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.
Martonen
T B
TB
Experimental Toxicology Division, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. martonen.ted@epa.gov
Musante
C J
CJ
Segal
R A
RA
Schroeter
J D
JD
Hwang
D
D
Dolovich
M A
MA
Burton
R
R
Spencer
R M
RM
Fleming
J S
JS
D000336:Aerosols / Q000493:pharmacokinetics*; D003198:Computer Simulation; D006801:Humans; D021621:Imaging, Three-Dimensional; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism*; D008961:Models, Structural; D015656:Respiratory Mechanics; D015899:Tomography, Emission-Computed, Single-Photon
D000336:Aerosols