COPD: systemic proteomic profiles in frequent and infrequent exacerbators
Patients with COPD can suffer acute episodes of exacerbation (AE) of their respiratory symptoms
This episodes negatively impact their health status and prognosis.
For reasons still unclear, some COPD patients are particularly prone to suffering frequent exacerbations (FE) while others are not (NFE).
AE can be triggered by viral and bacterial respiratory infections and are associated with lung microbiome changes and/or airway eosinophilic infiltration that can result in a dysregulated host immune response, leading to local and systemic inflammation.
Accordingly, we hypothesised that the plasma proteomic profile of FE patients is different from that of NFE and may share some characteristics with an actual episode of AE.
To explore these hypotheses, we used a complementary two-way quantitative proteomic approach that combines an unbiased label-free mass spectrometry-based method with a targeted immunoassay-based workflow to compare the plasma proteome of clinically stable COPD patients with and without FE.
As a reference, we also determined the proteomic profile observed during an actual episode of AE and in healthy controls (HC).
Background
Some patients with COPD suffer frequent exacerbations (FE). We hypothesised that their systemic proteomic profile would be different from that of non-frequent exacerbators (NFE).
The objective of the present study was to contrast the systemic proteomic profile in FE versus NFE. As a reference, we also determined the systemic proteomic profile of healthy controls (HC) and COPD patients during an actual episode of exacerbation (AE).
Methods
In the analysis we included 40 clinically stable COPD patients (20 FE and 20 NFE), and 20 HC and 10 AE patients.
Their plasma samples were analysed by combining two complementary proteomic approaches: label-free liquid chromatography-tandem mass spectrometry and multiplex immunoassays.
Gene Ontology annotation, pathway enrichment and network analyses were used to investigate molecular pathways associated with differentially abundant proteins/peptides (DAPs).
Results
Compared with HC, we identified 40 DAPs in FE, 10 in NFE and 63 in AE.
Also compared to HC, pathway functional and protein–protein network analyses revealed dysregulation of inflammatory responses involving innate and antibody-mediated immunity in COPD, particularly in the FE group, as well as during an AE episode. Besides, we only identified alterations in the complement and coagulation cascades in AE.
Conclusion
There are specific plasma proteome profiles associated with FE, which are partially shared with findings observed during AE, albeit others are uniquely present during the actual episode of AE.
Authors
Cesar Jessé Enríquez-Rodríguez, Carme Casadevall, Rosa Faner, Ady Castro-Costa, Sergi Pascual-Guàrdia, Luis Seijó, José Luis López-Campos, Germán Peces-Barba, Eduard Monsó, Esther Barreiro, Borja G. Cosío, Alvar Agustí, Joaquim Gea, on behalf of the BIOMEPOC group.
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