Long-term exposure to traffic-related air pollution and non-accidental mortality: A systematic review and meta-analysis.

BACKGROUND: The health effects of traffic-related air pollution (TRAP) continue to be of important public health interest across the globe. Following its 2010 review, the Health Effects Institute appointed a new expert Panel to systematically evaluate the epidemiological evidence regarding the associations between long-term exposure to TRAP and selected health outcomes. This paper describes the main findings of the systematic review on non-accidental mortality. METHODS: The Panel used a systematic approach to conduct the review. An extensive search was conducted of literature published between 1980 and 2019. A new exposure framework was developed to determine whether a study was sufficiently specific to TRAP, which included studies beyond the near-roadway environment. We performed random-effects meta-analysis when at least three estimates were available of an association between a specific exposure and outcome. We evaluated confidence in the evidence using a modified Office of Health Assessment and Translation (OHAT) approach, supplemented with a broader narrative synthesis. RESULTS: Thirty-six cohort studies were included. Virtually all studies adjusted for a large number of individual and area-level covariates-including smoking, body mass index, and individual and area-level socioeconomic status-and were judged at a low or moderate risk for bias. Most studies were conducted in North America and Europe, and a few were based in Asia and Australia. The meta-analytic summary estimates for nitrogen dioxide, elemental carbon and fine particulate matter-pollutants with more than 10 studies-were 1.04 (95% CI 1.01, 1.06), 1.02 (1.00, 1.04) and 1.03 (1.01, 1.05) per 10, 1 and 5 µg/m3, respectively. Effect estimates are interpreted as the relative risk of mortality when the exposure differs with the selected increment. The confidence in the evidence for these pollutants was judged as high, because of upgrades for monotonic exposure-response and consistency across populations. The consistent findings across geographical regions, exposure assessment methods and confounder adjustment resulted in a high confidence rating using a narrative approach as well. CONCLUSIONS: The overall confidence in the evidence for a positive association between long-term exposure to TRAP and non-accidental mortality was high.

Long-term exposure to traffic-related air pollution and stroke: A systematic review and meta-analysis.

BACKGROUND: Stroke remains the second cause of death worldwide. The mechanisms underlying the adverse association of exposure to traffic-related air pollution (TRAP) with overall cardiovascular disease may also apply to stroke. Our objective was to systematically evaluate the epidemiological evidence regarding the associations of long-term exposure to TRAP with stroke. METHODS: PubMed and LUDOK electronic databases were searched systematically for observational epidemiological studies from 1980 through 2019 on long-term exposure to TRAP and stroke with an update in January 2022. TRAP was defined according to a comprehensive protocol based on pollutant and exposure assessment methods or proximity metrics. Study selection, data extraction, risk of bias (RoB) and confidence assessments were conducted according to standardized protocols. We performed meta-analyses using random effects models; sensitivity analyses were assessed by geographic area, RoB, fatality, traffic specificity and new studies. RESULTS: Nineteen studies were included. The meta-analytic relative risks (and 95% confidence intervals) were: 1.03 (0.98-1.09) per 1 µg/m3 EC, 1.09 (0.96-1.23) per 10 µg/m3 PM10, 1.08 (0.89-1.32) per 5 µg/m3 PM2.5, 0.98 (0.92; 1.05) per 10 µg/m3 NO2 and 0.99 (0.94; 1.04) per 20 µg/m3 NOx with little to moderate heterogeneity based on 6, 5, 4, 7 and 8 studies, respectively. The confidence assessments regarding the quality of the body of evidence and separately regarding the presence of an association of TRAP with stroke considering all available evidence were rated low and moderate, respectively. CONCLUSION: The available literature provides low to moderate evidence for an association of TRAP with stroke.

Long-term exposure to traffic-related air pollution and selected health outcomes: A systematic review and meta-analysis.

