Grantee Research Project Results
2020 Progress Report: Center for the Study of Childhood Asthma in the Urban Environment (CCAUE)
EPA Grant Number: R836152Center: Center for the Study of Childhood Asthma in the Urban Environment
Center Director: Hansel, Nadia
Title: Center for the Study of Childhood Asthma in the Urban Environment (CCAUE)
Investigators: Hansel, Nadia , Diette, Greg , McCormack, Meredith , Koehler, Kirsten , Polotsky, Seva
Institution: The Johns Hopkins University
EPA Project Officer: Callan, Richard
Project Period: September 1, 2015 through August 31, 2019 (Extended to August 31, 2021)
Project Period Covered by this Report: September 1, 2019 through April 30,2020
Project Amount: $1,200,000
RFA: Children's Environmental Health and Disease Prevention Research Centers (2014) RFA Text | Recipients Lists
Research Category: Human Health , Children's Health
Objective:
Project 1 Title: AIRWEIGHS: Investigating Obesity as a Susceptibility Factor for Air Pollution in Childhood Asthma
Through both an observational and intervention study, this project aims to identify why obese children with asthma have increased susceptibility to air pollution compared to lean counterparts. We will examine the leading candidate mediators of the increased susceptibility to PM among overweight children, with asthma who are more susceptible to indoor particulate matter compared to normal weight children with asthma using an experimental study design with an air purifier intervention that targets indoor PM reduction.
Specific aims of the study include:
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To determine if overweight inner-city children, compared to lean inner-city children, have greater improvement in asthma with an air purifier intervention aimed at reducing indoor PM
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To determine whether increases in tidal volume and thereby increases in doses of inhaled particles mediate increased susceptibility to indoor PM among overweight versus lean children with asthma
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To determine whether increases in inflammatory and oxidative stress responses mediate increased susceptibility to indoor PM among overweight versus lean children with asthma.
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To determine whether increases in glucocorticoid resistance mediate increased susceptibility to indoor PM among overweight versus lean children with asthma.
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To determine whether differences in sleep disordered breathing mediate increased susceptibility to indoor PM among overweight versus lean children with asthma.
Project 2 Title: Novel exposure metrics for assessing the effects of ultrafine and fine particulate matter on asthma in children (PEAK)
The goal of this project is to determine which potentially modifiable factors of fine particulate matter (PM2.5), including ultrafine particles, micro-environmental and peak exposures that are associated with asthma symptoms in children. A second, related objective is to evaluate the effects of these fine PM factors on overweight children with asthma. Together, such evidence will allow us to build individualized environmental intervention strategies that target this susceptible population.
Specific Aim 1: Evaluate the relationship between ultrafine particles (UFP) and fine particles and asthma symptoms, lung function, and inflammatory biomarkers among asthmatic children. A backpack containing air pollution monitoring equipment for ultrafine particle number concentration (PNC) and fine particulates (PM2.5 mass) and a GPS receiver will be provided to each child for this repeated-measures panel study. Concurrent with the personal exposure assessment, we will collect information on participant symptoms, lung function, urinary leukotriene E4 (uLTE4) and exhaled NO daily.
Specific Aim 2: Evaluate the contribution of peak exposure to cumulative exposure and estimate its effects in inner-city children with asthma. We will calculate the contribution of peak exposures (PNC and PM2.5 mass) to 24-hour cumulative exposure. We will ask children and parents about activities during each 24-hour period to assess the role of sources on peak exposures (e.g. cooking).
Specific Aim 3: Evaluate the role of weight as a susceptibility factor for the impact of UFP and peak PM exposure on asthma outcomes. Approximately half the children in this study will have BMI > 85th percentile and half will be lean.
Project 3 Title: Animal Model
Childhood obesity, asthma and particulate matter (PM) exposure disproportionally affect low- income minority children in the US. Previous research from our group provided evidence that obesity may exacerbate effects of PM on asthma. The overall OBESE ASTHMA Program proposal focuses on the role of obesity in amplifying the pathogenic effects of PM on asthma in children. The underlying mechanisms by which obesity augments effects of PM are poorly understood.
Obesity causes chronic low grade inflammation resulting in type 2 diabetes, atherosclerosis and non-alcoholic fatty liver disease. Multiple studies have also shown that obesity is linked to asthma. Obesity-related asthma is phenotypically different from allergic Th2 cytokine dependent asthma. Weight loss appears to be more beneficial in treatment of asthma in obese patients with the non- allergic phenotype compared to the atopic Th2 phenotype. Obesity-induced asthma has been associated with increased circulating levels of pro-inflammatory cytokines IL-6, IL-1β and IL-17A as well as an adipokine leptin and decreased levels of an anti-inflammatory adipokine adiponectin. Inflammation induced by PM exposure in asthma is phenotypically similar to obesity-induced asthma involving the non Th2 response, chronic inflammation and oxidative stress. Our Preliminary Data show that obesity enhances PM-induced airway hyperresponsiveness (AHR) and increases IL-6 levels in the lungs. PM and obesity may interact leading to the AHR and chronic airway inflammation.
