The heterogeneity of systemic inflammation in bronchiectasis

Aarash D. Saleh, James D. Chalmers, Anthony De Soyza, Thomas C. Fardon, Spiro O. Koustas, Jonathan Scott, A. John Simpson, Jeremy S. Brown, John R. Hurst (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)
210 Downloads (Pure)

Abstract

Background Systemic inflammation in bronchiectasis is poorly studied in relation to aetiology and severity. We hypothesized that molecular patterns of inflammation may define particular aetiology and severity groups in bronchiectasis. Method We assayed blood concentrations of 31 proteins from 90 bronchiectasis patients (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 from other centres. Results There was significant heterogeneity in protein concentrations across the derivation population. Increasing severity of bronchiectasis (BSI) was associated with increasing fibrinogen (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. However, patients with primary immunodeficiency had exaggerated IL-17 responses, validated in a second cohort (n = 79, immunodeficient 12.82 pg/ml versus idiopathic/post-infectious 4.95 pg/ml, p = 0.001), and thus IL-17 discriminated primary immunodeficiency from other aetiologies (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 severity. More severe disease is associated with enhanced acute-phase responses. Plasma fibrinogen was associated with bronchiectasis severity in two cohorts, Pseudomonas colonisation and health status, and offers potential as a useful biomarker.

Original languageEnglish
Pages (from-to)33-39
Number of pages7
JournalRespiratory Medicine
Volume127
Early online date17 Apr 2017
DOIs
Publication statusPublished - Jun 2017

Keywords

  • Acute-phase reaction
  • Bronchiectasis
  • Fibrinogen
  • Inflammation
  • Interleukin-17

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