What we know about how air swirls and weaves its way through the lung's intricate passages is very limited. The approach to delivering drugs to the lung for asthma and cystic fibrosis, for example, says Hammersley, has been largely trial and error.
"We can image drugs reaching the main airways beyond the voicebox, but most particles are knocked out by turbulence and mixing in the central airways." Even in normal subjects, he adds, drugs often fail to reach the outlying, small airways where the airflow obstruction in asthma is seated. To get around these limitations, lab researchers try various particle sizes, and they alter particle properties and evaluate different propellants. "Nevertheless," he says, "all you can really do is toss it in and see what happens."
The problem is the complexity of the lung's structure and how this affects airflow. Most pulmonary medicine textbooks describe airflow as turbulent down through the windpipe into the two main bronchial tubes, and as a smooth, symmetrical flow through the smaller airways beyond. Research on scale models (much of it carried out by Hammersley's mentor and MCO colleague Dan Olson), shows that this simplistic view is deeply flawed.
Flows in the small airways are strongly affected by the 16 or more generations of branching that extend out to the air sacs. This structure is highly asymmetric; branches go off from the parent airway at different angles and extend for different lengths as the airways narrow from several centimeters to less than a millimeter at the end. As a result, airflows are irregular and skewed with difficult to predict effects on the delivery of inhaled aerosols.
go back to the main page