Abstract
Rationale: Systemic inflammation in bronchiectasis is poorly studied in relation to disease aetiology and severity.
Method: We assayed blood concentrations of 31 proteins from 90 patients with bronchiectasis (derivation cohort) and conducted PCA to examine relationships between these markers, disease aetiology and severity. Key results were validated in two separate cohorts of 97 and 79 patients.
Results: There was significant heterogeneity in protein concentrations across the derivation cohort. Increasing severity of bronchiectasis (BSI) was associated with increasing fibrinogen concentration (rho=0.34, p=0.001 – validated in a second cohort), and higher fibrinogen was associated with worse lung function, Pseudomonas colonisation and impaired health status. There were generally similar patterns of inflammation in patients with idiopathic and post-infectious disease. Patients with primary immunodeficiency had exaggerated IL-17 responses, validated in a second cohort (immunodeficient 12.82 vs. idiopathic/post-infectious 4.95pg/ml, p=0.001), and thus IL-17 was able to discriminate primary immunodeficiency from other aetiologies (ROC AUC 0.769 (95%CI 0.661-0.877)).
Conclusion: Bronchiectasis is associated with heterogeneity of systemic inflammatory proteins not adequately explained by differences in disease aetiology or disease severity. More severe disease is associated with an enhanced acute-phase response and we provide proof-of-principle that assay of systemic proteins may aid the diagnosis of specific conditions. Plasma fibrinogen was associated with bronchiectasis severity in two cohorts, Pseudomonas colonisation and health status, and offers potential as a useful biomarker.
- Copyright ©ERS 2015
