Airway Interleukin-33 and type 2 cytokines in adult patients with acute asthma

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 -