<p>Vegetation may influence asthma exacerbation through effects on aeroallergens, localized climates, air pollution, or children's behaviors and stress levels. We investigated the association between residential vegetation and asthma exacerbation by conducting a matched case-control study based on electronic health records of asthma patients, from the Children's Hospital of Philadelphia (CHOP). Our study included 17,639 exacerbation case events and 34,681 controls selected from non-exacerbation clinical visits for asthma, matched to cases by age, sex, race/ethnicity, public payment source, and residential proximity to the CHOP main campus ED and hospital. Overall greenness, tree canopy, grass/shrub cover, and impervious surface were assessed near children's homes (250&nbsp;m) using satellite imagery and high-resolution landcover data. We used generalized estimating equations to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between each vegetation/landcover measure and asthma exacerbation, with adjustment for seasonal and sociodemographic factors-for all cases, and for cases defined by diagnosis setting and exacerbation frequency. Lower odds of asthma exacerbation were observed in association with greater levels of tree canopy near the home, but only for children who experienced multiple exacerbations in a year (OR = 0.94 per 10.2% greater tree canopy coverage, 95% CI = 0.90-0.99). Our findings suggest possible protection for asthma patients from tree canopy, but differing results by case frequency suggest that potential benefits may be specific to certain subpopulations of asthmatic children.</p>

<p><strong>OBJECTIVES: </strong>High ambient temperatures may contribute to acute asthma exacerbation, a leading cause of morbidity in children. We quantified associations between hot-season ambient temperatures and asthma exacerbation in children ages 0-18 years in Philadelphia, PA.</p>

<p><strong>METHODS: </strong>We created a time series of daily counts of clinical encounters for asthma exacerbation at the Children's Hospital of Philadelphia linked with daily meteorological data, June-August of 2011-2016. We estimated associations between mean daily temperature (up to a 5-day lag) and asthma exacerbation using generalised quasi-Poisson distributed models, adjusted for seasonal and long-term trends, day of the week, mean relative humidity,and US holiday. In secondary analyses, we ran models with adjustment for aeroallergens, air pollutants and respiratory virus counts. We quantified overall associations, and estimates stratified by encounter location (outpatient, emergency department, inpatient), sociodemographics and comorbidities.</p>

<p><strong>RESULTS: </strong>The analysis included 7637 asthma exacerbation events. High mean daily temperatures that occurred 5 days before the index date were associated with higher rates of exacerbation (rate ratio (RR) comparing 33°C-13.1°C days: 1.37, 95% CI 1.04 to 1.82). Associations were most substantial for children ages 2 to &lt;5 years and for Hispanic and non-Hispanic black children. Adjustment for air pollutants, aeroallergens and respiratory virus counts did not substantially change RR estimates.</p>

<p><strong>CONCLUSIONS: </strong>This research contributes to evidence that ambient heat is associated with higher rates of asthma exacerbation in children. Further work is needed to explore the mechanisms underlying these associations.</p>

<p><strong>BACKGROUND: </strong>Water total trihalomethanes (TTHMs) are disinfectant byproducts found in municipal water supplies. TTHM exposure has been linked to cancer and may be associated with adverse reproductive outcomes. A non-optimal cervicovaginal microbiota and low cervicovaginal beta-defensin-2 levels are associated with increased risk of spontaneous preterm birth. Whether TTHM exposure increases the risk of spontaneous preterm birth or alters the cervicovaginal microbial or immune state is unknown.</p>

<p><strong>OBJECTIVE: </strong>Investigate associations of water TTHM levels with spontaneous preterm birth, a non-optimal cervicovaginal microbiota, and beta-defensin-2 levels in a completed, diverse, urban pregnancy cohort. We hypothesized that higher TTHM levels would be associated with spontaneous preterm birth, a non-optimal cervicovaginal microbiota, and lower beta-defensin-2 levels.</p>

<p><strong>DESIGN: </strong>/Methods: This was a secondary analysis of participants (n=474) in the Motherhood &amp; Microbiome (M&amp;M) study (n=2000), who lived in Philadelphia and had cervicovaginal samples analyzed for cervicovaginal microbiota composition and beta-defensin-2 levels. The microbiota was classified into community state types (CSTs). CST IV (non-optimal microbiota) is characterized by a paucity of Lactobacillus species and wide array of anaerobes. Municipal water TTHM levels were obtained from 16 sites monthly across the city of Philadelphia to establish mean residential water supply levels for each participant for the first four months of pregnancy (prior to vaginal swab collection at 16-20 weeks' gestation). Associations of water TTHM levels with spontaneous preterm birth and a non-optimal cervicovaginal microbiota birth were analyzed using multivariable logistic regression. Multivariable linear regression was used to model associations of water TTHM levels with log-transformed cervicovaginal beta-defensin-2 levels. Since water TTHM levels vary by season and Beta-defensin-2 levels have been shown to differ by race, stratified models by warm (April-September) and cold (October-March) seasons as well as by self-identified race were utilized.</p>

