Small but Mighty: Prenatal Ultrafine Particle Exposure Linked to Childhood Asthma Incidence.
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ABSTRACT:
SUBMITTER: Wright RJ
PROVIDER: S-EPMC6580671 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Prenatal and infant acetaminophen exposure has been associated with an increased risk of childhood asthma phenotypes. Demonstration of biologically plausible interactions between these exposures and maternal and child antioxidant gene polymorphisms would strengthen causal inference. OBJECTIVE:To explore potential interactions between prenatal and infant acetaminophen exposure and antioxidant genotypes on childhood asthma. METHODS:In the Avon Longitudinal Study of Parents and Children, we typed a functional nuclear erythroid 2 p45-related factor 2 (Nrf2) polymorphism and glutathione S-transferase (GST) M1, T1, and P1 polymorphisms. Effects of prenatal and infant acetaminophen exposure on asthma phenotypes at 7 years were stratified by genotype in >4000 mothers and >5000 children. RESULTS:Risk of asthma and wheezing associated with early gestation acetaminophen exposure was increased when maternal copies of the minor T allele of Nrf2 were present (P interactions, .02 and .04, respectively). Risk of asthma associated with late gestation exposure was higher when maternal GSTT1 genotype was present rather than absent (P interaction, .006), and risk of wheezing was increased when maternal GSTM1 was present (P interaction, .04). Although acetaminophen use in infancy was associated with an increased risk of atopy, child antioxidant genotype did not modify associations between infant acetaminophen use and asthma phenotypes. However, the increased risk of asthma and wheezing associated with late gestation acetaminophen exposure in the presence of maternal GSTM1 was further enhanced when GSTM1 was also present in the child. CONCLUSION:Maternal antioxidant gene polymorphisms may modify the relation between prenatal acetaminophen exposure and childhood asthma, strengthening evidence for a causal association. In contrast, relations between infant acetaminophen use and asthma and atopy were not modified by child genotype and may be confounded by pre-existing wheeze or allergy.
| S-EPMC4907348 | biostudies-literature
Project description:BACKGROUND:Exposure to ultrafine particles (UFP, particles with aerodynamic diameter?<?100?nm) is associated with reduced lung function and airway inflammation in individuals with asthma. Recently, elevated UFP number concentrations (PN) from aircraft landing and takeoff activity were identified downwind of the Los Angeles International Airport (LAX) but little is known about the health impacts of airport-related UFP exposure. METHODS:We conducted a randomized crossover study of 22 non-smoking adults with mild to moderate asthma in Nov-Dec 2014 and May-Jul 2015 to investigate short-term effects of exposure to LAX airport-related UFPs. Participants conducted scripted, mild walking activity on two occasions in public parks inside (exposure) and outside (control) of the high UFP zone. Spirometry, multiple flow exhaled nitric oxide, and circulating inflammatory cytokines were measured before and after exposure. Personal UFP PN and lung deposited surface area (LDSA) and stationary UFP PN, black carbon (BC), particle-bound PAHs (PB-PAH), ozone (O3), carbon dioxide (CO2) and particulate matter (PM2.5) mass were measured. Source apportionment analysis was conducted to distinguish aircraft from roadway traffic related UFP sources. Health models investigated within-subject changes in outcomes as a function of pollutants and source factors. RESULTS:A high two-hour walking period average contrast of ~34,000?particles·cm-3 was achieved with mean (std) PN concentrations of 53,342 (25,529) and 19,557 (11,131)?particles·cm-3 and mean (std) particle size of 28.7 (9.5) and 33.2 (11.5) at the exposure and control site, respectively. Principal components analysis differentiated airport UFPs (PN), roadway traffic (BC, PB-PAH), PM mass (PM2.5, PM10), and secondary photochemistry (O3) sources. A standard deviation increase in the 'Airport UFPs' factor was significantly associated with IL-6, a circulating marker of inflammation (single-pollutant model: 0.21, 95% CI?=?0.08-0.34; multi-pollutant model: 0.18, 0.04-0.32). The 'Traffic' factor was significantly associated with lower Forced Expiratory Volume in 1?s (FEV1) (single-pollutant model: -1.52, -2.28 to -0.77) and elevated sTNFrII (single-pollutant model: 36.47; 6.03-66.91; multi-pollutant model: 64.38; 6.30-122.46). No consistent associations were observed with exhaled nitric oxide. CONCLUSIONS:To our knowledge, our study is the first to demonstrate increased acute systemic inflammation following exposure to airport-related UFPs. Health effects associated with roadway traffic exposure were distinct. This study emphasizes the importance of multi-pollutant measurements and modeling techniques to disentangle sources of UFPs contributing to the complex urban air pollution mixture and to evaluate population health risks.
