Gruchalla, MD, PhD, FAAAAI7, Meyer Kattan, MD8, Stephen J. Teach, MD9 ... Chapel Hill, NC, 3Ann and Robert H. Lurie Children's Hospital of. Chicago ...
Abstracts AB103
J ALLERGY CLIN IMMUNOL VOLUME 137, NUMBER 2
Levels of Allergy Cluster with Asthma Severity in Inner-City Children.
Edward M. Zoratti, MD, FAAAAI1, Rebecca A. Zabel, MS2, Denise C. Babineau, PhD2, Jacqueline A. Pongracic, MD FAAAAI3, George T. O’Connor, MD4, Robert A. Wood, MD FAAAAI5, Gurjit K. Khurana Hershey, MD, PhD, FAAAAI6, Carolyn Kercsmar, MD6, Rebecca S. Gruchalla, MD, PhD, FAAAAI7, Meyer Kattan, MD8, Stephen J. Teach, MD9, Samuel J. Arbes, Jr2, Cynthia Visness, PhD, MPH2, William W. Busse, MD, FAAAAI10, Peter J. Gergen, MD, MPH11, Alkis Togias, MD, FAAAAI11, Andrew H. Liu, MD, FAAAAI12,13; 1Henry Ford Health System, Detroit, MI, 2Rho Federal Systems Division Inc., Chapel Hill, NC, 3Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, 4Boston University School of Medicine, Boston, MA, 5Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, 6Cincinnati Children’s Hospital, Cincinnati, OH, 7UT Southwestern Medical Center, Dallas, TX, 8NewYork-Presbyterian/Columbia, New York, NY, 9Children’s National Health System, Washington, DC, 10University of Wisconsin School of Medicine and Public Health, Madison, WI, 11NIAID/NIH, Bethesda, MD, 12National Jewish Health, Denver, CO, 13Children’s Hospital Colorado, Aurora, CO. RATIONALE: Phenotypic characterization of asthma among urban youth is lacking. Using unsupervised clustering techniques, we identified distinct asthma phenotypes in inner-city children who received one year of guidelines-based asthma management. METHODS: Nine sites in the NIAID-funded Inner City Asthma Consortium enrolled 717 children aged 6-17 years with mild to severe asthma. Data were collected at baseline and every 2 months for 1 year. Hierarchical cluster analysis was performed in participants completing >4 follow-up visits. Clusters were generated using 52 baseline characterization variables plus 12 longitudinal clinical variables reflecting lung function, asthma symptoms, exacerbations and controller treatment over 1 year. Univariate comparisons were used to determine distinguishing characteristics among clusters. RESULTS: 616 participants were eligible for analysis (58% male, 64% Black non-Hispanic, 29% Hispanic, 7% other). Four distinct clusters were characterized by differences in indicators of asthma severity, including level of controller therapy, prednisone use, bronchial hyperresponsiveness and lung function. Laboratory and clinical indicators of allergy were increased in the phenotypes with higher asthma severity. The cluster reflecting the most severe asthma included the highest proportions of selfreported eczema (77%) and food allergy (62%), along with the highest serum total IgE levels (geometric mean 763 kU/L), number of allergic sensitizations (median 15 of 20 allergens evaluated), exhaled nitric oxide levels (geometric mean 27.4 ppb), and peripheral blood eosinophil counts (median 400/microliter). CONCLUSIONS: Severe asthma phenotypes among inner city children exhibit high levels of allergy. Treatment and environmental control of allergy may be particularly important for optimal management of asthma in this population.
