Final Report: Johns Hopkins Center for Childhood Asthma in the Urban Environment

EPA Grant Number: R832139
Center: Johns Hopkins Center for Childhood Asthma in the Urban Environment
Center Director: Breysse, Patrick N.
Title: Johns Hopkins Center for Childhood Asthma in the Urban Environment
Investigators: Breysse, Patrick N. , Butz, Arlene , Diette, Greg , Georas, Steven , Wills-Karp, Marsha
Institution: The Johns Hopkins University
EPA Project Officer: Callan, Richard
Project Period: November 1, 2003 through October 31, 2008 (Extended to October 31, 2010)
Project Amount: $3,576,564
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2003) RFA Text |  Recipients Lists
Research Category: Human Health , Health , Children's Health , Health Effects

Objective:

The long term goal of the Center for Childhood Asthma in the Urban Environment was to examine how exposures to environmental pollutants and allergens may relate to airway inflammation and respiratory morbidity in children with asthma living in the inner city of Baltimore, and to search for new ways to reduce asthma morbidity by reducing exposure to these agents. To accomplish these goals, the Center included both basic and applied research programs in combination with a community-based intervention research project. These projects were supported by core facilities for data management, and exposure assessment. An administrative core supported research and general meetings to integrate the interests and activities of the Center. A community advisory committee contributed to the planning process both for the environmental epidemiology project and the community-based intervention research project, and the committee met periodically with Center researchers to discuss the Center’s findings and progress. A six-member External Advisory Committee was recruited. Information gained by this coordinated, interdisciplinary team facilitated plans for future studies to examine children’s susceptibility to asthma, and to plan even more effective interventions in future studies with collaborating families in the East Baltimore community.
 
Project 1: Epidemiology of Susceptibly to Particulates and Allergens in Asthma
Investigator: Greg Diette, MD, MS
The first project was a community-based epidemiologic study of 400 children, ages 6-12, and their homes to identify relevant airborne exposures and to examine genetic determinants of asthma morbidity resulting from these exposures
 
Project 2: A Randomized, Controlled Trial of Behavioral Changes in Home Exposure Control
Investigator: Arlene Butz, ScD
Project 2 is a community-based participatory research project that is a randomized controlled clinical trial of 120 children of the effectiveness of behavioral methods to reduce pollutant and allergen exposures and their adverse health effects.
 
Project 3: Mechanisms of Particulate-Induced Allergic Asthma
Investigator(s): Marsha Wills-Karp, PhD
The third project examines the mechanisms by which particulate matter may exacerbate an allergen-driven response in the airways. The fourth project will examine the effects of environmental particulates on the in vitro maturation of peripheral blood monocytes to dendritic cells.
 
Project 4: Effects of Particulate Matter on Dendritic Cell Maturation
Investigator(s): Steven Georas, MD
Project 4 examined the effect of Baltimore ambient particulates on maturation of peripheral blood monocytes to dendritic cells.

Summary/Accomplishments (Outputs/Outcomes):

During the No-Cost Extension period we completed a number of important analyses and published a number of important papers listed below. Highlights of these papers include a genome-wide association study on African-ancestry populations for asthma (#6); a paper describing a longitudinal study of indoor nitrogen dioxide levels and respiratory symptoms in inner-city children with asthma showing that indoor NO2 is a risk factor for asthma exacerbation (#8); and a description of sequential cyclone collector developed to collect particulate matter for toxicity studies (#1). In addition, we continued to publish results of toxicological studies including papers that describe the role of dendritic cell activation in TH2 mediated inflammation as well as the role of mucin-like molecules in dendritic cell activation through toll-like receptors.
 
Project 1: Project 1 has examined the relationship of polymorphisms in genes encoding IL13, TLR4 and BADr and exposure to pollutants and allergens in the homes of asthmatic and control children by enrolling 150 children with asthma and 150 control children without asthma. The children were 58% male, 91% African-American and 88% had public health insurance. Housing characteristics related to pollutant exposure and bedroom air pollutant levels did not differ significantly between asthmatic and control subjects [median: PM2.5 28.7 vs. 28.5 mg/m3, PM10 43.6 vs. 41.4 mg/m3, NO2 21.6 vs 20.9 ppb, Ozone 1.4 vs. 1.8 ppb, all p >0.05]. Settled dust allergen levels (cat, dust mite, cockroach, dog and mouse) were also similar in bedrooms of asthmatic and control children. From these analyses, we conclude that exposures to common home indoor pollutants and allergens are similar for inner city pre-school children with and without asthma. While these exposures may exacerbate existing asthma, this study does not support a causative role of these factors for risk of developing childhood asthma.
 
Our findings have several implications to the field of asthma. These studies do not support that the studied exposures (allergens and pollutants) cause asthma in the inner city by overabundance. The similar exposure levels in asthma and control subjects points toward individual susceptibility to these exposures if they are implicated in asthma pathogenesis. We have found low use of environmental control practices in this inner city population, and have found behavioral determinants of these practices. We have found a link between fear of violence (not awareness alone) and caregiver depression, which may be an important link to lower quality of asthma care of pre-school children. We have also reported very low compliance with guideline-recommended long-term control medications, which is a critical factor in the asthma health of this population.
 
Project 2: Use of portable air cleaners in households with smokers has been suggested to improve indoor air quality and subsequent health outcomes for other household members exposed to second hand smoke (SHS). We hypothesized that the combination of air cleaners and a behavioral intervention to promote home smoking bans would be more successful than air cleaners alone or a control condition in reducing levels of particulate matter (PM), air nicotine, urine cotinine and asthma morbidity in inner city children with asthma residing with a smoker.
 
A total of 126 inner-city children with asthma (mean age 9 years; 55% male; 90% Medicaid insured; 95% African American) who lived with at least one smoker in their household were recruited from an urban pediatric emergency department (ED) and community based pediatric practices. All children were randomized into three groups: 1) delayed air cleaners (control), 2) air cleaners only or 3) air cleaners plus health coach for reduction of home SHS exposure. Caregivers were interviewed regarding child health status and child urine cotinine assessments were collected at baseline and 6 months. Indoor air quality measures of particulate matter and air nicotine were collected and analyzed prior to randomization and at the 6 month follow-up. Kruskal-Wallis, Wilcoxon rank-sum and Cuzik’s test for trend were used to test for differences in fine (PM2.5) and coarse (PM2.5-10) particulate matter, air nicotine and urine cotinine concentrations between baseline and 6 months by group.
 
