Severe Asthma Phenotypes in Children
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1 Severe Asthma Phenotypes in Children Andy Liu, MD Pulmonary Section The Breathing Institute Children s Hospital Colorado University of Colorado Denver School of Medicine The National Jewish Experience: Phenotypes of Severe Asthma in Children Farr RS, Nelson HS. Coping styles in asthma. J Allergy Clin Immunol 1999; 103: Page 1
2 Coping Styles in Severe Asthma in Children Farr RS, Nelson HS. Coping styles in asthma. J Allergy Clin Immunol 1999; 103: Lung Physiologic Phenotypes of Asthma: Morning Dipper Turner-Warwick M. On observing patterns of airflow obstruction in chronic asthma. Br J Dis Chest 1977; 71: Page 2
3 Brittle Asthma Turner-Warwick M. On observing patterns of airflow obstruction in chronic asthma. Br J Dis Chest 1977; 71: Irreversible Turner-Warwick M. On observing patterns of airflow obstruction in chronic asthma. Br J Dis Chest 1977; 71: Page 3
4 The National Jewish Experience: Steroid-Insensitive Asthma 45% improvement in FEV1 7% improvement in FEV1 Chan MT, Leung DYM, Szefler SJ, Spahn JD. Difficult-to-control asthma: characteristics of steroid-insensitive asthma. J Allergy Clin Immunol 1998; 101: Steroid-Insensitive Asthma Non-Chaotic Chaotic Chan MT, Leung DYM, Szefler SJ, Spahn JD. Difficult-to-control asthma: characteristics of steroid-insensitive asthma. J Allergy Clin Immunol 1998; 101: Page 4
5 Asthma Phenotypes in the Inner- City (APIC) Inner- City Asthma Consor9um (NIH NIAID) APIC study participants & their families Investigators G. O Connor (Boston U) M. Kattan (Columbia, NYC) R. Wood (Johns Hopkins, Baltimore) J. Pongracic (Ann & Robert H Lurie Children s Hospital, Chicago) R. Gruchalla (U Texas, Dallas) A. Liu (Natl Jewish, Denver) S. Teach (Children s Natl, D.C.) E. Zoratti (Henry Ford, Detroit) G. Hershey (Children s, Cincinnati) Research staff at sites Rho D. Babineau, R. Krouse, C. Visness, S. Arbes Madison R. Burton, S. Doyle, P. Heinritz, C. Sorkness, J. Gern, W. Busse NIAID P. Gergen, S. Sigelman, A. Togias Funded by: NIAID/NIH (HHSN C, HHSN I, 1 UM1 AI & UM2AI117870) & NCRR/NIH grants (UL1TR000451, UL1TR000075, NCATS/NIH UL1 TR , UL1TR000040, UL1TR000150, and UL1TR001105) Asthma Phenotype- directed Care Uncontrolled Asthma Guidelines-based Management Difficult-to-Control Phenotypes & Causes Easy-to-Control Steroid Resistance Allergic IgE Eos Th2 eno Basophils Obstructive MMP-9/TIMP-1 IL-8 TGF-β - Teach SJ, et al. (PROSE) J Allergy Clin Immunol Exacerbators Cockroach IgE Impaired antiviral (pdc) Oxidant Stress Air pollutants Tobacco smoke Page 5
6 Asthma Phenotypes in the Inner-City Study (APIC) 717 enrolled Ages 6-17 years 619 with 4+ visits (86%) Male 58% Black 64% Hispanic 29% % % 40.9% Pongracic J, et al. (APIC) J Allergy Clin Immunol 2016;138: Asthma Phenotypes in the Inner-City Study Step level assignment Pongracic J, et al. (APIC) J Allergy Clin Immunol 2016;138: Page 6
7 Asthma Phenotypes in the Inner-City (APIC) study (NIH NIAID) 3 approaches to understand asthma phenotypes in inner-city children 1. Distinguishing Difficult-to-Control from Easy-to-Control Asthma (Pongracic) 2. Cluster-derived Phenotypes (Zoratti) 3. Determinants of Asthma Severity via Pathway Analysis (Liu) Pongracic J, et al. (APIC) J Allergy Clin Immunol 2016;138: Zoratti E, et al. (APIC) J Allergy Clin Immunol 2016;138: Liu AH, et al. (APIC) J Allergy Clin Immunol 2016;138: APIC Difficult-to-Control Asthma Controller Step Level by Visit Pongracic J, et al. (APIC) J Allergy Clin Immunol 2016;138: Page 7
8 APIC Difficult-to-Control Asthma Severity & Exacerbations by Calendar Year Pongracic J, et al. (APIC) J Allergy Clin Immunol 2016;138: APIC Difficult-to-Control Asthma Distinguishing Baseline Characteristics Pongracic J, et al. (APIC) J Allergy Clin Immunol 2016;138: Page 8
9 APIC Phenotypes Cluster analysis dendrogram Zoratti E, et al. (APIC) J Allergy Clin Immunol 2016;138: APIC Phenotypes TOTAL N=616 A: 15% N=92 B: 15% N=93 C: 24% N=147 D: 30% N=187 E: 16% N=97 Zoratti E, et al. (APIC) J Allergy Clin Immunol 2016;138: Page 9
10 APIC Cluster Phenotypes: Asthma Severity Zoratti E, et al. (APIC) J Allergy Clin Immunol 2016;138: APIC Cluster Phenotypes: Pulmonary Physiology Zoratti E, et al. (APIC) J Allergy Clin Immunol 2016;138: Page 10
11 APIC Cluster Phenotypes: Allergy Zoratti E, et al. (APIC) J Allergy Clin Immunol 2016;138: APIC Cluster Phenotypes: Allergic Inflammation Zoratti E, et al. (APIC) J Allergy Clin Immunol 2016;138: Page 11
12 APIC Pathways to Asthma Severity Liu AH, et al. (APIC) J Allergy Clin Immunol 2016;138: APIC Pathways to Asthma Severity Literature-based model for Path Analysis Liu AH, et al. (APIC) J Allergy Clin Immunol 2016;138: Page 12
13 APIC Pathways to Asthma Severity Explains 53.4% Variance in Asthma Severity Liu AH, et al. (APIC) J Allergy Clin Immunol 2016;138: APIC Pathways to Asthma Severity Explains 53.4% Variance in Asthma Severity Domain Standardized Total Effect P-value Allergen Sensitization 0.18±0.05 <0.001 Allergic Inflammation 0.22±0.06 <0.001 Environmental Tobacco Smoke 0.30±0.08 <0.001 Vitamin D 0.01± Stress 0.08± Obesity 0.06± Rhinitis Severity 0.48±0.06 <0.001 Impaired Pulmonary Physiology 0.51±0.06 <0.001 Liu AH, et al. (APIC) J Allergy Clin Immunol 2016;138: Page 13
14 APIC Trio Summary Based on guidelines-based management: Difficult-to-Control asthma was most distinguished by bronchodilator response and the ACT/C-ACT test Based on cluster differentiation: - asthma phenotypes were most distinguished by level of allergen sensitization and asthma severity - asthma severity was highest in a highly atopic cluster with impaired pulmonary physiology, and a distinct low-atopy cluster Based on severity pathways: - Greatest contributors to asthma severity were allergy and tobacco smoke exposure, via impaired lung function and rhinitis Asthma Clinical Research Unit (9W) Andy s Office (AP3) AIRE Lab Page 14
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