In addition to chronic inflammation, obesity predisposes to obstructive sleep apnea (OSA). The prevalence of OSA in obese children ranges from 20 to 40%. OSA is highly associated with asthma in children and treatment of OSA improves asthma control. The few studies that have evaluated a link between environmental pollution and OSA showed that pollution exposure is associated with a higher prevalence of OSA and reduction in air pollution decreases the severity of OSA. Thus, obesity and sleep apnea may interact with PM to exacerbate asthma and pulmonary inflammation. Animal studies of Project 3 will complement human Projects 1 and 2 enabling us to examine these relationships mechanistically. We will capitalize on our extensive experience with animal models of obesity and sleep apnea (Polotsky) as well as pulmonary inflammation and asthma (Mitzner). We will 1) utilize established models of diet-induced obesity (DIO) and PM exposure in the non-atopic obesity-prone mouse strain C56BL/6J to identify the effect of obesity on the AHR; 2) examine the role of adipokines and inflammatory cytokines, especially IL-6; 3) differentiate the effects of obesity and a high fat diet comparing weight loss on a low fat diet and calorie restriction on a high fat diet; 4) examine the role of sleep apnea using our novel model of upper airway obstruction during sleep induced by excessive tongue adiposity; this unique model has been engineered by overexpressing an adipogenic transcription factor peroxisome proliferator-activated receptor gamma (PPAR) in the tongue. The overarching hypothesis of the Project 3 is that obesity exacerbates the PM-induced AHR due to pathogenic effects of adiposity and comorbid sleep apnea and that the effects of obesity are mediated via IL-6. Furthermore, these detrimental effects of obesity can be attenuated by weight loss and sleep apnea treatment. Our hypothesis will be addressed in two Specific Aims:
In Specific Aim 1, we will test causal links between obesity and the PM-induced AHR and inflammation. (A) We will quantify the PM-induced AHR and inflammation in lean and DIO wildtype and IL-6 knockout mice; (B) To link to potential therapeutic actions, we will quantify the ability of weight loss to attenuate the PM-induced AHR and inflammation.
In Specific Aim 2, we will examine effects of sleep apnea on the PM-induced AHR and inflammation. We will quantify the PM-induced AHR and inflammation in DIO mice with recurrent upper airway obstruction during sleep caused by genetically induced excessive tongue adiposity. Experiments will also assess the effects of sleep apnea treatment, which will be modelled by supplemental oxygen.
Progress Summary:
Project 1 Title: AIRWEIGHS: Investigating Obesity as a Susceptibility Factor for Air Pollution in Childhood Asthma
We have continued to make significant progress since the initial launch of this study. Accomplishments to date include:
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Collection of clinical data, respiratory physiologic data, and biomarkers. Biomarkers include complete blood count with differential, hemoglobin A1C, peripheral blood mononuclear cells, serum stored for cytokines, oxidative stress and fatty acids from blood; nasal epithelial lining fluid; urine; skin, oral and nasal sampling for microbiota. Home environmental sampling has been completed for two one-week time periods per participant.
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Project 1 has worked with community core to launch the Lung Health Ambassadors Program. One-thousand and twenty-three (1023) 7th thru 12th grade school students representing 14 middle and high schools and two Recreation Centers have participated in and completed the Lung Health Ambassadors Program (LHAP) training on issues of smoking, air pollution, lung health, obstructive lung diseases.
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The AIRWEIGHS study supported the career development of early investigators with projects nested within Project 1. Early investigators include Dr. Emily Brigham, who has a K23 award; Lesliam Alcala-Quiros, who has a K01 award; David Wu, supported by a F32 award; and Parisa Kaviany, recipient of the institutionally awarded Bauernschmidt Award and JP Senter, medical student contributed work on neighborhood characteristics of asthmatic children and their families. The work of all these trainees hadled to abstracts and publications. Additional detail can be found in the Administrative Core section of the Center Report.
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The AIRWEIGHS study has provided preliminary data for an NIH R01 application (R01 HL 152419) submitted by Dr. McCormack to study the effect of environmental exposures and sleep in Baltimore City children with asthma. This was scored well and will be resubmitted in July 2020.
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The AIRWEIGHS Study has provided preliminary data for an NIH application UG3 HL154273 to study the implementation of a multi-level school based asthma intervention. This application was favorably reviewed and funding decisions are pending.
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The AIRWEIGHS Study received additional funding through the Bloomberg American Health Initiative Launchpad grant to study the impact of COVID 19 and COVID 19 pandemic conditions on study participants.
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The following abstracts were accepted for presentation at the American Thoracic Society Annual Meeting and the American Academy of Allergy Asthma & Immunology Annual Meeting during the past year:
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Kaviany P, Brigham EP, Collaco JM, Rice JL, Woo H, Wood M, Koehl R, Koehler K, Hansel NN, McCormack MC. Determinants of Adherence to Air Purifier Use for Inner City Children with Asthma. American Thoracic Society Annual Meeting. May 15-20, 2020. Philadelphia, PA.
