NYU Langone Translational Lung Biology Laboratory, Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine, NYU Langone Health, 550 First Avenue, MSB 594, New York, NY, USA.
Division of Pulmonology, Department of Medicine, Stellenbosch University & Tygerberg Hospital, South Africa.
Tuberculosis (Edinb). 2022 Sep;136:102244. doi: 10.1016/j.tube.2022.102244. Epub 2022 Aug 11.
Post Tuberculosis Lung Disease (PTLD) affects millions of tuberculosis survivors and is a global health burden. The immune mechanisms that drive PTLD are complex and have historically been under investigated. Here, we discuss two immune-mediated paradigms that could drive human PTLD. We review the characteristics of a fibrotic granuloma that favors the development of PTLD via an abundance of T-helper-2 and T-regulatory cells and an upregulation of TGF-β mediated collagen deposition. Next, we discuss the post-primary tuberculosis paradigm and the complex mixture of caseous pneumonia, cavity formation and fibrosis that can also lead to PTLD. We review the delicate balance between cellular subsets and cytokines of the innate and adaptive immune system in conjunction with host-derived proteases that can perpetuate the parenchymal lung damage seen in PTLD. Next, we discuss the role of novel host directed therapies (HDT) to limit the development of PTLD and in particular, the recent repurposing of established medications such as statins, metformin and doxycycline. Finally, we review the emerging role of novel imaging techniques as a non-invasive modality for the early recognition of PTLD. While access to computed tomography imaging is unlikely to be available widely in countries with a high TB burden, its use in research settings can help phenotype PTLD. Due to a lack of disease-specific biomarkers and controlled clinical trials, there are currently no evidence-based recommendations for the management of PTLD. It is likely that an integrated antifibrotic strategy that could simultaneously target inflammatory and pro-fibrotic pathways will probably emerge as a successful way to treat this complex condition. In a disease spectrum as wide as PTLD, a single immunologic or radiographic marker may not be sufficient and a combination is more likely to be a successful surrogate that could aid in the development of successful HDTs.
肺结核后肺病 (PTLD) 影响着数以百万计的肺结核幸存者，是全球的健康负担。导致 PTLD 的免疫机制复杂，且历史上研究不足。在这里，我们讨论两种可能导致人类 PTLD 的免疫介导模式。我们回顾了有利于通过丰富的辅助性 T 细胞 2 和调节性 T 细胞以及 TGF-β 介导的胶原蛋白沉积来发展 PTLD 的纤维化肉芽肿的特征。接下来，我们讨论原发性肺结核后模式以及干酪样肺炎、空洞形成和纤维化的复杂混合物，这也可能导致 PTLD。我们回顾了先天和适应性免疫系统细胞亚群和细胞因子之间的微妙平衡，以及宿主来源的蛋白酶，这些可以延续 PTLD 中看到的实质肺损伤。接下来，我们讨论了新型宿主定向治疗 (HDT) 的作用，以限制 PTLD 的发展，特别是最近重新利用已建立的药物，如他汀类药物、二甲双胍和强力霉素。最后，我们回顾了新兴的新型成像技术作为早期识别 PTLD 的非侵入性方法的作用。虽然在结核病负担高的国家中不太可能广泛获得计算机断层扫描成像，但它在研究环境中的使用可以帮助对 PTLD 进行表型分析。由于缺乏疾病特异性生物标志物和对照临床试验，目前没有针对 PTLD 管理的循证建议。很可能一种综合的抗纤维化策略，同时针对炎症和促纤维化途径，将成为治疗这种复杂疾病的成功方法。在像 PTLD 这样广泛的疾病谱中，单一的免疫或放射标记物可能不够，组合更有可能成为成功的替代物，可以帮助开发成功的 HDT。
