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2005 Progress Report: The Epidemiology of Susceptibility to Airborne Particulates and Allergens to Asthma in African Americans
EPA Grant Number: R832139C001Subproject: this is subproject number 001 , established and managed by the Center Director under grant R832139
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Johns Hopkins Center for Childhood Asthma in the Urban Environment
Center Director: Breysse, Patrick
Title: The Epidemiology of Susceptibility to Airborne Particulates and Allergens to Asthma in African Americans
Investigators: Diette, Greg
Institution: Johns Hopkins University
EPA Project Officer: Fields, Nigel
Project Period: November 1, 2003 through October 31, 2008 (Extended to October 31, 2010)
Project Period Covered by this Report: November 1, 2004 through October 31, 2005
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2003)
Research Category: Children's Health , Health Effects
Description:
Objective:The long-range goal of the epidemiologic study is to examine the genetic basis of asthma in African Americans with specific attention to genetic modifiers involved in the enhanced susceptibility of certain patients to particulate matter (PM) and allergens. Our strategy is to employ high-throughput genomic technologies to examine the patterns of gene expression to identified candidate genes and the genetic basis for polymorphisms in genes, which explain susceptibility to PM in an inner city African American population with asthma.
The specific objectives are to: (1) obtain and prioritize candidate genes for susceptibility to airborne PM through gene expression profiling in human CD4+ T-lymphocytes; (2) identify polymorphisms in candidate genes associated with susceptibility to PM exposures in asthma and with asthma severity; and (3) identify polymorphisms in candidate genes associated with an interactive effect of cockroach allergen and PM10 exposures on asthma severity.
An important secondary goal is to complete the case control study of home environments in inner-city children with and without asthma and the nested longitudinal followup of the asthmatic cases. The original goals and objectives of that study were to: (1) characterize and compare exposure to allergens and air pollutants among inner-city children with and without asthma; (2) in a subset of homes, characterize the within-home temporal variability in air pollution and allergen exposure; (3) estimate the occurrence of respiratory morbidity among inner-city children with asthma; (4) study environmental and hereditary determinants of childhood asthma; (5) assess independent and joint effects of exposure to indoor allergens and indoor air pollution on respiratory morbidity in children with asthma; (6) characterize current use of environmental control practices among inner-city children with asthma; (7) identify barriers through the use of guidelines on environmental control practices among primary care providers caring for inner-city children with asthma; (8) assess the differential impact of indoor and outdoor air pollution among asthmatic and nonasthmatic homes; and (9) understand the relative contribution of different structural, financial, and personal barriers to use of recommended environmental control practices for children with asthma.Once completed, the data needed to be cleaned, a database constructed, and outcome analyses begun.
Progress Summary:Identification and Recruitment of Asthma and Control Subjects
Our recruitment goals of 150 children with asthma and 150 control children without asthma were accomplished by November 2004.To date, we also have successfully completed the planned 3-month and 6-month followups in the children enrolled in the cohort study (children with asthma).
We have performed preliminary analyses on the children enrolled.Among enrolled children without asthma, the mean age was 3.8 years (SD 1.5 years), 45 percent were male, 99 percent were African American, and 3.5 percent were Hispanic.Approximately half the parents reported a total household income of less than $25,000 per year.Among the children with asthma enrolled in the study, 57 percent were male, 94 percent African American, and 1.4 percent Hispanic; 88 percent had Medicaid insurance. There was substantial evidence of poor asthma control in these children:36 percent had one or more emergency department visits for asthma in the previous 3 months, and 56 percent had one or more days of wheezing in the prior 2 weeks. Fifty-nine percent had one or more nights of awakening from asthma in the prior 2 weeks. Parents of asthmatics reported that they had seen roaches in their home (43%) and 54 percent had cats, 43 percent dogs, and 82 percent had seen evidence of mice. The mean age of asthma subjects was 4.17 years. Among asthmatics, 57 percent were male. Thirty-five percent of parents of asthmatics had not graduated from high school, and only 37 percent of parents were working full time. Approximately 29 percent of families of asthmatics had a total income that was less than $20,000 annually. Among control subjects, the mean age was 3.84 years, 45 percent were male, 35 percent had parents who had not graduated from high school, 34 percent of parents were working full time and 35 percent had household incomes less than $20,000 annually. Among the children with asthma, 58 percent are mild intermittent, 17 percent mild persistent, and 25 percent moderate or severe persistent, as characterized by National Heart, Lung, and Blood Institute (NHLBI) guidelines. Forty-five percent of asthmatic children are skin-test positive to cockroach antigen (Bla g 1). The median level of bedroom Bla g 1 is 6.0 U/g, a value slightly higher than seen in the intervention study. Median bedroom level of PM2.5 was 28.0 μg/m3 and median PM10 level was 40.6 μg/m3. Children with the greatest symptom severity had the highest levels of bedroom PM. For example, 38 percent of children in the highest quartile of PM2.5 values had moderate/severe persistent asthma versus only 21 percent of those in the lowest quartile. Likewise, 28 percent of children in the highest quartile of PM10 had moderate/severe persistent asthma versus only 17 percent in the lowest quartile. Asthmatic children in this study are re-evaluated at 3 and 6 months (parent survey and home environmental assessment).
