Grantee Research Project Results
2010 Progress Report: Mechanisms of Asthma -- Dietary Interventions against Environmental Triggers
EPA Grant Number: R834510Center: Center for the Study of Childhood Asthma in the Urban Environment
Center Director: Hansel, Nadia
Title: Mechanisms of Asthma -- Dietary Interventions against Environmental Triggers
Investigators: Diette, Greg , Matsui, Elizabeth C. , Peng, Roger D. , Shreffler, Wayne G. , Breysse, Patrick N. , Anderson, Cheryl , Rand, Cynthia , Gittelsohn, Joel , McCormack, Meredith , Hansel, Nadia , Sharma, Sangita , Biswal, Shyam
Institution: The Johns Hopkins University
EPA Project Officer: Hahn, Intaek
Project Period: August 1, 2009 through July 31, 2015
Project Period Covered by this Report: August 1, 2009 through July 31,2010
Project Amount: $4,107,128
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2009) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
Our program aims to understand how diet influences the asthmatic response to indoor and outdoor airborne pollutants and allergens, with an expectation of translating findings into practical dietary strategies to improve pediatric asthma health. In the first 8 months of the program award, we have made significant progress to integrate all components of the program, ensure tight collaboration between the leaders of the three projects and four cores, and exchange of ideas and data. Projects 1 and 2 have both obtained IRB approval to begin their respective studies and have been engaged in development of protocol materials, hiring and training of staff and enrollment of study subjects. Likewise, Project 3 has a series of experiments in mice that have been completed and are underway to support the project aims.
Investigators from each Project and Core have been meeting weekly at regularly scheduled staff and data meetings, with informal meetings even more frequently. The Cores are all fully functional and productive. Core A has been instrumental in organizing the Program, including a multi-investigator kick-off meeting held on November 24, 2009. Core B has embarked on many tasks, including forms development, database development and refinement, sample tracking and upgrade of a data web portal. Core C has developed exposure assessment protocols and begun collection of environmental data. Core D has begun planned activities, including the convening of our Community Advisory Board and is actively working with the CAB members to plan the conduct of Aim 2, Project 1.
The high level of enthusiasm and productivity of the investigator group is reflected in the details of the individual project and core reports that are attached.
Progress Summary:
In project 1, we finalized the study protocol, consent form, manual of procedures, and data collection forms and received Johns Hopkins IRB approval in March 2010. Study staff members have received training on questionnaire and PiKO (lung function) administration and exhaled nitric oxide, blood, urine and nasal lavage collection. The food frequency questionnaire and physical activity questionnaires were pilot tested in a subgroup of children. In addition, another training session to administer the Food Frequency Questionnaire (nutritional tool) for newly hired staff has been organized for June 2010. Recruitment is continuous and ongoing. Currently, five subjects have completed their consent visits and home visits have been scheduled (see enrollment report). This study will fill a significant gap between the evidence base for the effect of diet on susceptibility to indoor air pollutants on asthma health. To our knowledge, the proposed study will be the first to examine the interactive effect of diet with indoor pollutants (PM and NO2). The results of this study will help to establish the role and mechanism of effect of diet and indoor pollutants on inner city childhood asthma, and lay the groundwork for intervention treatments and strategies.
Significant progress has been made on Project 2. A study coordinator has been hired for the project and protocol, consent forms, manual of procedures, and data collection forms developed and finalized for the Sprouts Study. In addition, substantial work has been done in collaboration with the Johns Hopkins University ICTR Nutrition Core to develop a palatable means of ingesting the broccoli sprouts and a means of blinding participants to the sprouts content of the sandwiches (alfalfa vs. sprouts). A pilot tolerability study has just been launched to identify the maximal broccoli sprouts dose that causes minimal to no gastrointestinal complaints. IRB and ICTR approval have been obtained. In addition, pilot studies for oxidative stress biomarker and gene expression assays have been completed so that these assays are ready to be implemented in the planned Sprouts and Omni Heart Diet studies. Additional progress is detailed below:
- Since we proposed testing the efficacy of dietary interventions in treatment of mouse allergen-induced asthma, we have also spent the last year finalizing the environmental mouse allergen challenge (EMAC) protocol. Although bronchial challenges using allergen delivered by nebulizer is a well-accepted model for allergen-induced lower airways disease, the environmental allergen challenge (EAC) model simulates environmental exposure to allergen similar to that which may occur in homes. In the EAC, the exposure chamber is cured by housing the source animals in the chamber. When subjects enter the chamber, they are exposed to airborne allergen through both upper and lower airways, as would occur in a mouse-infested home. Since the EAC is a better model, we have developed an environmental mouse allergen challenge (EMAC) model as an alternative to the bronchial challenge model and have received IRB approval for this study. The first EMAC was performed May 12, 2010 without incident.
- Phase 2 Enzyme Gene Expression Pilot Studies
We have conducted pilot studies measuring Phase II gene expression in nasal epithelial cells from several study populations. Methods for collection of nasal epithelial cells have been piloted, and we have established the feasibility of collecting the samples and of extracting sufficient quantity and quality RNA for gene expression assays. For purposes of our pilot study, nasal epithelial cell samples were collected from an ongoing cohort of Baltimore City children with asthma, and levels of Phase II gene expression were compared to markers of asthma severity.