Caregivers were the primary household smoker in the majority (68%) of homes. Asthma severity was high with 80% children categorized with persistent asthma. At follow-up, mean differences in PM2.5 and PM 2.5-10 concentrations between baseline and follow-up were significantly lower in the air cleaner groups as compared to the control group (p<0.01) with no differences by group noted for air nicotine or urine cotinine. However, mean follow-up PM2.5 levels for all groups surpassed the U.S. EPA annual standard, 15 ug/m3, for outdoor air quality (Control: 38.9 ug/m3, Air cleaner only: 17.96 ug/m3, Air cleaner + Health Coach: 32.21 ug/m3). Mean differences in symptom free days and days without slowed activity due to asthma over the past 2 weeks were significantly lower in children assigned to the air cleaner groups as compared to control children. The addition of an intensive health coach intervention provided no additional reduction in PM concentrations or health effects when compared to the air cleaner only group.
 
In conclusion, the use of air cleaners in homes of children with asthma was associated with a significant reduction in indoor PM concentrations and a modest increase in symptom free days. However, even the reduced indoor PM concentrations surpassed the US EPA standards for outdoor air quality. Implementing a smoke-free home policy is the only justifiable practice to be recommended for children with asthma residing in homes with a smoker to prevent exposure to SHS.
 
Project 3: Project 3 has examined the mechanisms by which urban airborne particulate matter may exacerbate an allergen-driven inflammatory response in the airways: To determine the relationship between exposure to airborne indoor PM and asthma morbidity, a comparison was made of the biological effects of PM collected in homes of children with mild and severe asthma, stratified for the presence of smokers in the home, using the development of asthma symptoms in mice as a readout system. To determine the interaction with genetic factors, environmental exposure to allergens, and environmental PM exposures which contribute to asthma morbidity, we examined the biological effects of exposure to indoor urban Baltimore PM in non-allergic strains of mice. To determine the role of complement factor 3 in mediating urban indoor PM-induced inflammation and/or exacerbations of allergic asthmatic symptoms, we compared the biological effects of PM exposure in C3 deficient and wildtype mice.
 
We found that PM induces significant elevations in the numbers of lung derived myeloid DC as compared to the plasmacytoid subset. We found that plasmactyoid DCs confer tolerance to the development of allergic responses suggesting that PM exposure may enhance allergic responses by altering the balance of immunogenic to tolerogenic DCs present in the lung. We cultured mDCs isolated from the bone marrow (BMDDC) of A/J mice and measured the production of the Th1directing cytokine, IL-12 and the Th2-directing cytokines, IL-6. Interestingly, we find that AUB-conditioned epithelial supernatants preferentially induce the production of the Th2 directing cytokine, IL-6. These results suggest that AUB may induce the production of factors by the airway epithelium that activate DCs to provide Th2 promoting signals to T cells. Our studies suggest that AUB induces changes in the airway epithelial that skew the immune response towards a Th2 response. Studies are currently underway to determine whether differences in complement family genes, oxidative stress genes or prostaglandin genes playa role in the differential susceptibility of the two murine strains to AUB-induced dendritic cell activation and AHR. In addition, we have found that the development of AHR, is dependent activation of adaptive immune responses as Rag1-/- mice, which are devoid of lymphocytes, do not develop AHR in response to AUB exposure. Surprisingly airway inflammation is only partially dependent upon lymphocytes, suggesting that innate immune pathways are also activated in the airways in response to AUB.
 
To our knowledge these are the first studies to demonstrate that ambient particulates can directly induce the symptoms of asthma. Secondly, our finding that PM skews epithelial-dendritic cell interactions such that DC preferentially produce Th2/Th17-directing cytokines through oxidative signaling pathways provides a potential mechanism by which particulates induce AHR and inflammation as well as provide a potential therapeutic target.
 
Project 4: This project investigated how particulate matter (PM) impacted the function of dendritic cells. When we began these studies, very little was known about the ability of this key cell type to recognize ambient PM. Dendritic cells are key sentinel cells in the body, and express an array of pattern recognition receptors and other molecules that sense the presence of environmental danger. We conducted two general sets of experiments supported by this Project. First, we used human peripheral blood monocytes differentiated into dendritic cells in vivo using standard tissue culture techniques. Cells were obtained from peripheral blood and incubated with ambient Baltimore PM for different time frames and at different concentrations. These studies revealed that ambient PM induced a previously unreported phenotype in dendritic cells, allowing them to be better activators or T lymphocytes. Notably the responding T cells secreted greater amounts of Th2 than Th1 cytokines. Therefore, this suggested to us that ambient PM could be sensed as a danger signal that might foster pro-allergic, Th2-dependent immune responses.
 
The second series of experiments we conducted were aimed at identifying how ambient PM activated dendritic cells mechanistically. Given the strong link between PM and oxidative stress, we speculated that reactive oxygen intermediates may be an intermediary. We tested this hypothesis using mouse bone marrow-derived dendritic cells in vitro, and indeed found that PM induced oxidant generation and activated dendritic cells in an occident-dependent manner


