Characteristics associated with clinical severity and inflammatory phenotype of naturally occurring virus-induced exacerbations of asthma in adults

Asger Bjerregaard, Ingrid A. Laing, Nadia Poulsen, Vibeke Backer, Asger Sverrild, Markus Fally, Siew Kim Khoo, Lucy Barrett, Svetlana Baltic, Philip J. Thompson, Glenys Chidlow, Chisha Sikazwe, David William Smith, Yury A. Bochkov, Peter Le Souëf, Celeste Porsbjerg

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Abstract

Background In experimental studies viral infections have been shown to induce type 2 inflammation in asthmatics, but whether this is a feature of naturally occurring virus-induced asthma exacerbations is unknown. Thymic stromal lymphopoietin (TSLP) released from the airway epithelium in response to damage, has been suggested as a link between viral infection and type 2 inflammation, but the role of TSLP in asthma exacerbations is unknown. Objective To assess whether type 2 inflammation, as measured by sputum eosinophils and fractional exhaled nitric oxide (FeNO), is a feature of naturally occurring virus-induced exacerbations of asthma and whether TSLP is associated with this type 2 inflammation. Methods Patients presenting to hospital with acute asthma were examined during the exacerbation, and after 4 weeks recovery. The assessments included spirometry, FeNO and induced sputum for differential counts and TSLP mRNA levels. Nasal swabs were collected for viral detection. Results Sputum eosinophils and FeNO were similar between virus-positive (n = 44) and negative patients (n = 44). In virus-positive patients, TSLP expression was lower at exacerbation than follow-up (p = 0.03). High TSLP at exacerbation was associated with lower sputum eosinophils (p = 0.01) and higher FEV1 (p = 0.03). In virus-positive patients, %-predicted FEV1 negatively correlated with both FeNO and sputum eosinophils (p = 0.02 and p = 0.05, respectively). Conclusion Our findings support that type 2 inflammation is present in patients during virus-induced asthma exacerbations, to the same degree as non-viral exacerbations, and correlate negatively with FEV1. However, in virus-positive patients, high TSLP expression during exacerbation was associated with low sputum eosinophils, suggesting that the effect of TSLP in vivo, in the setting of an asthma exacerbation, might be different than the type 2 inducing effects observed in experimental studies.

Original languageEnglish
Pages (from-to)34-41
Number of pages8
JournalRespiratory Medicine
Volume123
DOIs
Publication statusPublished - 1 Feb 2017

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Asthma
Sputum
Viruses
Phenotype
Eosinophils
Inflammation
Nitric Oxide
Virus Diseases
thymic stromal lymphopoietin
Spirometry
Nose
Epithelium
Messenger RNA

Cite this

Bjerregaard, Asger ; Laing, Ingrid A. ; Poulsen, Nadia ; Backer, Vibeke ; Sverrild, Asger ; Fally, Markus ; Khoo, Siew Kim ; Barrett, Lucy ; Baltic, Svetlana ; Thompson, Philip J. ; Chidlow, Glenys ; Sikazwe, Chisha ; Smith, David William ; Bochkov, Yury A. ; Le Souëf, Peter ; Porsbjerg, Celeste. / Characteristics associated with clinical severity and inflammatory phenotype of naturally occurring virus-induced exacerbations of asthma in adults. In: Respiratory Medicine. 2017 ; Vol. 123. pp. 34-41.
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title = "Characteristics associated with clinical severity and inflammatory phenotype of naturally occurring virus-induced exacerbations of asthma in adults",
abstract = "Background In experimental studies viral infections have been shown to induce type 2 inflammation in asthmatics, but whether this is a feature of naturally occurring virus-induced asthma exacerbations is unknown. Thymic stromal lymphopoietin (TSLP) released from the airway epithelium in response to damage, has been suggested as a link between viral infection and type 2 inflammation, but the role of TSLP in asthma exacerbations is unknown. Objective To assess whether type 2 inflammation, as measured by sputum eosinophils and fractional exhaled nitric oxide (FeNO), is a feature of naturally occurring virus-induced exacerbations of asthma and whether TSLP is associated with this type 2 inflammation. Methods Patients presenting to hospital with acute asthma were examined during the exacerbation, and after 4 weeks recovery. The assessments included spirometry, FeNO and induced sputum for differential counts and TSLP mRNA levels. Nasal swabs were collected for viral detection. Results Sputum eosinophils and FeNO were similar between virus-positive (n = 44) and negative patients (n = 44). In virus-positive patients, TSLP expression was lower at exacerbation than follow-up (p = 0.03). High TSLP at exacerbation was associated with lower sputum eosinophils (p = 0.01) and higher FEV1 (p = 0.03). In virus-positive patients, {\%}-predicted FEV1 negatively correlated with both FeNO and sputum eosinophils (p = 0.02 and p = 0.05, respectively). Conclusion Our findings support that type 2 inflammation is present in patients during virus-induced asthma exacerbations, to the same degree as non-viral exacerbations, and correlate negatively with FEV1. However, in virus-positive patients, high TSLP expression during exacerbation was associated with low sputum eosinophils, suggesting that the effect of TSLP in vivo, in the setting of an asthma exacerbation, might be different than the type 2 inducing effects observed in experimental studies.",
keywords = "Asthma, Eosinophils, Exacerbation, TSLP, Viral infection",
author = "Asger Bjerregaard and Laing, {Ingrid A.} and Nadia Poulsen and Vibeke Backer and Asger Sverrild and Markus Fally and Khoo, {Siew Kim} and Lucy Barrett and Svetlana Baltic and Thompson, {Philip J.} and Glenys Chidlow and Chisha Sikazwe and Smith, {David William} and Bochkov, {Yury A.} and {Le Sou{\"e}f}, Peter and Celeste Porsbjerg",
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Bjerregaard, A, Laing, IA, Poulsen, N, Backer, V, Sverrild, A, Fally, M, Khoo, SK, Barrett, L, Baltic, S, Thompson, PJ, Chidlow, G, Sikazwe, C, Smith, DW, Bochkov, YA, Le Souëf, P & Porsbjerg, C 2017, 'Characteristics associated with clinical severity and inflammatory phenotype of naturally occurring virus-induced exacerbations of asthma in adults' Respiratory Medicine, vol. 123, pp. 34-41. https://doi.org/10.1016/j.rmed.2016.12.010

