The Legacy of Redlining: Increasing Childhood Asthma Disparities Through Neighborhood Poverty.

RATIONALE: Identifying the root causes of racial disparities in childhood asthma is critical for health equity. OBJECTIVES: To determine if the 1930's racist policy of redlining led to present-day disparities in childhood asthma by increasing community-level poverty and decreasing neighborhood socioeconomic position (SEP). METHODS: We categorized census tracts at birth of participants from the Children's Respiratory and Environmental Workgroup birth cohort consortium into A, B, C, or D categories as defined by the Home Owners Loan Corporation (HOLC), with D being the highest perceived risk. Surrogates of present-day neighborhood-level SEP were determined for each tract including the percentage of low-income households, the CDC's social vulnerability index (SVI), and other tract-level variables. We performed causal mediation analysis, which, under the assumption of no unmeasured confounding, estimates the direct and mediated pathways by which redlining may cause asthma disparities through census tract-level mediators adjusting for individual-level covariates. MEASUREMENTS AND MAIN RESULTS: Of 4,849 children, the cumulative incidence of asthma through age 11 was 26.6% and 13.2% resided in census tracts with a HOLC grade of D. In mediation analyses, residing in grade D tracts (aOR = 1.03 [95%CI 1.01,1.05]) was significantly associated with childhood asthma, with 79% of this increased risk mediated by percentage of low-income households; results were similar for SVI and other tract-level variables. CONCLUSIONS: The historical structural racist policy of redlining led to present-day asthma disparities in part through decreased neighborhood SEP. Policies aimed at reversing the effects of structural racism should be considered to create more just, equitable, and healthy communities.

Incidence rates of childhood asthma with recurrent exacerbations in the US Environmental influences on Child Health Outcomes (ECHO) program.

BACKGROUND: Descriptive epidemiological data on incidence rates (IRs) of asthma with recurrent exacerbations (ARE) are sparse. OBJECTIVES: This study hypothesized that IRs for ARE would vary by time, geography, age, and race and ethnicity, irrespective of parental asthma history. METHODS: The investigators leveraged data from 17,246 children born after 1990 enrolled in 59 US with 1 Puerto Rican cohort in the Environmental Influences on Child Health Outcomes (ECHO) consortium to estimate IRs for ARE. RESULTS: The overall crude IR for ARE was 6.07 per 1000 person-years (95% CI: 5.63-6.51) and was highest for children aged 2-4 years, for Hispanic Black and non-Hispanic Black children, and for those with a parental history of asthma. ARE IRs were higher for 2- to 4-year-olds in each race and ethnicity category and for both sexes. Multivariable analysis confirmed higher adjusted ARE IRs (aIRRs) for children born 2000-2009 compared with those born 1990-1999 and 2010-2017, 2-4 versus 10-19 years old (aIRR = 15.36; 95% CI: 12.09-19.52), and for males versus females (aIRR = 1.34; 95% CI 1.16-1.55). Black children (non-Hispanic and Hispanic) had higher rates than non-Hispanic White children (aIRR = 2.51; 95% CI 2.10-2.99; and aIRR = 2.04; 95% CI: 1.22-3.39, respectively). Children born in the Midwest, Northeast and South had higher rates than those born in the West (P < .01 for each comparison). Children with a parental history of asthma had rates nearly 3 times higher than those without such history (aIRR = 2.90; 95% CI: 2.43-3.46). CONCLUSIONS: Factors associated with time, geography, age, race and ethnicity, sex, and parental history appear to influence the inception of ARE among children and adolescents.

Fluoride exposure during early adolescence and its association with internalizing symptoms.

