2007 Progress Report: The Epidemiology of Susceptibility to Airborne Particulates and Allergens to Asthma in African Americans

EPA Grant Number: R832139C001
Subproject: 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 N.
Title: The Epidemiology of Susceptibility to Airborne Particulates and Allergens to Asthma in African Americans
Investigators: Diette, Greg
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 Period Covered by this Report: November 1, 2006 through October 31, 2007
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2003) RFA Text |  Recipients Lists
Research Category: Children's Health , Health Effects , Health

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 and allergens. Our Strategy is to employ high-throughput genomic technologies to examine the (i) patterns of gene expression to identified candidate genes and (ii) the genetic basis for polymorphisms in genes which explain susceptibility to PM in an inner city African American population with asthma.

The specific aims are (1) to obtain and prioritize and candidate genes for susceptibility to airborne particulate matter through gene expression profiling in human CD4+ T-lymphocytes; (2) to identify polymorphishms in candidate genes associated with susceptibility to PM exposures in asthma and with asthma severity; and (3) to identify polymorphisms in candidate genes associated with an interactive effect of cockroach allergen and PM10 exposures on asthma severity
An important secondary goal was to complete the Cohort study of home environments in inner city children with and without asthma and the nested longitudinal follow-up of the asthmatic cases. The original goals and objectives of that study were: (1) to characterize and compare exposure to allergens and air pollutants among inner city children with and without asthma; (2) in a subset of homes, to characterize the within-home temporal variability in air pollution and allergen exposure; (3) to estimate the occurrence of respiratory morbidity among inner city children with asthma; (4) to study environmental and hereditary determinants of childhood asthma; (5) to assess independent and joint effects of exposure to indoor allergens and indoor air pollution on respiratory morbidity in children with asthma; (6) to characterize current use of environmental control practices among inner city children with asthma; (7) to identify barriers through the use of guidelines on environmental control practices among primary care providers caring for inner city children with asthma; (8) to assess the differential impact of indoor and outdoor air pollution among asthmatic and non-asthmatic homes; and (9) to 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:

  1. 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 have also successfully completed the planned 3-month and 6-month follow-ups in the children enrolled in the cohort study (children with asthma).
  2. We have performed analyses on the children enrolled. 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.
  3. Analysis of the physician reported data shows that their adherence is low to environmental control measures recommended by the 1997 NHLBI asthma guidelines. While 80% ask all parents about exposure to tobacco smoke, only 60% ask about pets, 20% about dust mites and 10% about indoor molds. None of the physician routinely order skin testing for allergens, and only 10% advice 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% had a copy of them. Only 40% 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% reported a lack of time during a patient visit, 70% a lack of educational materials, 60% indicated they were inadequately trained, and 50% reported not having adequate support staff for these functions. Outcomes expectancy was low, too, with only 30% of physicians believing that there would be a modest or large benefit to counseling patients to reduce exposure to pets, dust mites and cockroaches.
  4. Analysis of environmental control practices (ECPs), which are an integral part of NAEPP guidelines, shows many inner-city families of asthmatics do not implement them. Caregivers of the children, age 2-6 years, with asthma completed a questionnaire about ECPs to manage asthma-related health of the child. Mean scores of emotional bother were calculated from the Children’s Health Survey for Asthma (CHSA), a validated, self-reported measure for parents of asthmatic children. Caregivers who reported being more bothered by their child’s asthma were significantly more likely to install devices to improve air quality (e.g., dehumidifiers and air conditioners) (OR, 1.04, 95% CI 1.01-1.07 and OR, 1.03, 95% CI 1.01-1.06, respectively, per 1 point increase in the 100-point emotional bother scale). Caregivers who were more bothered were also more likely to make changes to the family room (OR, 1.04, CI 1.01-1.07) and child’s bedroom (OR, 1.02, 95% CI 1.00-1.04, p=0.06) for the child’s health. Cockroach and mouse control were not related to emotional bother of the caregiver. The child’s NAEPP severity category did not predict ECPs and adjustment for severity did not alter the association between emotional bother and ECPs. These findings were presented at the American Academy of Allergy, Asthma and Immunology. March 2006, Miami Beach, FL.
  5. We also investigated the relationship of caregiver health beliefs and asthma experiences to ECP use in homes of children with asthma. Caregivers of children with asthma completed a survey about indoor environmental exposures, ECPs, physician ECP recommendations, caregiver health beliefs and experiences (outcome expectancy, self-efficacy, emotional bother) regarding ECPs, child’s respiratory symptoms and medication use. Allergic sensitization was determined by skin prick testing. Caregivers who had higher outcome expectancy were more likely to report use of ECP than those with lower outcome expectancy (smoking avoidance (70 vs. 33%), roach control (61 vs. 44%), pet avoidance (42 vs. 24%), allergen-proof mattress/pillow encasings (6 vs. 0%), carpet removal (12 vs. 2%), and stuffed-animal removal (8 vs. 1%) (all p<0.05)). Self-efficacy and emotional bother were not associated with use or failure to use most ECPs. Most caregivers (83%) reported that their child’s physician had recommended smoking avoidance; however, less than half had recommended avoidance of specific allergens. Caregivers who reported that physicians recommended pet avoidance, allergen-proof mattress/pillow encasings, washing bed linens or stuffed-animal removal were more likely to have high outcome expectancy for the ECP.
  6. Asthma morbidity has shown some signs of improvement nationally, but remains particularly high in inner city minority children. Recent trends have shown greater use of Long Term Controller (LTC) medications nationally as recommended by national guidelines, but it is not known whether these improvements have reached inner city minority children. Analysis of our data shows these children had substantial morbidity: 63% had persistent symptoms (46% were moderate/severe), 25% had had an ED visit in the prior 3 months and 8% were currently using oral steroids (OCS). Only 38% were currently using a LTC medication, including 44% with persistent symptoms, 58% with recent ED visit, and 50% with recent OCS use. LTC use was associated with symptom severity (p<0.02), but not recent ED visits (p=0.31) or OCS use (p=0.37). Subjects with private insurance were somewhat more likely than those with public insurance to use LTC (53 vs. 36%, p=0.37) and co-payment for medications had no effect. These findings were presented at the American Thorax Society International Meeting. May 2006, San Diego, CA.
  7. Caregiver depression has been associated with worse care and outcomes for children with asthma. We surveyed caregivers of children with asthma (n=150, age 2-6 years) in the Baltimore Indoor Environment Study of Asthma in Kids (BIESAK). The primary outcome was caregiver reports of feeling depressed in the past week (hardly ever or never, some, or most of the time). Caregivers were asked “Are you afraid of violence in your neighborhood?” and whether any of the following had happened in their neighborhood in the past 6 months: a fight in which a weapon was used, a violent argument between neighbors or friends, a gang fight, a robbery or mugging, or a murder. T-test and two-sample Wilcoxon rank-sum (Mann-Whitney) tests were performed, and odds ratios were calculated. Analysis of the data shows that 87% of caregivers were the mother of the child and 4.8% were the grandmother. 45% reported feeling depressed at least some of the time in the last week and 57% knew of a violent event in their neighborhood in the past 6 months. Of those who knew of a recent violent event, 65% were afraid of violence in their neighborhood, while only 25% of those who did not know of a recent violent event were afraid of neighborhood violence. Caregivers afraid of violence reported greater feelings of depression compared to those who were not afraid of violence (OR 2.44; 95% CI 1.51 to 3.57; p<0.01). In addition, caregivers who knew of recent violent events in their neighborhood were more likely to report greater feelings of depression, compared to those who did not know of recent violent events (OR 1.59; 95% CI 1.00 to 2.55; p=0.05). These findings were presented at the Mid-Atlantic Society for Internal Medicine Meeting. March 2006, Hershey, PA.
  8. Although mouse allergen exposure is common in inner-city homes, little is known about the relationships between exposure and humoral immune responses to Mus m 1 in this population. Inner-city, preschool children with asthma underwent skin testing and venipuncture for determination of mouse allergen-specific IgE and IgG levels. Their homes were inspected and settled dust samples were collected for allergen analysis. The study population was predominantly African American (92%) with a mean age of 4.4 years. The prevalence rate of mouse sensitization was 26%, and did not consistently increase with increasing Mus m 1 levels. Instead, the prevalence rate was lowest among those exposed to < 2 μg/g, increased among those exposed to 2-7.9, and 8-29.9 μg/g, and then decreased among participants exposed to > 29.9 μg/g (14%, 20%, 40%, and 28%, respectively). Similarly, the prevalence rates of mouse allergen-specific IgG and IgG4 did not increase across increasing exposure categories. Mouse allergen-specific IgG and IgG4 were positively associated with IgE sensitization (OR [95% CI]: 38.6 [12.8-116.4] and 27.8 [9.5-80.8], respectively). These findings suggest that high level exposure to Mus m 1 in preschool children may be associated with attenuated humoral responses of all isotypes, rather than a selective attenuation of IgE alone.
  9. We examined whether domestic mouse exposure was a cause for asthma morbidity. Analysis of the data showed 26% of the participants with asthma were sensitized to mouse. Mouse-sensitized children exposed to higher levels of Mus m 1 (> 0.5 μg/g) had 50% more days of symptoms (IRR [95% CI]: 1.5 [1.1-2.1]) and 80% more days of beta-agonist use than other children (IRR [95% CI]: 1.8 [1.3-2.5]). Children in the sensitized and highly exposed group were also more likely to have an unscheduled doctor visit (OR [95% CI]: 3.1 [1.6-6.3]), ED visit (OR [95% CI]: 2.1 [1.1-4.1]), and hospitalization (OR [95% CI]: 36.6 [4.1-327.3]) than other children. These associations between mouse allergen exposure and asthma symptoms and morbidity remained significant after adjusting for potential confounders, including atopy and cockroach sensitization and exposure. In mouse-sensitized inner-city children, exposure to mouse allergen may be an important cause of asthma morbidity.

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 like 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.

Future Activities:

This portion of the study depends on compilation of data for approximately 900 subjects, including a) home visits to characterize environmental exposures, b) obtaining a specimen containing DNA, c) administration of surveys and d) obtaining height, weight and lung function measurements. The primary source of subjects is graduates of other studies, during which much of the data has already 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 and the Future Subjects Database. This year we will begin contacting adult subjects from the BASS (N=624) for collection of environmental data. These subjects have all already provided a DNA sample and have undergoing phenotypic characterization. IRB approval for an amendment pertaining to the inclusion of these adult subjects is pending and we expect approval in August 2007. We will be performing environmental monitoring and updating the phenotypic characterization of the subjects.


Journal Articles on this Report : 16 Displayed | Download in RIS Format

Other subproject views: All 38 publications 38 publications in selected types All 38 journal articles
Other center views: All 113 publications 113 publications in selected types All 110 journal articles
Type Citation Sub Project Document Sources
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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  • Abstract: Journal of Allergy and Clinical Immunology
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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)
    R832139 (2007)
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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)
    R832139 (Final)
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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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  • 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)
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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)
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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)
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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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  • Full-text: American Journal of Respiratory and Critical Care Medicine - Full Text HTML
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  • Abstract: American Journal of Respiratory and Critical Care Medicine - abstract
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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)
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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)
    R832139C001 (2007)
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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)
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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 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)
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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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  • 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)
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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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  • Supplemental Keywords:

    RFA, Scientific Discipline, Health, PHYSICAL ASPECTS, Air, HUMAN HEALTH, particulate matter, Genetics, Health Risk Assessment, Epidemiology, Allergens/Asthma, Health Effects, Physical Processes, asthma, children's health, asthma triggers, air toxics, long term exposure, morbidity, airway variablity, exposure, air pollution, children, air pollutant, human exposure, airborne pollutants, minorities, epidemiological studies, PM, allergens, minority children, respiratory, asthma morbidity, cockroaches

    Progress and Final Reports:

    Original Abstract
  • 2004 Progress Report
  • 2005 Progress Report
  • 2006 Progress Report
  • 2008
  • 2009
  • Final 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