TY - JOUR

T1 - Eosinophilic and Noneosinophilic Asthma

T2 - An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort

AU - Heaney, Liam G.

AU - Perez de Llano, Luis

AU - Al-Ahmad, Mona

AU - Backer, Vibeke

AU - Busby, John

AU - Canonica, Giorgio Walter

AU - Christoff, George C.

AU - Cosio, Borja G.

AU - FitzGerald, J. Mark

AU - Heffler, Enrico

AU - Iwanaga, Takashi

AU - Jackson, David J.

AU - Menzies-Gow, Andrew N.

AU - Papadopoulos, Nikolaos G.

AU - Papaioannou, Andriana I.

AU - Pfeffer, Paul E.

AU - Popov, Todor A.

AU - Porsbjerg, Celeste M.

AU - Rhee, Chin Kook

AU - Sadatsafavi, Mohsen

AU - Tohda, Yuji

AU - Wang, Eileen

AU - Wechsler, Michael E.

AU - Alacqua, Marianna

AU - Altraja, Alan

AU - Bjermer, Leif

AU - Björnsdóttir, Unnur S.

AU - Bourdin, Arnaud

AU - Brusselle, Guy G.

AU - Buhl, Roland

AU - Costello, Richard W.

AU - Hew, Mark

AU - Koh, Mariko Siyue

AU - Lehmann, Sverre

AU - Lehtimäki, Lauri

AU - Peters, Matthew

AU - Taillé, Camille

AU - Taube, Christian

AU - Tran, Trung N.

AU - Zangrilli, James

AU - Bulathsinhala, Lakmini

AU - Carter, Victoria A.

AU - Chaudhry, Isha

AU - Eleangovan, Neva

AU - Hosseini, Naeimeh

AU - Kerkhof, Marjan

AU - Murray, Ruth B.

AU - Price, Chris A.

AU - Price, David B.

N1 - Publisher Copyright: © 2021 The Authors

PY - 2021

Y1 - 2021

N2 - Background: Phenotypic characteristics of patients with eosinophilic and noneosinophilic asthma are not well characterized in global, real-life severe asthma cohorts. Research Question: What is the prevalence of eosinophilic and noneosinophilic phenotypes in the population with severe asthma, and can these phenotypes be differentiated by clinical and biomarker variables? Study Design and Methods: This was an historical registry study. Adult patients with severe asthma and available blood eosinophil count (BEC) from 11 countries enrolled in the International Severe Asthma Registry (January 1, 2015-September 30, 2019) were categorized according to likelihood of eosinophilic phenotype using a predefined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic and clinical characteristics were defined at baseline (ie, 1 year before or closest to date of BEC). Results: One thousand seven hundred sixteen patients with prospective data were included; 83.8% were identified as most likely (grade 3), 8.3% were identified as likely (grade 2), and 6.3% identified as least likely (grade 1) to have an eosinophilic phenotype, and 1.6% of patients showed a noneosinophilic phenotype (grade 0). Eosinophilic phenotype patients (ie, grades 2 or 3) showed later asthma onset (29.1 years vs 6.7 years; P < .001) and worse lung function (postbronchodilator % predicted FEV1, 76.1% vs 89.3%; P = .027) than those with a noneosinophilic phenotype. Patients with noneosinophilic phenotypes were more likely to be women (81.5% vs 62.9%; P = .047), to have eczema (20.8% vs 8.5%; P = .003), and to use anti-IgE (32.1% vs 13.4%; P = .004) and leukotriene receptor antagonists (50.0% vs 28.0%; P = .011) add-on therapy. Interpretation: According to this multicomponent, consensus-driven, and evidence-based eosinophil gradient algorithm (using variables readily accessible in real life), the severe asthma eosinophilic phenotype was more prevalent than previously identified and was phenotypically distinct. This pragmatic gradient algorithm uses variables readily accessible in primary and specialist care, addressing inherent issues of phenotype heterogeneity and phenotype instability. Identification of treatable traits across phenotypes should improve therapeutic precision.

AB - Background: Phenotypic characteristics of patients with eosinophilic and noneosinophilic asthma are not well characterized in global, real-life severe asthma cohorts. Research Question: What is the prevalence of eosinophilic and noneosinophilic phenotypes in the population with severe asthma, and can these phenotypes be differentiated by clinical and biomarker variables? Study Design and Methods: This was an historical registry study. Adult patients with severe asthma and available blood eosinophil count (BEC) from 11 countries enrolled in the International Severe Asthma Registry (January 1, 2015-September 30, 2019) were categorized according to likelihood of eosinophilic phenotype using a predefined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic and clinical characteristics were defined at baseline (ie, 1 year before or closest to date of BEC). Results: One thousand seven hundred sixteen patients with prospective data were included; 83.8% were identified as most likely (grade 3), 8.3% were identified as likely (grade 2), and 6.3% identified as least likely (grade 1) to have an eosinophilic phenotype, and 1.6% of patients showed a noneosinophilic phenotype (grade 0). Eosinophilic phenotype patients (ie, grades 2 or 3) showed later asthma onset (29.1 years vs 6.7 years; P < .001) and worse lung function (postbronchodilator % predicted FEV1, 76.1% vs 89.3%; P = .027) than those with a noneosinophilic phenotype. Patients with noneosinophilic phenotypes were more likely to be women (81.5% vs 62.9%; P = .047), to have eczema (20.8% vs 8.5%; P = .003), and to use anti-IgE (32.1% vs 13.4%; P = .004) and leukotriene receptor antagonists (50.0% vs 28.0%; P = .011) add-on therapy. Interpretation: According to this multicomponent, consensus-driven, and evidence-based eosinophil gradient algorithm (using variables readily accessible in real life), the severe asthma eosinophilic phenotype was more prevalent than previously identified and was phenotypically distinct. This pragmatic gradient algorithm uses variables readily accessible in primary and specialist care, addressing inherent issues of phenotype heterogeneity and phenotype instability. Identification of treatable traits across phenotypes should improve therapeutic precision.

KW - Asia

KW - Europe

KW - International Severe Asthma Registry

KW - Middle East

KW - North America

U2 - 10.1016/j.chest.2021.04.013

DO - 10.1016/j.chest.2021.04.013

M3 - Journal article

C2 - 33887242

AN - SCOPUS:85111240890

VL - 160

SP - 814

EP - 830

JO - Chest

JF - Chest

SN - 0012-3692

IS - 3

ER -