verbal autopsy (VA) is an alternative to improve mortality data. This study aimed to evaluate the performance of an adapted and reduced version of VA in identifying the underlying causes of non-forensic deaths, in São Paulo, Brazil. This is the first time that a version of the questionnaire has been validated considering the autopsy as the gold standard. METHODS: The performance of a physician-certified verbal autopsy (PCVA) was evaluated considering conventional autopsy (macroscopy plus microscopy) as gold standard, based on a sample of 2060 decedents that were sent to the Post-Mortem Verification Service (SVOC-USP). All CoD, from the underlying to the immediate, were listed by both parties, and ICD-10 attributed by a senior coder. For each cause, sensitivity and chance corrected concordance (CCC) were computed considering first the underlying causes attributed by the pathologist and PCVA, and then any CoD listed in the death certificate given by PCVA. Cause specific mortality fraction accuracy (CSMF-accuracy) and chance corrected CSMF-accuracy were computed to evaluate the PCVA performance at the populational level. RESULTS: There was substantial variability of the sensitivities and CCC across the causes. Well-known chronic diseases with accurate diagnoses that had been informed by physicians to family members, such as various cancers, had sensitivities above 40% or 50%. However, PCVA was not effective in attributing Pneumonia, Cardiomyopathy and Leukemia/Lymphoma as underlying CoD. At populational level, the PCVA estimated cause specific mortality fractions (CSMF) may be considered close to the fractions pointed by the gold standard. The CSMF-accuracy was 0.81 and the chance corrected CSMF-accuracy was 0.49. CONCLUSIONS: The PCVA was efficient in attributing some causes individually and proved effective in estimating the CSMF, which indicates that the method is useful to establish public health priorities.

Pleural anthracosis as an indicator of lifetime exposure to urban air pollution: An autopsy-based study in Sao Paulo.

Many studies have been conducted to evaluate the association between air pollution and adverse health effects using a wide variety of methods to assess exposure. However, the assessment of individual long-term exposure to ambient air pollution is a challenging task and has not been evaluated in a large autopsy study. Our goal was to investigate whether exposure to urban air pollution is associated to the degree of lung anthracosis, considering modifying factors such as personal habits, mobility patterns and occupational activities. We conducted a study in Sao Paulo, Brazil from February 2017 to June 2018, combining epidemiological, spatial analysis and autopsy-based approaches. Information about residential address, socio-demographic details, occupation, smoking status, time of residence in the city and time spent commuting was collected via questionnaires applied to the next-of-kin. Images of the pleura surface from upper and lower lobes were used to quantify anthracosis in the lungs. We used multiple regression models to assess the association between the amount of carbon deposits in human lungs, measured by the fraction of pleural anthracosis (FA), and potential explanatory variables. We analyzed 413 cases and our data showed that for each additional hour spent in daily commuting, the ratio FA/(1-FA) is multiplied by 1.05 (95% confidence interval: [1.02; 1.08]). The estimated coefficient for daily hours spent in traffic was not considerably affected by the inclusion of socio-demographic variables and smoking habits. We estimate a tobacco equivalent dose of 5 cigarettes per day in a city where annual PM2.5 concentration oscillates around 25 µg/m3. Pleural anthracosis is a potential index of lifetime exposure to traffic-derived air pollution.

Accumulation of trace element content in the lungs of Sao Paulo city residents and its correlation to lifetime exposure to air pollution.

Heavy metals are natural and essential elements of the environment and living beings, produced from natural (e.g. volcanic activity and cosmic ray-induced spallation) and anthropogenic processes (e.g. industrial and fossil fuel combustion). High-concentrations of heavy metals and radionuclides are also originated from anthropogenic activities in urban and industrial areas. In this preliminary study, we analyzed the levels of heavy metals and Polonium-210 (210Po) in lung tissues in autopsies from residents of the city of Sao Paulo, SP, Brazil. In order to identify the link among sources of the heavy metals in lungs, factor analysis was performed. Of the first four factors, which explain 66% of the total variability, three were associated with vehicular sources. The fitting of a regression model with 210Po as the response variable and with the four factors as explanatory variables, controlling for age, sex and tobacco, showed a significant association between the concentration of polonium and the first factor that is generated by catalysts and brakes (coefficient = 0.90, standard error = 0.33, p = 0.016). Our findings suggest an association between traffic-related trace metals and 210Po in lung autopsies.

Urinary sodium excretion is low prior to acute kidney injury in patients in the intensive care unit.

