Background Sensitization to cockroach is one of the strongest identified risk factors for greater asthma morbidity in low-income urban communities; however, the timing of exposures relevant to the ...development of sensitization has not been elucidated fully. Furthermore, exposure to combustion byproducts, including polycyclic aromatic hydrocarbons (PAHs), can augment the development of allergic sensitization. Objective We sought to test the hypotheses that domestic cockroach allergen measured prenatally would predict cockroach sensitization in early childhood and that this association would be greater for children exposed to higher PAH concentrations. Methods Dominican and African American pregnant women living in New York City were enrolled. In the third trimester expectant mothers wore personal air samplers for measurement of 8 nonvolatile PAHs and the semivolatile PAH pyrene, and dust was collected from homes for allergen measurement. Glutathione-S-transferase μ 1 (GSTM1) gene polymorphisms were measured in children. Allergen-specific IgE levels were measured from the children at ages 2, 3, 5, and 7 years. Results Bla g 2 in prenatal kitchen dust predicted cockroach sensitization at the ages of 5 to 7 years (adjusted relative risk RR, 1.15; P = .001; n = 349). The association was observed only among children with greater than (RR, 1.22; P = .001) but not less than (RR, 1.07; P = .24) the median sum of 8 nonvolatile PAH levels. The association was most pronounced among children with higher PAH levels and null for the GSTM1 gene (RR, 1.54; P = .001). Conclusions Prenatal exposure to cockroach allergen was associated with a greater risk of allergic sensitization. This risk was increased by exposure to nonvolatile PAHs, with children null for the GSTM1 mutation particularly vulnerable.
Background Asthma prevalence varies widely among neighborhoods within New York City. Exposure to mouse and cockroach allergens has been suggested as a cause. Objective To test the hypotheses that ...children living in high asthma prevalence neighborhoods (HAPNs) would have higher concentrations of cockroach and mouse allergens in their homes than children in low asthma prevalence neighborhoods (LAPNs), and that these exposures would be related to sensitization and asthma. Methods In the New York City Neighborhood Asthma and Allergy Study, a case-control study of asthma, children 7 to 8 years old from HAPNs (n = 120) and LAPNs (n = 119) were recruited through the same middle-income health insurance plan. Children were classified as asthma cases (n = 128) or controls without asthma (n = 111) on the basis of reported symptoms or medication use. Allergens were measured in bed dust. Results HAPN homes had higher Bla g 2 ( P = .001), Mus m 1 ( P = .003), and Fel d 1 ( P = .003) and lower Der f 1 ( P = .001) than LAPN homes. Sensitization to indoor allergens was associated with asthma, but relevant allergens differed between LAPNs and HAPNs. Sensitization to cockroach was more common among HAPN than LAPN children (23.7% vs 10.8%; P = .011). Increasing allergen exposure was associated with increased probability of sensitization (IgE) to cockroach ( P < .001), dust mite ( P = .009), and cat ( P = .001), but not mouse ( P = .58) or dog ( P = .85). Conclusion These findings further demonstrate the relevance of exposure and sensitization to cockroach and mouse in an urban community and suggest that cockroach allergen exposure could contribute to the higher asthma prevalence observed in some compared with other New York City neighborhoods.
Phthalates are used widely in consumer products. Exposure to several phthalates has been associated with respiratory symptoms and decreased lung function. Associations between children's phthalate ...exposures and fractional exhaled nitric oxide (Fe(NO)), a biomarker of airway inflammation, have not been examined.
We hypothesized that urinary concentrations of four phthalate metabolites would be positively associated with Fe(NO) and that these associations would be stronger among children with seroatopy or wheeze.
In an urban ongoing birth cohort, 244 children had phthalate metabolites determined in urine collected on the same day as Fe(NO) measurement. Repeated sampling gathered 313 observations between ages 4.9 and 9.1 years. Seroatopy was assessed by specific IgE. Wheeze in the past year was assessed by validated questionnaire. Regression models used generalized estimating equations.
Log-unit increases in urinary concentrations of metabolites of diethyl phthalate (DEP) and butylbenzyl phthalate (BBzP) were associated with a 6.6% (95% confidence interval CI 0.5-13.1%) and 8.7% (95% CI, 1.9-16.0%) increase in Fe(NO), respectively, adjusting for other phthalate metabolites and potential covariates/confounders. There was no association between concentrations of metabolites of di(2-ethylhexyl) phthalate or di-n-butyl phthalate and Fe(NO). There was no significant interaction by seroatopy. The BBzP metabolite association was significantly stronger among children who wheeze (P = 0.016).
