Michael Schatz1, Jin-Wen Y Hsu2, Robert S Zeiger2, Wansu Chen2, Alejandro Dorenbaum3, Bradley E Chipps4, Tmirah Haselkorn3. 1. Departments of Allergy and of Research and Evaluation, Kaiser Permanente Southern California, San Diego and Pasadena, Calif. Electronic address: michael.x.schatz@kp.org. 2. Departments of Allergy and of Research and Evaluation, Kaiser Permanente Southern California, San Diego and Pasadena, Calif. 3. US Medical Affairs, Genentech Inc, South San Francisco, Calif. 4. Capital Allergy and Respiratory Disease Center, Sacramento, Calif.
Abstract
BACKGROUND: Asthma phenotyping can facilitate understanding of disease pathogenesis and potential targeted therapies. OBJECTIVE: To further characterize the distinguishing features of phenotypic groups in difficult-to-treat asthma. METHODS: Children ages 6-11 years (n = 518) and adolescents and adults ages ≥12 years (n = 3612) with severe or difficult-to-treat asthma from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study were evaluated in this post hoc cluster analysis. Analyzed variables included sex, race, atopy, age of asthma onset, smoking (adolescents and adults), passive smoke exposure (children), obesity, and aspirin sensitivity. Cluster analysis used the hierarchical clustering algorithm with the Ward minimum variance method. The results were compared among clusters by χ(2) analysis; variables with significant (P < .05) differences among clusters were considered as distinguishing feature candidates. Associations among clusters and asthma-related health outcomes were assessed in multivariable analyses by adjusting for socioeconomic status, environmental exposures, and intensity of therapy. RESULTS: Five clusters were identified in each age stratum. Sex, atopic status, and nonwhite race were distinguishing variables in both strata; passive smoke exposure was distinguishing in children and aspirin sensitivity in adolescents and adults. Clusters were not related to outcomes in children, but 2 adult and adolescent clusters distinguished by nonwhite race and aspirin sensitivity manifested poorer quality of life (P < .0001), and the aspirin-sensitive cluster experienced more frequent asthma exacerbations (P < .0001). CONCLUSION: Distinct phenotypes appear to exist in patients with severe or difficult-to-treat asthma, which is related to outcomes in adolescents and adults but not in children. The study of the therapeutic implications of these phenotypes is warranted.
BACKGROUND:Asthma phenotyping can facilitate understanding of disease pathogenesis and potential targeted therapies. OBJECTIVE: To further characterize the distinguishing features of phenotypic groups in difficult-to-treat asthma. METHODS:Children ages 6-11 years (n = 518) and adolescents and adults ages ≥12 years (n = 3612) with severe or difficult-to-treat asthma from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study were evaluated in this post hoc cluster analysis. Analyzed variables included sex, race, atopy, age of asthma onset, smoking (adolescents and adults), passive smoke exposure (children), obesity, and aspirin sensitivity. Cluster analysis used the hierarchical clustering algorithm with the Ward minimum variance method. The results were compared among clusters by χ(2) analysis; variables with significant (P < .05) differences among clusters were considered as distinguishing feature candidates. Associations among clusters and asthma-related health outcomes were assessed in multivariable analyses by adjusting for socioeconomic status, environmental exposures, and intensity of therapy. RESULTS: Five clusters were identified in each age stratum. Sex, atopic status, and nonwhite race were distinguishing variables in both strata; passive smoke exposure was distinguishing in children and aspirin sensitivity in adolescents and adults. Clusters were not related to outcomes in children, but 2 adult and adolescent clusters distinguished by nonwhite race and aspirin sensitivity manifested poorer quality of life (P < .0001), and the aspirin-sensitive cluster experienced more frequent asthma exacerbations (P < .0001). CONCLUSION: Distinct phenotypes appear to exist in patients with severe or difficult-to-treat asthma, which is related to outcomes in adolescents and adults but not in children. The study of the therapeutic implications of these phenotypes is warranted.
Authors: Arlene M Butz; Melissa Bellin; Mona Tsoukleris; Shawna S Mudd; Joan Kub; Jean Ogborn; Tricia Morphew; Cassia Lewis-Land; Mary Elizabeth Bollinger Journal: J Allergy Clin Immunol Pract Date: 2017-09-22