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- Title
A novel non-invasive method allowing for discovery of pathologically relevant proteins from small airways.
- Authors
Östling, Jörgen; Van Geest, Marleen; Olsson, Henric K.; Dahlen, Sven-Erik; Viklund, Emilia; Gustafsson, Per M.; Mirgorodskaya, Ekaterina; Olin, Anna-Carin
- Abstract
Background: There is a lack of early and precise biomarkers for personalized respiratory medicine. Breath contains an aerosol of droplet particles, which are formed from the epithelial lining fluid when the small airways close and re-open during inhalation succeeding a full expiration. These particles can be collected by impaction using the PExA® method (Particles in Exhaled Air), and are derived from an area of high clinical interest previously difficult to access, making them a potential source of biomarkers reflecting pathological processes in the small airways. Research question: Our aim was to investigate if PExA method is useful for discovery of biomarkers that reflect pathology of small airways. Methods and analysis: Ten healthy controls and 20 subjects with asthma, of whom 10 with small airway involvement as indicated by a high lung clearance index (LCI ≥ 2.9 z-score), were examined in a cross-sectional design, using the PExA instrument. The samples were analysed with the SOMAscan proteomics platform (SomaLogic Inc.). Results: Two hundred-seven proteins were detected in up to 80% of the samples. Nine proteins showed differential abundance in subjects with asthma and high LCI as compared to healthy controls. Two of these were less abundant (ALDOA4, C4), and seven more abundant (FIGF, SERPINA1, CD93, CCL18, F10, IgM, IL1RAP). sRAGE levels were lower in ex-smokers (n = 14) than in never smokers (n = 16). Gene Ontology (GO) annotation database analyses revealed that the PEx proteome is enriched in extracellular proteins associated with extracellular exosome-vesicles and innate immunity. Conclusion: The applied analytical method was reproducible and allowed identification of pathologically interesting proteins in PEx samples from asthmatic subjects with high LCI. The results suggest that PEx based proteomics is a novel and promising approach to study respiratory diseases with small airway involvement. Key messages: Key question: Can the PExA method identify individual protein profiles that reflect pathology of small airways, using the SOMAscan platform? What is the bottom line?: Two hundred-seven proteins were detected in up to 80% of the PEx samples, with a strong overrepresentation of proteins related to innate immune responses, including nine proteins that that discriminated subjects with asthma and high LCI as compared to healthy controls. Why read on: The results support that PEx based proteomics is a novel and promising approach to study respiratory diseases with small airway involvement.
- Subjects
LUNGS; AIRWAY (Anatomy); PROTEINS; INDIVIDUALIZED medicine; GENE ontology; RESPIRATORY diseases
- Publication
Clinical Proteomics, 2022, Vol 19, Issue 1, p1
- ISSN
1542-6416
- Publication type
Article
- DOI
10.1186/s12014-022-09348-y