Leticia Hernández-Cadena

Air pollution, airway inflammation, and lung function in a cohort study of Mexico City schoolchildren.

Background The biological mechanisms involved in inflammatory response to air pollution are not clearly understood. Objective In this study we assessed the association of short-term air pollutant exposure with inflammatory markers and lung function. Methods We studied a cohort of 158 asthmatic and 50 nonasthmatic school-age children, followed an average of 22 weeks. We conducted spirometric tests, measurements of fractional exhaled nitric oxide (FeNO), interleukin-8 (IL-8) in nasal lavage, and pH of exhaled breath condensate every 15 days during follow-up. Data were analyzed using linear mixed-effects models. Results An increase of 17.5 μg/m3 in the 8-hr moving average of PM2.5 levels (interquartile range) was associated with a 1.08-ppb increase in FeNO [95% confidence interval (CI), 1.01–1.16] and a 1.07-pg/mL increase in IL-8 (95% CI 0.98–1.19) in asthmatic children and a 1.16 pg/ml increase in IL-8 (95% CI, 1.00–1.36) in nonasthmatic children. The 5-day accumulated average of exposure to particulate matter < 2.5 μm in aerodynamic diamter (PM2.5) was significantly inversely associated with forced expiratory volume in 1 sec (FEV1) (p = 0.048) and forced vital capacity (FVC) (p = 0.012) in asthmatic children and with FVC (p = 0.021) in nonasthmatic children. FeNO and FEV1 were inversely associated (p = 0.005) in asthmatic children. Conclusions Exposure to PM2.5 resulted in acute airway inflammation and decrease in lung function in both asthmatic and nonasthmatic children.

Traffic-related air pollution and respiratory symptoms among asthmatic children, resident in Mexico City: the EVA cohort study

BackgroundTaffic-related air pollution has been related to adverse respiratory outcomes; however, there is still uncertainty concerning the type of vehicle emission causing most deleterious effects.MethodsA panel study was conducted among 147 asthmatic and 50 healthy children, who were followed up for an average of 22 weeks. Incidence density of coughing, wheezing and breathing difficulty was assessed by referring to daily records of symptoms and childs medication. The association between exposure to pollutants and occurrence of symptoms was evaluated using mixed-effect models with binary response and poisson regression.ResultsWheezing was found to relate significantly to air pollutants: an increase of 17.4 μg/m3 (IQR) of PM2.5 (24-h average) was associated with an 8.8% increase (95% CI: 2.4% to 15.5%); an increase of 34 ppb (IQR) of NO2 (1-h maximum) was associated with an 9.1% increase (95% CI: 2.3% to16.4%) and an increase of 48 ppb (IQR) in O3 levels (1 hr maximum) to an increase of 10% (95% CI: 3.2% to 17.3%). Diesel-fueled motor vehicles were significantly associated with wheezing and bronchodilator use (IRR = 1.29; 95% CI: 1.03 to 1.62, and IRR = 1.32; 95% CI: 0.99 to 1.77, respectively, for an increase of 130 vehicles hourly, above the 24-hour average).ConclusionRespiratory symptoms in asthmatic children were significantly associated with exposure to traffic exhaust, especially from natural gas and diesel-fueled vehicles.

Dietary intake, lung function and airway inflammation in Mexico City school children exposed to air pollutants.

IntroductionAir pollutant exposure has been associated with an increase in inflammatory markers and a decline in lung function in asthmatic children. Several studies suggest that dietary intake of fruits and vegetables might modify the adverse effect of air pollutants.MethodsA total of 158 asthmatic children recruited at the Childrens Hospital of Mexico and 50 non-asthmatic children were followed for 22 weeks. Pulmonary function was measured and nasal lavage collected and analyzed every 2 weeks. Dietary intake was evaluated using a 108-item food frequency questionnaire and a fruit and vegetable index (FVI) and a Mediterranean diet index (MDI) were constructed. The impact of these indices on lung function and interleukin-8 (IL-8) and their interaction with air pollutants were determined using mixed regression models with random intercept and random slope.ResultsFVI was inversely related to IL-8 levels in nasal lavage (p < 0.02) with a significant inverse trend (test for trend p < 0.001), MDI was positively related to lung function (p < 0.05), and children in the highest category of MDI had a higher FEV1 (test for trend p < 0.12) and FVC (test for trend p < 0.06) than children in the lowest category. A significant interaction was observed between FVI and ozone for FEV1 and FVC as was with MDI and ozone for FVC. No effect of diet was observed among healthy children.ConclusionOur results suggest that fruit and vegetable intake and close adherence to the Mediterranean diet have a beneficial effect on inflammatory response and lung function in asthmatic children living in Mexico City.

