Asthma Studies Raise Thorny Questions about Race and Genetics

May 1, 2017

Research shows that African-Americans don’t respond as well as their white counterparts to some of the most common asthma controller medications, raising questions about how those medications are tested in clinical trials. Photo: Thinkstock

By Linda Childers

Walking through the halls of West Oakland Middle School in Oakland, it’s not uncommon to hear the sounds of students wheezing and coughing mixed with preteen chatter.

According to school data, approximately 39 of the 220 students enrolled at this school have confirmed cases of asthma, and many more have breathing issues, including an increased incidence of respiratory infections.

Families and school officials face an uphill battle to curtail respiratory illnesses among the school’s predominantly black students as air pollution, a risk factor for lung diseases, exceeds state and federal standards.

Such differences in environment have long been understood as a potential underlying factor in racial health disparities in the U.S.

Yet the problems behind the disparities extend beyond the environment, says Esteban González Burchard, a pulmonologist and professor of bioengineering and therapeutic sciences in the UCSF schools of Pharmacy and Medicine. Participants in clinical trials to test out the effectiveness of medication are overwhelmingly white, Burchard notes. Medications, however, aren’t necessarily equally effective across ethnic groups.

“It’s been shown that African-Americans don’t respond as well as their white counterparts to some of the most common asthma controller medications,” Burchard says. The differences may be down to genetics.

“Almost all of the genetic studies on asthma were done using white patients only,” he notes.

In May 2016, Burchard published results of the largest single study of the genetic and environmental causes of asthma in African-American children. The study results, which appeared in the journal Immunogenetics, found that only 5 percent of the genetic traits linked to asthma in European Americans were found in African-Americans.

Burchard’s research team also discovered a novel variant in the PTCHD3 gene that could be a risk factor for asthma in African-American children. The top three genes linked to asthma in their study have also been associated with obesity and inflammation.

More Than Just Asthma

One solution to health disparities, researchers say, is to increase the number of minority patients participating in clinical trials.

Assuming that an investigational drug tested in clinical trials will work the same on patients of every ethnicity is a huge mistake, says Ingrid Oakley-Girvan, PhD, MPH, research scientist at the Cancer Prevention Institute of California (CPIC) in Fremont.

She references a 2015 study conducted by researchers at New York University and published in the Journal of the American College of Cardiology, that found one type of drug, angiotensin-converting-enzyme or ACE inhibitors, used to treat high blood pressure, had poor cardiovascular outcomes in black patients.

Although ACE inhibitors were shown to be effective in clinical trials, the medication showed a significant difference between black and white patients who were given the medication in a clinical setting. These findings led the Joint National Committee to recommend that black patients with high blood pressure be treated with drugs other than ACE inhibitors.

“Research has shown that some ethnic groups have a different response to medications, making it critical for people of all races and ethnicities to be involved in clinical trials,” Oakley-Girvan says.

“Racial and ethnic disparities exist in some of the most devastating health conditions including heart disease, diabetes, cancer and Alzheimer’s, “says Burchard. “And yet these same groups are less likely to be enrolled in clinical trials.”

In 1993, the National Institutes of Health Revitalization Act was passed by the U.S. Congress and signed into law by President Bill Clinton. The Act required all federally funded clinical research to prioritize the inclusion of women and minorities.

Despite the law, little progress has been made, Burchard says.

In a study released in Nature Medicine this month, Burchard and his colleagues found that genetic studies conducted on non-white rose from 4 to 6 percent in the last seven years. “A 2 percent increase shows this is a huge problem,” Burchard says.

Race in Medicine

While researchers agree that more minority patients are needed in clinical trials, some also express concerns about the role of race in medical research.

Sandra Soo-Jin Lee, Ph.D., a medical anthropologist at Stanford University’s Center for Biomedical Ethics in Palo Alto, cautions that mixing race with genetics may open the door to prejudice, racial stereotyping and overly simplistic theories on health outcomes and drug interactions, which in turn could ultimately lead to worse health.

“In biomedical research, one problem is we know that race functions as a proxy for a broad range of variables, that if identified and investigated, may have much more explanatory power for understanding health disparities,” Lee says. “For example, we know that social and environmental factors such as nutrition, access to health care, and exposure to pollutants are strong indicators for risk and disease, yet much of the research that cites race as the key axis for comparison, never attempt to investigate what operates beyond the proxy of race.”

While acknowledging concerns about the role of race in research, Burchard believes that although there are potential social costs associated with linking race or ethnic background with genetics; they are outweighed by the benefits in terms of diagnosis and research.

“Ignoring racial and ethnic differences in medicine and biomedical research won’t make them disappear,” he says. “Rather than ignoring these differences, researchers should use them as a starting point for further research.”

In an effort to increase the number of patients of color involved in clinical trials, Burchard and his colleagues at UCSF, along with other medical researchers, are collaborating with community and advocacy groups across the state to increase awareness of clinical trials.

Burchard, who is Latino, believes a key to recruiting more minority patients is having more minority scientists involved in these efforts.

“Being a bilingual physician-scientist from an ethnic minority has proven invaluable in brokering connections,” says Burchard of recruitment in his recent studies.

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