Krebs von den Lungen-6 as a potent indicator of the frequency of chronic obstructive pulmonary disease exacerbation

Objective To evaluate the potential of systemic Krebs von den Lungen-6 level in predicting acute exacerbations of chronic obstructive pulmonary disease. Methods This two-phase study included a derivation phase (January 2022 to December 2022) involving 156 patients with stable chronic obstructive pulmonary disease, in which optimal Krebs von den Lungen-6 thresholds were identified through multivariate modeling. Serum levels of Krebs von den Lungen-6 and surfactant protein D were analyzed for correlations with exacerbation frequency, Chronic Obstructive Pulmonary Disease Assessment Test score, modified British Medical Research Council score, forced expiratory volume in 1 second percent predicted, and forced expiratory volume in 1 second/forced vital capacity ratio. Prospective validation was performed in a separate cohort (January 2023 to December 2023, n = 121) stratified by Krebs von den Lungen-6 thresholds. Results Krebs von den Lungen-6 and surfactant protein D levels were significantly correlated with exacerbation frequency, Chronic Obstructive Pulmonary Disease Assessment Test, and modified British Medical Research Council scores and were inversely associated with forced expiratory volume in 1 second percent predicted and forced expiratory volume in 1 second/forced vital capacity ratio. Multivariate analysis identified Krebs von den Lungen-6, but not surfactant protein D, as an independent predictor of high-exacerbation phenotypes (≥2 events/year). In the validation phase, the high-Krebs von den Lungen-6 group (≥400.5 U/mL) exhibited significantly higher annual exacerbation rates than the low-Krebs von den Lungen-6 group after adjustment for baseline characteristics. Conclusions Serum Krebs von den Lungen-6 at ≥400.5 U/mL is an independent risk factor for frequent exacerbations of chronic obstructive pulmonary disease. Its association with inflammatory markers and lung function decline suggests potential utility in personalized treatment strategies.