The health effects of traffic-related air pollution (TRAP) continue to be of important public health interest. Following its well-cited 2010 critical review, the Health Effects Institute (HEI) appointed a new expert Panel to systematically evaluate the epidemiological evidence regarding the associations between long-term exposure to TRAP and selected adverse health outcomes. Health outcomes were selected based on evidence of causality for general air pollution (broader than TRAP) cited in authoritative reviews, relevance for public health and policy, and resources available. The Panel used a systematic approach to search the literature, select studies for inclusion in the review, assess study quality, summarize results, and reach conclusions about the confidence in the evidence. An extensive search was conducted of literature published between January 1980 and July 2019 on selected health outcomes. A new exposure framework was developed to determine whether a study was sufficiently specific to TRAP. In total, 353 studies were included in the review. Respiratory effects in children (118 studies) and birth outcomes (86 studies) were the most commonly studied outcomes. Fewer studies investigated cardiometabolic effects (57 studies), respiratory effects in adults (50 studies), and mortality (48 studies). The findings from the systematic review, meta-analyses, and evaluation of the quality of the studies and potential biases provided an overall high or moderate-to-high level of confidence in an association between long-term exposure to TRAP and the adverse health outcomes all-cause, circulatory, ischemic heart disease and lung cancer mortality, asthma onsetin chilldren and adults, and acute lower respiratory infections in children. The evidence was considered moderate, low or very low for the other selected outcomes. In light of the large number of people exposed to TRAP - both in and beyond the near-road environment - the Panel concluded that the overall high or moderate-to-high confidence in the evidence for an association between long-term exposure to TRAP and several adverse health outcomes indicates that exposures to TRAP remain an important public health concern and deserve greater attention from the public and from policymakers.

Clinical role of lung ultrasound for diagnosis and monitoring of COVID-19 pneumonia in pregnant women.

Lung ultrasound has been suggested recently by the Chinese Critical Care Ultrasound Study Group and Italian Academy of Thoracic Ultrasound as an accurate tool to detect lung involvement in COVID-19. Although chest computed tomography (CT) represents the gold standard to assess lung involvement, with a specificity superior even to that of the nasopharyngeal swab for diagnosis, lung ultrasound examination can be a valid alternative to CT scan, with certain advantages, particularly for pregnant women. Ultrasound can be performed directly at the bed-side by a single operator, reducing the risk of spreading the disease among health professionals. Furthermore, it is a radiation-free exam, making it safer and easier to monitor those patients who require a series of exams. We report on four cases of pregnant women affected by COVID-19 who were monitored with lung ultrasound examination. All patients showed sonographic features indicative of COVID-19 pneumonia at admission: irregular pleural lines and vertical artifacts (B-lines) were observed in all four cases, and patchy areas of white lung were observed in two. Lung ultrasound was more sensitive than was chest X-ray in detecting COVID-19. In three patients, we observed almost complete resolution of lung pathology on ultrasound within 96 h of admission. Two pregnancies were ongoing at the time of writing, and two had undergone Cesarean delivery with no fetal complications. Reverse transcription polymerase chain reaction analysis of cord blood and newborn swabs was negative in both of these cases. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

How to perform lung ultrasound in pregnant women with suspected COVID-19.

Under certain circumstances, such as during the current COVID-19 outbreak, pregnant women can be a target for respiratory infection, and lung examination may be required as part of their clinical evaluation, ideally while avoiding exposure to radiation. We propose a practical approach for obstetricians/gynecologists to perform lung ultrasound examination, discussing potential applications, semiology and practical aspects, which could be of particular importance in emergency situations, such as the current pandemic infection of COVID-19. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Serum level of testosterone, dihydrotestosterone and IGF-1 during an acute exacerbation of COPD and their relationships with inflammatory and prognostic indices: a pilot study.

AIM: Acute exacerbations (AECOPD) of negatively influence the natural history of chronic obstructive pulmonary (COPD) and they are related to muscle dysfunction. In this pathway hypogonadism could play a pivotal role. Our study wants to evaluate possible relationships among prognostic indexes of AECOPD, represented by Acute Physiology and Chronic Health Evaluation (APACHE) II, inflammation (serum amyloid A, SSA) and anabolic hormones, especially less studied steroids, like dihydrotestosterone (DHT) e free-testosterone (f-T). METHODS: Twenty-four patients (17 males; age 75 ± 13 yrs) were studied. On admission and at discharge a blood sample for total testosterone (T), DHT, insulin like grow factor 1 (IGF-1) and Serum Amyloid A (SSA) was obtained. f-T was calculated using Vermeulen's formula. RESULTS: Descriptive statistical analysis shows reduced of T values (1.85 ± 2.28 ng/mL), f-T (0.028 ± 0.030 ng/mL), DHT (0.18 ± 0.19 ng/mL) and IGF-1 (91.840 ± 74.19 pg/mL). Calculating tertile for Apache II and SSA and using them as cut off point, three categories were made and used in the analysis (SSA< 10 mg/mL; 10-160 mg/mL; > 160 mg/mL); (APACHE II ≤ 10; 11-12; > 12). Using this classification, an inverse correlation between SAA and T (P = 0.01), f-T (0.01), DHT (0.001) and IGF-1 (P = 0.05) was found. Data show the same inverse relationship between APACHE II tertiles on one hand and T (P = 0.01) and f-T (P = 0.02) on the other hand. CONCLUSION: Our data confirm systemic effects of AECOPD and the role of endocrinological derangements, suggesting a possible mechanism explaining them.

