Arachidonic Acid Metabolites in Self-collected Biospecimens Following Campfire Exposure: Exploring Non-invasive Biomarkers of Wildfire Health Effects.

Climate change has contributed to increased frequency and intensity of wildfire. Studying its acute effects is limited due to unpredictable nature of wildfire occurrence, which necessitates readily deployable techniques to collect biospecimens. To identify biomarkers of wildfire's acute effects, we conducted this exploratory study in eight healthy campers (four men and four women) who self-collected nasal fluid, urine, saliva, and skin wipes at different time points before, during, and after 4-hour exposure to wood smoke in a camping event. Concentrations of black carbon in the air and polycyclic aromatic hydrocarbons in participants' silicone wristbands were significantly elevated during the exposure session. Among 30 arachidonic acid metabolites measured, lipoxygenase metabolites were more abundant in nasal fluid and saliva, whereas cyclooxygenase and non-enzymatic metabolites were more abundant in urine. We observed drastic increases, at 8 hours following the exposure, in urinary levels of PGE2 (398%) and 15-keto-PGF2α (191%) (FDR<10%), with greater increases in men (FDR < 0.01%) than in women. No significant changes were observed for other metabolites in urine or the other biospecimens. Our results suggest urinary PGE2 and 15-keto-PGF2α as promising biomarkers reflecting pathophysiologic (likely sex-dependent) changes induced by short-term exposure to wildfire.

Systemic oxidative stress levels during the course of pregnancy: Associations with exposure to air pollutants.

Increased systemic oxidative stress, implicated in adverse pregnancy outcomes for both mothers and fetuses, has been associated with gestational exposure to air pollutants such as polycyclic aromatic hydrocarbons (PAHs), fine particulate matter (PM2.5), and nitrogen dioxide (NO2). However, it is unclear whether exposure to pollutants at levels below the current air quality standards can increase oxidative stress in pregnant women. In a cohort of 305 pregnant persons residing in western New York, we examined the association between exposure to PM2.5, NO2, and PAHs (measured as urinary 1-hydroxypyrene) and urinary biomarkers of oxidative stress (malondialdehyde [MDA] and 8-hydroxy-2'-deoxyguanosine [8-OHdG]) measured in each trimester. After controlling for gestational stage, maternal age, lifestyles, and socioeconomic factors, each interquartile range (IQR) increase in 1-hydroxypyrene concentration (65.8 pg/ml) was associated with a 7.73% (95%CI: 3.18%,12.3%) higher in MDA levels throughout the pregnancy and in the first and second trimester. An IQR increase in PM2.5 concentration (3.20 µg/m3) was associated with increased MDA levels in the first trimester (8.19%, 95%CI: 0.28%,16.1%), but not the 2nd (-7.99%, 95% CI: 13.8%, -2.23%) or 3rd trimester (-2.81%, 95% CI: 10.0%, 4.38%). The average cumulative PM2.5 exposures in the 3-7 days before urine collection were associated with increased 8-OHdG levels during the second trimester, with the largest difference (22.6%; 95% CI: 3.46%, 41.7%) observed in relation to a one IQR increase in PM2.5 concentration in the previous 7 days. In contrast, neither oxidative stress biomarker was associated with NO2 exposure. Observed in pregnant women exposed to low-level air pollution, these findings expanded previously reported associations between systemic oxidative stress and high-level PM2.5 and PAH concentrations. Further, the first and second trimesters may be a susceptible window during pregnancy for oxidative stress responses to air pollution exposure.

Urinary 1-hydroxypyrene in pregnant women in a Northeastern U.S. city: socioeconomic disparity and contributions from air pollution sources.

