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

Nadia Nicholine Poulsen, Asger Bjerregaard, Siew Kim Khoo, Ingrid A. Laing, Peter Le Souëf, Vibeke Backer, Laura Rapley, Suzanne E. Cohen, Lucy Barrett, Philip Thompson, Svetlana Baltic, Celeste Porsbjerg

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)50-56
Number of pages7
JournalRespiratory Medicine
Volume140
DOIs
Publication statusPublished - 1 Jul 2018

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Interleukin-2
Asthma
Cytokines
Interleukin-13
Inflammation
Interleukin-5
Sputum
Eosinophils
Interleukin-33
Messenger RNA
Nose
Hospital Emergency Service
Polymerase Chain Reaction
Pharmaceutical Preparations

Cite this

Poulsen, Nadia Nicholine ; Bjerregaard, Asger ; Khoo, Siew Kim ; Laing, Ingrid A. ; Le Souëf, Peter ; Backer, Vibeke ; Rapley, Laura ; Cohen, Suzanne E. ; Barrett, Lucy ; Thompson, Philip ; Baltic, Svetlana ; Porsbjerg, Celeste. / Airway Interleukin-33 and type 2 cytokines in adult patients with acute asthma. In: Respiratory Medicine. 2018 ; Vol. 140. pp. 50-56.
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title = "Airway Interleukin-33 and type 2 cytokines in adult patients with acute asthma",
abstract = "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{\circledR} 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.",
keywords = "Acute asthma, Adults, Exacerbation, Interleukin-33, Type 2 cytokines",
author = "Poulsen, {Nadia Nicholine} and Asger Bjerregaard and Khoo, {Siew Kim} and Laing, {Ingrid A.} and {Le Sou{\"e}f}, Peter and Vibeke Backer and Laura Rapley and Cohen, {Suzanne E.} and Lucy Barrett and Philip Thompson and Svetlana Baltic and Celeste Porsbjerg",
year = "2018",
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Poulsen, NN, Bjerregaard, A, Khoo, SK, Laing, IA, Le Souëf, P, Backer, V, Rapley, L, Cohen, SE, Barrett, L, Thompson, P, Baltic, S & Porsbjerg, C 2018, 'Airway Interleukin-33 and type 2 cytokines in adult patients with acute asthma' Respiratory Medicine, vol. 140, pp. 50-56. https://doi.org/10.1016/j.rmed.2018.05.016

Airway Interleukin-33 and type 2 cytokines in adult patients with acute asthma. / Poulsen, Nadia Nicholine; Bjerregaard, Asger; Khoo, Siew Kim; Laing, Ingrid A.; Le Souëf, Peter; Backer, Vibeke; Rapley, Laura; Cohen, Suzanne E.; Barrett, Lucy; Thompson, Philip; Baltic, Svetlana; Porsbjerg, Celeste.

In: Respiratory Medicine, Vol. 140, 01.07.2018, p. 50-56.

Research output: Contribution to journalArticle

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

PY - 2018/7/1

Y1 - 2018/7/1

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 asthma

KW - Adults

KW - Exacerbation

KW - Interleukin-33

KW - Type 2 cytokines

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U2 - 10.1016/j.rmed.2018.05.016

DO - 10.1016/j.rmed.2018.05.016

M3 - Article

VL - 140

SP - 50

EP - 56

JO - Respiratory Medicine

JF - Respiratory Medicine

SN - 0954-6111

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