Background: The incidence of acute kidney injury (AKI) is high in intensive care units (ICUs), and a better understanding of AKI is needed. Early chronic kidney disease is associated with urinary concentration inability and AKI recovery with increased urinary solutes in humans. Whether the inability of the kidneys to concentrate urine and excrete solutes at appropriate levels could occur prior to the diagnosis of AKI is still uncertain, and the associated mechanisms have not been studied. Methods: In this single-center prospective observational study, high AKI risk in ICU patients was followed up for 7 days or until ICU discharge. They were grouped as "AKI" or "No AKI" according to their AKI status throughout admission. We collected daily urine samples to measure solute concentrations and osmolality. Data were analyzed 1 day before AKI, or from the first to the fifth day of admission in the "No AKI" group. We used logistic regression models to evaluate the influence of the variables on future AKI diagnosis. The expression of kidney transporters in urine was evaluated by Western blotting. Results: We identified 29 patients as "No AKI" and 23 patients as "AKI," the latter being mostly low severity AKI. Urinary sodium excretion was lower in "AKI" patients prior to AKI diagnosis, particularly in septic patients. The expression of Na+/H+ exchanger (NHE3), a urinary sodium transporter, was higher in "AKI" patients. Conclusions: Urinary sodium excretion is low before an AKI episode in ICU patients, and high expressions of proximal tubule sodium transporters might contribute to this.

Validation of SmartVA using conventional autopsy: A study of adult deaths in Brazil.

Background: Accurate cause of death data are essential to guide health policy. However, mortality surveillance is limited in many low-income countries. In such settings, verbal autopsy (VA) is increasingly used to provide population-level cause of death data. VAs are now widely interpreted using the automated algorithms SmartVA and InterVA. Here we use conventional autopsy as the gold standard to validate SmartVA methodology. Methods: This study included adult deaths from natural causes in São Paulo and Recife for which conventional autopsy was indicated. VA was conducted with a relative of the deceased using an amended version of the SmartVA instrument to suit the local context. Causes of death from VA were produced using the SmartVA-Analyze program. Physician coded verbal autopsy (PCVA), conducted on the same questionnaires, and Global Burden of Disease Study data were used as additional comparators. Cause of death data were grouped into 10 broad causes for the validation due to the real-world utility of VA lying in identifying broad population cause of death patterns. Findings: The study included 2,060 deaths in São Paulo and 1,079 in Recife. The cause specific mortality fractions (CSMFs) estimated using SmartVA were broadly similar to conventional autopsy for: cardiovascular diseases (46.8% vs 54.0%, respectively), cancers (10.6% vs 11.4%), infections (7.0% vs 10.4%) and chronic respiratory disease (4.1% vs 3.7%), causes accounting for 76.1% of the autopsy dataset. The SmartVA CSMF estimates were lower than autopsy for "Other NCDs" (7.8% vs 14.6%) and higher for diabetes (13.0% vs 6.6%). CSMF accuracy of SmartVA compared to autopsy was 84.5%. CSMF accuracy for PCVA was 93.0%. Interpretation: The results suggest that SmartVA can, with reasonable accuracy, predict the broad cause of death groups important to assess a population's epidemiological transition. VA remains a useful tool for understanding causes of death where medical certification is not possible.

The time course of vasoconstriction and endothelin receptor A expression in pulmonary arterioles of mice continuously exposed to ambient urban levels of air pollution.

The present study aimed to verify the time course of the effects of environmental levels of urban air pollution toxicity on lung arterioles. BALB/c mice (n=56) were continuously exposed to selective chambers equipped with (filtered, F) or without (non-filtered, NF) filter devices for particles and toxic gases for 24h/day, over 14, 21, 30 or 45 days. After exposure, we evaluated the lumen-wall relationship (an estimator of arteriolar narrowing), endothelial nitric oxide synthase (eNOS) and endothelin type A receptor (ETAr) expression in the vascular wall and inflammatory influx of the peribronchiolar area. Concentrations of fine particulate matter (PM

GeoSES: A socioeconomic index for health and social research in Brazil.

