Ozone exposure, vitamin C intake, and genetic susceptibility of asthmatic children in Mexico City: a cohort study.

BACKGROUND: We previously reported that asthmatic children with GSTM1 null genotype may be more susceptible to the acute effect of ozone on the small airways and might benefit from antioxidant supplementation. This study aims to assess the acute effect of ozone on lung function (FEF(25-75)) in asthmatic children according to dietary intake of vitamin C and the number of putative risk alleles in three antioxidant genes: GSTM1, GSTP1 (rs1695), and NQO1 (rs1800566). METHODS: 257 asthmatic children from two cohort studies conducted in Mexico City were included. Stratified linear mixed models with random intercepts and random slopes on ozone were used. Potential confounding by ethnicity was assessed. Analyses were conducted under single gene and genotype score approaches. RESULTS: The change in FEF(25-75) per interquartile range (60 ppb) of ozone in persistent asthmatic children with low vitamin C intake and GSTM1 null was -91.2 ml/s (p = 0.06). Persistent asthmatic children with 4 to 6 risk alleles and low vitamin C intake showed an average decrement in FEF(25-75) of 97.2 ml/s per 60 ppb of ozone (p = 0.03). In contrast in children with 1 to 3 risk alleles, acute effects of ozone on FEF25-75 did not differ by vitamin C intake. CONCLUSIONS: Our results provide further evidence that asthmatic children predicted to have compromised antioxidant defense by virtue of genetic susceptibility combined with deficient antioxidant intake may be at increased risk of adverse effects of ozone on pulmonary function.

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 (Fe(NO)), 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 microg/m(3) in the 8-hr moving average of PM(2.5) levels (interquartile range) was associated with a 1.08-ppb increase in Fe(NO) [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 microm in aerodynamic diamter (PM(2.5)) was significantly inversely associated with forced expiratory volume in 1 sec (FEV(1)) (p=0.048) and forced vital capacity (FVC) (p=0.012) in asthmatic children and with FVC (p=0.021) in nonasthmatic children. Fe(NO) and FEV(1) were inversely associated (p=0.005) in asthmatic children. CONCLUSIONS: Exposure to PM(2.5) 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.

BACKGROUND: Taffic-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. METHODS: A 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 child's medication. The association between exposure to pollutants and occurrence of symptoms was evaluated using mixed-effect models with binary response and poisson regression. RESULTS: Wheezing was found to relate significantly to air pollutants: an increase of 17.4 microg/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% to 16.4%) 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). CONCLUSION: Respiratory symptoms in asthmatic children were significantly associated with exposure to traffic exhaust, especially from natural gas and diesel-fueled vehicles.

Effect of Personal Exposure to PM2.5 on Respiratory Health in a Mexican Panel of Patients with COPD.

BACKGROUND: Air pollution is a problem, especially in developing countries. We examined the association between personal exposure to particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) on respiratory health in a group of adults with chronic obstructive pulmonary disease (COPD). METHODS: All participants resided in Mexico City and during follow-up, personal exposure to PM2.5, respiratory symptoms, medications, and daily activity were registered daily. Peak expiratory flow (PEF) was measured twice daily, from February through December, 2000, in 29 adults with moderate, severe, and very severe COPD. PEF changes were estimated for each 10 µg/m³ increment of PM2.5, adjustment for severity of COPD, minimum temperature, and day of the sampling. RESULTS: For a 10-µg/m³ increase in the daily average of a two-day personal exposure to PM2.5, there was a significant 33% increase in cough (95% CI, range, 5-69%), and 23% in phlegm (95% CI, range, 2-54%), a reduction of the PEF average in the morning of -1.4 L/min. (95% CI , range, -2.8 to -0.04), and at night of -3.0 L/min (95% CI, range, -5.7 to -0.3), respectively. CONCLUSIONS: Exposure to PM2.5 was associated with reductions in PEF and increased respiratory symptoms in adults with COPD. The PEF reduction was observed both at morning and at night.

Infant mortality and air pollution: modifying effect by social class.

