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.

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.

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.

Acute exposure to diesel and sewage biodiesel exhaust causes pulmonary and systemic inflammation in mice.

Biodiesel is a renewable energy source that reduces particle emission, but few studies have assessed its effects. To assess the effects of acute inhalation of two doses (600 and 1200 µg/m3) of diesel (DE) and biodiesel (BD) fuels on the inflammatory pulmonary and systemic profile of mice. Animals were exposed for 2 h in an inhalation chamber inside the Container Laboratory for Fuels. Heart rate, heart rate variability (HRV) and blood pressure were determined 30 min after exposure. After 24 h, we analyzed the lung inflammation using bronchoalveolar lavage fluid (BALF); neutrophil and macrophage quantification in the lung parenchyma was performed, and blood and bone marrow biomarkers as well as receptor of endothelin-A (ET-Ar), receptor of endothelin-B (ET-Br), vascular cell adhesion molecule 1 (VCAM-1), inducible nitric oxide synthase (iNOs) and isoprostane (ISO) levels in the pulmonary vessels and bronchial epithelium were evaluated. HRV increased for BD600, D600 and D1200 compared to filtered air (FA). Both fuels (DE and BD) produced alterations in red blood cells independent of the dose. BALF from the BD600 and BD1200 groups showed an increase in neutrophils compared to those of the FA group. Numeric density of the polymorphonuclear and mononuclear cells was elevated with BD600 compared to FA. In the peribronchiolar vessels, there was an increase in ET-Ar and ET-Br expression following BD600 compared to FA; and there was a reduction in the iNOs expression for BD1200 and the VCAM-1 for D1200 compared to FA. In the bronchial epithelium, there was an increase in ETAr at BD600, ET-Br at two doses (600 and 1200 µg/m3) of DE and BD, iNOs at D600 and VCAM-1 at BD1200 and D600; all groups were compared to the FA group. Acute exposure to DE and BD derived from sewage methyl esters triggered pulmonary and cardiovascular inflammatory alterations in mice.

Characterization of the particulate matter and relationship between buccal micronucleus and urinary 1-hydroxypyrene levels among cashew nut roasting workers.

The present study is the first assessment of occupational risk associated with artisanal cashew nut roasting using exposure and effect biomarkers, as well as a characterization and dispersion analysis of the released particulate matter (PM). A real-time particle monitor was used to quantify PM1.0, PM2.5 and PM10. Furthermore, the PM was sampled using a Handi-vol sampler, and the physicochemical characteristics were determined by SEM-EDS analysis. Trajectories, dispersion and deposition of the emitted material were calculated using the NOAA-HYSPLIT model. Urinary 1-hydroxypyrene (1-OHP) levels were analyzed by HPLC. DNA damage, chromosomal instability and cell death were measured by a buccal micronucleus cytome assay (BMCyt). The PM concentrations for all measurements in the exposed area were higher than in the non-exposed area. SEM-EDS analyses exhibited a wide variety of particles, and K, Cl, S and Ca biomass burning tracers were the major inorganic compounds. In addition, atmospheric modeling analysis suggested that these particles can reach regions farther away than 40 kilometers. Occupational polycyclic aromatic hydrocarbon exposure was confirmed by increases in 1-OHP levels in cashew nut workers. Frequencies of BMCyt biomarkers of genotoxicity (micronuclei and nuclear bud) and cytotoxicity (pyknosis, karyolysis, karyorrhexis and condensed chromatin) were higher in the exposed group compared with the controls. The influence of factors, such as age, on the micronuclei frequencies was demonstrated, and a correlation between 1-OHP and micronuclei was observed. To the best of our knowledge, no other study has demonstrated a correlation between these types of biomarkers. The use of exposure (1-OHP) and effect (BMCyt) biomarkers were therefore efficient in assessing the occupational risk associated with artisanal cashew nut roasting, and the high rates of PM2.5 are considered to be a potential contributor to this effect.

Aerobic exercise in polluted urban environments: effects on airway defense mechanisms in young healthy amateur runners.