Samples were collected from a total of 22 adolescents. After RNA extraction, real-time qPCR was used to quantify gene expression of HMOX1 (heme oxygenase (decycling) (1) Spearman correlations were used to examine relationships between Phase II enzyme gene expression and symptom variables. HMOX1 expression in nasal epithelial cells was inversely correlated with days of short-acting beta-agonist (SABA) use in the previous 2 weeks as well as days of slowed activity due to asthma in the previous 2 weeks.These studies will provide important insight into: (1) the mechanisms by which dietary factors may promote or protect against environmentally induced airway inflammation; and (2) potential dietary interventions for asthma and allergies aimed at providing protection against allergen-induced asthma.
Asthma is a complex inflammatory disease characterized by airway hyper-responsiveness (AHR) and chronic airway inflammation, intermittent reversible airway remodeling, excessive mucus production and elevated levels of IgE and Th2 cytokines. Our previous showed greater asthmatic response after allergen challenge in mice with a global defect in Nrf2 dependent environmental stress response. The lungs of Nrf2 -/- mice have higher NF-kB and STAT-6 activity and greater expression of chemokines due to allergens. Thus, Nrf2 is a critical regulator of asthma pathogenesis, which may play an important role in protecting against oxidative stress and inflammatory diseases. Sulforaphane, the active ingredient derived from consumption of broccoli sprout and docosahexaenoic acid (DHA) omega-3 fatty acid that is present in high amount in the Mediterranean-type diet can target Nrf2 pathway and enhance cellular antioxidants. We have hypothesized that antioxidants in the diet such as Sulforaphane and DHA can activate Nrf2 pathway and protect against pulmonary asthmatic response after allergen exposure. This project will focus on investigating relationship between diet and asthma and mechanisms that help in counteracting oxidative stress and inflammation in a mouse model of asthma similar to the dietary modifications proposed in Project 2. The effect of Sulforaphane, main ingredient of broccoli sprout study, is in process. Protection of OVA-induced asthmatic features like airway inflammation, cytokines expression and AHR in mice have been studied further study on these mice in progress. The effect of antioxidant rich Mediterranean-type diet in mice model of asthma is in progress. We have developed and characterized Nrf2 & Keap knock-out mice by crossing of Nrf2/ keap flox/flox mice with Tamoxifen inducible CMV-CRE mice). OVA-induced asthmatic features like airway inflammation, cytokines expression and AHR in mice have been studied further study on these mice in progress. These studies are geared towards understanding the Nrf2 pathway as a critical modifier of pulmonary oxidative stress and asthma. Nrf2 activators could be lead molecules for therapeutic interventions.
In addition to maintenance of the data management system, the Data Management and Statistics Core (DMSC) has provided data support services for all Projects. The DMSC has developed forms, study participant recruitment and tracking systems, provided interim and final analyses of accumulated data, and participated in the preparation of scientific reports and manuscripts. The DMSC holds weekly meetings with Investigators and research staff of the Center for Childhood Asthma in the Urban Environment to present reports of interim analyses, troubleshoot data collection or quality issues, and this meeting also provides a forum for discussions regarding abstract and manuscript preparation. In addition to the weekly meetings, the following objectives have been met:
- Completion of a Tracking/Recruiting Database for Project 1; Tracking/Recruiting Database for Project 2 is under development.
- Completion of Data Collection Forms for Projects 1 and 2.
- Identification of potential study participants from the Future Subjects Database for Projects 1 and 2.
- Upgrade of the user interface and capabilities of the Environmental Data Web Portal.
- Expansion of a Web-based data portal to manage data generated in the Exposure Assessment Core, including PM, NO2, airborne nicotine, HOBO temperature and humidity, and MIE data.
- Implementation of a bar coding system to track biologic samples.
- Maintenance of a database of potential study participants (Future Subjects Database) to be used as a recruitment tool
The following projects are supported by the DMSC, but are not directly related to the CCAUE:
- Data analyses and manuscript preparation for the ICART study, a randomized controlled trial of cockroach allergen abatement for reduction of asthma morbidity.
- Form development, database development, and data analyses for several food allergy studies.
- Database development, data management, and data analyses for the JAXCohort study, a prospective cohort study of newly employed laboratory animal workers.
- Environmental data management and data analyses for the CODE study, a NIH-funded study of airborne and settled dust endotoxin and COPD.
- Forms and database development, environmental data management, and data analyses for COPD-PM, a study investigating the impact of indoor particulate matter exposure on COPD.
- Database development, data management and data analyses for the STOVE study, a HUD-funded study testing the effects of housing interventions on indoor NO2 levels.
These completed and in progress projects are in addition to the day-to-day work of form development, database construction, data entry, data cleaning, quality control checks, preparation of reports, and statistical analysis. The research projects supported by the Data Management and Statistics Core will result in important insights into the impact of diet on asthma, including whether diet interacts with PM and allergen exposure to cause greater asthma symptoms and morbidity, and whether diet interacts with PM or allergen induced symptoms via the oxidative stress pathway. Ultimately, these findings will provide the foundation and rationale for dietary recommendations for asthmatics as well as a rationale for the use of dietary interventions as therapy in the management of asthma.
Consistent with the specific aims of the Environmental Assessment Core, we have used the first 6 months of the project to collaborate in the development and conduct of exposure component of the clinically based and mechanistically based projects. This has included developing exposure assessment protocols for Projects 1 and 2, as well as environmental sample collection for Project 3. In addition, we have collaborated with the Data Management Core on the development and implementation of exposure assessment tools, forms and databases. The Core PI has attended all Community Advisory Board meetings and participated in planning for Community Outreach and Research Translation Core activities.
