Steroid resistance found in African-American teens
Steroid resistance found in African-American teens
Researchers suspect genetic predisposition
Steroid resistance among African-American teen-agers is offering an important insight into the high mortality rate among black asthmatics.
A team of researchers at National Jewish Medical and Research Center in Denver found resistance to steroids among young African-Americans, regardless of whether they had asthma.
"In every case, African-Americans required more steroids than whites to suppress lymphocyte proliferation," says Joseph Spahn, MD, assistant professor of pediatrics, staff physician, and director of immunopharmacology at the center. "This is not a disease-specific process. That’s why we suggest a genetic predisposition to steroid resistance."
The Centers for Disease Control and Prevention in Atlanta reports a 75% increase in the number of self-reported cases of asthma between 1980 and 1998. The mortality rate of blacks climbed 130% between 1979 and 1995.
While many researchers attribute the increase across the board to a dramatic increase in environmental triggers, Spahn and his team think there may be deeper causes.
"Clearly this is a multifactorial issue, and I am not discounting environmental and socioeconomic factors. But environmental factors had no role in what we did in our lab," Spahn says.
"This is probably one more factor contributing to the high morbidity and mortality rates," Spahn adds.
The most recent findings in this area reported at the March meeting of the American Academy of Allergy, Asthma and Immunology showed that African-American teen-agers required a 50% higher concentration of dexamethasone or hydrocortisone to inhibit lymphocyte proliferation.
It supports findings from the team’s earlier research published last year that showed African-Americans are more likely to be steroid insensitive.
"Someone who doesn’t respond to steroid treatment is between a rock and a hard place," Spahn says. "They are actually steroid dependent and if you take them off, they get worse. The steroids actually just keep them at their baseline."
National Jewish Medical and Research Center is a facility for children with chronic severe asthma from all over the country. It provides a unique opportunity to perform a study like Spahn’s, says Peyton Eggleston, MD, a professor of pediatrics at Johns Hopkins Medical Institutions in Baltimore and director of the National Institute of Environmental Health Sciences Center for the Study of Environmental Influences on Children’s Health.
"While they could collect 80-plus patients who are steroid-resistant, we probably have five or 10 patients like that, and it is difficult to monitor them because they are outpatients," Eggleston says.
"Genetic predisposition makes sense," says Eggleston. "It suggests that there are separable and identifiable patterns and predictors in the African-American background, but we don’t really know what that means."
But Eggleston says, "African-Americans are a very heterogeneous population. We’re talking more about ethnicity and what somebody looks like when there’s really very little information about their true genetic background. Maybe in five or 10 years there will be genetic markers that will make it more meaningful."
He offers another explanation for the steroid resistance in African-American teens. The lack of lability in the lungs of steroid-resistant adolescents may be caused by scarring or fixed obstructions. By the time the patient is 14 (the age of the subjects in the National Jewish study) they’ve really been poorly controlled for many years and "they’ve already had plenty of time to acquire those fixed obstructions," Eggleston says.
Eggleston cited his finding as part of the National Cooperative Inner City Asthma Study that showed 10% of the children who were subjects had been on respirators at birth and 25% of them had been premature.
"Of course, prematurity and the use of a ventilator are major risk factors for poor lung growth and poor flow," says Eggleston, "So this group of steroid-resistant African-Americans could well have started in the same way."
Eggleston also pointed out that steroid resistance is a characteristic feature of older adults in their 50s, 60s, or even 70s.
"Finding this fixed obstruction and steroid resistance in kids suggests there is a group predisposed to what looks more like COPD [chronic obstructive pulmonary disease] than asthma," Eggleston concludes.
Spahn says treatment is difficult, in any case.
"There are no great therapies. They just don’t respond well," he says.
Intravenous gamma globulin therapy has produced some positive results and is "fairly safe," Spahn says, but its high cost ($2,000 to $5,000 per month) and its experimental nature have made it unpalatable to managed care.
Cyclosporine therapy is not particularly desirable, he says, because of the possible kidney damage, hypertension, and general hyperplasia that can accompany it.
And, Spahn concludes, the high dosages of oral steroids necessary for very severe asthma cases like the steroid resistant teen-agers in his study, can cause serious side effects, including osteoporosis, cataracts, myopathy, steroid-induced diabetes, elevated cholesterol, and obesity.
[Joseph Spahn can be reached at (303) 398-1376 and Peyton Eggleston can be reached at (410) 955-5883.]
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