Brain injury is the most common cause of death for patients resuscitated from cardiac arrest. Magnesium is an attractive neuroprotective compound which protects neurons from ischemic injury by reducing neuronal calcium overload via NMDA receptor modulation and preventing calcium-induced mitochondrial permeability transition. Intramuscular (IM) delivery of MgSO4 during CPR has the potential to target these mechanisms within an early therapeutic window. We hypothesize that IM MgSO4 administrated during CPR could achieve therapeutic serum magnesium levels within 15 min after ROSC and improve neurologic outcomes in a rat model of asphyxial cardiac arrest. Male Long Evans rats were subjected to 8-min asphyxial cardiac arrest and block randomized to receive placebo, 107 mg/kg, 215 mg/kg, or 430 mg/kg MgSO4 IM at the onset of CPR. Serum magnesium concentrations increased rapidly with IM delivery during CPR, achieving twofold to fourfold increase by 15 min after ROSC in all magnesium dose groups. Rats subjected to cardiac arrest or sham surgery were block randomized to treatment groups for assessment of neurological outcomes. We found that IM MgSO4 during CPR had no effect on ROSC rate (p > 0.05). IM MgSO4 treatment had no statistically significant effect on 10-day survival with good neurologic function or hippocampal CA1 pyramidal neuron survival compared to placebo treatment. In conclusion, a single dose IM MgSO4 during CPR achieves up to fourfold baseline serum magnesium levels within 15 min after ROSC; however, this treatment strategy did not improve survival, recovery of neurologic function, or neuron survival. Future studies with repeated dosing or in combination with hypothermic targeted temperature management may be indicated.

Introduction: Brain injury is the most common cause of death for patients resuscitated from cardiac arrest. Magnesium is an attractive neuroprotective therapy that has the potential to reduce neuronal calcium overload via NMDA receptor modulation and prevent mitochondrial permeability transition. Intramuscular (IM) delivery of MgSO4 during CPR has the potential to target these mechanisms within their presumed therapeutic window. Hypothesis: IM MgSO4 administrated during CPR will achieve therapeutic serum magnesium levels, which is ≥ 2 times of baseline, within 15 minutes after ROSC and improve neurologic outcomes. Methods: Male Long Evans rats were subjected to 8-minute asphyxial cardiac arrest. For the dose-finding study (n = 4/group), rats were block randomized to receive placebo, 107 mg/kg, 215 mg/kg, or 430 mg/kg MgSO4 IM at the onset of CPR. Serial blood samples were collected at baseline, 15 min, 30 minutes, 1 hour and 2 hours after return of spontaneous circulation (ROSC) and analyzed for serum magnesium concentration. For the long-term outcome study (n = 9/group), rats subjected to cardiac arrest were blindly block randomized to the same treatment groups with the addition of a sham-operated group. Post-cardiac arrest care included maintenance of normothermia (36.7 °C - 37.3 °C) for 72 hours. Serial blood samples were collected at baseline, 15 min and 1 hour after ROSC and neurologic function score (NFS) was performed daily for 10 days. Good neurologic function was predefined as NFS ≥ 450. Results: IM MgSO4 during CPR had no effect on ROSC rate (p > 0.05). The serum magnesium concentrations at 15 min after ROSC of 107 mg/kg group, 215 mg/kg group and 430 mg/kg group were 3.9 ± 0.9, 6.2 ± 1.8, and 7.6 ± 1.8 mg/dl, which were 2.0 fold, 3.1 fold and 4.2 fold of baseline respectively. IM MgSO4 had no statistically significant effect on 10-day survival or 10-day survival with good neurologic function. Conclusion: Single dose IM MgSO4 during CPR achieves up to 4-fold baseline magnesium levels within 15 min after ROSC in a rat model of asphyxia cardiac arrest. This treatment strategy did not improve survival or recovery of neurologic function. Future studies with repeated dosing or in combination with hypothermic targeted temperature management may be indicated.