In this study, the effects of aerobic exercise on the upper airways and their defense mechanisms were investigated in athletes. The athletes ran in two different environments: the downtown streets of the city of São Paulo (Street), more polluted, and an urban forest (Forest), less polluted. Thirty-eight young healthy athletes ran for 45 min d-1 randomly during five consecutive days, with an interval of 48 h before changing environment. Clinical parameters and respiratory tract defense markers were evaluated before and after the first run on Mondays (1 d) and on Fridays (5 d). Street presented higher mean PM2.5 concentrations (65.1 ± 39.1 µg m-3, p < 0.001) and lower temperature (22.0 °C, p = 0.010) than Forest (22.6 ± 15.3 µg m-3 and 22.8 °C). After 1 d Street running, subjects showed an increment in heart rate (p < 0.001). At day 5, there was twice the number of athletes with impaired nasal mucociliary clearance (MCC) in the Street runners group when compared to the Forest runners group. Exhaled breath condensate pH values increased in the Forest group, with significant differences between groups in day 1 (p = 0.006) and day 5 (p < 0.001), despite the fact that both groups showed values within the normal range. After exposure to both environments, the number of cells in the nasal lavage fluid was reduced after exercise (p = 0.014), without alterations in cell type and IL-8 and IL-10 concentrations. Aerobic exercise can either maintain or acutely enhance MCC and it may help to regulate inflammatory responses in the airways. Here we show that exercise practice in polluted outdoor environment, over a 5 d period, impairs MCC. In contrast, athletes running in the less polluted environment (Forest) show higher exhaled breath condensate pH values when compared to those who exercised in a more polluted environment (Street).

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.

An approach to using heart rate monitoring to estimate the ventilation and load of air pollution exposure.

BACKGROUND: The effects of air pollution on health are associated with the amount of pollutants inhaled which depends on the environmental concentration and the inhaled air volume. It has not been clear whether statistical models of the relationship between heart rate and ventilation obtained using laboratory cardiopulmonary exercise test (CPET) can be applied to an external group to estimate ventilation. OBJECTIVES: To develop and evaluate a model to estimate respiratory ventilation based on heart rate for inhaled load of pollutant assessment in field studies. METHODS: Sixty non-smoking men; 43 public street workers (public street group) and 17 employees of the Forest Institute (park group) performed a maximum cardiopulmonary exercise test (CPET). Regression equation models were constructed with the heart rate and natural logarithmic of minute ventilation data obtained on CPET. Ten individuals were chosen randomly (public street group) and were used for external validation of the models (test group). All subjects also underwent heart rate register, and particulate matter (PM2.5) monitoring for a 24-hour period. RESULTS: For the public street group, the median difference between estimated and observed data was 0.5 (CI 95% -0.2 to 1.4) l/min and for the park group was 0.2 (CI 95% -0.2 to 1.2) l/min. In the test group, estimated values were smaller than the ones observed in the CPET, with a median difference of -2.4 (CI 95% -4.2 to -1.8) l/min. The mixed model estimated values suggest that this model is suitable for situations in which heart rate is around 120-140bpm. CONCLUSION: The mixed effect model is suitable for ventilation estimate, with good accuracy when applied to homogeneous groups, suggesting that, in this case, the model could be used in field studies to estimate ventilation. A small but significant difference in the median of external validation estimates was observed, suggesting that the applicability of the model to external groups needs further evaluation.

Cashew nut roasting: chemical characterization of particulate matter and genotocixity analysis.

BACKGROUND: Particulate matter (PM) is potentially harmful to health and related to genotoxic events, an increase in the number of hospitalizations and mortality from respiratory and cardiovascular diseases. The present study conducted the first characterization of elemental composition and polycyclic aromatic hydrocarbon (PAH) analysis of PM, as well as the biomonitoring of genotoxic activity associated to artisanal cashew nut roasting, an important economic and social activity worldwide. METHODS: The levels of PM2.5 and black carbon were also measured by gravimetric analysis and light reflectance. The elemental composition was determined using X-ray fluorescence spectrometry and PAH analysis was carried out by gas chromatography-mass spectrometry. Genotoxic activity was measured by the Tradescantia pallida micronucleus bioassay (Trad-MCN). Other biomarkers of DNA damage, such as nucleoplasmic bridges and nuclear fragments, were also quantified. RESULTS: The mean amount of PM2.5 accumulated in the filters (January 2124.2 µg/m(3); May 1022.2 µg/m(3); September 1291.9 µg/m(3)), black carbon (January 363.6 µg/m(3); May 70 µg/m(3); September 69.4 µg/m(3)) and concentrations of Al, Si, P, S, Cl, K, Ca, Ti, Cr, Mn, Fe, Ni, Cu, Zn, Se, Br and Pb were significantly higher than the non-exposed area. Biomass burning tracers K, Cl, and S were the major inorganic compounds found. Benzo[k]fluoranthene, indene[1,2,3-c,d]pyrene, benzo[ghi]perylene, phenanthrene and benzo[b]fluoranthene were the most abundant PAHs. Mean benzo[a]pyrene-equivalent carcinogenic power values showed a significant cancer risk. The Trad-MCN bioassay revealed an increase in micronucleus frequency, 2-7 times higher than the negative control and significantly higher in all the months analyzed, possibly related to the mutagenic PAHs found. CONCLUSIONS: This study demonstrated that artisanal cashew nut roasting is a serious occupational problem, with harmful effects on workers׳ health. Those involved in this activity are exposed to higher PM2.5 concentrations and to 12 PAHs considered potentially mutagenic and/or carcinogenic. The Trad-MCN with T. pallida was sensitive and efficient in evaluating the genotoxicity of the components and other nuclear alterations may be used as effective biomarkers of DNA damage.

