Associations of the Serum KL-6 with Severity and Prognosis in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Lung. 2024 Jun;202(3):245-255. doi: 10.1007/s00408-024-00702-5. Epub 2024 May 14.

Abstract

Background: As a biomarker of alveolar-capillary basement membrane injury, Krebs von den Lungen-6 (KL-6) is involved in the occurrence and development of pulmonary diseases. However, the role of the KL-6 in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has yet to be elucidated. This prospective study was designed to clarify the associations of the serum KL-6 with the severity and prognosis in patients with AECOPD.

Methods: This study enrolled 199 eligible AECOPD patients. Demographic data and clinical characteristics were recorded. Follow-up was tracked to evaluate acute exacerbation and death. The serum KL-6 concentration was measured via an enzyme-linked immunosorbent assay.

Results: Serum KL-6 level at admission was higher in AECOPD patients than in control subjects. The serum KL-6 concentration gradually elevated with increasing severity of AECOPD. Pearson and Spearman analyses revealed that the serum KL-6 concentration was positively correlated with the severity score, monocyte count and concentrations of C-reactive protein, interleukin-6, uric acid, and lactate dehydrogenase in AECOPD patients during hospitalization. A statistical analysis of long-term follow-up data showed that elevated KL-6 level at admission was associated with longer hospital stays, an increased risk of future frequent acute exacerbations, and increased severity of exacerbation in COPD patients.

Conclusion: Serum KL-6 level at admission is positively correlated with increased disease severity, prolonged hospital stay and increased risk of future acute exacerbations in COPD patients. There are positive dose-response associations of elevated serum KL-6 with severity and poor prognosis in COPD patients. The serum KL-6 concentration could be a novel diagnostic and prognostic biomarker in AECOPD patients.

Keywords: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD); KL-6; Prognosis; Severity.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers* / blood
  • C-Reactive Protein* / analysis
  • C-Reactive Protein* / metabolism
  • Case-Control Studies
  • Disease Progression*
  • Female
  • Humans
  • Interleukin-6* / blood
  • L-Lactate Dehydrogenase / blood
  • Leukocyte Count
  • Male
  • Middle Aged
  • Mucin-1* / blood
  • Prognosis
  • Prospective Studies
  • Pulmonary Disease, Chronic Obstructive* / blood
  • Pulmonary Disease, Chronic Obstructive* / diagnosis
  • Pulmonary Disease, Chronic Obstructive* / mortality
  • Pulmonary Disease, Chronic Obstructive* / physiopathology
  • Severity of Illness Index*
  • Uric Acid / blood

Substances

  • Mucin-1
  • MUC1 protein, human
  • Biomarkers
  • C-Reactive Protein
  • Interleukin-6
  • Uric Acid
  • L-Lactate Dehydrogenase