Multiomics links global surfactant dysregulation with airflow obstruction and emphysema in COPD

Autor: Ventzislava A. Hristova, Alastair Watson, Raghothama Chaerkady, Matthew S. Glover, Jodie Ackland, Bastian Angerman, Graham Belfield, Maria G. Belvisi, Hannah Burke, Doriana Cellura, Howard W. Clark, Damla Etal, Anna Freeman, Ashley I Heinson, Sonja Hess, Michael Hühn, Emily Hall, Alex Mackay, Jens Madsen, Christopher McCrae, Daniel Muthas, Steven Novick, Kristoffer Ostridge, Lisa Öberg, Adam Platt, Anthony D. Postle, C. Mirella Spalluto, Outi Vaarala, Junmin Wang, Karl J. Staples, Tom M.A Wilkinson
Rok vydání: 2022
Předmět:
Zdroj: ERJ Open Research. :00378-2022
ISSN: 2312-0541
Popis: RationalePulmonary surfactant is vital for lung homeostasis as it reduces surface tension to prevent alveolar collapse and provides essential immune-regulatory and anti-pathogenic functions. Previous studies demonstrated dysregulation of some individual surfactant components in COPD.ObjectivesWe investigated relationships between COPD disease measures and dysregulation of surfactant components to gain new insights about potential disease mechanisms.MethodsBronchoalveolar lavage proteome and lipidome were characterised in ex-smoking mild/moderate COPD subjects (n=26) and healthy ex-smoking (n=20) and never-smoking (n=16) controls using mass spectrometry. Serum surfactant protein analysis was performed.ResultsTotal phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol and surfactant protein (SP)-B, SP-A and SP-D concentrations were lower, COPDversuscontrols, log2 fold change (log2FC)=−2.0, −2.2, −1.5, −0.5, −0.7, −0.5 (adj. p-valueversuscontrols, log2FC of 0.40 (adj. p-value=0.0390) and inversely correlated with SP-A and SP-D. Serum SP-D was increased in COPDversusHV-ES, and predicted COPD status, AUC=0.85.ConclusionsUsing a multiomics approach we, for the first time, demonstrate global surfactant dysregulation in COPD which was associated with emphysema giving new insights about potential mechanisms underlying the cause or consequence of disease.
Databáze: OpenAIRE