Introduction: Post-cardiac arrest brain injury is a major cause of mortality and morbidity. Insulin has well-established CNS neuroprotecive properties mediated by the AKT survival signaling pathway, and known transnasal transport mechanisms make it possible to rapidly achieve therapeutic brain insulin levels after intranasal delivery. Hypothesis: We hypothesize that high-dose intranasal insulin (HD-IN-I) administered during CPR, could improve neurologic outcomes in a rat model of asphyxial cardiac arrest. Methods: Male Long Evans rats were subjected to 8-minute asphyxial cardiac arrest then block randomized to HD-IN-I (1.92 U/g brain wet weight) or placebo (PL) given at the onset of CPR by an experimental operator blinded to treatment. Sham operated rats were used as uninjured controls. For the long-term outcome study (n = 14/group), rats with return of spontaneous circulation (ROSC) were maintained at 37.0 ±0.5 °C for 72 hours and neurologic function was assessed on days 7 - 10. For the mechanistic study (n = 6/group), rats with ROSC were euthanized 30 minutes after ROSC and regional brain homogenates were analyzed by western blot for AKT phosporylation. Results: HD-IN-I during CPR had no statistically significant effect on ROSC rate (93% (13/14) HD-IN-I vs. 86% (12/14) PL, p > 0.05) or 10-day survival (71% (10/14) HD-INI vs. 43% (6/14) PL, p > 0.05). HD-IN-I had no significant impact on serum glucose concentrations. At 10 days post-ROSC, rats in the HD-IN-I group had significantly improved performance on rotarod (latency to fall 87±27 sec HD-IN-I vs. 41±18 sec PL, p < 0.05), Barnes maze (latency to escape box 27±15 sec HD-IN-I vs. 298±5 sec PL, p < 0.05), and passive avoidance (latency to re-enter shock chamber 300±0 sec HD-IN-I vs. 142±46 sec PL, p < 0.05) testing. Hippocampal phosph-AKT/total AKT ratio increased 2-fold in the placebo group and 5.7-fold in the HD-IN-I group relative to shams (p < 0.05). Conclusions: HD-IN-I administered during CPR causes rapid activation of brain AKT survival signaling and improves recovery of neurologic function in a rat cardiac arrest model. Additional studies are warranted to determine dose optimization, therapeutic window and effectiveness in large animal models to advance this novel therapy toward clinical trials.

BACKGROUND:Few longitudinal studies examine inflammation and lung function in asthma. We sought to determine the cytokines that reduce airflow, and the influence of respiratory viral infections on these relationships.METHODS:Children underwent home collections of nasal lavage during scheduled surveillance periods and self-reported respiratory illnesses. We studied 53 children for one year, analyzing 392 surveillance samples and 203 samples from 85 respiratory illnesses. Generalized estimated equations were used to evaluate associations between nasal lavage biomarkers (7 mRNAs, 10 proteins), lung function and viral infection.RESULTS:As anticipated, viral infection was associated with increased cytokines and reduced FVC and FEV1. However, we found frequent and strong interactions between biomarkers and virus on lung function. For example, in the absence of viral infection, CXCL10 mRNA, MDA5 mRNA, CXCL10, IL-4, IL-13, CCL4, CCL5, CCL20 and CCL24 were negatively associated with FVC. In contrast, during infection, the opposite relationship was frequently found, with IL-4, IL-13, CCL5, CCL20 and CCL24 levels associated with less severe reductions in both FVC and FEV1.CONCLUSIONS:In asthmatic children, airflow obstruction is driven by specific pro-inflammatory cytokines. In the absence of viral infection, higher cytokine levels are associated with decreasing lung function. However, with infection, there is a reversal in this relationship, with cytokine abundance associated with reduced lung function decline. While nasal samples may not reflect lower airway responses, these data suggest that some aspects of the inflammatory response may be protective against viral infection. This study may have ramifications for the treatment of viral-induced asthma exacerbations.

BackgroundUpper respiratory tract viral infections cause asthma exacerbations in children. However, the impact of natural colds on children with asthma in the community, particularly in the high-risk urban environment, is less well defined.ObjectiveWe hypothesized that children with high-symptom upper respiratory viral infections have reduced airway function and greater respiratory tract inflammation than children with virus-positive low-symptom illnesses or virus-negative upper respiratory tract symptoms.MethodsWe studied 53 children with asthma from Detroit, Michigan, during scheduled surveillance periods and self-reported respiratory illnesses for 1 year. Symptom score, spirometry, fraction of exhaled nitric oxide (FeNO), and nasal aspirate biomarkers, and viral nucleic acid and rhinovirus (RV) copy number were assessed.ResultsOf 658 aspirates collected, 22.9% of surveillance samples and 33.7% of respiratory illnesses were virus-positive. Compared with the virus-negative asymptomatic condition, children with severe colds (symptom score ≥5) showed reduced forced expiratory flow at 25% to 75% of the pulmonary volume (FEF25%-75%), higher nasal messenger RNA expression of C-X-C motif chemokine ligand (CXCL)-10 and melanoma differentiation-associated protein 5, and higher protein abundance of CXCL8, CXCL10 and C-C motif chemokine ligands (CCL)-2, CCL4, CCL20, and CCL24. Children with mild (symptom score, 1-4) and asymptomatic infections showed normal airway function and fewer biomarker elevations. Virus-negative cold-like illnesses demonstrated increased FeNO, minimal biomarker elevation, and normal airflow. The RV copy number was associated with nasal chemokine levels but not symptom score.ConclusionUrban children with asthma with high-symptom respiratory viral infections have reduced FEF25%-75% and more elevations of nasal biomarkers than children with mild or symptomatic infections, or virus-negative illnesses.

