Luis M. Acosta

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.

Predicting indoor heat exposure risk during extreme heat events.

Increased heat-related morbidity and mortality are expected direct consequences of global warming. In the developed world, most fatal heat exposures occur in the indoor home environment, yet little is known of the correspondence between outdoor and indoor heat. Here we show how summertime indoor heat and humidity measurements from 285 low- and middle-income New York City homes vary as a function of concurrent local outdoor conditions. Indoor temperatures and heat index levels were both found to have strong positive linear associations with their outdoor counterparts; however, among the sampled homes a broad range of indoor conditions manifested for the same outdoor conditions. Using these models, we simulated indoor conditions for two extreme events: the 10-day 2006 NYC heat wave and a 9-day event analogous to the more extreme 2003 Paris heat wave. These simulations indicate that many homes in New York City would experience dangerously high indoor heat index levels during extreme heat events. These findings also suggest that increasing numbers of NYC low- and middle-income households will be exposed to heat index conditions above important thresholds should the severity of heat waves increase with global climate change. The study highlights the urgent need for improved indoor temperature and humidity management.

Mite sensitization among Latina women in New York, where dust‐mite allergen levels are typically low

UNLABELLED In New York (NY), Latinos often have greater asthma morbidity than other ethnicities, and dust-mite sensitization is common despite low allergen levels. We investigated mite allergen exposure and sensitization in atopic and/or asthmatic women, the majority being Puerto Rican. Women (n = 274) recruited for a birth cohort study were visited postnatally. Dust from their homes was analyzed for mite allergens (Der f 1, Der p 1, and Blo t 5). Serum was analyzed for total and allergen-specific IgE. Thirty-seven percent were sensitized to Dermatophagoides pteronyssinus, 34% to Dermatophagoides farinae, and 21% to Blomia tropicalis. Only 5% of NY homes had levels of Der f 1 >2 microg/g; none had Blo t 5 or Der p 1 above this level. Caribbean or Latin American birthplace (a proxy for childhood exposure) was not associated with mite sensitization. Sensitization to D. pteronyssinus and D. farinae was associated with a report of doctor-diagnosed asthma [Odds ratio (OR) = 3.27, P = 0.003; OR = 2.81, P = 0.010, respectively]; sensitization to any mite was associated with asthma medication use in the past 12 months (OR = 3.12, P = 0.004). These associations held even after adjustment for cockroach, mouse, and cat sensitization. PRACTICAL IMPLICATIONS Despite the low concentrations of mite allergen in our community, many of the women in the atopically enriched cohort were sensitized to mites, even Blomia tropicalis which is typically found only in tropical environments.

Socioeconomic and Outdoor Meteorological Determinants of Indoor Temperature and Humidity in New York City Dwellings.

BACKGROUND Numerous mechanisms link outdoor weather and climate conditions to human health. It is likely that many health conditions are more directly affected by indoor rather than outdoor conditions. Yet, the relationship between indoor temperature and humidity conditions to outdoor variability, and the heterogeneity of the relationship among different indoor environments are largely unknown. METHODS We use 5-14 day measures of indoor temperature and relative humidity from 327 dwellings in New York City for the years 2008-2011 to investigate the relationship between indoor climate, outdoor meteorological conditions, socioeconomic conditions, and building descriptors. Study households were primarily middle-income and located across the boroughs of Brooklyn, Queens, Bronx, and Manhattan. RESULTS Indoor temperatures are positively associated with outdoor temperature during the warm season and study dwellings in higher socioeconomic status neighborhoods are significantly cooler. During the cool season, outdoor temperatures have little effect on indoor temperatures; however, indoor temperatures can range more than 10 °C between dwellings despite similar outdoor temperatures. Apartment buildings tend to be significantly warmer than houses and dwellings on higher floors are also significantly warmer than dwellings on lower floors. Outdoor specific humidity is positively associated with indoor specific and relative humidity, but there is no consistent relationship between outdoor and indoor relative humidity. CONCLUSIONS In New York City, the relationship between indoor and outdoor temperature and humidity conditions vary significantly between dwellings. These results can be used to inform studies of health outcomes for which temperature or humidity is an established factor affecting human health and highlights the need for more research on the determinants of indoor climate.

The New York City Puerto Rican Asthma Project: Study Design, Methods, and Baseline Results

Objective. We examined asthma risk factors among 274 Puerto Rican children born in New York to atopic mothers. Methods. We prospectively followed the cohort to measure aeroallergens in their homes and assess allergic sensitization. Baseline data are presented. Results. Maternal smoking was significantly higher among women born on the continental United States (25%) vs. those born elsewhere (11%). Cat ownership was more frequent among mainland-born women (15%) compared with those born in Puerto Rico (4%). While some aeroallergens were prevalent, few dust samples contained detectable dust mite allergens. Conclusions. By following this cohort, we hope to identify the roles that socio-cultural factors play in the process of allergic sensitization.

