Diagnostic and prognostic predictive values of circulating KL-6 for interstitial lung disease: A PRISMA-compliant systematic review and meta-analysis

BACKGROUND: Past investigations showed inconsistent results for diagnostic and prognostic predictive values of Krebs von den Lungen-6 (KL-6) for interstitial lung disease (ILD). METHODS: Web of Science and PubMed were systematically searched on for articles exploring the association of KL-6 and ILDs published between September 1993 and March 2019. For comparisons between-groups, the standard mean difference and 95% confidence intervals (CIs) were computed as the effect sizes. For diagnostic studies, a summary of sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, and diagnostic odds ratio, which indicated the accuracy of KL-6 in the differentiation of ILDs and no ILDs, were calculated from the true positive, true negative, false positive, and false negative of each study. In addition, the summary receive-operating characteristics curve was constructed to summarize the TP and FP rates. For follow-up study, we computed hazard ratios (HRs) and 95% CIs for mortality. ILD patients showed elevated concentrations of KL-6, compared to healthy controls and patients without ILD. RESULTS: The meta-analysis showed a sensitivity (0.85 [95% CI: 0.77–0.91]) and specificity (0.97 [95% CI: 0.90–0.99]) of KL-6 for ILDs. In addition, it showed elevated baseline circulating levels of KL-6 in subsequent active ILD, compared to subsequent inactive ILD. Moreover, there was a significant association between baseline levels of circulating KL-6 and mortality of ILD (HR 2.95, 95% CI 2.45–3.55, I(2) = 65.9%, P = .032). CONCLUSION: In conclusion, the study suggested that circulating KL-6 showed diagnostic and prognostic predictive values for ILDs.