Journal Articles: 110 Displayed | Download in RIS Format

Other center views: All 113 publications 113 publications in selected types All 110 journal articles
Type Citation Sub Project Document Sources
Journal Article Alberg AJ, Diette GB, Ford JG. Invited commentary: Attendance and absence as markers of health status—the example of active and passive cigarette smoking. American Journal of Epidemiology 2003;157(10):870-873. R832139 (2004)
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  • Journal Article Barekzi E, Roman J, Hise K, Georas S, Steinke JW. Lysophosphatidic Acid Stimulates Inflammatory Cascade in Airway Epithelial Cells. Prostaglandins, Leukotrienes & Essential Fatty Acids 2006;74(6):357-363. R832139 (2007)
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    Journal Article Barnes KC, Caraballo L, Munoz M, Zambelli-Weiner A, Ehrlich E, Burki M, Jimenez S, Mathias RA, Stockton ML, Deindl P, Mendoza L, Hershey GK, Nickel R, Wills-Karp M. A novel promoter polymorphism in the gene encoding complement component 5 receptor 1 on chromosome 19q13.3 is not associated with asthma and atopy in three independent populations. Clinical and Experimental Allergy 2004;34(5):736-744. R832139 (2004)
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  • Journal Article Barnes KC, Grant AV, Gao P. A review of the genetic epidemiology of resistance to parasitic disease and atopic asthma:common variants for common phenotypes? Current Opinion in Allergy and Clinical Immunology 2005;5(5):379-385. R832139 (2006)
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  • Journal Article Barnes KC. Genetic epidemiology of health disparities in allergy and clinical immunology. Journal of Allergy and Clinical Immunology 2006;117(2):243-254. R832139 (2006)
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  • Journal Article Barnes KC, Grant AV, Baltadzhieva D, Zhang S, Berg T, Shao L, Zambelli-Weiner A, Anderson W, Nelsen A, Pillai S, Yarnall DP, Dienger K, Ingersoll RG, Scott AF, Fallin MD, Mathias RA, Beaty TH, Garcia JG, Wills-Karp M. Variants in the gene encoding C3 are associated with asthma and related phenotypes among African Caribbean families. Genes and Immunity 2006;7(1):27-35. R832139 (2006)
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  • Journal Article Barnes KC, Grant A, Gao P, Baltadjieva D, Berg T, Chi P, Zhang S, Zambelli-Weiner A, Ehrlich E, Zardkoohi O, Brummet ME, Stockton M, Watkins T, Gao L, Gittens M, Wills-Karp M, Cheadle C, Beck LA, Beaty TH, Becker KG, Garcia JGN, Mathias RA. Polymorphisms in the novel gene acyloxyacyl hydroxylase (AOAH) are associated with asthma and associated phenotypes. Journal of Allergy and Clinical Immunology 2006;118(1):70-77. R832139 (2006)
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  • Journal Article Barnes KC, Grant AV, Hansel NN, Gao P, Dunston GM. African Americans with Asthma: Genetic Insights. Proceedings of the American Thoracic Society 2007;4(1):58-68. R832139 (2007)
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    Journal Article Bartlett SJ, Krishnan JA, Riekert KA, Butz AM, Malveaux FJ, Rand CS. Maternal depressive symptoms and adherence to therapy in inner-city children with asthma. Pediatrics 2004;113(2):229-237. R832139 (2004)
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  • Journal Article Bezemer GFG, Bauer SM, Oberdorster G, Breysse PN, Pieters RHH, Georas SN, Williams MA. Activation of pulmonary dendritic cells and Th2-type inflammatory responses on instillation of engineered, environmental diesel emission source or ambient air pollutant particles in vivo. Journal of Innate Immunity 2011;3(2):150-166. R832139 (Final)
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  • Journal Article Bollinger ME, Butz A, Mudd K, Hamilton RG. Contamination of nebulizers with environmental allergens. Annals of Allergy Asthma & Immunology 2005;95(5):429-432. R832139 (2006)
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  • Journal Article Breysse PN, Buckley TJ, Williams D, Beck CM, Jo SJ, Merriman B, Kanchanaraksa S, Swartz LJ, Callahan KA, Butz AM, Rand CS, Diette GB, Krishnan JA, Moseley AM, Curtin-Brosnan J, Durkin NB, Eggleston PA. Indoor exposures to air pollutants and allergens in the homes of asthmatic children in inner-city Baltimore. Environmental Research 2005;98(2):167-176. R832139 (2004)
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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. R832139 (Final)
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  • Journal Article Butz AM, Riekert KA, Eggleston P, Winkelstein M, Thompson RE, Rand C. Factors associated with preventive asthma care in inner-city children. Clinical Pediatrics 2004;43(8):709-719. R832139 (2004)
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  • Journal Article Butz AM, Tsoukleris M, Donithan M, Hsu VD, Mudd K, Zuckerman IH, Bollinger ME. Patterns of inhaled antiinflammatory medication use in young underserved children with asthma. Pediatrics 2006;118(6):2504-2513. R832139 (2007)
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  • Journal Article Butz AM, Tsoukleris MG, Donithan M, Hsu VD, Zuckerman I, Mudd KE, Thompson RE, Rand C, Bollinger ME. Effectiveness of nebulizer use--targeted asthma education on underserved children with asthma. Archives of Pediatric and Adolescent Medicine 2006;160(6):622-628. R832139 (2007)
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  • Journal Article Butz AM, Walker J, Pulsifer M. Shared Decision Making in Children with Asthma. Pediatric Nursing 2007;33(2):111-116. R832139 (Final)
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  • Journal Article Butz AM, Walker J, Land CL, Vibbert C, Winkelstein M. Improving asthma communication in high-risk children. Journal of Asthma 2007;44(9):739-745. R832139 (Final)
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  • Journal Article Butz AM, Thompson RE, Tsoukleris MG, Donithan M, Hsu VD, Mudd K, Zuckerman IH, Bollinger ME. Seasonal patterns of controller and rescue medication dispensed in underserved children with asthma. Journal of Asthma 2008;45(9):800-806. R832139 (Final)
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  • Journal Article Butz A, Pham L, Lewis L, Lewis C, Hill K, Walker J, Winkelstein M. Rural children with asthma: impact of a parent and child asthma education program. Journal of Asthma 2005;42(10):813-821. R832139 (2006)
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  • Journal Article Butz A. Evidence-Based Practice: What is the Evidence for Medication Adherence in Children? Journal of Pediatric Health Care 2006;20(5):338-341. R832139 (2007)
