Exacerbation-Prone Asthma: How Much Can Race, Ancestry Affect Patients?

Although asthma treatment has improved substantially in recent decades and the number of asthma-associated deaths has declined, a subset of patients continues to experience frequent exacerbations despite adherence to appropriate management strategies.¹ Pooled data from 6 studies show that nearly half the total exacerbation burden can be attributed to fewer than 5% of patients.² This group faces significant disability, morbidity, and mortality, underscoring the need for a greater understanding of exacerbation-prone asthma and personalized interventions for those affected.

Achieving these outcomes will require further elucidation of risk factors associated with frequent exacerbations, including environmental exposures such as viral respiratory infections, air pollution including tobacco smoke and high nitrous dioxide levels, and stress. Individual factors include biomarkers such as elevated levels of eosinophils, immunoglobulin E, and fractional exhaled nitric oxide, as well as comorbid conditions such as sinusitis, gastroesophageal reflux disease, psychiatric disorders, and obstructive sleep apnea.^3,4

In addition, emerging research highlights the role of genetic factors in exacerbation-prone asthma, including various susceptibility loci for recurrent, severe exacerbations.^3,5 Other findings implicate African ancestry, a genetic factor linked to greater susceptibility to exacerbations.⁶

In a study published in the Journal of Allergy and Clinical Immunology, researchers from numerous universities in the United States noted that “[m]inority groups of African descent experience disproportionately greater asthma morbidity compared with other racial groups, suggesting that genetic variation from a common ancestry could influence exacerbation risk.”⁶ They investigated this possibility using data from 1840 multiethnic participants from 12 Asthma Clinical Research Network and AsthmaNet trials, of whom 24% self-identified as black. Genetic data were available for 161 black participants.

In the latter group, the results demonstrated that African ancestry greater than the median (≥82%) was associated with a significantly higher exacerbation risk (rate ratio, 3.06; 95% CI, 1.09-8.60; P =.03). “Black [participants] have unique risk factors for asthma exacerbations, of which global African genetic ancestry had the strongest effect,” the authors concluded.

To further explore these findings, as well as treatment considerations and remaining challenges in exacerbation-prone asthma, Pulmonology Advisor spoke with Victor E. Ortega, MD, PhD, ATSF, associate professor in the Division of Pulmonary, Critical Care, Allergy and Immunologic Diseases at the Center for Precision Medicine at Wake Forest School of Medicine in Winston-Salem, North Carolina.

Pulmonology Advisor: What are recent developments regarding our understanding of exacerbation-prone asthma?

Dr Ortega: Individuals with asthma prone to recurrent exacerbations account for a large proportion of the costs related to asthma because of absence from school or work, as well as the need for urgent healthcare use despite taking a combination of different therapies.² Among individuals with asthma, 2 ethnic groups of recent African descent (African Americans and Puerto Ricans) experience the highest proportion of this morbidity compared with other ethnic groups, including non-Hispanic whites.⁶

The underlying mechanisms for interethnic differences in the expression of severe asthma are complex, but could result from one or more factors, including socioeconomic status, environmental exposures, differences in expression of specific biologic inflammatory pathways, interethnic differences in responsiveness to asthma drugs, and possibly genes from a common ancestry.⁶

During the last 2 decades, multiple risk factors for exacerbation-prone asthma have been identified in different asthma cohorts, including a recent longitudinal study of a severe asthma cohort. These risk factors include history of prior exacerbations and lower lung function, as well as comorbid conditions such as chronic sinusitis and gastroesophageal reflux disease.⁶

Recent developments for the treatment of asthma and prevention of exacerbations include the recognition of important biologic inflammatory pathways targeting allergic inflammation, which have been used to recognize important subgroups for targeted antibody treatments. Although these drugs are promising, they are indicated for asthma that is not controlled despite adherence to regular treatment with appropriate combination treatment strategies (eg, high-dose inhaled corticosteroids with long-acting bronchodilators and/or leukotriene modifiers).³

Pulmonology Advisor: What do your recent findings add to our understanding of this disease?

Dr Ortega: We evaluated risk factors for more frequent asthma exacerbations in patients with a confirmed diagnosis of asthma from different ethnic groups who participated in 1 or more asthma clinical trials from the National Heart, Lung, and Blood Institute at the National Institutes of Health. A subgroup of these patients had whole-genome genetic data available, which were used to estimate global African, European, and Native American ancestry. There have been few studies evaluating risk factors for more frequent asthma exacerbations in multiple racial and ethnic groups simultaneously recruited and longitudinally characterized in clinical trials, ensuring monitored access to medications and complemented by genetic data for estimating ancestry.⁶