Asthma is the most common chronic disease of childhood in the United States, causes significant morbidity, particularly in the inner-city, and accounts for billions of dollars in health care utilization, despite aggressive measures to identif remediable causes. Home environments are established sources of exposure that exacerbate symptoms and home-based interventions are proven effective. Prior to the inception of the School Inner-City Asthma Study (SICAS-1), no American study had comprehensively evaluated the relationship between urban exposures in school, classroom, and home environments and asthma morbidity. Nearly all elementary school children spend 7 to 12 hours a day in school, and most of that time is spent in one classroom. From SICAS-1, we learned that student classroom-specific mouse allergen, mold, and particulate pollutant exposure is associated with worsening symptoms. We also demonstrated our ability to reduce these exposures in a busy, school setting. Our proposal builds upon our established, successful school-based infrastructure to determine whether a school/classroom intervention will efficiently and effectively improve asthma morbidity by reducing these exposures. Our goal is to determine the efficacy of school/classroom based environmental intervention in reducing asthma morbidity in urban schoolchildren. Our central hypothesis is that reducing classroom/school exposure to mouse allergen, mold, and particulate pollutants will decrease asthma morbidity in students with asthma. We plan to test this hypothesis in an intervention study of 300 elementary students with asthma from multiple classrooms in 40 Boston inner-city elementary schools. Our clinical trial aims are to determine the effectiveness of a school/classroom based environmental intervention (school integrated pest management and classroom air purifying filter units within these schools) to reduce asthma morbidity. Our mechanistic aim is to test the hypothesis that effects of school/classroom- based environmental interventions on symptoms/other measures of asthma control occur through changes in gene methylation or expression in pathways (and secondarily, in genes) relevant to airway function and asthma. This will expand our understanding of asthma immunopathogenesis and create opportunities to identify potential novel targets for asthma therapy. Within pathways or networks of genes we will (a) determine how our interventions influence changes in nasal airway cell methylation or gene expression; (b) evaluate how our intervention-associated changes in methylation and gene expression influence asthma outcomes; and (c) estimate through mediation analysis how much of the intervention effects on asthma symptoms occurs through methylation/gene expression changes. This study is an unprecedented, high impact opportunity to test whether we can efficiently benefit a community of children in the school environment as opposed to individuals in single homes. It also adds a novel mechanistic application on health outcomes. It efficiently tackles a critical public health problem that affects a growing proportion of disadvantaged, urban U.S. children.

Public Health Relevance

Asthma is a disease that affects more than 12% of Americans under the age of 18 for over 14 million missed school days per year, and is the number one cause of school absences in America. The goals of this project are to provide an understanding of the role of a school/classroom based environmental intervention to reduce exposure risk factors specific to the classroom and its effects on asthma morbidity and learn more about molecular mechanisms induced by our clinical intervention. This is critical because the classroom environment is where nearly every child spends the majority of his/her day and could potentially be considered as an effective target for the prevention of inner-city asthma morbidity by reducing exposures to many symptomatic children through a school-based environmental intervention.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI110397-03
Application #
9199846
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Davidson, Wendy F
Project Start
2015-01-07
Project End
2019-12-31
Budget Start
2017-01-01
Budget End
2017-12-31
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Boston Children's Hospital
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Kantor, David B; Petty, Carter R; Phipatanakul, Wanda et al. (2018) Transcutaneous CO-oximetry differentiates asthma exacerbation and convalescence in children. J Allergy Clin Immunol 142:676-678.e5
Lai, Peggy S; Kolde, Raivo; Franzosa, Eric A et al. (2018) The classroom microbiome and asthma morbidity in children attending 3 inner-city schools. J Allergy Clin Immunol 141:2311-2313
Permaul, Perdita; Phipatanakul, Wanda (2018) School Environmental Intervention Programs. J Allergy Clin Immunol Pract 6:22-29
Lai, Peggy S; Massoud, Amir H; Xia, Mingcan et al. (2018) Gene-environment interaction between an IL4R variant and school endotoxin exposure contributes to asthma symptoms in inner-city children. J Allergy Clin Immunol 141:794-796.e3
Naja, Ahmad Salaheddine; Permaul, Perdita; Phipatanakul, Wanda (2018) Taming Asthma in School-Aged Children: A Comprehensive Review. J Allergy Clin Immunol Pract 6:726-735
Esty, Brittany; Phipatanakul, Wanda (2018) School exposure and asthma. Ann Allergy Asthma Immunol 120:482-487
Cardet, Juan Carlos; Louisias, Margee; King, Tonya S et al. (2018) Income is an independent risk factor for worse asthma outcomes. J Allergy Clin Immunol 141:754-760.e3
Louisias, Margee; Wright, Lakiea; Phipatanakul, Wanda (2018) Asthma in the melting pot. Ann Allergy Asthma Immunol :
Kantor, David B; Hirshberg, Eliotte L; McDonald, Molly C et al. (2018) Fluid Balance Is Associated with Clinical Outcomes and Extravascular Lung Water in Children with Acute Asthma Exacerbation. Am J Respir Crit Care Med 197:1128-1135
Gaffin, Jonathan M; Hauptman, Marissa; Petty, Carter R et al. (2018) Nitrogen dioxide exposure in school classrooms of inner-city children with asthma. J Allergy Clin Immunol 141:2249-2255.e2

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