UNLABELLED: Studies link air pollution with increased mortality; however, information on infants is scarce and inconclusive. OBJECTIVE: We studied short-term PM10 exposure, relating to increased respiratory-related infant mortality, and estimated for poor living conditions. METHODS: A case-crossover approach modeled the relationship between infant mortality (1 month-1 year of age), and ambient PM10 levels on days before death in Ciudad Juarez, Mexico (1997-2001). Socioeconomic level (SES) of the deceased was defined by residence location. RESULTS: Overall air pollutants did not affect infant mortality (odds ratio [OR] = 1.02, 95% confidence interval [CI] = 0.94-1.11 for PM10, lag1) but low SES increased risk. Each 20 microg/m3 in PM10 (24-hour average, lag1, cumulative over 2 previous days) increased respiratory-related mortality (OR = 1.61, 95% CI = 0.97-2.66; OR = 2.56; 95% CI = 1.06-6.17, respectively). Ozone levels did not affect infant mortality for any SES. CONCLUSIONS: Worse living conditions among lower SES concurred with increased mortality.

Measurements of personal exposure to nitrogen dioxide in four Mexican cities in 1996.

Nitrogen dioxide is a ubiquitous pollutant in urban areas. Indoor NO2 concentrations are influenced by penetration of outdoor concentrations and by indoor sources. The objectives of this study were to evaluate personal exposure to NO2, taking into account human time-activity patterns in four Mexican cities. Passive filter badges were used for indoor, outdoor, and personal NO2 measurements over 48 hr and indoor workplace measurements over 16 hr. Volunteers completed a questionnaire on exposure factors and a time-activity diary during the sample period. An unpaired t test, an analysis of variance (ANOVA), and a linear regression were performed to compare differences among cities and mean personal NO2 concentrations involving housing characteristics, as well as to determine which variables predicted the personal NO2 concentration. Sampling periods were in April, May, and June 1996 in Mexico City, Guadalajara, Cuernavaca, and Monterrey. All 122 volunteers in the study were working adults, with a mean age of 34 (SD +/- 7.38); 64% were female, and the majority worked in public offices and universities. The highest NO2 concentrations were found in Mexico City (36 ppb for outdoor, 57 ppb for indoor, and 39 ppb for personal concentration) and the lowest in Monterrey (19 ppb for outdoor, 24 ppb for indoor, and 24 ppb for personal concentration). Significant differences in NO2 concentrations were found among the cities in different microenvironments. During the sampling period, volunteers spent 85% of their time indoors. The highest personal NO2 concentration was found when volunteers kept their windows closed (p = 0.03). In the regression model adjusted by city and gender, the best predictors of personal NO2 concentration were outdoor levels and time spent outdoors (R2 = 0.68). These findings suggest that outdoor NO2 concentrations were an important influence on the personal exposure to NO2, due to the specific characteristics and personal behavior of the people in these Mexican cities.

Ozone exposure among Mexico City outdoor workers.

In researching health effects of air pollution, pollutant levels from fixed-site monitors are commonly assigned to the subjects. However, these concentrations may not reflect the exposure these individuals actually experience. A previous study of ozone (O3) exposure and lung function among shoe-cleaners working in central Mexico City used fixed-site measurements from a monitoring station near the outdoor work sites as surrogates for personal exposure. The present study assesses the degree to which these estimates represented individual exposures. In 1996, personal O3 exposures of 39 shoe-cleaners working outdoors were measured using an active integrated personal sampler. Using mixed models, we assessed the relationship between measured personal O3 exposure and ambient O3 measurements from the fixed-site monitoring station. Ambient concentrations were approximately 50 parts per billion higher, on average, than personal exposures. The association between personal and ambient O3 was highly significant (mixed model slope p < 0.0001). The personal/ambient ratio was not constant, so use of the outdoor monitor would not be appropriate to rank O3 exposure and evaluate health effects between workers. However, the strong within-worker longitudinal association validates previous findings associating day-to-day changes in fixed-site O3 levels with adverse health effects among these shoe-cleaners and suggests fixed-site O3 monitors may adequately estimate exposure for other repeated-measure health studies of outdoor workers.

Assessment of personal exposure to ozone in asthmatic children residing in Mexico City.