Independent associations between exposures to DEP and BBzP and Fe(NO) in a cohort of inner-city children were observed. These results suggest that these two ubiquitous phthalates, previously shown to have substantial contributions from inhalation, are positively associated with airway inflammation in children.
Background: Recent cross-sectional studies suggest a link between butylbenzyl phthalate (BBzP) in house dust and childhood eczema. Objectives: We aimed to evaluate whether concentrations of ...monobenzyl phthalate (MBzP), the main BBzP metabolite in urine, during pregnancy are associated prospectively with eczema in young children, and whether this association varies by the child's sensitization to indoor allergens or serological evidence of any allergies. Methods: MBzP was measured in spot urine samples during the third trimester of pregnancy from 407 African-American and Dominican women residing in New York City in 1999—2006. Repeated questionnaires asked mothers whether their doctor ever said their child had eczema. Child blood samples at 24, 36, and 60 months of age were analyzed for total, anti-cockroach, dust mite, and mouse IgE. Relative risks (RR) were estimated with multivariable modified Poisson regression. Analyses included a multinomial logistic regression model for early- and late-onset eczema versus no eczema through 60 months of age. Results: MBzP was detected in > 99% of samples (geometric mean = 13.6; interquartile range: 5.7—31.1 ng/mL). By 24 months, 30% of children developed eczema, with the proportion higher among African Americans (48%) than among Dominicans (21%) (p < 0.001). An interquartile range increase in log MBzP concentration was associated positively with early-onset eczema (RR = 1.52 for eczema by 24 months; 95% confidence interval: 1.21, 1.91, p = 0.0003, n = 113 reporting eczema/376 total sample), adjusting for urine specific gravity, sex, and race/ethnicity. MBzP was not associated with allergic sensitization, nor did seroatopy modify consistently the MBzP and eczema association. Conclusions: Prenatal exposure to BBzP may influence the risk of developing eczema in early childhood.
Social and environmental stressors may modify associations between environmental pollutants and asthma symptoms. We examined if neighborhood asthma prevalence (higher: HAPN vs. lower: LAPN), a ...surrogate for underlying risk factors for asthma, modified the relationship between pollutants and urgent asthma visits.
Through zip code, home addresses were linked to New York City Community Air Survey's land use regression model for street-level, annual average nitrogen dioxide (NO
), particulate matter (PM
), elemental carbon (EC), summer average ozone (O
), winter average sulfur dioxide (SO
) concentrations. Poisson regression models were fit to estimate the association (prevalence ratio, PR) between pollutant exposures and seeking urgent asthma care.
All pollutants, except O
were higher in HAPN than LAPN (P < 0.01). Neighborhood asthma prevalence modified the relationship between pollutants and urgent asthma (P-interaction < 0.01, for NO
and SO
). Associations between pollutants and urgent asthma were observed only in LAPN (NO
: PR = 1.38, P = 0.01; SO
: PR = 1.85, P = 0.04). No association was observed between pollutants and urgent asthma among children in HAPN (P > 0.05).
Relationships between modeled street-level pollutants and urgent asthma were stronger in LAPN compared to HAPN. Social stressors that may be more prevalent in HAPN than LAPN, could play a greater role in asthma exacerbations in HAPN vs. pollutant exposure alone.
Acetaminophen has been associated with asthma and is in part metabolised via the glutathione pathway. Inner-city minority children have high asthma morbidity and a relatively high frequency of a ...minor allele variant in the glutathione S transferase Pi gene (GSTP1). We hypothesised that prenatal acetaminophen exposure would predict wheeze at age 5 years in an inner-city minority cohort and examined whether this association was modified by common polymorphisms in genes related to the glutathione pathway.
An ongoing population-based birth cohort study of Dominican Republic and African-American children in New York prospectively assessed the use of analgesics during pregnancy and current wheeze at age 5 years in 301 children. Genotyping was conducted for GST polymorphisms. Binomial regression was used to adjust for potential confounders including postnatal acetaminophen use.