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Kaviany P, Collaco JM, Koehler K, Wood M, Woo H, Koehl R, Brigham EP, Hansel NN, McCormack MC. Seasonal Patterns of Adherence to Air Purifier Use in Inner City Children with Asthma. American Academy of Allergy Asthma & Immunology Annual Meeting, Accepted for Poster Presentation; 2020, March 13-16, Philadelphia, PA.
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Senter JO, Kaviany P, Galiatsatos P, Koehler K, Brigham EP, Hansel NN, McCormack MC. Geospatial Analysis of Neighborhood Characteristics and Pediatric Asthma Morbidity in Baltimore City. B52. Pediatric Allergy and Asthma, pp. A3706-A3706. American Thoracic Society, 2020.
Project 2 Title: Novel exposure metrics for assessing the effects of ultrafine and fine particulate matter on asthma in children (PEAK)
Collaborations and Developing Materials: We continue to closely collaborate with the Project 1 (AIRWEIGHS: Investigating Obesity as a Susceptibility Factor for Air Pollution in Childhood Asthma) study team in different aspects of the project. Bimonthly center meetings are held where all the lead investigators as well as the research coordinators and field and clinic staff for from both PEAK and AIRWEIGHS projects take part. One of the outcomes of this close collaboration with the AIRWEIGHS team has been the
development and review of the necessary Standards of Practice (SOPs) to be used in the PEAK study. All SOPs are complete and being followed by all field and laboratory staff. Study questionnaires have also been developed for the participating children and parents, which will ask about asthma health, medications, diet, and physical activity as part of their enrollment in the study. Questionnaires have also been developed to ask about daily exposures and activities that may contribute to asthma health. These questionnaires have been used throughout the study.
Approvals: We have obtained IRB approval and renewal for the PEAK study.
Results to Date: We have enrolled all 50 children with a targeted four days of sampling per child for the PEAK study. Enrollment and data collection is complete. Our data quality assurance and analysis are ongoing. Preliminarily, we found that the children were exposed to relatively high levels of PM2.5 mass (24-hr mean (N=164): 21.9 μg/m3; range: 4.9-178.9 μg/m3). These exposures show that 93% of children had personal exposures higher than the WHO ambient air recommendation of 10 μg/m3. Ultrafine particle (UFP) exposures (24-hr mean (N=166): 42 μm2/cm3; range: 3-262 μm2/cm3) typically varied over 2 orders of magnitude within a sampling day and were more sensitive to peak concentrations from sources like cooking at using transportation than PM2.5 mass concentrations. There are currently no recommendations for safe levels of exposure to ultrafine particle concentrations. For both for PM2.5 and for ultrafine particles, we found that peak exposures greatly exceeded recommendations, with peak 1-minute average concentrations typically an order of magnitude higher than the 24-hour average concentrations. Using the GPS data, we are currently completing the partitioning of exposures to different microenvironments to evaluate exposure variability by microenvironment.
Our preliminary analysis has also shown that 24-hour averaged exposures showed moderate correlation between PM2.5 mass concentrations and UFP concentrations, as expressed by LDSA, with a Pearson coefficient of 24-hr average concentrations 0.67. Correlations at finer temporal scales were generally lower and highly variable by child and day, depending on the specific sources encountered (e.g. cooking, secondhand smoke, bus exhast, etc.).
We deployed a text messaging interface for children or parents to provide information on child symptoms twice daily. Of participants who agreed to receive text messages, over 80% of text messages reminders sent were completed with symptom information. Children (or their parents) have reported cough on 46% of monitoring days and being awakened by symptoms on 13% of monitoring days. Three batches of urine samples have been sent for uLTE4 analysis and analysis of this data is ongoing.
Project 3 Title: Animal Model
Specific Aim 1
Experiments performed during Years 1-4 of the award have demonstrated that diet-induced obesity (DIO) induced AHR in association with low grade inflammation in lung tissue and, specifically, up-regulation of interleukin 1 β (IL-1β) expression. Experiments of Year 4 examined the role of IL-1β in DIO-induced AHR.
Our results showed that the IL-1β receptor blockade prevented both obesity-induced AHR and pulmonary inflammation, supporting the concept that up-regulation of IL-1β gene expression in the lung could be a mechanism linking obesity and asthma. Given that obesity increases AHR early in the time course and that anakinra was administered only during last two weeks of the 8-week experiment, our data suggest that IL-1β receptor blockers not merely prevent, but also reverse obese asthma. In our study, anakinra lowered fasting serum insulin levels without a significant change in fasting glucose levels indicating increased insulin sensitivity. Our finding suggests that anakinra could contribute to improvement in AHR due to its off-target effects by improving glucose metabolism.
