October 17, 2000
MEDIA CONTACT: Kate O'Rourke
PHONE: (410) 955-8665
Johns Hopkins researchers have successfully targeted aerosol particles to smaller, harder to reach airways in the lungs of people with cystic fibrosis (CF). The work, reported in the October issue of Chest, could lead to improved drug treatments for CF patients (30,000 in the United States) and in the future, to a means of optimizing the delivery of gene therapy.
"Aerosolized drugs often don't reach peripheral lung areas, where the disease begins, because the aerosol particles that contain the drug are too large to pass beyond airways that are partially obstructed by thick, sticky mucus, a condition resulting from the disease," says Beth Laube, Ph.D., an associate professor of pediatrics at Hopkins and lead author of the study. "This is the first study we know of to show that aerosols can be targeted to the smaller, harder to reach airways or the larger, central airways by generating fine particles and having patients inhale slowly or quickly. This is really good news."
Currently, CF inhalation therapies are only partially successful because certain areas of the lungs may be beyond reach. Experimenting with varying aerosol particle sizes and flow rates, the researchers discovered that when they used aerosols containing fine particles, they could direct the spray to different areas of the lungs. "We found that the fine particles allowed us greater manipulation in terms of targeting within the lung compartment, compared to the more coarse particles," says Laube. "When CF patients inhaled the fine particles at high flow rates, we found that deposition was predominantly in the larger, central airways. When they inhaled more slowly, the fine particles landed primarily in the smaller, peripheral airways. With the coarse particles, the aerosol deposited in the same pattern, regardless of how fast or slowly the patients inhaled."
During four visits, nine adult patients inhaled aerosols containing fine salt-water droplets (1.01 micrometers) or coarse droplets (3.68 micrometers), inhaling either slowly or quickly. The droplets contained a radioactive marker, and immediately after inhalation, the researchers used a gamma camera to record the deposition pattern of the radioaerosol in the lungs.
The scientists also found that fine particles were far more likely to make it past the 90 degree turn in the back of the throat and go on to deposit in the lungs compared to coarse particles. Minimizing the loss of particles in the back of the throat is important because most current drug therapies for patients with CF that involve aerosolized medications (e.g., antibiotics) and newer therapies that are under development (e.g., gene-carrying vectors) are very expensive to produce. It is important to deliver as much of the drug to the lungs as possible to reduce the cost.
Laube says the results from her study could be used to improve patient care because "once the areas of the lungs that need to receive specific drugs and gene therapy products are identified, this new information could be used to deliver them to the right targets efficiently."
Cystic fibrosis is an inherited disorder in which cell channels that regulate salt flow fail to open, wreaking havoc on a cell's delicate balance between salt and water. It commonly affects cells in the lungs and pancreas, and causes a buildup of abnormally thick, sticky mucus. This mucus causes malnutrition, stunted growth, frequent lung infection and breathing difficulties. CF eventually causes permanent lung damage resulting in death at an early age. Patients with CF often do not live past 30.
Other authors of the paper are Rajkumari Jashnani, Ph.D., Richard N. Dalby, Ph.D., at the University of Maryland; and Pamela L. Zeitlin, M.D., Ph.D., at Johns Hopkins. The study was funded by grants from the Cystic Fibrosis Foundation.