BACKGROUND: Maternal exposure to polycyclic aromatic hydrocarbons (PAHs), ubiquitous constituents of air pollution, has been associated with adverse birth outcomes. Yet it remains unclear whether and how socioeconomic status (SES) affects gestational PAH exposure. OBJECTIVE: To examine whether there are socioeconomic disparities in PAHs exposure among pregnant women from Rochester, NY, and if so, to what extent disproportionate proximity to air pollution sources, measured by residential distance to transportation-related sources, contributed to the exposure disparity. METHODS: We measured 1-hydroxypyrene concentrations in 726 urine samples collected from 305 pregnant women up to three samples throughout pregnancy. Residential distances to transportation-related sources were calculated based on participants' home addresses. We used linear mixed-effects models with random intercepts of participants to examine associations between 1-hydroxypyrene, SES indicators, and distance to transportation-related sources. We used structural equation modelling to assess to what extent distance to transportation-related sources contributes to the socioeconomic disparity in 1-hydroxypyrene concentrations. RESULTS: Reduced household income and maternal education level were both significant SES predictors of 1-hydroxypyrene concentrations, after the adjustment for other maternal demographic characteristics. Each interquartile range (IQR) increases in residential proximity to the airport (from 14.3 to 6.0 km), the railroad yard (from 22.3 to 6.0 km), and annual average daily traffic within 300 m (from 3796 to 99,933 vehicles/year) were associated with 15.0% (95%CI: 7.0-22.2%), 15.4% (95%CI: 6.5-23.5%), and 13.6% (95%CI: 4.7-23.3%) increases in 1-hydroxypyrene concentrations, respectively. Proximity to these sources jointly explained 10% (95%CI: 1.6-18.4%) of the 1-hydroxypyrene concentration change associated with decreases in SES as a latent variable defined by both household income and education level. IMPACT STATEMENT: Our findings suggest that efforts to address disproportionate residential proximity to transportation-related sources may reduce the socioeconomic disparity in PAH exposure.

Prenatal and Childhood Smoke Exposure Associations with Cognition, Language, and Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: To assess the relationships of prenatal and childhood smoke exposure with specific neurodevelopmental and behavioral problems during early childhood. STUDY DESIGN: A subsample (n = 386) of mother-child dyads from the Newborn Epigenetic Study (NEST) prebirth cohort participated in the study. Cotinine concentrations were used to objectively measure prenatal and childhood smoke exposure when youth were aged 3-13 years. Multivariable regression models were used to estimate associations of prenatal and childhood cotinine concentrations with performance on the National Institutes of Health (NIH) Toolbox and attention-deficit/hyperactivity disorder and behavioral symptoms, measured using the Behavior Assessment System for Children, 2nd edition (BASC-2). RESULTS: After adjusting for confounders, childhood cotinine concentrations were associated with poorer cognitive performance on tasks measuring cognitive flexibility (B = -1.29; P = .03), episodic memory (B = -0.97; P = .02), receptive language development (B = -0.58; P = .01), and inhibitory control and attention (B = -1.59; P = .006). Although childhood cotinine concentration was associated with higher levels of attention problems (B = 0.83; P = .004) on the BASC-2, after adjustment for confounders, the association is nonsignificant. Although associations for maternal cotinine concentrations were null, an interaction was detected between prenatal and childhood cotinine concentrations on the NIH Toolbox Picture Vocabulary Task (P = .02). CONCLUSIONS: Our findings suggest that childhood tobacco smoke exposure may lead to poorer attention regulation and language acquisition, complex visual processing ability, and attention problems.

Dried Blood Spot Biomarkers of Oxidative Stress and Inflammation Associated with Blood Pressure in Rural Senegalese Women with Incident Hypertension.

Blood biomarkers of oxidative stress and inflammation have been associated with increased risk of hypertension development; yet their application in sub-Saharan Africa has been limited due to the lack of blood collection facilities. In this study, we evaluated the usefulness of dried blood spots (DBS), a more feasible alternative to venous blood, in rural sub-Saharan residents. We recruited 342 women with incident hypertension from rural Senegal, and measured C-reactive protein (CRP) and malondialdehyde (MDA) in DBS and concurrent blood pressure (BP) at baseline and 1-year follow-up. Associations of DBS biomarkers with current levels of and 1-year changes in BP were examined after adjusting for demographic, medical, and socioeconomic covariates. DBS concentrations of MDA were significantly associated with concurrent systolic BP (SBP) (p < 0.05), while DBS baseline concentrations of CRP were associated with longitudinal changes in SBP between baseline and follow-up. Compared to participants with baseline CRP < 1 mg/L, those with CRP of 1-3 mg/L and 3-10 mg/L had 2.11 mmHg (95%CI: -2.79 to 7.02 mmHg) and 4.68 mmHg (95%CI: 0.01 to 9.36 mmHg) increases in SBP at follow-up, respectively. The results support the use of DBS biomarkers for hypertension prevention and control, especially in settings with limited clinical resources.

Malondialdehyde in dried blood spots: a biomarker of systemic lipid peroxidation linked to cardiopulmonary symptoms and risk factors.