BACKGROUND: Early, chronic, low-level fluoride exposure has been linked to attention-deficit hyperactivity disorder (ADHD) and learning deficits in children. Rodent studies suggest a link between fluoride exposure and internalizing behaviors. No human studies have examined the impact of fluoride on internalizing behaviors during adolescence. OBJECTIVE: Evaluate the relationship between urinary fluoride and early adolescent internalizing symptoms in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). METHODS: Participants in CCAAPS provided non-fasting spot urine samples at age 12 years (n = 286). Urine samples were analyzed using a microdiffusion method to determine childhood urinary fluoride (CUF) concentrations and were log-transformed for analyses. Caregivers of CCAAPS participants completed the Behavior Assessment System for Children-2 (BASC-2) at the age 12 study visit to assess internalizing symptoms (e.g., anxiety, depression, somatization), and a composite score of the three domains; T-scores ≥ 60 were used to identify adolescents in a clinically "at-risk" range. Race, age of the adolescent, household income, maternal age at birth, caregiver depression, caregiver-child relationships, and age 12-year serum cotinine concentrations were considered covariates in regression models. Sex-specific effects of fluoride exposures were investigated through the inclusion of interaction terms. RESULTS: Higher CUF concentrations were significantly associated with increased somatization (ß = 3.64, 95% CI 0.49, 6.81) and internalizing composite T-scores in a clinically "at-risk" range (OR = 2.9, 95% CI 1.24, 6.9). Compared to females, males with higher CUF concentrations had more internalizing (pinteraction = 0.04) and somatization symptoms (pinteraction = 0.02) and were nearly seven times more likely to exhibit "at-risk" internalizing symptomology. CUF concentrations were not significantly associated with depression or anxiety symptoms. CONCLUSIONS: This is the first study to link fluoride exposure and internalizing symptoms, specifically somatization. Somatization represents an interface of physical and psychological health. Continued follow-up will help shed light on the sex-specific relationship between fluoride and mental health and the role of somatization.

Residential greenness, asthma, and lung function among children at high risk of allergic sensitization: a prospective cohort study.

BACKGROUND: While benefits of greenness to health have been reported, findings specific to child respiratory health are inconsistent. METHODS: We utilized a prospective birth cohort followed from birth to age 7 years (n = 617). Residential surrounding greenness was quantified via Normalized Difference Vegetation Index (NDVI) within 200, 400, and 800 m distances from geocoded home addresses at birth, age 7 years, and across childhood. Respiratory health outcomes were assessed at age 7 years, including asthma and lung function [percent predicted forced expiratory volume in the first second (%FEV1), percent predicted forced vital capacity (%FVC), and percent predicted ratio of forced expiratory volume in the first second to forced vital capacity (%FEV1/FVC)]. We assessed associations using linear and logistic regression models adjusted for community deprivation, household income, and traffic-related air pollution. We tested for effect measure modification by atopic status. RESULTS: We noted evidence of positive confounding as inverse associations were attenuated upon adjustment in the multivariable models. We found evidence of effect measure modification of NDVI and asthma within 400 m at age 7 years by atopic status (p = 0.04), whereby children sensitized to common allergens were more likely to develop asthma as exposure to greenness increased (OR = 1.3, 95% CI: 0.9, 2.0) versus children not sensitized to common allergens (OR = 0.8, 95% CI: 0.5, 1.2). We found consistently positive associations between NDVI and %FEV1 and %FVC which similarly evidenced positive confounding upon adjustment. In the adjusted regression models, NDVI at 7 years of age was associated with %FEV1 (200 m: ß = 2.1, 95% CI: 0.1, 3.3; 400 m: ß = 1.6, 95% CI: 0.3, 2.9) and %FVC (200 m: ß = 1.8, 95% CI: 0.7, 3.0; 400 m: ß = 1.6, 95% CI: 0.3, 2.8; 800 m: ß = 1.5, 95% CI: 0.1, 2.8). Adjusted results for %FEV1/FVC were non-significant except exposure at birth in the 400 m buffer (ß = 0.81, 95% CI: 0.1, 1.5). We found no evidence of effect measure modification of NDVI by atopic status for objective measures of lung function. CONCLUSION: Sensitivity to allergens may modify the effect of greenness on risk for asthma in children but greenness is likely beneficial for concurrent lung function regardless of allergic status.

Pediatric asthma incidence rates in the United States from 1980 to 2017.

