Health Disparities In Our Genes: An Asthma Story
Despite significant advances across many areas in healthcare, asthma continue to be a disease of nearly epidemic proportions. One in every 13 people has asthma and almost 6.3 million people who suffer from asthma are under the age of 18. African Americans and Hispanics suffer more frequently from asthma than Caucasians. Disturbingly, African Americans are three times more likely to be hospitalized and die due to asthma complications. Why? We know that several factors impact healthcare in minority populations. Among those variables, access to healthcare and insurance, income, language and literacy barriers, and environment are at the top of most lists. But is there something more? Is there something at the very core of our genetic make-up that impacts how we as individuals respond to different medications and treatments? As we have learned in many other disease states, such as oncology and cardiology, the answer is clearly yes. In asthma, that genetic difference leads to an alarming disparity in outcomes for African American and Hispanic children.
Asthma is a chronic lung condition which results in reversible inflammation and narrowing of the airways. The treatment of asthma and related symptoms may be simple for some patients, but for certain patients, many of them African-American or Hispanic, treatment remains a challenge. It is estimated that approximately 70 to 80% of asthma patients exhibit variable responses to the current standard of care. These variations may range from subtle differences that can be treated with dosage adjustments to complete non-response to treatment. Data suggests that genetics and ethnicity are responsible for the majority of these differences in response.
Inhaled beta-adrenergic agonists (e.g., albuterol) are the most commonly used medications in the treatment of asthma. A number of studies have been conducted to examine the effects of genetic alterations at two codons (16 and 27) on the response to albuterol in patients with mild to moderate asthma. Results showed significant worsening of asthma symptoms and declines in airflow for the B16-Arg/Arg patients in comparison to patients with other genotypes. While the B16-Arg/Arg alteration occurs in both Caucasians and African Americans, it is significantly more common in African Americans. This could explain the poor response to albuterol in some African Americans. Additional studies have also found that among Hispanics, Puerto Ricans respond less favorably to albuterol than Mexicans as measured by lung function before and after inhalation. Data also suggests that there is substantial variability in the response to inhaled corticosteroids. A study compared the efficacy of the inhaled corticosteroid beclomethasone with montelukast and found that 22% of patients appeared to have an adverse response to treatment, evidenced as a decline in FEV1 after 12 weeks of treatment. So, if evidence exists of poor outcomes in AAs and Hispanics, why is albuterol frequently prescribed to these populations?
What can be done to tackle the genetic differences in asthma? Identification of patients who are most likely to respond unfavorably to asthma treatments is essential to the treatment algorithm.The FDA requires that drug manufacturers to submit pharmacogenetic information when reporting clinical trial results. Drug manufacturers and healthcare practitioners must be proactive in utilizing these results to investigate alternative treatment options for this subset of patients.And, perhaps more importantly, these patients must be better represented in clinical trials, especially for those disease states in which African Americans and Hispanics may have a higher incidence rate.
One fact has been made painfully clear through the study of currently available asthma treatments in relation to the genotypes of asthma patients: all treatments are not created equal. Unfortunately, the opportunity for genetic testing in order to narrow this treatment gap is not available to every patient, and frequently is not available to those patients who would most benefit from it. Asthma is a treatable condition. It behooves the pharmaceutical community to conduct further, more targeted research and seek out treatment options for those who do not benefit from the current standard of care. This would not only result in advances in care and improved quality of life for these patients, but also service a business opportunity. There is a clear financial upside to adding additional treatment avenues for currently underserved patient populations. However, unless these genetic insights are put into practice by expanding clinical trial populations and prescribing based on genotype, millions will continue to suffer and die from this very treatable condition.