Analysis of tissue lipidomics and computed tomography pulmonary fat attenuation volume (<scp>CT<sub>PFAV</sub></scp>) in idiopathic pulmonary fibrosis
Marissa O’Callaghan, John Duignan, Elizabeth J. Tarling, Darragh K. Waters, Megan McStay, Orla O’Carroll, James P. Bridges, Elizabeth F. Redente, Alessandro N. Franciosi, Emmet E. McGrath, Marcus W. Butler, Jonathan D. Dodd, Aurélie Fabre, David J. Murphy, Michael P. Keane, Cormac McCarthy
Abstract
Abstract Background and Objective There is increasing interest in the role of lipids in processes that modulate lung fibrosis with evidence of lipid deposition in idiopathic pulmonary fibrosis (IPF) histological specimens. The aim of this study was to identify measurable markers of pulmonary lipid that may have utility as IPF biomarkers. Study Design and Methods IPF and control lung biopsy specimens were analysed using a unbiased lipidomic approach. Pulmonary fat attenuation volume (PFAV) was assessed on chest CT images (CT PFAV ) with 3D semi‐automated lung density software. Aerated lung was semi‐automatically segmented and CT PFAV calculated using a Hounsfield‐unit (−40 to −200HU) threshold range expressed as a percentage of total lung volume. CT PFAV was compared to pulmonary function, serum lipids and qualitative CT fibrosis scores. Results There was a significant increase in total lipid content on histological analysis of IPF lung tissue (23.16 nmol/mg) compared to controls (18.66 mol/mg, p = 0.0317). The median CT PFAV in IPF was higher than controls (1.34% vs. 0.72%, p < 0.001) and CT PFAV correlated significantly with DLCO% predicted ( R 2 = 0.356, p < 0.0001) and FVC% predicted ( R 2 = 0.407, p < 0.0001) in patients with IPF. CT PFAV correlated with CT features of fibrosis; higher CT PFAV was associated with >10% reticulation (1.6% vs. 0.94%, p = 0.0017) and >10% honeycombing (1.87% vs. 1.12%, p = 0.0003). CT PFAV showed no correlation with serum lipids. Conclusion CT PFAV is an easily quantifiable non‐invasive measure of pulmonary lipids. In this pilot study, CT PFAV correlates with pulmonary function and radiological features of IPF and could function as a potential biomarker for IPF disease severity assessment.