TY -的T1 -主机lipidome和肺结核胎面tment failure JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.04532-2020 VL - 59 IS - 1 SP - 2004532 AU - Shivakoti, Rupak AU - Newman, John W. AU - Hanna, Luke Elizabeth AU - Queiroz, Artur T.L. AU - Borkowski, Kamil AU - Gupte, Akshay N. AU - Paradkar, Mandar AU - Satyamurthi, Pattabiraman AU - Kulkarni, Vandana AU - Selva, Murugesh AU - Pradhan, Neeta AU - Shivakumar, Shri Vijay Bala Yogendra AU - Natarajan, Saravanan AU - Karunaianantham, Ramesh AU - Gupte, Nikhil AU - Thiruvengadam, Kannan AU - Fiehn, Oliver AU - Bharadwaj, Renu AU - Kagal, Anju AU - Gaikwad, Sanjay AU - Sangle, Shashikala AU - Golub, Jonathan E. AU - Andrade, Bruno B. AU - Mave, Vidya AU - Gupta, Amita AU - Padmapriyadarsini, Chandrasekaran Y1 - 2022/01/01 UR - //www.qdcxjkg.com/content/59/1/2004532.abstract N2 - Introduction Host lipids play important roles in tuberculosis (TB) pathogenesis. Whether host lipids at TB treatment initiation (baseline) affect subsequent treatment outcomes has not been well characterised. We used unbiased lipidomics to study the prospective association of host lipids with TB treatment failure.Methods A case–control study (n=192), nested within a prospective cohort study, was used to investigate the association of baseline plasma lipids with TB treatment failure among adults with pulmonary TB. Cases (n=46) were defined as TB treatment failure, while controls (n=146) were those without failure. Complex lipids and inflammatory lipid mediators were measured using liquid chromatography mass spectrometry techniques. Adjusted least-square regression was used to assess differences in groups. In addition, machine learning identified lipids with highest area under the curve (AUC) to classify cases and controls.Results Baseline levels of 32 lipids differed between controls and those with treatment failure after false discovery rate adjustment. Treatment failure was associated with lower baseline levels of cholesteryl esters and oxylipin, and higher baseline levels of ceramides and triglycerides compared to controls. Two cholesteryl ester lipids combined in a unique classifier model provided an AUC of 0.79 (95% CI 0.65–0.93) in the test dataset for prediction of TB treatment failure.Conclusions We identified lipids, some with known roles in TB pathogenesis, associated with TB treatment failure. In addition, a lipid signature with prognostic accuracy for TB treatment failure was identified. These lipids could be potential targets for risk-stratification, adjunct therapy and treatment monitoring.In this study, unbiased lipidomics were used to identify host lipids prospectively associated with TB treatment failure. These lipids, some with known roles in TB pathogenesis, could be potential targets for adjunct therapy and treatment monitoring. https://bit.ly/3vHZ0Ec ER -