2014 Progress Report: Mechanisms of Asthma -- Dietary Interventions against Environmental Triggers

EPA Grant Number: R834510
Center: Mechanisms of Asthma-Dietary Interventions against Environmental Triggers - Johns Hopkins University
Center Director: Diette, Greg
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, 2013 through July 31,2014
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 , Health

Objective:

The long-term goal of the ASTHMA-DIET (A Study to Understand the Mechanisms of Asthma--Dietary Interventions to Protect Against Environmental Triggers) Program is to understand how diet influences the asthmatic response to indoor and outdoor airborne pollutants and allergens, with the expectation of translating these findings into practical dietary strategies to improve pediatric asthma health. The ASTHMA-DIET Center’s overall hypothesis is that a low anti-oxidant, pro-inflammatory diet impairs the capacity to respond to oxidative stressors, thereby increasing susceptibility to pollutant and allergen exposures. The aims of the Center grant are focused on the mechanistic underpinnings of airway inflammation, oxidative stress, and respiratory morbidity in predominantly African-American children with asthma, living in the inner city of Baltimore.

The specific aims are to (1) examine the effect of the poor “inner city” diet on susceptibility of asthmatic children to in-home pollutant (PM and NO2) exposure; (2) identify barriers and enabling factors to implementing dietary and environmental modifications in inner city homes of children with asthma; (3) conduct randomized, controlled trials of two dietary interventions: namely broccoli sprouts (BS), which increase OS capacity in respiratory epithelium, and the low-saturated fat, anti-inflammatory OmniHeart Diet (OHD); (4) test the effects of BS and the OHD on OS, inflammation, basophil activation, and clinical outcomes in Baltimore City adults with mouse allergen-induced asthma; (5) determine the effect of dietary constituents (proposed in Project 2-children intervention studies) on OVA and ambient particle induced-asthma in mice models (the mice will be fed either a normal diet or a modified Mediterranean-type diet from which we will compare diets with low DHA, high DHA and a high fat diet); (6) study asthma susceptibility by measuring different endpoints such as pulmonary inflammation, Th2 cytokines, and airway hyper-responsiveness; (7) study the regulation of the Nrf2 pathway and its downstream antioxidant gene activation due to sulforaphane using Nrf2 +/+ and -/- mice to dissect the mechanism; and (8) determine the effect of dietary constituents on DC maturation and Th2 polarization in the OVA and the ambient particle model of asthma. The proposed studies will help illustrate the mechanism by which diet modulates susceptibility and asthma pathogenesis.

Progress Summary:

In the last 12 months, we have made significant progress to integrate all components of the program, ensure tight collaboration among the leaders of the three projects and four cores, and exchange of ideas and data. 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. 

Project 1:

There has been significant progress on Project 1 in the past year. We have consented a total of 169 asthmatics to date. Of these, 121 participants have completed all home visits. While successfully recruiting, we continue to keep our focus on the routine follow-up home visits of those participants who already have consented. We continue to conduct regular study meetings to discuss recruitment strategies and issues involving home visits.

Our clinic visits continue to include collection of health information and lung function testing. On home visits, questionnaires, diet survey, home inspections, exhaled nitric oxide, skin assessments, peak flow measurements, dust sample collection, and air monitoring are done. Air monitoring includes PM2.5, PM10, NO2 measurements and samples were sent to the environmental assessment core. Added to the home visits are a questionnaire on barriers to healthy eating, administered at the third and final home visit, and a 24-hour dietary recall to validate the Food Frequence Questionnaires (FFQs) being used in this population. In a subset of participants, we have implemented a 7-day diary to monitor NO2 exposure in conjunction with measuring NO2 in the home using daily Ogawa badges. FFQs collected to date have been sent to Dr. Gita Sharma for analysis. Blood, urine, and nasal lavage samples have been collected for all the participants who have completed at least one season and delivered to Dr. Biswal’s lab for processing to measure inflammatory and oxidative stress markers. Blood samples also have been delivered to Dr. Detrick’s lab to measure serum 25-hydroxyvitamin D levels. 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.

An abstract on links between fast food consumption and asthma control in urban asthmatic children was presented at the 2013 American Thoracic Society International Conference.

Project 2:

For Project 2, a new protocol has been developed using a nasal allergen challenge model instead of an environmental challenge model. This protocol has received IRB and ICTR approval at Johns Hopkins and the revised protocol and Manual of Procedures are undergoing review by the EPA before initiation of the study. An IND was obtained for the FDA for the study protocol that covers two investigational agents: the whole broccoli sprouts and the mouse epithelial extract to be used in the nasal challenges. All regulatory and data management requirements have been met and all supplies are on hand to launch the study. EPA review of the revised protocol was completed in May 2012; the study was approved by EPA for re-launching, and recruitment began. After launching the study with the nasal challenge procedure, it became clear that it would not be possible to meet recruitment goals, so the protocol was revised with a new primary outcome variable, exhaled nitric oxide, which is a measure of pulmonary allergic inflammation. The trial design was thus a parallel arm randomized controlled trial of 3 days of ingestion of 100 g of broccoli sprouts vs. alfalfa sprouts. Adults with asthma who had at least one positive skin test were eligible. This amendment was reviewed by the IRB and approved on 12/19/2013. Recruitment began in January 2014, and as of 7/31/2014, 35 participants completed clinic screening, 23 participants were randomized, and 17 had completed the study. The sample size is 40 participants. The DSMB has received quarterly reports and has recommended that the study continue after all of their reviews.

