Childhood asthma and household exposures to nitrogen dioxide and fine particles: a triple-crossover randomized intervention trial.

OBJECTIVE: Triple-crossover randomized controlled intervention trial to test whether reduced exposure to household NO2 or fine particles results in reduced symptoms among children with persistent asthma. METHODS: Children (n = 126) aged 5-11 years with persistent asthma living in homes with gas stoves and levels of NO2 15 ppb or greater recruited in Connecticut and Massachusetts (2015-2019) participated in an intervention involving three air cleaners configured for: (1) NO2 reduction: sham particle filtration and real NO2 scrubbing; (2) particle filtration: HEPA filter and sham NO2 scrubbing; (3) control: sham particle filtration and sham NO2 scrubbing. Air cleaners were randomly assigned for 5-week treatment periods using a three-arm crossover design. Outcome was number of asthma symptom-days during final 14 days of treatment. Treatment effects were assessed using repeated measures, linear mixed models. RESULTS: Measured NO2 was lower (by 4 ppb, p < .0001) for NO2-reducing compared to control or particle-reducing treatments. NO2-reducing treatment did not reduce asthma morbidity compared to control. In analysis controlling for measured NO2, there were 1.8 (95% CI -0.3 to 3.9, p = .10) fewer symptom days out of 14 in the particle-reducing treatment compared to control. CONCLUSIONS: It remains unknown if using an air cleaner alone can achieve levels of NO2 reduction large enough to observe reductions in asthma symptoms. We observed that in small, urban homes with gas stoves, modest reductions in asthma symptoms occurred using air cleaners that remove fine particles. An intervention targeting exposures to both NO2 and fine particles is complicated and further research is warranted. REGISTRATION NUMBER: NCT02258893.

Investigating the Impact of Maternal Residential Mobility on Identifying Critical Windows of Susceptibility to Ambient Air Pollution During Pregnancy.

Identifying periods of increased vulnerability to air pollution during pregnancy with respect to the development of adverse birth outcomes can improve understanding of possible mechanisms of disease development and provide guidelines for protection of the child. Exposure to air pollution during pregnancy is typically based on the mother's residence at delivery, potentially resulting in exposure misclassification and biasing the estimation of critical windows of pregnancy. In this study, we determined the impact of maternal residential mobility during pregnancy on defining weekly exposure to particulate matter less than or equal to 10 µm in aerodynamic diameter (PM10) and estimating windows of susceptibility to term low birth weight. We utilized data sets from 4 Connecticut birth cohorts (1988-2008) that included information on all residential addresses between conception and delivery for each woman. We designed a simulation study to investigate the impact of increasing levels of mobility on identification of critical windows. Increased PM10 exposure during pregnancy weeks 16-18 was associated with an increased probability of term low birth weight. Ignoring residential mobility when defining weekly exposure had only a minor impact on the identification of critical windows for PM10 and term low birth weight in the data application and simulation study. Identification of critical pregnancy windows was robust to exposure misclassification caused by ignoring residential mobility in these Connecticut birth cohorts.

A community-based evaluation of proximity to unconventional oil and gas wells, drinking water contaminants, and health symptoms in Ohio.

Over 4 million Americans live within 1.6 km of an unconventional oil and gas (UO&G) well, potentially placing them in the path of toxic releases. We evaluated relationships between residential proximity to UO&G wells and (1) water contamination and (2) health symptoms in an exploratory study. We analyzed drinking water samples from 66 Ohio households for 13 UO&G-related volatile organic compounds (VOCs) (e.g., benzene, disinfection byproducts [DBPs]), gasoline-range organics (GRO), and diesel-range organics. We interviewed participants about health symptoms and calculated metrics capturing proximity to UO&G wells. Based on multivariable logistic regression, odds of detection of bromoform and dibromochloromethane in surface water decreased significantly as distance to nearest UO&G well increased (odds ratios [OR]: 0.28-0.29 per km). Similarly, distance to nearest well was significantly negatively correlated with concentrations of GRO and toluene in ground water (rSpearman: -0.40 to -0.44) and with concentrations of bromoform and dibromochloromethane in surface water (rSpearman: -0.48 to -0.50). In our study population, those with higher inverse-distance-squared-weighted UO&G well counts within 5 km around the home were more likely to report experiencing general health symptoms (e.g. stress, fatigue) (OR: 1.52, 95%CI: 1.02-2.26). This exploratory study, though limited by small sample size and self-reported health symptoms, suggests that those in closer proximity to multiple UO&G wells may be more likely to experience environmental health impacts. Further, presence of brominated DBPs (linked to UO&G wastewater) raises the question of whether UO&G activities are impacting drinking water sources in the region. The findings from this study support expanded studies to advance knowledge of the potential for water quality and human health impacts; such studies could include a greater number of sampling sites, more detailed chemical analyses to examine source attribution, and objective health assessments.