34% of mothers reported acetaminophen use during pregnancy and 27% of children had current wheeze at 5 years. Prenatal exposure to acetaminophen predicted current wheeze (multivariate relative risk 1.71; 95% CI 1.20 to 2.42; p=0.003), and the risk increased monotonically with increasing number of days of prenatal acetaminophen exposure (p trend <0.001). 68% of children had at least one copy of the GSTP1 minor allele (Val). The risk of wheeze was modified by GSTP1 (additive interaction p=0.009) and was observed only among children with the GSTP1 minor allele.
Prenatal exposure to acetaminophen predicted wheeze at age 5 years in an inner-city minority cohort. The risk was modified by a functional polymorphism in GSTP1, suggesting a mechanism involving the glutathione pathway.
Specific patterns of allergic sensitization to common allergens may provide relevant clinical insight into asthma risk.
To identify patterns of allergic sensitization based on multiple individual ...allergens and link these to current and persistent asthma using baseline and 3-year follow-up data.
Children 7 to 8 years old with (n = 196) and without (n = 136) asthma from the New York City Neighborhood Asthma and Allergy Study were studied. IgE against a panel of 112 antigens was measured using the ISAC multiplex panel array. Latent class analysis (LCA) was used to identify patterns of allergic sensitization among the 26 most common allergens against which children had measurable IgE. The association between patterns of allergic sensitization and risk of asthma and other allergic diseases was examined.
LCA identified 4 patterns of allergic sensitization as follows: low risk of sensitization (prevalence of 53% in children with asthma and 76% in children without asthma), indoor (prevalence of 23% in children with asthma and 15% in children without asthma), pollen and indoor group 1 (prevalence of 16% in children with asthma and 5% in children without asthma), and pollen and indoor group 2 (prevalence of 9% in children with asthma and 4% in children without asthma). Compared with the low risk of sensitization pattern, children belonging to the 3 sensitized patterns had significantly higher risk of asthma at ages 7 to 8 years and 3 years later, with the highest risk for children in the pollen and indoor group 1 pattern.
LCA facilitates the study of sensitization profiles to a large number of common allergens. Analyzing patterns of allergic sensitization from multiple allergens reveals additional relevant associations with asthma than the study of a single allergen or total IgE.
Byproducts from fossil fuel combustion are common in urban air and are the most well-established anthropogenic environmental adjuvants of allergic sensitization.4 Black carbon and elemental carbon ...(EC), indicators of combustion exposure, vary across cities such as New York (NYC) because of vehicle and residential heating sources.5,6 Among NYC children, we previously demonstrated an interaction between exposure to combustion byproducts and cockroach allergen on cockroach sensitization7 and an association between black carbon measured inside homes and fractional exhaled nitric oxide (Feno), a marker of airway inflammation.5 Therefore, combustion byproducts might enhance the effect of fungal exposure on allergic disease outcomes among NYC children. Other mold taxa that we did not measure may also affect the risk of allergic sensitization to A alternata and asthma morbidity, especially because homologs of the major allergen from A alternata, Alt a 1, are also produced by other species in the Pleosporaceae family. ...our species-specific nucleic acid–based measurement of A alternata has implications for exposure misclassification.9 In summary, A alternata appears to be relevant to asthma morbidity for children living in NYC. The interaction P value was 0.051. ...those high values appear to have contributed to the association, but excluding them did not eliminate the association between A alternata and Feno among children in the higher EC neighborhoods. Included in analyses (n = 270) Not included in the analyses (n = 77) P value for difference High asthma prevalence neighborhood, %∗ 50.0 49.4 .92 Asthma cases, % 