Grant Number:
Principal Investigator:
Brooks, Daniel R; Lenburg, Marc Elliott; Spira, Avrum E (Contact)
Institution:
Boston University
Most Recent Award Year:
2011
Lifestage of Participants:
Exposure:
Youth (1-18 years)
Assessment:
Youth (1-18 years)
Exposures:
Air Pollutants:
Tobacco smoke
Health Outcomes:
Biological Sample:
Buccal epithelium; Nasal epithelium
Environmental Sample:
Air sample
Other Participant Data:
Questionnaire as one method of assessing environmental tobacco smoke exposure
Genes or Other DNA Products Studied:
Gene- and miRNA-based expression signatures in the bronchial airway that reflect environmental tobacco smoke exposure
Abstract:
Second-hand tobacco-smoke (SHS) has a profoundly negative impact on the health of exposed individuals. In adults, where the long-term impacts of SHS exposure are more apparent, SHS is responsible for 50,000 deaths annually. In children, the effects of SHS are likely even more profound. Children exposed to SHS have median nicotine metabolite levels twice those of adults, and SHS exposure is a substantial source of childhood morbidity; resulting in lower respiratory illnesses; cough, phlegm, wheeze, and breathlessness; middle ear disease; and a lower level of lung function. A critical need in the area of research into the health consequences of SHS is the development of effective tools for assessing the early biological response to SHS. These tools could facilitate rapid insights into the causes and consequences of differences in the response to SHS exposure; and, unlike direct measures of SHS exposure levels, could also be used to assess the likely long-term health effects of interventions to minimize SHS exposure in both children and adults. Using genome-wide microarray technologies for assessing mRNA and miRNA expression together with the concept that tobacco smoke creates an airway-wide field of epithelial cell injury, we have developed innovative genomic biomarkers to assess the biologic response to SHS by profiling cells that can be collected from the mouth or nose using minimally invasive procedures. These biomarkers combine the expression levels of multiple genes or miRNAs into composite measures of tobacco-smoke exposure thereby amplifying the tobacco-smoke signal while dampening the otherwise noisy expression levels of individual genes. Preliminary studies show that expression biomarkers measured in buccal or nasal epithelium distinguish young adults with SHS exposure from unexposed individuals. The studies proposed here will validate these biomarkers for assessing the biological response to SHS in 80 SHS-exposed and 80 unexposed children participating in the CCCEH, DISCOVER and ASTHMA-DIET cohorts. Biomarkers of tobacco-smoke exposure derived from microarray-based measurements of nasal or buccal epithelial mRNA or miRNA expression will be compared to measures of SHS exposure derived from questionnaire, air sampling and cotinine. The repeatability of the genomic biomarker measurements will be assessed by repeat sampling of 40 children after 6 months. The proposed research applies innovative tools for measuring the biological response to SHS exposure to multiple established cohorts with carefully characterized exposures, including children at risk for SHS-related disease. The studies bring together a team with expertise in pulmonary medicine, epidemiology, genomics, and biostatistics, a long-term interest in understanding responses to tobacco smoke, and an established record of effective collaboration, to take a critical step in establishing the potential and feasibility of applying these SHS-exposure assessment tools to large-scale epidemiology and gene-environment studies. By measuring the response to exposure, rather than the exposure itself, these studies have the potential to broadly change the paradigm for research into the effects of environmental exposures.
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Related NIEHS-Funded Study Populations
New York City Mothers and Newborns Study
Principal Investigator:
Perera, Frederica
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Institution:
Columbia University
Location:
New York, New York
Number of Participants::
~725 Mother-infant pairs
Brief Description::
This is a birth cohort study of minority mothers and children in New York City that examines the effects of early life exposures to air pollutants, environmental tobacco smoke, pesticides, and endocrine disrupting chemicals on children's neurodevelopment, respiratory health, growth, and development. The study has recruited approximately 725 pregnant mothers since 1998.
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Principal Investigator:
Diette, Gregory
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Institution:
Johns Hopkins University
Location:
Baltimore, Maryland
Number of Participants::
~200
Brief Description::
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