Effect of personal exposure to black carbon on changes in allergic asthma gene methylation measured 5 days later in urban children: importance of allergic sensitization

Background Asthma gene DNA methylation may underlie the effects of air pollution on airway inflammation. However, the temporality and individual susceptibility to environmental epigenetic regulation of asthma has not been fully elucidated. Our objective was to determine the timeline of black carbon (BC) exposure, measured by personal sampling, on DNA methylation of allergic asthma genes 5 days later to capture usual weather variations and differences related to changes in behavior and activities. We also sought to determine how methylation may vary by seroatopy and cockroach sensitization and by elevated fractional exhaled nitric oxide (FeNO). Methods Personal BC levels were measured during two 24-h periods over a 6-day sampling period in 163 New York City children (age 9–14 years), repeated 6 months later. During home visits, buccal cells were collected as noninvasive surrogates for lower airway epithelial cells and FeNO measured as an indicator of airway inflammation. CpG promoter loci of allergic asthma genes (e.g., interleukin 4 (IL4), interferon gamma (IFNγ), inducible nitric oxide synthase (NOS2A)), arginase 2 (ARG2)) were pyrosequenced at the start and end of each sampling period. Results Higher levels of BC were associated with lower methylation of IL4 promoter CpG−48 5 days later. The magnitude of association between BC exposure and demethylation of IL4 CpG−48 and NOS2A CpG+5099 measured 5 days later appeared to be greater among seroatopic children, especially those sensitized to cockroach allergens (RR [95% CI] 0.55 [0.37–0.82] and 0.67 [0.45–0.98] for IL4 CpG−48 and NOS2A CpG+5099, respectively), compared to non-sensitized children (RR [95% CI] 0.87 [0.65–1.17] and 0.95 [0.69–1.33] for IL4 CpG−48 and NOS2A CpG+5099, respectively); however, the difference was not statistically different. In multivariable linear regression models, lower DNA methylation of IL4 CpG−48 and NOS2A CpG+5099 were associated with increased FeNO. Conclusions Our results suggest that exposure to BC may exert asthma proinflammatory gene demethylation 5 days later that in turn may link to airway inflammation. Our results further suggest that seroatopic children, especially those sensitized to cockroach allergens, may be more susceptible to the effect of acute BC exposure on epigenetic changes

High Rate of Hospital Admissions Among Patients with Cirrhosis Seeking Care in US Emergency Departments

BACKGROUND AND AIMS: Emergency Departments (ED) can serve as a gateway to specialty care for patients with cirrhosis with limited care access. We described the rates and characteristics of patients with cirrhosis who access United States (US) EDs, and identified factors associated with subsequent hospitalization. METHODS: Using data from the National Hospital Ambulatory Medical Care Survey, cirrhosis-related ED from 2000 to 2009 were identified and compared to all other ED visits. RESULTS: From 2000 to 2009, there were an estimated 1,029,693 cirrhosis and 877 million non-cirrhosis visits. Compared to the general ED population, those with cirrhosis were more frequently male (58 vs. 44 %, p = 0.02), Hispanic (18.6 vs. 10.6 %, p<0.05), seeking care in urban areas (91.6 vs. 73.4 %, p<0.05) and had Medicaid/no insurance (43 vs. 35 %, p < 0.01). Patients with cirrhosis were more frequently triaged immediately or emergently (72.3 vs. 54.2 %, p < 0.01). The majority were admitted or transferred to another hospital (66.8 vs. 17.4 %, p < 0.01). Among patients with cirrhosis, patients with age ≥ 65 - years were more likely to be admitted (adjusted OR 2.49, 95 % CI 1.08–5.73), and Medicaid/uninsured (adjusted OR 0.34; 95 % CI 0.17–0.67) were less likely to be admitted, after adjusting for patient demographics, hospital characteristics, and triage score. CONCLUSIONS: Patient with cirrhosis account for approximately 100,000 US ED visits annually. The higher admission rates among patients with cirrhosis indicate a high acuity of illness. Older age among those admitted may reflect poorer functional status. Finally, high visit but low admission rates among those with Medicaid/no insurance suggest a gap in specialty care