KL‑6, ET‑1 and S100A9 levels in patients with idiopathic pulmonary fibrosis and obstructive sleep apnea

Obstructive sleep apnea (OSA) and idiopathic pulmonary fibrosis (IPF) frequently coexist. Elevated levels of Krebs von den Lungen-6 (KL-6), endothelin-1 (ET-1) and S100 calcium-binding protein A9 (S100A9) have been observed in patients with IPF, suggesting their potential role as biomarkers for lung fibrosis. The aim of the present study was to measure the levels of KL-6, ET-1 and S100A9 in patients with IPF-OSA and to test the potential of these biomarkers as a characteristic OSA signature with diagnostic and prognostic potential for IPF. A total of 55 subjects with newly-diagnosed IPF participated in the present cross-sectional study. In addition to performing overnight attended polysomnography and pulmonary function tests, serum and bronchoalveolar lavage (BAL) levels of KL-6, along with serum levels of ET-1 and S100A9, were also assessed. A total of 15 patients with IPF and 40 patients with IPF-OSA were included. Age, sex, comorbidities and pulmonary function tests did not differ between the groups. Although there was no significant difference between groups in the levels of KL-6, ET-1 and S100A9 (P>0.05), the serum ET-1 levels tended to be elevated in patients with OSA-IPF compared with patients with IPF (1.78 vs. 1.07 pg/ml; P=0.06). Additionally, a significant association was observed between serum KL-6 levels and the severity of IPF, and also between BAL KL-6 levels and nocturnal mean SaO₂ levels, even after taking into account factors such as obesity and smoking. S100A9 levels were associated with the oxygen desaturation index, even after adjustments for obesity, smoking and the gender-age-physiology index, only in the IPF-OSA group. Conclusively, the present findings suggested significant associations between serum ET-1, S100A9 and BAL KL-6 levels and specific OSA severity parameters in the IPF-OSA group. This evidence suggested that these molecules could serve as biomarkers for the identification of patients with IPF-OSA, offering a distinct OSA signature that has diagnostic and potential treatment value. Larger studies are crucial to substantiate the present findings and reinforce this hypothesis.