Understanding the genetics of asthma and implications for clinical practice

Asthma is one of the most common heritable diseases globally, with variable clinical expression and response to treatment that is attributed to underlying genetic differences. Hundreds of loci on multiple chromosomes are associated with asthma. Although routine genetic screening is not recommended, testing for medication responsiveness might soon play a role in clinical management. Pharmacogenetic research remains early stage but has demonstrated potential for both clinical and cost effectiveness. Furthermore, recognition of clinically apparent asthma phenotypes, the result of genetic and environmental interactions, can help to inform treatment decisions. Phenotypes are divided into two broad categories of atopic and nonatopic disease, with further subdivisions that are associated with clinical presentation patterns and responsiveness to treatment. In general, earlier onset and allergic disease will respond well to traditional therapy with inhaled corticosteroids (ICSs) and leukotrienes because these medications target inflammatory pathways for allergic disease. However, patients with late-onset, symptom predominant (lacking inflammation), and obese asthma might be resistant to standard therapy and may require treatment modification. These patients are at risk for overuse of ICSs with poor response and may benefit more by use of long-acting beta agonists, long-acting muscarinic agonists, weight reduction, and exercise.