Indoor microbial communities: Influence on asthma severity in atopic and nonatopic children.

BACKGROUND: Allergic and nonallergic asthma severity in children can be affected by microbial exposures. OBJECTIVE: We sought to examine associations between exposures to household microbes and childhood asthma severity stratified by atopic status. METHODS: Participants (n = 196) were selected from a cohort of asthmatic children in Connecticut and Massachusetts. Children were grouped according to asthma severity (mild with no or minimal symptoms and medication or moderate to severe persistent) and atopic status (determined by serum IgE levels). Microbial community structure and concentrations in house dust were determined by using next-generation DNA sequencing and quantitative PCR. Logistic regression was used to explore associations between asthma severity and exposure metrics, including richness, taxa identification and quantification, community composition, and concentration of total fungi and bacteria. RESULTS: Among all children, increased asthma severity was significantly associated with an increased concentration of summed allergenic fungal species, high total fungal concentrations, and high bacterial richness by using logistic regression in addition to microbial community composition by using the distance comparison t test. Asthma severity in atopic children was associated with fungal community composition (P = .001). By using logistic regression, asthma severity in nonatopic children was associated with total fungal concentration (odds ratio, 2.40; 95% CI, 1.06-5.44). The fungal genus Volutella was associated with increased asthma severity in atopic children (P = .0001, q = 0.04). The yeast genera Kondoa might be protective; Cryptococcus species might also affect asthma severity. CONCLUSION: Asthma severity among this cohort of children was associated with microbial exposure, and associations differed based on atopic status.

Spatiotemporal calibration and resolution refinement of output from deterministic models.

Spatiotemporal calibration of output from deterministic models is an increasingly popular tool to more accurately and efficiently estimate the true distribution of spatial and temporal processes. Current calibration techniques have focused on a single source of data on observed measurements of the process of interest that are both temporally and spatially dense. Additionally, these methods often calibrate deterministic models available in grid-cell format with pixel sizes small enough that the centroid of the pixel closely approximates the measurement for other points within the pixel. We develop a modeling strategy that allows us to simultaneously incorporate information from two sources of data on observed measurements of the process (that differ in their spatial and temporal resolutions) to calibrate estimates from a deterministic model available on a regular grid. This method not only improves estimates of the pollutant at the grid centroids but also refines the spatial resolution of the grid data. The modeling strategy is illustrated by calibrating and spatially refining daily estimates of ambient nitrogen dioxide concentration over Connecticut for 1994 from the Community Multiscale Air Quality model (temporally dense grid-cell estimates on a large pixel size) using observations from an epidemiologic study (spatially dense and temporally sparse) and Environmental Protection Agency monitoring stations (temporally dense and spatially sparse). Copyright © 2016 John Wiley & Sons, Ltd.

Household levels of nitrogen dioxide and pediatric asthma severity.

