Classification of childhood asthma phenotypes and long-term clinical responses to inhaled anti-inflammatory medications Judie A. Howrylak, MD, Anne L.

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Presentation transcript:

Classification of childhood asthma phenotypes and long-term clinical responses to inhaled anti-inflammatory medications Judie A. Howrylak, MD, Anne L. Fuhlbrigge, MD, Robert C. Strunk, MD, Robert S. Zeiger, MD, Scott T. Weiss, MD, Benjamin A. Raby, MD Journal of Allergy and Clinical Immunology Volume 133, Issue 5, Pages 1289-1300.e12 (May 2014) DOI: 10.1016/j.jaci.2014.02.006 Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Kaplan-Meier plots by cluster of the cumulative probability of a first course of prednisone (A) or initiation of additional asthma controller therapies (beclomethasone or other; B) during the 4-year follow-up period of the CAMP trial. Journal of Allergy and Clinical Immunology 2014 133, 1289-1300.e12DOI: (10.1016/j.jaci.2014.02.006) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Mean pulmonary function measurements for each phenotypic cluster evaluated over 48 months of follow-up. P values for between-cluster differences among all longitudinal measures were less than .0001, as calculated by using linear mixed-effects models. Journal of Allergy and Clinical Immunology 2014 133, 1289-1300.e12DOI: (10.1016/j.jaci.2014.02.006) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Kaplan-Meier estimate by treatment group of the cumulative probability of prednisone use during 4 years of follow-up stratified by phenotypic cluster. B, Budesonide; N, Nedocromil. Journal of Allergy and Clinical Immunology 2014 133, 1289-1300.e12DOI: (10.1016/j.jaci.2014.02.006) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 A, The gap statistic as a function of the number of clusters. A higher gap statistic indicates greater between-cluster separation. B, Heat map depicting the differences among normalized clinical variables used for clustering and the different phenotypic clusters. The cluster assignments are grouped along the horizontal axis, and the variables used to determine the cluster assignments appear along the vertical axis. The lighter shades of blue denote relatively higher magnitudes for each variable, and the darker shades denote relatively lower magnitudes. *P < .0001 for difference in distribution across clusters. Variables demonstrating more distinct between-cluster differences in magnitude, such as hospital history, AD, PC20, and hay fever history, were the primary drivers of the cluster assignments. BD, Bronchodilator. Journal of Allergy and Clinical Immunology 2014 133, 1289-1300.e12DOI: (10.1016/j.jaci.2014.02.006) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Kaplan-Meier plots by cluster of the cumulative probability of a first course of prednisone during the 4-year follow-up period of the CAMP trial. Clusters were determined based on a single clinical variable indicated at the top of each figure. Journal of Allergy and Clinical Immunology 2014 133, 1289-1300.e12DOI: (10.1016/j.jaci.2014.02.006) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Kaplan-Meier plots by cluster of the cumulative probability of a first course of prednisone during the 4-year follow-up period of the CAMP trial. Clusters were determined based on a single clinical variable indicated at the top of each figure. Journal of Allergy and Clinical Immunology 2014 133, 1289-1300.e12DOI: (10.1016/j.jaci.2014.02.006) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Comparison of phenotypic clusters generated by means of hierarchical clustering (new clusters) versus spectral clustering (old clusters). A, Comparison of study subject cluster assignments. B, Survival analysis for time to first use of prednisone (left) and time to use of additional asthma controller therapy (right) for hierarchical clusters. Journal of Allergy and Clinical Immunology 2014 133, 1289-1300.e12DOI: (10.1016/j.jaci.2014.02.006) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions