NEW TREATMENT FOUND FOR SEVERE BREATHING DISORDER
Last-resort approach, successful in the laboratory, saves young patient
MADISON, Wis. -- "Waiting to Exhale" may have been a hit movie, but inability to exhale normally is the hallmark of a dangerous and under-recognized breathing disorder known as apneusis (ap-noo'-sis). Now, research by an international team of scientists on brain chemicals that control breathing may have paid off for the stroke patients and brain-damaged children who most commonly suffer from apneusis.
Scientists from the University of Wisconsin Medical School and the University of Gottingen Physiological Institute and Hospital in Germany collaborated on the project, reported in the January issue of the Journal of Pediatrics.
The success story involves a German toddler who developed the respiratory problem following surgical removal of a tumor located near the brain region that controls the length of each inhalation. Apneusis disturbed the child's breathing rhythm as many as seven times daily. Each episode severely impaired oxygen and carbon dioxide exchange in the child's brain and other tissues, requiring resuscitation every time the apneusis occurred.
"Under normal circumstances, a cellular switch in the brain sends a signal that causes us to stop inhaling and begin exhaling," said UW Medical School Associate Professor of Physiology Peter Lalley, Ph.D., a member of the research group. "But with apneusis, the switch has failed."
Lalley has worked for years on brain chemicals that influence respiration, particularly serotonin. Trained as a pharmacologist, he is an expert on drugs that affect the docking sites, or receptors, where serotonin binds to influence the activities of respiratory nerve cells. In the past dozen years, he has spent his summers collaborating with Profesor Diethelm Richter, M.D., one of the world's leading respiratory neurophysiologists, at the University of Gotingen.
Experiments conducted in Madison and Gottingen by Lalley, Richter and colleague Anne Bischoff revealed that drugs that stimulate certain types of serotonin receptors in the brain shorten the length of inspiration.
"We also found that the drugs reversed apneusis and restored normal breathing in animals whose inspiration off-on switch was impaired by oxygen deprivation or heavy anesthesia," said Lalley. "This success prompted us to conduct more animal tests, which showed that the widely available drug Buspirone, which also binds to the same serotonin receptor, can halt apneusis."
Richter was first approached by the young patient's neurologist, Bernd Wilken, M.D., two years ago. Attempts by Wilken and his associates to treat the apneusis with different kinds of drugs were unsuccessful. Since Buspirone was effective in stopping apneusis in animal experiments, permission to use it to treat the girl was granted by the ethics committee of the University of Gottingen Medical School.
"Dr. Wilken and his clinical coworkers established an appropriate dose of Buspirone that greatly reduced the severity of the patient's apneustic attacks so that resuscitation was no longer needed," reported Lalley. "No side effects were noted as the child recovered. Buspirone was then reduced gradually and discontinued completely after 10 months."
At present, the girl has apneustic attacks at most about once a month, and only at night, when they usually subside spontaneously.
"We believe this case may have far-reaching implications for the treatment of this respiratory disorder," said Lalley. "Drugs that selectively activate the type of receptor on which Buspirone acts appear highly effective in treating apneustic breathing disturbances."
Lalley and his associates also emphasized that apneusis may occur more often than physicians previously recognized. "Apneusis, which is characterized by sustained inspiration interrupted by a short, inefficient expiratory effort, may be confused with apnea, an absence of inspiratory effort."
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