Clinical subtyping for patients with acute exacerbations of interstitial lung diseases guided by serum KL-6 measurement

Introduction: Serum Krebs von den Lungen-6 (KL-6) measurement is widely used to assess disease activity or prognosis in patients with interstitial lung diseases (ILDs). However, the clinical differences between high and low serum KL-6 levels at the time of acute exacerbation (AE) of ILD are not well known.Methods: Clinical parameters including age, sex, Charlson Comorbidity Index score (CCIS), blood biomarkers, high-resolution CT findings, and disease mortality were retrospectively compared between high and low KL-6 (cut-off value: 1000 U/mL) patients at the time of diagnosis of AE of ILDs.Results: 38 high serum KL-6 and 57 low serum KL-6 patients were included. There was no significant difference in 6-month mortality between them (P = 0.685). Whereas serum lactate dehydrogenase was a significant predictor of 6-month mortality in the high serum KL-6 patients (odds ratio (OR), 1.006; 95% confidence interval (CI), 1.003-1.009; P < 0.001), CCIS (OR, 1.502; 95% CI, 1.242-1.838; P < 0.001) and sex (OR, 5.751; 95% CI, 1.121-105.163; P = 0.033) were significant predictors in low serum KL-6 patients. In addition, the incidences of congestive heart failure, symptomatic chronic pulmonary disease, cerebrovascular disease, and second metastatic solid tumours were significantly higher in non-survivors with low serum KL-6 than in other groups (p < 0.05).Conclusions: The clinical features in patients with AEs of ILDs may differ depending on the serum KL-6 level, and clinicopathological examination according to this subtyping guided by the serum KL-6 level is essential.