For such a common malady, asthma sure is one hell of a killer: Every day in the United States, it kills 10 people.
For the uninitiated, the condition might seem benign due to its ubiquity—the Centers for Disease Control says one in 13 adults and one in 12 children have it—but the reality is much more complicated than two puffs on an albuterol inhaler. Asthma is responsible for 2 million visits to the emergency department annually and is the No. 1 reason kids miss school—in 2013, that meant about 13.8 million days, combined. And it’s not an equal opportunity killer: Black children are 10 times more likely to die from it than white children.
Compounding this is the fact that one of the top asthma treatments used worldwide is failing minority children because of a lack of diversity in research. The grim truth is that albuterol doesn’t work the same for everyone, and medicine’s failure to recognize that stems from discrimination that’s been baked into the system for decades.
According to a 2007 study published in the Journal of Asthma, of children with moderate to severe asthma, 47 percent of African-American children and 67 percent of Puerto Rican children did not respond to albuterol. The king of the asthma drugs, with a spot on the World Health Organization’s list of essential medicines, stashed in school nurse’s offices and waiting to be deployed as prescribed at a moment’s notice—this drug flat out doesn’t work for everyone.
How did researchers miss this? The answer lies in the fact that most lung research is done in populations of European descent: white people.
Most of the researchers in the United States are white, “and they tend to do research on populations that they feel most comfortable with,” Dr. Esteban Burchard, a physician scientist and professor of medicine and pharmacy at the University of California San Francisco, told The Daily Beast.
But more than that, there is discrimination in the grant review process, meaning minority scientists are less likely to be approved. With the help of FOIA, Burchard’s team showed systematic bias in the review process going back 30 years, in a report published in December 2015 in PLOS Medicine.
“So if you’re African-American, you have a 10 percent lower likelihood of being funded, if you are Asian you have an 8 percent lower likelihood of being funded. And that’s important because scientists tend to study populations that they’re most comfortable with,” he said. For groups already at a disadvantage, that makes research more difficult.
Burchard pointed to a federal law passed in 1993 requiring the inclusion of women and minorities in all federally funded research. “We did a study of all the lung studies that were done over the last 20 years and less than 4 ½ percent were done in non-white populations—despite the fact that 47 percent of the United States is non-European,” he explained. Minority populations have asthma at higher rates than white Americans, but as lung research has historically focused on people of European descent, our ability to understand the causes of these discrepancies and effectively treat patients of all backgrounds has been seriously compromised.
According to Burchard, that means the NIH law has no teeth. “There’s no enforcement,” he said. He noted that in the last two years, the NIH has changed its tune and is taking steps to make including diversity a priority. The NIH Heart, Lung, and Blood Institute has started a program called TOPMed, a whole genome sequencing program that has dedicated one-third of its budget to minority inclusion.
The FDA said it does not track data related to how minority populations are underserved due to a lack of diversity in lung research. However, the FDA told The Daily Beast via email that “meaningful representation of minorities in clinical trials for regulated medical products is fundamental to the FDA’s regulatory mission and public health” and that it is “working to increase the participation of people in racial, ethnic and other minority groups in the clinical trials that test new medical products.”
The need for diversity in lung research is critical to minority asthma patients because treatment plans suffer when we fail to understand what is causing these differences in asthma prevalence, severity, and medication responsiveness. To this end, Burchard and his team at UCSF set out to examine why some people don’t get relief from albuterol inhalers. They did this by sequencing the entire genomes of 1,441 diverse children with asthma. Specifically, the kids in the study were either high- or low-albuterol responders. Albuterol works as a bronchodilator, widening the constricted airways of asthmatic lungs hungry for air; these kids were either helped by this drug very much or very little.
By looking at the whole genomes of these children, the researchers were able to cast a wide net for genetic variants (differences within the same gene) that could be associated with diminished response to albuterol. Of interest is a variant of gene NFKB1, which is more prevalent for people of African ancestry and may be involved with a neighbor gene known to help protect the lungs and airways.
Burchard’s research seems to suggest that there is some evidence of a genetic reason for why certain minority populations are not as responsive to albuterol, beyond environmental and social factors.
“It shines a spotlight that there’s a big issue that has significant public health implications, clinical implications, as well as scientific implications,” Burchard said. Now the goal is to home in on the biology of those particular genes to try to create new drugs that target them.
Take, for instance, the most recently FDA-approved drugs for cholesterol: PCSK9 inhibitors. These are antibodies designed to go after a specific liver protein that results from a specific gene. The result is less harmful LDL circulating in the blood stream. The reason we know about this gene is because of increased diversity in research.
“[The gene] was identified in African-American populations simply because they had a higher gene frequency than whiles,” Burchard said. “They studied whites but they completely missed it, but when they studied African Americans, they identified this gene and they were able to develop antibody against the gene product.” These antibodies find the protein that results from the gene in question and stick to it, marking the doomed protein for destruction by the immune system.
The best part? It works. On everyone. “When they tested the drug, it actually worked well whether you’re black, white, Asian, blue, green, purple, or pink,” he said.
It’s a compelling example of how biological differences within groups can be leveraged for the benefit of the masses, but even without broad-scale community benefits, inclusivity and diversity in research should be an integral part of the process. As current research into asthma has shown, what works for some people won’t work for others. And everyone deserves treatments that work for them.