Eosinophilic and Noneosinophilic Asthma: An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort

Liam G Heaney; Luis Perez de Llano; Mona Al-Ahmad; Vibeke Backer; John Busby; Giorgio Walter Canonica; George C Christoff; Borja G Cosio; J Mark FitzGerald; Enrico Heffler; Takashi Iwanaga; David J Jackson; Andrew N Menzies-Gow; Nikolaos G Papadopoulos; Andriana I Papaioannou; Paul E Pfeffer; Todor A Popov; Celeste M Porsbjerg; Chin Kook Rhee; Mohsen Sadatsafavi; Yuji Tohda; Eileen Wang; Michael E Wechsler; Marianna Alacqua; Alan Altraja; Leif Bjermer; Unnur S Björnsdóttir; Arnaud Bourdin; Guy G Brusselle; Roland Buhl; Richard W Costello; Mark Hew; Mariko Koh Siyue; Sverre Lehmann; Lauri Lehtimäki; Matthew Peters; Camille Taillé; Christian Taube; Trung N Tran; James Zangrilli; Lakmini Bulathsinhala; Victoria A Carter; Isha Chaudhry; Neva Eleangovan; Naeimeh Hosseini; Marjan Kerkhof; Ruth B Murray; Chris A Price; David B Price

doi:10.1016/j.chest.2021.04.013

Eosinophilic and Noneosinophilic Asthma: An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort

Liam G Heaney, Luis Perez de Llano, Mona Al-Ahmad, Vibeke Backer, John Busby, Giorgio Walter Canonica, George C Christoff, Borja G Cosio, J Mark FitzGerald, Enrico Heffler, Takashi Iwanaga, David J Jackson, Andrew N Menzies-Gow, Nikolaos G Papadopoulos, Andriana I Papaioannou, Paul E Pfeffer, Todor A Popov, Celeste M Porsbjerg, Chin Kook Rhee, Mohsen SadatsafaviYuji Tohda, Eileen Wang, Michael E Wechsler, Marianna Alacqua, Alan Altraja, Leif Bjermer, Unnur S Björnsdóttir, Arnaud Bourdin, Guy G Brusselle, Roland Buhl, Richard W Costello, Mark Hew, Mariko Koh Siyue, Sverre Lehmann, Lauri Lehtimäki, Matthew Peters, Camille Taillé, Christian Taube, Trung N Tran, James Zangrilli, Lakmini Bulathsinhala, Victoria A Carter, Isha Chaudhry, Neva Eleangovan, Naeimeh Hosseini, Marjan Kerkhof, Ruth B Murray, Chris A Price, David B Price

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Abstract

BACKGROUND: Phenotypic characteristics of eosinophilic and non-eosinophilic asthma patients are not well-characterized in global, real life severe asthma cohorts.

RESEARCH QUESTION: What is the prevalence of eosinophilic and non-eosinophilic phenotypes in the severe asthma population, and can they be differentiated by clinical and biomarker variables?

STUDY DESIGN AND METHODS: This was an historical, registry study. Adult severe asthma patients with available blood eosinophil count (BEC) from 11 countries enrolled into the International Severe Asthma Registry (01/01/2015 to 09/30/2019) were categorized according to likelihood of eosinophilic phenotype using a pre-defined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic/clinical characteristics were defined at baseline (i.e. 1-year prior or closest to date of BEC).

RESULTS: 1,716 patients with prospective data were included; 83.8% were identified as "most likely" (Grade 3), 8.3% were "likely" (Grade 2), and 6.3% "least likely" (Grade 1) to have an eosinophilic phenotype. 1.6% of patients had a non-eosinophilic phenotype (Grade 0). Eosinophilic phenotype patients (i.e. Grade 2 or 3) had later asthma onset (29.1 vs 6.7 yrs; p<0.001), and worse lung function (post-bronchodilator % predicted FEV1: 76.1% vs 89.3%; p=0.027) than those with a non-eosinophilic phenotype. Non-eosinophilic-phenotype patients were more likely to be female (81.5% vs 62.9%; p=0.047), have eczema (20.8% vs 8.5%; p=0.003) and use anti-IgE (32.1% vs 13.4%; p=0.004) and leukotriene receptor antagonists (50.0% vs 28.0%; p=0.011) add-on therapy.

INTERPRETATION: According to this multi-component, 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 phenotypically distinct. This pragmatic gradient algorithm utilizes 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.