Consistent with the specific aims of the Community Outreach and Translation Core, we have used the first 6 months of the project to meet with our Community Advisory Board (CAB) to discuss the overall goals of the Mechanisms of AsthmaDietary Interventions against Environmental Triggers projects and solicit their advice on project implementation and strategies for sharing new information with the community. We have also sought CAB input in identifying palatable ways of serving broccoli sprouts in every day foods acceptable to members of the community (as a part of Project 2) by holding a taste test of different preparations including broccoli sprout tacos and broccoli sprout wraps. We have discussed with the CAB strategies that we might use to assess community concerns, issues, barriers and resources related to environmental exposures, diet and asthma, as well as which factors we should consider in developing appropriate measures of dietary barriers for Project 1, Aim 2.
Future Activities:
Core B plans for Year 2 include the following:
- Expand the Environmental Data Management website to improve functionality of current features and expand capabilities.
- Conduct preliminary analyses for Projects 1 and 2.
- Interface with Project 3 to collect assay data and merge assay data with Projects 1 and 2 clinical and environmental datasets.
- Maintain and improve Future Subjects Database, the database of children and adults who have participated in previous studies who may be contacted for participation in future studies.
Core C plans for the future include providing support for conducting exposure assessments (indoor air sampling, allergen sampling, home inspections); and collecting, interpreting and summarizing ambient air quality data from air monitoring sites run by the Maryland Department of the Environment.
Core D personnel will be conducting focus groups with community members in the next project year specifically to assess dietary barriers to healthy eating for East Baltimore parents and children. Going forward, they will be meeting with their CAB regularly to elicit community involvement and effort in the development of new projects and translation to action, as well as serving as a local community resource to schools, community centers and health fairs for information about asthma and the environment.
Project 1 plans for Year 2 include accrual and data collection. Project 2 plans to complete accrual and data collection for the Sprouts tolerability pilot study, to launch the Sprouts intervention stud, and to start planning the Omni Heart Diet intervention study. Project 3 investigators plan to define the role diet in asthma pathogenesis and would like to explore Nrf2 as modifier the disease pathogenesis. We have projected diet-based rf2 activators in preclinical studies for developing Nrf2 activator as therapeutic lead molecule in asthma.
Journal Articles: 90 Displayed | Download in RIS Format
| Other center views: | All 92 publications | 90 publications in selected types | All 90 journal articles |
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Ahluwalia SK, Peng RD, Breysse PN, Diette GB, Curtin-Brosnan J, Aloe C, Matsui EC. Mouse allergen is the major allergen of public health relevance in Baltimore City. The Journal of Allergy and Clinical Immunology 2013;132(4):830-835.e2. |
R834510 (2014) |
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Ahluwalia S, Matsui EC. The indoor environment and its effects on childhood asthma. Current Opinion in Allergy and Clinical Immunology 2011;11(2):137-143. |
R834510 (2012) |
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Arbes Jr. SJ, Matsui EC. Can oral pathogens influence allergic disease? The Journal of Allergy and Clinical Immunology 2011;127(5):1119-1127. |
R834510 (2012) |
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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. |
R834510 (Final) R836152 (Final) |
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Bose S, Breysse PN, McCormack MC, Hansel NN, Rusher RR, Matsui E, Peng R, Curtin-Brosnan J, Diette GB; Center for Childhood Asthma in the Urban Environment. Outdoor exposure and vitamin D levels in urban children with asthma. Nutrition Journal 2013;12:81 (7 pp.). |
R834510 (2014) R834510 (Final) |
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Bose S, Diette GB, Woo H, Koehler K, Romero K, Rule AM, Detrick B, Brigham E, McCormack MC, Hansel NN. Vitamin D Status Modifies the Response to Indoor Particulate Matter in Obese Urban Children with Asthma. Journal of Allergy and Clinical Immunology-In Practice2019;7(6):1815. |
R834510 (Final) R832139 (Final) |
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Breysse PN, Diette GB, Matsui EC, Butz AM, Hansel NN, McCormack MC. Indoor air pollution and asthma in children. Proceedings of the American Thoracic Society 2010;7(2):102-106. |
R834510 (2010) R834510 (2011) R834510 (Final) R832139 (Final) |
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Brigham EP, Kolahdooz F, Hansel N, Breysse PN, Davis M, Sharma S, Matsui EC, Diette G, McCormack MC. Association between Western diet pattern and adult asthma: a focused review. Annals of Allergy, Asthma & Immunology 2015;114(4):273-280. |
R834510 (Final) |
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Brigham EP, McCormack MC, Takemoto CM, Matsui EC. Iron status is associated with asthma and lung function in US women. PLoS One 2015;10(2):e0117545 (12 pp.). |
