Association of pulmonary function testing abnormalities and severe veno-occlusive disease of the liver after marrow transplantation

Abstract

We investigated an association between pulmonary function testing (PFT) before bone marrow transplantation and the development of severe veno-occlusive disease (VOD) of the liver. We previously noted that reductions in diffusing capacity of the lung for carbon monoxide (corrected for hemoglobin) (D_LCO_c) were associated with mortality after transplantation, but this was not caused by respiratory failure. We performed a case-series review of prospectively collected data from 307 marrow recipients who underwent PFT within 2 weeks of transplantation. Of these, 170 (56%) developed VOD; 39 (13%) mild, 81 (26%) moderate, and 50 (16%) severe or fatal. Both total lung capacity (TLC) and D_LCO_c were associated with severe VOD in univariate analysis (P = 0.006 for each). However, D_LCO_c entered logistic regression models that contained variables for all known risk factors for severe VOD, while TLC did not contribute additional predictive information. The odds ratio (OR) associated with a D_LCO_c below the lower limits of normal (70% of predicted) was 2.4 (95% CI, 1.0 to 5.4; P = 0.04). We conclude that reduced diffusion capacity of the lung measured before marrow transplantation is an independent risk for severe hepatic VOD. We speculate that the decreased D_LCO_c indicates pre-existing systemic endothelial cell damage and a susceptibility to severe hepatic injury from chemotherapy.