Activation of the Complement and Coagulation Systems in the Small Airways in Asthma.

Lowie E G W Vanfleteren, Spela Kokelj, Jörgen Östling, Karin Fromell, Henric K Olsson, Kristina Nilsson Ekdahl, Bo Nilsson, Anna-Carin Olin

Journal: Respiration; international review of thoracic diseases 2023;102(8):621-631

PMID: 37423212

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Abstract

BACKGROUND

Several studies have shown the importance of the complement and coagulation systems in the pathogenesis of asthma.

OBJECTIVES

We explored whether we could detect differentially abundant complement and coagulation proteins in the samples obtained from the small airway lining fluid by collection of exhaled particles in patients with asthma and whether these proteins are associated with small airway dysfunction and asthma control.

METHOD

Exhaled particles were obtained from 20 subjects with asthma and 10 healthy controls (HC) with the PExA method and analysed with the SOMAscan proteomics platform. Lung function was assessed by nitrogen multiple breath washout test and spirometry.

RESULTS

53 proteins associated with the complement and coagulation systems were included in the analysis. Nine of those proteins were differentially abundant in subjects with asthma as compared to HC, and C3 was significantly higher in inadequately controlled asthma as compared to well-controlled asthma. Several proteins were associated with physiological tests assessing small airways.

CONCLUSIONS

The study highlights the role of the local activation of the complement and coagulation systems in the small airway lining fluid in asthma and their association with both asthma control and small airway dysfunction. The findings highlight the potential of complement factors as biomarkers to identify different sub-groups among patients with asthma that could potentially benefit from a therapeutic approach targeting the complement system.

Address: Occupational and Environmental Medicine, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; PExA AB, Gothenburg, Sweden.; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.; COPD Center, Department of Respiratory Medicine and Allergology, Sahlgrenska University Hospital, Gothenburg, Sweden.; Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.; Linnaeus Centre for Biomaterials Chemistry, Linnaeus University, Kalmar, Sweden.

DOI: 10.1159/000531374