Hypothesis: Lowering insulin resistance in mice DIO will have an independent effect on AHR
Methods: C57BL/6J mice were fed with a high fat diet (HFD) ad libitum for 8 weeks and treated with metformine at 300 mg/mouse/day added receptor blocker (anakinra) or placebo during the last 2 weeks of the experiment (n = 10 per group). Upon completion of the experiment, mice were anesthetized with ketamine/xylazine i.p., tracheostomized and the total respiratory resistance (Rrs) was measured by forced oscillation (Flexivent, SCIREQ Québec, Canada). at baseline and after methacholine aerosol challenge at 3 and 30 mg/mL
Results: Mice in the Meformin and Control groups were of the age and body weight. They consumed the same amount of water and food. Metformin did not affect fasting blood glucose levels. Plasma fasting insulin, leptin and adiponectin levels are pending. Metformin did not affect Rrs at baseline and at 3 mg/ml of methacholine, but there was a nearly two-fold decrease in total respiratory system resistance at 30 mg/ml of methacholine. Surprisingly, metformin increased cellularity of the bronchoalveolar lavage fluid. There was an increase in the percentage of lymphocytes with a corresponding decrease in the percentage of macrophages. There was no evidence of systemic inflammation on CBC (Table 3). IL-1β, TNF-α, IL-6 in the lungs and plasma cytokine levels are pending.
Conclusions: Metformin significantly decreased the airway response to methacholine, which may suggest the role of insulin resistance in increased airway reactivity in obese asthma.
Specific Aim 2. During Years 1-3 of the award we have developed a mouse model of sleep disordered breathing by expressing inhibitory designer receptor exclusively activated by designer drugs (DREADD) in hypoglossal motoneurons 3. During Year 4 we examine the effect of sleep disordered breathing on AHR. Methods: DIO C57BL/6J mice (n = 18) were treated with an inhibitory DREADD harbored by a retrograde adeno-associated virus, AAV9-HA- hM4D-mCherry (Gi). AAV9-DREADD was administered to the genioglossal (GG) muscle of the tongue bilaterally (7 x 1010 vg/10 μl in total). Four weeks after viral infection mice ( n = 9) underwent daily injection of a novel DREADD ligand (JHU37160 dihydrochloride, 0.1mg/kg in 250 µl saline i.p.) vs saline ( n = 9) for 2 weeks. Upon completion of treatment, GG EMG was recorded followed by sleep study and AHR measurements.
Results:
J60 injections did not affect mouse body weight, food intake or blood glucose level.
There was a significant decrease of GG muscle EMG activity, which strongly suggests the development of sleep apnea (as we have demonstrated previously.However, J60 administration was not associated with an increase in AHR.
Conclusion: Obstruction of upper airway in our mouse model of sleep disordered breathing was not associated with AHR. This data suggest that OSA does not cause or exacerbate asthma. However, in our model mice were obese which already predisposes to AHR. So, ‘the ceiling’ effect is possible. We will repeat the experiment in lean mice.
Future Activities:
Project 1 Title: AIRWEIGHS: Investigating Obesity as a Susceptibility Factor for Air Pollution in Childhood Asthma
During the next reporting period, we plan to complete enrollment of the goal of 200 participants. We were on target to meet our recruitment goal of 200. Unfortunately, due to the COVID pandemic and subsequent limitations to clinical research studies, we had to pause in-person visits. In light of this, we implemented remote work procedures, which included cancelling screening visits (11), pre-intervention clinic and home visits (5), and overnight sleep visits (18). Additionally, we have cancelled post-intervention clinic and home visits (15) and rescheduled these participants to complete a modified phone interview.
Specific milestones include:
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As soon as the COVID-19 situation improves and we are given permission from the institution and IRB to resume in-person study visits, we will resume and complete study visits.
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Stored biospecimens will be batch processed and analyzed for markers of inflammation and oxidative stress.
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We will analyze results and prepare manuscripts to communicate study findings.
We feel confident given the success of our efforts over the past year that we will be able to complete the project by June of 2021.
Each of the remaining children to enter the study will complete clinic visit 1 in which they will be screened and enrolled; clinic visit 2, in which they will be randomly assigned to one of the intervention groups (either the group that will receive two of the active air purifiers or the group that will receive air purifiers with filters removed).
Depending on COVID-related restrictions, we hope to have participants complete an overnight sleep study to identify and characterize sleep disordered breathing. In addition, to the extent permissible under COVID safety guidelines for re-opening, participant homes will be visited two times, once to install environmental monitoring equipment, collect settled dust samples and complete a home inspection, and a second time to remove the environmental monitoring equipment and place the air purifiers. These protocols may be modified to address safety concerns. By the end of the no cost extension, we will have completed the study. We anticipate that we will have collected and stored urine and blood samples at each of three time points for study participants. We will analyze results and prepare manuscripts to communicate study findings.