Objective: Optimization of post-cardiac arrest hypothermic-targeted temperature management (HTTM) is limited by an inadequate understanding of the fundamental mechanisms of action. This study tested the hypothesis that post-cardiac arrest HTTM reduces delayed secondary neuronal cytosolic Ca 2+ overload that causes pathologic calpain activity and neuronal death after cardiac arrest (CA) Methods: Male Long Evens rats were subjected to 8-minute asphyxial CA (ACA) followed by CPR. Rats that achieved return of spontaneous circulation (ROSC) were block randomized to normothermic- targeted temperature management (NTTM; n=13), hypothermic-TTM at 36 o C (HTTM-36;n=13) or 33 o C (HTTM-33;n=10). HTTM was initiated 1h after ROSC and maintained for 24h. Neurologic function score was assessed daily. Rats were euthanized at 48h post-ROSC. Regional brain homogenates were generated in a subset of animals for Western blot analysis of calpain-cleaved alpha-spectrin as a measure of pathologic calpain activity (n=6/group). Sham rats were used as uninjured controls (n=9) Results: Survival at 48h post-ROSC was 69%, 69%, and 90% in the NTTM, HTTM-36 and HTTM-33 groups respectively (p>0.05: chi-squared). Survival with good neurologic function (GNF: defined as NFS > 450 out of 500) was 0%, 15%, and 60% in the NTTM, HTTM-36 and HTTM-33 groups respectively (p<0.05 for HTTM-33 vs. HTTM-36 and NTTM: chi-squared). Compared to NTTM, pathologic calpain activity in the hippocampus, cortex, caudoputamen, and cerebellum was decreased by 23±20%, 38±56%, 40±55%, 62±20% in the HTTM-36 groups and 33±13%, 55±72%, 66±89%, 69±17% in the HTTM-33 group respectively (p <0.05 for HTTM-33 and HTTM-36 cerebellum, p> 0.05 for all other regions: ANOVA, Tukey’s post-hoc) Conclusion: In this rat model of asphyxial cardiac arrest, HTTM with a target temperature of 33°C improved 48-hour survival with GNF compared to HTTM with a target temperature of 36°C and NTTM. Post-cardiac arrest regional brain calpain activity was significantly reduced with HTTM at 33°C and 36°C compared to NTTM in the cerebellum, but not other brain regions. Further work is needed to explore the potential causal link between the reduction of pathologic calpain activity and the neuroprotective effect of post-cardiac arrest HTTM

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) is a feasible and effective resuscitation strategy for refractory cardiac arrest, but often fails to restore heart and brain functi...

Objectives: High-dose valproic acid in combination with hypothermic- targeted temperature management has been reported to synergistically improve neurologic outcomes after cardiac arrest. This study investigated the potential synergistic mechanisms. Design: Prospective, randomized, experimental study. Setting: University research institution. Subjects: Male Long Evans rats. Intervention: Rats resuscitated from asphyxial cardiac arrest were randomized to one of the three groups: normothermic-targeted temperature management (37 degrees C +/- 1 degrees C), hypothermic-targeted temperature management (33 degrees +/- 1 x 24 hr + placebo infusion), hypothermic-targeted temperature management plus high-dose valproic acid (300 mg/kg IV x 1 initiated 5 min post return of spontaneous circulation and infused over 20 min) (hypothermictargeted temperature management + valproic acid). Measurements and Main Results: Seventy-two-hour survival was significantly greater with hypothermic-targeted temperature management + valproic acid, compared to hypothermic-targeted temperature management and normothermic-targeted temperature management (p < 0.05). Survival with good neurologic function, neurodegeneration, expression of HSP70, phosphorylation of Akt and Erk1/2 were not significantly different between hypothermictargeted temperature management and hypothermic-targeted temperature management + valproic acid. The prevalence of seizures during the first 72-hour postcardiac arrest was significantly lower with hypothermic-targeted temperature management + valproic acid compared to hypothermic-targeted temperature management and normothermic-targeted temperature management (p = 0.01). Conclusions: High-dose valproic acid combined with hypothermictargeted temperature management prevents postcardiac arrest seizures and improves survival. It remains to be determined if the mechanism of seizure prevention is through the antiepileptic effect of valproic acid or direct neuroprotection. Overall, the combination of high-dose valproic acid and hypothermic-targeted temperature management remains a promising strategy to improve cardiac arrest outcomes.

