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Independent and Opposing Associations of Habitual Exercise and Chronic PM2.5 Exposures on Hypertension Incidence.
Guo, C, Zeng, Y, Chang, LY, Yu, Z, Bo, Y, Lin, C, Lau, AK, Tam, T, Lao, XQ
Circulation. 2020;(7):645-656
Abstract
BACKGROUND We investigated the joint associations of habitual physical activity (PA) and long-term exposure to fine particulate matter (PM2.5) with the development of hypertension in a longitudinal cohort in Taiwan. METHODS We selected 140 072 adults (≥18 years of age) without hypertension who joined a standard medical screening program with 360 905 medical examinations between 2001 and 2016. PM2.5 exposure was estimated at each participant's address using a satellite data-based spatiotemporal model with 1 km2 resolution. Information on habitual PA and a wide range of covariates was collected using a standard self-administered questionnaire. We used the Cox regression model with time-dependent covariates to examine the joint associations. RESULTS The mean age of all observations was 41.7 years, and 48.8% were male. The mean value for systolic and diastolic blood pressure was 112.5 and 68.7mm Hg, respectively. Approximately 34.2% of all observations were inactive (0 metabolic equivalence values-hours), 29.8% had moderate-PA (median [interquartile range]; 3.75 [3.38 to 4.38] metabolic equivalence values-hours), and 36.0% had high-PA (15.7 [10.3 to 24.8] metabolic equivalence values-hours). The mean±SD of PM2.5 was 26.1±7.3 μg/m3. The prevalence of cardiovascular disease, diabetes mellitus, and cancer was 2.1%, 2.9%, and 1.5%, respectively. After adjusting for a wide range of covariates (including a mutual adjustment for PA or PM2.5), a higher PA level was associated with a lower risk of hypertension (hazard ratio [HR] for the moderate- and high-PA was 0.93 [95% CI, 0.89-0.97] and 0.92 [95% CI, 0.88-0.96], respectively, as compared with the inactive-PA), whereas a higher level of PM2.5 was associated with a higher risk of hypertension (HR for the moderate- and high-PM2.5 was 1.37 [95% CI, 1.32-1.43] and 1.92 [95% CI, 1.81-2.04], respectively, as compared with the low-PM2.5 group]. No significant interaction was observed between PA and PM2.5 (HR 1.01 [95% CI, 1.00-1.02]). CONCLUSIONS A high-PA and low PM2.5 exposure were associated with a lower risk of hypertension. The negative association between PA and hypertension remained stable in people exposed to various levels of PM2.5, and the positive association between PM2.5 and hypertension was not modified by PA. Our results indicated that PA is a suitable hypertension prevention strategy for people residing in relatively polluted regions.
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Particulate metal exposures induce plasma metabolome changes in a commuter panel study.
Ladva, CN, Golan, R, Liang, D, Greenwald, R, Walker, DI, Uppal, K, Raysoni, AU, Tran, V, Yu, T, Flanders, WD, et al
PloS one. 2018;(9):e0203468
Abstract
INTRODUCTION Advances in liquid chromatography-mass spectrometry (LC-MS) have enabled high-resolution metabolomics (HRM) to emerge as a sensitive tool for measuring environmental exposures and corresponding biological response. Using measurements collected as part of a large, panel-based study of car commuters, the current analysis examines in-vehicle air pollution concentrations, targeted inflammatory biomarker levels, and metabolomic profiles to trace potential metabolic perturbations associated with on-road traffic exposures. METHODS A 60-person panel of adults participated in a crossover study, where each participant conducted a highway commute and randomized to either a side-street commute or clinic exposure session. In addition to in-vehicle exposure characterizations, participants contributed pre- and post-exposure dried blood spots for 2-hr changes in targeted proinflammatory and vascular injury biomarkers and 10-hr changes in the plasma metabolome. Samples were analyzed on a Thermo QExactive MS system in positive and negative electrospray ionization (ESI) mode. Data were processed and analyzed in R using apLCMS, xMSanalyzer, and limma. Features associated with environmental exposures or biological endpoints were identified with a linear mixed effects model and annotated through human metabolic pathway analysis in mummichog. RESULTS HRM detected 10-hr perturbations in 110 features associated with in-vehicle, particulate metal exposures (Al, Pb, and Fe) which reflect changes in arachidonic acid, leukotriene, and tryptophan metabolism. Two-hour changes in proinflammatory biomarkers hs-CRP, IL-6, IL-8, and IL-1β were also associated with 10-hr changes in the plasma metabolome, suggesting diverse amino acid, leukotriene, and antioxidant metabolism effects. A putatively identified metabolite, 20-OH-LTB4, decreased after in-vehicle exposure to particulate metals, suggesting a subclinical immune response. CONCLUSIONS Acute exposures to traffic-related air pollutants are associated with broad inflammatory response, including several traditional markers of inflammation.