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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. |
R834510 (Final) R836152 (Final) |
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Butz AM, Matsui EC, Breysse P, Curtin-Brosnan J, Eggleston P, Diette G, Williams D, Yuan J, Bernert JT, Rand C. A randomized trial of air cleaners and a health coach to improve indoor air quality for inner-city children with asthma and secondhand smoke exposure. Archives of Pediatrics & Adolescent Medicine 2011;165(8):741-748. |
R834510 (2011) R834510 (2012) R834510 (2013) R834510 (2014) R834510 (Final) |
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Butz AM, Breysse P, Rand C, Curtin-Brosnan J, Eggleston P, Diette GB, Williams D, Bernert JT, Matsui EC. Household smoking behavior: effects on indoor air quality and health of urban children with asthma. Maternal and Child Health Journal 2011;15(4):460-468. |
R834510 (2010) R834510 (2011) R834510 (Final) |
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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. |
R834510 (Final) R836152 (Final) |
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Chong LK, Ong MJ, Curtin-Brosnan J, Matsui EC. Skin test sensitivity to mouse predicts allergic symptoms to nasal challenge in urban adults. Asthma and Allergy Proceedings 2010;31(6):472-476. |
R834510 (2011) R834510 (Final) |
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Curtin-Brosnan J, Paigen B, Hagberg KA, Langley S, O’Neil EA, Krevans M, Eggleston PA, Matsui EC. Occupational mouse allergen exposure among non-mouse handlers. Journal of Occupational and Environmental Hygiene 2010;7(12):726-734. |
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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. |
R834510 (Final) R836152 (2018) R836152 (2020) R836152 (Final) |
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Filep S, Tsay A, Vailes L, Gadermaier G, Ferreira F, Matsui E, King EM, Chapman MD. A multi-allergen standard for calibration of immunoassays: CREATE principles applied to eight purified allergens. Allergy 2012; 67(2):235-241. |
R834510 (2011) R834510 (2012) R834510 (Final) |
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Filep S, Tsay A, Vailes LD, Gadermaier G, Ferreira F, Matsui E, King EM, Chapman MD. Specific allergen concentration of WHO and FDA reference preparations measured using a multiple allergen standard. The Journal of Allergy and Clinical Immunology 2012;129(5):1408-1410. |
R834510 (2012) R834510 (2013) R834510 (2014) |
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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.). |
R834510 (Final) R836152 (2018) R836152 (2020) |
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Fujimura KE, Rauch M, Matsui E, Iwai S, Calatroni A, Lynn H, Mitchell H, Johnson CC, Gern JE, Togias A, Boushey HA, Kennedy S, Lynch SV. Development of a standardized approach for environmental microbiota investigations related to asthma development in children. Journal of Microbiological Methods 2012;91(2):231-239. |
R834510 (2013) R834510 (2014) |
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Gergen PJ, Teach SJ, Mitchell HE, Freishtat RF, Calatroni A, Matsui E, Kattan M, Bloomberg GR, Liu AH, Kercsmar C, O'Connor G, Pongracic J, Rivera-Sanchez Y, Morgan WJ, Sorkness CA, Binkley N, Busse W. Lack of a relation between serum 25-hydroxyvitamin D concentrations and asthma in adolescents. American Journal of Clinical Nutrition 2013;97(6):1228-1234. |
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Gruchalla RS, Sampson HA, Matsui E, David G, Gergen PJ, Calatroni A, Brown M, Liu AH, Bloomberg GR, Chmiel JF, Kumar R, Lamm C, Smartt E, Sorkness CA, Steinbach SF, Stone KD, Szefler SJ, Busse WW. Asthma morbidity among inner-city adolescents receiving guidelines-based therapy: role of predictors in the setting of high adherence. Journal of Allergy and Clinical Immunology 2009;124(2):213-221. |
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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). |
R834510 (Final) R836152 (Final) |
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Hackstadt AJ, Matsui EC, Williams DL, Diette GB, Breysse PN, Butz AM, Peng RD. Inference for environmental intervention studies using principal stratification. Statistics in Medicine 2014;33(28):4919‐4933. |
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Hansel NN, Matsui EC, Rusher R, McCormack MC, Curtin-Brosnan J, Peng RD, Mazique D, Breysse PN, Diette GB. Predicting future asthma morbidity in preschool inner-city children. Journal of Asthma 2011;48(8):797-803. |
R834510 (2011) R834510 (2012) R834510 (2013) R834510 (2014) R834510 (Final) |
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Hansel NN, McCormack MC, Belli AJ, Matsui EC, Peng RD, Aloe C, Paulin L, Williams DL, Diette GB, Breysse PN. In-home air pollution is linked to respiratory morbidity in former smokers with chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine 2013;187(10):1085-1090. |
R834510 (2013) R834510 (2014) |
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Jassal MS, Diette GB, Dowdy DW. Cost-consequence analysis of multimodal interventions with environmental components for pediatric asthma in the state of Maryland. Journal of Asthma 2013;50(6):672-680. |
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Kaji DA, Belli AJ, McCormack MC, Matsui EC, Williams DL, Paulin L, Putcha N, Peng RD, Diette GB, Breysse PN, Hansel NN. Indoor pollutant exposure is associated with heightened respiratory symptoms in atopic compared to non-atopic individuals with COPD. BMC Pulmonary Medicine 2014;14:147. |