| S-EPMC6368339 | biostudies-literature
Project description:BACKGROUND:The potential for prenatal antibiotic exposure to influence asthma risk is not clear. We aim to determine the effect of timing, dose, and spectrum of prenatal antibiotic exposure on the risk of childhood asthma. METHODS:We conducted a population-based cohort study of 84,214 mother-child dyads to examine the association of prenatal antibiotic exposure and childhood asthma using multivariable logistic regression models. RESULTS:Sixty-four percent of pregnant women received antibiotics. Prenatal antibiotic exposure was associated dose-dependently with increased odds of childhood asthma (adjusted odds ratio [aOR] for interquartile increase of 2 courses [0, 2]: 1.26, 95% confidence interval [95%CI]: 1.20, 1.33). Among children exposed to at least one course in utero, the effect of timing at the first course was moderated by total maternal courses. Among pregnant women receiving a single antibiotic course, timing of exposure had no effect on childhood asthma risk. Among women receiving more than one course, early exposure of the first course was associated with greater childhood asthma risk. Compared to narrow-spectrum only antibiotic use, broad-spectrum only antibiotic exposure was associated with increased odds of asthma (aOR: 1.14, 95%CI: 1.05,1.24). There were effect modifications (p<0.001) by maternal asthma on total courses, and on timing of the first course, significant only among those without maternal asthma. CONCLUSIONS:Increased cumulative dose, early pregnancy first course, and broad-spectrum antibiotic exposure were associated with childhood asthma risk. Our study provides important evidence supporting judicious prenatal antibiotic use, particularly timing of use and choice of antibiotics, in preventing subsequent childhood asthma.
| S-EPMC7850553 | biostudies-literature
Project description:BackgroundPrevious studies of prenatal phthalate exposure and childhood asthma are inconsistent. These studies typically model phthalates as individual, rather than co-occurring, exposures. We investigated whether prenatal phthalates are associated with childhood wheeze and asthma using a mixtures approach.MethodsWe studied dyads from two prenatal cohorts in the ECHO-PATHWAYS consortium: CANDLE, recruited 2006-2011 and TIDES, recruited 2011-2013. Parents reported child respiratory outcomes at age 4-6 years: ever asthma, current wheeze (symptoms in past 12 months) and current asthma (two affirmative responses from ever asthma, recent asthma-specific medication use, and/or current wheeze). We quantified 11 phthalate metabolites in third trimester urine and estimated associations with child respiratory outcomes using weighted quantile sum (WQS) logistic regression, using separate models to estimate protective and adverse associations, adjusting for covariates. We examined effect modification by child sex and maternal asthma.ResultsOf 1481 women, most identified as White (46.6%) or Black (44.6%); 17% reported an asthma history. Prevalence of ever asthma, current wheeze and current asthma in children was 12.3%, 15.8% and 12.3%, respectively. Overall, there was no adverse association with respiratory outcomes. In sex-stratified analyses, boys' phthalate index was adversely associated with all outcomes (e.g., boys' ever asthma: adjusted odds ratio per one quintile increase in WQS phthalate index (AOR): 1.42; 95% confidence interval (CI): 1.08, 1.85, with mono-ethyl phthalate (MEP) weighted highest). Adverse associations were also observed in dyads without maternal asthma history, driven by MEP and mono-butyl phthalate (MBP), but not in those with maternal asthma history. We observed protective associations between the phthalate index and respiratory outcomes in analysis of all participants (e.g., ever asthma: AOR; 95% CI: 0.81; 0.68, 0.96), with di(2-ethylhexyl)phthalate (DEHP) metabolites weighted highest.ConclusionsResults suggest effect modification by child sex and maternal asthma in associations between prenatal phthalate mixtures and child asthma and wheeze.