BACKGROUND: Adverse respiratory effects in children with asthma are associated with exposures to nitrogen dioxide (NO2). Levels indoors can be much higher than outdoors. Primary indoor sources of NO2 are gas stoves, which are used for cooking by one-third of U.S. households. We investigated the effects of indoor NO2 exposure on asthma severity among an ethnically and economically diverse sample of children, controlling for season and indoor allergen exposure. METHODS: Children 5-10 years of age with active asthma (n = 1,342) were recruited through schools in urban and suburban Connecticut and Massachusetts (2006-2009) for a prospective, year-long study with seasonal measurements of NO2 and asthma severity. Exposure to NO2 was measured passively for four, month-long, periods with Palmes tubes. Asthma morbidity was concurrently measured by a severity score and frequency of wheeze, night symptoms, and use of rescue medication. We used adjusted, hierarchical ordered logistic regression models to examine associations between household NO2 exposure and health outcomes. RESULTS: Every 5-fold increase in NO2 exposure above a threshold of 6 ppb was associated with a dose-dependent increase in risk of higher asthma severity score (odds ratio = 1.37 [95% confidence interval = 1.01-1.89]), wheeze (1.49 [1.09-2.03]), night symptoms (1.52 [1.16-2.00]), and rescue medication use (1.78 [1.33-2.38]). CONCLUSIONS: Asthmatic children exposed to NO2 indoors, at levels well below the U.S. Environmental Protection Agency outdoor standard (53 ppb), are at risk for increased asthma morbidity. Risks are not confined to inner city children, but occur at NO2 concentrations common in urban and suburban homes.

Effects of ambient pollen concentrations on frequency and severity of asthma symptoms among asthmatic children.

BACKGROUND: Previous studies on the associations between ambient pollen exposures and daily respiratory symptoms have produced inconsistent results. We investigated these relationships in a cohort of asthmatic children using pollen exposure models to estimate individual ambient exposures. METHODS: Daily symptoms of wheeze, night symptoms, shortness of breath, chest tightness, persistent cough, and rescue medication use were recorded in a cohort of 430 children with asthma (age 4-12 years) in Connecticut, Massachusetts, and New York. Daily ambient exposures to tree, grass, weed, and total pollen were estimated using mixed-effects models. We stratified analyses by use of asthma maintenance medication and sensitization to grass or weed pollens. Separate logistic regression analyses using generalized estimating equations were performed for each symptom outcome and pollen type. We adjusted analyses for maximum daily temperature, maximum 8-hour average ozone, fine particles (PM2.5), season, and antibiotic use. RESULTS: Associations were observed among children sensitized to specific pollens; these associations varied by use of asthma maintenance medication. Exposures to even relatively low levels of weed pollen (6-9 grains/m(3)) were associated with increased shortness of breath, chest tightness, rescue medication use, wheeze, and persistent cough, compared with lower exposure among sensitized children on maintenance medication. Grass pollen exposures ≥ 2 grains/m(3) were associated with wheeze, night symptoms, shortness of breath, and persistent cough compared with lower exposure among sensitized children who did not take maintenance medication. CONCLUSION: Even low-level pollen exposure was associated with daily asthmatic symptoms.

Association of variants in innate immune genes with asthma and eczema.

BACKGROUND: The innate immune pathway is important in the pathogenesis of asthma and eczema. However, only a few variants in these genes have been associated with either disease. We investigate the association between polymorphisms of genes in the innate immune pathway with childhood asthma and eczema. In addition, we compare individual associations with those discovered using a multivariate approach. METHODS: Using a novel method, case control based association testing (C2BAT), 569 single nucleotide polymorphisms (SNPs) in 44 innate immune genes were tested for association with asthma and eczema in children from the Boston Home Allergens and Asthma Study and the Connecticut Childhood Asthma Study. The screening algorithm was used to identify the top SNPs associated with asthma and eczema. We next investigated the interaction of innate immune variants with asthma and eczema risk using Bayesian networks. RESULTS: After correction for multiple comparisons, 7 SNPs in 6 genes (CARD25, TGFB1, LY96, ACAA1, DEFB1, and IFNG) were associated with asthma (adjusted p-value<0.02), while 5 SNPs in 3 different genes (CD80, STAT4, and IRAKI) were significantly associated with eczema (adjusted p-value < 0.02). None of these SNPs were associated with both asthma and eczema. Bayesian network analysis identified 4 SNPs that were predictive of asthma and 10 SNPs that predicted eczema. Of the genes identified using Bayesian networks, only CD80 was associated with eczema in the single-SNP study. Using novel methodology that allows for screening and replication in the same population, we have identified associations of innate immune genes with asthma and eczema. Bayesian network analysis suggests that additional SNPs influence disease susceptibility via SNP interactions. CONCLUSION: Our findings suggest that innate immune genes contribute to the pathogenesis of asthma and eczema, and that these diseases likely have different genetic determinants.