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Prevalence and risk factors for allergic rhinitis in two resource-limited settings in Peru with disparate degrees of urbanization.
Baumann, LM, Romero, KM, Robinson, CL, Hansel, NN, Gilman, RH, Hamilton, RG, Lima, JJ, Wise, RA, Checkley, W, ,
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2015;(1):192-9
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Abstract
BACKGROUND Allergic rhinitis is a disease with a high global disease burden, but risk factors that contribute to this condition are not well understood. OBJECTIVE To assess the prevalence and risk factors of allergic rhinitis in two Peruvian populations with disparate degrees of urbanization. METHODS We conducted a population-based, cross-sectional study on 1441 children aged 13-15 years at enrollment (mean age 14.9 years, 51% boys) to investigate the prevalence of allergic disease. We used a standardized, Spanish validated questionnaire to determine the prevalence of allergic rhinitis and asked about sociodemographics and family history of allergies. Children also underwent spirometry, exhaled nitric oxide, allergy skin testing to 10 common household allergens and provided a blood sample for measurement of 25OH vitamin D and total serum IgE. RESULTS Overall prevalence of allergic rhinitis was 18% (95% CI 16% to 20%). When stratified by site, the prevalence of allergic rhinitis was 23% Lima vs. 13% in Tumbes (P < 0.001); however, this difference was no longer significant after controlling for subject-specific factors (P = 0.95). There was a strong association with other allergic diseases: 53% of children with asthma had allergic rhinitis vs. 15% in those without asthma (P < 0.001) and 42% of children with eczema vs. 17% of those without eczema (P < 0.001). Important risk factors for allergic rhinitis were parental rhinitis (adjusted OR = 3.0, 95% CI 1.9-4.7 for 1 parent and adjusted OR = 4.4, 95% CI 1.5-13.7 for 2 parents); allergic sensitization to common household aeroallergens (1.6, 1.1-2.3); being overweight (1.5, 1.0-2.3); exhaled nitric oxide ≥ 20 ppb (1.9, 1.3-2.7); and total serum IgE ≥ 95th percentile (2.4, 1.2-4.8). Population attributable risk of important factors for allergic rhinitis were 25% for high exhaled nitric oxide, 22% for allergic sensitization to common household aeroallergens, 22% for paternal rhinitis, 10% for being overweight and 7% for an elevated total serum IgE. CONCLUSION AND CLINICAL RELEVANCE Allergic rhinitis was prevalent in both settings, and important risk factors include elevated exhaled nitric oxide, allergic sensitization to common household aeroallergens, parental rhinitis, being overweight and high total serum IgE. When considering subject-specific factors, the difference in prevalence between the urban and rural settings became non-important.
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Elevated serum polybrominated diphenyl ethers and alteration of thyroid hormones in children from Guiyu, China.
