Black children respond differently to step-up asthma therapy

USF Health’s Dr. Juan Carlos Cardet was among the authors of a new multi-site clinical study reported in the New England Journal of Medicine

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Black children respond differently to step-up asthma therapy than black adolescents and adults, report authors of a major study published Sept. 26 in the New England Journal of Medicine. Among the NEJM authors of the multi-site Best African American Response to Asthma Drugs (BARD) clinical study was Juan Carlos Cardet, MD, MPH, assistant professor in the USF Health Morsani College of Medicine Division of Allergy and Immunology.

Nearly half of black children with poorly controlled asthma (46%) fare better by increasing their dose of inhaled steroid (glucocorticoids) alone, without adding a long-acting beta agonist (LABA), the researchers found. Just as many black children (46%) experience improved asthma control by adding a LABA to their lower-dose inhaled glucocorticoid regimen.

In contrast, black adolescents and adults are more likely to have a superior response by adding a LABA to their inhaled glucocorticoid treatment rather than only escalating (stepping up) the dose of inhaled glucocorticoids, the BARD researchers reported.

Dr. Cardet was an investigator for the BARD study when he was faculty member at Harvard Medical School. At USF Health, he is an investigator for several clinical research networks supported by the National Institutes of Health’s National Heart, Lung and Blood Institute (NHLBI), including its Precision Interventions for Severe and/or Exacerbation Prone Asthma (PrecISE) network.

Inhaled glucocorticoids, which reduce airway inflammation, are a first-line therapy to control asthma. When asthma becomes severe and difficult to control, physicians often recommend adding a LABA (long-lasting bronchodilator that relaxes constricted airways) to the inhaled steroid treatment as the gold standard step-up therapy. However, this standard was based on other studies that historically included by too few black people, who suffer higher rates of serious asthma attacks, hospitalizations and asthma-related deaths than white people, Dr. Cardet said.

To address this disparity, two parallel randomized double-blind sequential cross-over BARD trials compared the effectiveness of different doses of inhaled glucocorticoids, with or without the addition of the LABA (salmeterol) in two groups: children ages 5 to 11, and adolescents and adults (ages 12 and older). All 574 participants had at least one grandparent who identified as black and asthma inadequately controlled while on a low dose of inhaled glucocorticoids. A composite measure incorporating frequency of asthma attacks and asthma control days as well as changes in lung function was used to calculate treatment response during each 14-week regimen.

Juan Carlos Cardet, MD, MPH

While several previous retrospective studies suggested otherwise, most of the black adolescents and adults with poorly controlled asthma responded better to adding a LABA to step-up treatment compared to those only receiving increased inhaled steroid doses. This BARD trial finding was similar to that in previous mixed (largely white) population studies – although 20-25% of the black adolescents and adults showed no difference in their responses to these approaches.

“But the black children responded differently. They had an equal chance of responding best to increasing their dose of inhaled steroid as they did to the addition of a long-acting beta agonist,” Dr. Cardet said.

The researchers also found that neither the percentage of African ancestry (evaluated by genotyping) nor baseline biomarkers could predict the response to step-up therapy.

A larger, more simplified trial is needed to determine which step-up therapy option works best for which black children, the researchers wrote, adding that their study demonstrates a need for trials of specific subgroups: “These findings suggest that data cannot be extrapolated from mixed populations to specific subgroups, including those of different ages and races.”

An NIH-funded physician scientist, Dr. Cardet says he is driven to improve asthma therapy through translational research by a family history of the chronic disease and by racial and ethnic disparities in asthma illness and deaths, including in his native Puerto Rican community. He is a co-investigator for the PREPARE Study for PeRson EmPowered Asthma Relief, a multisite trial sponsored by the Patient-Centered Outcomes Research Institute (PCORI), which focuses on African-American, Hispanic and Latino adults. Dr. Cardet is also the local principal investigator for a NHLBI PrecISE grant aiming to identify biomarkers to guide development of targeted treatments for severe asthma.

As the principal investigator for a five-year K23 National Institute of Allergy and Infectious Diseases (NIAID) grant, he has been examining whether higher levels of the gut microbe metabolite enterolactone may benefit asthma control. Dr. Cardet is testing the effects of enterolactone, a plant estrogen with antioxidant and anti-inflammatory properties, in preclinical models of allergic airway inflammation.