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    Journal Article Butz A, Sellers MD, Land C, Walker J, Tsoukleris M, Bollinger ME. Factors affecting primary care provider and caregiver concordance for pediatric asthma medications. Journal of Asthma 2009;46(3):308-313. R832139 (Final)
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  • Journal Article Callahan KA, Eggleston PA, Rand CS, Kanchanaraksa S, Swartz LJ, Wood RA. Knowledge and practice of dust mite control by specialty care. Annals of Allergy, Asthma & Immunology 2003;90(3):302-307. R832139 (2004)
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  • Journal Article Cheadle C, Becker KG, Cho-Chung YS, Nesterova M, Watkins T, Wood W 3rd, Prabhu V, Barnes KC. A Rapid Method for Microarray Cross Platform Comparisons using Gene Expression Signatures. Molecular and Cellular Probes 2007;21(1):35-46. R832139 (2007)
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    Journal Article Chen R, Roman J, Guo J, West E, McDyer J, Williams MA, Georas SN. Lysophosphatidic acid modulates the activation of human monocyte-derived dendritic cells. Stem Cells and Development 2006;15(6):797-804. R832139 (2007)
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    Journal Article Curtin-Brosnan J, Matsui EC, Breysse P, McCormack MC, Hansel NN, Tonorezos ES, Eggleston PA, Williams DL, Diette GB. Parent report of pests and pets and indoor allergen levels in inner-city homes. Annals of Allergy, Asthma & Immunology 2008;101(5):517-523. R832139 (Final)
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  • Journal Article Diette GB, Krishnan JA, Wolfenden LL, Skinner EA, Steinwachs DM, Wu AW. Relationship of physician estimate of underlying asthma severity to asthma outcomes. Annals of Allergy, Asthma & Immunology 2004;93(6):546-552. R832139 (2004)
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  • Journal Article Diette GB, Patino CM, Merriman B, Paulin L, Riekert K, Okelo S, Thompson K, Krishnan JA, Quartey R, Perez-Williams D, Rand C. Patient factors that physicians use to assign asthma treatment. Archives of Internal Medicine 2007;167(13):1360-1366. R832139 (2007)
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  • Journal Article Eggleston PA. Cockroach allergen abatement in inner-city homes. Annals of Allergy, Asthma & Immunology 2003;91(6):512-514. R832139 (2004)
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  • Journal Article Eggleston PA. Environmental control for fungal allergen exposure. Current Allergy and Asthma Reports 2003;3(5):424-429. R832139 (2004)
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  • Journal Article Eggleston PA, Butz A, Rand C, Curtin-Brosnan J, Kanchanaraksa S, Swartz L, Breysse P, Buckley T, Diette G, Merriman B, Krishnan JA. Home environmental intervention in inner-city asthma:a randomized controlled clinical trial. Annals of Allergy, Asthma & Immunology 2005;95(6):518-524. R832139 (2004)
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  • Journal Article Eggleston PA. Improving indoor environments: reducing allergen exposures. Journal of Allergy and Clinical Immunology 2005;116(1):122-126. R832139 (2004)
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  • Journal Article Eggleston PA, Diette G, Lipsett M, Lewis T, Tager I, McConnell R, Chrischilles E, Lanphear B, Miller R, Krishnan J. Lessons learned for the study of childhood asthma from the Centers for Children’s Environmental Health and Disease Prevention Research. Environmental Health Perspectives 2005;113(10):1430-1436. R832139 (2004)
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  • Journal Article Ferrari E, Tsay A, Eggleston PA, Spisni A, Chapman MD. Environmental detection of mouse allergen by means of immunoassay for recombinant Mus m 1. Journal of Allergy and Clinical Immunology 2004;114(2):341-346. R832139 (2004)
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  • Journal Article Gao L, Grant AV, Rafaels N, Stockton-Porter M, Watkins T, Gao P, Chi P, Munoz M, Watson A, Dunston G, Togias A, Hansel N, Sevransky J, Maloney JP, Moss M, Shanholtz C, Brower R, Garcia JGN, Grigoryev DN, Cheadle C, Beaty TH, Mathias RA, Barnes KC. Polymorphisms in the Myosin Light Chain Kinase Gene that Confer Risk of Severe Sepsis are Associated with a Lower Risk of Asthma. Journal of Allergy and Clinical Immunology 2007;119(5):1111-1118. R832139 (2007)
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    Journal Article Gao P-S, Shimizu K, Grant AV, Rafaels N, Zhou L-F, Hudson SA, Konno S, Zimmermann N, Araujo MI, Ponte EV, Cruz AA, Nishimura M, Su S-N, Hizawa N, Beaty TH, Mathias RA, Rothenberg ME, Barnes KC, Bochner BS. Polymorphisms in the sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) gene are associated with susceptibility to asthma. European Journal of Human Genetics 2010;18(6):713-719. R832139 (Final)
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  • Journal Article Garg A, Serwint J, Higman S, Kanof A, Schell D, Colon I, Butz A. Self-Efficacy at Smoking Cessation Counseling Parents in Primary Care: An Office-Based Intervention for Pediatricians and Family Physicians. Clinical Pediatrics 2007;46(3):252-257. R832139 (2007)
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    Journal Article Georas SN. Inhaled glucocorticoids, lymphocytes, and dendritic cells in asthma and obstructive lung diseases. Proceedings of the American Thoracic Society 2004;1(3):215-221. R832139 (Final)
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  • Journal Article Georas SN, Guo J, De Fanis U, Casolaro V. T-helper type 2 regulation in allergic disease. European Respiratory Journal 2005;26(6):1119-1137. R832139 (2006)
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  • Journal Article Georas SN, Berdyshev E, Hubbard W, Gorshkova IA, Usatyuk PV, Saatian B, Myers AC, Williams MA, Xiao HQ, Liu M, Natarajan V. Lysophosphatidic acid is detectable in human bronchoalveolar lavage fluids at baseline and increased after segmental allergen challenge. Clinical and Experimental Allergy 2007;37(3):311-322. R832139 (2007)
    R832139 (Final)
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  • Journal Article Gilliland F, Avol E, Kinney P, Jerrett M, Dvonch T, Lurmann F, Buckley T, Breysse P, Keeler G, de Villiers T, McConnell R. Air pollution exposure assessment for epidemiologic studies of pregnant women and children: lessons learned from the Centers for Children's Environmental Health and Disease Prevention Research. Environmental Health Perspectives 2005;113(10):1447-1454. R832139 (2006)
