Serum KL-6 Levels at Acute Exacerbation in Patients With Interstitial Lung Disease

Background/Aim: Serum KL-6 is widely used to monitor interstitial lung disease (ILD), but its short-term behavior around acute exacerbation (AE) and its prognostic value at AE onset remain unclear. This study evaluated serial KL-6 changes before AE and their association with survival. Patients and Methods: We retrospectively reviewed patients with idiopathic pulmonary fibrosis or progressive pulmonary fibrosis who underwent KL-6 measurement at two hospitals between May 2015 and June 2025. KL-6 at AE onset was compared with values one month earlier, the highest value during the preceding year, and maximum values in patients without AE. Associations with post-AE survival were assessed. Results: Among 409 patients with ILD, KL-6 was measured at onset in 109 AE episodes among 97 patients; 142 patients without AE had at least one measurement. Median KL-6 at AE onset was higher than the median maximum value in patients without AE (1,100 vs. 690 U/ml, p=0.0001). However, paired analyses showed no significant difference between KL-6 at AE onset and the value one month earlier (n=32, p=0.092) or the highest value during the preceding year (n=58, p=0.145). KL-6 at AE onset did not differ among patients who died within 30 days, died between 30 and 90 days, or survived beyond 90 days (p=0.4307). A high KL-6 level (≥1,100 U/ml) was not associated with survival. Conclusion: Although KL-6 levels were higher in patients with interstitial lung disease experiencing AE compared to patients without AE, they did not consistently increase immediately before AE and had limited prognostic value at AE onset.