CRP, Fibrinogen, White Blood Cells, and Blood Cell Indices as Prognostic Biomarkers of Future COPD Exacerbation Frequency: The TIE Cohort Study.

Background/Objective : Systemic inflammation is common in chronic obstructive pulmonary disease (COPD), and evidence suggests that inflammatory biomarkers can predict acute exacerbations (AECOPDs). The aim of this study was to analyse whether C-reactive protein (CRP), fibrinogen, white blood cell count (WBC), or the blood cell indices PLR (platelet-to-lymphocyte ratio), SII (systemic immune inflammation index), SIRI (systemic inflammation response index), and AISI (aggregate index of systemic inflammation) can predict future AECOPDs. Methods: In the Tools Identifying Exacerbations (TIE) cohort study, participants with spirometry-confirmed COPD were recruited from primary and secondary care in three Swedish regions and assessed during a stable phase of COPD. AECOPD frequency during the three-year follow-up was reviewed in medical records. Associations were analysed via ordinal logistic regressions. Results: Of the 571 participants, 46% had ≥1 AECOPD during follow-up, and the mean ± SD AECOPD frequency was 0.63 ± 1.2/year. In unadjusted analyses, high levels of CRP (odds ratio 1.86, 95% CI 1.29-2.67), fibrinogen (2.09, 1.38-3.16), WBCs (2.18, 1.52-3.13), SII (1.52, 1.05-2.19), SIRI (1.76, 1.23-2.52), and AISI (1.99, 1.38-2.87) were associated with a higher AECOPD frequency. After adjustment for AECOPD history, age, sex, smoking, body mass index, COPD Assessment Test score, lung function, and inhaled corticosteroid use, associations remained for high levels of CRP (adjusted odds ratio of 1.64; 95% CI of 1.08-2.49), fibrinogen (1.55; 1.07-2.24), and WBC (1.65; 1.10-2.47). Conclusions: CRP, fibrinogen, and WBC, assessed during stable-phase COPD, enhanced AECOPD prediction, whereas PLR, SII, SIRI, and AISI did not.