Different childhood asthma phenotypes may need different treatment strategies

By Reuters Staff

NEW YORK (Reuters Health) - Different childhood asthma phenotypes respond differently to inhaled anti-inflammatory medications, suggesting a need for differential treatment strategies, according to research from the Childhood Asthma Management Program (CAMP) Research Group.

Subsets of asthmatic children not only respond differently to medications, but also exhibit markedly different disease trajectories, Dr. Benjamin A. Raby from Brigham and Women's Hospital in Boston and colleagues write in the Journal of Allergy and Clinical Immunology, online March 24. Most classification schemes, though, have limited utility in guiding management strategies or predicting long-term morbidity.

The researchers undertook a phenotype-based cluster analysis of more than 1,000 asthmatic children who participated in the 48-month CAMP trial to determine whether subsets of children would show differing responses to medical therapy.

Spectral analysis of 18 baseline phenotypic characteristics (divided into atopic burden, lung function and airway lability, and baseline exacerbation history) produced five distinct phenotypic clusters.

The largest group of patients (cluster 1, 28.8% of the sample) had the fewest prior exacerbations, the lowest prevalence of atopic features, and preserved lung function; the smallest group (cluster 5, 9.3%) had the most prior exacerbations, a very high atopic burden, and reduced lung function.

Cluster 2 (19.3%) had high atopic burden, preserved lung function, intermediate airways hyperresponsiveness, and a low prior exacerbation rate. Cluster 3 (20.9%) had high atopic burden, the most-compromised lung function, and intermediate prior exacerbations. And cluster 4 (21.6%) was less atopic than cluster 2, had reduced lung function similar to cluster 3, and nearly all had prior hospitalizations for exacerbations.

"It is clear that no single feature is sufficient to characterize these groups," the researchers note.

During four years of follow-up, clusters remained consistent in their phenotypic features, according to the report.

Children in the three "milder" clusters (1, 2, and 3) showed significant reductions in asthma exacerbations with inhaled budesonide treatment, but nedocromil did not significantly reduce exacerbation rates or controller therapy use.

In the most "severe" clusters (4 and 5), however, the therapeutic efficacy of nedocromil was more similar to that of budesonide. In cluster 4, both nedocromil and budesonide brought significant reductions in the exacerbation rate. In cluster 5, however, neither nedocromil nor budesonide brought significant decreases in exacerbation rates.

"Our data suggest that although inhaled corticosteroids, such as budesonide, should serve as the primary treatment choice for asthma control in children with mild-to-moderate asthma, there are several subgroups of patients, including those with the poorest level of baseline asthma control, who appear to respond to nedocromil at levels similar to budesonide," the researchers write.

"The observed between-cluster differences in environmental and genetic factors suggest that important etiologic differences underlie the configuration of different asthma subgroups," they conclude. "Future studies that consider more homogeneous subsets of patients should improve research precision in characterizing the genetic and environmental causes."

"Thus in addition to helping inform clinical management, these more refined phenotypic classification schemes should help accelerate research efforts in defining the molecular and environmental underpinnings of this complex airways disease," the authors add.

Dr. Raby did not respond to a request for comments.

SOURCE: http://bit.ly/1k8aYhh

J Allergy Clin Immunol 2014.

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