Lung models: strengths and limitations.

The most widely used particle dosimetry models are those proposed by the National Council on Radiation Protection, International Commission for Radiological Protection, and the Netherlands National Institute of Public Health and the Environment (the RIVM model). Those models have inherent problems that may be regarded as serious drawbacks: for example, they are not physiologically realistic. They ignore the presence and commensurate effects of naturally occurring structural elements of lungs (eg, cartilaginous rings, carinal ridges), which have been demonstrated to affect the motion of inhaled air. Most importantly, the surface structures have been shown to influence the trajectories of inhaled particles transported by air streams. Thus, the model presented herein by Martonen et al may be perhaps the most appropriate for human lung dosimetry. In its present form, the model's major "strengths" are that it could be used for diverse purposes in medical research and practice, including: to target the delivery of drugs for diseases of the respiratory tract (eg, cystic fibrosis, asthma, bronchogenic carcinoma); to selectively deposit drugs for systemic distribution (eg, insulin); to design clinical studies; to interpret scintigraphy data from human subject exposures; to determine laboratory conditions for animal testing (ie, extrapolation modeling); and to aid in aerosolized drug delivery to children (pediatric medicine). Based on our research, we have found very good agreement between the predictions of our model and the experimental data of Heyder et al, and therefore advocate its use in the clinical arena. In closing, we would note that for the simulations reported herein the data entered into our computer program were the actual conditions of the Heyder et al experiments. However, the deposition model is more versatile and can simulate many aerosol therapy scenarios. For example, the core model has many computer subroutines that can be enlisted to simulate the effects of aerosol polydispersity, aerosol hygroscopicity, patient ventilation, patient lung morphology, patient age, and patient airway disease.

Importance of cloud motion on cigarette smoke deposition in lung airways.

Deposition patterns of mainstream cigarette smoke were studied in casts of human extrathoracic and lung airways. The laboratory tests were designed to simulate smoking (i.e., the behavior of undiluted cigarette smoke in smokers' lungs), not secondary exposures to non-smokers. The experimental data revealed concentrated deposits at well-defined sites, particularly at bifurcations (most notably at inclusive carinal ridges) and certain segments of tubular airways. The measurements suggest the occurrence of cloud motion wherein particles are not deposited by their individual characteristics but behave as an entity. The observed behavior is consistent with the theory of Martonen (1992), where it was predicted that cigarette smoke could behave aerodynamically as a large cloud (e.g., 20 microns diameter) rather than as submicrometer constituent particles. The effects of cloud motion on deposition are pronounced. For example, an aerosol with a mass median aerodynamic diameter (MMAD) of 0.443 micron and geometric standard deviation (GSD) of 1.44 (i.e., published cigarette smoke values) will have the following deposition fractions: lung (TB + P) = 0.14, tracheobronchial (TB) = 0.03, and pulmonary (P) = 0.11. When cloud motion is simulated, total deposition increases to 0.99 and is concentrated in the TB compartment, especially the upper bronchi; pulmonary deposition is negligible. Cloud motion produces heterogeneous deposition resulting in increased exposures of underlying airway cells to toxic and carcinogenic substances. The deposition sites correlated with incidence of cancers in vivo. At present, cloud motion concentration effects per se are not addressed in federal regulatory standards. The experimental and theoretical data suggest that concentrations of particulate matter may be an important factor to be integrated into U.S. Environmental Protection Agency (EPA) risk assessment protocols.