Preliminary analysis of the physician-reported data shows that adherence to environmental control measures recommended by the 1997 NHLBI asthma guidelines is low.Although 80 percent of physicians ask all parents about exposure to tobacco smoke, only 60 percent ask about pets, 20 percent about dust mites, and 10 percent about indoor molds. None of the physician routinely order skin testing for allergens, and only 10 percent advise all of their asthma patients to stay indoors on high ozone days. Barriers to the use of the guidelines, based on a conceptual model of problems with awareness of, agreement with, and ability to use the guidelines, were apparent for all studied guideline recommendations.For example, no physicians reported being very or extremely familiar with the NHLBI guidelines, and only 50 percent had a copy of them.Only 40 percent of physicians agree that children should undergo skin testing to assess sensitivity to seasonal allergens, even though all agree that physicians should help parents to reduce allergen exposure. Citing ability barriers to counseling parents to reduce inhaled allergen exposure for children, 90 percent of physicians reported a lack of time during a patient visit, 70 percent a lack of educational materials, 60 percent indicated they were inadequately trained, and 50 percent reported not having adequate support staff for these functions. Outcomes expectancy was low, with only 30 percent of physicians believing that there would be a modest or large benefit to counseling patients to reduce exposure to pets, dust mites, and cockroaches.
Objective 1
This year, we completed analysis and reporting of microarray analysis of CD4+ lymphocytes from severe and mild asthma subjects. Fifteen subjects were characterized, and genes were identified with two-fold mean expression differences or greater. Thirty-seven genes were upregulated, including transforming growth factor beta and those involved in T-cell activation, proliferation, and cytoskeletal changes. Three genes were downregulated, including the T-cell-receptor delta locus. Future studies will focus on susceptibility to PM exposure.
Objectives 2 and 3
This portion of the study depends on compilation of data for approximately 900 subjects, including: (1) home visits to characterize environmental exposures; (2) obtaining a specimen containing DNA; (3) administration of surveys; and (4) obtaining height, weight, and lung function measurements. The primary source of subjects is graduates of other studies, during which much of the data already has been collected. These other studies include the Cohort Study (N = 300), the Intervention Study (N = 100), and the Future Subjects Database (N = 400-500). Our focus this past year has been on graduates of the Cohort Study.
Home Visits
Home visits for Cohort Study participants began in June 2004.The majority of the homes are located in Baltimore City; some are in Baltimore and Harford counties. Visits were made mostly in the evenings and weekends to accommodate work and school schedules. Some of the families were located in homeless shelters, and 32 percent had moved at least one time since contact was made during the previous study.
To date, 277 of the 300 families (92%) have been contacted. For 251 families, we have completed home visits, 17 are noncontactable (1 deceased, 16 have moved out of state or country), and 26 have refused to participate in the study.We are attempting to contact the last six participants.We have asked the permission of the Johns Hopkins Institutional Review Board to use the other sources for subject recruitment and expect to begin using the other two sources by August 2005.