BACKGROUND: Few studies have examined longitudinal asthma incidence rates (IRs) from a public health surveillance perspective. OBJECTIVE: Our aim was to calculate descriptive asthma IRs in children over time with consideration for demographics and parental asthma history. METHODS: Data from 9 US birth cohorts were pooled into 1 population covering the period from 1980 to 2017. The outcome was earliest parental report of a doctor diagnosis of asthma. IRs per 1,000 person-years were calculated. RESULTS: The racial/ethnic backgrounds of the 6,283 children studied were as follows: 55% European American (EA), 25.5% African American (AA), 9.5% Mexican-Hispanic American (MA) and 8.5% Caribbean-Hispanic American (CA). The average follow-up was 10.4 years (SD = 8.5 years; median = 8.4 years), totaling 65,291 person-years, with 1789 asthma diagnoses yielding a crude IR of 27.5 per 1,000 person-years (95% CI = 26.3-28.8). Age-specific rates were highest among children aged 0 to 4 years, notably from 1995 to 1999, with a decline in EA and MA children in 2000 to 2004 followed by a decline in AA and CA children in 2010 to 2014. Parental asthma history was associated with statistically significantly increased rates. IRs were similar and higher in AA and CA children versus lower but similar in EA and MA children. The differential rates by sex from birth through adolescence principally resulted from a decline in rates among males but relatively stable rates among females. CONCLUSIONS: US childhood asthma IRs varied dramatically by age, sex, parental asthma history, race/ethnicity, and calendar year. Higher rates in the 0- to 4-year-olds group, particularly among AA/CA males with a parental history of asthma, as well as changes in rates over time and by demographic factors, suggest that asthma is driven by complex interactions between genetic susceptibility and variation in time-dependent environmental and social factors.

NAT1 genetic variation increases asthma risk in children with secondhand smoke exposure.

OBJECTIVE: We previously reported that children exposed to secondhand smoke (SHS) that carried variants in the NAT1 gene had over two-fold higher hair cotinine levels. Our objective was to determine if NAT1 polymorphisms confer increased risk for developing asthma in children exposed to SHS. METHODS: White participants in the Cincinnati Childhood Allergy and Air Pollution Study (n = 359) were genotyped for 10 NAT1 variants. Smoke exposure was defined by hair cotinine and parental report. Asthma was objectively assessed by spirometry and methacholine challenge. Findings were replicated in the Genomic Control Cohort (n = 638). RESULTS: Significant associations between 5 NAT1 variants and asthma were observed in the CCAAPS exposed group compared to none in the unexposed group. There was a significant interaction between NAT1 rs13253389 and rs4921581 with smoke exposure (p = 0.02, p = 0.01) and hair cotinine level (p = 0.048, p = 0.042). Children wildtype for rs4921581 had increasing asthma risk with increasing hair cotinine level, whereas those carrying the NAT1 minor allele had an increased risk of asthma regardless of cotinine level. In the GCC, 13 NAT1 variants were associated with asthma in the smoke-exposed group, compared to 0 in the unexposed group, demonstrating gene-level replication. CONCLUSIONS: Variation in the NAT1 gene modifies asthma risk in children exposed to secondhand-smoke. To our knowledge, this is the first report of a gene-environment interaction between NAT1 variants, smoke exposure, cotinine levels, and pediatric asthma. NAT1 genotype may have clinical utility as a biomarker of increased asthma risk in children exposed to smoke.

The mycobiomes and bacteriomes of sputum, saliva, and home dust.

Respiratory microbiome is an understudied area of research compared to other microbiomes of the human body. The respiratory tract is exposed to an array of environmental pollutants, including microbes. Yet, we know very little about the relationship between environmental and respiratory microbiome. The primary aim of our study was to compare the mycobiomes and bacteriomes between three sample types from the same participants, including home dust, saliva, and sputum. Samples were collected from 40 adolescents in a longitudinal cohort. We analyzed the samples using 16s bacterial rDNA and ITS fungal rDNA gene sequencing, as well as quantitative PCR with universal fungal and bacterial primers. Results showed that home dust had the greatest alpha diversity between the three sample types for both bacteria and fungi. Dust had the highest total fungal load and the lowest total bacterial load. Sputum had greater bacterial diversity than saliva, but saliva had greater fungal diversity than sputum. The distribution of major bacterial phyla differed between all sample types. However, the distribution of major fungal classes differed only between sputum and saliva. Future research should examine the biological significance of the taxa found in each sample type based on microbial ecology and associations with health effects.

