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BACKGROUND: Indoor environments contain a broad diversity of non-pathogenic Basidiomycota yeasts, but their role in exacerbating adverse health effects has remained unclear. OBJECTIVE: To understand the role of Vishniacozyma victoriae exposure and its impact on human health. METHODS: A qPCR assay was developed to detect and quantify an abundant indoor yeast species, Vishniacozyma victoriae (syn. Cryptococcus victoriae), from homes participating in the New York City Neighborhood Asthma and Allergy Study (NAAS). We evaluated the associations between V. victoriae, housing characteristics, and asthma relevant health endpoints. RESULTS: V. victoriae was quantified in 236 of the 256 bedroom floor dust samples ranging from less than 300 to 45,918 cell equivalents/mg of dust. Higher concentrations of V. victoriae were significantly associated with carpeted bedroom floors (P=0.044), mean specific humidity (P=0.004), winter (P

Mold growth indoors is associated with negative human health effects, and this growth is limited by moisture availability. Dust deposited in carpet is an important source of human exposure due to potential elevated resuspension compared to hard floors. However, we need an improved understanding of fungal growth in dust and carpet to better estimate human exposure. The goal of this study was to compare fungal growth quantity and morphology in residential carpet under different environmental conditions, including equilibrium relative humidity (ERH) (50%, 85%, 90%, 95%, 100%), carpet fiber material (nylon, olefin, wool) and presence/absence of dust. We analyzed incubated carpet and dust samples from three Ohio homes for total fungal DNA, fungal allergen Alt a 1, and fungal morphology. Dust presence and elevated ERH (≥85%) were the most important variables that increased fungal growth. Elevated ERH increased mean fungal DNA concentration (P < 0.0001), for instance by approximately 1000 times at 100% compared to 50% ERH after two weeks. Microscopy also revealed more fungal growth at higher ERH. Fungal concentrations were up to 100 times higher in samples containing house dust compared to no dust. For fiber type, olefin had the least total fungal growth, and nylon had the most total fungi and A. alternata growth in unaltered dust. Increased ERH conditions were associated with increased Alt a 1 allergen concentration. The results of this study demonstrate that ERH, presence/absence of house dust, and carpet fiber type influence fungal growth and allergen production in residential carpet, which has implications for human exposure.

Background Whether concomitant home exposures modify the effectiveness of mouse allergen reduction among mouse-sensitized children with asthma is unknown. Objective To determine whether a lower baseline home mouse allergen level, lower particulate matter 10 μ or less (PM10), and the absence of sensitization and exposure to other indoor allergens are associated with greater improvements in asthma associated with mouse allergen reduction. Methods A secondary analysis of a randomized clinical trial of a home mouse allergen intervention was performed to examine the effect of 3 indoor factors on the relationship between mouse allergen reduction and a range of asthma outcomes. Results Participants (N = 297) were predominantly minority (78% African American, 22% Hispanic) and publicly insured (88%). Higher baseline mouse allergen levels were associated with a greater response to mouse allergen reduction for several symptom and exacerbation outcomes. Lower indoor PM10 levels were associated with a greater response to mouse allergen reduction for several symptom outcomes, but not exacerbation outcomes. Overall, sensitization and exposure to other indoor allergens did not appear to modify the effect of mouse allergen reduction. Conclusions In this population of predominantly low-income children with persistent asthma and mouse sensitization, mouse allergen reduction was associated with improvements in asthma, especially among those with high baseline mouse allergen exposure. Lower indoor PM10 was associated with greater improvements in asthma symptoms.

Background Specific patterns of allergic sensitization to common allergens may provide relevant clinical insight into asthma risk. Objective 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. Methods 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. Results 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. Conclusions 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.

BACKGROUND: Current childhood asthma therapies have little effect on lung function trajectory. OBJECTIVE: To determine if mouse allergen exposure reduction is associated with lung function growth in mouse-sensitized/exposed asthmatic children. METHODS: 350 mouse-sensitized/exposed asthmatic children (5–17y) were enrolled in a 1-year randomized trial of integrated pest management+education versus education alone. Pre-/post-bronchodilator (BD) spirometry was performed at baseline, 6 and 12 months, and bedroom floor mouse allergen was measured every 3 months. Mouse allergen reduction was defined as ≥75% decrease in mouse allergen from baseline. Treatment groups were combined for analyses, as there were no differences in outcomes between groups. Changes in lung function over time were modeled, adjusting for age, gender, race, atopy, group, BD reversibility and including an interaction term (allergen reduction*time). RESULTS: The study population was predominantly black (79.4%) and low-income (66.3%

The overall goal of the PRISMS Program is to develop sensor-based measurement and informatics platforms of environmental, physiological, and behavioral factors for epidemiological studies of asthma...

