Sputum proteomic signature of gastro-oesophageal reflux in patients with severe asthma - 08/04/19

Doi : 10.1016/j.rmed.2019.02.008

K. Tariq ^a,^c,^{^{1
contributed equally as first authors.}}, J.P.R. Schofield ^a,^b,^{^{1
contributed equally as first authors.}}, B.L. Nicholas ^a,^c, D. Burg ^a,^b, J. Brandsma ^a, A.T. Bansal ^d, S.J. Wilson ^a, R. Lutter ^e,^f, S.J. Fowler ^h, Bakke ^j, M. Caruso ^k, B. Dahlen ^l, I. Horváth ^m, N. Krug ⁿ, P. Montuschi ^o, M. Sanak ^p, T. Sandström ^q, T. Geiser ^r, I. Pandis ^s, A.R. Sousa ^t, I.M. Adcock ^u, D.E. Shaw ⁱ, C. Auffray ^v, P.H. Howarth ^a,^c, P.J. Sterk ^f, K.F. Chung ^g, P.J. Skipp ^b, B. Dimitrov ^a, R. Djukanović ^a,^c,^⁎
the U-BIOPRED Study Group
^a NIHR Southampton Respiratory Biomedical Research Centre, University Hospital Southampton, Southampton, UK
^b Centre for Proteomic Research, University of Southampton, Highfield, Southampton, UK
^c Clinical Experimental Sciences Unit, Faculty of Medicine, University of Southampton, University Hospital Southampton, South Academic Block, Southampton, UK
^d Acclarogen Ltd, Cambridge, UK
^e AMC, Department of Experimental Immunology, University of Amsterdam, Amsterdam, the Netherlands
^f AMC, Department of Respiratory Medicine, University of Amsterdam, Amsterdam, the Netherlands
^g Airways Disease, National Heart and Lung Institute, Imperial College, London & Royal Brompton NIHR Biomedical Research Unit, London, United Kingdom
^h Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester, NHS Foundation Trust, Manchester, UK
ⁱ Respiratory Research Unit, University of Nottingham, Nottingham, UK
^j Department of Clinical Science, University of Bergen, Bergen, Norway
^k Dept. of Clinical and Experimental Medicine Hospital University, Policlinico-Vittorio Emanuele, University of Catania, Catania, Italy
^l Division of Respiratory Medicine and Allergy, Department of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden
^m Dept. of Pulmonology, Semmelweis University, Budapest, Hungary
ⁿ Fraunhofer Institute for Toxicology and Experimental Medicine Hannover, Hannover, Germany
^o Dept. of Pharmacology, Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy
^p Division of Molecular Biology and Clinical Genetics, Medical College, Jagiellonian University Medical College, Krakow, Poland
^q Dept. of Medicine, Dept of Public Health and Clinical Medicine Respiratory Medicine Unit, Umeå University, Umeå, Sweden
^r University Hospital Bern, Bern, Switzerland
^s Data Science Institute, Imperial College, London, UK
^t Respiratory Therapeutic Unit, GSK, Stockley Park, UK
^u Cell and Molecular Biology Group, Airways Disease Section, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London, UK
^v European Institute for Systems Biology and Medicine, CNRS-ENS-UCBL-INSERM, Lyon, France

^∗Corresponding author. mailpoint 810, Level F, Sir Henry Wellcome Laboratories, South Block, Southampton University Hospital, Southampton, SO16 6YD, UK.Southampton University Hospitalmailpoint 810Level FSir Henry Wellcome LaboratoriesSouth BlockSouthamptonSO16 6YDUK

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-MS^E. 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 anti-microbial 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.

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Highlights

•	5 proteins different in severe asthmatics with GORD.
•	Ig lambda variable 1–47 was associated with active GORD in severe asthma.
•	Lipocalin-1 was associated with active GORD in severe asthma.
•	Plasma protease C1 inhibitor was associated with active GORD in severe asthma.

Le texte complet de cet article est disponible en PDF.

Plan

Sample collection and analysis

Mass spectrometry

Statistical analysis

Role of the funding source

Results

Clinical characteristics and associations with GORD in the complete U-BIOPRED cohort

Proteins associated with GORD

Discussion

Authors contribution

Declaration of interests

Funding information

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P. 66-73 - avril 2019 Retour au numéro

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Sputum proteomic signature of gastro-oesophageal reflux in patients with severe asthma - 08/04/19

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