July 5, 2000 CHAPEL HILL -- Unusual infections and lumps of fat called emboli that clog arteries in the lungs appear to be under-appreciated causes of acute chest syndrome in sickle cell disease patients. The syndrome, which is a group of debilitating symptoms, is the leading cause of death among sickle cell patients, according to a major new study.
Earlier diagnosis and more aggressive treatment of those symptoms might save many victims of the illness, which is the most common inherited disorder among black people in the United States, researchers say.
Improved treatment may include earlier use of oxygen, more effective antibiotics, incentive spirometry and chest physical therapy in patients who develop the chest syndrome, they say. When appropriate, earlier use of blood transfusion and mechanical ventilation also should be considered.
A report on the 30-medical center study appears in Thursday’s (June 22) issue of the New England Journal of Medicine. Authors include Drs. Elliot P. Vichinsky and Lynne D. Neumayr and Anne N. Earles of Children’s Hospital Oakland in Oakland, Calif., Dr. Eugene P. Orringer, professor of medicine at the University of North Carolina at Chapel Hill School of Medicine, and Dr. Charles Daeschner, professor of pediatrics at East Carolina University.
"This is a very important study because acute chest syndrome is a major cause of both morbidity and mortality in sickle cell patients," said Orringer, a hematologist specializing in sickle cell disease. "The work provides an improved understanding of this serious illness. It is clear that we must identify acute chest syndrome earlier and treat it more aggressively."
Included in the study were 538 sickle cell patients from across the country who, together, experienced 671 episodes of acute chest syndrome. About 20 percent of enrolled patients came from medical centers at UNC-CH and East Carolina. Doctors grouped patients with the syndrome in a uniform way and analyzed their experiences to determine causes of the illness and outcomes during and following treatment.
"A surprise of the study was that evidence of infection was found in only 249 of the 671 episodes," Orringer said. "In cases where some type of infection was observed, the offending agent turned out to be chlamydia, mycoplasma or respiratory syncytial virus rather than more typical bacteria such as staphylococcus and streptococcus pneumoniae. Another surprise was the high frequency of fat embolism, a finding that was particularly common in patients over age 20."
Although still incompletely understood, acute chest syndrome in sickle cell disease appears to result from inadequate air exchange in the lungs, he said. Blockage of lung blood vessels or airways produces inadequate oxygenation. In SCD patients, poor oxygenation causes red blood cells to become bent or sickled. Such misshapen cells, which do not occur in people without the disease, then lead to further blood vessel blockage.
"This results in a vicious cycle," Orringer said. "Unless this vicious cycle is interrupted, it can lead to respiratory failure and even death."
One of the most effective treatments for acute chest syndrome has been exchange transfusions.
"In this procedure, the patient is connected to a special device which removes a high percentage of the sickled red blood cells and replaces them with normal red blood cells obtained from healthy blood bank donors," he said. "In some instances, physicians treating sickle cell patients with acute chest syndrome should turn more quickly to exchange transfusion. Patients also must be monitored very carefully since 13 percent of subjects in the national study required support from mechanical ventilators."
Despite being cared for by physicians experienced in managing the disease, 18 of the enrolled patients died. The two major causes of death were blockage of blood vessels in the lung (emboli) and severe, infectious pneumonias.
In 1995, Orringer, executive associate dean at the UNC-CH School of Medicine, and colleagues reported results of another major study of sickle cell disease. In that 21-center investigation, researchers found that the drug hypoxyurea could cut in half the number of severe pain episodes -- sometimes called crises -- that occurred in SCD patients. The same study also demonstrated that hypoxyurea could reduce by more than 50 percent the frequency of acute chest syndrome.
"Between one in 10 and one in 12 African-Americans carry a single sickle cell gene," Orringer said. "These individuals are said to have sickle cell trait. When a person is born with two sickle cell genes -- one from each parent -- he or she is said to have the disease."
Sickle cell disease is found in about one in every 400 African-American births, and current estimates suggest that about 75,000 U.S. blacks suffer from it. The National Institutes of Health supported the research.
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