Urban air pollution: a representative survey of PM(2.5) mass concentrations in six Brazilian cities.

In urban areas of Brazil, vehicle emissions are the principal source of fine particulate matter (PM(2.5)). The World Health Organization air quality guidelines state that the annual mean concentration of PM(2.5) should be below 10 µg m(-3). In a collaboration of Brazilian institutions, coordinated by the University of São Paulo School of Medicine and conducted from June 2007 to August 2008, PM(2.5) mass was monitored at sites with high traffic volumes in six Brazilian state capitals. We employed gravimetry to determine PM(2.5) mass concentrations, reflectance to quantify black carbon concentrations, X-ray fluorescence to characterize elemental composition, and ion chromatography to determine the composition and concentrations of anions and cations. Mean PM(2.5) concentrations and proportions of black carbon (BC) in the cities of São Paulo, Rio de Janeiro, Belo Horizonte, Curitiba, Recife, and Porto Alegre were 28.1 ± 13.6 µg m(-3) (38% BC), 17.2 ± 11.2 µg m(-3) (20% BC), 14.7 ± 7.7 µg m(-3) (31% BC), 14.4 ± 9.5 µg m(-3) (30% BC), 7.3 ± 3.1 µg m(-3) (26% BC), and 13.4 ± 9.9 µg m(-3) (26% BC), respectively. Sulfur and minerals (Al, Si, Ca, and Fe), derived from fuel combustion and soil resuspension, respectively, were the principal elements of the PM(2.5) mass. We discuss the long-term health effects for each metropolitan region in terms of excess mortality risk, which translates to greater health care expenditures. This information could prove useful to decision makers at local environmental agencies.

Vehicle emissions and PM(2.5) mass concentrations in six Brazilian cities.

In Brazil, the principal source of air pollution is the combustion of fuels (ethanol, gasohol, and diesel). In this study, we quantify the contributions that vehicle emissions make to the urban fine particulate matter (PM(2.5)) mass in six state capitals in Brazil, collecting data for use in a larger project evaluating the impact of air pollution on human health. From winter 2007 to winter 2008, we collected 24-h PM(2.5) samples, employing gravimetry to determine PM(2.5) mass concentrations; reflectance to quantify black carbon concentrations; X-ray fluorescence to characterize elemental composition; and ion chromatography to determine the composition and concentrations of anions and cations. Mean PM(2.5) concentrations in the cities of São Paulo, Rio de Janeiro, Belo Horizonte, Curitiba, Porto Alegre, and Recife were 28, 17.2, 14.7, 14.4, 13.4, and 7.3 µg/m(3), respectively. In São Paulo and Rio de Janeiro, black carbon explained approximately 30% of the PM(2.5) mass. We used receptor models to identify distinct source-related PM(2.5) fractions and correlate those fractions with daily mortality rates. Using specific rotation factor analysis, we identified the following principal contributing factors: soil and crustal material; vehicle emissions and biomass burning (black carbon factor); and fuel oil combustion in industries (sulfur factor). In all six cities, vehicle emissions explained at least 40% of the PM(2.5) mass. Elemental composition determination with receptor modeling proved an adequate strategy to identify air pollution sources and to evaluate their short- and long-term effects on human health. Our data could inform decisions regarding environmental policies vis-à-vis health care costs.

Endothelial dysfunction in the pulmonary artery induced by concentrated fine particulate matter exposure is associated with local but not systemic inflammation.

Clinical evidence has identified the pulmonary circulation as an important target of air pollution. It was previously demonstrated that in vitro exposure to fine particulate matter (aerodynamic diameter≤2.5 µm, PM2.5) induces endothelial dysfunction in isolated pulmonary arteries. We aimed to investigate the effects of in vivo exposure to urban concentrated PM2.5 on rat pulmonary artery reactivity and the mechanisms involved. For this, adult Wistar rats were exposed to 2 weeks of concentrated São Paulo city air PM2.5 at an accumulated daily dose of approximately 600 µg/m3. Pulmonary arteries isolated from PM2.5-exposed animals exhibited impaired endothelium-dependent relaxation to acetylcholine without significant changes in nitric oxide donor response compared to control rats. PM2.5 caused vascular oxidative stress and enhanced protein expression of Cu/Zn- and Mn-superoxide dismutase in the pulmonary artery. Protein expression of endothelial nitric oxide synthase (eNOS) was reduced, while tumor necrosis factor (TNF)-α was enhanced by PM2.5 inhalation in pulmonary artery. There was a significant positive correlation between eNOS expression and maximal relaxation response (Emax) to acetylcholine. A negative correlation was found between vascular TNF-α expression and Emax to acetylcholine. Plasma cytokine levels, blood cells count and coagulation parameters were similar between control and PM2.5-exposed rats. The present findings showed that in vivo daily exposure to concentrated urban PM2.5 could decrease endothelium-dependent relaxation and eNOS expression on pulmonary arteries associated with local high TNF-α level but not systemic pro-inflammatory factors. Taken together, the present results elucidate the mechanisms underlying the trigger of cardiopulmonary diseases induced by urban ambient levels of PM2.5.