| S-EPMC7708520 | biostudies-literature
Project description:BackgroundEpigenetic modifications, including DNA methylation, act as one potential mechanism underlying the detrimental effects associated with prenatal tobacco smoke (PTS) exposure. Methylation in a gene called AXL was previously reported to differ in response to PTS.MethodsWe investigated the association between PTS and epigenetic changes in AXL and how this was related to childhood asthma phenotypes. We tested the association between PTS and DNA methylation at multiple CpG loci of AXL at birth using Pyrosequencing in two separate study populations, the Children's Health Study (CHS, n = 799) and the Newborn Epigenetic Study (NEST, n = 592). Plasma cotinine concentration was used to validate findings with self-reported smoking status. The inter-relationships among AXL mRNA and miR-199a1 expression, PTS, and AXL methylation were examined. Lastly, we evaluated the joint effects of AXL methylation and PTS on the risk of asthma and related symptoms at age 10 years old.ResultsPTS was associated with higher methylation level in the AXL gene body in both CHS and NEST subjects. In the pooled analysis, exposed subjects had a 0.51% higher methylation level in this region compared to unexposed subjects (95% CI 0.29, 0.74; p < 0.0001). PTS was also associated with 21.2% lower expression of miR-199a1 (95% CI - 37.9, - 0.1; p = 0.05), a microRNA known to regulate AXL expression. Furthermore, the combination of higher AXL methylation and PTS exposure at birth increased the risk of recent episodes of bronchitic symptoms in childhood.ConclusionsPTS was associated with methylation level of AXL and the combination altered the risk of childhood bronchitic symptoms.
| S-EPMC6054742 | biostudies-literature
Project description:High ambient ultrafine particle (UFP) concentrations may play an important role in the adverse health effects associated with living near busy roadways. However, UFP size distributions change rapidly as vehicle emissions dilute and age. These size changes can influence UFP lung deposition rates and dose because deposition in the respiratory system is a strong function of particle size. Few studies to date have measured and characterized changes in near-road UFP size distributions in real-time, thus missing transient variations in size distribution due to short-term fluctuations in wind speed, direction, or particle dynamics. In this study we measured important wind direction effects on near-freeway UFP size distributions and gradients using a mobile platform with 5-s time resolution. Compared to more commonly measured perpendicular (downwind) conditions, parallel wind conditions appeared to promote formation of broader and larger size distributions of roughly one-half the particle concentration. Particles during more parallel wind conditions also changed less in size with downwind distance and the fraction of lung-deposited particle number was calculated to be 15% lower than for downwind conditions, giving a combined decrease of about 60%. In addition, a multivariate analysis of several variables found meteorology, particularly wind direction and temperature, to be important in predicting UFP concentrations within 150 m of a freeway (R2 = 0.46, p = 0.014).
| S-EPMC3886859 | biostudies-literature
Project description:Epidemiology studies have linked exposure to pollutant particles to increased cardiovascular mortality and morbidity, however, the mechanism remains unknown. In this study, we hypothesized that the ultrafine fraction of ambient pollutant particles would cause endothelial cells dysfunction. We profiled gene expression of human pulmonary artery endothelial cells (HPAEC) exposed to ultrafine Chapel Hill particles (UFP) (100μg/ml) or vehicle for 4h with Affymetrix HG U133 Plus 2.0 chips (N = 4 each). Using an unpaired t-test (p <0.01, 5% false discovery rate) we found 426 unique genes to be differentially expressed with 320 upregulated genes and 106 downregulated genes. Among these genes, we noted upregulation of genes related to coagulation-inflammation circuitry including tissue factor (F3), coagulation factor II receptor-like 2 (F2RL2, PAR3), interleukin (IL)-6 and IL-8. Upregulation of these genes were independently confirmed by RT-PCR and/or protein release. Genes related to the CXC chemokine family that have been implicated in the pathogenesis of vascular disease were upregulated, including MCP-1 (2.60 fold), IL-8 (2.47 fold), CXCL1 (1.41 fold), CXCL2 (1.95 fold), CXCL3 (2.28 fold) and CXCR4 (1.30 fold). In addition, genes related to clotting independent signaling of F3 were also differentially expressed, including FOS, JUN and NFKBIA. Treatment of HPAEC with UFP for 16 hours increased the release of IL6 and IL8 by 1.9-fold and 1.8-fold respectively. Pretreatment of HPAEC with a blocking antibody against F3 attenuated IL6 and IL8 release by 30% and 70% respectively. Thus using gene profiling, we uncovered that UFP may induce vascular endothelial cells to express genes related to clotting and angiogenesis. These results provide a novel hypothesis that PM may cause cardiovascular adverse health effects via induction of tissue factor in vascular endothelial cells which then triggers clotting dependent and independent downstream signaling. Keywords: particle treatment