Assessing exposure to outdoor air pollution for epidemiological studies: Model-based and personal sampling strategies.

Epidemiologic studies have found air pollution to be causally linked to respiratory health including the exacerbation and development of childhood asthma. Accurately characterizing exposure is paramount in these studies to ensure valid estimates of health effects. Here, we provide a brief overview of the evolution of air pollution exposure assessment ranging from the use of ground-based, single-site air monitoring stations for population-level estimates to recent advances in spatiotemporal models, which use advanced machine learning algorithms and satellite-based data to accurately estimate individual-level daily exposures at high spatial resolutions. In addition, we review recent advances in sensor technology that enable the use of personal monitoring in epidemiologic studies, long-considered the "holy grail" of air pollution exposure assessment. Finally, we highlight key advantages and uses of each approach including the generalizability and public health relevance of air pollution models and the accuracy of personal monitors that are useful to guide personalized prevention strategies. Investigators and clinicians interested in the effects of air pollution on allergic disease and asthma should carefully consider the pros and cons of each approach to guide their application in research and practice.

A Pediatric Asthma Risk Score to better predict asthma development in young children.

BACKGROUND: Asthma phenotypes are currently not amenable to primary prevention or early intervention because their natural history cannot be reliably predicted. Clinicians remain reliant on poorly predictive asthma outcome tools because of a lack of better alternatives. OBJECTIVE: We sought to develop a quantitative personalized tool to predict asthma development in young children. METHODS: Data from the Cincinnati Childhood Allergy and Air Pollution Study (n = 762) birth cohort were used to identify factors that predicted asthma development. The Pediatric Asthma Risk Score (PARS) was constructed by integrating demographic and clinical data. The sensitivity and specificity of PARS were compared with those of the Asthma Predictive Index (API) and replicated in the Isle of Wight birth cohort. RESULTS: PARS reliably predicted asthma development in the Cincinnati Childhood Allergy and Air Pollution Study (sensitivity = 0.68, specificity = 0.77). Although both the PARS and API predicted asthma in high-risk children, the PARS had improved ability to predict asthma in children with mild-to-moderate asthma risk. In addition to parental asthma, eczema, and wheezing apart from colds, variables that predicted asthma in the PARS included early wheezing (odds ratio [OR], 2.88; 95% CI, 1.52-5.37), sensitization to 2 or more food allergens and/or aeroallergens (OR, 2.44; 95% CI, 1.49-4.05), and African American race (OR, 2.04; 95% CI, 1.19-3.47). The PARS was replicated in the Isle of Wight birth cohort (sensitivity = 0.67, specificity = 0.79), demonstrating that it is a robust, valid, and generalizable asthma predictive tool. CONCLUSIONS: The PARS performed better than the API in children with mild-to-moderate asthma. This is significant because these children are the most common and most difficult to predict and might be the most amenable to prevention strategies.

Myo-inositol mediates the effects of traffic-related air pollution on generalized anxiety symptoms at age 12 years.

BACKGROUND: Exposure to traffic-related air pollution (TRAP) has been linked to childhood anxiety symptoms. Neuroimaging in patients with anxiety disorders indicate altered neurochemistry. OBJECTIVES: Evaluate the impact of TRAP on brain metabolism and its relation to childhood anxiety symptoms in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). METHODS: Adolescents (n = 145) underwent magnetic resonance spectroscopy. Brain metabolites, including myo-inositol, N-acetylaspartate, creatine, choline, glutamate, glutamate plus glutamine, and glutathione were measured in the anterior cingulate cortex. Anxiety symptoms were assessed using the Spence Children's Anxiety Scale. TRAP exposure in early-life, averaged over childhood, and during the 12 months prior to imaging was estimated using a validated land use regression model. Associations between TRAP exposure, brain metabolism, and anxiety symptoms were estimated using linear regression and a bootstrapping approach for testing mediation by brain metabolite levels. RESULTS: Recent exposure to high levels of TRAP was associated with significant increases in myo-inositol (ß = 0.26; 95%CI 0.01, 0.51) compared to low TRAP exposure. Recent elevated TRAP exposure (ß = 4.71; 95% CI 0.95, 8.45) and increased myo-inositol levels (ß = 2.98; 95% CI 0.43, 5.52) were also significantly associated with increased generalized anxiety symptoms with 12% of the total effect between TRAP and generalized anxiety symptoms being mediated by myo-inositol levels. CONCLUSIONS: This is the first study of children to utilize neuroimaging to link TRAP exposure, metabolite dysregulation in the brain, and generalized anxiety symptoms among otherwise healthy children. TRAP may elicit atypical excitatory neurotransmission and glial inflammatory responses leading to increased metabolite levels and subsequent anxiety symptoms.