R834510 (2014) |
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Kattan M, Kumar R, Bloomberg GR, Mitchell HE, Calatroni A, Gergen PJ, Kercsmar CM, Visness CM, Matsui EC, Steinbach SF, Szefler SJ, Sorkness CA, Morgan WJ, Teach SJ, Gan VN. Asthma control, adiposity, and adipokines among inner-city adolescents. Journal of Allergy and Clinical Immunology 2010;125(3):584-592. |
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Keet CA, Matsui EC, Dhillon G, Lenehan P, Paterakis M, Wood RA. The natural history of wheat allergy. Annals of Allergy, Asthma, and Immunology 2009;102(5):410-415. |
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Keet CA, McCormack MC, Peng RD, Matsui EC. Age-and atopy-dependent effects of vitamin D on wheeze and asthma. The Journal of Allergy and Clinical Immunology 2011:128(2):414-416.e5. |
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Keet CA, Wood RA, Matsui EC. Personal and parental nativity as risk factors for food sensitization. The Journal of Allergy and Clinical Immunology 2012;129(1):169-175.e5. |
R834510 (2012) R834510 (2013) R834510 (2014) |
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Keet CA, Matsui EC, Savage JH, Neuman-Sunshine DL, Skripak J, Peng RD, Wood RA. Potential mechanisms for the association between fall birth and food allergy. Allergy: European Journal of Allergy and Clinical Immunology 2012;67(6):775-782. |
R834510 (2012) R834510 (2013) R834510 (2014) |
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Keet CA, Wood RA, Matsui EC. Limitations of reliance on specific IgE for epidemiologic surveillance of food allergy. The Journal of Allergy and Clinical Immunology 2012;130(5):1207-1209.e10. |
R834510 (2013) R834510 (2014) |
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Kolahdooz F, Butler JL, Christiansen K, Diette GB, Breysse PN, Hansel NN, McCormack MC, Sheehy T, Gittelsohn J, Sharma S. Food and nutrient intake in African American children and adolescents aged 5 to 16 years in Baltimore City. Journal of the American College of Nutrition 2015;35(3):205-216. |
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Krishan JA, Lemanske Jr. RF, Canino GJ, Elward KS, Kattan M, Matsui EC, Mitchell H, Sutherland ER, Minnicozzi M. Asthma outcomes: symptoms. The Journal of Allergy and Clinical Immunology 2012;129(3 Suppl):S124-S135. |
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Kumar S, Singh BK, Arya P, Malhotra S, Thimmulappa R, Prasad AK, Van der Eycken E, Olsen CE, DePass AL, Biswal S, Parmar VS, Ghosh B. Novel natural product-based cinnamates and their thio and thiono analogs as potent inhibitors of cell adhesion molecules on human endothelial cells. European Journal of Medicinal Chemistry 2011;46(11):5498-5511. |
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Kumar S, Reddy CS, Kumar Y, Kumar A, Singh BK, Kumar V, Malhotra S, Pandey MK, Jain R, Thimmulappa R, Sharma SK, Prasad AK, Biswal S, Van der Eycken E, DePass AL, Malhotra SV, Ghosh B, Parmar VS. Arylalkyl ketones, benzophenones, desoxybenzoins and chalcones inhibit TNF-α induced expression of ICAM-1: structure-activity analysis. Archiv der Pharmazie 2012;345(5):368-377. |
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Kumar S, Singh BK, Prasad AK, Parmar VS, Biswal S, Ghosh B. Ethyl 3',4',5'-trimethoxythionocinnamate modulates NF-κB and Nrf2 transcription factors. European Journal of Pharmacology 2013;700(1-3):32-41. |
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Kumar V, Kumar S, Hassan M, Wu H, Thimmulappa RK, Kumar A, Sharma SK, Parmar VS, Biswal S, Malhotra SV. Novel chalcone derivatives as potent Nrf2 activators in mice and human lung epithelial cells. Journal of Medicinal Chemistry 2011;54(12):4147-4159. |
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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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Lin JH, Matsui W, Aloe C, Peng RD, Diette GB, Breysse PN, Matsui EC. Relationships between folate and inflammatory features of asthma. The Journal of Allergy and Clinical Immunology 2013;131(3):918-920.e6. |
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Little FF, Delgado DM, Wexler PJ, Oppenheim FG, Mitchell P, Feldman JA, Walt DR, Peng RD, Matsui EC. Salivary inflammatory mediator profiling and correlation to clinical disease markers in asthma. PLoS One 2014;9(1):e84449 (10 pp.). |
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Lu KD, Breysse PN, Diette GB, Curtin-Brosnan J, Aloe C, Williams DL, Peng RD, McCormack MC, Matsui EC. Being overweight increases susceptibility to indoor pollutants among urban children with asthma. The Journal of Allergy and Clinical Immunology 2013;131(4):1017-1023.e3. |
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Malhotra D, Portales-Casamar E, Singh A, Srivastava S, Arenillas D, Happel C, Shyr C, Wakabayashi N, Kensler TW, Wasserman WW, Biswal S. Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis. Nucleic Acids Research 2010;38(17):5718-5734. |
R834510 (2011) R834510 (2012) R834510 (2013) R834510 (2014) R834510 (Final) |
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Malhotra D, Thimmulappa RK, Mercado N, Ito K, Kombairaju P, Kumar S, Feller-Kopman D, Wise R, Barnes PJ, Biswal S. Denitrosylation of HDAC2 by targeting Nrf2 restores glucocorticosteroid sensitivity in macrophages from COPD patients. Journal of Clinical Investigation 2011;121(11):4289-4302 (ARTICLE WAS RETRACTED). |