58.5 59.7 .85 Sex: male, % 45.2 41.6 .57 Race, %† Black 48.5 40.3 .20 White 14.8 14.3 .91 Asian 10.4 14.3 .34 Other/mixed 22.2 28.6 .25 Hispanic ethnicity, %‡ 29.9 35.9 .32 Household income (<$25K), % 9.3 10.4 .77 Household incomes for surrounding 500 m, median§ $34.2K $31.5K .57 Maternal asthma, %‖ 20.8 17.3 .51 Live in apartment, % 54.8 51.9 .66 Carpeted bedroom floor, % 45.9 55.8 .12 Report of mold odor, % 12.2 6.5 .24 Report of visible mold, % 38.7 35.5 .62 Report wet mopping, % 20.7 19.7 .85 Geometric mean A alternata (spore equivalent/mg) 57.3 52.0 .63 Median neighborhood EC (ng/m3) 1.1 1.1 .99 Table E1 Demographic characteristics of cohort for children included and not included in the analyses Characteristic n Geometric mean (95% CI) spore equivalent/mg P value for difference∗ Neighborhood asthma prevalence HAPN 135 81 (63-104) <.001 LAPN 135 40 (31-52) Housing type Single 52 84 (58-122) .003 Multifamily 70 80 (55-114) Apartment 148 43 (34-55) Carpeted bedroom floor No 146 40 (32-52) <.001 Yes 124 86 (67-111) Report of mold odor No 236 56 (46-67) .74 Yes 33 69 (35-138) Report of visible mold No 165 57 (46-71) .94 Yes 104 59 (43-81) Report of unrepaired water damage No 211 57 (46-70) .87 Yes 59 59 (41-85) Report of leaky pipes No 242 50 (49-72) .32 Yes 26 43 (24-76) Report adding water to air No 168 60 (48-75) .54 Yes 102 53 (39-73) Wet mop No 214 52 (42-63) .025 Yes 56 86 (57-130) Cat in home No 236 57 (47-70) .93 Yes 34 58 (39-88) Dog in home No 233 55 (45-67) .28 Yes 37 74 (48-114) Season of collection Winter 58 60 (43-84) .49 Spring 71 45 (33-61) Summer 99 63 (46-87) Fall 42 64 (37-111) Table E2 Geometric mean of A alternata in bedroom floor dust by home and neighborhood characteristics and household behavior Characteristic Correlation coefficient∗ P value Neighborhood asthma prevalence† −0.23 <.001 Year home built −0.12 .058 Median neighborhood household income (500 m) in $10K‡ 0.28 <.001 Family household income in $10K 0.21 .001 Neighborhood EC§ −0.12 .043 Der f 1 (μg/g)‖ 0.12 .053 Bla g 2 (μg/g)‖ −0.063 .31 Mus m 1 (μg/g)‖ −0.081 .18 Fel d 1 (μg/g)‖ −0.031 .61 Can f 1 (μg/g)‖ <0.001 1.0 Mean relative humidity# −0.071 .26 Table E3 Correlation between A alternata in bedroom floor dust and home and neighborhood characteristics and allergens Characteristic Beta (95% CI) P value Apartment building −0.16 (−0.60 to 0.28) .48 Carpet 0.58 (0.20 to 0.95) .003 Wet mop 0.39 (−0.074 to 0.84) .10 Neighborhood asthma prevalence∗ −0.012 (−0.064 to 0.041) .66 Median neighborhood household income (500 m) in $10K† 0.019 (−0.002 to 0.039) .073 Family household income in $10K 0.002 (−0.005 to 0.10) .57 Table E4 Multivariable model (n = 255) Asthma-related outcome Frequency among children with asthma PR for outcome with IgE to A alternata∗ Frequent wheeze (≥4 times past year) 21% 3.7 (1.8-7.8), P < .001 Frequent nighttime waking without cold (≥4 times past year) 20% 3.3 (1.6-7.3), P = .002 Frequent sleep disturbance by wheeze (≥ once per month) 13% 2.4 (0.97-3.0), P = .060 Frequent difficulty breathing (≥4 times past year) 17% 2.8 (1.3-4.0), P = .011 Frequent exercise-induced wheeze (≥4 times past year) 11% 2.5 (0.85-3.1), P = .096 Urgent medical visits for asthma past year 26% 2.1 (1.1-4.1), P = .033 Feno highest quartile (among cases and controls) 31% 2.2 (1.2-4.2), P = .015 FEV1/FVC lowest quartile (among cases and controls)† 28% 2.3 (1.1-4.6), P = .019 Table E5 PR for increased asthma symptoms, higher Feno, and lower FEV1/FVC among children with asthma with IgE to A alternata (≥0.1 IU/mL) (n = 155) Asthma-related outcome Overall Lower EC Higher EC Pinteraction Asthma (case vs control) PR = 1.0, P = .97 (n = 269) PR = 1.0, P = .84 (n = 133) PR = 1.0, P = .94 (n = 136) .99 Frequent wheeze among (vs no frequent wheeze among asthma cases) PR = 1.0, P = .93 (n = 157) PR = 1.0, P = .86 (n = 74) PR = 1.1, P = .80 (n = 83) .72 Feno (among cases and controls) β = 0.043, P = .078 (n = 269) β = −0.021, P = .59 (n = 133) β = 0.089, P = .008 (n = 135) .028 FEV1/FVC lowest quartile (among cases and controls) PR = 1.0, P = .98 (n = 237) PR = 1.0, P = .95 (n = 113) PR = 0.99, P = .95 (n = 124) .99 Table E6 Associations∗ between A alternata in bedroom floor dust and frequent wheeze, Feno, and FEV1/FVC, stratified by neighborhood EC Allergen (μg/g)† Lower EC‡ Higher EC‡ Pinteraction§ Der f 1 0.012 (−0.059 to 0.084) 0.068 (−0.009 to 0.15) .46 Bla g 2 −0.093 (−0.21 to 0.027) 0.094 (0.012 to 0.18)∗ .033 Mus m 1 0.018 (−0.036 to 0.073) 0.031 (−0.020 to 0.082) .43 Fel d 1 −0.022 (−0.094 to 0.049) 0.042 (−0.024 to 0.11) .22 Can f 1 −0.017 (−0.067 to 0.033) 0.023 (−0.034 to 0.080) .30 Table E7 Association (β coefficient 95% CI)∗ between indoor allergens and Feno, stratified by neighborhood EC
