Patients’ characteristics
Table 1 shows the clinical characteristics of the patients with AEs of ILDs; there were 38 (40%) patients with high serum KL-6 and 57 (60%) patients with low serum KL-6 levels. The diagnoses of the 95 patients who were all treated with corticosteroid pulse therapy were AE of idiopathic ILDs in 62 patients (65%) and AE of secondary ILDs in 33 patients (35%). There was no significant difference in the diagnoses between the high and low serum KL-6 groups. Other clinical parameters including age, sex, CCIS, symptom onset, blood biomarkers (P/F ratio and SP-D), ground-glass opacity scores calculated from HRCT, and treatment regimens except serum LDH and honeycomb score showed similar tendencies between these groups. High serum KL-6 patients with AEs of idiopathic or secondary ILDs and low serum KL-6 patients with AEs of idiopathic or secondary ILDs had similar 6-month mortality rates (Fig. 1).
Stepwise multiple logistic regression analysis
In both patients with high and low serum KL-6 levels, clinical parameters including age, sex, CCIS, diagnosis of ILDs, P/F ratio, serum LDH and SP-D, and the GGO and honeycomb scores were evaluated using stepwise multiple logistic regression analysis. Whereas serum LDH was a significant predictor of 6-month mortality in high serum KL-6 patients (OR, 1.006; 95% 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 KL-6 patients (Table 2).
Relationship between 6-month mortality and serum LDH levels
In the patients with low serum KL-6 levels, the area under the ROC curve (AUC) was 0.541 in the evaluation of serum LDH as a predictor of 6-month mortality (Fig. 2A). The 57 patients were assigned to groups with either low LDH (N = 11) or high LDH (N = 46) levels based on the optimal cut-off (206 IU/mL). Log-rank tests showed that the Kaplan-Meier survival curves of these groups did not differ significantly (P = 0.227) (Fig. 2A). On the other hand, in the patients with high serum KL-6 levels, the AUC was 0.897 in the evaluation of serum LDH as a predictor of 6-month mortality (Fig. 2B). The optimal cut-off LDH level for estimating 6-month mortality was 381 IU/mL (p < 0.001). The 38 patients were assigned to groups with either low serum LDH (N = 23) or high serum LDH (N = 15) levels based on this cut-off. Log-rank tests showed that the Kaplan-Meier survival curves of these groups differed significantly (P < 0.001 (Fig. 2B)).
Relationship between 6-month mortality and CCIS
In the patients with low serum KL-6 levels, the AUC was 0.836 in the evaluation of CCIS as a predictor of 6-month mortality (Fig. 3A). The optimal cut-off CCIS value for predicting 6-month mortality was 4 points (p < 0.001). The 57 patients were assigned to groups with either low CCIS (N = 41) or high CCI (N = 16) levels based on this cut-off value. Log-rank tests showed that the Kaplan-Meier survival curves of these groups differed significantly (P < 0.001 (Fig. 3A)). On the other hand, in the patients with high serum KL-6 levels, the AUC was 0.663 in the evaluation of CCIS as a predictor of 6-month mortality (Fig. 3B). The 57 patients were assigned to groups with either low CCIS (N = 27) or high CCIS (N = 11) levels based on the same cut-off value. Log-rank tests showed that the Kaplan-Meier survival curves of these groups did not differ significantly (P = 0.083) (Fig. 3B).
Incidence of complications according to the serum KL-6 level and 6-month outcomes
Figure 4 shows a comparison of comorbidities in survivors with low serum KL-6 levels (A), non-survivors with low KL-6 levels (B), survivors with high serum KL-6 levels (C), and non-survivors with high serum KL-6 levels (D), respectively, from the left bar. The incidences of congestive heart failure (12%, 33%, 0%, 17%), symptomatic chronic pulmonary disease (29%, 73%, 46%, 50%), cerebrovascular disease (2%, 27%, 4%, 8%), and second metastatic solid tumours (2%, 33%, 4%, 17%) were the highest in non-survivors with low serum KL-6 levels (all p < 0.05). In this cohort, there was no difference in the rate of death from comorbidities between the high and low serum KL-6 groups (data not shown).