ß-Glucan exacerbates allergic asthma independent of fungal sensitization and promotes steroid-resistant TH2/TH17 responses.

BACKGROUND: Allergic sensitization to fungi has been associated with asthma severity. As a result, it has been largely assumed that the contribution of fungi to allergic disease is mediated through their potent antigenicity. OBJECTIVE: We sought to determine the mechanism by which fungi affect asthma development and severity. METHODS: We integrated epidemiologic and experimental asthma models to explore the effect of fungal exposure on asthma development and severity. RESULTS: We report that fungal exposure enhances allergen-driven TH2 responses, promoting severe allergic asthma. This effect is independent of fungal sensitization and can be reconstituted with ß-glucan and abrogated by neutralization of IL-17A. Furthermore, this severe asthma is resistant to steroids and characterized by mixed TH2 and TH17 responses, including IL-13+IL-17+CD4+ double-producing effector T cells. Steroid resistance is dependent on fungus-induced TH17 responses because steroid sensitivity was restored in IL-17rc-/- mice. Similarly, in children with asthma, fungal exposure was associated with increased serum IL-17A levels and asthma severity. CONCLUSION: Our data demonstrate that fungi are potent immunomodulators and have powerful effects on asthma independent of their potential to act as antigens. Furthermore, our results provide a strong rationale for combination treatment strategies targeting IL-17A for this subgroup of fungus-exposed patients with difficult-to-treat asthma.

Characteristics of Pediatric Emergency Revisits After an Asthma-Related Hospitalization.

STUDY OBJECTIVE: We identify and characterize factors related to subsequent emergency revisits among children hospitalized for asthma. METHODS: This population-based, prospective, observational cohort included children aged 2 to 16 years, hospitalized for asthma at an urban pediatric facility and followed for greater than or equal to 12 months. The primary outcome was asthma-related emergency revisit within 12 months of discharge. Revisits were identified by billing codes, respiratory chief complaints, and medications administered (eg, albuterol, systemic corticosteroids), dispensed, or prescribed. Predictors and covariates include demographic, socioeconomic, access, and environmental exposure variables collected during index admission. Multivariable logistic regression was used to evaluate the association between predictors and odds of asthma-related revisit. RESULTS: A total of 671 children were enrolled; the majority were boys (65%), aged 4 to 11 years (59%), black (59%), and publicly insured (73%). There were 274 patients (41%) who were treated for asthma-related emergency revisits within 12 months of the index admission. In adjusted models, younger children, black children, children with excellent reported access to primary care, and children with a history of inhaled steroids were more likely to experience emergency revisits. Low income, detectable cotinine levels, and traffic exposure did not independently predict revisit. CONCLUSION: Asthma-related emergency revisit is common after hospitalization, with more than 40% of children returning within 12 months. Socioeconomic and exposure-related risk factors typically predictive of asthma morbidity were not independently associated with emergency revisit among children in this cohort.

Childhood exposure to Libby amphibole asbestos and respiratory health in young adults.