Lifetime childhood asthma prevalence (LCAP) percentages in Puerto Rico Health Regions (HR) are substantially higher in northeastern vs. southwestern HR. Higher average relative humidity in the northeast might promote mold and mite exposures and possibly asthma prevalence. To test this hypothesis, mold contamination, Environmental Relative Moldiness Index (ERMI) values were measured in floor dust (n = 26) and dust mite allergen concentrations in bed dust (n = 14). For this analysis, the eight HR were divided into those with LCAP > 30 % (n = 3) and < 30 % (n = 5). The average ERMI value was significantly greater (Wilcoxon Rank Sum, p < 0.001) in high than in low LCAP HR (14.5 vs. 9.3). The dust mite antigens Der p 1, Der f 1, and Blo t 5 were detected in 90 % of bed samples, but the concentrations were not significantly different in high vs. low LCAP HR. Mold exposures might partially explain the differences in LCAP HR in Puerto Rico.

In the United States, Puerto Ricans have a higher prevalence of asthma than other Latino ethnicities. Low vitamin D levels for children living in northern climates could be a factor.To assess serum 25-hydroxyvitamin D [25(OH)D] distributions (a marker of vitamin D) and associations among vitamin D, allergic sensitization, early wheeze, and home/demographic factors.Puerto Rican infants born in New York City, with a maternal history of atopy, were enrolled in a birth cohort. Blood was collected at age 2 years (n = 154; 82 males and 72 females). Serum 25(OH)D and immunoglobulin E (IgE) (indoor allergen-specific and total) were determined using immunoassays. Home/demographic characteristics and respiratory symptoms were assessed by questionnaire.The median concentration of 25(OH)D was 22.6 ng/mL; 32% were at risk of deficiency or inadequacy (12 or 12-19 ng/mL). Serum 25(OH)D levels were lower in the heating (a surrogate for less sun exposure in colder months) compared with nonheating (26.1 vs 22.7 ng/mL, P = .02) season, but were not associated with allergen-specific IgE levels or with level of acculturation (measured by maternal birthplace). However, low 25(OH)D levels (below median) were associated with high total IgE100 IU/mL (P = .01). Also, 25(OH)D concentrations differed between children who attended daycare and those who did not (21.8 vs 24.5 ng/mL; t test, P = .02). Serum 25(OH)D was not associated with wheeze or asthma by 2 years of age (P = .43).Vitamin D deficiency, possibly linked with allergic pathways, may partially explain the trajectory for disproportionate asthma burden among Puerto Ricans, especially those born and raised in colder climates.

Chronic exposure to mouse allergen may contribute greatly to the inner-city asthma burden. We hypothesized that reducing mouse allergen exposure may modulate the immunopathology underlying symptomatic pediatric allergic asthma, and that this occurs through epigenetic regulation. To test this hypothesis, we studied a cohort of mouse sensitized, persistent asthmatic inner-city children undergoing mouse allergen-targeted integrated pest management (IPM) vs education in a randomized controlled intervention trial. We found that decreasing mouse allergen exposure, but not cockroach, was associated with reduced FOXP3 buccal DNA promoter methylation, but this was unrelated to mouse specific IgE production. This finding suggests that the environmental epigenetic regulation of an immunomodulatory gene may occur following changing allergen exposures in some highly exposed cohorts. Given the clinical and public health importance of inner-city pediatric asthma and the potential impact of environmental interventions, further studies will be needed to corroborate changes in epigenetic regulation following changing exposures over time, and determine their impact on asthma morbidity in susceptible children.