OBJECTIVE: A study was conducted to evaluate personal ozone exposure (O3p) among asthmatic children residing in Mexico City. MATERIAL AND METHODS: A total of 158 children were recruited from December 1998 to April 2000. On average, three O3p measurements were obtained per child using passive badges. Time-activity patterns were recorded in a diary. Daily ambient ozone measurements (O3a) were obtained from the fixed station, according to children's residence. Levels of O3a and ozone, weighted by time spent in different micro-environments (O3w), were used as independent variables in order to model O3p concentrations using a mixed-effects model. RESULTS: Mean O3p was 7.8 ppb. The main variables in the model were: time spent indoors, distance between residence and fixed station, follow-up group, and two interaction terms (overall R(2)=0.50, p<0.05). CONCLUSIONS: The O3w concentrations can be used as a proxy for O3p, taking into account time-activity patterns and the place of residence of asthmatic Mexican children.

International study of temperature, heat and urban mortality: the 'ISOTHURM' project.

BACKGROUND: This study describes heat- and cold-related mortality in 12 urban populations in low- and middle-income countries, thereby extending knowledge of how diverse populations, in non-OECD countries, respond to temperature extremes. METHODS: The cities were: Delhi, Monterrey, Mexico City, Chiang Mai, Bangkok, Salvador, São Paulo, Santiago, Cape Town, Ljubljana, Bucharest and Sofia. For each city, daily mortality was examined in relation to ambient temperature using autoregressive Poisson models (2- to 5-year series) adjusted for season, relative humidity, air pollution, day of week and public holidays. RESULTS: Most cities showed a U-shaped temperature-mortality relationship, with clear evidence of increasing death rates at colder temperatures in all cities except Ljubljana, Salvador and Delhi and with increasing heat in all cities except Chiang Mai and Cape Town. Estimates of the temperature threshold below which cold-related mortality began to increase ranged from 15 degrees C to 29 degrees C; the threshold for heat-related deaths ranged from 16 degrees C to 31 degrees C. Heat thresholds were generally higher in cities with warmer climates, while cold thresholds were unrelated to climate. CONCLUSIONS: Urban populations, in diverse geographic settings, experience increases in mortality due to both high and low temperatures. The effects of heat and cold vary depending on climate and non-climate factors such as the population disease profile and age structure. Although such populations will undergo some adaptation to increasing temperatures, many are likely to have substantial vulnerability to climate change. Additional research is needed to elucidate vulnerability within populations.

Trends in the prevalence of asthma and other allergic diseases in schoolchildren from Cuernavaca, Mexico.

Several studies suggest that the prevalence of allergic diseases have increased worldwide in recent years. However, in Mexico, those diseases have not been assessed throughout time. The aim of this study was to determine whether there has been a change in the prevalence of childhood asthma, eczema, and atopic rhinitis in Mexican schoolchildren. Following the methodology recommended by the International Study of Asthma and Allergy in Childhood, we performed two cross-sectional assessments (1995/2002) using a standardized questionnaire-based survey answered by the parents of schoolchildren aged 6-8 years and 11-14 years randomly selected from schools in Cuernavaca, Mexico. The prevalence of asthma diagnosed by a doctor was 5.8% (95% CI, 5.2, 6.4) for 1995 versus 9.1% (95% CI, 8.3, 10.0) for 2002, with a greater prevalence in children aged 6-8 years in 2002 (5.7% versus 9.0%). No significant differences were found over time for wheezing in the last 12 months: 7.7% (95% CI, 7.1, 8.4) in 1995 and 8.0% (95% CI, 7.3, 8.8) in 2002. The prevalence of nasal and eye symptoms without colds was slightly higher in 1995 than it was in 2002: 9.9% (95% CI, 9.1, 10.7) versus 8.2% (95% CI, 7.4, 9.0), respectively. The results suggest an increase in the prevalence of asthma diagnosed by a doctor. However, no difference was observed in the prevalence of wheezing in the last 12 months, which may indicate a possible absence of "epidemic asthma" in the city of Cuernavaca among schoolchildren.