Objective: Mechanistic optimization of inta-arrest hypothermic-targeted temperature management (HTTM) is necessary for successful translation to clinical practice. Our study evaluates the potential...

Aim: Post-cardiac arrest hypothermic-targeted temperature management (HTTM) improves outcomes in preclinical cardiac arrest studies. However, inadequate understanding of the mechanisms and therapeutic windows remains a barrier to optimization. We tested the hypothesis that combined intra- and post cardiac arrest HTTM provides a synergistic outcome benefit compared to either strategy alone.Methods: Rats subjected to 8-min asphyxial cardiac arrest were block randomized to 4 treatment groups (n = 12/group): NTTM) normothermic-targeted temperature management; 1-24 HTTM) HTTM initiated 1 h post-ROSC and maintained for 24 h; Intra-1 HTTM) HTTM initiated at CPR onset and maintained for 1 h; and Intra-24 HTTM) HTTM initiated at CPR onset and maintained for 24 h. HTTM was induced by nasopharyngeal cooling and maintained using an automated temperature regulation system. Target temperature range was 36.5-37.5 degrees C for NTTM and 32.0-34.0 degrees C for HTTM. Post-arrest neurologic function score (NFS) was measured daily, and rats surviving 72 h were euthanized for histological analysis of neurodegeneration.Results: Target brain temperature was achieved 7.8 +/- 3.3 min after initiating intra-arrest cooling. The survival rate was 42%, 50%, 50%, and 92% in the NTTM, 1-24 HTTM, Intra-1 HTTM, and Intra-24 HTTM groups, respectively (p < 0.05, Intra-24 group vs. all other groups). The rate of survival with good neurologic function (NFS >= 450) was 33% in the Intra-24 HTTM group vs. 0% in all other groups (mid p < 0.05). Hippocampal CA1 sector neurodegeneration was significantly reduced in the Intra-24 HTTM group compared to all other groups (p < 0.05).Conclusion: Combined intra- and post-cardiac arrest HTTM has greater outcome benefits than either strategy alone. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Introduction: While hypothermic target temperature management (HTTM) has been regarded as a reliable strategy for post-cardiac arrest treatment, there are no pharmacologic agents proved to be neuroprotective against post-cardiac arrest brain injury. In recent years, many studies have shown that valproic acid (VPA), a well-known antiepileptic drug, is neuroprotective against various brain insults. VPA inhibits histone deacetylase activity and causes hyperacetylation of histones, followed by transcriptional activation of anti-apoptotic genes. In this study we tested the hypothesis that combination therapy of hypothermia and VPA could enhance neuroprotection and improve outcome. Methods: Male Long-Evans rats were instrumented for continuous telemetric EEG recording with video and then subjected to 8-minute asphyxia cardiac arrest. Nine rats that achieved the return of spontaneous circulation (ROSC) were allocated into the following 3 groups. Controlled normothermia (N group, 36.5-37.5 °C, n=3), HTTM (H group, 32-33 °C for 24 hours, n=3) and HTTM with VPA administration (HV group, 32-33 °C for 24 hours, 300 mg/kg, IV, n=3). Three-day survival, best achieved neurologic function score (NFS), the number of seizure event was compared between the 3 groups. Results: The 3-day survival was 33.3% in N group, 33.3 % in H group and 100 % in HV group (p=0.12). The best NFS averaged 263.33 ± 36.67 in N group, 380 ± 64.29 in H group and 468.33 ± 15.90 in HV group (p=0.13). The total number of seizure events in each group averaged 0.33 ± 0.33 in N group, 4.33 ± 2.96 in H group, 0 in HV group (p=0.20). Conclusions: These early results suggest that the combination of HTTM and VPA is a promising strategy that could result in synergistic neuroprotection after cardiac arrest.

