Contrary to the belief that the practice of tobacco smoking by waterpipes (`hookah?) is less harmful than smoking combustion cigarettes, the health risks of waterpipe smoking (WPS) may be even greater than smoking cigarettes. The risks of WPS include adverse cardiovascular and pulmonary effects. Many of the compounds in WPS impact the cardiovascular and respiratory systems: Elevated heart rate and blood pressure has been linked to nicotine and the increased carbon monoxide concentrations measured in WPS. Also, WPS generates destructive reactive oxygen species or depletes SH-containing antioxidants. Irreversible oxidative stress-induced damage of the lung epithelium may occur and has been linked to the pathogenesis of coronary artery disease and obstructive pulmonary disease. Our overall objective is to determine how changes in WPS components and smoking patterns effect the chemical composition of both the gaseous and size-resolved particulate constituents and their role in the development and exacerbation of cardiopulmonary diseases. We will specifically examine the role of inflammation and oxidative stress as mechanisms of action in tobacco smoke-related disease pathogenesis. We will use a combination of in vitro tests and in-vivo inhalation exposures with a genetically modified mouse model to quantify adverse effects on the cardiopulmonary system to specific toxicants present in WPS. Our overarching hypothesis is that exposure to hookah smoking will be associated with inflammation and oxidative stress that will induce or exacerbate cardiopulmonary responses in our in vivo mice model. We further hypothesize that these associations will be due to semi-volatile WPS components with high inflammation and oxidative potential and that removal of these compounds will mitigate the adverse effects. We will test our hypotheses with the following three aims: 1. Use state-of-the-art high resolution analytical methods to generate, sample, and quantify potentially harmful constituents in WPS to a degree that was not possible in earlier studies. 2. Assess the redox & electrophilic properties of gas- and particle-phase components present in WPS extracts using in vitro systems that explore several potentially important mechanisms of action. 3. Assess and compare cardiopulmonary toxicities of hookah smoke in mice in acute and chronic exposures with an emphasis on defining the role of inflammation and oxidative stress in lung, brain and cardiovascular systems using a sensitive, atherosclerosis-prone animal model. This will be among the first studies to evaluate differential cardiopulmonary toxicities of chemically characterized hookah smoke by in vitro and in vivo assays. The study will employ innovative state of the art telemetry to measure changes in respiration, electrocardiographic patterns and cardiac function during and after sub-chronic and chronic exposures in mice that are genetically susceptible to atherosclerosis.

Public Health Relevance

Waterpipe (hookah or sisha) smoking in the United States has increased in the last ten years, especially among women, adolescents, and young adults. The majority of hokaah smokers may be unaware that waterpipe smoking is not a ?healthy? alternative to cigarettes and that waterpipe smoke related health risks may include the development of various respiratory and atherosclerotic vascular diseases. The proposed study will contribute to the knowledge and methods needed to evaluate the potential cardiopulmonary toxicities of chemically characterized hookah smoke by a combination of in vitro and in vivo assays.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES027232-03
Application #
9552162
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Tyson, Frederick L
Project Start
2016-09-01
Project End
2019-08-31
Budget Start
2018-09-01
Budget End
2019-08-31
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Type
Schools of Medicine
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92617