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. Findings from this pilot study were published in the Journal of Allergy and Clinical Immunology in 2011.

Pilot Tolerability Study

A pilot study examining tolerability of 100 g and 75 g broccoli sprouts (BS) delivered in sandwiches was completed. Five healthy adults were enrolled for the 100 g dose and five enrolled for the 75 g dose pilot. Participants consumed sandwiches daily for 5 days. Participants reported that the sandwiches were very palatable and consistently consumed at least 85% of the sandwich at each meal. Plasma sulforaphane (SFN) concentrations before ingestion were undetectable and 1 hour after ingesting the last sandwich, sulforaphane concentrations were detectable in the 600-2290 nM range. The only side effects were gastrointestinal with bloating and abdominal pain reported most commonly. There was no vomiting or diarrhea reported. There were no differences in side effects between the 75 g and 100 g BS sandwiches. There were no significant changes in thyroid function tests associated with ingestion of BS sandwiches. The 100 g BS sandwiches were associated with somewhat higher plasma SFN concentrations and were selected for the efficacy trial. Results of this pilot study were presented at the 2011 meeting of the American Thoracic Society.

Omni Heart Diet Study

We now have completed a randomized, crossover trial of a dietary intervention that replaces the usual diet with a Mediterranean-like diet. We used databases from previous studies as a source of recruitment and also distributed flyers to Johns Hopkins and Johns Hopkins Community Physicians offices and used mass mailings. We phone screened 82 individuals and consented 19. Of these, 6 were found to be ineligible at the initial screening clinic visit. Two individuals withdrew during the initial screening period, which was comprised of three visits for the purpose of orienting participants to the study protocol and the study foods. Eleven adults were randomized and four withdrew during the study period. Seven participants completed the study protocol. During the period of the study, the participants were provided a 4-week dietary intervention and were instructed to consume only foods provided by the study during this period. The dietary intervention consisted of food that was prepared and packaged at the ProHealth Research facility. Participants consumed lunch onsite 3-4 days per week and received the remainder of their meals and snacks at ProHealth. These foods were packaged to be consumed at home. There was a 4-week washout period in between interventions. During the control period, participants consumed their usual diet. Participants completed 24-hour dietary recalls administered over the phone three times during both the control and the intervention periods. Participant had health outcomes assessed at baseline and at the end of each 4-week intervention period, control, and dietary intervention. These included questionnaires, lung function assessment, collection of biomarkers, including exhaled nitric oxide, blood, urine, nasal lavage, and nasal epithelial cells. Participants overall reported a very positive experience in the study. We have completed data entry and now are analyzing results.

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.

Project 3:

Broccoli sprouts are rich in glucoraphanin, which is converted to sulforaphane by bacterial myrosinases in the colon during digestion. Sulforaphane is an activator of Nrf2. Our ongoing studies have shown that sulforaphane attenuates ovalbumin-induced asthmatic features, including eosinophilic inflammation, TH2 cytokine secretion, and airways hypersensitive response (AHR). Moreover, sulforaphane is protective when given either during sensitization or challenge. We currently are investigating the underlying mechanism by which sulforaphane-mediated induction of Nrf2 signaling attenuates asthma.

Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is found in the Mediterranean-type diet. Mice that were fed a diet containing 0.6% DHA starting 2 weeks prior to sensitization exhibited a significant decrease in OVA-induced eosinophilic inflammation, compared to mice fed a diet lacking DHA. However, we did not observe a significant improvement in AHR. We currently are examining whether prolonged feeding of DHA results in more profound effects.

Under basal conditions, Nrf2 is bound to Keap1 in the cytoplasm, which inhibits Nrf2 activity and signals its degradation. Deletion of Keap1 in mice results in lethality at approximately 2 weeks of age, making studies of genetic activation of Nrf2 difficult. To overcome this, we are utilizing a novel mouse strain that contains a tamoxifen-inducible deletion of Keap1. Genetic activation of Nrf2, through tamoxifen-mediated deletion of Keap1, results in significant reductions in AHR (APTI), eosinophilic inflammation, and TH2 cytokine secretion. We also have engineered mice that contain Keap1 deletions specifically in airway epithelial cells (CC10) or CD4 T cells (CD4). These mice exhibit significant reductions in AHR (APTI), eosinophilic inflammation, and TH2 cytokine secretion.

Data Management and Statistics Core

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 and 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 both Project 2 studies is complete

• 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 barcoding system to track biologic samples.