[Validity of peak flow record in asthmatic children residing in Mexico City]. / Validez en el registro del pico espiratorio máximo de niños asmáticos de la Ciudad de México.

OBJECTIVE: To determine the concordance between maximum peak expiratory flow records (PEFr) reported by the parents of asthmatic children and the electronic values stored by the AirWatch device (PEFe). MATERIAL AND METHODS: Records of PEF measurements between October 1998 and 1999 were obtained from 42 asthmatic children 5 to 15 years of age recruited at the Hospital Infantil de Mexico Federico Gomez, in Mexico City. Parents recorded the maximum value in the health diary. Spearman correlation was calculated between PEFe and PEFr and a mixed-effects logistic model was used. RESULTS: The correlation between PEFe and PEFr was r=0.96 (p<0.05) among children with a diagnosis of moderate or severe asthma and r=0.40 (p<0.05) among children diagnosed with mild asthma. Follow-up time, asthma severity, gender and age of the child and their interactions were predictors of the differences between PEFe and PEFr. CONCLUSIONS: Parents of children with moderate or severe asthma from 6 to 8 years of age report PEF values with greater accuracy during follow-up than others.

[Infant morbidity caused by respiratory diseases and its relation with the air pollution in Juarez City, Chihuahua, Mexico]. / Morbilidad infantil por causas respiratorias y su relación con la contaminación atmosférica en Ciudad Juárez, Chihuahua, México.

OBJECTIVE: To assess the impact of atmospheric pollutants on the respiratory health of children of different age groups in Juarez City, Chihuahua, Mexico. MATERIAL AND METHODS: Data on emergency room visits between 1997 and 2001 for respiratory diseases in children less than 17 years old were obtained from hospitals in the Juarez City belonging to the Mexican Social Security Institute (IMSS). Diseases were classified into three groups according to ICD 9th and 10th codes: a) upper respiratory diseases, b) lower respiratory diseases, and c) asthma attacks. This information was stratified by age group (< = 5 years and > 5 years). Daily air pollution data (ozone and PM10) and weather conditions were obtained from the Monitoring Network System in Juarez City. Statistical analysis was carried out using a Generalized Additive Model assuming a Poisson distribution. RESULTS: Ozone concentrations, but not PM 10, were statistically associated with emergency room visits for respiratory diseases, mainly among children 5 years old or younger. In this group, an increase of 20 ppb 1-hr maximum for ozone was associated with an increase of 8.3% in the number of emergency room visits for upper respiratory diseases, with a 3-day exposure lag; and an increase of 12.7% in the number of emergency room visits for lower respiratory diseases when considering a 4-day exposure lag in a maximum 8-hr mobile average. The largest effect for the complete sample and for the group 6 to 16 years of age was observed for 3-day lag (5.1% for an increase of 20 ppb 1-hr maximum for ozone). For the 6 to 16 year old group we did not find a significant effect. CONCLUSION: The wide range of risk is quite important and might represent a substantial cost for the health system as well as for the society. Our results emphasize the need to implement preventive and control measures for air pollution and avoid the worsening of the present situation.

Genetic variation in S-nitrosoglutathione reductase (GSNOR) and childhood asthma.

BACKGROUND: S-nitrosothiols are potent endogenous bronchodilators depleted in asthmatic airway lining fluid. S-nitrosoglutathione reductase (GSNOR; also known as alcohol dehydrogenase 5 or formaldehyde dehydrogenase) catalyzes the metabolism of S-nitrosoglutathione (GSNO) and controls intracellular levels of S-nitrosothiols. GSNOR knockout mice have increased lung S-nitrosothiol levels and are therefore protected from airway hyperresponsiveness after methacholine or allergen challenge. OBJECTIVE: We sought to investigate whether genetic variation in GSNOR is associated with childhood asthma and atopy. METHODS: We genotyped 5 tagging and 2 additional single nucleotide polymorphisms (SNPs) in GSNOR in 532 nuclear families consisting of asthmatic children aged 4 to 17 years and both parents in Mexico City. Atopy was determined by means of skin prick testing. RESULTS: Carrying 1 or 2 copies of the minor allele of SNP rs1,154,404 was associated with decreased risk of asthma (relative risk [RR], 0.77; 95% CI, 0.61-0.97; P = .028 for 1 copy and RR, 0.66; 95% CI, 0.44-0.99; P = .046 for 2 copies). Homozygosity for the minor allele of SNP rs28,730,619 was associated with increased risk of asthma (RR, 1.60; 95% CI, 1.13-2.26; P = .0077). Haplotype analyses supported the single SNP findings. GSNOR SNPs were not associated with the degree of atopy. CONCLUSION: This is the first study of genetic polymorphisms in GSNOR and asthma. These data suggest that genetic variation in GSNOR might play a role in asthma susceptibility. CLINICAL IMPLICATIONS: The association of GSNOR polymorphisms with asthma suggests a potential therapeutic target.