Project 2 Title: Novel exposure metrics for assessing the effects of ultrafine and fine particulate matter on asthma in children (PEAK)
Continue Data analysis: We have completed data collection and are currently analyzing data and writing papers. Two manuscripts are currently in preparation for submission to the peer-reviewed literature. One will focus on the exposure assessment for PM2.5 and UFP (Aim 1). This will consider both daily exposures and variability and variability by microenvironment. The second paper will focus on the relationship between PM2.5 and UFP exposures and symptoms and uLTE4 (Aim 1). This paper will also explore the influence of obesity on the relationships between exposure and asthma (Aim 3). The next paper will use our new analysis software to identify peak exposures and to determine whether there are different relationships between peak exposure and health than observed for daily mean exposures (Aim 2).
Domestic Conferences: Next year we anticipate that we will present at the join International Society of Exposure Scientists and International Society of Environmental Epidemiologists meetings to share preliminary results with the scientific community. These meetings are subject to change due to COVID-19.
Project 3 Title: Animal Model
Our work during the previous funding period convincingly demonstrated that the pathogenesis of non-eosinophilic asthma in our mouse model is determined by the presence of obesity and ensuing low grade pulmonary inflammation (aim 1a of this project). Experiments with anakinra also demonstrated that improvement in airway hyperresponsiveness was associated with a decrease in insulin resistance. We performed a pilot experiment with metformin, the results of which strongly suggest that the main underlying mechanism of airway hyperresponsiveness (AHR) in obese asthma is insulin resistance which overrides effects of sleep apnea. What remains is the completion of specific aim 1b of his project, to link to potential therapeutic actions.
Specific milestones will be:
1. To establish the relationship between PM exposure and AHR in the sleep apnea model – by December 2021.
2. To establish the role of insulin resistance in PM- and obesity induced AHR in our mouse model- by June 2021.
Journal Articles: 48 Displayed | Download in RIS Format
Other center views: | All 73 publications | 48 publications in selected types | All 48 journal articles |
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Belli AJ, Bose S, Aggarwal N, DaSilva C, Thapa S, Grammer L, Paulin LM, Hansel NN. Indoor particulate matter exposure is associated with increased black carbon content in airway macrophages of former smokers with COPD. Environmental Research 2016;150:398-402. |
R836152 (2019) R836152 (2020) R836150 (2017) R836150 (2019) R836150 (2020) |
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Berger S, Pho H, Fleury-Curado T, Bevans-Fonti S, Younas H, Shin M, Jun J, Anokye-Danso F, ahima R, Enquist L, Mendelowitz D, Schwartz A, Polotsky V. Intranasal Leptin Relieves Sleep-disordered Breathing in Mice with Diet-induced Obesity. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 2019;199(6):773-783. |
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Berman JD, McCormack MC, Koehler KA, Connolly F, Clemons-Erby D, Davis MF, Gummerson C, Leaf PJ, Jones TD, Curriero FC. School environmental conditions and links to academic performance and absenteeism in urban, mid-Atlantic public schools. International Journal of Hygiene and Environmental Health 2018;221(5):800-808. |
R836152 (Final) R835639 (2016) R835639 (2017) R835639 (2018) |
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Brigham EP, Matsui EC, Appel LJ, Bull DA, Curtin-Brosnan J, Zhai S, White K, Charleston JB, Hansel NN, Diette GB, McCormack MC. A pilot feeding study for adults with asthma: the healthy eating better breathing trial. PLoS One 2017;12(7):e0180068 (14 pp.). |
R836152 (2018) R836152 (2020) |
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Brigham EP, Steffen LM, London SJ, Boyce D, Diette GB, Hansel NN, Rice J, McCormack MC. Diet pattern and respiratory morbidity in the Atherosclerosis Risk in Communities Study. Annals of the American Thoracic Society 2018;15(6):675-682. |
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Brigham E, Woo H, McCormack M, Rice J, Koehler K, Vulcain T, Wu T, Koch A, Sharma S, Kolandooz F, Bose S, Hanson C, Romero K, Diette G, Hansel N. Omega-3 and Omega-6 Intake Modifies Asthma Severity and Response to Indoor Air Pollution in Children. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 2019;199(12):1478-1486. |
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Caballero-Eraso C, Shin M, Pho H, Kim L, Pichard L, Wu Z, Gu C, Berger S, Pham L, Yeung H, Shirahata M, Schwartz A, Tang W, Sham J, Polotsky V. Leptin acts in the carotid bodies to increase minute ventilation during wakefulness and sleep and augment the hypoxic ventilatory response. JOURNAL OF PHYSIOLOGY-LONDON 2019;597(1):151-172. |
