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However, the pathologic mechanisms that contribute to post-TB lung disease are not well understood, thus limiting the development of therapeutic interventions to improve long-term outcomes after TB. This report summarizes the work of the Pathogenesis and Risk Factors Committee for the Second International Post-Tuberculosis Symposium, which took place in Stellenbosch, South Africa, in April 2023. The committee first identified six areas with high translational potential: 1) tissue matrix destruction, including the role of matrix metalloproteinase dysregulation and neutrophil activity; 2) fibroblasts and profibrotic activity; 3) granuloma fate and cell death pathways; 4) mycobacterial factors, including pathogen burden; 5) animal models; and 6) the impact of key clinical risk factors, including HIV, diabetes, smoking, malnutrition, and alcohol. We share the key findings from a literature review of those areas, highlighting knowledge gaps and areas where further research is needed.<\/jats:p>","DOI":"10.1164\/rccm.202402-0374so","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T12:58:57Z","timestamp":1723640337000},"page":"979-993","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":42,"title":["Pathogenesis of Post-Tuberculosis Lung Disease: Defining Knowledge Gaps and Research Priorities at the Second International Post-Tuberculosis Symposium"],"prefix":"10.1093","volume":"210","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8972-3736","authenticated-orcid":false,"given":"Sara C.","family":"Auld","sequence":"first","affiliation":[{"name":"Departments of Medicine, Epidemiology, and Global Health, Emory University School of Medicine and Rollins School of Public Health, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3806-2381","authenticated-orcid":false,"given":"Amy K.","family":"Barczak","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts"},{"name":"Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, Massachusetts"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8734-4118","authenticated-orcid":false,"given":"William","family":"Bishai","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7086-2621","authenticated-orcid":false,"given":"Anna K.","family":"Coussens","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immune Defence Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia"},{"name":"Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4910-9651","authenticated-orcid":false,"given":"Intan M. 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