Environmental polycyclic aromatic hydrocarbon (PAH) exposure and DNA damage in Mexican children.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants presenting a public health risk, particularly to children, a vulnerable population. PAHs have genotoxic and carcinogenic properties, which depend on their metabolism. Many enzymes involved in PAH metabolism, including CYP1A1, CYP1B1, GSTM and GSTT are polymorphic, which may modulate the activation/deactivation of these compounds. We evaluated PAH exposure and DNA damage in children living in the vicinity of the main petrochemical complex located in the Gulf of Mexico, and explored the modulation by genetic polymorphisms of PAH excretion and related DNA damage. The participants (n=82) were children aged 6-10y attending schools near the industrial area. Urinary 1-hydroxypyrene (1-OHP; a biomarker of PAH exposure) was determined by reverse-phase-HPLC; DNA damage by the comet assay (Olive Tail Moment (OTM) parameter); CYP1A1*2C and CYP1B1*3 polymorphisms by real time-PCR; and GSTM1*0 and GSTT1*0 by multiplex PCR. The median value of 1-OHP was 0.37μmol/mol creatinine; 59% of children had higher 1-OHP concentrations than those reported in environmentally exposed adults (0.24μmol/mol creatinine). A stratified analysis showed increased DNA damage in children with 1-OHP concentrations greater than the median value. We observed higher 1-OHP concentrations in children with CYP1A1*2C or GSTM1*0 polymorphisms, and a positive influence of CYP1A1*2C on OTM values in children with the highest PAH exposure. The data indicate that children living in the surroundings of petrochemical industrial areas are exposed to high PAH levels, contributing to DNA damage and suggesting an increased health risk; furthermore, data suggest that polymorphisms affecting activation enzymes may modulate PAH metabolism and toxicity.

Biological markers of fetal lead exposure at each stage of pregnancy.

It has been suggested that plasma lead (Pb) represents the fraction of circulating Pb that crosses the placenta. Whole-blood Pb levels, the conventional method for measuring circulating Pb, may not adequately reflect plasma Pb levels. The objective of this study was to assess the relationship between whole-blood and plasma Pb in a cohort of pregnant women. A group of 237 pregnant women, recruited in Mexico City from 1997 to 1999, was studied. whole-blood and plasma lead concentrations were evaluated at 12, 24, and 34 wk of gestation by inductively coupled plasma–mass spectrometry. Data were analyzed using a mixed-effects regression model. An exponential relationship was found between plasma and whole-blood Pb levels and significant modification of the association by stage of pregnancy. The association was stronger in the second trimester relative to the first, and it further increased in the third trimester. The model predicts increased plasma Pb levels for a given whole-blood Pb value as pregnancy advances for whole-blood Pb levels greater than ∼110 µg/L, but not for blood Pb levels less than 100 µg/L. These findings could be due to physiologic changes during pregnancy, such as decreasing hematocrit, saturation of red cell Pb binding capacity, and increased bone resorption or intestinal absorption. Collectively, these data suggest that at elevated maternal blood Pb levels the developing fetus may be at greater risk of Pb exposure from increased maternal plasma Pb than otherwise predicted from whole-blood Pb levels.

Genome-wide interaction studies reveal sex-specific asthma risk alleles

Asthma is a complex disease with sex-specific differences in prevalence. Candidate gene studies have suggested that genotype-by-sex interaction effects on asthma risk exist, but this has not yet been explored at a genome-wide level. We aimed to identify sex-specific asthma risk alleles by performing a genome-wide scan for genotype-by-sex interactions in the ethnically diverse participants in the EVE Asthma Genetics Consortium. We performed male- and female-specific genome-wide association studies in 2653 male asthma cases, 2566 female asthma cases and 3830 non-asthma controls from European American, African American, African Caribbean and Latino populations. Association tests were conducted in each study sample, and the results were combined in ancestry-specific and cross-ancestry meta-analyses. Six sex-specific asthma risk loci had P-values < 1 × 10(-6), of which two were male specific and four were female specific; all were ancestry specific. The most significant sex-specific association in European Americans was at the interferon regulatory factor 1 (IRF1) locus on 5q31.1. We also identify a Latino female-specific association in RAP1GAP2. Both of these loci included single-nucleotide polymorphisms that are known expression quantitative trait loci and have been associated with asthma in independent studies. The IRF1 locus is a strong candidate region for male-specific asthma susceptibility due to the association and validation we demonstrate here, the known role of IRF1 in asthma-relevant immune pathways and prior reports of sex-specific differences in interferon responses.

