TY - JOUR
T1 - Airway Interleukin-33 and type 2 cytokines in adult patients with acute asthma
AU - Poulsen, Nadia Nicholine
AU - Bjerregaard, Asger
AU - Khoo, Siew-Kim
AU - Laing, Ingrid A
AU - Le Souëf, Peter
AU - Backer, Vibeke
AU - Rapley, Laura
AU - Cohen, Suzanne E
AU - Barrett, Lucy
AU - Thompson, Philip
AU - Baltic, Svetlana
AU - Porsbjerg, Celeste
N1 - Copyright © 2018 Elsevier Ltd. All rights reserved.
PY - 2018/7
Y1 - 2018/7
N2 - Background: Several animal studies, and one inoculation study in adult asthmatics have shown that interleukin-33 (IL-33) is a major contributor to type-2 inflammation in acute asthma. However, the link between IL-33 and type-2 inflammation has not been shown in naturally occurring asthma exacerbations. Objectives: To determine if airway IL-33 is associated with type-2 inflammation measured by type-2 cytokines, FeNO and sputum eosinophils in patients presenting to the Emergency Department with an asthma exacerbations. Methods: Adult patients hospitalized due to acute asthma were enrolled. Upper airways were sampled with nasal swabs and lower airways with induced sputum. Cytokines were measured at protein level using a Luminex® assay and mRNA expression level using droplet-digital-PCR. Airway sampling was repeated four weeks after exacerbation. Results: At the time of exacerbation, upper airway IL-33 correlated with upper airway IL-5 and IL-13 (R = 0.84, p < 0.01 and R = 0.76, p < 0.01, respectively) and with lower airway IL-13 (R = 0.49, p = 0.03). Similar associations were observed for mRNA expression. Lower airway IL-33 positively correlated with lower airway IL-13 (R = 0.84, p < 0.01). IL-13 and IL-33 were positively correlated with FeNO, and IL-5 with eosinophils. The association between IL-33 and type-2 cytokines were still present four weeks after exacerbation. Conclusion: This is the first study to demonstrate that airway IL-33 is associated with type-2 cytokines in naturally occurring asthma exacerbations in adults, providing in vivo evidence supporting that IL-33 may be driving type-2 inflammation in acute asthma. Thus supporting IL-33 as a potential future drug target due to its role, upstream in the immunological cascade.
AB - Background: Several animal studies, and one inoculation study in adult asthmatics have shown that interleukin-33 (IL-33) is a major contributor to type-2 inflammation in acute asthma. However, the link between IL-33 and type-2 inflammation has not been shown in naturally occurring asthma exacerbations. Objectives: To determine if airway IL-33 is associated with type-2 inflammation measured by type-2 cytokines, FeNO and sputum eosinophils in patients presenting to the Emergency Department with an asthma exacerbations. Methods: Adult patients hospitalized due to acute asthma were enrolled. Upper airways were sampled with nasal swabs and lower airways with induced sputum. Cytokines were measured at protein level using a Luminex® assay and mRNA expression level using droplet-digital-PCR. Airway sampling was repeated four weeks after exacerbation. Results: At the time of exacerbation, upper airway IL-33 correlated with upper airway IL-5 and IL-13 (R = 0.84, p < 0.01 and R = 0.76, p < 0.01, respectively) and with lower airway IL-13 (R = 0.49, p = 0.03). Similar associations were observed for mRNA expression. Lower airway IL-33 positively correlated with lower airway IL-13 (R = 0.84, p < 0.01). IL-13 and IL-33 were positively correlated with FeNO, and IL-5 with eosinophils. The association between IL-33 and type-2 cytokines were still present four weeks after exacerbation. Conclusion: This is the first study to demonstrate that airway IL-33 is associated with type-2 cytokines in naturally occurring asthma exacerbations in adults, providing in vivo evidence supporting that IL-33 may be driving type-2 inflammation in acute asthma. Thus supporting IL-33 as a potential future drug target due to its role, upstream in the immunological cascade.
KW - Acute Disease
KW - Adult
KW - Asthma/immunology
KW - Cytokines/genetics
KW - Eosinophils/immunology
KW - Female
KW - Follow-Up Studies
KW - Gene Expression/immunology
KW - Humans
KW - Inflammation Mediators/metabolism
KW - Interleukin-13/genetics
KW - Interleukin-33/genetics
KW - Interleukin-5/genetics
KW - Male
KW - Middle Aged
KW - Nasal Mucosa/immunology
KW - RNA, Messenger/genetics
KW - Severity of Illness Index
KW - Sputum/immunology
KW - Young Adult
U2 - 10.1016/j.rmed.2018.05.016
DO - 10.1016/j.rmed.2018.05.016
M3 - Journal article
C2 - 29957280
SN - 0954-6111
VL - 140
SP - 50
EP - 56
JO - Respiratory Medicine
JF - Respiratory Medicine
ER -