Departments of Medicine, Epidemiology, and Global Health, Emory University School of Medicine and Rollins School of Public Health, Atlanta, Georgia.
Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts.
Am J Respir Crit Care Med. 2024 Oct 15;210(8):979-993. doi: 10.1164/rccm.202402-0374SO.
Post-tuberculosis (post-TB) lung disease 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 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: ) tissue matrix destruction, including the role of matrix metalloproteinase dysregulation and neutrophil activity; ) fibroblasts and profibrotic activity; ) granuloma fate and cell death pathways; ) mycobacterial factors, including pathogen burden; ) animal models; and ) 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.
肺结核（post-TB）后肺部疾病日益被视为导致全球慢性肺部疾病负担的主要因素之一，最近的估计表明，在成功完成结核病治疗后，超过一半的结核病幸存者的肺功能受损。然而，导致肺结核后肺部疾病的病理机制尚不清楚，从而限制了治疗干预措施的发展，以改善结核病后的长期结局。本报告总结了于 2023 年 4 月在南非斯泰伦博斯举行的第二届国际肺结核后研讨会发病机制和危险因素委员会的工作。委员会首先确定了六个具有高转化潜力的领域：组织基质破坏，包括基质金属蛋白酶失调和中性粒细胞活性的作用；成纤维细胞和促纤维化活性；肉芽肿命运和细胞死亡途径；分枝杆菌因素，包括病原体负担；动物模型；以及关键临床危险因素的影响，包括艾滋病毒、糖尿病、吸烟、营养不良和酒精。我们分享了对这些领域的文献综述的主要发现，突出了知识差距和需要进一步研究的领域。