<p><strong>RESULTS: </strong>Participants' water supply TTHM levels (mean μg/L [SD]) were higher in the warm (53.5 [9.4]) than cold (33.4 [7.5]) season (p&lt;0.0001). TTHM levels were non-significantly higher among Black participants than non-Black participants (44.8[13.5] vs. 41.8[11.8], p=0.07). No associations were detected between TTHM with spontaneous preterm birth (per SD increment of TTHM, aOR 0.94, 95%CI: 0.66, 1.34) or with CST IV (aOR 0.94, 95%CI: 0.86, 1.16). Counter to our hypothesis, we observed positive associations of water TTHM with log-transformed cervicovaginal beta-defensin-2 levels in unadjusted models (β 0.20 [95%CI: 0.02, 0.39)] per SD increment of TTHM), but the association was null after adjustment for season. However, in models adjusted for covariates including season and stratified by race, TTHM was significantly associated with lower beta-defensin-2 levels among non-Black participants (β -0.75 [95%CI: -1.43, -0.08]) but not among Black participants (β 0.17 [95%CI: -0.15, 0.49]), interaction p=0.013).</p>

<p><strong>CONCLUSION: </strong>We did not detect associations of water TTHM levels with spontaneous preterm birth or the structure of the cervicovaginal microbiota. However, the finding of a significant interaction between TTHM and race on beta-defensin-2 levels suggest that environmental exposures may contribute to differences in reproductive tract innate immune function by race. Future studies to delineate environmental contributions to the cervicovaginal microbial-immune state, a potentially important biologic underpinning for preterm birth, are warranted.</p>

<p>Fine particulate matter (PM) and ozone (O) air pollutants are known risk factors for asthma exacerbation. We studied the association of these air pollutants with pediatric asthma exacerbation in the Philadelphia metropolitan region, and evaluated potential effect modification by children's characteristics (e.g., race/ethnicity, atopic conditions) and environmental factors (e.g., neighborhood tree canopy, meteorological factors, aeroallergens). We conducted a time-stratified case-crossover study of 54,632 pediatric (age ≤18 years) asthma exacerbation cases occurring from 2011-2014, identified through electronic health records (EHR) of the Children's Hospital of Philadelphia (CHOP) health system. We applied conditional logistic regression to estimate associations between air pollution and asthma exacerbation, using daily census-tract level pollutant concentrations estimated from the EPA Fused Air Quality Surface Using Downscaling (FAQSD) files. The associations were estimated within warm (Apr - Sep) and cold (Oct - Mar) months for unlagged exposure and for cumulative effects up to 5 days after exposure, with adjustment for temperature, relative humidity, and holidays. We found small increases in odds of asthma exacerbation with higher pollutant concentrations, with positive associations (OR, comparing concentrations of 75 to 25 percentile) observed for PM during both warm (1.03, 95% CI: 0.98 - 1.08) and cold months (1.05, 95% CI: 1.02 - 1.07), and for O during cold months (1.08, 95% CI: 1.02 - 1.14). The exposure-response relationship with PM during the cold months was essentially linear, whereas thresholds of effect were observed for the other associations at low-medium pollutant concentrations. Results were robust to multi-pollutant modeling and adjustment for additional covariates. We found no effect modification by most children's characteristics, while effect sizes were higher on days with detected tree and grass pollens during warm months. Our results suggest that even small decreases in pollutant concentrations could potentially reduce risk of childhood asthma exacerbation - an important finding, given the high burden of childhood asthma and known disparities in asthma control.</p>

