When inhaled, the drug albuterol opens up the airways of the lungs, providing fast-acting relief to the wheezing and shortness of breath that often accompany an asthma attack. It was discovered in 1966 by a team of British researchers, and went on to become an extremely popular medication for the widespread childhood condition. It is on the World Health Organization’s list of essential medicines. But it often fails minority children.
This failure is a form of discrimination embedded deep in the annals of medicine. One study found that 47 percent of African-American children and 67 percent of Puerto Rican children with moderate to severe asthma did not respond to albuterol. In 2014, African American people were almost three times more likely to die from asthma-related causes than their white counterparts. Part of the reason is that genetic differences affect how people respond to medical treatment. And the vast majority of participants in studies of both lung disease and genetics are of European descent.
Now a new study from UCSF published in the American Journal of Respiratory and Critical Care Medicine sheds some light on why.
“There is dramatic racial disparity in asthma prevalence, mortality, and albuterol drug response,” Angel Mak, a study author, told Gizmodo. “Puerto Ricans and African Americans have the highest asthma prevalence and mortality and lowest drug response compared to whites. Yet, over 95 percent of lung research [is] done on populations of European decent.”
Researchers conducted an unprecedented whole genome sequencing study of minority children, examining the genomes of a diverse group of 1,441 children with asthma who had either very high or very low response to albuterol. Doing so unveiled several genetic variants which appeared to be associated with a reduced response. One of those variants, for a gene named NFKB1, is more prevalent in people with African ancestry. That gene may play a role in the regulation of a neighboring gene, SLC39A8, which is known to help protect the airways and lungs from inflammation and cellular damage.
The end goal is to provide for effective treatment for diverse populations, and this work points researchers in the direction of how to do so.
“Our findings increase our understanding on albuterol drug response, provide new direction for asthma drug design and build the foundation of precision medicine for patients who have these genetic risks,” said Mak.
Eric Topol, a geneticist at the Scripps Research Institutes not associated with the work, told Gizmodo that while the study isn’t the first to show an ancestry-specific inhaler response for asthma, there is certainly a need for a multi-ancestry assessment for pharmacogenomic interactions.
Several past studies, including others by UCSF, have demonstrated that genetic risk factors for asthma vary according to ancestral background. This study, though, was larger than previous ones and identified new genetic risk factors.
Environmental factors, like air quality, also put minorities at increased risk for asthma. But genetics are also a factor, and ethnic background is a key predictor of how well someone will respond to the drugs that treat it.
In 1993, Congress passed legislation requiring publicly funded medical studies to include more minorities. But in 2015, a review of lung disease studies found that only 5 percent of publicly funded research included patients of color. Similarly, a 2016 analysis found that 80 percent of participants in genome-wide association studies were European.
Figuring out how to better treat diverse populations will require more research like that coming out of UCSF. And that research is sorely needed.
Update: This story was updated to clarify that it utilized whole genome sequencing.