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Pathogenesis of post-tuberculosis lung disease: defining knowledge gaps and research priorities at the 2nd International Post-Tuberculosis Symposium

Pathogenesis of post-tuberculosis lung disease: defining knowledge gaps and research priorities at the 2nd International Post-Tuberculosis Symposium
Pathogenesis of post-tuberculosis lung disease: defining knowledge gaps and research priorities at the 2nd International Post-Tuberculosis Symposium

Post-tuberculosis (TB) lung disease (PTLD) is increasingly recognized as a major contributor to the global burden of chronic lung disease, with recent estimates indicating that over half of TB survivors have impaired lung function after successful completion of TB treatment. However, the pathologic mechanisms that contribute to PTLD 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 here the key findings from a literature review of those areas, highlighting knowledge gaps and areas where further research is needed.

1073-449X
Auld, Sara C.
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Barczak, Amy K.
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Bishai, William
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Coussens, Anna K.
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Dewi, Intan M.W.
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Mitini-Nkhoma, Steven C.
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Muefong, Caleb
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Naidoo, Threnesan
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Pooran, Anil
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Stek, Cari
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Steyn, Adrie J.C.
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Tezera, Liku
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Walker, Naomi F.
e586ffdf-ae4b-46fa-83a1-db72501d17c1
Auld, Sara C.
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Barczak, Amy K.
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Bishai, William
d12021cd-50f9-4ac7-b89b-ecb8a73f735b
Coussens, Anna K.
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Dewi, Intan M.W.
90f3728b-e417-4565-bf95-48da3a1e7825
Mitini-Nkhoma, Steven C.
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Muefong, Caleb
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Naidoo, Threnesan
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Pooran, Anil
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Stek, Cari
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Steyn, Adrie J.C.
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Tezera, Liku
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Walker, Naomi F.
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Auld, Sara C., Barczak, Amy K., Bishai, William, Coussens, Anna K., Dewi, Intan M.W., Mitini-Nkhoma, Steven C., Muefong, Caleb, Naidoo, Threnesan, Pooran, Anil, Stek, Cari, Steyn, Adrie J.C., Tezera, Liku and Walker, Naomi F. (2024) Pathogenesis of post-tuberculosis lung disease: defining knowledge gaps and research priorities at the 2nd International Post-Tuberculosis Symposium. American Journal of Respiratory and Critical Care Medicine. (doi:10.1164/rccm.202402-0374SO).

Record type: Article

Abstract

Post-tuberculosis (TB) lung disease (PTLD) is increasingly recognized as a major contributor to the global burden of chronic lung disease, with recent estimates indicating that over half of TB survivors have impaired lung function after successful completion of TB treatment. However, the pathologic mechanisms that contribute to PTLD 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 here the key findings from a literature review of those areas, highlighting knowledge gaps and areas where further research is needed.

Text
Pathogenesis Post-TB Lung Disease (Stellenbosch Review) AJRCCM 2024 - Accepted Manuscript
Restricted to Repository staff only until 14 August 2025.
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More information

Accepted/In Press date: 13 August 2024
e-pub ahead of print date: 14 August 2024

Identifiers

Local EPrints ID: 493787
URI: http://eprints.soton.ac.uk/id/eprint/493787
ISSN: 1073-449X
PURE UUID: 4e4746dd-6867-4b14-9992-32bf2666e40d
ORCID for Liku Tezera: ORCID iD orcid.org/0000-0002-7898-6709

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Date deposited: 12 Sep 2024 16:55
Last modified: 13 Sep 2024 01:46

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Contributors

Author: Sara C. Auld
Author: Amy K. Barczak
Author: William Bishai
Author: Anna K. Coussens
Author: Intan M.W. Dewi
Author: Steven C. Mitini-Nkhoma
Author: Caleb Muefong
Author: Threnesan Naidoo
Author: Anil Pooran
Author: Cari Stek
Author: Adrie J.C. Steyn
Author: Liku Tezera ORCID iD
Author: Naomi F. Walker

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