Genetic polymorphisms in transforming growth factor beta-1 (TGFB1) and childhood asthma and atopy.

Transforming growth factor beta-1 (TGFB1) may influence asthma by modulating allergic airway inflammation and airway remodeling. The role of single nucleotide polymorphisms (SNPs) of TGFB1 in asthma remains inconclusive. We examined TGFB1 SNPs in relation to asthma risk and degree of atopy among 546 case-parent triads, consisting of asthmatics aged 4-17 years and their parents in Mexico City. Atopy to 24 aeroallergens was determined by skin prick tests. We genotyped five TGFB1 SNPs, including two known functional SNPs [C-509T (rs1800469), T869C (rs1982073)] and three others (rs7258445, rs1800472, rs8179181), using TaqMan and Masscode assays. We analyzed the data using log-linear and polytomous logistic methods. Three associated SNPs, including the two known functional SNPs, were statistically significantly related to asthma risk. Individuals carrying the T allele of C-509T had an increased risk of asthma [relative risk (RR)=1.42, 95% confidence interval (CI)=1.08-1.87 for one copy; RR (95%CI)=1.95 (1.36-2.78) for two copies]. For T869C, the RRs (95%CI) were 1.47 (1.09-1.98) for one and 2.00 (1.38-2.90) for two copies of the C allele. Similar results were found for rs7258445. The haplotype containing all three risk alleles conferred an increased risk of asthma (RR=1.48, 95% CI=1.11-1.95 for one copy; RR=1.77, 95% CI=1.22-2.57 for two copies). These three SNPs were also related to the degree of atopy. This largest study to date of genetic variation in TGFB1 and asthma and atopy adds to increasing evidence for a role in these disorders.

Identification of asthma risk factors in Mexico City in an International Study of Asthma and Allergy in Childhood survey.

The International Study of Asthma and Allergy in Childhood (ISAAC) has assessed the prevalence of asthma, as well as the factors related to the disease in different countries. The aim of this study was to identify asthma risks factors in Mexico City. Data were obtained from questionnaires of children participating in a phase 3b ISAAC survey. Two thousand ninety-eight boys and 2008 girls were recruited in the 6- to 7-year-old group and 3243 boy and 3333 girls were recruited in the 13- to 14-year-old group. Logistic regression was used to determine the asthma risks factors. In the logistic regression for cumulative and current asthma prevalence, the variables allergic rhinitis and atopic dermatitis were the most important risk factors with the highest odds ratios (OR > 1.5; p < 0.05). The use of antibiotics and paracetamol in the first 12 months of life were related to cumulative asthma in both genders in the 6- to 7-year-old group. Contact of pregnant mother with farm animals was positively related with cumulative asthma in boys in the 6- to 7-year-old group. The main factors associated with the cumulative and current prevalence of asthma in both age groups were atopic dermatitis and allergic rhinitis. Future interventions for the prevention and early diagnosis and treatment could be focused in the natural history of the atopic march.

Genetic polymorphisms in arginase I and II and childhood asthma and atopy.