Composition of diesel particles influences acute pulmonary toxicity: an experimental study in mice.

Ambient particles have been consistently associated with adverse health effects, yielding mainly high cardiorespiratory morbidity and mortality. Diesel engines represent a major source of particles in the urban scenario. We aimed to modify the composition of diesel particles, by means of different extraction procedures, to relate changes in chemical profile to corresponding indicators of respiratory toxicity. Male BALB/c mice were nasally instilled with saline, or with diesel particles, treated or not, and assigned to five groups: saline (SHAM), intact diesel particles (DEP), and diesel particles previously treated with methanol (METH), hexane (HEX), or nitric acid (NA). Elemental composition and organic compounds were analyzed. Twenty-four hours after nasal instillation, respiratory parameters were measured and lung tissue was collected for histological analysis. Static elastance was significantly increased in groups DEP and MET in relation to the other groups. HEX and NA were different from DEP but not significantly different from SHAM and METH groups. The difference between dynamic and static elastance was increased in DEP, METH, and NA treatments; HEX was not statistically different from SHAM. DEP and METH groups presented significantly increased upper airways resistance, while DEP, METH, and NA showed higher peripheral airways resistance values. All groups had a higher total resistance than SHAM. DEP, METH, and NA showed significant increased infiltration of polymorphonuclear cells. In conclusion, diesel particles treated with hexane (HEX) resulted in a respiratory-system profile very similar to that in SHAM group, indicating that hexane treatment attenuates pulmonary inflammation elicited by diesel particles.

Chronic exposure to ambient levels of urban particles affects mouse lung development.

RATIONALE: Chronic exposure to air pollution has been associated with adverse effects on children's lung growth. OBJECTIVES: We analyzed the effects of chronic exposure to urban levels of particulate matter (PM) on selected phases of mouse lung development. METHODS: The exposure occurred in two open-top chambers (filtered and nonfiltered) placed 20 m from a street with heavy traffic in São Paulo, 24 hours/day for 8 months. There was a significant reduction of the levels of PM(2.5) inside the filtered chamber (filtered = 2.9 +/- 3.0 microg/m(3), nonfiltered = 16.8 +/- 8.3 microg/m(3); P = 0.001). At this exposure site, vehicular sources are the major components of PM(2.5) (PM

Decreased fertility in mice exposed to environmental air pollution in the city of Sao Paulo.

It has largely been shown that air pollution can affect human health. Effects on human fertility have been shown mainly in males by a decrease in semen quality. Few studies have focused on the environmental effects on female fertility. The aim of the present study was to analyze the effects of air pollution in the city of Sao Paulo on mouse female fertility. Four groups of female Balb/c mice were placed in two chambers 10 days (newborn) or 10 weeks (adults) after birth. Mice were maintained in the chambers 24 h a day, 7 days a week, for 4 months. The first chamber received air that had passed through an air filter (clean chamber) and the second received ambient air (polluted chamber). We measured PM10 and NO2 inside both chambers. Mice belonging to the adult groups were bred to male mice after living for 3 months inside the chambers. The newborn groups mated after reaching reproductive age (12 weeks). After 19 days of pregnancy the numbers of live-born pups, reabsorptions, fetal deaths, corpora lutea, and implantation failures were determined. PM10 and NO2 concentrations in the clean chamber were 50% and 77.5% lower than in the polluted chamber, respectively. Differences in fertility parameters between groups were observed only in animals exposed to air pollution at an early age (10 days after birth). We observed a higher number of live-born pups per animal in the clean chamber than per animal from the polluted chamber (median=6.0 and 4.0, respectively; P=0.037). There was a higher incidence of implantation failures in the polluted group than in the clean group (median=3.5 and 2.0, respectively; P=0.048). There were no significant differences in the other reproductive parameters between groups. These results support the concept that female reproductive health represents a target of air pollutants.