Importance Professionally delivered integrated pest management (IPM) interventions can reduce home mouse allergen concentrations, but whether they reduce asthma morbidity among mouse-sensitized and exposed children and adolescents is unknown. Objective To determine the effect of an IPM intervention on asthma morbidity among mouse-sensitized and exposed children and adolescents with asthma. Design, Setting, and Participants Randomized clinical trial conducted in Baltimore, Maryland, and Boston, Massachusetts. Participants were mouse-sensitized and exposed children and adolescents (aged 5-17 years) with asthma randomized to receive professionally delivered IPM plus pest management education or pest management education alone. Enrollment occurred between May 2010 and August 2014; the final follow-up visit occurred on September 25, 2015. Interventions Integrated pest management consisted of application of rodenticide, sealing of holes that could serve as entry points for mice, trap placement, targeted cleaning, allergen-proof mattress and pillow encasements, and portable air purifiers. Infestation was assessed every 3 months, and if infestation persisted or recurred, additional treatments were delivered. All participants received pest management education, which consisted of written material and demonstration of the materials needed to set traps and seal holes. Main Outcomes and Measures The primary outcome was maximal symptom days defined as the highest number of days of symptoms in the previous 2 weeks among 3 types of symptoms (days of slowed activity due to asthma; number of nights of waking with asthma symptoms; and days of coughing, wheezing, or chest tightness) across 6, 9, and 12 months. Results Of 361 children and adolescents who were randomized (mean [SD] age, 9.8 [3.2] years; 38% female; 181 in IPM plus pest management education group and 180 in pest management education alone group), 334 were included in the primary analysis. For the primary outcome, there was no statistically significant between-group difference for maximal symptom days across 6, 9, and 12 months with a median of 2.0 (interquartile range, 0.7-4.7) maximal symptom days in the IPM plus pest management education group and 2.7 (interquartile range, 1.3-5.0) maximal symptom days in the pest management education alone group ( P = .16) and a ratio of symptom frequencies of 0.86 (95% CI, 0.69-1.06). Conclusions and Relevance Among mouse-sensitized and exposed children and adolescents with asthma, an intensive year-long integrated pest management intervention plus pest management education vs pest management education alone resulted in no significant difference in maximal symptom days from 6 to 12 months. Trial Registration clinicaltrials.gov Identifier:NCT01251224

Exposure to ambient metals in urban environments has been associated with wheeze, and emergency room visits and hospitalizations due to respiratory illness. However, the effect of ambient metals exposure on airway inflammation, and how these associations may be modified by seroatopy, has not been determined. Fractional exhaled nitric oxide (FENO) is a reliable proxy marker of airway inflammation. We hypothesized that recent ambient concentrations of Ni, V, Zn and Fe would be associated differentially with proximal and distal fractions of exhaled NO, and that these associations would be modified by seroatopy. As part of the Columbia Center for Children’s Environmental Health (CCCEH) birth cohort study, 9-11 year old children (n=192) were evaluated. Ambient measures of Ni, V, Zn and Fe were obtained from a local central monitoring site and averaged over nine days based on three 24 hour measures every third day. Fractional exhaled nitric oxide (FENO) samples were obtained at constant flows of 50 (FENO50), 83 and 100 mL/sec, and used to determine surrogate measures for proximal (JNO) and alveolar (Calv) inflammation. Seroatopy was determined by specific IgE at age 7. Data were analyzed using multivariable linear regression. Ambient V and Fe concentrations were associated positively with FENO50 (p = 0.018, p = 0.027). Ambient Fe was associated positively with JNO (p = 0.017). Ambient Ni and V concentrations were associated positively with Calv (p = 0.004, p = 0.018 respectively). A stronger association of Ni concentrations with Calv was observed among the children with seroatopy. These results suggest that ambient metals are associated differentially with different fractions of FENO production, and this relationship may be modified by seroatopy.

Background 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. Methods IgE antibodies, leptin, and hsCRP concentrations were measured in serum from Puerto Rican toddlers (n = 143) born in New York City with a maternal history of allergy and/or asthma. Demographic and home characteristics questionnaires were administered to the mother, postpartum and two years later. Children's weight and height were measured to determine BMI percentiles. Results More girls (60%) had leptin levels above the median compared with boys (37%) (p = 0.0063). Leptin was positively correlated with BMI (r = 0.25; p = 0.0042). Children in daycare were more likely to be obese (40% vs. 24% p

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.

