Managing asthma in the 21st century: role of pharmacogenetics.
As discussed above, pharmacogenetics offers the opportunity to ascertain associations between genetic variability and response (both salutary and adverse) to various asthma medications. Although there have been multiple asthma pharmacogenetic studies, the field of pharmacogenetics is still in its infancy. As this field advances, it is estimated that an increasing proportion of individual variation in responses to pharmacotherapy will be predictable based on associations with particular genetic polymorphisms or patterns of polymorphisms. These associations hold out the promise of being able to individualize pharmacotherapy by providing specific therapy to those most likely to respond, while avoiding therapy in those most likely to suffer adverse effects. Currently, only the pharmacogenetic effects of position 16 of the beta-adrenergic receptor appear to be of sufficient magnitude to affect asthma therapy, but further understanding of the mechanism of this association as well as prospective replication with long-acting beta-agonists is still required to bring pharmacogenetics into the clinical arena. Most other pharmacogenetic effects are likely to be of smaller magnitude or, as with 5-LO or CRHR1 polymorphisms, less common. Thus, ultimately, we most likely will use "panels" of polymorphisms to calculate the relative risk-benefit ratio of a particular therapeutic course for an individual patient. It is hoped that, within the next decade, pharmacogenetic information will allow us to treat those who can benefit most from particular asthma medications and to avoid toxicity by administering medications to those unlikely to experience toxicity. If pharmacogenetics fulfills its promise, then not only will we be able to administer corticosteroids and other therapies to pediatric patients with asthma who are most likely to respond or to those least likely to experience adverse effects but we also will be able to introduce or develop drugs for asthma that would otherwise have been held back due to potential toxicity in a subset of patients.
Wechsler
Michael E
ME
Asthma Research Center, Partners Asthma Center, Division of Pulmonary and Critical Care, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. mwechsler@partners.org
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