Identifying serum molecular biomarkers that distinguish emphysema and early fibrotic interstitial lung disease

Abstract

Numerous circulating molecular biomarkers, including MMP1, MMP7 and VEGF have been described in patients with emphysema and idiopathic pulmonary fibrosis (IPF). Fibrotic interstitial pneumonias including IPF often co-exist with emphysema. We sought to determine if these biomarkers can distinguish emphysema from fibrosis in patients with very early fibrotic interstitial lung disease. Subjects for this retrospective cohort study were identified from an existing local database and biobank (ELFMEN, NCT04016181). High Resolution Computerised Tomography (HRCT) diagnosis of emphysema, Minimal Fibrosis (<2% of lung volume) and emphysema plus Minimal Fibrosis was made in a multidisciplinary setting. Serum MMP1, MMP7 and VEGF was measured by Luminex assay. Serum MMP7 was higher in Minimal Fibrosis (n=8) than in healthy controls (n=13) or subjects with emphysema (n=32) (p=0.039;p<0.001). Serum MMP1 and VEGF do not differ between these three cohorts. MMP7 in emphysema plus Minimal Fibrosis (n=9) was higher than MMP7 in solitary emphysema (p<0.001), but not significantly higher than MMP7 in healthy controls. These results suggest that serum MMP7 is raised in patients with Minimal Fibrosis and is not impacted by coexisting emphysema. MMP7 may complement HRCT scanning enabling the detection of early fibrotic disease.