Domestic airborne black carbon levels and 8-isoprostane in exhaled breath condensate among children in New York City

BACKGROUND 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. MATERIALS AND METHODS 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. RESULTS 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). CONCLUSIONS Our findings suggest the BC fraction of PM might contain exposure relevant to increased oxidative stress in the airways.

Exercise-Induced Wheeze, Urgent Medical Visits, and Neighborhood Asthma Prevalence

OBJECTIVE: Exercise-induced wheeze (EIW) may identify a distinct population among asthmatics and give insight into asthma morbidity etiology. The prevalence of pediatric asthma and associated urgent medical visits varies greatly by neighborhood in New York City and is highest in low-income neighborhoods. Although increased asthma severity might contribute to the disparities in urgent medical visits, when controlling for health insurance coverage, we previously observed no differences in clinical measures of severity between asthmatic children living in neighborhoods with lower (3%–9%) versus higher (11%–19%) asthma prevalence. Among these asthmatics, we hypothesized that EIW would be associated with urgent medical visits and a child’s neighborhood asthma prevalence. METHODS: Families of 7- to 8-year-old children were recruited into a case-control study of asthma through an employer-based health insurance provider. Among the asthmatics (n = 195), prevalence ratios (PRs) for EIW were estimated. Final models included children with valid measures of lung function, seroatopy, and waist circumference (n = 140). RESULTS: EIW was associated with urgent medical visits for asthma (PR, 2.29; P = .021), independent of frequent wheeze symptoms. In contrast to frequent wheeze, EIW was not associated with seroatopy or exhaled NO, suggesting a distinct mechanism. EIW prevalence among asthmatics increased with increasing neighborhood asthma prevalence (PR, 1.09; P = .012), after adjustment for race, ethnicity, maternal asthma, environmental tobacco smoke, household income, and neighborhood income. CONCLUSIONS: EIW may contribute to the disparities in urgent medical visits for asthma between high- and low-income neighborhoods. Physicians caring for asthmatics should consider EIW an indicator of risk for urgent medical visits.

Sociocultural characteristics, obesity and inflammatory biomarkers in Puerto Rican toddlers born in New York City

In the USA, Puerto Rican children have a higher prevalence of asthma than other Latino ethnicities, and acculturation is one of hypothesized reasons for this difference. We examined associations between sociocultural characteristics and serum leptin, high‐sensitivity C‐reactive protein (hsCRP), and body mass index (BMI), and further, among hsCRP, leptin levels, BMI percentiles, and allergic sensitization in 2‐year‐old children.

Infant rhinitis and watery eyes predict school-age exercise-induced wheeze, emergency department visits and respiratory-related hospitalizations

BACKGROUND Rhinitis and conjunctivitis are often linked to asthma development through an allergic pathway. However, runny nose and watery eyes can result from nonallergic mechanisms. These mechanisms can also underlie exercise-induced wheeze (EIW), which has been associated with urgent medical visits for asthma, independent of other indicators of asthma severity or control. OBJECTIVE To test the hypothesis that rhinitis or watery eyes without cold symptoms (RWWC) in infancy predict development of EIW and urgent respiratory-related medical visits at school age, independent of seroatopy. METHODS Within a prospective birth cohort of low-income, urban children (n = 332), RWWC was queried during the first year of life. Relative risks (RRs) for EIW, emergency department (ED) visits, and hospitalizations for asthma and other breathing difficulties at 5 to 7 years of age were estimated with multivariable models. Seroatopy was determined at 7 years of age. RESULTS Infant RWWC was common (49% of children) and predicted school-age EIW (RR, 2.8; P < .001), ED visits (RR, 1.8; P = .001), and hospitalizations (RR, 9.8; P = .002). These associations were independent of infant wheeze. They were also independent of birth order, an indicator of increased risk of exposure to viruses in infancy, and infant ear infections, an indicator of sequelae of upper airway infections. The association between infant RWWC and ED visits at 5 to 7 years of age was attenuated (RR, 1.2; P = .23) when EIW at 5 to 7 years of age was included in the model, suggesting EIW mediates the association. Adjustment for seroatopy did not diminish the magnitudes of any of these associations. CONCLUSION These findings suggest a nonallergic connection between infant nonwheeze symptoms and important consequences of urban respiratory health by school age through EIW.