• Maintenance of a database of potential study participants (Future Subjects Database) to be used as a recruitment tool.

• Development of additional data capture and data quality control tools for both Projects 1 and 2.

• Development of reporting tools for Projects 1 and 2.

In the past year, significant progress has been made in cleaning, managing, and developing methods for analysis of real-time particle concentration data generated from the nephelometry-based MIE monitors that are deployed in the field as a part of Diet Project 1.

The research projects supported by the DMSC 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.

Environmental Assessment Core

Consistent with the specific aims of the Environmental Assessment Core we continue to support environmental sampling and exposure assessment aspects of the projects. This has included implementing exposure assessment protocols for Project 1 and 2, as well as environmental sample collection for Project 3. In addition, we have collaborated with the DMSC 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.

New exposure assessment activities include implementing the Limulus Assay for endotoxin assessment and developing the Whole Blood Assay and to assess the overall biogenic activity of indoor air pollution.

Community Outreach and Translation Core

As in the first 3 years of the study, the Community Outreach and Translation Core (COTC) of the ASTHMA-DIET study continues to work within the Baltimore City community around issues of pediatric asthma, environmental exposure, and diet. We continue to meet every 2 months with our CAB to present information about our study results and get member input on study implementation, dissemination, and community concerns. Project leaders attend meetings to present current updates on their study progress and share community-disseminable summaries of their project’s goals, design, and findings.

Our community outreach activity has continued in the past year, with our outreach worker now participating in as many as six Baltimore City community activities (e.g., health fairs, community health days, screenings, etc.) in any given month. Outreach activities include education around second hand smoke, avoidance of allergens and indoor and outdoor PM, and asthma management. Further, we continue to work closely with Baltimore City Head Start programs as a part of their efforts to reduce ETS exposure for preschool children. In this context we continue to offer Head Start staff training sessions related to second hand smoke reduction, and participate in Head Start Health Advisory Committee Meetings.

Based on qualitative research related to barriers to healthy eating in urban families we conducted in 2012, we have developed and piloted a measure of beliefs about healthy eating for children in urban families. This IRB approved measure now is administered by the field staff to ASTHMA-DIET participants at one point during the week of their third home visit, which occurs 6 months after their baseline home visit.

Future Activities:

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.

Plans for the future include providing support for conducting ongoing 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. The PI and Core collaborators will collaborate on Center publications and presentations. We aim to further define the roles that dietary Nrf2 activation and DHA dietary supplementation play in asthma pathogenesis and will further explore Nrf2 as a modifier of disease pathogenesis.

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. Our evidence to date indicates that activation of Nrf2 attenuates asthmatic phenotypes. We have demonstrated this phenomenon by using genetic approaches as well as through treatment with sulforaphane, a chemical found in broccoli sprouts. Furthermore, we see that DHA, found in a Mediterranean-style diet, attenuates allergic inflammation. These studies suggest that dietary interventions that target the antioxidant response may reduce asthmatic sensitization or acute allergic responses.

The research projects supported by the DMSC 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.


Journal Articles: 78 Displayed | Download in RIS Format

Other center views: All 78 publications 78 publications in selected types All 78 journal articles
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Journal Article 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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  • Journal Article 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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  • Journal Article 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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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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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  • Journal Article 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.). R834510 (Final)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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. R834510 (2010)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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. R834510 (2013)
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  • Journal Article 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. R834510 (2010)
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  • Journal Article 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. R834510 (2014)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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. R834510 (2014)
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  • Journal Article 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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  • Journal Article 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. R834510 (2010)
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  • Journal Article 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. R834510 (2010)
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  • Journal Article 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. R834510 (2011)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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. R834510 (Final)
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  • Journal Article 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. R834510 (2013)
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  • Journal Article 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. R834510 (2012)
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  • Journal Article 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. R834510 (2012)
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  • Journal Article 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. R834510 (2013)
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  • Journal Article 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. R834510 (2011)
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  • Journal Article 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. R834510 (2013)
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  • Journal Article 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.). R834510 (2014)
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  • Journal Article 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. R834510 (2013)
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  • Journal Article 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)
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  • Journal Article 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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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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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  • Journal Article 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)
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  • Journal Article 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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  • Journal Article 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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  • Journal Article 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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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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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  • Journal Article 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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  • Journal Article 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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  • Journal Article 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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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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)
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  • Journal Article 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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  • Journal Article 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)
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  • Journal Article 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)
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    R834510 (2014)
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  • Journal Article 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)
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    R834510 (Final)
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  • Journal Article 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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  • Supplemental Keywords:

    Health, Scientific Discipline, Health Risk Assessment, Epidemiology, Allergens/Asthma, Biology, asthma triggers, asthma indices, air pollution, children, airway inflammation, diet, oxidant stress

    Progress and Final Reports:

    Original Abstract
  • 2010 Progress Report
  • 2011 Progress Report
  • 2012 Progress Report
  • 2013 Progress Report
  • Final Report
  • 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