Albuterol Less Effective in Minority Children for Genetic Reasons

Esteban Gonzalez Burchard, MD, MPH

New research is shedding light on the genetic reasons albuterol doesn’t seem to work as well against asthma in minority children.

Researchers from the University of California, San Francisco, have completed a whole-genome sequencing study specifically looking at asthma drug response in minority children. The study looked at the genomes of 1441 children across a diverse range of ethnic backgrounds. Each of the children in the study had either a very high or a very low response to albuterol.

The analysis helped the researchers identify new genetic variants that correspond with lower response to albuterol, including a variant of the NFKB1 gene, a variant that is more common in people of African ancestry. Broadly speaking, the variants identified related to genes that regulate lung capacity and immune response.

Esteban González Burchard, MD, MPH, who directs the Asthma Collaboratory at UCSF, said the study will help point to better answers for how to treat children with different genetic traits.

“Our results demonstrate that we can identify children who are more or less likely to respond to albuterol using pharmacogenetic testing,” Burchard told MD Magazine. “Those children who are less likely to respond to albuterol should be on more aggressive therapy. We have also identified novel drug targets which would be amenable to newer and more targeted therapies.”

In addition to making strides toward more personalized treatment of asthma, the study also helps expose a frustrating paradox about asthma research: despite the fact that African-Americans and people of Puerto Rican descent have higher rates of childhood asthma, the vast majority of studies of asthma treatments are based almost exclusively on data from children of European heritage.

Sam Oh, PhD, MPH, told MD Magazine the study is one of a string of studies UCSF has conducted to bring awareness to racial disparities in clinical trials. He noted a 2015 study the team conducted looking at the racial makeup of participants in studies funded by the National Institutes of Health.

“[W]e found that non-White study participants were markedly underrepresented in NIH-sponsored publications of pulmonary disease—less than 4.5% of all NIH-funded publications since 1993 included sufficient minorities to be statistically meaningful,” he said.

Oh and his colleagues cited a number of potential reasons for the lack of minority representation in studies. One reason might simply be a lack of training in the importance of accounting for racial disparities when designing and implementing studies. Another challenge is recruitment—it can be difficult in some communities to enroll minority patients, and there often are no incentives to reward the extra effort it takes to enroll more minority patients.

However, Oh and colleagues also suggested it might have to do with a lack of minorities among the respiratory scientists at major academic medical institutions.

“This problem could be remedied by implementing short-, medium-, and long-term strategies, such as creating incentives to conduct minority research, ensuring fair review of grant applications focusing on minorities, developing the careers of minority scientists, and facilitating and valuing research on minorities by investigators of all backgrounds,” the authors wrote.

The new study, “Whole Genome Sequencing of Pharmacogenetic Drug Response in Racially Diverse Children with Asthma,” was published March 6 in the American Journal of Respiratory and Critical Care Medicine.