Collection of DNA
Mouthwash Procedure.Genomic DNA is extracted from the buccal cells of the study subjects by having each child rinse his/her mouth vigorously for 30 to 60 seconds with approximately 10 ml of Act mouthwash for children. At the end of the 30 to 60 seconds, the child expels the mouthwash (containing the buccal cells) into a plastic container. The child should not have anything to eat or drink for at least 45 minutes before performing this procedure. Of the 251 completed home visits, 226 children successfully completed the mouthwash procedure. 16 parents refused to allow their child to perform this part of the study and 9 children were unable to complete the mouthwash procedure.All genomic mouthwash samples are taken to Dr. Kathleen Barnes’ laboratory in the Asthma and Allergy Center at the Johns Hopkins Bayview Campus.Although the published literature and our pilot study suggested yields of DNA using the mouthwash procedure would be adequate, the yield of DNA from the mouthwash procedure in this study has been limited in many of the samples. Because of the limited yield, we have decided to amend the protocol to collect a blood sample. We will plan to use blood as the primary source for subjects not already contacted, and we will revisit those who already have been sampled via mouthwash so that we can assure a sufficient sample for multiple analyses.In addition, the serum obtained will allow us to update the allergy status of our subjects.
Venipuncture Procedure.We will begin to revisit the study participants (target date is June 27, 2005) to perform venipuncture to obtain a blood sample. This method will assure that we have sufficient DNA to support several genetic analyses. A research assistant trained and certified in phlebotomy will accompany a community home visitor to the home visit. Approximately 6 mL of blood will be obtained in 2-3 mL lavender tubes for the DNA sample. This procedure will be done at a second home visit, or if the parent/guardian chooses the visit can take place at the Asthma and Allergy Center at the Johns Hopkins Bayview Campus, the East Baltimore Medical Center, or the Pediatric Clinical Research Unit. To date, 61 families have completed the venipuncture, and 9 families have refused. Of the nine families that have refused venipuncture, we have mouthwash samples on eight participants.
Allergy Status
Additional serum (10 mL) will be obtained to allow us to obtain or update the allergy status of our subjects. Total IgE and radioallergosorbent testing for specific allergens (dust mites, cockroach, cat, dog, rat, mouse, oak, ragweed, and aspergillus). All samples will be taken to Dr. Peyton Eggleston’s laboratory at the Johns Hopkins Campus.
Surveys and Measurements
A brief survey is administered that updates the health status information about the child. Two children who were controls have been diagnosed with asthma. Height, weight, and three peak flow measurements are obtained on each subject. Height and weight will be compared to previous measurements, and weight of controls will be compared to cases.
Findings, Relevance to Field
Our findings have several implications to the field of asthma. First, to our knowledge they are the first studies to demonstrate that ambient particulates can directly induce the symptoms of asthma. Second, our finding that particulates induce complement component 3 activation may provide a potential mechanism by which particulates induce airway hyperresponsiveness and inflammation as well as provide a potential therapeutic target.
Future Activities:We will continue compiling data for approximately 900 subjects. This includes:(1) conducting home visits to characterize environmental exposures; (2) obtaining a specimen containing DNA; (3) administering surveys; and (4) obtaining height, weight, and lung function measurements.
Journal Articles on this Report : 5 Displayed | Download in RIS Format
| Other subproject views: | All 35 publications | 35 publications in selected types | All 35 journal articles |
| Other center views: | All 103 publications | 103 publications in selected types | All 100 journal articles |
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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) R832139 (2005) R832139 (2006) R832139C001 (2005) |
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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) R832139C001 (2005) R832139C001 (2006) |
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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) R832139 (2005) R832139C001 (2005) |
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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) R832139 (2005) R832139C001 (2005) |
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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) R832139 (2006) R832139C001 (2005) R832139C001 (2006) |
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airborne particulates, allergens, asthma, genetic modifiers, particulate matter, PM, children’s health,
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HUMAN HEALTH, Air, Scientific Discipline, Health, RFA, PHYSICAL ASPECTS, Health Effects, Health Risk Assessment, Physical Processes, Epidemiology, particulate matter, Allergens/Asthma, Genetics, minority children, allergens, children's health, cockroaches, air toxics, respiratory, minorities, airway variablity, indoor-outdoor relationships, air pollution, airborne pollutants, children, epidemiological studies, asthma morbidity, exposure, long term exposure, asthma triggers, asthma, human exposure, morbidity, PM
Progress and Final Reports:
2004 Progress Report
Original Abstract
2006 Progress Report
2007 Progress Report
Main Center Abstract and Reports:
R832139 Johns Hopkins Center for Childhood Asthma in the Urban Environment
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