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

Bibliographic Data

ID19591430
AuthorsPeter D Jackson (0000-0001-5108-9381, Virginia Commonwealth University, corresponding author), Madeline Helwig (0009-0003-3860-4168, Virginia Commonwealth University), Mudarshiru Bbuye (0000-0002-8635-2925, Makerere University), Margaret A Freeberg, M A T Freeberg (0000-0001-7301-7880, Virginia Commonwealth University), Thomas H Thatcher (0000-0001-7177-3041, Virginia Commonwealth University), Stella Zawedde, Stella Muyanja Zawedde (Makerere University), Bruce Kirenga (0000-0002-2023-2840, Makerere University), William Worodria (0000-0002-8531-5567, Makerere University), Krishnarao Maddipati (Wayne State University), Trishul Siddharthan (0000-0001-9914-1839, University of Miami), Joaquin Reyna (0000-0002-8468-2840, Virginia Commonwealth University), Patricia J Sime (0000-0002-5101-634X, Virginia Commonwealth University)
EditorsPaulo Jorge Gonçalves de Bettencourt
Year2026
Volume6
Issue4
Pagese0006097
Publication date2026-04-08
Open AccessYes
TypeARTICLE
VenuePLOS Global Public Health (JOURNAL)
Journal identifiersISSN: 2767-3375 • E-ISSN: 2767-3375
PublisherPublic Library of Science (PLoS) (PUBLISHER)
DOI10.1371/journal.pgph.0006097
PMID41950292
OpenAlexW7152023155
LanguageEN
References cited34

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

Cohort · Cohort study · Inflammation · Longitudinal study · Lung · Lung function · Mediator · Prospective cohort study · Chronic Obstructive Pulmonary Disease (COPD) Research · Inhalation and Respiratory Drug Delivery · Tuberculosis Research and Epidemiology

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