Relationship between birth weight and exposure to airborne fine particulate potassium and titanium during gestation.

Airborne particles are linked to numerous health impacts, including adverse pregnancy outcomes. Most studies of particles examined total mass, although the chemical structure of particles varies widely. We investigated whether mother's exposure to potassium (K) and titanium (Ti) components of airborne fine particulate matter (PM(2.5)) during pregnancy was associated with birth weight or risk of low birth weight (<2500 g) for term infants. The study population was 76,788 infants born in four counties in Connecticut and Massachusetts, US, for August 2000-February 2004. Both K and Ti were associated with birth weight. An interquartile range (IQR) increase K was associated with an 8.75% (95% confidence interval (CI): 1.24-16.8%) increase in risk of low birth weight. An IQR increase in Ti was associated with a 12.1% (95% CI: 3.55-21.4%) increase in risk of low birth weight, with an estimate of 6.41% (95% CI: -5.80-20.2%) for males and 16.4% (95% CI: 5.13-28.9%) for females. Results were robust to sensitivity analysis of first births only, but not adjustment by co-pollutants. Disentangling the effects of various chemical components is challenging because of the covariance among some components due to similar sources. Central effect estimates for infants of African-American mothers were higher than those of white mothers, although the confidence intervals overlapped. Our results indicate that exposure to airborne potassium and titanium during pregnancy is associated with lower birth weight. Associations may relate to chemical components of sources producing K and Ti.

Household mold and dust allergens: exposure, sensitization and childhood asthma morbidity.

BACKGROUND: Few studies address concurrent exposures to common household allergens, specific allergen sensitization and childhood asthma morbidity. OBJECTIVE: To identify levels of allergen exposures that trigger asthma exacerbations in sensitized individuals. METHODS: We sampled homes for common indoor allergens (fungi, dust mites (Der p 1, Der f 1), cat (Fel d 1), dog (Can f 1) and cockroach (Bla g 1)) for levels associated with respiratory responses among school-aged children with asthma (N=1233) in a month-long study. Blood samples for allergy testing and samples of airborne fungi and settled dust were collected at enrollment. Symptoms and medication use were recorded on calendars. Combined effects of specific allergen sensitization and level of exposure on wheeze, persistent cough, rescue medication use and a 5-level asthma severity score were examined using ordered logistic regression. RESULTS: Children sensitized and exposed to any Penicillium experienced increased risk of wheeze (odds ratio [OR] 2.12 95% confidence interval [CI] 1.12, 4.04), persistent cough (OR 2.01 95% CI 1.05, 3.85) and higher asthma severity score (OR 1.99 95% CI 1.06, 3.72) compared to those not sensitized or sensitized but unexposed. Children sensitized and exposed to pet allergen were at significantly increased risk of wheeze (by 39% and 53% for Fel d 1>0.12 µg/g and Can f 1>1.2 µg/g, respectively). Increased rescue medication use was significantly associated with sensitization and exposure to Der p 1>0.10 µg/g (by 47%) and Fel d 1>0.12 µg/g (by 32%). CONCLUSION: Asthmatic children sensitized and exposed to low levels of common household allergens Penicillium, Der p 1, Fel d 1 and Can f 1 are at significant risk for increased morbidity.

Effects of endotoxin exposure on childhood asthma risk are modified by a genetic polymorphism in ACAA1.

BACKGROUND: Polymorphisms in the endotoxin-mediated TLR4 pathway genes have been associated with asthma and atopy. We aimed to examine how genetic polymorphisms in innate immunity pathways interact with endotoxin to influence asthma risk in children. METHODS: In a previous analysis of 372 children from the Boston Home Allergens and the Connecticut Childhood Asthma studies, 7 SNPs in 6 genes (CARD15, TGFB1, LY96, ACAA1, DEFB1 and IFNG) involved in innate immune pathways were associated with asthma, and 5 SNPs in 3 genes (CD80, STAT4, IRAK2) were associated with eczema. We tested these SNPs for interaction with early life endotoxin exposure (n = 291), in models for asthma and eczema by age 6. RESULTS: We found a significant interaction between endotoxin and a SNP (rs156265) in ACAA1 (p = 0.0013 for interaction). Increased endotoxin exposure (by quartile) showed protective effects for asthma in individuals with at least one copy of the minor allele (OR = 0.39 per quartile increase in endotoxin, 95% CI 0.15 to 1.01). Endotoxin exposure did not reduce the risk of asthma in children homozygous for the major allele. CONCLUSION: Our findings suggest that protective effects of endotoxin exposure on asthma may vary depending upon the presence or absence of a polymorphism in ACAA1.