OBJECTIVES: Vermiculite ore containing Libby amphibole asbestos (LAA) was mined in Libby, MT, from the 1920s-1990. Recreational and residential areas in Libby were contaminated with LAA. This objective of this study was to characterize childhood exposure to LAA and investigate its association with respiratory health during young adulthood. METHODS: Young adults who resided in Libby prior to age 18 completed a health and activity questionnaire, pulmonary function testing, chest x-ray and HRCT scan. LAA exposure was estimated based on participant report of engaging in activities with potential LAA exposure. Quantitative LAA estimates for activities were derived from sampling data and literature reports. RESULTS: A total of 312 participants (mean age 25.1 years) were enrolled and reported respiratory symptoms in the past 12 months including pleuritic chest pain (23%), regular cough (17%), shortness of breath (18%), and wheezing or whistling in the chest (18%). Cumulative LAA exposure was significantly associated with shortness of breath (aOR = 1.12, 95% CI 1.01-1.25 per doubling of exposure). Engaging in recreational activities near Rainy Creek Road (near the former mine site) and the number of instances heating vermiculite ore to make it expand or pop were also significantly associated with respiratory symptoms. LAA exposure was not associated with pulmonary function or pleural or interstitial changes on either chest x-ray or HRCT. CONCLUSIONS: Pleural or interstitial changes on x-ray or HRCT were not observed among this cohort of young adults. However, childhood exposure to LAA was significantly associated with respiratory symptoms during young adulthood. Pleuritic chest pain, in particular, has been identified as an early symptom associated with LAA exposure and therefore warrants continued follow-up given findings of progressive disease in other LAA exposed populations.

Ten-eleven translocation 1 (TET1) methylation is associated with childhood asthma and traffic-related air pollution.

BACKGROUND: Asthma is a complex disorder influenced by genetics and the environment. Recent findings have linked abnormal DNA methylation in T cells with asthma; however, the potential dysregulation of methylation in airway epithelial cells is unknown. Studies of mouse models of asthma have observed greater levels of 5-hydroxymethylcytosine (5-hmC) and ten-eleven translocation 1 (TET1) expression in lungs. TET proteins are known to catalyze methylation through modification of 5-methylcytosine to 5-hmC. OBJECTIVE: We sought to examine the association of TET1 methylation with asthma and traffic-related air pollution (TRAP). METHODS: TET1 methylation levels from DNA derived from nasal airway epithelial cells collected from 12 African American children with physician-diagnosed asthma and their nonasthmatic siblings were measured by using Illumina 450K arrays. Regions of interest were verified by means of locus-specific pyrosequencing in 35 sibling pairs and replicated in an independent population (n = 186). Exposure to TRAP in participants' early life and at current home addresses was estimated by using a land-use regression model. Methylation studies in saliva, PBMCs, and human bronchial epithelial cells were done to support our findings. RESULTS: Loss of methylation at a single CpG site in the TET1 promoter (cg23602092) and increased global 5-hmC levels were significantly associated with asthma. In contrast, TRAP exposure at participants' current homes significantly increased methylation at the same site. Patterns were consistent across tissue sample types. 5-Aza-2'-deoxycytidine and diesel exhaust particle exposure in human bronchial epithelial cells was associated with altered TET1 methylation and expression and global 5-hmC levels. CONCLUSIONS: Our findings suggest a possible role of TET1 methylation in asthmatic patients and response to TRAP.

Areas with High Rates of Police-Reported Violent Crime Have Higher Rates of Childhood Asthma Morbidity.

OBJECTIVES: To assess whether population-level violent (and all) crime rates were associated with population-level child asthma utilization rates and predictive of patient-level risk of asthma reutilization after a hospitalization. STUDY DESIGN: A retrospective cohort study of 4638 pediatric asthma-related emergency department visits and hospitalizations between 2011 and 2013 was completed. For population-level analyses, census tract asthma utilization rates were calculated by dividing the number of utilization events within a tract by the child population. For patient-level analyses, hospitalized patients (n = 981) were followed until time of first asthma-related reutilization. The primary predictor was the census tract rate of violent crime as recorded by the police; the all crime (violent plus nonviolent) rate was also assessed. RESULTS: Census tract-level violent and all crime rates were significantly correlated with asthma utilization rates (both P < .0001). The violent crime rate explained 35% of the population-level asthma utilization variance and remained associated with increased utilization after adjustment for census tract poverty, unemployment, substandard housing, and traffic exposure (P = .002). The all crime rate explained 28% of the variance and was similarly associated with increased utilization after adjustment (P = .02). Hospitalized children trended toward being more likely to reutilize if they lived in higher violent (P = .1) and all crime areas (P = .01). After adjustment, neither relationship was significant. CONCLUSIONS: Crime data could help facilitate early identification of potentially toxic stressors relevant to the control of asthma for populations and patients.

