Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 133, Issue 5, Pages 1289-U494Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2014.02.006
Keywords
Childhood asthma; asthma phenotypes; inhaled corticosteroids; cluster analysis; asthma classification; longitudinal study
Categories
Funding
- National Heart, Lung, and Blood Institute (NHLBI)
- General Clinical Research Center [M01RR00051, M01RR0099718-24, M01RR02719-14, RR00036]
- National Center for Research Resources
- NHLBI/ National Institutes of Health [R01-086601, R01-093076, RC2-HL101543.]
- [NO1-HR16044]
- [16045]
- [16046]
- [16047]
- [16048]
- [16049]
- [16050]
- [16051]
- [16052]
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Background: Although recent studies have identified the presence of phenotypic clusters in asthmatic patients, the clinical significance and temporal stability of these clusters have not been explored. Objective: Our aim was to examine the clinical relevance and temporal stability of phenotypic clusters in children with asthma. Methods: We applied spectral clustering to clinical data from 1041 children with asthma participating in the Childhood Asthma Management Program. Posttreatment randomization follow-up data collected over 48 months were used to determine the effect of these clusters on pulmonary function and treatment response to inhaled anti-inflammatory medication. Results: We found 5 reproducible patient clusters that could be differentiated on the basis of 3 groups of features: atopic burden, degree of airway obstruction, and history of exacerbation. Cluster grouping predicted long-term asthma control, as measured by the need for oral prednisone (P <.0001) or additional controller medications (P =.001), as well as longitudinal differences in pulmonary function (P <.0001). We also found that the 2 clusters with the highest rates of exacerbation had different responses to inhaled corticosteroids when compared with the other clusters. One cluster demonstrated a positive response to both budesonide (P =.02) and nedocromil (P =.01) compared with placebo, whereas the other cluster demonstrated minimal responses to both budesonide (P =.12) and nedocromil (P =.56) compared with placebo. Conclusion: Phenotypic clustering can be used to identify longitudinally consistent and clinically relevant patient subgroups, with implications for targeted therapeutic strategies and clinical trials design.
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