Association of maternal anemia with increased wheeze and asthma in children.

BACKGROUND: Increasing interest has focused on maternal nutrition and micronutrient status during pregnancy and respiratory disease development in the offspring. OBJECTIVE: To examine the relationship between maternal anemia in pregnancy with wheeze and asthma in early childhood. METHODS: The cohort included children of women followed through pregnancy and recontacted when the child was 6 years of age to evaluate respiratory health. Exposure was assessed using maternal anemia diagnosis and hemoglobin (Hgb) < 11 during delivery hospitalization. Study outcomes include wheezing in early childhood; patterns of wheeze from birth to age 6 (early-onset transient wheeze; late-onset wheeze; early-onset persistent wheeze); and diagnosis of childhood asthma. RESULTS: Maternal anemia was reported by 11.9% of mothers and was associated with recurrent infant wheeze in the first year (adjusted odds ratio [ORa] = 2.17, 95% confidence interval [CI] 1.18, 4.00), wheezing before age 3 (Ora = 2.42, 95% CI 1.38, 4.23), and early-onset transient and early-onset persistent wheeze patterns (Ora = 2.81, 95%CI 1.38, 5.72, and Ora = 2.07, 95% CI 1.02, 4.22), respectively. Among children of mothers with asthma, maternal anemia was associated with recurrent wheeze in year 1 (Ora = 4.22, 95% CI 1.65, 10.80) and wheeze before age 3 (Ora = 2.73, 95% CI 1.17, 6.35). Offspring of mothers with asthma also had increased odds of asthma diagnosis (Ora = 2.53, 95% CI 1.04, 6.17) and current asthma (Ora = 3.46, 95% CI 1.45, 8.26). CONCLUSIONS: Maternal anemia during pregnancy is associated with infant respiratory health outcomes. If this observation is replicated, maternal anemia may be a target for intervention and future research.

Urban land-use and respiratory symptoms in infants.

BACKGROUND: Children's respiratory health has been linked to many factors, including air pollution. The impacts of urban land-use on health are not fully understood, although these relationships are of key importance given the growing populations living in urban environments. OBJECTIVES: We investigated whether the degree of urban land-use near a family's residence is associated with severity of respiratory symptoms like wheeze among infants. METHODS: Wheeze occurrence was recorded for the first year of life for 680 infants in Connecticut for 1996-1998 from a cohort at risk for asthma development. Land-use categories were obtained from the National Land Cover Database. The fraction of urban land-use near each subject's home was related to severity of wheeze symptoms using ordered logistic regression, adjusting for individual-level data including smoking in the household, race, gender, and socio-economic status. Nitrogen dioxide (NO(2)) exposure was estimated using integrated traffic exposure modeling. Different levels of urban land-use intensity were included in separate models to explore intensity-response relationships. A buffer distance was selected based on the log-likelihood value of models with buffers of 100-2000 m by 10 m increments. RESULTS: A 10% increase in urban land-use within the selected 1540 m buffer of each infant's residence was associated with 1.09-fold increased risk of wheeze severity (95% confidence interval, 1.02-1.16). Results were robust to alternate buffer sizes. When NO(2), representing traffic pollution, was added to the model, results for urban land-use were no longer statistically significant, but had similar central estimates. Higher urban intensity showed higher risk of prevalence and severity of wheeze symptoms. CONCLUSIONS: Urban land-use was associated with severity of wheeze symptoms in infants. Findings indicate that health effect estimates for urbanicity incorporate some effects of traffic-related emissions, but also involve other factors. These may include differences in housing characteristics or baseline healthcare status.