BACKGROUND: A recent microarray study implicated arginase I (ARG1) and arginase II (ARG2) in mouse allergic asthma models and human asthma. OBJECTIVES: To examine the association between genetic variation in ARG1 and ARG2 and childhood asthma and atopy risk. METHODS: We enrolled 433 case-parent triads, consisting of patients with asthma 4 to 17 years old and their biologic parents, from the allergy clinic of a public hospital in Mexico City between 1998 and 2003. Atopy to 24 aeroallergens was determined by skin prick tests. We genotyped 4 single nucleotide polymorphisms (SNPs) of ARG1 and 4 SNPs of ARG2 with minor allele frequencies higher than 10% by using the TaqMan assay (Roche Molecular Systems, Pleasanton, Calif). RESULTS: ARG1 SNPs and haplotypes were not associated with asthma, but all 4 ARG1 SNPs were associated with the number of positive skin tests (P = .007-.018). Carrying 2 copies of minor alleles for either of 2 highly associated ARG2 SNPs was associated with a statistically significant increased relative risk (RR) of asthma (1.5, 95% CI = 1.1-2.1 for arg2s1; RR = 1.6, 95% CI = 1.1-2.3 for arg2s2). The association was slightly stronger among children with a smoking parent (arg2s1 RR = 2.1, 95% CI = 1.2 - 3.9 with a smoking parent; RR = 1.2, 95% CI = 0.8-1.9 without; interaction P = .025). Haplotype analyses reduced the sample size but supported the single SNP results. One ARG2 SNP was related to the number of positive skin tests (P = .027). CONCLUSION: Variation in arginase genes may contribute to asthma and atopy in children.

Impact of control for air pollution and respiratory epidemics on the estimated associations of temperature and daily mortality.

We assessed the influence of control for air pollution and respiratory epidemics on associations between apparent temperature (AT) and daily mortality in Mexico City and Monterrey. Poisson regressions were fit to mortality among all ages, children (ages 0-14 years) and the elderly (ages >or=65 years). Predictors included mean daily AT, season, day of week and public holidays for the base model. Respiratory epidemics and air pollution (particulate matter <10 microm in aerodynamic diameter and O3) were added singly and then jointly for a fully adjusted model. Percent changes in mortality were calculated for days of relatively extreme temperatures [cold (10-11 degrees C) for both cities and heat (35-36 degrees C) for Monterrey], compared to days at the overall mean temperature in each city (15 degrees C in Mexico City, 25 degrees C in Monterrey). In Mexico City, total mortality increased 12.4% [95% confidence interval (CI) 10.5%, 14.5%] on cold days (fully adjusted). Among children, the adjusted association was similar [10.9% (95% CI: 5.4%, 16.7%)], but without control for pollution and epidemics, was nearly twice as large [19.7% (95% CI: 13.9%, 25.9)]. In Monterrey, the fully adjusted heat effect for all deaths was 18.7% (95% CI: 11.7%, 26.1%), a third lower than the unadjusted estimate; the heat effect was lower among children [5.5% (95% CI: -10.1%, 23.8%)]. Cold had a similar effect on all-age mortality as in Mexico City [11.7% (95% CI: 3.7%, 20.3%)]. Responses of the elderly differed little from all-ages responses in both cities. Associations between weather and health persisted even with control for air pollution and respiratory epidemics in two Mexican cities, but risk assessments and climate change adaptation programs are best informed by analyses that account for these potential confounders.

Nicotinamide adenine dinucleotide (phosphate) reduced:quinone oxidoreductase and glutathione S-transferase M1 polymorphisms and childhood asthma.

Nicotinamide adenine dinucleotide (phosphate) reduced:quinone oxidoreductase (NQO1) and glutathione S-transferase (GST) M1 are phase II enzymes important in response to oxidative stress, such as occurs during exposure to ozone. We examined the relationship between functionally significant polymorphisms in NQO1 (Pro187Ser) and GSTM1 (homozygous deletion) and asthma risk in children with high lifetime exposure to ozone. We enrolled children with asthma from the allergy referral clinic at a public pediatric hospital in Mexico City, together with their parents. We assayed for the Pro187Ser polymorphism in NQO1 using a polymerase chain reaction-restriction fragment length polymorphism assay and for the presence of GSTM1 by polymerase chain reaction among 218 case-parent triads. We did not find strong evidence of an association between NQO1 genotype alone and asthma risk. However, among subjects with homozygous deletion of GSTM1, carriers of a serine allele were at significantly reduced risk of asthma compared with Pro/Pro homozygotes (relative risk = 0.4; 95% confidence interval, 0.2-0.8). The p value for difference in relative risk for NQO1 by GSTM1 genotype = 0.013. These data are consistent with a protective effect of the NQO1 Ser allele in this population of GSTM1-null children with high ozone exposure.

