Elevated Serum Level of Krebs von den Lungen-6 Predicts Death in Patients With Comorbid Idiopathic Pulmonary Fibrosis and Obstructive Sleep Apnea

Abstract

Background: Obstructive sleep apnea (OSA) is prevalent in patients with idiopathic pulmonary fibrosis (IPF). This study evaluated the prognostic significance of Krebs von den Lungen-6 (KL-6) levels in patients with comorbid OSA and IPF.

Methods: This retrospective research included 115 individuals diagnosed with IPF between January 2015 and December 2020, all of whom completed sleep tests and underwent measurement of serum KL-6 levels during hospitalization. To ascertain the risk factors associated with all-cause death, a multivariate Cox regression model was employed, adjusted for confounding variables of age, sex, and pulmonary function.

Results: During the 40-month follow-up, 24 (20.9%) deaths occurred, with 17 (28.8%) in the OSA group and 7 (12.5%) in the non-OSA group. Patients with OSA had higher baseline KL-6 levels than did those without OSA. Both apnea-hypopnea index (hazard ratio [HR] = 1.023, 95% confidence interval [CI] 1.000-1.047, p = 0.049) and serum KL-6 levels (HR = 1.001, 95% CI 0.999-1.002, p = 0.032) were identified as independent risk factors for death in multivariable Cox analysis. For the overall cohort of patients with IPF, those with a KL-6 levels ≥1200 U/mL had a higher risk of death in both univariate analysis (HR = 5.694, 95% CI 1.945-16.669, p = 0.002) and adjusted models (HR = 5.245, 95% CI 1.775-15.494, p = 0.003). In the subgroup analysis, the independent prognostic significance of KL-6 levels ≥1200 U/mL for death was evident only in IPF patients with concurrent OSA (HR = 4.887, 95% CI 1.082-22.067, p = 0.039), whereas it was not observed yet in IPF patients without OSA (HR = 4.652, 95% CI 0.616-35.131, p = 0.136).

Conclusion: KL-6 level is of prognostic value in patients with comorbid IPF and OSA. These findings underscore the need for sleep tests and KL-6 measurement for IPF patients at high risk.

Keywords: death; idiopathic pulmonary fibrosis; obstructive sleep apnea; serum Krebs von den Lungen-6.

Figure 1

Receiver operating characteristic curve of the serum KL-6 for predicting death in patients with IPF.

Figure 2

Kaplan–Meier curves of survival probability of patients with IPF. Non-OSA vs OSA groups in the overall cohort of patients with IPF (A); KL-6 <1200 U/mL vs KL-6 ≥1200 U/mL subgroups in the overall cohort of patients with IPF(B); IPF patients without OSA (C), with OSA (D), with MinSpO₂ ≥85% (E), and with MinSpO₂ < 85% (F), respectively.