Key Point

Black patients with asthma have a significantly diminished response to corticosteroids compared to white asthma patients and may require higher doses to control their symptoms.

DENVER—In the United States, asthma-related mortality and hospitalization rates are four times higher among black children than white children. Even after controlling for variables such as socioeconomic level, access to health care, and urban environment, the discrepancy remains. That asthma has an inflammatory component and usually responds to corticosteroid therapy is well known. However, not all patients with asthma respond to corticosteroids.

Researchers at the National Jewish Medical and Research Center and the University of Colorado Health Sciences Center in Denver conducted a cross-sectional study to determine whether black patients with asthma have a diminished response to corticosteroids. They found that in vitro, blood samples from black patients and controls needed larger concentrations of corticosteroids to suppress proliferation of T-lymphocytes.¹

The study included 395 black and non-Hispanic white asthma patients and 202 nonasthmatic controls. Patients underwent spirometry and skin-prick testing. Before the patients’ morning corticosteroid dose, blood was drawn and clinical glucocorticoid lymphocyte stimulation assays were performed. Sensitivity to corticosteroids was determined by measuring the concentration of dexamethasone needed to suppress phytohemagglutinin-induced lymphocyte proliferation by 50% (log₁₀ IC₅₀).

SIGNIFICANT DIFFERENCE IN CORTICOSTEROID RESPONSE

About 27% of the asthmatic group and 52% of the nonasthmatic group were black. Nineteen percent of black patients with asthma and 35% of white patients required long-term therapy with oral corticosteroids. Significant differences were noted in the response to corticosteroid treatment as measured by dexamethasone log₁₀ IC₅₀ values, which were a median of 1.10 nmol in black patients versus 0.85 nmol in white patients. Differences were also seen with regard to the percentage of inhibition at the maximum inhibitory concentration of dexamethasone, which was a median of 78.8% and 90.2% in black and white patients, respectively. These differences were present regardless of the patient’s disease state.

Black members of the control group also had higher log₁₀ IC₅₀ values than their white counterparts—1.26 nmol versus 0.95 nmol, respectively. Black persons (with or without asthma) required greater concentrations of dexamethasone to suppress T-lymphocyte activation by 50%.

After the researchers controlled for the effects of age, duration of asthma, age at diagnosis, FEV₁ percent of predicted, inhaled and oral corticosteroid doses, and the number of unstimulated and PHA-stimulated T-lymphocytes, only inhaled corticosteroid dose and basal T-lymphocyte activity were correlated to log₁₀ IC₅₀ values in the group with asthma.

DO BLACK PATIENTS NEED HIGHER DOSES OF CORTICOSTEROIDS?

“Lower glucocorticoid responsiveness does not translate into complete resistance,” pointed out Ronina A. Covar, MD, Assistant Professor in the Department of Pediatrics at National Jewish Medical and Research Center. However, it does illustrate the importance of patients’ adhering to their drug regimens at the doses recommended. “After making sure other confounders are ruled out or treated and that adherence to the recommended regimen is acceptable, a step-up approach may be necessary.” If high doses of corticosteroids are needed, Dr. Covar emphasized, patients must be followed closely and monitored for adverse events. The addition of steroid-sparing agents would also be warranted.

In situations where suboptimal response is evident—especially with difficult-to-control symptoms or when compliance is questionable—tests such as the assay used in the present study can be employed to measure the patient’s response to glucocorticoids, observed Dr. Covar.

Although both black and white asthma patients had moderate airflow limitation with comparable controller medication requirements, black patients needed about 50% more dexamethasone to suppress PHA-stimulated lymphocytes. This diminished corticosteroid responsiveness may contribute to the higher levels of morbidity and mortality among black patients with asthma, the authors theorized.

DISEASE ITSELF MAY NOT BE THE ONLY FACTOR

Dr. Covar pointed out that the asthma itself was not the only factor determining the degree of unresponsiveness to corticosteroids. “There is evidence from other studies that an exuberant inflammatory response can lead to steroid resistance. But since differences were also found in nonasthmatic subjects, then disease itself may not be the only factor. For instance, age could be a factor as well,” she added.

The racial differences in corticosteroid responsiveness could also be related to differences in the immune response that is associated with asthma (eg, overproduction of inflammatory cytokines and a subsequent reduction in corticosteroid responsiveness) or to certain genetic mechanisms directly related to corticosteroid responsiveness. The observation that black, nonasthmatic patients required greater concentrations of corticosteroid supports the possibility of an inherent genetic predisposition toward diminished corticosteroid responsiveness.

The findings from this study offer another reason why black asthma patients have greater difficulty controlling their asthma symptoms, despite therapy, Dr. Covar pointed out. “It offers an immunologic basis—since studies have also implicated sociocultural possibilities.”

—Gale Jurasek

Reference
1. Federico MJ, Covar RA, Brown EE, et al. Racial differences in T-lymphocyte response to glucocorticoids. Chest. 2005;127:571-578.

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