    R826708 (2000)
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    R832141 (2006)
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  • Journal Article Guajardo JR, Schleifer KW, Daines MO, Ruddy RM, Aronow BJ, Wills-Karp M, Hershey GK. Altered gene expression profiles in nasal respiratory epithelium reflect stable versus acute childhood asthma. Journal of Allergy and Clinical Immunology 2005;115(2):243-251. R832139 (2007)
    R832139C003 (2006)
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  • Full-text: Journal of Allergy and Clinical Immunology HTML
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  • Journal Article Hansel NN, Hilmer SC, Georas SN, Cope LM, Guo J, Irizarry RA, Diette GB. Oligonucleotide-microarray analysis of peripheral-blood lymphocytes in severe asthma. The Journal of Laboratory and Clinical Medicine 2005;145(5):263-274. R832139 (2004)
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  • Journal Article Hansel NN, Eggleston PA, Krishnan JA, Curtin-Brosnan J, Rand CS, Patino CM, Diette GB. Asthma-related health status determinants of environmental control practices for inner-city preschool children. Annals of Allergy, Asthma & Immunology 2006;97(3):409-417. R832139 (2007)
    R832139C001 (2007)
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  • Abstract: Annals of Allergy, Asthma & Immunology - abstract
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  • Journal Article Hansel NN, Rand CS, Krishnan JA, Okelo S, Breysse PN, Eggleston PA, Matsui E, Curtin-Brosnan J, Diette GB. Influence of caregivers' health beliefs and experiences on their use of environmental control practices in homes of pre-school children with asthma. Pediatric Asthma, Allergy & Immunology 2006;19(4):231-242. R832139 (2007)
    R832139C001 (2007)
  • Abstract: Mary Ann Liebert Inc. - abstract
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  • Journal Article Hansel NN, Diette GB. Gene expression profiling in human asthma. Proceedings of the American Thoracic Society 2007;4(1):32-36. R832139 (2007)
    R832139 (Final)
    R832139C001 (2007)
    R832139C001 (Final)
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  • Full-text: ATS Journals-Full Text HTML
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  • Journal Article Hansel NN, Breysse PN, McCormack MC, Matsui EC, Curtin-Brosnan J, Williams DL, Moore JL, Cuhran JL, Diette GB. A longitudinal study of indoor nitrogen dioxide levels and respiratory symptoms in inner-city children with asthma. Environmental Health Perspectives 2008;116(10):1428-1432. R832139 (Final)
    R832139C001 (Final)
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  • Abstract: EHP-Abstract
  • Journal Article Hawlisch H, Wills-Karp M, Karp CL, Kohl J. The anaphylatoxins bridge innate and adaptive immune responses in allergic asthma. Molecular Immunology 2004;41(2-3):123-131. R832139 (2004)
    R832139 (2005)
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  • Journal Article Huang I-C, Frangakis C, Dominici F, Diette GB, Wu AW. Application of a propensity score approach for risk adjustment in profiling multiple physician groups on asthma care. Health Services Research 2005;40(1):253-278. R832139 (2004)
    R832139 (2005)
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    R832139C001 (2004)
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  • Journal Article Huang I-C, Dominici F, Frangakis C, Diette GB, Damberg CL, Wu AW. Is risk-adjustor selection more important than statistical approach for provider profiling? Asthma as an example. Medical Decision Making 2005;25(1):20-34. R832139 (2004)
    R832139 (2005)
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    R832139C001 (2005)
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  • Journal Article Huang I-C, Diette GB, Dominici F, Frangakis C, Wu AW. Variations of physician group profiling indicators for asthma care. The American Journal of Managed Care 2005;11(1):38-44. R832139 (2004)
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  • Journal Article Israel BA, Parker EA, Rowe Z, Salvatore A, Minkler M, Lopez J, Butz A, Mosley A, Coates L, Lambert G, Potito PA, Brenner B, Rivera M, Romero H, Thompson B, Coronado G, Halstead S. Community-based participatory research:lessons learned from the Centers for Children's Environmental Health and Disease Prevention Research. Environmental Health Perspectives 2005;113(10):1463-1471. R832139 (2006)
    R826710 (Final)
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  • Journal Article Keen JC, Cianferoni A, Florio G, Guo J, Chen R, Roman J, Wills-Karp M, Casolaro V, Georas SN. Characterization of a novel PMA-inducible pathway of interleukin-13 gene expression in T cells. Immunology 2006;117(1):29-37. R832139 (2006)
    R832139 (2007)
    R832139C001 (2007)
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  • Journal Article Kohl J, Baelder R, Lewkowich IP, Pandey MK, Hawlisch H, Wang L, Best J, Herman NS, Sproles AA, Zwirner J, Whitsett JA, Gerard C, Sfyroera G, Lambris JD, Wills-Karp M. A regulatory role for the C5a anaphylatoxin in type 2 immunity in asthma. Journal of Clinical Investigation 2006;116(3):783-796. R832139 (2007)
    R832139C003 (2006)
    R832139C003 (2007)
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  • Full-text: Journal of Clinical Investigation HTML
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  • Journal Article Kohl J, Wills-Karp M. Complement regulates inhalation tolerance at the dendritic cell/T cell interface. Molecular Immunology 2007;44(1-3):44-56. R832139 (Final)
    R832139C003 (2007)
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  • Journal Article Kohl J, Wills-Karp M. A dual role for complement in allergic asthma. Current Opinion in Pharmacology 2007;7(3):283-289. R832139 (Final)
    R832139C003 (2007)
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  • Journal Article Krishnan V, Diette GB, Rand CS, Bilderback AL, Merriman B, Hansel NN, Krishnan JA. Mortality in patients hospitalized for asthma exacerbations in the United States. American Journal of Respiratory and Critical Care Medicine 2006;174(6):633-638. R832139 (2007)
    R832139C001 (2007)
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  • Journal Article Lewkowich IP, Herman NS, Schleifer KW, Dance MP, Chen BL, Dienger KM, Sproles AA, Shah JS, Kohl J, Belkaid Y, Wills-Karp M. CD4+CD25+ T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function. Journal of Experimental Medicine 2005;202(11):1549-1561. R832139 (2006)
    R832139 (2007)
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  • Full-text: Journal of Experimental Medicine PDF