Characteristics associated with clinical severity and inflammatory phenotype of naturally occurring virus-induced exacerbations of asthma in adults. / Bjerregaard, Asger; Laing, Ingrid A.; Poulsen, Nadia; Backer, Vibeke; Sverrild, Asger; Fally, Markus; Khoo, Siew Kim; Barrett, Lucy; Baltic, Svetlana; Thompson, Philip J.; Chidlow, Glenys; Sikazwe, Chisha; Smith, David William; Bochkov, Yury A.; Le Souëf, Peter; Porsbjerg, Celeste.

In: Respiratory Medicine, Vol. 123, 01.02.2017, p. 34-41.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Characteristics associated with clinical severity and inflammatory phenotype of naturally occurring virus-induced exacerbations of asthma in adults

AU - Bjerregaard, Asger

AU - Laing, Ingrid A.

AU - Poulsen, Nadia

AU - Backer, Vibeke

AU - Sverrild, Asger

AU - Fally, Markus

AU - Khoo, Siew Kim

AU - Barrett, Lucy

AU - Baltic, Svetlana

AU - Thompson, Philip J.

AU - Chidlow, Glenys

AU - Sikazwe, Chisha

AU - Smith, David William

AU - Bochkov, Yury A.

AU - Le Souëf, Peter

AU - Porsbjerg, Celeste

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Background In experimental studies viral infections have been shown to induce type 2 inflammation in asthmatics, but whether this is a feature of naturally occurring virus-induced asthma exacerbations is unknown. Thymic stromal lymphopoietin (TSLP) released from the airway epithelium in response to damage, has been suggested as a link between viral infection and type 2 inflammation, but the role of TSLP in asthma exacerbations is unknown. Objective To assess whether type 2 inflammation, as measured by sputum eosinophils and fractional exhaled nitric oxide (FeNO), is a feature of naturally occurring virus-induced exacerbations of asthma and whether TSLP is associated with this type 2 inflammation. Methods Patients presenting to hospital with acute asthma were examined during the exacerbation, and after 4 weeks recovery. The assessments included spirometry, FeNO and induced sputum for differential counts and TSLP mRNA levels. Nasal swabs were collected for viral detection. Results Sputum eosinophils and FeNO were similar between virus-positive (n = 44) and negative patients (n = 44). In virus-positive patients, TSLP expression was lower at exacerbation than follow-up (p = 0.03). High TSLP at exacerbation was associated with lower sputum eosinophils (p = 0.01) and higher FEV1 (p = 0.03). In virus-positive patients, %-predicted FEV1 negatively correlated with both FeNO and sputum eosinophils (p = 0.02 and p = 0.05, respectively). Conclusion Our findings support that type 2 inflammation is present in patients during virus-induced asthma exacerbations, to the same degree as non-viral exacerbations, and correlate negatively with FEV1. However, in virus-positive patients, high TSLP expression during exacerbation was associated with low sputum eosinophils, suggesting that the effect of TSLP in vivo, in the setting of an asthma exacerbation, might be different than the type 2 inducing effects observed in experimental studies.

AB - Background In experimental studies viral infections have been shown to induce type 2 inflammation in asthmatics, but whether this is a feature of naturally occurring virus-induced asthma exacerbations is unknown. Thymic stromal lymphopoietin (TSLP) released from the airway epithelium in response to damage, has been suggested as a link between viral infection and type 2 inflammation, but the role of TSLP in asthma exacerbations is unknown. Objective To assess whether type 2 inflammation, as measured by sputum eosinophils and fractional exhaled nitric oxide (FeNO), is a feature of naturally occurring virus-induced exacerbations of asthma and whether TSLP is associated with this type 2 inflammation. Methods Patients presenting to hospital with acute asthma were examined during the exacerbation, and after 4 weeks recovery. The assessments included spirometry, FeNO and induced sputum for differential counts and TSLP mRNA levels. Nasal swabs were collected for viral detection. Results Sputum eosinophils and FeNO were similar between virus-positive (n = 44) and negative patients (n = 44). In virus-positive patients, TSLP expression was lower at exacerbation than follow-up (p = 0.03). High TSLP at exacerbation was associated with lower sputum eosinophils (p = 0.01) and higher FEV1 (p = 0.03). In virus-positive patients, %-predicted FEV1 negatively correlated with both FeNO and sputum eosinophils (p = 0.02 and p = 0.05, respectively). Conclusion Our findings support that type 2 inflammation is present in patients during virus-induced asthma exacerbations, to the same degree as non-viral exacerbations, and correlate negatively with FEV1. However, in virus-positive patients, high TSLP expression during exacerbation was associated with low sputum eosinophils, suggesting that the effect of TSLP in vivo, in the setting of an asthma exacerbation, might be different than the type 2 inducing effects observed in experimental studies.

KW - Asthma

KW - Eosinophils

KW - Exacerbation

KW - TSLP

KW - Viral infection

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U2 - 10.1016/j.rmed.2016.12.010

DO - 10.1016/j.rmed.2016.12.010

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JO - Respiratory Medicine

JF - Respiratory Medicine

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