Prenatal exposure to fine particulate matter and birth weight: variations by particulate constituents and sources.

BACKGROUND: Exposure to fine particles (PM2.5) during pregnancy has been linked to lower birth weight; however, the chemical composition of PM2.5 varies widely. The health effects of PM2.5 constituents are unknown. METHODS: We investigated whether PM2.5 mass, constituents, and sources are associated with birth weight for term births. PM2.5 filters collected in 3 Connecticut counties and 1 Massachusetts county from August 2000 through February 2004 were analyzed for more than 50 elements. Source apportionment was used to estimate daily contributions of PM2.5 sources, including traffic, road dust/crustal, oil combustion, salt, and regional (sulfur) sources. Gestational and trimester exposure to PM2.5 mass, constituents, and source contributions were examined in relation to birth weight and risk of small-at-term birth (term birth <2500 g) for 76,788 infants. RESULTS: Road dust and related constituents such as silicon and aluminum were associated with lower birth weight, as were the motor-vehicle-related species such as elemental carbon and zinc, and the oil-combustion-associated elements vanadium and nickel. An interquartile range increase in exposure was associated with low birthweight for zinc (12% increase in risk), elemental carbon (13%), silicon (10%), aluminum (11%), vanadium (8%), and nickel (11%). Analysis by trimester showed effects of third-trimester exposure to elemental carbon, nickel, vanadium, and oil-combustion PM2.5. CONCLUSIONS: Exposures of pregnant women to higher levels of certain PM2.5 chemical constituents originating from specific sources are associated with lower birth weight.

Integrated exposure modeling: a model using GIS and GLM.

Traffic exhaust is a source of air contaminants that have adverse health effects. Quantification of traffic as an exposure variable is complicated by aerosol dispersion related to variation in layout of roads, traffic density, meteorology, and topography. A statistical model is presented that uses Geographic Information Systems (GIS) technology to incorporate variables into a generalized linear model that estimates distribution of traffic-related pollution. Exposure from a source is expressed as an integral of a function proportional to average daily traffic and a nonparametric dispersion function, which takes the form of a step, polynomial, or spline model. The method may be applied using standard regression techniques for fitting generalized linear models. Modifiers of pollutant dispersion such as wind direction, meteorology, and landscape features can also be included. Two examples are given to illustrate the method. The first employs data from a study in which NO(2) (a known pollutant from automobile exhaust) was monitored outside of 138 Connecticut homes, providing a model for estimating NO(2) exposure. In the second example, estimated levels of nitrogen dioxide (NO(2)) from the model, as well as a separate spatial model, were used to analyze traffic-related health effects in a study of 761 infants.

Modeling effects of traffic and landscape characteristics on ambient nitrogen dioxide levels in Connecticut.

An integrated exposure model was developed that estimates nitrogen dioxide (NO(2)) concentration at residences using geographic information systems (GIS) and variables derived within residential buffers representing traffic volume and landscape characteristics including land use, population density and elevation. Multiple measurements of NO(2) taken outside of 985 residences in Connecticut were used to develop the model. A second set of 120 outdoor NO(2) measurements as well as cross-validation were used to validate the model. The model suggests that approximately 67% of the variation in NO(2) levels can be explained by: traffic and land use primarily within 2 km of a residence; population density; elevation; and time of year. Potential benefits of this model for health effects research include improved spatial estimations of traffic-related pollutant exposure and reduced need for extensive pollutant measurements. The model, which could be calibrated and applied in areas other than Connecticut, has importance as a tool for exposure estimation in epidemiological studies of traffic-related air pollution.

A pooled investigation of Toll-like receptor gene variants and risk of non-Hodgkin lymphoma.