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Davis MF, Ludwig S, Brigham EP, McCormack MC, Matsui EC. Effect of home exposure to Staphylococcus aureus on asthma in adolescents. Journal of Allergy and Clinical Immunology 2018;141(1):402-405.e10. |
R836152 (2018) R836152 (2020) R836152 (Final) R834510 (Final) |
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Fleury Curado T, Fishbein K, Pho H, Brennick M, Dergacheva O, Sennes LU, Pham LV, Ladenheim EE, Spencer R, Mendelowitz D, Schwartz AR, Polotsky VY. Chemogenetic stimulation of the hypoglossal neurons improves upper airway patency. Scientific Reports 2017;7:44392. |
R836152 (2017) R836152 (2020) |
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Fleury Curado T, Pho H, Berger S, Caballero-Eraso C, Shin MK, Sennes LU, Pham L, Schwartz AR, Polotsky VY. Sleep-disordered breathing in C57BL/6J mice with diet-induced obesity. Sleep 2018;41(8).zsy089 (9 pp.). |
R836152 (2018) R836152 (2020) |
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Fricke K, Vieira M, Younas H, Shin MK, Bevans-Fonti S, Berger S, Lee R, D’Alessio FR, Zhong Q, Nelson A, Loube J. Sanchez I, Hansel NN, Mitzner W, Polotsky VY. High fat diet induces airway hyperresponsiveness in mice. Scientific Reports 2018;8(1):6404 (6 pp.). |
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Galiatsatos P, Kineza C, Hwang S, Pietri J, Brigham E, Putcha N, Rand CS, McCormack M, Hansel NN. Neighbourhood characteristics and health outcomes:evaluating the association between socioeconomic status, tobacco store density and health outcomes in Baltimore City. Tobacco Control 2018;27(e1):e19-e24. |
R836152 (2018) R836152 (2019) R836152 (2020) R836150 (2018) R836150 (2020) |
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Grant T, McCormack M, Peng R, Keet C, Davis M, Newman M, Balcer-Whaley S, Matsui E. Comprehensive home environmental intervention did not reduce allergen concentrations or controller medication requirements among children in Baltimore. JOURNAL OF ASTHMA 2022;1-10 |
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Grant T, LIlley T, McCormack M, Rathouz P, Pent R, Keeo C, Rule A, Davis M, Balcer-Whaley S, Newman M, Matsui E. Indoor environmental exposures and obstructive lung disease phenotypes among children with asthma living in poor urban neighborhoods. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 2023;151(3):716. |
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Gu C, Loube J, Lee R, Bevans-Fonti S, Wu T, Barmine J, Jun J, McCormack M, Hansel N, Mitzner W, Polotsky V. Metformin Alleviates Airway Hyperresponsiveness in a Moe Model of Diet-Induced Obesity. FRONTIERS IN PHYSIOLOGY 2022;13(883275). |
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Javaheri S, Barbe F, Campos-Rodriguez F, Dempsey JA, Khayat R, Javaheri S, Malhotra A, Martinez-Garcia MA, Mehra R, Pack AI, Polotsky VY, Redline S, Somers VK. Sleep apnea: types, mechanisms, and clinical cardiovascular consequences. Journal of the American College of Cardiology 2017;69(7):841-858. |
R836152 (2017) R836152 (2020) |
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Kaviany P, Brighham E, Collaco J, Rice J, Woo H, Wood M, Koehl R, Wu T, Eakin M, koehler K, Hansel N, McCormack M. Patterns and predictors of air purifier adherence in children with asthma living in low-income, urban Households. JOURNAL OF ASTHMA 2022;59(5):946-955 |
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Lambert AA, Putcha N, Drummond MB, Boriek AM, Hanania NA, Kim V, Kinney GL, McDonald MN, Brigham EP, Wise RA, McCormack MC, Hansel NN, COPDGene Investigators. Obesity is associated with increased morbidity in moderate to severe COPD. Chest 2017;151(1):68-77. |
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Lemoine S, Brigham E, Woo H, Hanson C, McCormack M, Koch A, Putcha N, hansel N. Omega-3 fatty acid intake and prevalent respiratory symptoms among adults with COPD. BMC PULMONARY MEDICINE 2019;19. |
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Levy JI, Quiros-Alcala L, Fabian MP, Basra K, Hansel NN. Established and emerging environmental contributors to disparities in asthma and chronic obstructive pulmonary disease. Current Epidemiology Reports 2018;5(2):114-124. |
R836152 (2018) R836152 (2019) R836152 (2020) R836150 (2019) R836150 (2020) R836156 (2018) R836156 (2019) R836156 (2020) |
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Lu KD, Phipatanakul W, Perzanowski MS, Balcer-Whaley S, Matsui EC. Atopy, but not obesity is associated with asthma severity among children with persistent asthma. Journal of Asthma 2016;53(10):1033-1044. |
R836152 (2017) R836152 (2020) |
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McCormack MC, Belli AJ, Waugh D, Matsui EC, Peng RD, Williams DL, Paulin L, Saha A, Aloe CM, Diette GB, Breysse PN, Hansel NN. Respiratory effects of indoor heat and the interaction with air pollution in chronic obstructive pulmonary disease. Annals of the American Thoracic Society 2016;13(12):2125-2131. |
R836152 (2018) R836152 (2019) R836152 (2020) R836150 (2019) R836150 (2020) |