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  • Journal Article Limb SL, Brown KC, Wood RA, Wise RA, Eggleston PA, Tonascia J, Adkinson NF Jr. Irreversible lung function deficits in young adults with a history of childhood asthma. Journal of Allergy and Clinical Immunology 2005;116(6):1213-1219. R832139 (2006)
  • Abstract from PubMed
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  • Journal Article Limb SL, Brown KC, Wood RA, Wise RA, Eggleston PA, Tonascia J, Hamilton RG, Adkinson Jr NF. Adult asthma severity in individuals with a history of childhood asthma. Journal of Allergy and Clinical Immunology 2005;115(1):61-66. R832139 (2004)
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  • Journal Article Mathias RA, Gao P, Goldstein JL, Wilson AF, Pugh EW, Furbert-Harris P, Dunston GM, Malveaux FJ, Togias A, Barnes KC, Beaty TH, Huang S-K. A graphical assessment of p-values from sliding window haplotype tests of association to identify asthma susceptibility loci on chromosome 11q. BMC Genetics 2006;7:38. R832139 (2007)
    not available
    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. R832139 (Final)
    R834510 (2010)
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  • Journal Article Matsui EC, Wood RA, Rand C, Kanchanaraksa S, Swartz L, Curtin-Brosnan J, Eggleston PA. Cockroach allergen exposure and sensitization in suburban middle-class children with asthma. Journal of Allergy and Clinical Immunology 2003;112(1):87-92. R832139 (2004)
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  • Journal Article Matsui EC, Wood RA, Rand C, Kanchanaraksa S, Swartz L, Eggleston PA. Mouse allergen exposure and mouse skin test sensitivity in suburban, middle-class children with asthma. The Journal of Allergy and Clinical Immunology 2004;113(5):910-915. R832139 (2004)
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  • Journal Article Matsui EC, Krop EJM, Diette GB, Aalberse RC, Smith AL, Eggleston PA. Mouse allergen exposure and immunologic responses: IgE-mediated mouse sensitization and mouse-specific IgG and IgG4 levels. Annals of Allergy, Asthma & Immunology 2004;93(2):171-178. R832139 (2004)
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  • Journal Article Matsui EC, Diette GB, Krop EJM, Aalberse RC, Smith AL, Curtin-Brosnan J, Eggleston PA. Mouse allergen-specific immunoglobulin G and immunoglobulin G4 and allergic symptoms in immunoglobulin E-sensitized laboratory animal workers. Clinical & Experimental Allergy 2005;35(10):1347-1353. R832139 (2006)
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  • Journal Article Matsui EC, Simons E, Rand C, Butz A, Buckley TJ, Breysse P, Eggleston PA. Airborne mouse allergen in the homes of inner-city children with asthma. Journal of Allergy and Clinical Immunology 2005;115(2):358-363. R832139 (2004)
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  • Journal Article Matsui EC, Diette GB, Krop EJ, Aalberse RC, Smith AL, Eggleston PA. Mouse allergen-specific immunoglobulin G4 and risk of mouse skin test sensitivity. Clinical & Experimental Allergy 2006;36(8):1097-1103. R832139 (2007)
    R832139 (Final)
    R832139C001 (2006)
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  • Journal Article Matsui EC, Eggleston PA, Buckley TJ, Krishnan JA, Breysse P, Rand C, Diette GB. Household mouse allergen exposure and asthma morbidity in inner-city preschool children. Annals of Allergy, Asthma & Immunology 2006;97(4):514-520. R832139 (2007)
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  • Abstract: Annals of Allergy, Asthma & Immunology - abstract
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  • Journal Article Matsui EC, Eggleston PA, Breysse PN, Rand CS, Diette GB. Mouse allergen-specific antibody responses in inner-city children with asthma. Journal of Allergy and Clinical Immunology 2007;119(4):910-915. R832139 (2007)
    R832139C001 (2007)
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  • Journal Article Mudd KE, Bollinger ME, Hsu VD, Manning A, Tsoukleris MG, Butz AM. Concordance of Medicaid and pharmacy record data in inner-city children with asthma. Contemporary Clinical Trials 2008;29(1):13-20. R832139 (Final)
    R832139C002 (Final)
  • Abstract from PubMed
  • Full-text: Hopkins - Full Text PDF
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  • Journal Article Mudd K, Bollinger ME, Hsu VD, Donithan M, Butz A. Pharmacy fill patterns in young urban children with persistent asthma. Journal of Asthma 2006;43(8):597-600. R832139 (2007)
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    Journal Article Okelo SO, Wu AW, Krishnan JA, Rand CS, Skinner EA, Diette GB. Emotional quality-of-life and outcomes in adolescents with asthma. Journal of Pediatrics 2004;145(4):523-529. R832139 (2004)
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  • Journal Article Okelo SO, Wu AW, Merriman B, Krishnan JA, Diette GB. Are physician estimates of asthma severity less accurate in black than in white patients? Journal of General Internal Medicine 2007;22(7):976-981. R832139 (2007)
    R832139C001 (2007)
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  • Journal Article Paasche-Orlow MK, Riekert KA, Bilderback A, Chanmugam A, Hill P, Rand CS, Brancati FL, Krishnan JA. Tailored education may reduce health literacy disparities in asthma self-management. American Journal of Respiratory and Critical Care Medicine 2005;172(8):980-986. R832139 (2006)
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  • Journal Article Perkins C, Wills-Karp M, Finkelman FD. IL-4 induces IL-13-independent allergic airway inflammation. Journal of Allergy and Clinical Immunology 2006;118(2):410-419. R832139 (Final)
    R832139C003 (2007)
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  • Journal Article Perry TT, Wood RA, Matsui EC, Curtin-Brosnan J, Rand C, Eggleston PA. Room-Specific Characteristics of Suburban Homes as Predictors of Indoor Allergen Concentrations. Annals of Allergy, Asthma & Immunology 2006;97(5):628-635. R832139 (2007)
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    Journal Article Perry T, Matsui E, Merriman B, Duong T, Eggleston P. The prevalence of rat allergen in inner-city homes and its relationship to sensitization and asthma morbidity. Journal of Allergy and Clinical Immunology 2003;112(2):346-352. R832139 (2004)
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  • Journal Article Phipatanakul W, Cronin B, Wood RA, Eggleston PA, Shih M-C, Song L, Tachdjian R, Oettgen HC. Effect of environmental intervention on mouse allergen levels in homes of inner-city Boston children with asthma. Annals of Allergy, Asthma & Immunology 2004:92(4):420-425. R832139 (2004)