R834510 (2014) |
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Mathias RA, Grant AV, Rafaels N, Hand T, Gao L, Vergara C, Tsai YJ, Yang M, Campbell M, Foster C, Gao P, Togias A, Hansel NN, Diette G, Adkinson NF, Liu MC, Faruque M, Dunston GM, Watson HR, Bracken MB, Hoh J, Maul P, Maul T, Jedlicka AE, Murray T, Hetmanski JB, Ashworth R, Ongaco CM, Hetrick KN, Doheny KF, Pugh EW, Rotimi CN, Ford J, Eng C, Burchard EG, Sleiman PMA, Hakonarson H, Forno E, Raby BA, Weiss ST, Scott AF, Kabesch M, Liang L, Abecasis G, Moffatt MF, Cookson WOC, Ruczinski I, Beaty TH, Barnes KC. A genome-wide association study on African-ancestry populations for asthma. The Journal of Allergy and Clinical Immunology 2010;125(2):336-346. |
R834510 (2010) R834510 (2011) R834510 (Final) R832139 (Final) |
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Matsui EC, Matsui W. Higher serum folate levels are associated with a lower risk of atopy and wheeze. Journal of Allergy and Clinical Immunology 2009;123(6):1253-1259. |
R834510 (2010) R834510 (Final) |
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Matsui EC, Sampson HA, Bahnson HT, Gruchalla RS, Pongracic JA, Teach SJ, Gergen PJ, Bloomberg GR, Chmiel JF, Liu AH, Kattan M, Sorkness CA, Steinbach SF, Story RE, Visness CM. Allergen-specific IgE as a biomarker of exposure plus sensitization in inner-city adolescents with asthma. Allergy 2010;65(11):1414-1422. |
R834510 (2010) R834510 (Final) |
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Matsui EC, Ahluwalia S. The impact of an urban environment on a child's lungs. Expert Review of Respiratory Medicine 2011;5(4):465-468. |
R834510 (2012) |
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Matsui EC. Respiratory symptoms in asthma: the view through a wide-angle lens. The Journal of Allergy and Clinical Immunology 2012;130(2):408-409. |
R834510 (2013) R834510 (2014) |
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Matsui EC. Role of environmental control in the management of asthma and allergy. The Journal of Allergy and Clinical Immunology 2012;129(1):271-272.e3. |
R834510 (2012) |
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Matsui EC. Environmental control for asthma: recent evidence. Current Opinion in Allergy and Clinical Immunology 2013;13(4):417‐425. |
R834510 (2014) |
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Matsui EC. Management of rodent exposure and allergy in the pediatric population. Current Allergy and Asthma Reports 2013;13(6):681‐686. |
R834510 (2014) |
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Matsui EC, Hansel NN, Aloe C, Schiltz AM, Peng RD, Rabinovitch N, Ong MJ, Williams DL, Breysse PN, Diette GB, Liu AH. Indoor pollutant exposures modify the effect of airborne endotoxin on asthma in urban children. American Journal of Respiratory and Critical Care Medicine 2013;188(10):1210-1215. |
R834510 (2014) R834515 (2012) R834515 (2013) R834515 (2014) R834515 (2015) R834515 (Final) R834515C001 (2014) R834515C001 (2015) R834515C002 (2014) R834515C003 (2014) |
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Mazique D, Diette GB, Breysse PN, Matsui EC, McCormack MC, Curtin-Brosnan J, Williams DL, Peng RD, Hansel NN. Predictors of airborne endotoxin concentrations in inner city homes. Environmental Research 2011;111(4):614-617. |
R834510 (2011) R834510 (2012) R834510 (Final) |
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McCormack MC, Breysse PN, Matsui EC, Hansel NN, Williams D, Curtin-Brosnan J, Eggleston P, Diette GB. In-home particle concentrations and childhood asthma morbidity. Environmental Health Perspectives 2009;117(2):294-298. |
R834510 (2010) R834510 (Final) |
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McCormack MC, Breysse PN, Matsui EC, Hansel NN, Peng RD, Curtin-Brosnan J, Williams DL, Wills-Karp M, Diette GB, Center for Childhood Asthma in the Urban Environment. Indoor particulate matter increases asthma morbidity in children with non-atopic and atopic asthma. Annals of Allergy, Asthma and Immunology 2011;106(4):308-315. |
R834510 (2011) R834510 (2012) R834510 (2013) R834510 (2014) R834510 (Final) |
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McCormack MC, Aloe C, Curtin‐Brosnan J, Diette GB, Breysse PN, Matsui EC. Guideline-recommended fractional exhaled nitric oxide is a poor predictor of health-care use among inner-city children and adolescents receiving usual asthma care. Chest 2013;144(3):923‐929. |
R834510 (2013) R834510 (2014) R834510 (Final) |
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Mudd K, Paterakis M, Curtin-Brosnan J, Matsui E, Wood RA. Predicting outcome of repeat milk, egg, or peanut oral food challenges. Journal of Allergy and Clinical Immunology 2009;124(5):1115-1116. |
R834510 (2010) R834510 (Final) |
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Narisety SD, Skripak JM, Steele P, Hamilton RG, Matsui EC, Burks AW, Wood RA. Open-label maintenance after milk oral immunotherapy for IgE-mediated cow’s milk allergy. Journal of Allergy and Clinical Immunology 2009;124(3):610-612. |
R834510 (2010) R834510 (Final) |
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Neuman-Sunshine DL, Eckman JA, Keet CA, Matsui EC, Peng RD, Lenehan PJ, Wood RA. The natural history of persistent peanut allergy. Annals of Allergy, Asthma, and Immunology 2012;108(5):326-331.e3. |
R834510 (2012) R834510 (2013) R834510 (2014) |