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McCormack MC, Paulin LM, Gummerson CE, Peng RD, Diette GB, Hansel NN. Colder temperature is associated with increased COPD morbidity. European Respiratory Journal 2017;49(6):1601501. |
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McCormack M, Balsubramanian A, Wise R, Keet C, Matsui E, Peng R. Reply by McCormack et al. to Townsend and Cowl, and to Miller et al. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 2022;206(6):795-796. |
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Mesarwi OA, Shin MK, Bevans-Fonti S, Schlesinger C, Shaw J, Polotsky VY. Hepatocyte hypoxia inducible factor-1 mediates the development of liver fibrosis in a mouse model of nonalcoholic fatty liver disease. PLoS One 2016;11(12):e0168572. |
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Nnodum BN, McCormack MC, Putcha N, Hwang S, Paulin LM, Brigham EP, Fawzy A, Romero K, Diette GB, Hansel NN. Impact of physical activity on reporting of childhood asthma symptoms. Lung 2017;195(6):693-698. |
R836152 (2018) R836152 (2020) |
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Paulin LM, Williams DA, Peng R, Diette GB, McCormack MC, Breysse P, Hansel NN. 24-h Nitrogen dioxide concentration is associated with cooking behaviors and an increase in rescue medication use in children with asthma. Environmental Research 2017;159:118-123. |
R836152 (2018) R836152 (2020) |
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Peters KO, Williams AL, Abubaker S, Curtin-Brosnan J, McCormack MC, Peng R, Breysse PN, Matsui EC, Hansel NN, Diette GB, Strickland PT. Predictors of polycyclic aromatic hydrocarbon exposure and internal dose in inner city Baltimore children. Journal of Exposure Science and Environmental Epidemiology 2017;27(3):290-298. |
R836152 (2017) R836152 (2020) |
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Pham LV, Polotsky VY. Genome-wide association studies in obstructive sleep apnea. Will we catch a black cat in a dark room? American Journal of Respiratory and Critical Care Medicine 2016;194(7):789-791. |
R836152 (2017) R836152 (2020) |
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Pham LV, Miele CH, Schwartz NG, Arias RS, Rattner A, Gilman RH, Miranda JJ, Polotsky VY, Checkley W, Schwartz AR. Cardiometabolic correlates of sleep disordered breathing in Andean highlanders. European Respiratory Journal 2017;49(6):1601705 (20 pp.). |
R836152 (2018) R836152 (2020) |
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Pham LV, Meinzen C, Arias RS, Schwartz NG, Rattner A, Miele CH, Smith PL, Schneider H, Miranda JJ, Gilman RH, Polotsky VY, Checkley W, Schwartz AR. Cross-sectional comparison of sleep-disordered breathing in native Peruvian highlanders and lowlanders. High Altitude Medicine & Biology 2017;18(1):11-19. |
R836152 (2018) R836152 (2020) |
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Rice JL, Brigham E, Dineen R, Muqueeth S, O'Keefe G, Regenold S, Koehler K, Rule A, McCormack M, Hansel NN, Diette GB. The feasibility of an air purifier and secondhand smoke education intervention in homes of inner city pregnant women and infants living with a smoker. Environmental Research 2018;160:524-530. |
R836152 (2018) R836152 (2020) R834510 (Final) |
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Shin M, Eraso C, Mu Y, Gu C, Yeung B, Kim L, Liu X, Wu Z, Paudel O, Prchard L, Shirahata M, Tang W, Sham J, Polotsky V. Leptin Induces Hypertension Acting on Transient Receptor Potential Melastatin 7 Channel in the Carotid Body. CIRCULATION RESEARCH 2019;125(11):989-1002. |
R836152 (Final) R834510 (Final) |
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Shin M-K, Han W, Joo H, Bevans-Fonti S, Shiota M, Stefanovski D, Polotsky VY. Effect of adrenal medullectomy on metabolic responses to chronic intermittent hypoxia in the frequently sampled intravenous glucose tolerance test. Journal of Applied Physiology 2017;122(4):767-774. |
R836152 (2017) R836152 (2020) |
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Stauber CE, Ortiz GM, Loomis DP, Sobsey MD. A randomized controlled trial of the concrete biosand filter and its impact on diarrheal disease in Bonao, Dominican Republic. American Journal of Tropical Medicine and Hygiene 2009;80(2):286-293. |
R836152 (2017) R836152 (2020) SU832463 (Final) |
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Tejwani V, McCormack A, Suresh K, Woo H, Xu N, Davis M, Brigham E, Hansel N, McCormack M, D'Alessio F. Dexamethasone-Induced FKBP51 Expression in CD4+ T-Lymphocytes Is Uniquely Associated With Worse Asthma Control in Obese Children With Asthma. FRONTIERS IN IMMUNOLOGY 2021;12(74482) |
R836152 (Final) |
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Wu TD, Brigham EP, Peng R, Koehler K, Rand C, Matsui EC, Diette GB, Hansel NN, McCormack MC. Overweight/obesity enhances associations between secondhand smoke exposure and asthma morbidity in children. The Journal of Allergy and Clinical Immunology: In Practice 2018;6(6):2157-2159.e5. |
R836152 (2018) R836152 (2020) |