Timing and Duration of Traffic-related Air Pollution Exposure and the Risk for Childhood Wheeze and Asthma.

RATIONALE: The timing and duration of traffic-related air pollution (TRAP) exposure may be important for childhood wheezing and asthma development. OBJECTIVES: We examined the relationship between TRAP exposure and longitudinal wheezing phenotypes and asthma at age 7 years. METHODS: Children completed clinical examinations annually from age 1 year through age 4 years and age 7 years. Parental-reported wheezing was assessed at each age, and longitudinal wheezing phenotypes (early-transient, late-onset, persistent) and asthma were defined at age 7 years. Participants' time-weighted exposure to TRAP, from birth through age 7 years, was estimated using a land-use regression model. The relationship between TRAP exposure and wheezing phenotypes and asthma was examined. MEASUREMENTS AND MAIN RESULTS: High TRAP exposure at birth was significantly associated with both transient and persistent wheezing phenotypes (adjusted odds ratio [aOR] = 1.64; 95% confidence interval [CI], 1.04-2.57 and aOR = 2.31; 95% CI, 1.28-4.15, respectively); exposure from birth to age 1 year and age 1 to 2 years was also associated with persistent wheeze. Only children with high average TRAP exposure from birth through age 7 years were at significantly increased risk for asthma (aOR = 1.71; 95% CI, 1.01-2.88). CONCLUSIONS: Early-life exposure to TRAP is associated with increased risk for persistent wheezing, but only long-term exposure to high levels of TRAP throughout childhood was associated with asthma development.

Exposure to allergen and diesel exhaust particles potentiates secondary allergen-specific memory responses, promoting asthma susceptibility.

BACKGROUND: Exposure to traffic pollution particulate matter, predominantly diesel exhaust particles (DEPs), increases the risk of asthma and asthma exacerbation; however, the underlying mechanisms remain poorly understood. OBJECTIVE: We sought to examine the effect of DEP exposure on the generation and persistence of allergen-specific memory T cells in asthmatic patients and translate these findings by determining the effect of early DEP exposure on the prevalence of allergic asthma in children. METHODS: The effect of DEPs on house dust mite (HDM)-specific memory responses was determined by using an asthma model. Data from children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study birth cohort were analyzed to determine the effect of DEP exposure on asthma outcomes. RESULTS: DEP coexposure with HDM resulted in persistent TH2/TH17 CD127(+) effector/memory cells in the lungs, spleen, and lymph nodes of adult and neonatal mice. After 7 weeks of rest, a single exposure to HDM resulted in airway hyperresponsiveness and increased TH2 cytokine levels in mice that had been previously exposed to both HDM and DEPs versus those exposed to HDM alone. On the basis of these data, we examined whether DEP exposure was similarly associated with increased asthma prevalence in children in the presence or absence of allergen exposure/sensitization in the Cincinnati Childhood Allergy and Air Pollution Study birth cohort. Early-life exposure to high DEP levels was associated with significantly increased asthma prevalence among allergic children but not among nonallergic children. CONCLUSION: These findings suggest that DEP exposure results in accumulation of allergen-specific TH2/TH17 cells in the lungs, potentiating secondary allergen recall responses and promoting the development of allergic asthma.

Air pollution and allergic diseases.