Chest pain caused by tracheostomy tube malposition: the importance of choosing the right tube.

We describe a case of chest pain caused by tracheostomy tube malposition in a 65-year old woman with chronic respiratory failure due to chronic obstructive pulmonary disease. This report highlights the importance of the correct choice of tracheostomy tube devices for mechanically ventilated and/or spontaneously breathing patients.

Variation of daily warm season mortality as a function of micro-urban heat islands.

BACKGROUND: Little attention has been paid to how heat-related health effects vary with the micro-urban variation of outdoor temperatures. This study explored whether people located in micro-urban heat islands are at higher risk of mortality during hot summer days. METHODS: Data used included (1) daily mortality for Montreal (Canada) for June-August 1990-2003, (2) daily mean ambient outdoor temperatures at the local international airport and (3) two thermal surface images (Landsat satellites, infrared wavelengths). A city-wide temperature versus daily mortality function was established on the basis of a case-crossover design; this function was stratified according to the surface temperature at decedents' place of death. RESULTS: The risk of death on warm summer days in areas with higher surface temperatures was greater than in areas with lower surface temperatures. CONCLUSIONS: This study suggests that measures aimed at reducing the temperature in micro-urban heat islands (eg, urban greening activities) may reduce the health impact of hot temperatures. Further studies are needed to document the variation of heat-related risks within cities and to evaluate the health benefits of measures aimed at reducing the temperature in micro-urban heat islands.

Blood manganese content at birth and cord serum prolactin levels.

Manganese (Mn) is both an essential element and, at a high dose, a potent neurotoxin that can interact with dopaminergic neurotransmission. Plasma prolactin (PRL), an indirect indicator of dopaminergic functioning, has been shown to vary with Mn exposure in adults, but little is known about this relation in the developing brain. The objective of this study was to examine the relations between maternal and cord Mn blood concentrations at birth and PRL cord blood levels. Blood Mn levels were determined in 87 pregnant women at delivery, and PRL was measured in the cord blood plasma. Mn cord blood concentration (mean 34.4 microg/l, range 16.7-89.4) was significantly and positively related to cord PRL levels. These findings suggest that Mn accumulation in utero could contribute to PRL level variation in neonates, which, in turn, may influence important developmental parameters.

Assessment of exposure to manganese in welding operations during the assembly of heavy excavation machinery accessories.

Welder exposure to metals in various industrial sectors is poorly characterized. We had the opportunity to carry out an exploratory study to characterize manganese exposure in welding operations in a recently established Quebec factory that assembled accessories for heavy excavation machinery. Ten workers were sampled for total manganese for at least two consecutive days out of three followed by two consecutive days for respirable manganese (with a size selective sampler with a median cut-off of 4 microns), during a typical week in the summer of 1998. Parts being welded were characterized as large or small. Small parts were those being welded on tables during subassembly. Workers were divided into two groups according to the parts they were welding. Seventy-eight percent of the total manganese exposure levels of welding operations during the assembly of large accessories of heavy excavation machinery exceeded the manganese American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value (TLV) of 0.20 mg/m3 (GM 0.24 mg/m3, n = 14) while none exceeded the TLV during the assembly of small pieces (GM 0.06 mg/m3, n = 8). Welding operations during the assembly of large heavy excavation machinery accessories may pose a significant health hazard. Considering the importance of task-related variables affecting exposure among workers, further studies are needed to better characterize exposure determinants of welding operations during the assembly of heavy excavation machinery accessories.

Peripheral biomarkers and exposure to manganese.