To advance asthma cohort research, we need a method that can use longitudinal data, including when collected at irregular intervals, to model multiple phenotypes of wheeze and identify both ...time-invariant (eg, sex) and time-varying (eg, environmental exposure) risk factors.
To demonstrate the use of latent class growth analysis (LCGA) in defining phenotypes of wheeze and examining the effects of causative factors, using repeated questionnaires in an urban birth cohort study.
We gathered repeat questionnaire data on wheeze from 689 children ages 3 through 108 months (n = 7,048 questionnaires) and used LCGA to identify wheeze phenotypes and model the effects of time-invariant (maternal asthma, ethnicity, prenatal environmental tobacco smoke, and child sex) and time-varying (cold/influenza flu season) risk factors on prevalence of wheeze in each phenotype.
LCGA identified four wheezing phenotypes: never/infrequent (47.1%), early-transient (37.5%), early-persistent (7.6%), and late-onset (7.8%). Compared with children in the never/infrequent phenotype, maternal asthma was a risk factor for the other 3 phenotypes; Dominican versus African American ethnicity was a risk factor for the early-transient phenotype; and male sex was a risk factor for the early-persistent phenotype. The prevalence of wheeze was higher during the cold/flu season than otherwise among children in the early-persistent phenotype (P = .08).
This is the first application of LCGA to identify wheeze phenotypes in asthma research. Unlike other methods, this modeling technique can accommodate questionnaire data collected at irregularly spaced age intervals and can simultaneously identify multiple trajectories of health outcomes and associations with time-invariant and time-varying causative factors.
Exposure to airborne black carbon (BC) has been associated with asthma development, respiratory symptoms and decrements in lung function. However, the mechanism through which BC may lead to ...respiratory symptoms has not been completely elucidated. Oxidative stress has been suggested as a potential mechanism through which BC might lead to adverse health outcomes. Exhaled breath condensate (EBC) allows for the non-invasive collection of airway lining fluid containing biomarkers of oxidative stress like 8-isoprostane, a stable by-product of lipid peroxidation. Therefore, we sought to characterize the association between domestic airborne BC concentrations and 8-isoprostane in EBC.
Seven- and eight-year-old children participated in an asthma case–control study in New York City. During home visits, air samples and EBC were collected. Seven day averages of domestic levels of particulate matter <2.5μm (PM2.5), BC and environmental tobacco smoke (ETS) were measured. Urea and 8-isoprostane were measured by liquid chromatography tandem mass spectrometry (LC/MS/MS) in EBC.
In univariate models, PM2.5 and BC, but not ETS, were significantly associated with increases in 8-isoprostane in the EBC (β=0.006 and β=0.106 respectively, p<0.05 for both). These associations remained statistically significant for both PM2.5 and BC after adjustment for covariates. In a co-pollutant model including PM2.5, BC and ETS, only BC remained a statistically significant predictor of 8-isoprostane (p<0.05).
Our findings suggest the BC fraction of PM might contain exposure relevant to increased oxidative stress in the airways.
•PM2.5, BC and ETS measured inside children׳s homes.•8-isoprostane, marker of oxidative stress measured in EBC.•Analyzed association between PM2.5, BC, ETS and 8-isoprostane.•Domestic BC associated with increased 8-isoprostane.
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