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

Pulmonary surfactant is vital for lung homeostasis as it reduces surface tension to prevent alveolar collapse and provides essential immune-regulatory and antipathogenic functions. Previous studies demonstrated dysregulation of some individual surfactant components in COPD. We investigated relationships between COPD disease measures and dysregulation of surfactant components to gain new insights into potential disease mechanisms. Bronchoalveolar 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. Total phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, surfactant protein (SP)-B, SP-A and SP-D concentrations were lower in COPD Using a multiomics approach, we demonstrate, for the first time, global surfactant dysregulation in COPD that was associated with emphysema, giving new insights into potential mechanisms underlying the cause or consequence of disease.

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Conflicts of interest: This project was funded by AstraZeneca. V.A. Hristova, R. Chaerkady, M.S. Glover, B. Angermann, G. Belfield, M.G. Belvisi, D. Etal, S. Hess, M. Hühn, C. McCrae, D. Muthas, S. Novick, K. Ostridge, L. Öberg, A. Platt and J. Wang are employees of AstraZeneca, and hold AstraZeneca employee stocks and/or stock options. A. Mackay was an employee of AstraZeneca during the conduct of the study and an employee of Novartis upon submission of this article; Novartis played no role and made no contribution, financial or otherwise, to the work in this manuscript. O. Vaarala was employee of AstraZeneca from 2014 to 2019, and an employee of OrionPharma from 2019 and during the conduct of this study, and owns AstraZeneca stock. K.J. Staples reports receiving grants from AstraZeneca within the submitted work. T.M.A Wilkinson reports grants and personal fees from AstraZeneca during the conduct of the study; and personal fees and other support from MMH, grants and personal fees from GSK, personal fees from BI, and grants and personal fees from Synairgen, outside the submitted work. A. Watson, J. Ackland, H. Burke, D. Cellura, H.W. Clark, A. Freeman, E. Hall, A.I. Heinson, J. Madsen, A.D. Postle and C. Mirella Spalluto report no conflicts of interest.