Biochemical mechanisms underlying manganese (Mn) toxicity include dopamine (DA) auto-oxidation and free radical generation with subsequent neuronal damage. A neuroendocrine approach based on the measurement of serum prolactin (PRL) has been proposed to assess the tonic inhibition of pituitary lactotrope cells by the tubero-infundibular DA system. Low level exposure to Mn oxides in industrial settings is associated with a shift in the distribution of serum PRL towards higher levels as compared to matched controls. The follow-up of a small cohort of workers from a ferro-manganese plant showed that the increased prevalence of abnormally high PRL values is stable over time. Although the mechanistic basis for their application is less straightforward, other biochemical markers such as dopamine beta hydroxylase and monoamine oxidase Type B, have also been assessed. Contrary to PRL levels, these markers cannot be recommended to monitor early biochemical effects of manganese exposure at the workplace. Early biochemical events can be modified by genetically determined individual differences. Owing to the possible role of a reduced capacity of glutathione conjugation as a risk factor increasing the susceptibility to the action of free radicals generated in the presence of Mn, the class mu glutathione S transferase (GSTM1) genotype has also been assessed in workers occupationally exposed. However, the GSTM1 null genotype does not appear to play an important role in the susceptibility to biochemical effects of Mn. A logistic model of the dose-response relationship based on urinary Mn as marker of exposure indicates that the benchmark dose corresponds to Mn levels as low as 0.4 microgram/l. This would imply that environmental exposure to Mn may contribute to abnormally high serum PRL in the general population.

An in vitro model for the assessment of manganese neurotoxicity.

PC12 (undifferentiated and differentiated) and C6 cells have been used to investigate kinetics, morphological and functional endpoints following exposure to MnCl(2) and manganic transferrin (Mn-Tf). [Mn](i) in undifferentiated (non-differentiated cells) exposed to both free (MnCl(2)) and bound Mn (Mn-Tf), was three- to fivefold lower as compared to differentiated (differentiated) PC12 cells and higher by one order of magnitude as compared to glial C6 cells. Exposure to both MnCl(2) and Mn-Tf was followed by time- and dose-dependent morphological changes characteristic of apoptosis, which was never observed in Mn-exposed C6 glial cells. Results from cell viability assays were consistent with apoptotic response rates quantified by cell count. Threshold concentrations for undifferentiated and differentiated PC12 cells were 10(-6) and 10(-5)m, respectively. Thus, despite their greater ability to accumulate Mn, differentiated PC12 cells are less sensitive to Mn-induced apoptosis. This model might be relevant to neuronal degeneration induced by Mn occurring in the developing brain and possibly in clinical manganism. Such critical doses at the cellular level seem to be consistent with Mn levels (5x10(-6)m) recorded in the basal ganglia of monkeys chronically exposed to Mn and developing clinical signs of manganism.

A case-control study of occupational and environmental risk factors for Parkinson's disease in the Emilia-Romagna region of Italy.

A questionnaire-based case-control study was carried out on 86 patients with neurologist-confirmed idiopathic Parkinson's disease (PD) and 86 controls similar in sex and age. The control group was recruited in outpatient specialist centers of the same University Hospital (glaucoma, psoriasis vulgaris, essential arterial hypertension and renal diseases). Exposure was defined as occupational or residential contact with a given factor for at least 10 consecutive years prior to the onset of PD. Smoking habits were defined by exclusion of those subjects who never smoked. The following risk factors were identified: cranial trauma (OR: 2.88; 95% CI: 0.98-8.49), well water use (OR: 2.78; 95% CI: 1.46-5.28) and occupational exposure to industrial chemicals (OR: 2.13; 95% CI: 1.16-3.91). Among industrial chemicals, only organic solvents were identified as significant risk factors for PD (O.R. : 2.78, 95% C.I. : 1.23-6.26). Whereas no exposure to neurotoxic metals occurred among controls, making the assessment of the O.R. impossible, exposure pesticides and herbicides was similar in the two groups (O.R. : 1.15; 95% C. : 0.56-2-36). Smoking habits was negatively associated with PD (OR: 0.41; 95% CI: 0.22-0.75), confirming the "protective" role of tobacco smoking suggested by many studies. As a whole, these results support the role of environmental factors in the etiology of PD.

Predictive validity of the Q16 questionnaire: a comparison between reported symptoms and neurobehavioral tests.

