Correction: Inducible Nitric Oxide Synthase Promoter Haplotypes and Residential Traffic-Related Air Pollution Jointly Influence Exhaled Nitric Oxide Level in Children.
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ABSTRACT:
SUBMITTER: Salam MT
PROVIDER: S-EPMC4861268 | biostudies-other | 2016
REPOSITORIES: biostudies-other
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Project description:BACKGROUND:Exhaled nitric oxide (FeNO), a biomarker of airway inflammation, predicts asthma risk in children. We previously found that the promoter haplotypes in inducible nitric oxide synthase (NOS2) and exposure to residential traffic independently influence FeNO level. Because NOS2 is inducible by environmental exposures such as traffic-related exposure, we tested the hypothesis that common NOS2 promoter haplotypes modulate the relationship between residential traffic-related exposure and FeNO level in children. METHODS:In a cross-sectional population-based study, subjects (N = 2,457; 7-11 year-old) were Hispanic and non-Hispanic white children who participated in the Southern California Children's Health Study and had FeNO measurements. For residential traffic, lengths of local roads within circular buffers (50m, 100m and 200m radii around homes) around the subjects' homes were estimated using geographic information system (GIS) methods. We interrogated the two most common NOS2 promoter haplotypes that were found to affect FeNO level. RESULTS:The relationship between local road lengths within 100m and 200m circular buffers and FeNO level varied significantly by one of the NOS2 promoter haplotypes (P-values for interaction between road length and NOS2 promoter haplotype = 0.02 and 0.03, respectively). In children who had ?250m of local road lengths within 100m buffer around their homes, those with two copies of the haplotype had significantly lower FeNO (adjusted geometric mean = 11.74ppb; 95% confidence intervals (CI): 9.99 to 13.80) than those with no copies (adjusted geometric mean = 15.28ppb; 95% CI: 14.04 to 16.63) with statistically significant trend of lower FeNO level with increasing number of haplotype copy (P-value for trend = 0.002). In contrast, among children who had >250m of local road lengths within 100m buffer, FeNO level did not significantly differ by the haplotype copy-number (P-value for trend = 0.34). Similar interactive effects of this haplotype and local road lengths within 200m buffer on FeNO were also observed. CONCLUSIONS:Higher exposure from residential traffic nullifies the protective effect of one common NOS2 promoter haplotype on FeNO level. Regulation of traffic-related pollution may protect children's respiratory health.
| S-EPMC4695093 | biostudies-literature
Project description:The fractional concentration of nitric oxide in exhaled air (FeNO) potentially detects airway inflammation related to air pollution exposure. Existing studies have not yet provided conclusive evidence on the association of FeNO with traffic-related pollution (TRP).We evaluated the association of FeNO with residential TRP exposure in a large cohort of children.We related FeNO measured on 2,143 children (ages 7-11 years) who participated in the Southern California Children's Health Study (CHS) to five classes of metrics of residential TRP: distances to freeways and major roads; length of all and local roads within circular buffers around the home; traffic densities within buffers; annual average line source dispersion modeled nitrogen oxides (NOx) from freeways and nonfreeway roads; and predicted annual average nitrogen oxide, nitrogen dioxide, and NOx from a model based on intracommunity sampling in the CHS.In children with asthma, length of roads was positively associated with FeNO, with stronger associations in smaller buffers [46.7%; 95% confidence interval (CI), 14.3-88.4], 12.4% (95% CI, -8.8 to 38.4), and 4.1% (95% CI, -14.6 to 26.8) higher FeNO for 100-, 300-, and 1,000-m increases in the length of all roads in 50-, 100-, and 200-m buffers, respectively. Other TRP metrics were not significantly associated with FeNO, even though the study design was powered to detect exposures explaining as little as 0.4% of the variation in natural log-transformed FeNO (R2 = 0.004).Length of road was the only indicator of residential TRP exposure associated with airway inflammation in children with asthma, as measured by FeNO.