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Noel S, Saams J, Ong MJC, Breysse P, Diette G, Biswal S, Matsui EC. Opposing effects of nasal epithelial NAD(P)H dehydrogenase quinine 1 and heme oxygenase 1 expression on upper and lower airway symptoms in adolescents with asthma. The Journal of Allergy and Clinical Immunology 2011;128(2):422-424.e3. |
R834510 (2011) R834510 (2012) R834510 (2013) R834510 (2014) R834510 (Final) |
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Okelo SO, Eakin MN, Patino CM, Teodoro AP, Bilderback AL, Thompson DA, Loiaza-Martinez A, Rand CS, Thyne S, Diette GB, Riekert KA. The Pediatric Asthma Control and Communication Instrument asthma questionnaire: for use in diverse children of all ages. The Journal of Allergy and Clinical Immunology 2013;132(1):55-62.e10. |
R834510 (2014) |
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Okelo SO, Butz AM, Sharma R, Diette GB, Pitts SI, King TM, Linn ST, Reuben M, Chelladurai Y, Robinson KA. Interventions to modify health care provider adherence to asthma guidelines: a systematic review. Pediatrics 2013;132(3):517-534. |
R834510 (2014) |
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Okelo SO, Riekert KA, Eakin MN, Bilderback AL, Diette GB, Rand CS, Yenokyan G. Pediatrician qualifications and asthma management behaviors and their association with patient race/ethnicity. Journal of Asthma 2014;51(2):155-161. |
R834510 (2014) |
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Okelo SO, Eakin MN, Riekert KA, Teodoro AP, Bilderback AL, Thompson DA, Loiaza-Martinez A, Rand CS, Thyne S, Diette GB, Patino CM. Validation of parental reports of asthma trajectory, burden, and risk by using the pediatric asthma control and communication instrument. The Journal of Allergy and Clinical Immunology: In Practice 2014;2(2):186-192.e7. |
R834510 (2014) |
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Okupa AY, Lemanske Jr. RF, Jackson DJ, Evans MD, Wood RA, Matsui EC. Early-life folate levels are associated with incident allergic sensitization. The Journal of Allergy and Clinical Immunology 2013;131(1):226-228.e2. |
R834510 (2013) R834510 (2014) |
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Pandey MK, Kumar S, Thimmulappa RK, Parmar VS, Biswal S, Watterson AC. Design, synthesis and evaluation of novel PEGylated curcumin analogs as potent Nrf2 activators in human bronchial epithelial cells. European Journal of Pharmaceutical Science 2011;43(1-2):16-24. |
R834510 (2011) R834510 (2012) R834510 (2013) R834510 (2014) R834510 (Final) |
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Paulin LM, Williams D, Oberweiser C, Diette GB, Breysse PN, McCormack MM, Matsui EC, Peng R, Metts TA, Hansel NN. Indoor air quality in central Appalachia homes impacted by wood and coal use. Journal of Environmental Protection 2013;4(1):67-71. |
R834510 (2013) R834510 (2014) |
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Paulin LM, Diette GB, Scott M, McCormack MC, Matsui EC, Curtin-Brosnan J, Williams DL, Kidd-Taylor A, Shea M, Breysse PN, Hansel NN. Home interventions are effective at decreasing indoor nitrogen dioxide concentrations. Indoor Air 2014;24(4):416-424. |
R834510 (2014) |
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Peng RD, Paigen B, Eggleston PA, Hagberg KA, Krevans M, Curtin-Brosnan J, Benson C, Shreffler WG, Matsui EC. Both the variability and level of mouse allergen exposure influence the phenotype of the immune response in workers at a mouse facility. Journal of Allergy and Clinical Immunology 2011;128(2):390-396.e7. |
R834510 (2011) R834510 (2012) R834510 (Final) |
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Phipatanakul W, Matsui E, Portnoy J, Williams PB, Barnes C, Kennedy K, Bernstein D, Blessing-Moore J, Cox L, Khan D, Lang D, Nicklas R, Oppenheimer J, Randolph C, Schuller D, Spector S, Tilles SA, Wallace D, Sublett J, Bernstein J, Grimes C, Miller JD, Seltzer J, Joint Task Force on Practice Parameters. Environmental assessment and exposure reduction of rodents: a practice parameter. Annals of Allergy, Asthma, and Immunology 2012;109(6):375-387. |
R834510 (2013) R834510 (2014) |
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Portnoy JM, Kennedy K, Sublett JL, Phipatanakul W, Matsui E, Barnes C, Grimes C, Miller JD, Seltzer JM, Williams PB, Bernstein JA, Bernstein DI, Blessing-Moore J, Cox L, Khan DA, Lang DM, Nicklas RA, Oppenheimer J. Environmental assessment and exposure control: a practice parameter—furry animals. Annals of Allergy, Asthma, and Immunology 2012;108(4):223.e1-223.e15. |
R834510 (2013) R834510 (2014) |
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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. |
R834510 (Final) R836152 (2018) R836152 (2020) |
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Rivera-Mariani FE, Matsui EC, Breysse PN. Performance of the halogen immunoassay to assess airborne mouse allergen-containing particles in a laboratory animal facility. Journal of Exposure Science & Environmental Epidemiology 2014;24(1):3-8. |
R834510 (2013) R834510 (2014) |
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Sandford AJ, Malhotra D, Boezen HM, Siedlinski M, Postma DS, Wong V, Akhabir L, He JQ, Connett JE, Anthonisen NR, Pare PD, Biswal S. NFE2L2 pathway polymorphisms and lung function decline in chronic obstructive pulmonary disease. Physiological Genomics 2012;44(15):754-763. |
R834510 (2013) R834510 (2014) |
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Savage JH, Kaeding AJ, Matsui EC, Wood RA. The natural history of soy allergy. Journal of Allergy and Clinical Immunology 2010;125(3):683-686. |