<p>Pollen from trees, grasses, and weeds can trigger asthma exacerbation in sensitized individuals. However, there are gaps in knowledge about the effects, such as the relative risks from different plant taxa and threshold levels of effect. We aimed to describe the local association between pollen and asthma exacerbation among children in the City of Philadelphia, and to evaluate whether effects are modified by children's characteristics and clinical factors (e.g., child's age, race/ethnicity, comorbidities). We conducted a time-stratified case-crossover study of pediatric (age &lt;18 years) asthma exacerbation, with cases identified through electronic health records (EHR) of the Children's Hospital of Philadelphia (CHOP) health system from March through October in the years 2011-2016. Daily pollen counts were obtained from the local National Allergy Bureau certified pollen counter. We applied conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between the pollen level (vs. none detected) and odds of asthma exacerbation, adjusting for temperature, relative humidity, and holidays. We estimated same-day exposure effects, as well as effects from exposure lagged by up to 5 days. There were 35,040 asthma exacerbation events during the study period, with the majority occurring among black, non-Hispanic children (81.8%) and boys (60.4%). We found increased odds of asthma exacerbation among Philadelphia children in association with tree pollen, both for total tree pollen and most individual tree types. Increased odds from total tree pollen were observed at the lowest levels studied (≤5 grains/m, unlagged, OR&nbsp;=&nbsp;1.06, 95% CI: 1.02, 1.10), and exhibited a positive exposure-response pattern of effect; tree pollen levels above 1000 grains/m (unlagged) were associated with 64% increased odds of asthma exacerbation (95% CI: 1.45, 1.84). Grass pollen was associated with asthma exacerbation only at levels above the 99 percentile (52 grains/m), which occurred, on average, two days per year during the study period (with 2-day lag, OR&nbsp;=&nbsp;1.38, 95% CI: 1.19, 1.60). There was an inverse association (reduced asthma exacerbation) with ragweed pollen that was consistent across analyses. Pollen from other weeds was associated with increased odds of asthma exacerbation, without a clear exposure-response pattern (2-day lag, significant increases ranging from 8% to 19%). Increased odds from tree pollen and weeds (other than ragweed) were higher among children with allergic rhinitis. While there are known benefits from urban vegetation for human health, there are risks as well. It is important to note, however, that pollen is released during a limited time frame each year, and advisories informed by local data can enable susceptible individuals to avoid outdoor exposure on high-risk days.</p>

<p>Extreme precipitation events may be an important environmental trigger for asthma exacerbations in children. We used a time stratified case-crossover design and data from a large electronic health record database at the Children's Hospital of Philadelphia (CHOP) to estimate associations of daily heavy precipitation (defined as&nbsp;&gt;&nbsp;95th percentile of the summertime distribution) with asthma exacerbation among children. We defined control days as those falling on the same day of the week within the same month and year as the case. We restricted our primary analyses to the summer months in years 2011-2016 and used conditional logistic regression models to estimate associations between heavy precipitation and acute asthma exacerbations in both outpatient (primary care, specialty care, and emergency department) and inpatient settings. We investigated numerous individual-level (e.g., age, sex, eczema diagnosis) and environmental measures (e.g., greenspace, particulate matter) as potential effect modifiers. The analysis include 13,483 asthma exacerbations in 10,434 children. Odds of asthma exacerbation were 11% higher on heavy precipitation vs. no precipitation days (95% CI: 1.02-1.21). There was little evidence of effect modification by most measures. These results suggest that heavy summertime precipitation events may contribute to asthma exacerbations. Further research using larger datasets from other health systems is needed to confirm these results, and to explore underlying mechanisms.</p>

<p><strong>OBJECTIVES: </strong>Our objectives were to (1) quantify the frequency of wheezing episodes and asthma diagnosis in young children in a large pediatric primary care network and (2) assess the variability in practice-level asthma diagnosis, accounting for common asthma risk factors and comorbidities. We hypothesized that significant variability in practice-level asthma diagnosis rates would remain after adjusting for associated predictors.</p>

<p><strong>METHODS: </strong>We generated a retrospective longitudinal birth cohort of children who visited one of 31 pediatric primary care practices within the first 6 months of life from 1/2005-12/2016. Children were observed for up to 8 years or until the end of the observation window. We used multivariable discrete time survival models to evaluate predictors of asthma diagnosis by 3-month age intervals. We compared unadjusted and adjusted proportions of children diagnosed with asthma by practice.</p>

<p><strong>RESULTS: </strong>Of the 161,502 children in the cohort, 34,578 children (21%) received at least one asthma diagnosis. In multivariable modeling, male gender, minority race/ethnicity, gestational age &lt;34 weeks, allergic rhinitis, food allergy, and prior wheezing episodes were associated with asthma diagnosis. After adjusting for variation in these predictors across practices, the cumulative incidence of asthma diagnosis by practice by age 6 years ranged from 11-47% (interquartile range (IQR): 24-29%).</p>

<p><strong>CONCLUSIONS: </strong>Across pediatric primary care practices, adjusted incidence of asthma diagnosis by age 6 years ranged widely, though variation gauged by the IQR was more modest. Potential sources of practice-level variation, such as differing diagnosis thresholds and labeling of different wheezing phenotypes as "asthma", should be further investigated.</p>