| S-EPMC3230449 | biostudies-other
Project description:BackgroundTraffic-related air pollution (TRAP) has been associated with increased risk of airway inflammation in children with asthma. While epigenetic changes could potentially modulate TRAP-induced inflammatory responses, few studies have assessed the temporal pattern of exposure to TRAP, epigenetic changes and inflammation in children with asthma. Our goal was to test the time-lag patterns of personal exposure to TRAP, airway inflammation (measured as fractional exhaled nitric oxide, FeNO), and DNA methylation in the promoter regions of genes involved in nitric oxide synthesis among children with asthma.MethodsWe measured personal exposure to black carbon (BC) and FeNO for up to 30 days in a panel of children with asthma. We collected 90 buccal cell samples for DNA methylation analysis from 18 children (5 per child). Methylation in promoter regions of nitric oxide synthase (NOS1, NOS2A, NOS3) and arginase (ARG1, ARG2) was assessed by bisulfite pyrosequencing. Linear-mixed effect models were used to test the associations of BC at different lag periods, percent DNA methylation at each site and FeNO level.ResultsExposure to BC was positively associated with FeNO, and negatively associated with DNA methylation in NOS3. We found strongest association between FeNO and BC at lag 0-6 h while strongest associations between methylation at positions 1 and 2 in NOS3 and BC were at lag 13-24 h and lag 0-24 h, respectively. The strengths of associations were attenuated at longer lag periods. No significant associations between exposure to TRAP and methylation levels in other NOS and ARG isoforms were observed.ConclusionsExposure to TRAP was associated with higher levels of FeNO and lower levels of DNA methylation in the promoter regions of the NOS3 gene, indicating that DNA methylation of the NOS3 gene could be an important epigenetic mechanism in physiological responses to TRAP in children with asthma.
| S-EPMC7879528 | biostudies-literature
Project description:To assess the effects of long-term variations in ambient air pollutants on longitudinal changes in exhaled nitric oxide (FeNO), a potentially useful biomarker of eosinophilic airway inflammation, based on data from the southern California Children's Health Study.Based on a cohort of 1211 schoolchildren from eight Southern California communities with FeNO measurements in 2006-2007 and 2007-2008, regression models adjusted for short-term effects of air pollution were fitted to assess the association between changes in annual long-term exposures and changes in FeNO.Increases in annual average concentrations of 24-h average NO2 and PM2.5 (scaled to the IQR of 1.8?ppb and 2.4??g/m(3), respectively) were associated with a 2.29?ppb (CI 0.36 to 4.21; p=0.02) and a 4.94?ppb (CI 1.44 to 8.47; p=0.005) increase in FeNO, respectively, after adjustments for short-term effects of the respective pollutants. In contrast, changes in annual averages of PM10 and O3 were not significantly associated with changes in FeNO. These findings did not differ significantly by asthma status.Changes in annual average exposure to current levels of ambient air pollutants are significantly associated with changes in FeNO levels in children, independent of short-term exposures and asthma status. Use of this biomarker in population-based epidemiological research has great potential for assessing the impact of changing real world mixtures of ambient air pollutants on children's respiratory health.
| S-EPMC4310696 | biostudies-literature
Project description:Mechanisms for the adverse respiratory effects of traffic-related air pollution (TRAP) have yet to be established. We evaluated the acute effects of TRAP exposure on proximal and distal airway inflammation by relating indoor nitric oxide (NO), a marker of TRAP exposure in the indoor microenvironment, to airway and alveolar sources of exhaled nitric oxide (FeNO).FeNO was collected online at four flow rates in 1635 schoolchildren (aged 12-15 years) in southern California (USA) breathing NO-free air. Indoor NO was sampled hourly and linearly interpolated to the time of the FeNO test. Estimated parameters quantifying airway wall diffusivity (DawNO) and flux (J'awNO) and alveolar concentration (CANO) sources of FeNO were related to exposure using linear regression to adjust for potential confounders.We found that TRAP exposure indoors was associated with elevated alveolar NO. A 10 ppb higher indoor NO concentration at the time of the FeNO test was associated with 0.10 ppb higher average CANO (95% CI 0.04-0.16) (equivalent to a 7.1% increase from the mean), 4.0% higher J'awNO (95% CI -2.8-11.3) and 0.2% lower DawNO (95% CI -4.8-4.6).These findings are consistent with an airway response to TRAP exposure that was most marked in the distal airways.