Distinct Serum Sphingolipid Profiles among School-aged Children with Exercise-induced Wheeze and Asthma Persistence

Alterations in sphingolipids have been associated with chronic lung diseases (1). A role for altered sphingolipid metabolism in asthma pathogenesis is suggested by single-nucleotide polymorphisms in the most replicated gene locus associated with childhood asthma, 17q21, which includes the gene for ORM-like protein isoform 3, a regulator of sphingolipid synthesis (2). Also, decreased sphingolipid synthesis is associated with airway hyperreactivity (3). Childhood asthma includes multiple disease phenotypes, the disentangling of which would lead to better understanding of the underlying etiologies and potential treatments. Exercise-induced wheezing (EIW) in school-aged children has been identified as an asthma phenotype that includes both atopic and nonatopic asthma (4). Because many school-aged children with asthma will not continue to have asthma symptoms, identifying risk factors that predict persistence of wheezing has been challenging. We hypothesized that serum sphingolipids would be altered with asthma symptoms, EIW, and asthma persistence among a case–control study of children with and without asthma, the New York City Neighborhood Asthma and Allergy Study, described previously (4). Briefly, during home visits, spirometry, fractional exhaled nitric oxide testing, and waist circumference measurements were conducted and serum was collected in 7to 8-year-old children. Three years after enrollment, parents of all the willing subjects with asthma were queried about ongoing asthma symptoms. Children were classified as cases on the basis of symptoms or asthma medication use in the past year (4). Children classified as a case at baseline (age 7–8 yr) were considered to have asthma persistence if they again met the case definition at age 10 to 11 years. EIW was defined as an affirmative response to questions about (1) wheezing after running or active play, and/or (2) child’s chest sounding wheezy during or after exercise in the past 12 months. Children with specific IgE greater than or equal to 0.35 IU/ml against any of the inhalant allergens tested were considered seroatopic. Sphingolipids were analyzed by mass spectrometry (5). Multivariable analyses to examine asthma outcomes (dependent variables) were conducted using logistic regression. Variables conventionally considered as potential confounders were included in the multivariable models, including sex, race, Hispanic ethnicity, maternal asthma, environmental tobacco smoke, and material hardship. Serum was available for 243 children at age 7 to 8 years, of whom 152 were classified as having asthma. Of those 152 subjects with asthma at age 7 to 8 years, 147 participated in the follow-up at age 10 to 11 years. Of those 147 children meeting the case definition of asthma at age 7 to 8 years, 102 (69%) also met that definition 3 years later and were considered to have asthma persistence between ages 7 to 8 and 10 to 11 years. Clinically, children with asthma had mostly mild disease with relatively normal lung function; however, they had significantly lower FEV1/FVC, higher total IgE, and were more likely to be seroatopic than the children without asthma. Children included in these analyses did not differ significantly from those lost to follow-up. Seventeen sphingolipid species were measurable in serum. Dihydroceramides C16 and C18:1 and long-chain bases sphinganine and sphingosine were below the limit of detection in most samples and were excluded from analyses. In multivariable analyses, there were no statistically significant differences in sphingolipid concentrations among the children with and without asthma (Table 1). Among the children with asthma, concentrations of dihydroceramide C18 (DHC18); ceramides C18, C20, C24, and deoxy C24:1; and sphingomyelin SM24:1 were higher among those with EIW than among those without EIW. Asthma persistence between ages 7 to 8 years and 10 to 11 years was associated with increased serum DHC18 and C20:0 (Figure 1). To our knowledge, this is the first study to evaluate the association between serum sphingolipid profiles and asthma in children. We identified a distinct serum dihydroceramide and ceramide profile associated with EIW and found that elevated concentrations of DHC18 and C20:0 at age 7 to 8 years predicted asthma persistence to age 10 to 11 years. These associations were not altered by seroatopy, suggesting a mechanism independent of allergic sensitization. This is consistent with the observation that nonallergic childhood asthma was the major phenotype found associated with single-nucleotide polymorphisms that affect expression of ORM-like protein isoform 3 (6). Although it is not known whether serum sphingolipid profiles reflect those tissues of the respiratory tract, these results strongly support that altered systemic sphingolipid metabolism is present with EIW and that increased serum DHC18 and C20 may predict asthma persistence. We acknowledge the possibility of spurious findings, given the number of sphingolipids tested in these analyses. As such, these findings must be interpreted with caution. Still, we believe that these findings are compelling for replication in future studies. All serum sphingolipids that distinguished EIW and asthma persistence were higher than levels measured among control subjects. Notably, these serum signatures are opposite from what we found in murine models with impaired de novo sphingolipid synthesis demonstrating airway hyperreactivity. In this mouse model, genetic or pharmacologic inhibition of serine Supported by the National Institute of Environmental Health Sciences grants R01 ES 014400 and P30 ES 009089, Housing and Urban Development Healthy Homes Technical Studies grant NYHHU 0003-11, Columbia University’s Department of Pathology and Cell Biology (T.S.W. and B.I.K.), and the National Center for Advancing Translational Sciences grant KL2TR000458 (J.G.O.).