Original language	English
Pages (from-to)	814-830
Journal	Chest
Volume	160
Issue number	3
Early online date	19 Apr 2021
DOIs	https://doi.org/10.1016/j.chest.2021.04.013
Publication status	Published - Sept 2021

Keywords

Asia
Europe
International Severe Asthma Registry
Middle East
North America

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Eosinophilic and Noneosinophilic Asthma: An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort
Copyright 2021 the authors. This is an open access article published under a Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits distribution and reproduction for non-commercial purposes, provided the author and source are cited
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Heaney, L. G., Perez de Llano, L., Al-Ahmad, M., Backer, V., Busby, J., Canonica, G. W., Christoff, G. C., Cosio, B. G., FitzGerald, J. M., Heffler, E., Iwanaga, T., Jackson, D. J., Menzies-Gow, A. N., Papadopoulos, N. G., Papaioannou, A. I., Pfeffer, P. E., Popov, T. A., Porsbjerg, C. M., Rhee, C. K., ... Price, D. B. (2021). Eosinophilic and Noneosinophilic Asthma: An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort. Chest, 160(3), 814-830. https://doi.org/10.1016/j.chest.2021.04.013

@article{ba31346cff4c44f997ebd3483b203f2e,

title = "Eosinophilic and Noneosinophilic Asthma: An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort",

abstract = "BACKGROUND: Phenotypic characteristics of eosinophilic and non-eosinophilic asthma patients are not well-characterized in global, real life severe asthma cohorts.RESEARCH QUESTION: What is the prevalence of eosinophilic and non-eosinophilic phenotypes in the severe asthma population, and can they be differentiated by clinical and biomarker variables?STUDY DESIGN AND METHODS: This was an historical, registry study. Adult severe asthma patients with available blood eosinophil count (BEC) from 11 countries enrolled into the International Severe Asthma Registry (01/01/2015 to 09/30/2019) were categorized according to likelihood of eosinophilic phenotype using a pre-defined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic/clinical characteristics were defined at baseline (i.e. 1-year prior or closest to date of BEC).RESULTS: 1,716 patients with prospective data were included; 83.8% were identified as {"}most likely{"} (Grade 3), 8.3% were {"}likely{"} (Grade 2), and 6.3% {"}least likely{"} (Grade 1) to have an eosinophilic phenotype. 1.6% of patients had a non-eosinophilic phenotype (Grade 0). Eosinophilic phenotype patients (i.e. Grade 2 or 3) had later asthma onset (29.1 vs 6.7 yrs; p<0.001), and worse lung function (post-bronchodilator % predicted FEV1: 76.1% vs 89.3%; p=0.027) than those with a non-eosinophilic phenotype. Non-eosinophilic-phenotype patients were more likely to be female (81.5% vs 62.9%; p=0.047), have eczema (20.8% vs 8.5%; p=0.003) and use anti-IgE (32.1% vs 13.4%; p=0.004) and leukotriene receptor antagonists (50.0% vs 28.0%; p=0.011) add-on therapy.INTERPRETATION: According to this multi-component, 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 phenotypically distinct. This pragmatic gradient algorithm utilizes 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.",

keywords = "Asia, Europe, International Severe Asthma Registry, Middle East, North America",

author = "Heaney, {Liam G} and {Perez de Llano}, Luis and Mona Al-Ahmad and Vibeke Backer and John Busby and Canonica, {Giorgio Walter} and Christoff, {George C} and Cosio, {Borja G} and FitzGerald, {J Mark} and Enrico Heffler and Takashi Iwanaga and Jackson, {David J} and Menzies-Gow, {Andrew N} and Papadopoulos, {Nikolaos G} and Papaioannou, {Andriana I} and Pfeffer, {Paul E} and Popov, {Todor A} and Porsbjerg, {Celeste M} and Rhee, {Chin Kook} and Mohsen Sadatsafavi and Yuji Tohda and Eileen Wang and Wechsler, {Michael E} and Marianna Alacqua and Alan Altraja and Leif Bjermer and Bj{\"o}rnsd{\'o}ttir, {Unnur S} and Arnaud Bourdin and Brusselle, {Guy G} and Roland Buhl and Costello, {Richard W} and Mark Hew and Siyue, {Mariko Koh} and Sverre Lehmann and Lauri Lehtim{\"a}ki and Matthew Peters and Camille Taill{\'e} and Christian Taube and Tran, {Trung N} and James Zangrilli and Lakmini Bulathsinhala and Carter, {Victoria A} and Isha Chaudhry and Neva Eleangovan and Naeimeh Hosseini and Marjan Kerkhof and Murray, {Ruth B} and Price, {Chris A} and Price, {David B}",

