Asthma in African Americans: What can we do about the higher rates of disease?

The last several decades have seen a dramatic surge in the prevalence of asthma. In 2009, there were an estimated 17.5 million adults and almost 7.1 million children with asthma in the United States,¹ up from 9.5 million adults and slightly more than 5 million children in 1995.²

While better management has reduced the rates of asthma morbidity and death in recent years, specific groups remain at higher risk of poor outcomes. Compared with whites, African Americans are not only more likely to have asthma, but they often also have more severe disease. For example, in a study in Philadelphia, PA, at all levels of poverty, asthma hospitalization rates for African Americans were substantially higher than for whites.³ African Americans with asthma are also more likely to die of asthma (Figure 1).

Multiple factors contribute to these disparities, including genetics, socioeconomic factors, cultural factors, health maintenance behaviors, provider-patient communication, air quality, and obesity.

This article is based on a literature review with PubMed conducted in November 2010 using combinations of the following search terms: African American, asthma, epidemiology, genetics, obesity, and environment. Below, we review the evidence regarding a number of these factors (Table 1) and their association with the higher asthma prevalence, morbidity, and mortality rates in African Americans.

GENETICS: 70% OF DESTINY?

The trend towards personalized medicine has spurred extensive research into the genetics of asthma. Studies in twins and familial aggregation studies suggest genetics plays a significant role, with estimates of the heritability of asthma as high as 70%.^4,5 More than 100 candidate genes have been shown to be associated with asthma and atopy, 30 of them in five or more independent studies.⁶

Researchers face many challenges when investigating the genetics involved in asthma for a particular race. Race is both a biologic and a social construct and, as such, is a poor substitute for genetics. Race constitutes not only genetic differences in individuals, but also the behaviors, beliefs, and experiences that vary among races.

The clinical disease—the phenotype—is the product of the interaction of genes and these differing behaviors and exposures. Genetics can affect how environmental factors found in association with socioeconomic factors relate to asthma morbidity and mortality.

For example, as we will discuss below, African Americans are more likely than whites to be sensitized to cockroach allergen, even after controlling for socioeconomic variables that may be associated with greater exposure.⁷ High-level exposure to cockroach allergen in sensitized children has been associated with poor asthma outcomes.⁸ This suggests that a genetic difference may exist between African Americans and whites with respect to the potential to develop cockroach sensitization, and this difference may be of particular importance for those African Americans living in areas with higher levels of cockroach exposure.

Two polymorphisms

Two polymorphisms have garnered attention for their influence on African Americans with asthma:

TheADRB2gene. This gene codes for the beta-2 adrenergic receptor and resides at chromosome 5q13.⁹ The receptor is found on several types of cells in the lung, including airway smooth muscle and epithelial cells, and is responsible for the salutary effects of inhaled beta-2 agonists such as albuterol (eg, Proventil).

Allelic polymorphisms of this gene are clinically relevant. The substitution of arginine (Arg) for glycine (Gly) at codon 16 of this gene is responsible for differences in response to short-acting beta-2 agonists. The allelic frequency of Arg16 is lower in white Americans (39.3%) than in African Americans (49.2%), and thus African Americans are more likely to be homozygous for Arg16 (ie, to have the Arg/Arg genotype).¹⁰

People who are homozygous for Arg16 who use albuterol on a regular basis are at higher risk of untoward asthma outcomes.¹¹ This is important, for several reasons. In general, adherence to inhaled corticosteroids is poor (not only in African Americans),¹² and patients who do not take their inhaled corticosteroids as they should may rely on short-acting beta-2 agonists more frequently. Furthermore, African Americans may have a poorer response to the repeated doses of albuterol that are typically given in the emergency department and in the hospital for severe asthma exacerbations.¹³ Additionally, data suggest that Arg/Arg individuals have more frequent exacerbations independent of beta-agonist use,¹⁴ although curiously, patients who are homozygous for Arg16 have a greater benefit from single doses of short-acting beta-2 agonists than those who are Gly16 homozygous.¹⁵

TheCD14gene. An interesting relationship between innate immunity and asthma has recently been described. Polymorphisms of CD14, which codes for a receptor for endotoxin, have been uncovered. The single-nucleotide polymorphism variant thymine (T) at position −260 has been found in greater frequency in whites than in African Americans, who are more likely to have the cytosine (C) allele.¹⁶ An association between the CC genotype and atopy has been reported,¹⁶ although this has not been consistent.¹⁷

A possible explanation for these inconsistencies may lie in complex gene-environment interactions. The amount of endotoxin exposure may play a role in phenotypic expression. Individuals with the CC genotype were at lower risk of developing atopy when exposed to high levels of endotoxin; however, when exposed to lower levels of endotoxin, the CC genotype was associated with a higher risk of atopy.¹⁸ Nonfarm homes in westernized countries tend to have lower levels of endotoxin than farm homes, even in low-income urban areas.¹⁹ This implies that individuals with the CC allele, who are more likely to be African American, would be at greater risk for atopy in the United States. Greater knowledge of these types of gene-environment interactions may lead to improved understanding of the observations that have generated controversy concerning the “hygiene hypothesis.”

The details of how microbial exposure can influence the human immune response to antigen exposure are still being elucidated.²⁰

These examples highlight not only the importance of genetics in the development of asthma, but also the role genes play in variation of treatment response and subsequent risk of morbidity and death. An understanding of these genetic differences among patients is clearly important for moving towards personalized treatment strategies for asthma.