The Fate of Inhaled Particles

Simulation of three-dimensional deposition locations of aerosol particles (shown in red) with a diameter of three micrometers—typical of pharmaceutical drugs inhaled into the lung— in an anatomically-based human large-medium airway model under steady slow inhalation conditions. The airway model starts from the mouth and extends through ten generations of bifurcations, and its predictions were consistent with experimental results. Courtesy of Baoshun Ma.A new computational model simulates how particles in the air get deposited in the lungs during breathing. Depending on their nature, microscopic particles suspended in air—called aerosols—can cause or treat disease when inhaled. A key factor in both cases is how the particles accumulate throughout the respiratory system. A new study uses fluid dynamics and an anatomically accurate human airway model to simulate this process, potentially paving the way for improved disease understanding and patient-specific drug delivery.

 

“It is one of the first computational studies that uses anatomically correct models to predict aerosol deposition,” says principal author Kenneth Lutchen, PhD, of Boston University, principal author of the study published in the February 2009 issue of Annals of Biomedical Engineering.

 

Starting with the windpipe, airways in the human respiratory system branch out, producing about 23 levels of branching or “generations.” The resulting structure includes nearly 10 million microscopic airways, making it hard to study aerosol deposition. According to Lutchen, experimental methods relying on in vivo rat studies or lung-shaped casts have yielded useful, but preliminary, data. Prior computational studies have dealt with more complex respiratory structures, but typically used idealized lung models instead of the actual anatomy. Further, many of them ignore the upper airways where most of the deposition occurs, Lutchen says.

 

In contrast, Lutchen and his collaborator Baoshun Ma, PhD, modeled their lung from MRI and CT images of healthy men and included the upper airway. The limited resolution of the images restricted the model to the first ten airway generations. For simplicity, the researchers assumed a steady flow of air through rigid airways instead of a natural breath pattern. They then used a computational fluid dynamics framework with a standard turbulence model to simulate aerosol deposition for different particle sizes and airflow rates. Results indicated that large particles (with a diameter of 30 micrometers—about the width of a human hair) end up mostly in the mouth and upper throat, whereas small (1 micrometer) particles typical of pharmaceutical drugs inhaled into the lung spread out more evenly. Typically, the left lung absorbed more particles—as much as 5 times more for some parameter settings—compared to the right lung. “These predictions are consistent with experimental data,” says Lutchen.

 

Inhaled aerosols have emerged as an important method for delivering drugs for lung-related conditions ranging from asthma to cystic fibrosis. However, proper dosing requires accurate, patient-specific prediction of aerosol deposition patterns under a variety of conditions. Lutchen hopes that the new approach will eventually facilitate this task. “This model will tell you what particle sizes and inhaled volumes you need to get the desired dose for a specific patient,” he says.

 

“This article is of significant interest in the field of respiratory dosimetry,” says Worth Longest, PhD, of the Virginia Commonwealth University in Richmond. “It extends the state-of-the-art in the use of computational fluid dynamics to predict local and regional respiratory particle deposition.” To be of use in clinical applications, however, the system should be extended to include transient effects over a breathing cycle, effects of airway wall motion, and a more robust turbulence model, he adds.
 



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