BACKGROUND: There are few oxidative biomarkers that can be used in resource-limited settings (e.g., rural Africa) where blood collection facilities are lacking. This study aims to evaluate the potential of malondialdehyde (MDA) in dried blood spots (DBS) as a useful biomarker to monitor cardiopulmonary health. METHODS: We first conducted a cross-validation comparison of matched capillary DBS, plasma, and whole venous blood collected from nine healthy volunteers for the measurement of total MDA (free + conjugated) and C-reactive protein (CRP), a well-established biomarker of systemic inflammation. Then a field study was conducted in a rural Senegal with a population of 441 women routinely exposed to severe household air pollution, examining associations of MDA and CRP levels in 882 DBS with self-reported cardiopulmonary symptoms. RESULTS: In the cross-validation study, CRP levels were strongly correlated across DBS, plasma, and whole blood. MDA levels were correlated between DBS and whole blood and were 1-2 orders of magnitude lower in plasma, suggesting that DBS MDA may reflect total oxidation levels in intracellular and extracellular compartments. In the field study, we observed significantly higher MDA levels in women with secondhand smoke exposure. An interquartile range increase in MDA concentration was associated with 27.0% (95% CI: 3.1-56.5%) and 21.1% (95% CI: -3.5% to 52.0%) increases in the incidence of chest tightness and breath difficulty, respectively. In contrast, CRP levels were not associated with worse outcomes or risk factors. CONCLUSIONS: These results support the use of DBS as a convenient alternative to venous blood when MDA is measured as a biomarker for cardiopulmonary health risk.

Nitrated Polycyclic Aromatic Hydrocarbons and Arachidonic Acid Metabolisms Relevant to Cardiovascular Pathophysiology: Findings from a Panel Study in Healthy Adults.

Concerns on nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) in the environment have mainly arisen from their mutagenic and carcinogenic effects. The objective of this study is to investigate whether nitro-PAH exposures are associated with biomarkers of cardiovascular pathophysiology. In a panel study design, urines and blood samples were collected up to four times with a 2-week interval from 89 healthy adults. We measured 1-naphthylamine, 2-naphthylamine, 9-aminophenanthrene, 2-aminofluorene, and 1-aminopyrene as biomarkers of nitro-PAH exposures. We measured three urinary metabolites of arachidonic acid (AA) including 20-hydroxyeicosatetraenoic acid (20-HETE) from the cytochrome P450 (CYP) pathway, 8-isoprostane from the nonenzymatic pathway, and 11-dehydro-thromboxane B2 (11-dhTXB2) from the cyclooxygenase (COX) pathway. Urinary malondialdehyde, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and 6-sulfatoxymelatonin (aMT6s) were measured to reflect systemic oxidative stress. Plasma concentrations of the soluble P-selectin and von Willebrand factor (vWF) were measured as biomarkers of platelet activation and endothelial dysfunction. We found that increased urinary concentrations of amino-PAHs were significantly associated with increased 20-HETE, 11-dhTXB2, and 8-OHdG and with decreased 8-isoprostane and aMT6s. Increased amino-PAHs were positively associated with P-selectin and vWF, respectively. These results suggest that exposure to nitro-PAHs increases systemic oxidative stress and alters AA metabolism toward CYP and COX pathways, leading to an increased cardiovascular disease risk.

Associations of ozone exposure with urinary metabolites of arachidonic acid.

