Sublingual assessment of the endothelial glycocalyx reveals vascular endothelial dysfunction in patients with fibrotic interstitial lung disease

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Background: The endothelial glycocalyx (EG) has been postulated as a key mediator of organ fibrosis and may have a role in the aberrant vascular remodelling observed in pulmonary fibrosis. Aims: We aimed to compare EG health between patients with fibrotic-ILD and healthy controls. Methods: Patients with idiopathic pulmonary fibrosis (IPF) and non-IPF fibrotic ILD and age and sex matched healthy controls (HCs) were recruited to a prospective observational study. EG assessment was performed using sublingual side-stream darkfield video-microscopy (GlycoCheckTM) and the perfused boundary region (PBR) in vessels 5-25μm in width, a recognised surrogate for EG width, was recorded. Results: 18 IPF, 16 non-fibrotic ILD and 18 HCs underwent baseline EG assessment with 16, 10 and 15 participants, respectively, undergoing repeat assessment at 6 months. Reasons for missing repeat values included death (4), availability of testing (4) and patient tolerance (5). PBR (5-25μm) was higher in the IPF group compared to HCs at baseline (2.11μm +/- 0.14 vs 1.97μm +/- 0.15, p<0.05) but was not observed at 6 months (p=0.79). In the IPF group at baseline the PBR (5-25μm) correlated significantly with %FVC (r=-0.582, p=0.01) and %TLCO (r=-0.60, p=0.008). PBR (5-25μm) was numerically lower in patients with progression free survival at 12 months (2.05μm +/- 0.11 vs 2.17μm +/-0.16, p=0.064). Conclusions: Sublingual video-microscopy reveals EG dysfunction at baseline in patients with IPF. The role of the EG in the progression of pulmonary fibrosis is yet to be determined and larger studies are required to examine the prognostic significance of EG dysfunction.

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