Potential soluble biomarkers in peripheral blood/bronchoalveolar lavage fluid (BALF) for the diagnosis of systemic sclerosis interstitial lung disease (SSc-ILD) include Krebs von den Lungen-6 (KL-6), surfactant protein-D (SP-D), and interleukin-8 (IL-8), according to a systematic review and meta-analysis published in Thorax.
Systemic sclerosis-associated interstitial lung disease (SSc-ILD) — a rare, poorly understood disorder with heterogeneous features — is difficult to diagnose. Investigators therefore conducted a systematic review and meta-analysis of soluble biomarkers in peripheral blood or BALF in order to identify mediators of SSc-ILD.
The authors searched 5 databases for observational or interventional, peer-reviewed studies conducted in adults that were published between January 2000 and September 2021. All qualifying studies needed to have evaluated biomarkers in peripheral blood or BALF among patients with SSc-ILD compared with healthy controls. Qualitative assessment was carried out via use of Critical Appraisal Skills Programme checklists.
Screening identified 768 publications for systematic review of soluble biomarkers in patients with SSc-ILD. Ultimately, a total of 38 articles were included in the qualitative synthesis. Additionally, 13 studies were included in the random effects meta-analysis that represented the following 3 biomarkers: KL-6, SP-D, and IL-8.
Results of the analysis showed that greater levels of IL-8 were associated with SSc-ILD in both peripheral blood and BALF (overall standardized mean difference [SMD], 0.88; 95% CI, 061-1.15; I2=1%). Higher levels of both SP-D and KL-6 were estimated in
SSc-ILD peripheral blood compared with healthy controls (SMD, 1.78; 95% CI, 1.50-2.17; I2=8% and SMD, 1.66; 95% CI, 1.17-2.14; I2=76%, respectively).
Several limitations of the current analysis warrant mention. Although they are not disease-specific, KL-6, SP-D, and IL-8 are useful biomarkers for an SSc-ILD diagnosis; however, verification of their utility as prognostic or severity indicators is still needed. Additionally, because many of the identified soluble markers were represented only by a single study, further investigations are needed into the mediators of fibrotic lung diseases.
The researchers concluded, “We provide robust evidence that KL-6, SP-D and IL-8 have the potential to serve as reliable biomarkers in blood/BALF for supporting the diagnosis of SSc-ILD,” said review authors. “However, while several other biomarkers have been proposed, the evidence of their independent value
in diagnosis and prognosis is currently lacking and needs further investigation,” the researchers added.
Fields A, Potel KN, Cabuhal R, Aziri B, Stewart ID, Schock BC. Mediators of systemic sclerosis-associated interstitial lung disease (SSc-ILD): systematic review and meta-analyses. Thorax. Published online October 19, 2022. doi:10.1136/thorax-2022-219226