Elemental carbon exposure and lung function in schoolchildren from Mexico City

Though exposure to air pollution has a detrimental effect on respiratory health, few studies have examined the association between elemental carbon exposure and lung function among schoolchildren. The aim of the present study was to present the association between short-term elemental carbon exposure and lung function in schoolchildren from Mexico City. 55 asthmatic and 40 non-asthmatic children were followed for an average of 22 weeks. A spirometry test was performed every 15 days during follow-up. Portable air samplers collected particulate matter onto Teflon filters. Gravimetric analysis was conducted and elemental carbon was quantified using transmission densitometry. The association between the main variables was analysed using linear mixed effects models. The mean±sd of elemental carbon light absorption was 92.7±54.7 Mm−1. An increase of one interquartile range in the 24-h average of elemental carbon (100.93 Mm−1) was associated with a significant negative impact on forced expiratory volume in 1 s (FEV1) (-62.0 (95% CI -123.3– -1.2) mL) and forced expiratory flow at 25–75% of forced vital capacity (FVC) (FEF25–75%) (-111 (95% CI -228.3– -4.1) mL) among asthmatic children, equal to 3.3% and 5.5%, respectively; and on FEV1 (-95.0 (95% CI -182.3– -8.5) mL) and FVC (-105.0 (95% CI -197.0– -13.7) mL) among non-asthmatic children. Exposure to elemental carbon resulted in an important negative effect on lung function in atopic schoolchildren, regardless of asthma status.

Relación entre consultas a urgencias por enfermedad respiratoria y contaminación atmosférica en Ciudad Juárez, Chihuahua

Objective. To assess the relationship of ≤10 μm particles (PM 10 ) and atmospheric ozone concentrations, with the daily number of emergency visits due to asthma and acute respiratory diseases, among children aged under 15, living in Ciudad Juarez, Chihuahua, Mexico. Material and methods. Between 1998 and 1999, an ecologic study was conducted. Atmospheric data were obtained from the Environmental Protection Agency (EPA), from eight monitoring stations located in Ciudad Juarez, Chihuahua, and El Paso,

High dietary calcium intake decreases bone mobilization during pregnancy in humans

UNLABELLED Calcium metabolism of the mother is modified during pregnancy because of the mineralization of the fetus skeleton. OBJECTIVE To evaluate the association of calcium intake and bone demineralization during pregnancy. MATERIAL AND METHODS At each trimester of pregnancy a validated food frequency intake questionnaire was administered to assess individual daily calcium intake in a cohort of 206 pregnant women, residents of Mexico City. Samples of urine were collected to measure levels of the cross-linked N-telopeptide of type I collagen (NTx), which is a biomarker of bone resorption. The association between calcium ingestion and bone resorption was analyzed using random effects models; non-linear associations were explored using generalized additive models. RESULTS Progressive increases in NTx levels were observed during pregnancy; with mean and standard deviation (SD) values during the first, second and third trimester of 76.50 (SD=38), 101.02 (SD=48.86) and 144.83 (SD=61.33) nmol BCE/mmol creatinine, respectively. Higher dietary calcium intake was associated with lower bone resorption (beta=-0.015; p<0.05). The association between age and NTx showed a non-linear trend with an inflexion point around 33 years: increase in maternal age below that point was associated with a decrease in bone resorption, while in older women the increase in age was associated with an increased resorption. CONCLUSIONS Our results suggest that calcium ingestion, specifically from dairy products, reduces bone resorption during pregnancy. For each 300 mg (a glass of milk) of calcium intake there is an estimated reduction in NTx level of 4.8 nmol BCE/mmol of creatinine (p<0.05).

Increased levels of outdoor air pollutants are associated with reduced bronchodilation in children with asthma.

BACKGROUND Increased outdoor air pollution levels are associated with more frequent use of rescue inhalers in subjects with asthma. However, it is unknown whether this phenomenon is explained by an air pollution-mediated increase in respiratory symptom severity or whether air pollutants decrease the efficacy of short-acting beta-agonists (SABAs). METHODS We examined the relationship between the percentage change in FEV(1) after SABA use with outdoor air pollution exposure in 85 children with asthma who were 7 to 12 years of age. Outdoor air pollution exposure was determined by measuring nitrogen dioxide (NO(2)), ozone (O(3)), and fine particulate matter (ie, particulate matter with an aerodynamic diameter < 2.5 microm [PM(2.5)]) levels. These measurements were obtained from the Mexico City Automated Monitoring Network from network sites located within a 5-km radius of each childs home and school. RESULTS We found that a same-day interquartile increase of 10 parts per billion (ppb) in NO(2) concentration was associated with a reduced response of FEV(1) to SABA therapy (-15%; 95% CI, -29 to -0.5). This association was also significant when considering NO(2) levels in each of the preceding 3 days. An interquartile O(3) increase (16 ppb) in the preceding fifth day was associated with a reduced response to SABA (-11%; 95% CI, -23 to -1); an interquartile PM(2.5) increase (14 microg/m(3)) was not associated with any significant reductions in the response to SABA therapy. These associations were not observed in children receiving therapy with inhaled corticosteroids. CONCLUSIONS Our results suggest that recent exposure to NO(2) and possibly O(3) may reduce the response to SABAs in producing bronchodilation in children with asthma. The association between NO(2) and FEV(1) response to SABA administration may have important implications in understanding how outdoor air pollution levels relate to asthma control.