Inge F. Goldstein

Snow on Cholera

John Snow (1813–1858) was the son of a farmer in York, England. At the age of 14 he was apprenticed to a surgeon in Newcastle, who sent him when he was 18 to attend the victims of a major outbreak of cholera in the vicinity. In 1838 Snow passed his examination in London and became a member of the Royal College of Surgeons. He quickly made significant contributions to medical research: he participated in the development of an air pump for administering artificial respiration to newborn children unable to breathe and invented an instrument for performing thoracic surgery. He made major contributions to the new technique of anesthesia, becoming the leading specialist in London in the administration of ether, but switching to the easier-to-use chloroform when his own experimental studies convinced him of its practicality. He administered chloroform to Queen Victoria on the birth of her children, Prince Leopold and Princess Beatrice. His greatest achievement was his study of cholera, which he described in his monograph “On the Mode of Communication of Cholera,” one of the classics of scientific method and a fascinating story fascinatingly written. Snow died in 1858, a relatively young man, while at work on a book entitled On Chloroform and Other Anaesthetics.

Prenatal acetaminophen exposure and risk of wheeze at age 5 years in an urban, low-income cohort

Background 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. Methods 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. Results 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. Conclusions 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.

Early-life cockroach allergen and polycyclic aromatic hydrocarbon exposures predict cockroach sensitization among inner-city children

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.

Prenatal Exposure to Butylbenzyl Phthalate and Early Eczema in an Urban Cohort

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.

Children’s Urinary Phthalate Metabolites and Fractional Exhaled Nitric Oxide in an Urban Cohort

RATIONALE Phthalates are used widely in consumer products. Exposure to several phthalates has been associated with respiratory symptoms and decreased lung function. Associations between childrens phthalate exposures and fractional exhaled nitric oxide (Fe(NO)), a biomarker of airway inflammation, have not been examined. OBJECTIVES 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. METHODS 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. MEASUREMENTS AND MAIN RESULTS 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). CONCLUSIONS 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.

Analysis of air pollution patterns in New York City—I. Can one station represent the large metropolitan area?

Abstract Results of our analyses on the New York City Aerometric Network data show that the procedure of using one aerometric station to represent the daily fluctuations of air pollution throughout the large metropolitan area of New York City risks the use of an unreliable or invalid measure of the short term variation in air pollution.

Domestic airborne black carbon and exhaled nitric oxide in children in NYC

Differential exposure to combustion by-products and allergens may partially explain the marked disparity in asthma prevalence (3–18%) among New York City neighborhoods. Subclinical changes in airway inflammation can be measured by fractional exhaled nitric oxide (FeNO). FeNO could be used to test independent effects of these environmental exposures on airway inflammation. Seven- and eight-year-old children from neighborhoods with lower (range 3–9%, n=119) and higher (range 11–18%, n=121) asthma prevalence participated in an asthma case–control study. During home visits, FeNO was measured, and samples of bed dust (allergens) and air (black carbon; BC) were collected. Neighborhood built-environment characteristics were assessed for the 500 m surrounding participants’ homes. Airborne BC concentrations in homes correlated with neighborhood asthma prevalence (P<0.001) and neighborhood densities of truck routes (P<0.001) and buildings burning residual oil (P<0.001). FeNO concentrations were higher among asthmatics with than in those without frequent wheeze (≥4 times/year) (P=0.002). FeNO concentrations correlated with domestic BC among children without seroatopy (P=0.012) and with dust mite allergen among children with seroatopy (P=0.020). The association between airborne BC in homes and both neighborhood asthma prevalence and FeNO suggest that further public health interventions on truck emissions standards and residual oil use are warranted.

Cat ownership is a risk factor for the development of anti-cat IgE but not current wheeze at age 5 years in an inner-city cohort

BACKGROUND Cat ownership is inversely associated with atopy and asthma in some areas of the world, but the relevance of cat ownership to allergic disease in the inner city is less known. OBJECTIVE We sought to evaluate the relationship between cat ownership and the development of early sensitization and wheeze. METHODS By using a prospective birth cohort study, Dominican and African American mothers living in New York City underwent repeated questionnaires about their child from birth to age 5 years. Sera collected from children at ages 2 (n = 323), 3 (n = 336), and 5 (n = 242) years were assayed for anti-cat IgE and anti-Fel d 1 IgG antibodies. RESULTS Cat ownership was a significant risk factor for the development of anti-cat IgE by age 2 years (risk ratio [RR], 6.4; 95% CI, 1.9-22) but not for anti-cat IgE development between the ages of 2 and 5 years (RR, 0.88; 95% CI, 0.24-2.3). Current wheeze was significantly more common among those children with anti-cat IgE at ages 3 (RR, 3.5; 95% CI, 2.1-6.0) and 5 (RR, 3.4; 95% CI, 2.3-4.9) years. Cat ownership was inversely associated with current wheeze at age 5 years among children without anti-cat IgE (RR, 0.26; 95% CI, 0.083-0.81). Among children with anti-cat IgE, a similar trend was observed (RR, 0.57; P = .044, Fisher exact test), although one with borderline statistical significance. CONCLUSIONS Despite a positive association with sensitization, cat ownership in this inner-city cohort was inversely associated with wheeze, potentially suggesting an IgE-independent protective mechanism in this community.

Weather patterns and asthma epidemics in New York City and New Orleans, U.S.A.

Twenty-five years of data on asthmatic attacks in New Orleans (covering approximately 170,000 asthma attacks) have been analyzed to identify “asthma epidemic” days, defined as days on which an unusually high number of asthmatic individuals had attacks. Similar data covering three years was obtained for New York City. A preliminary examination of detailed meteoroligical data revealed a consistent meteorological pattern preceding and associated with such “asthma epidemic” days which consisted of a cold front preceding an asthma epidemic by one to three days followed by a high pressure system. The significance of these meteorological findings and their relationship to other environmental agents such as natural or man-made atmospheric pollutants that are likely to be associated with asthma attacks will be discussed.

On the Front Lines: An Environmental Asthma Intervention in New York City

Asthma is now the leading cause of school absence among children of color in impoverished urban neighborhoods. Environmental interventions have the potential to augment clinical approaches to asthma management by directly reducing exposure to environmental triggers (e.g., cockroaches, rodents, and mold). We implemented an apartment-based intervention to reduce exposures to indoor allergens among children living with asthma in 2 areas in New York City with rates of asthma morbidity and mortality that rank among the highest in the United States. Although the intervention phase of the present study is not yet complete, timely reporting of our field experiences may prove useful to other groups engaged in environmental intervention trials in urban communities.