Antioxidant supplementation and lung functions among children with asthma exposed to high levels of air pollutants.

To evaluate whether acute effects of ozone, nitrogen dioxide, and particulates with mass median diameter less than 10 micro m could be attenuated by antioxidant vitamin supplementation, we conducted a randomized trial using a double-blinded design. Children with asthma (n = 158) who were residents of Mexico City were randomly given a daily supplement of vitamins (50 mg/day of vitamin E and 250 mg/day of vitamin C) or a placebo and were followed from October 1998 to April 2000. Pulmonary function tests were carried out twice a week in the morning. During the follow-up observation period, the mean 1-hour maximum ozone level was 102 ppb (SD = 47), and the mean 24-hour average PM(10) level was 56.7 micro g/m(3) (SD = 27.4). In children with moderate and severe asthma, ozone levels 1 day before spirometry were inversely associated significantly with forced expiratory flow (FEF(25-75)) (-13.32 ml/second/10 ppb; p = 0.000), FEV(1) (-4.59 ml/10 ppb; p = 0.036), and peak expiratory flow (PEF) (-15.01 ml/second/10 ppb; p = 0.04) in the placebo group after adjusting for potential confounding factors. No association between ozone and lung functions was observed in the supplement group. We observed significant differences in lung function decrements between groups for FEF(25-75) and PEF. Our results suggest that supplementation with antioxidants might modulate the impact of ozone exposure on the small airways of children with moderate to severe asthma.

Assessment of personal exposure to ozone in asthmatic children residing in Mexico City / Evaluación de la exposición personal a ozono en niños asmáticos de la Ciudad de México

OBJECTIVE: A study was conducted to evaluate personal ozone exposure (O3p) among asthmatic children residing in Mexico City. MATERIAL AND METHODS: A total of 158 chil-dren were recruited from December 1998 to April 2000. On average, three O3p measurements were obtained per child using passive badges. Time-activity patterns were recorded in a diary. Daily ambient ozone measurements (O3a) were obtained from the fixed station, according to children’s residence. Levels of O3a and ozone, weighted by time spent in different micro-environments (O3w), were used as independent variables in order to model O3p concentrations using a mixed-effects model. RESULTS: Mean O3p was 7.8 ppb. The main variables in the model were: time spent indoors, distance between residence and fixed station, follow-up group, and two interaction terms (overall R²=0.50, p<0.05). CONCLUSIONS: The O3w concentrations can be used as a proxy for O3p, taking into account time-activity patterns and the place of residence of asthmatic Mexican children.

OBJETIVO: Realizamos este estudio para evaluar la exposición personal a ozono (O3p) en niños asmáticos de la Ciudad de México. MATERIAL Y MÉTODOS: Se incluyeron 158 niños entre diciembre de 1998 y abril de 2000. En promedio se obtuvieron tres mediciones por niño, utilizando filtros pasivos para medir O3p. Se caracterizaron los patrones de actividad y las concentraciones ambientales diarias de ozono (O3a) se obtuvieron de estaciones fijas cercanas a la residencia del niño. Los niveles promedio de O3a y las concentraciones ponderadas por el tiempo en diferentes microambientes (O3w) fueron usados como variables independientes para modelar las concentraciones de O3p, utilizando modelos de efectos mixtos. RESULTADOS: La media de O3p fue 7.8 ppb. Las principales variables en el modelo fueron: tiempo en exteriores, distancia, periodo de seguimiento y dos términos de interacción (R²=0.50, p<0.05). CONCLUSIONES: Las concentraciones de O3w pueden usarse como "proxi" de O3p, tomando en cuenta patrones de actividad y lugar de residencia.