The individual's socioeconomic conditions are the most relevant to predict the quality of someone's health. However, such information is not usually found in medical records, making studies in the area difficult. Therefore, it is common to use composite indices that characterize a region socioeconomically, such as the Human Development Index (HDI). The main advantage of the HDI is its understanding and adoption on a global scale. However, its applicability is limited for health studies since its longevity dimension presents mathematical redundancy in regression models. Here we introduce the GeoSES, a composite index that summarizes the main dimensions of the Brazilian socioeconomic context for research purposes. We created the index from the 2010 Brazilian Census, whose variables selection was guided by theoretical references for health studies. The proposed index incorporates seven socioeconomic dimensions: education, mobility, poverty, wealth, income, segregation, and deprivation of resources and services. We developed the GeoSES using Principal Component Analysis and evaluated its construct, content, and applicability. GeoSES is defined at three scales: national (GeoSES-BR), Federative Unit (GeoSES-FU), and intra-municipal (GeoSES-IM). GeoSES-BR dimensions showed a good association with HDI-M (correlation above 0.85). The model with the poverty dimension best explained the relative risk of avoidable cause mortality in Brazil. In the intra-municipal scale, the model with GeoSES-IM was the one that best explained the relative risk of mortality from circulatory system diseases. By applying spatial regressions, we demonstrated that GeoSES shows significant explanatory potential in the studied scales, being a compelling complement for future researches in public health.

Levels of Polonium-210 in brain and pulmonary tissues: Preliminary study in autopsies conducted in the city of Sao Paulo, Brazil.

The accumulation of detectable amounts of radon progeny in human tissues may be a risk factor for development and progression of chronic diseases. In this preliminary study, we analyzed the levels of alpha-emitting radon progeny Polonium-210 (210Po) in the olfactory epithelium, olfactory bulb, frontal lobe, and lung tissues in cadavers from the city of Sao Paulo, SP, Brazil. We also assessed the association between 210Po levels and exposure parameters for urban air pollution using linear regression models adjusted for age, sex, smoke, time living in Sao Paulo, daily commuting, socioeconomic index, and anthracosis (traffic-related black carbon accumulation in the pleural region and in lymph). Our findings show that the concentration of 210Po was associated with anthracosis in lungs of non-smokers (coefficient = 6.0; standard error = 2.9; p = 0.04). Individuals with lower socioeconomic status also had significantly higher 210Po levels in lungs (coefficient = -1.19; standard error = 0.58; p = 0.042). The olfactory bulb had higher 210Po levels than either olfactory epithelium (p = 0.071), frontal lobe (p < 0.001), or lungs (p = 0.037). Our findings of the deposition of 210Po in autopsy tissues suggest that airborne radionuclides may contribute to the development of chronic diseases, including neurodegenerative diseases.

Association between Traffic Air Pollution and Reduced Forced Vital Capacity: A Study Using Personal Monitors for Outdoor Workers.

BACKGROUND: The effects of outdoor air pollution on lung function in adults are still controversial. OBJECTIVE: Evaluate the effects of exposure to different levels of traffic-generated PM2.5 on workers' lung functions in São Paulo, Brazil. METHODS: To cover a wide range of exposures, 101 non-smoking workers from three occupations (taxi drivers, traffic controllers, and forest rangers) were selected for the study. After clinical evaluation, the participants were scheduled to attend four consecutive weekly visits in which they received a 24-hour personal PM2.5 sampler and had lung function tests measured on the following day. The association between the spirometric variables and the averaged PM2.5 levels was assessed using robust regression models adjusted for age, waist circumference, time at the job, daily work hours, diabetes or hypertension and former smoking habits. RESULTS: Relative to workers in the lowest exposed group (all measures < 25 µg/m3), those with the highest level of exposure (all measures > 39.6 µg/m3) showed a reduction of predicted FVC (-12.2%; CI 95%: [-20.0% to -4.4%]), a marginal reduction of predicted FEV1 (-9.1%; CI 95%: [-19.1% to 0.9%]) and an increase of predicted FEF25-75%/FVC (14.9%; CI 95%: [2.9% to 26.8%]) without changes of FEV1/FVC. CONCLUSIONS: Exposure to vehicular traffic air pollution is associated with a small but significant reduction of FVC without a reduction of FEV1/FVC.

Estimation of post mortem interval by tomographic images of intra-cardiac hypostasis.

The determination of the post mortem interval (PMI) is important in many instances, especially in criminal investigations. So, we consider post mortem tomographic evaluation of intra-cardiac hypostasis as an additional method for such purpose. Tomographic images of the thoraces of the corpses of 23 patients who died in a hospital were obtained sequentially at one hour intervals to allow the analysis of changes in density due to hypostasis over time. The right and left atria, which appear in the mediastinal window, were selected for measurements of the average organ density. An exponential model was used to relate the difference between the attenuation coefficients of the anterior segment of the right atrium and the posterior segment of the left atrium to the PMI. In spite of the large variability of the data from this observational study, PMI estimates during the first 12 h after death can be estimated with a margin of error smaller than two hours. The results suggest that the difference between the attenuation coefficients stabilizes around 12 h post mortem and may be used as an additional method to estimate the PMI.