Longitudinal analysis of lipid mediators in post-tuberculosis lung disease identifies significant differences

Post-tuberculosis lung disease (PTLD) is a frequent complication after TB cure, affecting millions globally. Yet, its mechanisms, particularly the role of lipid mediators (LMs) in resolution of inflammation are not clear. This study aimed to identify inflammatory and resolution signatures by comparing longitudinal LM profiles in plasma and exhaled breath condensate (EBC) between TB patients who developed PTLD and those with normal lung recovery.In this prospective cohort study, plasma and EBC were collected at diagnosis and post-TB treatment (generally 6 months). Twenty subjects were selected for analysis following TB treatment, 10 cases (impaired lung function indicative of PTLD) and 10 controls (normal lung function). LM analysis was performed using LC-MS/MS. Group comparisons and longitudinal changes were analyzed using differential abundance analyses (limma) with multiple testing correction with sequential goodness-of-fit adjusted p-values.Baseline plasma analysis showed higher PD1, 12-HEPE, 10-HDoHE, 11-HDoHE, 12-HETE, and 13(14)-EpDPE with significantly lower concentrations of PGA2 in cases vs. controls. Post-treatment, cases had lower AT-RvD6 and 15-oxo-LXA4. Longitudinal plasma analysis with linear modeling showed decreased PD1 in cases during treatment relative to controls. EBC analysis showed no significant differences between group or longitudinal linear comparisons.Distinct systemic lipid mediator profiles and their longitudinal trajectories differ between TB patients who subsequently develop PTLD and those who achieve normal lung recovery. Cases showed an altered LM profile at diagnosis that evolved into a post-treatment state with pro-resolving mediator deficiencies and failed to normalize baseline alterations, suggesting dysregulated resolution pathways in PTLD pathogenesis.