The correspondence between the answers to the Q16 questions regarding memory and attention-concentration and relevant neurobehavioral performance test scores has been evaluated. The sensitivity, specificity and diagnostic validity of Q16 have been assessed, taking the relevant neurobehavioral test score as a reference diagnostic criterion, the lower quartile of performance being considered as a poor response. The group under study consisted of 74 volunteers (24 females), aged 40 years on average (SD:7.5) and recruited among styrene-exposed workers and healthy controls. The test battery included the logical memory (short- and long-term) and the verbal learning (short- and long-term) tests of the Wechsler Adult Intelligence Scale (WAIS). The answers to the Q16 questions were poorly related to the performance: self-perceived forgetfulness showed a limited agreement with the long-term logical memory test (r=-0.23, p<0.05). The number of false negatives (no symptom but low test scores) was generally high, giving rise to a very low sensitivity of the questionnaire, despite a relatively high specificity. Accordingly, the positive diagnostic validity was low (<30%), whereas the negative diagnostic validity was high (>80%). Different methods used to investigate subtle neurological changes give rise to inconsistencies between self-perceived disturbances and objective measurements of relevant functions. Owing to its low sensitivity and positive diagnostic value, the Q16 cannot be recommended as a screening tool among workers occupationally exposed to neurotoxic chemicals.

Selective vulnerability of dopaminergic systems to industrial chemicals: risk assessment of related neuroendocrine changes.

Increased serum prolactin (PRL) is a common finding among subjects exposed to styrene, perchloroethylene, lead (Pb), and manganese (Mn) at levels below the current threshold limit values. On a group basis, abnormally high basal PRL shows a dose-related distribution among workers exposed to styrene, Pb, and Mn. On the basis of dose-response relationships, the benchmark doses (BMD) for styrene metabolites in urine, lead in blood (Pb-B), and Mn in urine (Mn-U), are 4 mg/g creatinine, 112 micrograms/L, and 0.3 microgram/L, respectively. Noteworthy, the BMD for Mn-U and Pb-B is well below the upper reference limit. A shift in the distribution but not in the prevalence of abnormally high values of serum PRL was observed among perchloroethylene-exposed dry cleaners, which makes interpretation in terms of risk difficult. The measurement of PRL thus provides opportunities for early identification of excess exposure to neurotoxic chemicals affecting dopaminergic control of pituitary secretion. For styrene, Pb, and Mn the BMD provides an objective and statistically determined threshold, which seems to be in good agreement with the estimated no-observed-adverse-effect-level (NOAEL). The NOAEL, however, is based on traditional approaches that require the application of uncertainty factors, e.g., a default factor of 10 when extrapolating the NOAEL from the lowest-observed-adverse-effect-level (LOAEL). Due to its sensitivity to a number of potential confounders, caution must be exercised when using PRL as a screening test at the individual level. Also, age and sex dependent variations in susceptibility may hamper extrapolations from the occupational settings to the general population.

Motor function, olfactory threshold, and hematological indices in manganese-exposed ferroalloy workers.

A cross-sectional study was conducted in 35 male subjects randomly selected from workers of a ferroalloy production plant and exposed to manganese (Mn) oxides; the objective was to detect early signs of neurologic impairment. The subjects' mean age was 39.4 years (SD, 8. 4); the average exposure duration was 14.5 years (range, 5-29 years). A control group of industrial workers not exposed to neurotoxic chemicals and comparable in age and confounding factors was recruited. The intensity of Mn exposure was moderate, as reflected by airborne Mn concentrations in total dust averaging 193 [corrected] micro g/m3. Mn levels in blood (MnB) and urine (MnU) were significantly higher in the Mn-exposed workers than in control workers. A relationship (not found with MnU) was found between MnB and a cumulative exposure index calculated on the basis of air concentration and exposure history for each subject (r = 0.52; r2 = 0.27; P = 0.002). Psychomotor function scores were lower among Mn-exposed subjects. The Aiming score was negatively correlated with MnB in the exposed group. The olfactory threshold did not differ between the two groups, although it was negatively associated with MnU in the exposed group. The white blood cell count results were significantly higher in Mn-exposed subjects than in controls. These findings show that an increase in Mn body burden is associated with an impairment of motor functions, whereas the increased excretion of Mn is related to an increased olfactory perception. Changes in numbers of leukocytes could indicate possible interferences of Mn with the immunological system.