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  • Journal Article Porter M, Karp M, Killedar S, Bauer SM, Guo J, Williams D, Breysse P, Georas SN, Williams MA. Diesel-enriched particulate matter functionally activates human dendritic cells. American Journal of Respiratory Cell and Molecular Biology 2007;37(6):706-719. R832139 (2007)
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    Journal Article Rangasamy T, Guo J, Mitzner WA, Roman J, Singh A, Fryer AD, Yamamoto M, Kensler TW, Tuder RM, Georas SN, Biswal S. Disruption of Nrf2 enhances susceptibility to severe airway inflammation and asthma in mice. Journal of Experimental Medicine 2005;202(1):47-59. R832139 (2006)
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  • Full-text: Journal of Experimental Medicine - full text html
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  • Journal Article Riekert KA, Butz AM, Eggleston PA, Huss K, Winkelstein M, Rand CS. Caregiver-physician medication concordance and undertreatment of asthma among inner-city children. Pediatrics 2003;111(3):e214-e220. R832139 (2004)
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  • Full-text: Pediatrics Full Text
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  • Journal Article Rubenfeld J, Guo J, Sookrung N, Chen R, Chaicumpa W, Casolaro V, Zhao Y, Natarajan V, Georas S. Lysophosphatidic Acid Enhances Interleukin-13 Gene Expression and Promoter Activity in T Cells. Lung Cellular and Molecular Physiology 2006;290(1):L66-L74. R832139 (2007)
    not available
    Journal Article Rubinson L, Wu AW, Haponik EF, Diette GB. Why is it that internists do not follow guidelines for preventing intravascular catheter infections? Infection Control and Hospital Epidemiology 2005;26(6):525-533. R832139 (2004)
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    R832139 (Final)
    R832139C001 (2005)
    R832139C001 (2006)
  • Abstract from PubMed
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  • Journal Article Rule AM, Geyh AS, Ramos-Bonilla JP, Mihalic JN, Margulies JD, Polyak LM, Kesavan J, Breysse PN. Design and characterization of a sequential cyclone system for the collection of bulk particulate matter. Journal of Environmental Monitoring 2010;12(10):1807-1814. R832139 (Final)
    R832417 (Final)
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  • Journal Article Saatian B, Zhao Y, He D, Georas SN, Watkins T, Spannhake EW, Natarajan V. Transcriptional Regulation of Lysophosphatidic Acid-Induced Interleukin-8 Expression and Secretion by p38 MAPK and JNK in Human Bronchial Epithelial Cells. Biochemical Journal 2006;393(3):657-668. R832139 (2007)
    not available
    Journal Article Sapkota A, Symons JM, Kleissl J, Wang L, Parlange MB, Ondov J, Breysse PN, Diette GB, Eggleston PA, Buckley TJ. Impact of the 2002 Canadian forest fires on particulate matter air quality in Baltimore city. Environmental Science & Technology 2005;39(1):24-32. R832139 (2004)
    R832139 (2005)
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    R832139 (Final)
    R832139C001 (2005)
    R832139C001 (2006)
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  • Journal Article Saunders V, Breysse P, Clark J, Sproles A, Davila M, Wills-Karp M. Particulate matter-induced airway hyperresponsiveness is lymphocyte dependent. Environmental Health Perspectives 2010;118(5):640-646. R832139 (Final)
    R832139C003 (Final)
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  • Journal Article Schmier JK, Manjunath R, Halpern MT, Jones ML, Thompson K, Diette GB. The impact of inadequately controlled asthma in urban children on quality of life and productivity. Annals of Allergy, Asthma & Immunology 2007;98(3):245-251. R832139 (2007)
    R832139C001 (2007)
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  • Abstract: Annals of Allergy, Asthma & Immunology - abstract
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  • Journal Article Schweitzer IB, Smith E, Harrison DJ, Myers DD, Eggleston PA, Stockwell JD, Paigen B, Smith AL. Reducing exposure to laboratory animal allergens. Comparative Medicine 2003;53(5):487-492. R832139 (2004)
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  • Journal Article Sharma HP, Hansel NN, Matsui EC, Diette GB, Eggleston PA, Breysee PN. Indoor environmental influences on children's asthma. Pediatric Clinics of North America 2007;54(1):103-120. R832139 (2007)
    R832139C001 (2007)
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  • Abstract: Science Direct - abstract
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  • Journal Article Sharma HP, Matsui EC, Eggleston PA, Hansel NN, Curtin-Brosnan J, Diette GB. Does current asthma control predict future health care use among black preschool-aged inner-city children? Pediatrics 2007;120(5):e1174-1181. R832139 (Final)
    R832139C001 (Final)
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  • Abstract: Pediatrics-Abstract
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  • Journal Article Simons E, Curtin-Brosnan J, Buckley TJ, Breysse P, Eggleston PA. Indoor Environmental Differences between Inner City and Suburban Homes of Children with Asthma. Journal of Urban Health 2007;84(4):577-590. R832139 (2007)
    not available
    Journal Article Skinner EA, Diette GB, Algatt-Bergstrom PJ, Nguyen TT, Clark RD, Markson LE, Wu AW. The Asthma Therapy Assessment Questionnaire (ATAQ) for children and adolescents. Disease Management 2004;7(4):305-313. R832139 (2004)
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  • Journal Article Smith A, Krishnan JA, Bilderback A, Riekert KA, Rand CS, Bartlett SJ. Depressive symptoms and adherence to asthma therapy after hospital discharge. Chest 2006;130(4):1034-1038. R832139 (2007)
    not available
    Journal Article Swartz LJ, Callahan KA, Butz AM, Rand CS, Kanchanaraksa S, Diette GB, Krishnan JA, Breysse PN, Buckley TJ, Mosley AM, Eggleston PA. Methods and issues in conducting a community-based environmental randomized trial. Environmental Research 2004;95(2):156-165. R832139 (2004)
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  • Journal Article Walker J, Lewis-Land C, Kub J, Tsoukleris M, Butz A. The effect of violence on asthma:are our children facing a double-edged sword? Journal of Community Health 2008;33(6):384-388. R832139 (Final)
    R832139C002 (Final)
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  • Full-text: Hopkins - Full Text PDF
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  • Abstract: Springer-Abstract
