Pulmonary deposition: determinants and measurement techniques

Evaluating the response of animals to a toxic or therapeutic agent requires the knowledge of the dose of the agent in the respiratory tract. Dose is the amount retained in the lungs. It is the difference between the amount deposited and the amount cleared. Many factors influence the amount of and the site of deposition in the respiratory tract. For particles, the characteristics of the aerosol, most importantly size, the physiology of the animal, most importantly breathing pattern, and the geometry of the respiratory tract all play a role in determining local dose. These factors and their relative importance in determining regional deposition are discussed. Finally, ways in which dose can be measured in the respiratory tract are explored. These range from simple estimates of total dose using whole lung digests to the precise localization of dose in well-defined lung compartments using morphometry or in cellular or subcellular compartments using electron energy loss spectroscopy. The techniques utilized by an investigator depend on the amount of resolution desired. Their use and implementation in inhalation studies are the key to fully understanding the response of an animal to an inhaled toxic or therapeutic agent.