Stanley J. Szefler, MD Helen Wohlberg and Herman Lambert Chair in Pharmacokinetics Divisions of Pediatric Clinical Pharmacology and Allergy and Immunology Department of Pediatrics National Jewish Medical and Research Center Denver, CO

In a recent issue of the Journal of Allergy and Clinical Immunology, Stoloff and Boushey discussed the differences among the terms “severity,” “control,” and “responsiveness,” emphasizing that physicians should base initial treatment on assessment of asthma severity but subsequent treatment on level of control.¹ They pointed out that responsiveness to treatment is heterogeneous and variable, however, even among asthmatic patients with asthma of similar severity. Variability in treatment response calls attention to the importance of assessing control and adjusting treatment accordingly. Applying a guidelines-based approach to management requires an awareness of asthma as causing current symptoms and functional impairment, as well as risk of future adverse events. The update to the national asthma guidelines, currently in review and scheduled for final release in 2007, emphasizes these points.

Potential treatment guides. Clinicians treating the disease are now moving toward goals of improving asthma control and identifying therapies that will induce remission, at least during treatment. Clinicians also recognize the limitations of current therapy in resolving asthma symptoms completely and altering the natural history of asthma. An individualized approach to asthma management would address the variability in response to therapy. This individualized approach seeks to apply biomarkers and genetics as resources to guide treatment. Exhaled nitric oxide (eNO) and β-adrenergic polymorphisms are prototypes for this approach. However, clinicians must validate their application to clinical care.

Exhaled nitric oxide. eNO, for example, could prove useful in measuring, predicting, and monitoring response to corticosteroids. Clinicians consider eNO a surrogate marker specific for eosinophilic airway inflammation, which is usually steroid responsive. Silkoff et al. provided the most comprehensive review of eNO measurement and the application to clinical care a few years ago.² eNO now appears useful for guiding steroid requirements for managing asthma, but more studies will be helpful in refining the principles of application.³ A new handheld device to measure eNO levels, which is not yet available in the United States, could expand the application for home monitoring and imminent acute asthma exacerbations.⁴

Urinary leukotrienes. Another potentially useful biomarker for clinical management is the measurement of urinary leukotrienes. Clinicians associate elevated urinary leukotrienes with a favorable pulmonary response to leukotriene receptor antagonist (LTRA) treatment.⁵ Measuring leukotrienes in exhaled breath condensates, Montuschi et al. studied the effect of montelukast, an LTRA, on exhaled leukotriene E₄ (LTE₄), 8-isoprostane, and prostaglandin E₂ in children with asthma—along with eNO measurements indicating that LTRA decreased exhaled LTE₄ in atopic children with asthma dependent on baseline exhaled LTE₄ values.⁶ Therefore, exhaled LTE4 might help identify children with asthma most likely to benefit from LTRAs.

Looking ahead. Hopefully, an individualized approach to asthma management will lead to new data on driving factors in poorly controlled asthma and potential new targets for therapeutic intervention. Whether an agent that hits multiple targets (eg, inhaled corticosteroids) or selective targets (eg, an LTRA and anti-immunoglobulin E) will remain within our current armamentarium will be a topic for future research advancing asthma care for children. The application of biomarkers should not only improve asthma care but also point to reasons for treatment failure. Careful study and application of biomarkers should also illuminate new treatment strategies and medications.

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