# Correlation of a combined serum biomarker panel with the composite physiologic index in connective tissue disease-associated interstitial lung disease

## TL;DR

A panel of blood markers can accurately detect and assess the severity of lung disease in patients with connective tissue disorders.

## Contribution

A combined serum biomarker panel shows high accuracy and strong correlation with disease severity in CTD-ILD.

## Key findings

- The combined biomarker panel achieved 94.20% sensitivity and 95.60% specificity for CTD-ILD detection.
- All four biomarkers showed moderate to high positive correlations with the Composite Physiologic Index.
- The panel outperformed individual biomarkers in diagnostic accuracy.

## Abstract

To evaluate the diagnostic performance of a combined serum biomarker panel for connective tissue disease-associated interstitial lung disease (CTD-ILD) and its correlation with disease severity.

This retrospective, cross-sectional study enrolled 200 CTD patients during October 2023 and October 2025, classifying them into CTD-ILD (n = 86) and CTD (n = 114) groups. General clinical characteristics, routine laboratory parameters, serum Krebs von den Lungen-6 (KL-6), surfactant protein A (SP-A), and surfactant protein D (SP-D) levels, serum ferritin (SF), pulmonary function, and the Composite Physiologic Index (CPI) were compared. The predictive power of the biomarker panel was evaluated via receiver operating characteristic (ROC) curves and DeLong’s test, while correlations with the CPI were assessed via Spearman’s correlation analysis.

The groups were comparable in baseline characteristics and routine laboratory parameters. The CTD-ILD group exhibited significantly higher levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and all four serum biomarkers (KL-6, SP-A, SP-D, and SF) (all P < 0.05), alongside impaired pulmonary function and a higher CPI (P < 0.05). The combined biomarker panel achieved an area under the curve of 0.980 (95% CI: 0.964–0.996), with 94.20% sensitivity and 95.60% specificity, significantly outperforming individual biomarkers (all P < 0.05). All biomarkers demonstrated moderate to high positive correlations with the CPI (r = 0.620, 0.520, 0.495, 0.402, respectively; P < 0.001).

The combined serum biomarker panel demonstrated strong discrimination for CTD-ILD in this retrospective cohort and was significantly associated with disease severity.