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Sputum proteomic signature of gastro-oesophageal reflux in patients with severe asthma

Sputum proteomic signature of gastro-oesophageal reflux in patients with severe asthma
Sputum proteomic signature of gastro-oesophageal reflux in patients with severe asthma
Gastro-oesophageal reflux disease (GORD) has long been associated with poor asthma control without an established cause-effect relationship.

610 asthmatics (421 severe/88 mild-moderate) and 101 healthy controls were assessed clinically and a subset of 154 severe asthmatics underwent proteomic analysis of induced sputum using untargeted mass spectrometry, LC-IMS-MSE. Univariate and multiple logistic regression analyses (MLR) were conducted to identify proteins associated with GORD in this cohort. When compared to mild/moderate asthmatics and healthy individuals, respectively, GORD was three- and ten-fold more prevalent in severe asthmatics and was associated with increased asthma symptoms and oral corticosteroid use, poorer quality of life, depression/anxiety, obesity and symptoms of sino-nasal disease. Comparison of sputum proteomes in severe asthmatics with and without active GORD showed five differentially abundant proteins with described roles in antimicrobial
defences, systemic inflammation and epithelial integrity. Three of these were associated with active GORD by multiple linear regression analysis: Ig lambda variable 1-47 (p=0·017) and plasma protease C1 inhibitor (p=0·043), both in lower concentrations, and lipocalin-1 (p=0·034) in higher concentrations in active GORD.

This study provides evidence which suggests that reflux can cause subtle perturbation of proteins detectable in the airways lining fluid and that severe asthmatics with GORD may represent a distinct phenotype of asthma.
Asthma, Proteomics
0954-6111
66-73
Tariq, K.
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Schofield, J.P.R.
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Nicholas, B.L.
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Burg, D.
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Brandsma, J.
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Bansal, A.T.
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Wilson, S.J.
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Lutter, R.
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Fowler, S.J.
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Bakke, M.
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Caruso, M.
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Dahlen, B.
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Horvath, I.
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Krug, N.
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Montuschi, P.
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Sanak, M.
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Sandstrom, T.
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Pandis, I.
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Sousa, A.R.
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Adcock, I.M.
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Shaw, D.E.
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Auffray, C.
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Howarth, P.H.
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Sterk, P.J.
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Chung, K.F.
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Skipp, P.J.
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Dimitrov, B.
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Djukanovic, R.
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Tariq, K.
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Schofield, J.P.R.
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Nicholas, B.L.
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Burg, D.
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Brandsma, J.
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Bansal, A.T.
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Wilson, S.J.
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Lutter, R.
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Fowler, S.J.
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Bakke, M.
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Caruso, M.
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Dahlen, B.
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Horvath, I.
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Krug, N.
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Montuschi, P.
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Sanak, M.
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Sandstrom, T.
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Geiser, T.
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Pandis, I.
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Sousa, A.R.
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Adcock, I.M.
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Shaw, D.E.
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Auffray, C.
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Howarth, P.H.
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Sterk, P.J.
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Chung, K.F.
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Skipp, P.J.
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Dimitrov, B.
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Djukanovic, R.
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Tariq, K., Schofield, J.P.R., Nicholas, B.L., Burg, D., Brandsma, J., Bansal, A.T., Wilson, S.J., Lutter, R., Fowler, S.J., Bakke, M., Caruso, M., Dahlen, B., Horvath, I., Krug, N., Montuschi, P., Sanak, M., Sandstrom, T., Geiser, T., Pandis, I., Sousa, A.R., Adcock, I.M., Shaw, D.E., Auffray, C., Howarth, P.H., Sterk, P.J., Chung, K.F., Skipp, P.J., Dimitrov, B. and Djukanovic, R. (2019) Sputum proteomic signature of gastro-oesophageal reflux in patients with severe asthma. Respiratory Medicine, 150, 66-73. (doi:10.1016/j.rmed.2019.02.008).

Record type: Article

Abstract

Gastro-oesophageal reflux disease (GORD) has long been associated with poor asthma control without an established cause-effect relationship.

610 asthmatics (421 severe/88 mild-moderate) and 101 healthy controls were assessed clinically and a subset of 154 severe asthmatics underwent proteomic analysis of induced sputum using untargeted mass spectrometry, LC-IMS-MSE. Univariate and multiple logistic regression analyses (MLR) were conducted to identify proteins associated with GORD in this cohort. When compared to mild/moderate asthmatics and healthy individuals, respectively, GORD was three- and ten-fold more prevalent in severe asthmatics and was associated with increased asthma symptoms and oral corticosteroid use, poorer quality of life, depression/anxiety, obesity and symptoms of sino-nasal disease. Comparison of sputum proteomes in severe asthmatics with and without active GORD showed five differentially abundant proteins with described roles in antimicrobial
defences, systemic inflammation and epithelial integrity. Three of these were associated with active GORD by multiple linear regression analysis: Ig lambda variable 1-47 (p=0·017) and plasma protease C1 inhibitor (p=0·043), both in lower concentrations, and lipocalin-1 (p=0·034) in higher concentrations in active GORD.

This study provides evidence which suggests that reflux can cause subtle perturbation of proteins detectable in the airways lining fluid and that severe asthmatics with GORD may represent a distinct phenotype of asthma.

Text
1-s2.0-S0954611119300447-main - Accepted Manuscript
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More information

Accepted/In Press date: 4 February 2019
e-pub ahead of print date: 11 February 2019
Published date: April 2019
Keywords: Asthma, Proteomics

Identifiers

Local EPrints ID: 428375
URI: http://eprints.soton.ac.uk/id/eprint/428375
ISSN: 0954-6111
PURE UUID: ad42b2fa-8644-4cd2-9657-db35f67f1445
ORCID for B.L. Nicholas: ORCID iD orcid.org/0000-0003-1467-9643
ORCID for S.J. Wilson: ORCID iD orcid.org/0000-0003-1305-8271
ORCID for P.J. Skipp: ORCID iD orcid.org/0000-0002-2995-2959
ORCID for R. Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612

Catalogue record

Date deposited: 22 Feb 2019 17:30
Last modified: 10 Jan 2022 02:48

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Contributors

Author: K. Tariq
Author: J.P.R. Schofield
Author: B.L. Nicholas ORCID iD
Author: D. Burg
Author: J. Brandsma
Author: A.T. Bansal
Author: S.J. Wilson ORCID iD
Author: R. Lutter
Author: S.J. Fowler
Author: M. Bakke
Author: M. Caruso
Author: B. Dahlen
Author: I. Horvath
Author: N. Krug
Author: P. Montuschi
Author: M. Sanak
Author: T. Sandstrom
Author: T. Geiser
Author: I. Pandis
Author: A.R. Sousa
Author: I.M. Adcock
Author: D.E. Shaw
Author: C. Auffray
Author: P.H. Howarth
Author: P.J. Sterk
Author: K.F. Chung
Author: P.J. Skipp ORCID iD
Author: B. Dimitrov
Author: R. Djukanovic ORCID iD

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