Personalizing the approach to childhood asthma
Published Online: March 24, 2104
Clinicians treating asthmatic children have long recognized the wide-ranging heterogeneity in response to asthma medications, particularly to inhaled corticosteroids. Often, despite large doses of anti-inflammatory medications, a subset of asthmatic children will continue to have persistent symptoms and poor overall asthma control. Though many of these children will subsequently develop airway remodeling and fixed airflow obstruction later in life, there are no individual clinical features that reliably stratify patient risk. Initial recent efforts to tackle this heterogeneity by developing multivariable phenotypic classifiers (so-called endophenotypes) have defined 4 or 5 main asthma subtypes. However, the clinical significance of these classifications, particularly with respect to their utility in predicting patient’s natural history and response to anti-inflammatory therapies, are unknown.
In a study recently published in The Journal of Allergy and Clinical Immunology, Howrylak and colleagues took the first steps toward addressing these questions by classifying 1,041 asthmatics who participated in the Childhood Asthma Management Program (CAMP) clinical trial that assessed long-term response to inhaled anti-inflammatory asthma therapies. Using baseline clinical assessments of atopy, lung function, and exacerbation rate, data-driven algorithms defined five phenotypic clusters. With an average of 48-months of prospectively collected follow-up data, they assessed whether cluster membership predicted subsequent clinical course, including treatment response.
Clinically significant differences were noted between the five asthma clusters. Children in the three clusters with more mild asthma symptoms demonstrated a positive response to inhaled corticosteroids compared to nedocromil and placebo, with decreased rates of exacerbation. Conversely, children in the two more severe clusters diverged in their responsiveness to corticosteroid therapy, with one cluster showing decreased rates of exacerbation among children using either budesonide or nedocromil, and the other cluster showing no improvement in rates of exacerbation with any of the medications.
Given the risks associated with long-term corticosteroid use, the authors’ findings suggest that phenotypic clustering approaches using baseline clinical characteristics may help risk stratify patients and identify patient subsets with steroid refractory asthma and others for which alternative treatment options are available.
The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of asthma and clinical immunology.