Xu, X, Liu, J, Zeng, X, Lu, F, Chen, A, Huo, X
PloS one. 2014;(11):e113699
Abstract
Informal electronic waste (e-waste) recycling results in serious environmental pollution of polybrominated diphenyl ethers (PBDEs) and heavy metals. This study explored whether there is an association between PBDEs, heavy metal and key growth- and development-related hormones in children from Guiyu, an e-waste area in southern China. We quantified eight PBDE congeners using gas chromatographic mass spectrometry, lead and cadmium utilizing graphite furnace atomic absorption spectrometry, three thyroids with radioimmunoassay and two types of growth hormones by an enzyme-linked immune-sorbent assay (ELISA) in 162 children, 4 to 6 years old, from Guiyu. In blood, median total PBDE was 189.99 ng/g lipid. Lead and cadmium concentrations in blood averaged 14.53±4.85 µg dL-1 and 0.77±0.35 µg L-1, respectively. Spearman partial correlation analysis illustrated that lead was positively correlated with BDE153 and BDE183. Thyroid-stimulating hormone (TSH) was positively correlated with almost all PBDE congeners and negatively correlated with insulin-like growth factor binding protein-3 (IGFBP-3), whereas free triiodothyronine (FT3) and free thyroxine (FT4) were negatively correlated with BDE154. However, no correlation between the hormones and blood lead or cadmium levels was found in this study. Adjusted multiple linear regression analysis showed that total PBDEs was negatively associated with FT3 and positively associated with TSH. Notably, FT4 was positively correlated with FT3, house functions as a workshop, and father's work involved in e-waste recycling and negatively correlated with vitamin consumptions. TSH was negatively related with FT4, paternal residence time in Guiyu, working hours of mother, and child bean products intake. IGFBP-3 was positively correlated with IGF-1 and house close to an e-waste dump. These results suggest that elevated PBDEs and heavy metals related to e-waste in Guiyu may be important risk factors for hormone alterations in children.
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Association between inflammatory marker, environmental lead exposure, and glutathione S-transferase gene.
Sirivarasai, J, Wananukul, W, Kaojarern, S, Chanprasertyothin, S, Thongmung, N, Ratanachaiwong, W, Sura, T, Sritara, P
BioMed research international. 2013;:474963
Abstract
A number of studies suggested that lead is related to the induction of oxidative stress, and alteration of immune response. In addition, modifying these toxic effects varied partly by GST polymorphism. The objectives of this study were to assess the association between the lead-induced alteration in serum hs-CRP, with GSTM1, GSTT1, and GSTP1 Val105Ile genetic variations and the health consequence from environmental lead exposure. The 924 blood samples were analyzed for blood lead, CRP, and genotyping of three genes with real-time PCR. Means of blood lead and serum hs-CRP were 5.45 μ g/dL and 2.07 mg/L. Both CRP and systolic blood pressure levels were significantly higher for individuals with blood lead in quartile 4 (6.48-24.63 μ g/dL) compared with those in quartile 1 (1.23-3.47 μ g/dL, P < 0.01). In particular, in men with blood lead >6.47 μ g/dL the adjusted odds ratio (OR) of CRP levels for individuals with GSTP1 variants allele, GSTM1 null, GSTT1 null, double-null GSTM1, and GSTT1 compared with wild-type allele was 1.46 (95% CI; 1.05-2.20), 1.32 (95% CI; 1.03-1.69), 1.65 (95% CI; 1.17-2.35), and 1.98 (95% CI; 1.47-2.55), respectively. Our findings suggested that lead exposure is associated with adverse changes in inflammatory marker and SBP. GST polymorphisms are among the genetic determinants related to lead-induced inflammatory response.
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Manganese in children with attention-deficit/hyperactivity disorder: relationship with methylphenidate exposure.
Farias, AC, Cunha, A, Benko, CR, McCracken, JT, Costa, MT, Farias, LG, Cordeiro, ML
Journal of child and adolescent psychopharmacology. 2010;(2):113-8
Abstract
Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder that affects children worldwide. The etiology of ADHD is complex and not fully understood. Earlier studies associated elevated levels of manganese (Mn) with learning problems, attention deficits, and ADHD. Furthermore, it has also been shown that the dopamine (DA) system, the primary site of action of pharmacological ADHD treatments, is influenced by high levels of Mn. Recent studies have suggested that Mn accumulates in dopaminergic neurons via the presynaptic dopamine transporter (DAT). A role for altered functioning of the dopaminergic system in the etiology of ADHD has been well established through neurochemical, neurophysiological, imaging, and genetics studies. Methylphenidate (MPH) is a psychostimulant commonly used to manage ADHD symptoms. The pharmacotherapeutic effect of MPH occurs primarily through its action of inhibiting DAT, and thus increasing dopamine, as well as other catecholamines, at the synapse. We assessed a group of children with ADHD and matched control children without psychopathology attending public schools in a southern Brazilian city and reported elevated serum concentrations of Mn in treatment-naïve children with ADHD compared to normal controls. Interestingly, children with ADHD receiving concurrent MPH showed no difference in Mn serum levels versus controls. We then prospectively assessed the impact of naturalistic treatment with MPH and determined that Mn concentrations were significantly reduced from baseline values following MPH exposure.
