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 W Smith; Yury A Bochkov; Peter Le Souëf; Celeste Porsbjerg

doi: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

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 W Smith, Yury A Bochkov, Peter Le Souëf, Celeste Porsbjerg

Institut for Klinisk Medicin

11 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Respiratory Medicine
Vol/bind	123
Sider (fra-til)	34-41
ISSN	0954-6111
DOI	https://doi.org/10.1016/j.rmed.2016.12.010
Status	Udgivet - 1 feb. 2017

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10.1016/j.rmed.2016.12.010

Citationsformater

Bjerregaard, A., Laing, I. A., Poulsen, N., Backer, V., Sverrild, A., Fally, M., Khoo, S-K., Barrett, L., Baltic, S., Thompson, P. J., Chidlow, G., Sikazwe, C., Smith, D. W., Bochkov, Y. A., 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, 123, 34-41. https://doi.org/10.1016/j.rmed.2016.12.010

Bjerregaard, A, Laing, IA, Poulsen, N, Backer, V, Sverrild, A, Fally, M, Khoo, S-K, 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, bind 123, s. 34-41. https://doi.org/10.1016/j.rmed.2016.12.010

@article{9330905d87444946af16550baf61d4cc,

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 = "Acute Disease, Adult, Asthma/metabolism, Cytokines/biosynthesis, Eosinophilia/virology, Female, Forced Expiratory Volume/physiology, Gene Expression/physiology, Humans, Inflammation/metabolism, Male, Middle Aged, Nitric Oxide/metabolism, Phenotype, Prospective Studies, RNA, Messenger/genetics, Respiratory Tract Infections/complications, Severity of Illness Index, Spirometry, Sputum/cytology, Virus Diseases/complications, Young Adult",

author = "Asger Bjerregaard and Laing, {Ingrid A} and Nadia Poulsen and Vibeke Backer and Asger Sverrild and Markus Fally and Siew-Kim Khoo and Lucy Barrett and Svetlana Baltic and Thompson, {Philip J} and Glenys Chidlow and Chisha Sikazwe and Smith, {David W} and Bochkov, {Yury A} and {Le Sou{\"e}f}, Peter and Celeste Porsbjerg",

year = "2017",

month = feb,

day = "1",

doi = "10.1016/j.rmed.2016.12.010",

language = "English",

volume = "123",

pages = "34--41",

journal = "Respiratory Medicine",

issn = "0954-6111",

publisher = "Elsevier",

}

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 W

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 - Acute Disease

KW - Adult

KW - Asthma/metabolism

KW - Cytokines/biosynthesis

KW - Eosinophilia/virology

KW - Female

KW - Forced Expiratory Volume/physiology

KW - Gene Expression/physiology

KW - Humans

KW - Inflammation/metabolism

KW - Male

KW - Middle Aged

KW - Nitric Oxide/metabolism

KW - Phenotype

KW - Prospective Studies

KW - RNA, Messenger/genetics

KW - Respiratory Tract Infections/complications

KW - Severity of Illness Index

KW - Spirometry

KW - Sputum/cytology

KW - Virus Diseases/complications

KW - Young Adult

U2 - 10.1016/j.rmed.2016.12.010

DO - 10.1016/j.rmed.2016.12.010

M3 - Journal article

C2 - 28137494

SN - 0954-6111

VL - 123

SP - 34

EP - 41

JO - Respiratory Medicine

JF - Respiratory Medicine

ER -

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

Abstract

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