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

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.

Evaluation of common protein biomarkers involved in the pathogenesis of respiratory diseases with proteomic methods: A systematic review

“…Finally, 119 studies were selected in this systematic review. Details and related findings of selected papers (age, sex, sample type, type of technique used, statistical analysis, number of increased or decreased proteins, model characteristics, validation test) are shown in supplementary files 20–123 . It listed for COPD, IPF, Asthma, BO, and mustard gas‐exposed victims, respectively.…”

“…In IPF, the most commonly used selection was Broncho‐alveolar lavage fluid (BALF) (12 out of 27) 31–41,45 . In Asthma, PB was the most commonly used sample (12 out of 27) 25–30,49,50,63,115,117,124 . In one study, the exosome was used; in another, one nasal brush was used as a sample.…”

Integration of multi-source gene interaction networks and omics data with graph attention networks to identify novel disease genes

“…Cytokine-cytokine receptor interaction is enriched because of the vital role of cytokines in asthma discussed above. Complement and coagulation system is found to be in association with asthma control 38 . The PI3K-Akt signaling pathway can promote airway inflammation and hyperresponsiveness 39 , therefore is crucial in asthma.…”

Particles in Exhaled Air (PExA): Clinical Uses and Future Implications

“…A total of 32 proteins were identified with differential expression between asthma and control groups. Of interest was also that proteins belonging to the complement system seem to be associated with asthma control [46]. SomaScan was also used to explore the effect of smoking by Kokelj et al, and 203 different proteins were detected, and 81 proteins differed between the groups, where a difference depending on sex was apparent [47].…”

“…However, improvements after ICS were only seen in FeNO, exhaled breath temperature (EBT), and six selected VOCs, and there were no dynamic changes in PEx measurements [45]. More recently, an exploratory study showed that complement and coagulation markers in RTLF are associated with asthma control and small airway dysfunction, highlighting the potential contribution of the complement cascade in the pathogenesis of asthma [46].…”