BACKGROUND: Ozone (O3) exposure has been associated with biomarkers of platelet activation and oxidative stress. The metabolism of arachidonic acid (AA) plays an important role in platelet activation and oxidative stress. However, AA metabolic pathways have not been examined in relation to O3 and other air pollutants. METHODS: Early morning urine and fasting blood were longitudinally collected up to four times from 89 healthy adults (22-52 years old, 25 women) in Changsha City, China. We measured three urinary AA metabolites, namely 11-dehydro-Thromboxane B2 (11-dhTXB2) produced from the arachidonic cyclooxygenase pathway, 20-hydroxyeicosatetraenoic acid (20-HETE) from the CYPs pathway, and 8-isoprostane from the non-enzymatic pathway. Urinary malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured as indicators of oxidative damage to lipids and DNA, respectively. We measured soluble P-selectin (sCD62p) concentrations in plasma as an indicator of platelet activation. Indoor and outdoor air pollutants were measured and combined with participants' time-activity pattern to calculate personal exposure to O3, PM2.5, NO2, and SO2 averaged over 12-hour, 24-hour, 1-week, and 2-week periods prior to biospecimen collection, respectively. Linear mixed-effects models were used to examine the relationships of AA metabolites with air pollutant exposures, plasma sCD62p, and urinary MDA & 8-OHdG. RESULTS: We found that a 10% increase in 12 h and 24 h O3 exposure were associated with increases in urinary11-dhTXB2 by 1.4% (95%, 0.1% to 2.6%) and 1.3% (0.05% to 2.5%), respectively. These associations remained robust after adjusting for co-pollutant exposures. No significant associations were observed between 11-dhTXB2 and other pollutants or between O3 exposures and other AA metabolites. All the three AA metabolites were significantly and positively associated with urinary MDA and 8-OHdG, whereas only urinary 11-dhTXB2 was significantly and positively associated with plasma sCD62p. CONCLUSIONS: A metabolite of AA from the cyclooxygenase pathway was positively associated with short-term O3 exposure, and with a plasma marker of platelet activation and two urinary markers of oxidative stress. The results suggest that O3 exposure may contribute to increased platelet activation and oxidative damages via altering the metabolism of AA.

Preoperative selective portal vein embolization in two-step hepatectomy for hepatocellular carcinoma in injured livers: a preliminary report.

OBJECTIVE: To study the effect of preoperative selective portal vein embolization (SPVE) in the two-step hepatectomy for patients with primary hepatocellular carcinoma (HCC) in injured livers. METHODS: Twenty-six patients with HCC and cirrhosis who were not suitable for curative hepatectomy were treated by ultrasound-guided percutaneous transhepatic SPVE with a fine needle. The success rate, side-effects and complications of SPVE, serial changes of hepatic lobe volume and rate of two-step curative hepatectomy after SPVE were observed. RESULTS: SPVE was performed in 24 patients (92.3%). In patients whose right portal vein branches were embolized, the right hepatic volume decreased but the left hepatic volume increased gradually. The ratio of the right hepatic volume to the total hepatic volume decreased from 64.0% before SPVE to 60.8% after l week, 55.1% after 2 weeks and 52.7% after 3 weeks, respectively. The side-effects included different degree of pain in the liver quandrant (17 patients), lower fever (9), and nausea and vomiting (7). The levels of aspartate alanine transaminase (AST), alanine transaminase (ALT) and total bilirubin (TBIL) increased after SPVE, but returned to the preoperative levels in 1 week. After 2-4 weeks, two-step curative hepatectomy for HCC was performed in 13 patients (54.2%). CONCLUSIONS: Ultrasound-guided percutaneous transhepatic SPVE with a fine needle is feasible and safe. It can extend the indications of curative hepatectomy for HCC in injured livers, and increase the safety of two-step hepatectomy.

Role of preoperative selective portal vein embolization in two-step curative hepatectomy for hepatocellular carcinoma.

AIM: To determine the feasibility and role of ultrasound-guided preoperative selective portal vein embolization (POSPVE) in the two-step hepatectomy of patients with advanced primary hepatocellular carcinoma (HCC). METHODS: Fifty patients with advanced HCC who were not suitable for curative hepatectomy were treated by ultrasound-guided percutaneous transhepatic POSPVE with fine needles. The successful rate, side effects and complications of POSPVE, changes of hepatic lobe volume and two-step curative hepatectomy rate after POSPVE were observed. RESULTS: POSPVE was successfully performed in 47 (94.0 %) patients. In patients whose right portal vein branches were embolized, their right hepatic volume decreased and left hepatic volume increased gradually. The ratio of right hepatic volume to total hepatic volume decreased from 62.4 % before POSPVE to 60.5 %, 57.2 % and 52.8 % after 1, 2 and 3 weeks respectively. The side effects included different degree of pain in liver area (38 cases), slight fever (27 cases), nausea and vomiting (9 cases). The level of aspartate alanine transaminase (AST), alanine transaminase (ALT) and total bilirubin (TBIL) increased after POSPVE, but returned to preoperative level in 1 week. After 2-4 weeks, two-step curative hepatectomy for HCC was successfully performed on 23 (52.3 %) patients. There were no such severe complications as ectopic embolization, local hemorrhage and bile leakage. CONCLUSION: Ultrasound-guided percutaneous transhepatic POSPVE with fine needles is feasible and safe. It can extend the indications of curative hepatectomy of HCC, and increase the safety of hepatectomy.