R834510 (2010) R834510 (2011) R834510 (Final) |
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Savage JH, Matsui EC, Wood RA, Keet CA. Urinary levels of triclosan and parabens are associated with aeroallergen and food sensitization. The Journal of Allergy and Clinical Immunology 2012;130(2):453-460.e7. |
R834510 (2013) R834510 (2014) |
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Sharma S, Zhou X, Thibault DM, Himes BE, Liu A, Szefler SJ, Strunk R, Castro M, Hansel NN, Diette GB, Vonakis BM, Adkinson Jr. NF Jr, Avila L, Soto-Quiros M, Barraza-Villareal A, Lemanske Jr. RF, Solway J, Krishnan J, White SR, Cheadle C, Berger AE, Fan J, Boorgula MP, Nicolae D, Gilliland F, Barnes K, London SJ, Martinez F, Ober C, Celedon JC, Carey VJ, Weiss ST, Raby BA. A genome-wide survey of CD4+ lymphocyte regulatory genetic variants identifies novel asthma genes. The Journal of Allergy and Clinical Immunology 2014;134(5):1153-1162. |
R834510 (2014) R834510 (Final) |
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Sheehan WJ, Rangsithienchai PA, Wood RA, Rivard D, Chinratanapisit S, Perzanowski MS, Chew GL, Seltzer JM, Matsui EC, Phipatanakul W. Pest and allergen exposure and abatement in inner-city asthma: a work group report of the American Academy of Allergy, Asthma & Immunology Indoor Allergy/Air Pollution Committee. Journal of Allergy and Clinical Immunology 2010;125(3):575-581. |
R834510 (2010) R834510 (2011) 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. |
R834510 (Final) R836152 (Final) |
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Sussan TE, Gajghate S, Chatterjee S, Mandke P, McCormick S, Sudini K, Kumar S, Breysse PN, Diette GB, Sidhaye VK, Biswal S. Nrf2 reduces allergic asthma in mice through enhanced airway epithelial cytoprotective function. American Journal of Physiology: Lung Cellular and Molecular Physiology 2015;309(1):L27-L36. |
R834510 (Final) |
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Thimmulappa RK, Gang X, Kim JH, Sussan TE, Witztum JL, Biswal S. Oxidized phospholipids impair pulmonary antibacterial defenses: evidence in mice exposed to cigarette smoke. Biochemical and Biophysical Research Communications 2012;426(2):253-259. |
R834510 (2013) R834510 (2014) R834510 (Final) |
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Torgerson DG, Ampleford EJ, Chiu GY, Gauderman WJ, Gignoux CR, Graves PE, Himes BE, Levin AM, Mathias RA, Hancock DB, Baurley JW, Eng C, Stern DA, Celedon JC, Rafaels N, Capurso D, Conti DV, Roth LA, Soto-Quiros M, Togias A, Li X, Myers RA, Romieu I, Van Den Berg DJ, Hu D, Hansel NN, Hernandez RD, Israel E, Salam MT, Galanter J, Avila PC, Avila L, Rodriquez-Santana JR, Chapela R, Rodriguez-Cintron W, Diette GB, Adkinson NF, Abel RA, Ross KD, Shi M, Faruque MU, Dunston GM, Watson HR, Mantese VJ, Ezurum SC, Liang L, Ruczinski I, Ford JG, Huntsman S, Chung KF, Vora H, Li X, Calhoun WJ, Castro M, Sienra-Monge JJ, del Rio-Navarro B, Deichmann KA, Heinzmann A, Wenzel SE, Busse WW, Gern JE, Lemanske Jr. RF, Beaty TH, Bleecker ER, Raby BA, Meyers DA, London SJ, Gilliland FD, Burchard EG, Martinez FD, Weiss ST, Williams LK, Barnes KC, Ober C, Nicolae DL. Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations. Nature Genetics 2011;43(9):887-892. |
R834510 (2012) R834510 (2013) R834510 (2014) |
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Torjusen EN, Diette GB, Breysse PN, Curtin-Brosnan J, Aloe C, Matsui EC. Dose-response relationships between mouse allergen exposure and asthma morbidity among urban children and adolescents. Indoor Air 2013;23(4):268-274. |
R834510 (2013) R834510 (2014) R834510 (Final) |
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Waugh D, He Z, Zaitchik B, Peng R, Diette G, Hansel N, Matsui E, Breysse P, Breysse D, Koehler K, Williams D, McCormack M. Indoor heat exposure in Baltimore:does outdoor temperature matter?. INTERNATIONAL JOURNAL OF BIOMETEOROLOGY 2021;65(4):479-788. |
R834510 (Final) |
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Sudini K, Diette GB, Breysse PN, McCormack MC, Bull D, Biswal S, Zhai S, Brereton N, Peng RD,Matsui EC. A randomized controlled trial of the effect of broccoli sprouts on antioxidant gene expression and airway inflammation in asthmatics. The Journal of Allergy and Clinical Immunology: In Practice 2016;4(5):932-940. |
R834510 (Final) |
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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. |
R834510 (Final) R836150 (2020) R836152 (Final) |
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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. |
R834510 (Final) R832139 (Final) R836150 (2020) R836152 (Final) |
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Supplemental Keywords:
Health, Scientific Discipline, Health Risk Assessment, Epidemiology, Allergens/Asthma, Biology, asthma triggers, asthma indices, air pollution, airway inflammation, children, diet, oxidant stressProgress 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).
R834510C001 Urban Dietary Effects on the Asthmatic Response to Pollutants
R834510C002 Dietary Interventions in Asthma Treatment
R834510C003 Dissecting the Diet-Asthma Relationship in Mice Models of Asthma
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
- 2014 Progress Report
- 2013 Progress Report
- 2012 Progress Report
- 2011 Progress Report
- Original Abstract
90 journal articles for this center