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Wu T, Fawzy A, Brigham E, McCormack M, Rosas I, Villareal D, Hanania N. Association of Triglyceride-Glucose Index and Lung Health A Population-Based Study. CHEST 2021;160(3):1026-1034 |
R836152 (Final) R836150 (2021) |
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Wu T, Zaeh S, Eakin M, Koehler K, Davis M, Wohn C, Diibor I, Psoter K, Cronister C, Connolly F, Stein M, McCormack M. Association of School Infrastructure on Health and Achievement Among Children With Asthma. ACADEMIC PEDIATRICS 2023;23(4):814-820. |
R836152 (Final) R835639 (Final) |
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Zaeh S, McCormack M, Eakin M. Key policies to support asthma medication management for children. ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY 2019;123(5):428-429 |
R836152 (Final) R835639 (Final) |
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Zaeh S, Koehler K, Eakin M, WOhn C, Diibor I, Eckmann T, Wu T, Clemons-Erby D, Gummerson C, Green T, Wood M, Majid E, Stein M, Rule A, Davis M, McCormack M. Indoor Air Quality Prior to and Following School Building Renovation in a Mid-Atlantic School District. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021;18(22). |
R836152 (Final) R835639 (Final) |
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Fawzy A, Putcha N, Paulin LM, Aaron CP, Labaki WW, Han MK, Wise RA, Kanner RE, Bowler RP, Barr RG, Hansel NN. Association of thrombocytosis with COPD morbidity:the SPIROMICS and COPDGene cohorts. Respiratory Research 2018;19(1):20. |
R836152 (2019) R836152 (2020) |
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Galiatsatos P, Brigham EP, Pietri J, Littleton K, Hwang S, Grant MC, Hansel NN, Chen ES. The effect of community socioeconomic status on sepsis-attributable mortality. Journal of Critical Care 2018;46:129-133. |
R836152 (2019) R836152 (2020) |
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Younas H, Vieira M, Gu C, Lee R, Shin MK, Berger S, Loube J, Nelson A, Bevans-Fonti S, Zhong Q, D’Alessio FR. Caloric restriction prevents the development of airway hyperresponsiveness in mice on a high fat diet. Scientific reports 2019;9(1):1-9. |
R836152 (Final) R834510 (Final) R836150 (2020) |
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Raju S, Keet CA, Paulin LM, Matsui EC, Peng RD, Hansel NN, McCormack MC. Rural residence and poverty are independent risk factors for chronic obstructive pulmonary disease in the United States. American journal of respiratory and critical care medicine. 2019;199(8):961-969. |
R836152 (2019) R836152 (2020) R836150 (2019) R836150 (2020) |
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Tsou PY, McCormack MC, Matsui EC, Peng RD, Diette GB, Hansel NN, Davis MF. The effect of dog allergen exposure on asthma morbidity among inner‐city children with asthma. Pediatric Allergy and Immunology 2020;31(2):210-3. |
R836152 (Final) R832139 (Final) R834510 (Final) R836150 (2020) |
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Wu TD, Fawzy A, Kinney GL, Bon J, Neupane M, Tejwani V, Hansel NN, Wise RA, Putcha N, McCormack MC. Metformin use and respiratory outcomes in asthma-COPD overlap. Respiratory research 2021;22(1):1-8. |
R836152 (Final) R836150 (2021) |
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Afshar-Mohajer N, Wu TD, Shade R, Brigham E, Woo H, Wood M, Koehl R, Koehler K, Kirkness J, Hansel NN, Ramchandran G. Obesity, tidal volume, and pulmonary deposition of fine particulate matter in children with asthma. European Respiratory Journal 2022;59(3). |
R836152 (Final) R836150 (2021) |
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Supplemental Keywords:
Project 1 Title: AIRWEIGHS: Investigating Obesity as a Susceptibility Factor for Air Pollution in Childhood Asthma air pollution, obesity, asthma exacerbation, inner city. Project 2 Title: Novel exposure metrics for assessing the effects of ultrafine and fine particulate matter on asthma in children (PEAK) ultrafine particles, peak exposure, overweight children, asthma exacerbation, and inner city Project 3 Title: Animal Model n/aRelevant Websites:
Project 1 Title: AIRWEIGHS: Investigating Obesity as a Susceptibility Factor for Air Pollution in Childhood Asthma
clinicaltrials.gov (NCT02763917)
Project 2 Title: Novel exposure metrics for assessing the effects of ultrafine and fine particulate matter on asthma in children (PEAK)
n/a
Project 3 Title: Animal Model
n/a
Progress and Final Reports:
Original Abstract Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R836152C001 Investigating obesity as a susceptibility factor for air pollution in childhood
R836152C002 Novel exposure metrics for assessing the effects of ultrafine and fine particulate matter on asthma in children
R836152C003 The Role of Obesity in Biological Responses to Particulate Matter in Mice
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.
Project Research Results
- Final Report
- 2019 Progress Report
- 2018 Progress Report
- 2017 Progress Report
- 2016 Progress Report
- Original Abstract
48 journal articles for this center