The fate of an inhaled cigarette puff in the human respiratory tract

Inhal Toxicol. 2024 Jul;36(6):378-390. doi: 10.1080/08958378.2024.2367419. Epub 2024 Jun 23.

Abstract

Objective: Cigarette smoking can lead to a host of adverse health effects such as lung and heart disease. Increased lung cancer risk is associated with inhalation of carcinogens present in a puff of smoke. These carcinogenic compounds deposit in the lung at different sites and trigger a cascade of events leading to adverse outcomes. Understanding the site-specific deposition of various smoke constituents will inform the study of respiratory diseases from cigarette smoking. We previously developed a deposition model for inhalation of aerosol from electronic nicotine delivery systems. In this study, the model was modified to simulate inhalation of cigarette smoke consisting of soluble and insoluble tar, nicotine, and cigarette-specific constituents that are known or possible human carcinogens.

Materials and methods: The deposition model was further modified to account for nicotine protonation and other cigarette-specific physics-based mechanisms that affect smoke deposition. Model predictions showed a total respiratory tract uptake in the lung for formaldehyde (99%), nicotine (80%), and benzo[a]pyrene (60%).

Results: The site of deposition and uptake depended primarily on the constituent's saturation vapor pressure. High vapor pressure constituents such as formaldehyde were preferentially absorbed in the oral cavity and proximal lung regions, while low vapor pressure constituents such as benzo[a]pyrene were deposited in the deep lung regions. Model predictions of exhaled droplet size, droplet retention, nicotine retention, and uptake of aldehydes compared favorably with experimental data.

Conclusion: The deposition model can be integrated into exposure assessments and other studies that evaluate potential adverse health effects from cigarette smoking.

Keywords: Lung deposition modeling; cigarette puff inhalation; cigarette smoke constituents; nicotine lung deposition; nicotine retention.

MeSH terms

  • Administration, Inhalation
  • Aerosols
  • Benzo(a)pyrene / analysis
  • Benzo(a)pyrene / pharmacokinetics
  • Cigarette Smoking
  • Electronic Nicotine Delivery Systems
  • Formaldehyde / analysis
  • Formaldehyde / toxicity
  • Humans
  • Inhalation Exposure / adverse effects
  • Lung / drug effects
  • Lung / metabolism
  • Models, Biological
  • Nicotine* / administration & dosage
  • Nicotine* / pharmacokinetics
  • Respiratory System / drug effects
  • Respiratory System / metabolism
  • Smoke / adverse effects
  • Smoke / analysis
  • Tobacco Products / analysis

Substances

  • Nicotine
  • Smoke
  • Formaldehyde
  • Benzo(a)pyrene
  • Aerosols