Clinical Significance of SP-D Biomarker in the Diagnosis of Connective Tissue Disease-Associated Interstitial Lung Disease: A Systematic Review and Meta-Analysis

OBJECTIVES: Several studies have explored the diagnostic effects of Surfactant protein D (SP-D) as a biomarker in diagnosing connective tissue diseases associated interstitial lung disease (CTD-ILD). Chest high-resolution computed tomography is the gold standard for ILD diagnosis, but costs and ionizing radiation may limit its use in clinical practice. We conducted a meta-analysis to assess the clinical significance of SP-D as a biomarker in patients with CTD-ILD when compared to patients with CTD non-ILD and healthy controls (HC).

METHODS: Comprehensive searches of electronic databases, including MEDLINE, Google Scholar, and Cochrane Library were conducted till December 25^th, 2023. Studies were screened based on a pre-specified protocol. A meta-analysis evaluating the impact of SP-D biomarker was conducted using a random-effects model (REM) as a priori. The impact of heterogeneity was evaluated through sensitivity and subgroup analyses. Impact of outlier studies was assessed using leave-one study out analysis and Galbraith plot.

RESULTS: Thirteen studies evaluating 735 patients with CTD-ILD, 528 patients with CTD non-ILD and 382 HC met the inclusion criteria. In a REM, the overall pooled mean difference (MD) showed a significantly higher SP-D when comparing CTD-ILD with CTD non-ILD [MD:70.82, 95%CI:35.72-105.93, I²=98.62%, p=0.001] and when comparing CTD-ILD with HC [MD:141.29, 95%CI:80.21-202.38, I²=99.12%, p=0.001]. Of the included studies, five studies didn’t show a clinically meaningful difference. Although statistical heterogeneity was high (I²>90%), individual study MDs were directionally aligned with the pooled estimate. A subgroup analysis of studies by study design, study population, region, and biomarker test showed consistent findings aligned with the base case meta-analysis. Assessments of clinical, and statistical heterogeneity indicated the meta-analysis was robust. No publication bias was observed.

CONCLUSIONS: A statistically significantly higher SP-D levels were observed in CTD-ILD patients compared to CTD non ILD and HC. More research must be conducted to strengthen the evidence for SP-D as a biomarker.