PURPOSE OF REVIEW: Exposure to traffic-related air pollutants (TRAPs) has been implicated in asthma development, persistence, and exacerbation. This exposure is highly significant because increasingly large segments of the population worldwide reside in zones that have high levels of TRAP, including children, as schools are often located in high traffic pollution exposure areas. RECENT FINDINGS: Recent findings include epidemiologic and mechanistic studies that shed new light on the impact of traffic pollution on allergic diseases and the biology underlying this impact. In addition, new innovative methods to assess and quantify traffic pollution have been developed to assess exposure and identify vulnerable populations and individuals. SUMMARY: This review will summarize the most recent findings in each of these areas. These findings will have a substantial impact on clinical practice and research by the development of novel methods to quantify exposure and identify at-risk individuals, as well as mechanistic studies that identify new targets for intervention for individuals most adversely affected by TRAP exposure.

Significant predictors of poor quality of life in older asthmatics.

BACKGROUND: Morbidity and mortality from asthma are high in older adults and quality of life (QOL) might be lower, although standardized measurements of QOL have not been validated in this population. OBJECTIVE: To determine predictors of asthma-related QOL in older adults. METHODS: Allergy and pulmonary outpatients (n = 164) at least 65 years old with an objective diagnosis of asthma completed the Mini-Asthma Quality of Life Questionnaire (mAQLQ). Demographics, medical history, and mean value for daily elemental carbon attributable to traffic, a surrogate for diesel exposure, were obtained. Regression analysis was used to determine predictors of mAQLQ scores. RESULTS: Total mAQLQ (mean ± SD 5.4 ± 1.1) and symptom, emotional, and activity domain scores were similar to those of younger populations, whereas environmental domain scores (4.4 ± 1.7) appeared lower. Poorer mAQLQ scores were significantly associated with emergency department visits (adjusted ß [aß] = -1.3, where ß values indicate the strength and direction of association, P < .0001) and with poorer scores on the Asthma Control Questionnaire (aß = -0.7, P < .0001). Greater ECAT exposure (aß = -1.6, P < .02), female sex (aß = -0.4, P < .006), body mass index of at least 30 kg/m(2) (aß = -0.4, P < .01), gastroesophageal reflux (aß = -0.4, P < .01), nonatopic status (aß = -0.5, P < .002), and asthma onset before 40 years of age (aß = -0.5, P < .004) were significantly associated with poorer mAQLQ scores. CONCLUSION: The mAQLQ scores in older adults with stable asthma were similar to those in younger populations and were predictive of other measurements of asthma control, verifying that the mAQLQ is an appropriate tool in older adults with asthma. Traffic pollution exposure was the strongest predictor of poorer asthma-related QOL in older adults with asthma.

Traffic pollution is associated with early childhood aeroallergen sensitization.

BACKGROUND: No large, prospective, epidemiologic study has investigated the association between diesel exhaust particle (DEP) exposure and early aeroallergen sensitization and allergic rhinitis (AR) at 4 years of age. OBJECTIVE: To determine how exposure to traffic exhaust during infancy is associated with aeroallergen sensitization and AR at 4 years of age and the predictive utility of the wheal area at 1 to 3 years of age on AR at 4 years of age. METHODS: Infants born to aeroallergen sensitized parents were evaluated annually with skin prick tests to 15 aeroallergens with measurement of wheal areas. At 4 years of age, AR was defined as at least one positive aeroallergen skin prick test result and the presence of sneezing and a runny nose without a cold or flu. Infant (DEP) exposure was estimated using data from 27 air sampling monitors and a land use regression model. RESULTS: Complete data were available for 634 children at 4 years of age. Prevalence of AR increased annually from 6.9% to 21.9%. A positive trend was observed for high DEP exposure and aeroallergen sensitization at 2 and 3 years of age (odds ratio, 1.40; 95% confidence interval, 0.97-2.0) and (odds ratio, 1.35; 95% confidence interval, 0.98-1.85) but not with AR. At 2 years of age, every 1-mm(2) increase in the wheal area of timothy and Alternaria significantly increased the odds of AR at 4 years of age. At 3 years of age, every 1-mm(2) increase in the wheal area of fescue, dog, and Penicillium significantly increased the odds of AR at 4 years of age. CONCLUSION: DEP exposure enhances the risk of early aeroallergen sensitization. Aeroallergen wheal area at 2 and 3 years of age is associated with AR at 4 years of age.