Association between serial changes in serum C-reactive protein levels and mortality among patients with pleural empyema: a database research.

backgroundAlthough previous studies have evaluated C-reactive protein (CRP) as a diagnostic marker for pleural empyema, the prognostic value of baseline and serial CRP measurements has not been adequately assessed. The aim of this study was to assess the association between serial measurements of serum CRP levels and mortality risk among patients with empyema.

methodsThis database research was performed using the RWD database. Patients with pleural empyema aged ≥ 40 years who underwent thoracostomy (chest tube insertion) on admission or the next day were included. The exclusion criteria were missing covariates, death within 24 h, or transfer to another hospital within 24 h. Baseline and serial CRP levels were assessed as exposures. The primary outcome was the time to death within 90 days after admission. A multivariate Cox proportional hazards model was used to evaluate the association between baseline CRP levels and death. Because the timing of CRP measurements depended on each patient’s clinical course, a joint regression model was applied to evaluate each patient’s serial serum CRP measurements and death. A joint regression model combines longitudinal data analysis for exposure with survival analysis for the outcome. We simultaneously used a linear mixed-effects model to estimate the latent trajectory of serial CRP levels and a relative risk model to estimate the association between serial CRP measurements and death, with adjustment for clinically important confounders.

resultsWe included 823 patients in the analysis. Of these, 82 (10%) died, and 85 (10%) underwent thoracic surgery. Ninety days after admission, 430 patients (52%) were censored. The log of baseline CRP levels was not associated with mortality risk (hazard ratio: 0.84 [95% confidence interval, 0.59–1.20]), whereas a higher cumulative log of serum CRP levels was associated with a higher mortality risk over time (hazard ratio: 2.08 [95% confidence interval, 3.28–5.18]).

conclusionsBaseline serum CRP levels were not associated with mortality risk, whereas a serial upward trend in serum CRP levels was strongly associated with increased mortality risk. Physicians can consider serial serum CRP levels as a biomarker for monitoring the treatment response in patients with pleural empyema.