Hopkins suspended the study after the death and notified three federal agencies that oversee medical experiments involving human subjects.
In the experiment, volunteers were given a drug that is known to cause airways of the lung to constrict, according to a brief Hopkins statement. They were then asked to take deep breaths so physicians could observe whether this relaxed the airways and caused them to reopen.
"The exact cause of death has not been determined," Hopkins spokeswoman Joann Rodgers said.
Medical school officials refused to discuss many key facts, including the volunteer's identity. They would not describe the circumstances of the death or even when it occurred, though a faculty member said the accident happened about 10 days ago.
Officials also declined to say whether the person was a healthy volunteer or someone with asthma. People in both groups have been involved in phases of this research at the Johns Hopkins Asthma and Allergy Center. The center is located on the Bayview campus in East Baltimore. A pool of volunteers regularly participates in related research studies there.
"The family asked that we not make any further comment or say anything else," said Rodgers. "I can only tell you that the family was very, very clear about what we could release, and we felt an obligation to accommodate them at this time."
The death was discussed at a meeting last week of the Johns Hopkins Bayview Medical Center's Institutional Review Board, according to the faculty member. The panel oversees the safety of medical experiments and takes steps to ensure that patients have been adequately informed of the risks of participating in such research.
Concern about the safety of medical experiments mounted two years ago following the death of 18-year-old Jesse Gelsinger in a gene therapy trial at the University of Pennsylvania. Federal officials cited Penn researchers for numerous violations of safety standards. That incident and other lapses have prompted calls for more government monitoring of clinical trials, better self- policing by academic medical centers and creation of an agency to oversee medical experiments.
The Hopkins study, called Lung Inflation and Airways Hyperresponsiveness, was directed by Dr. Solbert Permutt, a professor of pulmonary medicine and asthma expert. The $384,000 study was funded by the National Institutes of Health. That agency was informed of the volunteer's death, along with the U.S. Food and Drug Administration and the federal Office of Human Research Protections, according to Hopkins.
Reached yesterday in his office, Permutt said he was not permitted to discuss the matter. "I can't say anything right now, except to refer you to public relations," he said.
His study was not a clinical trial, in which a potential therapy or drug is tested for safety and effectiveness. Instead, it was a "baseline physiological study," one designed to observe lung function.
In its statement, Hopkins said that volunteers inhaled a drug, hexamethonium, which has been used safely to look at lung function in several clinical studies at leading academic medical centers. The drug was long used to lower blood pressure and decrease bleeding during surgery, according to the statement.
Though the medical school provided scant details of the experi- ment, a description of the research is available in past press releases and on the hospital's Web site.
Doctors were investigating a theory that asthmatics lack a protective mechanism that keeps their airways from closing down - causing coughing and, in extreme cases, choking - when they inhale certain irritants.
Healthy people have this mechanism. When their airways begin to close, they take a few deep breaths and the airways open.
In what appears to be an earlier phase of the experiment, nine healthy and eight asthmatic volunteers were asked to take several deep breaths and then to inhale hexamethonium. In the healthy volunteers, the breaths appeared to relieve the effects of the constricting drug by 85 percent. But it produced no benefits for those with asthma.
Dr. Arthur Caplan, a medical ethicist at the University of Pennsylvania, said "challenge studies" - experiments in which people are given a substance that provokes symptoms - are among the most controversial in medicine.
"In my view, the studies can be ethically done," he said. Researchers must be extremely careful in gaining consent, use the smallest doses possible and have people standing by who can rescue volunteers in distress. Review boards must also monitor studies as they unfold, and prepare to stop them at the slightest hint of danger.
"It's very difficult to justify these studies, and we want to do as few of these as possible," he said. "But without a baseline understanding of certain mechanisms, it's hard to know what is going on with a disease."
