Asthma is a chronic health problem affecting millions of people resulting in substantial patient morbidity. There are several triggers for asthma including re-exposure to allergens, cold, exercise and other unspecified challenges. We have discovered that acute ethanol ingestion will trigger asthma like pulmonary inflammation in mice sensitized to cockroach allergens. Within 30 minutes of ethanol gavage, there is an increase in epithelial cell mucin, increased eosinophil recruitment into the air spaces, and enhanced airways hyperreactivity. None of these changes were observed in non-allergen sensitized mice gavaged with ethanol. Within the 30 minute timeframe there was significant mast cell degranulation, however, mast cell stabilization did not reduce any of the asthma inflammatory parameters. The rapid timeframe, lack of mast cell participation, and potential esophageal irritation during the gavage procedure provide the basis for the proposed studies. This proposal will test the hypothesis that in cockroach allergen sensitized mice, ethanol gavage will activate neuronal systems to rapidly induced asthma like pulmonary inflammation. We will specifically focus on the vagus nerve. The vagus nerve signals through parasympathetic pathways resulting activation of muscarinic and nicotinic receptors. Experiments will be done with blockade of specific muscarinic receptors to determine whether this will reduce the ability of ethanol to trigger asthma. Multiple asthma parameters will be measured to determine the full range of inflammation triggered by ethanol in the allergen sensitized mice. A second specific aim will determine whether afferent vagus nerve fibers triggered by the combination of ethanol and gavage induce release of neurotransmitters such as substance P, tachykinins, or calcitonin gene related peptide. The studies will also be done the specific receptor agonists and antagonists. Innovation: Most studies show that ethanol depresses inflammation, while our preliminary data clearly indicate that ethanol will trigger asthma like pulmonary inflammation in appropriately sensitized mice. There are no studies examining the neuronal control of this event. Significance: Clinical studies show that 40% of asthmatics report that drinking alcohol exacerbates their symptoms. The studies will find the mechanisms of how ethanol triggers asthma.

Public Health Relevance

Four out of ten people with asthma say that drinking alcohol triggers their asthma symptoms. We have developed a mouse model of asthma where acute alcohol consumption will trigger asthma within 30 minutes. In this application we examine if the nervous system is responsible for the ability of alcohol to trigger asthma.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AA022122-01A1
Application #
8635717
Study Section
Health Services Research Review Subcommittee (AA)
Program Officer
Jung, Kathy
Project Start
2014-03-05
Project End
2016-02-29
Budget Start
2014-03-05
Budget End
2015-02-28
Support Year
1
Fiscal Year
2014
Total Cost
$235,319
Indirect Cost
$91,569
Name
Boston University
Department
Pathology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118