note = "Copyright {\textcopyright} 2021. Published by Elsevier Inc.",

year = "2021",

month = sep,

doi = "10.1016/j.chest.2021.04.013",

language = "English",

volume = "160",

pages = "814--830",

journal = "Chest",

issn = "0012-3692",

publisher = "Elsevier Inc.",

number = "3",

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Heaney, LG, Perez de Llano, L, Al-Ahmad, M, Backer, V, Busby, J, Canonica, GW, Christoff, GC, Cosio, BG, FitzGerald, JM, Heffler, E, Iwanaga, T, Jackson, DJ, Menzies-Gow, AN, Papadopoulos, NG, Papaioannou, AI, Pfeffer, PE, Popov, TA, Porsbjerg, CM, Rhee, CK, Sadatsafavi, M, Tohda, Y, Wang, E, Wechsler, ME, Alacqua, M, Altraja, A, Bjermer, L, Björnsdóttir, US, Bourdin, A, Brusselle, GG, Buhl, R, Costello, RW, Hew, M, Siyue, MK, Lehmann, S, Lehtimäki, L, Peters, M, Taillé, C, Taube, C, Tran, TN, Zangrilli, J, Bulathsinhala, L, Carter, VA, Chaudhry, I, Eleangovan, N, Hosseini, N, Kerkhof, M, Murray, RB, Price, CA & Price, DB 2021, 'Eosinophilic and Noneosinophilic Asthma: An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort', Chest, vol. 160, no. 3, pp. 814-830. https://doi.org/10.1016/j.chest.2021.04.013

TY - JOUR

T1 - Eosinophilic and Noneosinophilic Asthma: 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 - Siyue, Mariko Koh

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

PY - 2021/9

Y1 - 2021/9

N2 - BACKGROUND: Phenotypic characteristics of eosinophilic and non-eosinophilic asthma patients are not well-characterized in global, real life severe asthma cohorts.RESEARCH QUESTION: What is the prevalence of eosinophilic and non-eosinophilic phenotypes in the severe asthma population, and can they be differentiated by clinical and biomarker variables?STUDY DESIGN AND METHODS: This was an historical, registry study. Adult severe asthma patients with available blood eosinophil count (BEC) from 11 countries enrolled into the International Severe Asthma Registry (01/01/2015 to 09/30/2019) were categorized according to likelihood of eosinophilic phenotype using a pre-defined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic/clinical characteristics were defined at baseline (i.e. 1-year prior or closest to date of BEC).RESULTS: 1,716 patients with prospective data were included; 83.8% were identified as "most likely" (Grade 3), 8.3% were "likely" (Grade 2), and 6.3% "least likely" (Grade 1) to have an eosinophilic phenotype. 1.6% of patients had a non-eosinophilic phenotype (Grade 0). Eosinophilic phenotype patients (i.e. Grade 2 or 3) had later asthma onset (29.1 vs 6.7 yrs; p<0.001), and worse lung function (post-bronchodilator % predicted FEV1: 76.1% vs 89.3%; p=0.027) than those with a non-eosinophilic phenotype. Non-eosinophilic-phenotype patients were more likely to be female (81.5% vs 62.9%; p=0.047), have eczema (20.8% vs 8.5%; p=0.003) and use anti-IgE (32.1% vs 13.4%; p=0.004) and leukotriene receptor antagonists (50.0% vs 28.0%; p=0.011) add-on therapy.INTERPRETATION: According to this multi-component, 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 phenotypically distinct. This pragmatic gradient algorithm utilizes 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 eosinophilic and non-eosinophilic asthma patients are not well-characterized in global, real life severe asthma cohorts.RESEARCH QUESTION: What is the prevalence of eosinophilic and non-eosinophilic phenotypes in the severe asthma population, and can they be differentiated by clinical and biomarker variables?STUDY DESIGN AND METHODS: This was an historical, registry study. Adult severe asthma patients with available blood eosinophil count (BEC) from 11 countries enrolled into the International Severe Asthma Registry (01/01/2015 to 09/30/2019) were categorized according to likelihood of eosinophilic phenotype using a pre-defined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic/clinical characteristics were defined at baseline (i.e. 1-year prior or closest to date of BEC).RESULTS: 1,716 patients with prospective data were included; 83.8% were identified as "most likely" (Grade 3), 8.3% were "likely" (Grade 2), and 6.3% "least likely" (Grade 1) to have an eosinophilic phenotype. 1.6% of patients had a non-eosinophilic phenotype (Grade 0). Eosinophilic phenotype patients (i.e. Grade 2 or 3) had later asthma onset (29.1 vs 6.7 yrs; p<0.001), and worse lung function (post-bronchodilator % predicted FEV1: 76.1% vs 89.3%; p=0.027) than those with a non-eosinophilic phenotype. Non-eosinophilic-phenotype patients were more likely to be female (81.5% vs 62.9%; p=0.047), have eczema (20.8% vs 8.5%; p=0.003) and use anti-IgE (32.1% vs 13.4%; p=0.004) and leukotriene receptor antagonists (50.0% vs 28.0%; p=0.011) add-on therapy.INTERPRETATION: According to this multi-component, 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 phenotypically distinct. This pragmatic gradient algorithm utilizes 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 - Article

C2 - 33887242

SN - 0012-3692

VL - 160

SP - 814

EP - 830

JO - Chest

JF - Chest

IS - 3

ER -

Eosinophilic and Noneosinophilic Asthma: An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort

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