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Molecular and Cellular Phenotyping of Second Hand Smoke-Related Asthma

Institution: Stanford University
Investigator(s): Rebecca Bauer, Ph.D.
Award Cycle: 2015 (Cycle 24) Grant #: 24FT-0011 Award: $47,769
Subject Area: Environmental Exposure/Toxicology
Award Type: Postdoctoral Fellowship Awards

Initial Award Abstract

Exposure to second hand smoke (SHS) is associated with elevated life risk of asthma development and more severe asthma symptoms, suggesting that SHS exposure promotes a more severe form of asthma. Recent scientific findings suggest that there are numerous subtypes of asthma, and that specific therapies for each type of asthma may more successfully control asthma symptoms. Understanding the type of asthma associated with SHS exposure is important to develop specific treatments for individuals with SHS-related asthma.

Tobacco smoke exposure alters the function of immune cells and is associated with increased levels of neutrophils in the blood and airway. Neutrophils are very reactive immune cells that produce inflammatory mediators that can damage the lung and worsen asthma symptoms. Previous studies have shown that increased numbers of neutrophils in asthmatic airways is partially mediated by the activity of a specific type of immune cell termed Type 17 T helper (Th17) cells, which produce immune signaling molecules that recruit neutrophils to the airway. This research proposal will test the hypothesis that SHS exposure increases the severity of asthma symptoms by promoting the development of Th17 cells and neutrophil-driven inflammation.

To test this hypothesis, I will use blood samples from identical twin pairs in which at least one twin has asthma and/or SHS exposure to perform the following experiments: 1) I will characterize the types of T helper cells in the blood, including Th17 cells, from twin pairs with or without SHS exposure or asthma and correlate the types of T helper cells with the number of neutrophils in the blood; 2) I will assess how SHS modifies expression of important immune genes by T cells leading to altered development of T helper cells and more severe asthma symptoms.

These studies will determine how SHS exposure affects the immune cells that promote more severe asthma symptoms and identify diagnostic markers of SHS-related asthma that may help determine the most appropriate asthma treatment in the clinic. The use of samples from twins enables us to more easily distinguish the effects of SHS exposure on asthma while controlling for genetics and other exposures during childhood. Additionally, increased understanding of how SHS impacts asthma will lead to the development of more informed regulatory and promotional material to control tobacco smoke exposure.