Identification of airway mucosal type 2 inflammation by using clinical biomarkers in asthmatic patients
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Identification of airway mucosal type 2 inflammation by using clinical biomarkers in asthmatic patients. / Silkoff, Philip E; Laviolette, Michel; Singh, Dave; FitzGerald, J Mark; Kelsen, Steven; Backer, Vibeke; Porsbjerg, Celeste M; Girodet, Pierre-Olivier; Berger, Patrick; Kline, Joel N; Chupp, Geoffrey; Susulic, Vedrana S; Barnathan, Elliot S; Baribaud, Frédéric; Loza, Matthew J; Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study investigators.
I: Journal of Allergy and Clinical Immunology, Bind 140, Nr. 3, 2017, s. 710-719.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Identification of airway mucosal type 2 inflammation by using clinical biomarkers in asthmatic patients
AU - Silkoff, Philip E
AU - Laviolette, Michel
AU - Singh, Dave
AU - FitzGerald, J Mark
AU - Kelsen, Steven
AU - Backer, Vibeke
AU - Porsbjerg, Celeste M
AU - Girodet, Pierre-Olivier
AU - Berger, Patrick
AU - Kline, Joel N
AU - Chupp, Geoffrey
AU - Susulic, Vedrana S
AU - Barnathan, Elliot S
AU - Baribaud, Frédéric
AU - Loza, Matthew J
AU - Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study investigators
N1 - Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.
PY - 2017
Y1 - 2017
N2 - BACKGROUND: The Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study profiled patients with mild, moderate, and severe asthma and nonatopic healthy control subjects.OBJECTIVE: We explored this data set to define type 2 inflammation based on airway mucosal IL-13-driven gene expression and how this related to clinically accessible biomarkers.METHODS: IL-13-driven gene expression was evaluated in several human cell lines. We then defined type 2 status in 25 healthy subjects, 28 patients with mild asthma, 29 patients with moderate asthma, and 26 patients with severe asthma based on airway mucosal expression of (1) CCL26 (the most differentially expressed gene), (2) periostin, or (3) a multigene IL-13 in vitro signature (IVS). Clinically accessible biomarkers included fraction of exhaled nitric oxide (Feno) values, blood eosinophil (bEOS) counts, serum CCL26 expression, and serum CCL17 expression.RESULTS: Expression of airway mucosal CCL26, periostin, and IL-13-IVS all facilitated segregation of subjects into type 2-high and type 2-low asthmatic groups, but in the ADEPT study population CCL26 expression was optimal. All subjects with high airway mucosal CCL26 expression and moderate-to-severe asthma had Feno values (≥35 ppb) and/or high bEOS counts (≥300 cells/mm3) compared with a minority (36%) of subjects with low airway mucosal CCL26 expression. A combination of Feno values, bEOS counts, and serum CCL17 and CCL26 expression had 100% positive predictive value and 87% negative predictive value for airway mucosal CCL26-high status. Clinical variables did not differ between subjects with type 2-high and type 2-low status. Eosinophilic inflammation was associated with but not limited to airway mucosal type 2 gene expression.CONCLUSION: A panel of clinical biomarkers accurately classified type 2 status based on airway mucosal CCL26, periostin, or IL-13-IVS gene expression. Use of Feno values, bEOS counts, and serum marker levels (eg, CCL26 and CCL17) in combination might allow patient selection for novel type 2 therapeutics.
AB - BACKGROUND: The Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study profiled patients with mild, moderate, and severe asthma and nonatopic healthy control subjects.OBJECTIVE: We explored this data set to define type 2 inflammation based on airway mucosal IL-13-driven gene expression and how this related to clinically accessible biomarkers.METHODS: IL-13-driven gene expression was evaluated in several human cell lines. We then defined type 2 status in 25 healthy subjects, 28 patients with mild asthma, 29 patients with moderate asthma, and 26 patients with severe asthma based on airway mucosal expression of (1) CCL26 (the most differentially expressed gene), (2) periostin, or (3) a multigene IL-13 in vitro signature (IVS). Clinically accessible biomarkers included fraction of exhaled nitric oxide (Feno) values, blood eosinophil (bEOS) counts, serum CCL26 expression, and serum CCL17 expression.RESULTS: Expression of airway mucosal CCL26, periostin, and IL-13-IVS all facilitated segregation of subjects into type 2-high and type 2-low asthmatic groups, but in the ADEPT study population CCL26 expression was optimal. All subjects with high airway mucosal CCL26 expression and moderate-to-severe asthma had Feno values (≥35 ppb) and/or high bEOS counts (≥300 cells/mm3) compared with a minority (36%) of subjects with low airway mucosal CCL26 expression. A combination of Feno values, bEOS counts, and serum CCL17 and CCL26 expression had 100% positive predictive value and 87% negative predictive value for airway mucosal CCL26-high status. Clinical variables did not differ between subjects with type 2-high and type 2-low status. Eosinophilic inflammation was associated with but not limited to airway mucosal type 2 gene expression.CONCLUSION: A panel of clinical biomarkers accurately classified type 2 status based on airway mucosal CCL26, periostin, or IL-13-IVS gene expression. Use of Feno values, bEOS counts, and serum marker levels (eg, CCL26 and CCL17) in combination might allow patient selection for novel type 2 therapeutics.
KW - Adolescent
KW - Adult
KW - Asthma/blood
KW - Biomarkers/blood
KW - Cell Adhesion Molecules/immunology
KW - Cell Line
KW - Chemokine CCL17/blood
KW - Chemokine CCL26
KW - Chemokines, CC/blood
KW - Eosinophils/immunology
KW - Female
KW - Gene Expression
KW - Humans
KW - Interleukin-13/genetics
KW - Leukocyte Count
KW - Male
KW - Middle Aged
KW - Nitric Oxide/metabolism
KW - Respiratory Function Tests
KW - Respiratory Mucosa/immunology
KW - Severity of Illness Index
KW - Young Adult
U2 - 10.1016/j.jaci.2016.11.038
DO - 10.1016/j.jaci.2016.11.038
M3 - Journal article
C2 - 28089872
VL - 140
SP - 710
EP - 719
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 3
ER -
ID: 194814697