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Cardiovascular and physiologic effects of conducted electrical weapon discharge in resting adults.
Ho, JD, Miner, JR, Lakireddy, DR, Bultman, LL, Heegaard, WG
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2006;(6):589-95
Abstract
OBJECTIVES The TASER is a conducted electrical weapon (CEW) that has been used on people in custody. Individuals occasionally die unexpectedly while in custody, proximal to the application of a CEW. In this study, the authors sought to examine the effects of CEW application in resting adult volunteers to determine if there was evidence of induced electrical dysrhythmia or direct cellular damage that would indicate a causal relationship between application of the device and in-custody death. METHODS Human subjects (N = 66) underwent 24-hour monitoring after a standard CEW application. Blood samples were collected before and after exposure and again at 16 and 24 hours after exposure. A subpopulation (n = 32) had 12-lead electrocardiography performed at similar time intervals. Blood samples were analyzed for markers of skeletal and cardiac muscle injury and renal impairment. The electrocardiograms were read by a cardiologist blinded to the study. Data were analyzed using descriptive statistics. RESULTS There was no significant change from baseline at any of the four time points for serum electrolyte levels and the blood urea nitrogen/creatinine ratio. An increase in serum bicarbonate and creatine kinase levels was noted at 16 and 24 hours. An increase in serum lactate level was noted immediately after exposure that decreased at 16 and 24 hours. Serum myoglobin level was increased from baseline at all three time points. All troponin levels measured were < 0.3 ng/mL, except for a single value of 0.6 ng/mL in a single subject. This subject was evaluated, and no evidence of acute myocardial infarction or disability was identified. At baseline, 30 of 32 electrocardiograms were interpreted as normal. The two abnormal electrocardiograms were abnormal at baseline and remained the same at all four time points. CONCLUSIONS In this resting adult population, the TASER X26 CEW did not affect the recordable cardiac electrical activity within a 24-hour period following a standard five-second application. The authors were unable to detect any induced electrical dysrhythmias or significant direct cardiac cellular damage that may be related to sudden and unexpected death proximal to CEW exposure. Additionally, no evidence of dangerous hyperkalemia or induced acidosis was found. Further study in the area of the in-custody death phenomenon to better understand its causes is recommended.
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Mixed mold mycotoxicosis: immunological changes in humans following exposure in water-damaged buildings.
Gray, MR, Thrasher, JD, Crago, R, Madison, RA, Arnold, L, Campbell, AW, Vojdani, A
Archives of environmental health. 2003;(7):410-20
Abstract
The study described was part of a larger multicenter investigation of patients with multiple health complaints attributable to confirmed exposure to mixed-molds infestation in water-damaged buildings. The authors present data on symptoms; clinical chemistries; abnormalities in pulmonary function; alterations in T, B, and natural killer (NK) cells; the presence of autoantibodies (i.e., antinuclear autoantibodies [ANA], autoantibodies against smooth muscle [ASM], and autoantibodies against central nervous system [CNS] and peripheral nervous system [PNS] myelins). A total of 209 adults, 42.7 +/- 16 yr of age (mean +/- standard deviation), were examined and tested with (a) self-administered weighted health history and symptom questionnaires; (b) standardized physical examinations; (c) complete blood counts and blood and urine chemistries; (d) urine and fecal cultures; (e) thyroid function tests (T4, free T3); (f) pulmonary function tests (forced vital capacity [FVC], forced expiratory volume in 1 sec [FEV1.0], and forced expiratory flow at 25%, 50%, 75%, and 25-75% of FVC [FEF25, FEF50, FEF75, and FEF2(25-75)]); (g) peripheral lymphocyte phenotypes (T, B, and NK cells) and mitogenesis determinations; and (h) a 13-item autoimmune panel. The molds-exposed patients reported a greater frequency and intensity of symptoms, particularly neurological and inflammatory symptoms, when compared with controls. The percentages of exposed individuals with increased lymphocyte phenotypes were: B cells (CD20+), 75.6%; CD5+CD25+, 68.9%; CD3+CD26+, 91.2%; CD8+HLR-DR+, 62%; and CD8+CD38+, 56.6%; whereas other phenotypes were decreased: CD8+CD11b+, 15.6% and CD3-CD16+CD56+, 38.5%. Mitogenesis to phytohemagglutinin was decreased in 26.2% of the exposed patients, but only 5.9% had decreased response to concanavalin A. Abnormally high levels of ANA, ASM, and CNS myelin (immunoglobulins [Ig]G, IgM, IgA) and PNS myelin (IgG, IgM, IgA) were found; odds ratios for each were significant at 95% confidence intervals, showing an increased risk for autoimmunity. The authors conclude that exposure to mixed molds and their associated mycotoxins in water-damaged buildings leads to multiple health problems involving the CNS and the immune system, in addition to pulmonary effects and allergies. Mold exposure also initiates inflammatory processes. The authors propose the term "mixed mold mycotoxicosis" for the multisystem illness observed in these patients.