2007-01-26 | GSE4567 | GEO
Project description:Background: How prenatal smoke exposure affects DNA methylation leading to atopic disorders remains to be addressed. Epigenetic biomarkers informative of prenatal smoke exposure and atopic disorders are wanting. Since most children suffering from atopic dermatitis (AD) continue to develop asthma later in life, we explored whether prenatal smoke exposure e induces DNA methylation and searched for predictive epigenetic biomarkers for smoke related atopic disorders. Methods: Methylation differences associated with smoke exposure were screened by Illumina methylation panel for children from the Taiwan birth panel study cohort initially. Information about development of atopic dermatitis (AD) and risk factors were collected. Cord blood cotinine levels were measured to represent prenatal smoke exposure. CpG loci that demonstrated a statistically significant difference in methylation were validated by methylation-dependent fragment separation (MDFS). Differential methylation in three genes (TSLP, GSTT1, and CYB5R3) was identified through the screen and their functions were investigated. Results: Among these, only thymic stromal lymphopoietin (TSLP) gene displayed significant difference in promoter methylation percentage after being validated by MDFS (p=0.029). TSLP gene was further investigated in a larger sample of 92 children from the cohort. Methylation status of the TSLP 5′-CpG island (CGI) was found to be significantly associated with prenatal smoke exposure (OR=3.59, 95%CI=1.49-8.64; cotinine level 0.10 ng/ml, sensitivity= 77%; specificity = 61%) and with AD (OR=4.77, 95%CI=1.47-15.53). The degree of TSLP 5′CGI methylation inversely correlated with TSLP protein expression levels (per unit: β=－6.69 ng/ml; 95% CIs, －12.80~－0.59; p=0.032). Conclusions: The effect of prenatal tobacco smoke exposure on the risk for AD may be mediated through DNA methylation. Cord blood methylated TSLP 5′CGI may be a potential epigenetic biomarker for environmentally-related atopic disorders. The buffy coat and plasma samples were separated and stored at −80°C. DNA (100 ng-500 ng) was extracted from cord white blood cells. Microarrays have been performed to investigate fourteen samples, which were classified as two groups according to cotinine exposure dosage (7 versus 7 : high exposure verses low exposure).
2013-12-31 | E-GEOD-35222 | biostudies-arrayexpress
Project description:BACKGROUND:Early-life exposure to traffic-related air pollution exacerbates childhood asthma, but it is unclear what role it plays in asthma development. METHODS:The association between exposure to primary mobile source pollutants during pregnancy and during infancy and asthma incidence by ages 2 through 6 was examined in the Kaiser Air Pollution and Pediatric Asthma Study, a racially diverse birth cohort of 24,608 children born between 2000 and 2010 and insured by Kaiser Permanente Georgia. We estimated concentrations of mobile source fine particulate matter (PM2.5, µg/m), nitrogen oxides (NOX, ppb), and carbon monoxide (CO, ppm) at the maternal and child residence using a Research LINE source dispersion model for near-surface releases. Asthma was defined using diagnoses and medication dispensings from medical records. We used binomial generalized linear regression to model the impact of exposure continuously and by quintiles on asthma risk. RESULTS:Controlling for covariates and modeling log-transformed exposure, a 2.7-fold increase in first year of life PM2.5 was associated with an absolute 4.1% (95% confidence interval, 1.6%, 6.6%) increase in risk of asthma by age 5. Quintile analysis showed an increase in risk from the first to second quintile, but similar risk across quintiles 2-5. Risk differences increased with follow-up age. Results were similar for NOX and CO and for exposure during pregnancy and the first year of life owing to high correlation. CONCLUSIONS:Results provide limited evidence for an association of early-life mobile source air pollution with childhood asthma incidence with a steeper concentration-response relationship observed at lower levels of exposure.
| S-EPMC5718963 | biostudies-literature
Project description:Bacterial and viral infections occur early and recurrently in life and thereby impose a substantial disease burden. Besides causing clinical symptoms, a potential role of infection in the development of the asthma syndrome later in life has also been suggested. However, whether bacterial and viral infections unmask host factors in children at risk of asthma or whether they directly cause asthma remains unclear; both viewpoints could be justified, but the underlying mechanisms are complex and poorly understood. Recently, the role of the bacterial microbiome has been emphasised. But data are still sparse and future studies are needed for definitive conclusions to be made. In this Review, we discuss present knowledge of viruses and bacteria that infect and colonise the respiratory tract and mucosal surfaces, including their timepoint of action, host factors related to infection, and their effect on childhood asthma. Childhood asthma could be the result of a combination of altered host susceptibility and infectious agents.
| S-EPMC7104105 | biostudies-literature