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Pulmonary biology and lung diseases

Support innovative, timely and high impact research addressing basic, translational or clinical aspects of tobacco-related pulmonary biology and lung diseases. TRDRP will support studies on lung diseases that the Report of the Surgeon General has identified as being caused by tobacco-related products. TRDRP will also support projects in which tobacco-related products or their constituents are integral to the proposed study. Research that can inform FDA regulations on new and emerging tobacco products is of particular interest.

Tobacco smoke is a key factor in the development and progression of chronic obstructive pulmonary disease (COPD), one of the leading causes of death in the United States. The prevalence of COPD has a large social and economic impact in California, creating an enormous amount of human suffering especially in disproportionately affected populations such as people of low socioeconomic status, American Indian/Alaska Natives, multiracial non-Hispanics, and women.

Under this priority, TRDRP supports research crucial to understanding the effects of tobacco products on the lung, the etiology and mechanisms of pulmonary diseases that are caused by tobacco use or exposure, and studies that translate this knowledge into improved diagnostics and treatments.

An important area of research relates to new and emerging tobacco products. A recent consensus study report by the National Academies of Sciences, Engineering and Medicine concluded that switching from combustible tobacco cigarettes to e-cigarettes reduces exposure to numerous toxicants and carcinogens present in combustible tobacco cigarettes. However, e-cigarettes contain highly variable amounts of potentially toxic substances and it is not known whether or not e-cigarettes cause respiratory diseases in humans. Recently, there have been reports of an increase in severe pulmonary disease associated with using e-cigarettes, triggering a health advisory from the Center for Disease Control and Prevention (CDC) and the California Department of Public Health (CDPH). The continuously changing landscape of electronic nicotine delivery systems poses a particular challenge to understanding their health effects, and TRDRP is especially interested in studies that investigate the pulmonary effects of new and emerging tobacco products, or their individual constituents such as e-liquid vehicle or flavorants. In never smokers, what is the harm of e-cigarette use? In smokers who completely switch to e-cigarette use, is there a relative benefit or is there additional harm of e-cigarette use?  In addition, since some new tobacco products, such as e-cigarettes, deliver nicotine in the absence of well-known toxins present in tobacco smoke, it is of interest to better understand the potential effects of nicotine itself on lung health.

In light of the recent legalization of cannabis in California, it is important to understand its impact on tobacco-related disease. TRDRP invites proposals to study the effects of smoking or vaping cannabis on the initiation and progression of tobacco-related lung diseases and the pulmonary effects caused by co-use of tobacco and cannabis.

TRDRP has a cross-cutting emphasis on research to reduce health disparities and invites proposals that seek to improve our understanding and treatment of tobacco-related lung diseases in groups disproportionately affected by tobacco use and exposure (see Appendix B, Research Award for a list of priority groups).

Sub-focus areas and examples of relevant research topics

Sub-focus areas and examples of relevant research topics:

Mechanistic studies to better define the effects of tobacco products and their constituents on lung biology

  • Epigenetic changes in various lung cell types in animals or humans exposed to inhaled e-cigarette aerosol, role of nicotine or flavorants
  • Cellular interactions or molecular pathways that drive the inflammatory response in the lungs of hookah users

Mechanistic studies to better define the etiology and progression of lung diseases caused by tobacco products or their constituents

  • The molecular mechanisms and genetics of differences in COPD susceptibility and progression, including sex differences
  • The role of combusted tobacco smoke or new and emerging tobacco products in the development and exacerbation of asthma or idiopathic pulmonary fibrosis
  • Big data / data-driven approaches to understand factors contributing to COPD exacerbations in different priority populations

Development of diagnostic and therapeutic approaches for the prevention and treatment of tobacco-related lung diseases

  • Development of wearable devices to diagnose tobacco-related lung disease and track its progression
  • Drug repurposing for the treatment of COPD
  • Development of targeted, precision medicine approaches to treating COPD in American Indian / Alaska Natives

Discovery and understanding of lung disease related to co-use of different tobacco products and co-use of tobacco products with other substances of abuse

  • Inflammatory responses and mechanisms that lead to COPD in response to co-use of tobacco and cannabis
  • Characterization of molecular and cellular effects and functional differences in the lungs of combustible cigarette smokers, e-cigarette users and dual users.

Effects of pre-natal and neonatal exposure to tobacco products or their constituents on lung development and disease

  • Development of an animal model of e-cigarette inhalation during pregnancy and analysis of the effects of nicotine and different flavorants on lung development in offspring

NOTE: Lung cancer-related research topics are being addressed under the “Cancer Prevention, Treatment and Biology” research priority.