OBJECTIVE:To investigate the effects of the combination of extracorporeal cardiopulmonary resuscitation and thrombolytic therapy on the recovery of vital organ function after prolonged cardiac arrest.DESIGN:Laboratory investigation.SETTING:University laboratory.SUBJECTS:Pigs.INTERVENTIONS:Animals underwent 30-minute untreated ventricular fibrillation cardiac arrest followed by extracorporeal cardiopulmonary resuscitation for 6 hours. Animals were allocated into two experimental groups: t-extracorporeal cardiopulmonary resuscitation (t-ECPR) group, which received streptokinase 1 million units, and control extracorporeal cardiopulmonary resuscitation (c-ECPR), which did not receive streptokinase. In both groups, the resuscitation protocol included the following physiologic targets: mean arterial pressure greater than 70 mm Hg, cerebral perfusion pressure greater than 50 mm Hg, PaO2 150 ± 50 torr (20 ± 7 kPa), PaCO2 40 ± 5 torr (5 ± 1 kPa), and core temperature 33°C ± 1°C. Defibrillation was attempted after 30 minutes of extracorporeal cardiopulmonary resuscitation.MEASUREMENTS AND MAIN RESULTS:A cardiac resuscitability score was assessed on the basis of success of defibrillation, return of spontaneous heart beat, weanability from extracorporeal cardiopulmonary resuscitation, and left ventricular systolic function after weaning. The addition of thrombolytic to extracorporeal cardiopulmonary resuscitation significantly improved cardiac resuscitability (3.7 ± 1.6 in t-ECPR vs 1.0 ± 1.5 in c-ECPR). Arterial lactate clearance was higher in t-ECPR than in c-ECPR (40% ± 15% vs 18% ± 21%). At the end of the experiment, the intracranial pressure was significantly higher in c-ECPR than in t-ECPR. Recovery of brain electrical activity, as assessed by quantitative analysis of electroencephalogram signal, and ischemic neuronal injury on histopathologic examination did not differ between groups. Animals in t-ECPR group did not have increased bleeding complications, including intracerebral hemorrhages.CONCLUSIONS:In a porcine model of prolonged cardiac arrest, t-ECPR improved cardiac resuscitability and reduced brain edema, without increasing bleeding complications. However, early electroencephalogram recovery and ischemic neuronal injury were not improved.

Introduction: Hypothermic targeted temperature management (TTM) has greatly improved post-cardiac arrest patient outcomes, but also makes prognostication more difficult. In this study, we tested the hypothesis that early continuous EEG biomarkers are associated with neurologic outcome in post-cardiac arrest rats treated with normothermic and hypothermic TTM. Methods: Male rats were instrumented for continuous telemetric EEG (cEEG) recording and then subjected to 8-minute asphyxia cardiac arrest. Eight rats that achieved ROSC underwent either normothermic or hypothermic TTM (37 ± 0.5 °C or 33 ± 0.5 °C) for 24 hours and cEEG monitoring up to 72 hours. Quantitative EEG analysis determined the power density of delta (0.1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz) and sigma (13-18 Hz) frequency bands in all 10 second windows. The mean spectral power and Spearman correlation with time for the first 12 hours after return of spontaneous circulation (ROSC) were calculated and correlated with best neurologic function score (NFS) and survival with good NFS (NFS ≥ 450 out of 500). Results: Over all rats tested, the mean delta band power in the first 12 hours after ROSC was inversely correlated with best neurologic function score and associated with poor outcome (Table and Figure). There was no statistical difference in other frequency bands. Similar findings were present when stratifying into normothermic and hypothermic treatment groups. Conclusions: This study suggests that, the early power density of delta frequency bands from cEEG is a potential predictor of neurologic outcome in a mixed population of rats treated with normothermic and hypothermic TTM.