Toll-like receptors (TLRs) may influence the development of non-Hodgkin lymphoma (NHL) given their important roles in recognizing microbial pathogens and stimulating multiple immune pathways. We conducted an investigation of TLR gene variants in a pooled analysis including three population-based case-control studies of NHL (1946 cases and 1808 controls). Thirty-six tag single-nucleotide polymorphisms (SNPs) in TLR2, TLR4 and the TLR10-TLR1-TLR6 gene cluster were genotyped. Two TLR10-TLR1-TLR6 variants in moderate linkage disequilibrium were significantly associated with NHL: rs10008492 [odds ratio for CT genotype (OR(CT)) 1.12, 95% confidence interval (CI) 0.97-1.30; OR(TT) 1.40, 95% CI 1.15-1.71; P(trend) = 0.001] and rs4833103 (OR(AC) 0.75, 95% CI 0.64-0.88; OR(AA) 0.74, 95% CI 0.62-0.90; P(trend) = 0.002; P(dominant) = 0.0002). Associations with these SNPs were consistent across all the three studies and did not appreciably differ by histologic subtype. We found little evidence of association between TLR2 variation and all NHL, although the rare variant rs3804100 was significantly associated with marginal zone lymphoma (MZL), both overall (OR(CT/CC) 1.89, 95% CI 1.27-2.81; P(dominant) = 0.002) and in two of the three studies. No associations with TLR4 variants were observed. This pooled analysis provides strong evidence that variation in the TLR10-TLR1-TLR6 region is associated with NHL risk and suggests that TLR2 variants may influence susceptibility to MZL.

Association of pediatric asthma severity with exposure to common household dust allergens.

BACKGROUND: Reducing exposure to household dust inhalant allergens has been proposed as one strategy to reduce asthma. OBJECTIVE: To examine the dose-response relationships and health impact of five common household dust allergens on disease severity, quantified using both symptom frequency and medication use, in atopic and non-atopic asthmatic children. METHODS: Asthmatic children (N=300) aged 4-12 years were followed for 1 year. Household dust samples from two indoor locations were analyzed for allergens including dust mite (Der p 1, Der f 1), cat (Fel d 1), dog (Can f 1), cockroach (Bla g 1). Daily symptoms and medication use were collected in monthly telephone interviews. Annual disease severity was examined in models including allergens, specific IgE sensitivity and adjusted for age, gender, atopy, ethnicity, and mother's education. RESULTS: Der p 1 house dust mite allergen concentration of 2.0 microg/g or more from the main room and the child's bed was related to increased asthma severity independent of allergic status (respectively, OR 2.93, 95% CI 1.37, 6.30 for 2.0-10.0 microg/g and OR 2.55 95% CI 1.13, 5.73 for 10.0 microg/g). Higher pet allergen levels were associated with greater asthma severity, but only for those sensitized (cat OR 2.41 95% CI 1.19, 4.89; dog OR 2.06 95% CI 1.01, 4.22). CONCLUSION: Higher levels of Der p 1 and pet allergens were associated with asthma severity, but Der p 1 remained an independent risk factor after accounting for pet allergens and regardless of Der p 1 specific IgE status.

Nutrients contributing to one-carbon metabolism and risk of non-Hodgkin lymphoma subtypes.

Because little is known about the etiology of non-Hodgkin lymphoma (NHL), a heterogeneous disease, and because dietary factors are modifiable, the authors examined the associations between nutrients related to one-carbon metabolism and risk of NHL in a population-based case-control study of Connecticut women diagnosed between 1996 and 2000. A total of 594 cases and 710 controls completed a food frequency questionnaire for determination of intakes of folate, vitamins B(2), B(6), and B(12), and methionine. Through unconditional logistic regression, the authors estimated the risk of NHL associated with intake of each nutrient. Comparing the highest quartile of intake with the lowest, the authors found lower risks of all NHL associated with increasing intakes of folate and methionine. Analysis by NHL subtype indicated lower risks of diffuse large B-cell lymphoma (highest quartile vs. lowest: odds ratio (OR) = 0.54, 95% confidence interval (CI): 0.30, 0.98; p-trend = 0.02) and marginal zone lymphoma (highest quartile vs. lowest: OR = 0.08, 95% CI: 0.02, 0.26; p-trend < 0.0001) associated with folate. Vitamin B(6) intake was also associated with lower risk of NHL overall and of marginal zone lymphoma (highest quartile vs. lowest: OR = 0.23, 95% CI: 0.08, 0.65; p-trend = 0.002). These findings suggest that these nutrients may be important for susceptibility to NHL.