Altered Lipid Metabolism in the Follow Up of Cystic Fibrosis Lung Transplant Patients

Abstract

<h3>Purpose</h3> This study is aimed at characterizing lipid metabolism alteration in Cystic Fibrosis (CF) patients before and after lung transplant (LuTX), in association with pharmacological therapies, dietary patterns and clinical features, at the aim of elucidating its role in LuTX rejection versus graft tolerance. In spite of reduced body weight, among CF comorbidities, plasma hypertriglyceridemia and low HDL, associated with ectopic lipid accumulation including the airways, liver steatosis and CF related diabetes are reported. An altered ability to oxidize lipids for energy requests was recently suggested in these patients and a high ratio between fat mass and lean mass correlates with clinical worsening, such as reduced FEV and recurrent infections. LuTX causes an increase in fat trunk; it is per se a cause of diabetes insurgence, partially dependent on immunosuppressive therapy. Both reduced and increased weight are considered in the prognosis of rejection and pharmacological reduction of lipid synthesis, by means of statins or activation lipid oxidation by glitazones, may implement survival in LuTX patients. Leptin and adiponectin ratio is altered in CF and in LuTX rejecting patients and CF LuTx exhibit a significantly higher risk to develop hyperlipidemia than non CF. The hypothesis of this study is that CF dyslipidemia and altered ability to use lipids for energy requirement can negatively impact on LuTX, worsening the graft implantation related comorbidities <h3>Methods</h3> The cohort includes adults CF in list for LuTX. Evaluations are performed either before and after LuTX (up to 6 months post). Lipidomic profile is obtained by untargeted LC-MS analyses from plasma, plasma derived microvesicles, explanted lungs and surveillance transbronchial biopsies. Transcriptional profile of lipid metabolism related genes is obtained in lung biopsies by RT-PCR. Lipid metabolism related hormones are evaluated by Luminex multiplex assays from patients' plasma. Clinical biochemistry, lung functional analyses, and nutritional evaluation are routinely performed. <h3>Endpoints</h3> We aim at identifying a lipid metabolism derangement in association with CF LuTX adverse prognosis. The study will provide evidence on the importance of introducing novel nutritional and pharmacological intervention in the follow up of these patients.