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) after prolonged cardiac arrest (CA) often fails to restore cardiac and cerebral function. The primary limiting factor is presumed to be ischemia duration. An alternative hypothesis is that intravascular coagulation prevents tissue reperfusion. Hypothesis: Adding thrombolytics to ECPR after prolonged untreated CA improves cardiac and cerebral recovery when compared to ECPR alone. Methods: We developed a porcine model of 30 minute untreated ventricular fibrillation followed by ECPR for 6 hours. Animals were instrumented for hemodynamic and intracranial pressure (ICP) monitoring and continuous EEG. Two groups were studied: t-ECPR (n=7) with streptokinase 1 MU added to prime circuit; c-ECPR (n=6) with no streptokinase. ECPR goals included: flow >50 ml/kg/min, MAP >70 mmHg, PaO2 150±50 mmHg, PaCO2 40±5 mmHg, core temperature 33±1 °C. Recovery of heart function was assessed by echocardiography and weanability from ECPR. After 6 hours, animals were euthanized and brain harvested for quantification of intracerebral hemorrhage and neuronal injury. Results: Recovery of heart function following defibrillation occurred in 1/6 c-ECPR and 7/7 t-ECPR animals (p <0.05). Successful weaning from ECPR within 6 hours was achieved in 1/6 c-ECPR and 4/7 t-ECPR animals. Six-hour lactate clearance was significantly lower in c-ECPR than in t-ECPR (18±2 % vs 40±15 %, p <0.05). Marked increase in post-arrest ICP occurred in c-ECPR but not in t-ECPR (19±13 mmHg vs 1±3 mmHg, p <0.05). Quantitative EEG analysis revealed no recovery of brain activity in either group. Thrombolytics did not result in increased intracerebral hemorrhage (c-ECPR 0.011±0.001 % vs 0.003±0.002 % t-ECPR, p <0.05). Composite histologic damage score (scale 0 to 5) was not different between groups (c-ECPR 3.2±0.9 vs. 3.2±1.1 t-ECPR, p >0.05). Conclusions: Thrombolytic enhanced ECPR after prolonged untreated CA improves recovery of cardiac function and reduces brain edema without increasing bleeding. However, we detected no effect on early EEG recovery or ischemic neuronal injury. Additional studies are needed to determine if thrombolytic enhanced ECPR improves long-term survival and neurologic outcomes after prolonged CA.

Background and Aims: Asthma is a complex chronic disease with heterogeneous clinical expression and waxing and waning activity over the life cycle. Epigenetic modifications may be a mechanism to explain clinical variability. However, the relationship between environmental exposures, epigenetic changes, and health outcomes is unclear, particularly in young vulnerable populations. Methods: This study builds on an investigation of the impact of near-highway residence on the health of asthmatic children, "The Community Action Against Asthma (CAAA) Diesel Study." In this pilot study, we measured global DNA methylation in cells from saliva in a cohort of urban asthmatic children. Children aged 6-14 with asthma were recruited based on the proximity of their residence to highways. DNA was extracted from saliva samples from 79 children and assessed for degree of DNA methylation at four loci within LINE-1. We assessed the association between methylation and gender, age, and exposure to highways. Results: Methylation of LINE-1 loci was heterogeneous and ranged from a mean of 66% at site 3, to 74% at site 2, with an overall mean of 70% across the four sites. Girls were hypomethylated at site 3 (65.64%) compared to boys (67.11%, p=0.048) and this difference remained significant after adjustment for gender, race, asthma severity, exposure to tobacco smoke, and highway exposure. Neither current highway exposure status nor asthma severity were significant independent predictors of methylation. However, changes in methylation pattern with age differed across exposure groups, showing a steeper declining gradient in the high diesel exposure group. Conclusions: Differences in global methylation measured at LINE-1 are site-specific, present relatively early in life and may vary by exposure to roadway-associated air pollution. There may be important gender-specific differences in methylation. Expanded studies of the epigenome in exposed populations will help clarify the role of epigenetic modifications in asthma phenotype.

This study evaluates effects of air filters on the pollutant exposures experienced by children with asthma in Detroit Michigan. 126 households were randomized into three groups: a control group; a standard intervention group receiving a free-standing HEPA filter placed in the child's sleeping area; and an enhanced intervention group receiving the filter and an air conditioner (AC). All three groups received community health worker home visits. Information regarding the building, emission sources and occupant activities was obtained using surveys and a household inspection. Parameters monitored included particulate matter (PM), particle number, carbon dioxide, volatile organic compounds, environmental tobacco smoke (ETS), air exchange rates, and filter use. Filter use greatly reduced PM levels, e.g., concentrations were lowered by 69 ± 24% immediately after filter installation. However, most participants decreased their use of the filters over time and when environmental monitoring was not being conducted.