Roles of C-reactive protein and its composite index in predicting acute exacerbation of bronchiectasis.

Background: Acute exacerbation of bronchiectasis is a critical driver of hospitalization and mortality, yet reliable biomarkers for predicting the frequency of adverse events (AEs) remain underexplored. C-reactive protein (CRP) and its composite indices (CAR: CRP/albumin ratio; CPR: CRP/prealbumin ratio) may reflect systemic inflammation and nutritional status.

Objectives: This study aimed to evaluate the ability of the CRP level, CAR, and CPR to predict the frequency of acute exacerbation among bronchiectasis patients.

Methods: A retrospective cohort of 223 stable bronchiectasis patients (2009-2019) was stratified into three groups according to the annual acute exacerbation frequency: Groups A (0), B (1-2), and C (≥ 3). Serum CRP, albumin, prealbumin, the CAR, and the CPR were analyzed. Multivariable analyses included ANOVA, Spearman's correlation, logistic regression adjusted for clinical confounders (dyspnea, COPD, nutritional markers), and ROC curve evaluation with DeLong's test for AUC comparison.

Results: Significant differences were observed across exacerbation frequency groups (A: 0, B: 1-2, C: ≥ 3 events/year), with Group C exhibiting the highest serum levels of CRP (12.25 ± 8.34 mg/L), CAR (0.31 ± 0.25), and CPR (60.83 ± 52.68), and the lowest albumin (41.07 ± 5.61 g/L; all P < 0.05). Acute exacerbation frequency showed strong positive correlations with CRP (r = 0.643), CAR (r = 0.637), and CPR (r = 0.603; all P < 0.05). Following multivariable adjustment for confounders (including demographics, dyspnea, COPD, and nutritional markers), CRP (adjusted odds ratio [aOR] = 1.092, P = 0.006), CAR (aOR = 1.104, P = 0.002), and CPR (aOR = 1.025, P = 0.001) remained independent predictors of frequent exacerbations (≥ 3/year). Receiver operating characteristic (ROC) analysis for predicting frequent exacerbations identified CAR > 0.15 as the most sensitive cutoff (74.3%) and CPR > 32.1 as the most specific (70.6%). Integrating CRP, CAR, or CPR with a clinical model (age, sex, albumin, prealbumin, dyspnea, COPD) significantly enhanced predictive accuracy compared to the clinical model alone (AUC range: 0.815-0.828 vs. 0.762; all P < 0.001). However, the differences in AUC between CRP (0.815), CAR (0.828), and CPR (0.821) were minimal.

Conclusions: Elevated CRP, CAR, and CPR levels correlate with increased exacerbation frequency and independently predict high-risk patients (≥ 3 events/year). While CAR and CPR offer modest improvements over CRP alone, their additional predictive value is limited due to the inherent biological relationship between these markers. Measuring CRP alone may be sufficient for clinical risk stratification to guide early interventions. Prospective validation of these inflammatory markers is warranted.

Clinical Trial Number: Not applicable.