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The Identification and Description of Severe Asthma Patients in a Cross-Sectional Study the Ideal Study
Robert Y. Suruki, Sc.D.1, Necdet Gunsoy, PhD2, Ji-Yeon Shin3, Jonas Daugherty4, Linda Nelsen5, Eric Bradford, MD6, Frank C. Albers, MD, PhD7; 1GlaxoSmithKline, Worldwide Epidemiology, Research Triangle Park, NC, 2GlaxoSmithKline, Clinical Statistics, Stockley Park, United Kingdom, 3GlaxoSmithKline, South Korea, 4PAREXEL, Value Outcomes and Epidemiology, Research Triangle Park, NC, 5GlaxoSmithKline, King of Prussia, PA, 6GlaxoSmithKline, Respiratory R&D, Research Triangle Park, NC, 7GlaxoSmithKline, Respiratory Medical Franchise, Research Triangle Park, NC. RATIONALE: Studies have shown that mepolizumab (anti-IL5), reslizumab (anti-IL5), and omalizumab (anti-IgE) are effective treatments for
asthma in patients with overlapping phenotypic characteristics. The IDEAL study described the eligibility for treatment with these biologics for asthma according to label criteria or study protocols that will form the basis for approved labeling. METHODS: This cross-sectional, single-visit, non-drug interventional _12 years with severe asthma study in 6 countries included subjects aged > defined according to ATS/ERS guidelines by treatment with high-dose ICS _12 months. Assessments included a blood plus additional controller(s) for > sample, spirometry, and symptom/burden of illness questionnaires. RESULTS: 748 subjects were enrolled, of which 670 met analysis criteria (mean age550.5 years; 62% female). After exclusion of patients currently treated with omalizumab, 502 subjects were included in this analysis. 101 (20.1% [95% Exact CI: 16.7-23.9]) were eligible for mepolizumab and 107 (21.3% [17.8-25.2]) were eligible for omalizumab by US label criteria. 28 subjects (5.6% [3.7-8.0]) were eligible for reslizumab. Among 101 mepolizumab eligible subjects, 37 (36.6% [27.3-46.8]) were also eligible for omalizumab and 18 (17.8% [10.9-26.7]) for reslizumab. CONCLUSIONS: In this severe asthma population defined by high-dose ICS use plus a controller(s) not currently taking omalizumab, one-fifth are mepolizumab-eligible (i.e., uncontrolled with eosinophilic inflammation). In those mepolizumab eligible subjects, about one-third may also be eligible for omalizumab; this is equivalent to 7.4% of the severe asthma patient population not currently treated with omalizumab. These data highlight a high unmet need in this uncontrolled population that is currently underserved by existing therapies. (Funded by GSK; 201722/ NCT02293265).
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The C159T Polymorphism of the CD-14 Gene in Adult Patients with Corticosteroid-Sensitive and Refractory Bronchial Asthma in Crimea, Ukraine
Yuri Bisyuk1, Andrey I. Kurchenko1, A. I. Dubovyi2, Ganna V. Bisyuk1, Lawrence M. DuBuske, MD, FAAAAI3,4; 1Bogomolets National Medical University, Kiev, Ukraine, 2Crimean State Medical University, Simferopol, Ukraine, 3George Washington University School of Medicine, Washington, DC, 4Immunology Research Institute of New England, Gardner, MA. RATIONALE: C-to-T transition has been identified at position 159 in the promoter region of the CD14 gene. This functional single-nucleotide polymorphism, C159T has been associated with asthma and allergic rhinitis in various ethnic populations. This association has not yet been confirmed in patients with refractory or corticosteroid-sensitive asthma in Ukrainian population. METHODS: C159T polymorphism of CD-14 receptor gene was assessed in 40 patients with refractory and 291 with corticosteroid-sensitive asthma. The control group included 285 non-atopic volunteers. Single nucleotide polymorphism of C159T was detected by PCR. Patients and volunteers were recruited at the Crimean State Medical University, Simferopol, Crimea, Ukraine. RESULTS: In the control group, the frequency distribution of genotypes (CC – 97 (34%), CT – 146 (51%), TT – 42 (15%)) was not significantly different from asthma with refractory (CC – 21 (52%), CT– 14 (35%), TT – 5 (13%), x2 5 5.292, p 5 0.070) versus corticosteroid-sensitive (CC – 84 (29%), CT – 155 (53%), TT – 52 (18%), x2 5 2.204, p 5 0.332) phenotypes. The risk analysis for the T allele ([SS][CT+TT]) showed that the frequency of the genotype CT + TT in patients with refractory asthma (49%) was significantly lower (OR 5 0.467, CI 5 [0.240-0.910], x2 5 5.17, p 5 0.023) compared to the control group (66%). CONCLUSIONS: The C159T polymorphism of CD14 is associated with refractory asthma in the Crimean population of Ukraine.
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