| S-EPMC5402887 | biostudies-literature
Project description:We assessed the effect of daily variations in ambient air pollutants on exhaled nitric oxide fraction (F(eNO)) using data from a cohort of school children with large differences in air pollutant exposures from the Children's Health Study. Based on a cohort of 2,240 school children from 13 Southern Californian communities, cumulative lagged average regression models were fitted to determine the association between F(eNO) and ambient air pollution levels from central site monitors with lags of up to 30 days prior to F(eNO) testing. Daily 24-h cumulative lagged averages of particles with a 50% cut-off aerodynamic diameter of 2.5 µm (PM₂.₅; over 1-8 days) and particles with a 50% cut-off aerodynamic diameter of 10 µm (PM₁₀; over 1-7 days), as well as 10:00-18:00 h cumulative lagged average of O₃ (over 1-23 days) were significantly associated with 17.42% (p<0.01), 9.25% (p<0.05) and 14.25% (p<0.01) higher F(eNO) levels over the interquartile range of 7.5 μg·m⁻³, 12.97 μg·m⁻³ and 15.42 ppb, respectively. The effects of PM₂.₅, PM₁₀ and O₃ were higher in the warm season. The particulate matter effects were robust to adjustments for effects of O₃ and temperature and did not vary by asthma or allergy status. In summary, short-term increases in PM₂.₅, PM₁₀ and O₃ were associated with airway inflammation independent of asthma and allergy status, with PM₁₀ effects significantly higher in the warm season.
| S-EPMC4340653 | biostudies-literature
Project description:BackgroundResearch has shown associations between pediatric asthma outcomes and airborne particulate matter (PM). The importance of particle components remains to be determined.MethodsWe followed a panel of 45 schoolchildren with persistent asthma living in Southern California. Subjects were monitored over 10 days with offline fractional exhaled nitric oxide (FeNO), a biomarker of airway inflammation. Personal active sampler exposures included continuous particulate matter < 2.5 microm in aerodynamic diameter (PM2.5), 24-hr PM2.5 elemental and organic carbon (EC, OC), and 24-hr nitrogen dioxide. Ambient exposures included PM2.5, PM2.5 EC and OC, and NO2. Data were analyzed with mixed models controlling for personal temperature, humidity and 10-day period.ResultsThe strongest positive associations were between FeNO and 2-day average pollutant concentrations. Per interquartile range pollutant increase, these were: for 24 microg/m3 personal PM2.5, 1.1 ppb FeNO [95% confidence interval (CI), 0.1-1.9]; for 0.6 microg/m3 personal EC, 0.7 ppb FeNO (95% CI, 0.3-1.1); for 17 ppb personal NO2, 1.6 ppb FeNO (95% CI, 0.4-2.8). Larger associations were found for ambient EC and smaller associations for ambient NO2. Ambient PM2.5 and personal and ambient OC were significant only in subjects taking inhaled corticosteroids (ICS) alone. Subjects taking both ICS and antileukotrienes showed no significant associations. Distributed lag models showed personal PM2.5 in the preceding 5 hr was associated with FeNO. In two-pollutant models, the most robust associations were for personal and ambient EC and NO2, and for personal but not ambient PM2.5.ConclusionPM associations with airway inflammation in asthmatics may be missed using ambient particle mass, which may not sufficiently represent causal pollutant components from fossil fuel combustion.
| S-EPMC1665398 | biostudies-literature
Project description:Household air pollution is estimated to be responsible for nearly three million premature deaths annually. Measuring fractional exhaled nitric oxide (FeNO) may improve the limited understanding of the association of household air pollution and airway inflammation. We evaluated the cross-sectional association of FeNO with exposure to household air pollution (24-h average kitchen and personal fine particulate matter and black carbon; stove type) among 139 women in rural Honduras using traditional stoves or cleaner-burning Justa stoves. We additionally evaluated interaction by age. Results were generally consistent with a null association; we did not observe a consistent pattern for interaction by age. Evidence from ambient and household air pollution regarding FeNO is inconsistent, and may be attributable to differing study populations, exposures, and FeNO measurement procedures (e.g., the flow rate used to measure FeNO).
| S-EPMC6267103 | biostudies-literature
Project description:BackgroundInducible nitric oxide synthase (iNOS; encoded by nitric oxide synthase isoform 2 [NOS2]) is the major enzyme for nitric oxide synthesis in airways. As such, measurement of fractional concentration of exhaled nitric oxide (Feno) provides an in vivo assessment of iNOS activity. Short-term exposure to air pollution, haplotypes, and DNA methylation in the NOS2 promoter has been associated independently with iNOS expression, Feno levels, or both.ObjectiveWe aimed to examine the effects of ambient air pollutants, NOS2 promoter haplotypes, and NOS2 promoter methylation on Feno levels in children.MethodsWe selected 940 participants in the Children's Health Study who provided buccal samples and had undergone Feno measurement on the same day. DNA methylation was measured with a bisulfite-PCR Pyrosequencing assay. Seven single nucleotide polymorphisms captured the haplotype diversity in the NOS2 promoter. Average particulate matter with an aerodynamic diameter of 2.5 ?m or less (PM(2.5)) and 10 ?m (PM(10)) or less and ozone and nitrogen dioxide levels 7 days before Feno measurement were estimated based on air pollution data obtained at central monitoring sites.ResultsWe found interrelated effects of PM(2.5), NOS2 promoter haplotypes, and iNOS methylation on Feno levels. Increased 7-day average PM(2.5) exposure was associated with lower iNOS methylation (P = .01). NOS2 promoter haplotypes were globally associated with NOS2 promoter methylation (P = 6.2 × 10(-8)). There was interaction among 1 common promoter haplotype, iNOS methylation level, and PM(2.5) exposure on Feno levels (P(interaction) = .00007).ConclusionPromoter variants in NOS2 and short-term PM(2.5) exposure affect iNOS methylation. This is one of the first studies showing contributions of genetic and epigenetic variations in air pollution-mediated phenotype expression.
| S-EPMC3487398 | biostudies-literature
Project description:The consequences of air pollution pose one of the most serious threats to human health, and especially impact children from large agglomerations. The measurement of nitric oxide concentration in exhaled air (FeNO) is a valuable biomarker in detecting and monitoring airway inflammation. However, only a few studies have assessed the relationship between FeNO and the level of air pollution. The study aims to estimate the concentration of FeNO in the population of children aged 8-9 attending the third grade of public primary schools in Krakow, as well as to determine the relationship between FeNO concentration and dust and gaseous air pollutants. The research included 4580 children aged 8-9 years who had two FeNO measurements in the winter-autumn and spring-summer periods. The degree of air pollution was obtained from the Regional Inspectorate of Environmental Protection in Krakow. The concentration of pollutants was obtained from three measurement stations located in different parts of the city. The FeNO results were related to air pollution parameters. The study showed weak but significant relationships between FeNO and air pollution parameters. The most significant positive correlations were found for CO8h (r = 0.1491, p < 0.001), C6H6 (r = 0.1420, p < 0.001), PM10 (r = 0.1054, p < 0.001) and PM2.5 (r = 0.1112, p < 0.001). We suggest that particulate and gaseous air pollutants impact FeNO concentration in children aged 8-9 years. More research is needed to assess the impact of air pollution on FeNO concentration in children. The results of such studies could help to explain the increase in the number of allergic and respiratory diseases seen in children in recent decades.
| S-EPMC8296872 | biostudies-literature