Classification of childhood asthma phenotypes and long-term clinical responses to inhaled anti-inflammatory medications

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:133

Article

Howrylak, Judie A.¹  Fuhlbrigge, Anne L.^2,3,4  Strunk, Robert C.^5,6  Zeiger, Robert S.^7,8  Weiss, Scott T.^2,3,4  Raby, Benjamin A.^2,3,4 

[1] Penn State Milton S Hershey Med Ctr, Dept Med, Div Pulm Allergy & Crit Care Med, Hershey, PA USA

[2] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA

[3] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Boston, MA USA

[5] Washington Univ, Sch Med, Dept Pediat, Div Allergy & Pulm Med, St Louis, MO 63130 USA

[6] St Louis Childrens Hosp, St Louis, MO USA

[7] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA

[8] Kaiser Permanente, Dept Allergy, San Diego, CA USA

关键词: Childhood asthma;    asthma phenotypes;    inhaled corticosteroids;    cluster analysis;    asthma classification;    longitudinal study;   

DOI  :  10.1016/j.jaci.2014.02.006

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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