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Environmental lead exposure and progression of chronic renal diseases in patients without diabetes.
Lin, JL, Lin-Tan, DT, Hsu, KH, Yu, CC
The New England journal of medicine. 2003;(4):277-86
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Abstract
BACKGROUND Previous research suggests that environmental lead exposure correlates with age-related decreases in renal function. METHODS Two hundred two patients with chronic renal insufficiency (indicated by a serum creatinine level between 1.5 mg per deciliter and 3.9 mg per deciliter) who had a normal total-body lead burden and no history of exposure to lead were observed for 24 months. After the observation period, 64 subjects with an elevated body lead burden were randomly assigned to the chelation control groups. For three months, the patients in the chelation group received lead-chelation therapy with calcium disodium EDTA, and the control group received placebo. During the ensuing 24 months, repeated chelation therapy was administered weekly to 32 patients with high-normal body lead burdens (at least 80 microg but less than 600 microg) unless on repeated testing the body lead burden fell below 60 microg; the other 32 patients served as controls and received weekly placebo infusions for 5 weeks every 6 months. The primary end point was an increase in the serum creatinine level to 1.5 times the base-line value during the observation period. A secondary end point was the change in renal function during the intervention period. RESULTS The primary end point occurred in 24 patients during the observation period; the serum creatinine levels and body lead burden at base line were the most important risk factors. The glomerular filtration rate improved significantly by the end of the 27-month intervention period in patients receiving chelation therapy: the mean (+/-SD) change in the glomerular filtration rate in the patients in the chelation group was 2.1+/-5.7 ml per minute per 1.73 m2 of body-surface area, as compared with -6.0+/-5.8 ml per minute per 1.73 m2 of body-surface area in the controls (P<0.001). The rate of decline in the glomerular filtration rate in the chelation group was also lower than that in the controls during the 24-month period of repeated chelation therapy or placebo. CONCLUSIONS Low-level environmental lead exposure may accelerate progressive renal insufficiency in patients without diabetes who have chronic renal disease. Repeated chelation therapy may improve renal function and slow the progression of renal insufficiency.
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Testicular effect of mustard gas.
Safarinejad, MR
Urology. 2001;(1):90-4
Abstract
OBJECTIVES To explain the testicular effect of mustard gas. METHODS Eighty-one patients who had been exposed to sulfur mustard and had the presenting symptom of infertility underwent evaluation of their reproductive system. Three semen analyses, serum hormonal determinations (luteinizing hormone, follicle-stimulating hormone, and testosterone), and genital examinations were completed for all patients, as were testicular biopsies in 24 patients. RESULTS Azoospermia and severe oligospermia were diagnosed in 42.5% and 57.5% of patients, respectively. Hormone studies revealed an elevated plasma follicle-stimulating hormone level and normal plasma luteinizing hormone and testosterone concentrations. Testicular biopsy showed selective atrophy of the germinal epithelium, intact Sertoli cells, and normal-appearing Leydig cells. CONCLUSIONS Mustard gas can cause defective spermatogenesis years after exposure.