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  • Journal Article Williams MA, Porter M, Roman J, Breysse P, Williams D, Georas SN. Ambient Baltimore Particulate Matter Directs Non-Classical Immune Activation of Human Myeloid Dendritic Cells. Journal of Allergy and Clinical Immunology 2007;119(2):488-497. R832139 (2007)
    R832139C004 (2007)
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    Journal Article Williams MA, Cheadle C, Watkins T, Killedar S, Tailor A, Barnes K, Georas S. TLR2 and TLR4 are potential biomarkers of environmental particulate matter exposed human myeloid dendritic cells. Biomarker Insights 2007;2:225-239. R832139C004 (2007)
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    Journal Article Williams MA, Bauer S, Lu W, Guo J, Walter S, Bushnell TP, Lillehoj EP, Georas SN. Deletion of the mucin-like molecule muc1 enhances dendritic cell activation in response to toll-like receptor ligands. Journal of Innate Immunity 2010;2(2):123-143. R832139 (Final)
    R832139C004 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: Karger-Full Text PDF
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  • Abstract: Karger-Abstract
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  • Journal Article Williams MC, Georas S. Gene expression patterns and susceptibility to allergic responses. Expert Review of Clinical Immunology 2006;2(1):59-73. R832139 (2006)
    R832139 (2007)
    R832139C001 (2007)
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  • Abstract: Expert Reviews - abstract
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  • Journal Article Wills-Karp M, Ewart SL. Time to draw breath: asthma-susceptibility genes are identified. Nature Reviews Genetics 2004;5(5):376-387. R832139 (2004)
    R832139 (2005)
    R832139C003 (2004)
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  • Journal Article Wills-Karp M, Koehl J. New insights into the role of the complement pathway in allergy and asthma. Current Allergy and Asthma Reports 2005;5(5):362-369. R832139 (2007)
    R832139C003 (2006)
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  • Journal Article Wills-Karp M. Complement activation pathways: a bridge between innate and adaptive immune responses in asthma. Proceedings of the American Thoracic Society 2007;4:247-251. R832139C003 (2007)
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    Journal Article Winkelstein ML, Quartey R, Pham L, Lewis-Boyer L, Lewis C, Hill K, Butz A. Asthma education for rural school nurses: resources, barriers, and outcomes. Journal of School Nursing 2006;22(3):170-177. R832139 (2007)
    R832139C002 (2006)
    R832139C002 (2007)
  • Abstract from PubMed
  • Full-text: Sage Publications - full text html
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  • Abstract: Sage Publications
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  • Journal Article Wolfenden LL, Diette GB, Krishnan JA, Skinner EA, Steinwachs DM, Wu AW. Lower physician estimate of underlying asthma severity leads to undertreatment. Archives of Internal Medicine 2003;163(2):231-236. R832139 (2004)
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    R832139C001 (2004)
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  • Full-text: AMA Full Text
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  • Journal Article Yurk RA, Diette GB, Skinner EA, Dominici F, Clark RD, Steinwachs DM, Wu AW. Predicting patient-reported asthma outcomes for adults in managed care. The American Journal of Managed Care 2004;10(5):321-328. R832139 (2004)
    R832139 (2005)
    R832139 (2007)
    R832139C001 (2004)
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  • Full-text: AJMC Full Text
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  • Journal Article Zambelli-Weiner A, Ehrlich E, Stockton ML, Grant AV, Zhang S, Levett PN, Beaty TH, Barnes KC. Evaluation of the CD14/-260 polymorphism and house dust endotoxin exposure in the Barbados Asthma Genetics Study. Journal of Allergy and Clinical Immunology 2005;115(6):1203-1209. R832139 (2006)
  • Abstract from PubMed
  • Full-text: Journal of Allergy and Clinical Immunology - full text html
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  • Abstract: Journal of Allergy and Clinical Immunology - abstract
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  • Other: Journal of Allergy and Clinical Immunology - PDF
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  • Journal Article Zeldin DC, Eggleston P, Chapman M, Piedimonte G, Renz H, Peden D. How exposures to biologics influence the induction and incidence of asthma. Environmental Health Perspectives 2006;114(4):620-626. R832139 (2004)
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    R832139C002 (2005)
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  • Abstract from PubMed
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  • Full-text: Environmental Health Perspectives Full Text
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  • Other: Environmental Health Perspectives PDF
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  • Journal Article Zhao Y, He D, Zhao J, Wang L, Leff AR, Spannhake EW, Georas S, Natarajan V. Lysophosphatidic acid induces interleukin-13 (IL-13) receptor alpha2 expression and inhibits IL-13 signaling in primary human bronchial epithelial cells. Journal of Biological Chemistry 2007;282(14):10172-10179. R832139 (2007)
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    Supplemental Keywords:

    Childhood asthma, air pollutants, allergens, asthma morbidity, Health, Scientific Discipline, Geographic Area, HUMAN HEALTH, Health Risk Assessment, Epidemiology, State, Risk Assessments, Biochemistry, Health Effects, asthma, particulate matter, children's health, adolescents, morbidity, airway disease, ozone, respiratory disease, allergic airway disease, air pollution, human exposure, Maryland (MD), asthmatic children, cigarette smoke, environmental tobacco smoke, urban environment, human health risk

    Progress and Final Reports:

    Original Abstract
  • 2004 Progress Report
  • 2005 Progress Report
  • 2006 Progress Report
  • 2007 Progress Report
  • 2008
  • 2009
  • Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R832139C001 The Epidemiology of Susceptibility to Airborne Particulates and Allergens to Asthma in African Americans
    R832139C002 A Randomized Controlled Trial of Behavior Changes in Home Exposure Control
    R832139C003 Mechanisms of Particulate-Induced Allergic Asthma
    R832139C004 Dendritic Cell Activation by Particulate Matter and Allergen