Summary. Objectives and Hypothesis: To determine the feasibility of using a multiple flow offline fractional exhaled nitric oxide (FeNO) collection method in an inner-city cohort and determine this population’s alveolar and conducting airway contributions of NO. We hypothesized that the flow independent NO parameters would be associated differentially with wheeze and seroatopy. Methods: As part of a birth cohort study, 9-year-old children (n ¼ 102) of African-American and Dominican mothers living in low-income NYC neighborhoods had FeNO samples collected offline at constant flow rates of 50, 83, and 100 ml/sec. Seroatopy was defined as having measurable (� 0.35 IU/ml) specific IgE to any of the five inhalant indoor allergens tested. Current wheeze (last 12 months) was assessed by ISAAC questionnaire. Bronchial NO flux (JNO) and alveolar NO concentration (Calv) were estimated by the Pietropaoli and Hogman methods. Results: Valid exhalation flow rates were achieved in 96% of the children. Children with seroatopy (53%) had significantly higher median JNO (522 pl/sec vs. 161 pl/sec, P < 0.001) when compared to nonseroatopic children; however, median Calv was not significantly different between these two groups (5.5 vs. 5.8, P ¼ 0.644). Children with wheeze in the past year (21.6%) had significantly higher median Calv (8.4 ppb vs. 4.9 ppb, P < 0.001), but not JNO (295 pl/sec vs. 165 pl/sec, P ¼ 0.241) when compared with children without wheeze. These associations remained stable after adjustment for known confounders/covariates. Conclusions: The multiple flow method was easily implemented in this pediatric inner-city cohort. In this study population, alveolar concentration of NO may be a better indicator of current wheeze than single flow FeNO. Pediatr Pulmonol. 2010 Wiley-Liss, Inc.

OBJECTIVE: Conidia derived from a small number of common fungal genera are widely accepted as the etiological agents responsible for fungal allergic sensitization. The contribution of fungal conidia, spores, airborne hyphae, and subcellular fragments from other uncharacterized fungal genera remains unclear. In this proof-of-concept study, we examined the composition of mycoaerosols that atopic women were exposed and sensitized to in their own indoor environment using the fluorescent halogen immunoassay (fHIA). PATIENTS AND METHODS: Mycoaerosols were collected onto mixed cellulose ester protein binding membranes (PBMs) for 30 minutes with volumetric air sampling pumps. The PBMs were laminated with an adhesive cover slip and indirectly immunostained with individual patient serum IgE using the fHIA. Samples were examined using confocal laser scanning microscopy and immunostained particles were expressed as a percentage of total particles. RESULTS: All air samples contained a broad spectrum of fungal spores, conidia, hyphae, and other fungal particulates. Airborne concentrations varied between individual study participant environments. Positively immunostained conidia belonging to moniliaceous amerospores, Cladosporium, Alternaria, and many unknown species were observed in the majority of air samples. Other fungal genera including Bipolaris, Curvularia, Pithomyces, and Stachybotrys, in addition to, ascospore genera and dematiaceous hyphal fragments released detectable allergen. Twelve percent of all fHIA haloes quantified in the analysis were directed towards fungal particles. No immunostaining was detected to conidia belonging to Epicoccum, Fusarium, and Spegazzinia species. CONCLUSION: In addition to characterized fungal aeroallergens, we observed a wider composition of fungi that bound human IgE. Field surveillance studies that utilize immunodiagnostic techniques such as the fHIA will provide further insight into the diversity of fungi that function as aeroallergen sources in individual study participant environments.

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.

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 matter2.5μm (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, p0.05 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 (p0.05).Our findings suggest the BC fraction of PM might contain exposure relevant to increased oxidative stress in the airways.

A variety of skin disorders are referred to allergists, especially when they are associated with other atopic symptoms and/or blood eosinophilia. Although urticaria and atopic dermatitis are the most common skin manifestations of allergic disease in children and adults, the clinician must maintain a high degree of suspicion with regards to other potential sources of IgE, including biting insects, in a patient with these symptoms.

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) were collected. Neighborhood built-environment characteristics were assessed for the 500m surrounding participants’ homes. Airborne black carbon concentrations in homes correlated with neighborhood asthma prevalence (P

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 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.