结核后肺疾病:被忽视的全球健康负担、发病机制及临床管理研究进展

doi:10.19982/j.issn.1000-6621.20250486

摘要/Abstract

摘要：

结核后肺疾病(post-tuberculosis lung disease,PTLD)是一种复杂的慢性多因素疾病,逐渐成为全球不容忽视的公共卫生负担,影响超过半数的结核病幸存者。目前,PTLD标准化定义正在不断完善,其发病机制也尚不清楚,限制了改善结核病后长期预后的治疗干预措施的发展。本综述通过梳理近年来的系统综述、专家共识与临床研究,旨在整合国际学术界关于PTLD的前沿研究进展,系统阐述其临床特征、诊断标准及发病机制,并探讨当前的临床管理策略与未来研究方向,为临床精准决策及结核病幸存者的长期慢性病管理提供循证依据。

关键词: 结核, 肺疾病, 病理学, 临床, 健康促进

Abstract:

Post-tuberculosis lung disease (PTLD) is a complex, chronic, and multifactorial condition that has increasingly become a significant global public health burden, affecting more than half of all tuberculosis (TB) survivors. Currently, although the standardized definition of PTLD is being continuously refined, its underlying pathogenesis remains poorly understood, thereby constraining the development of therapeutic interventions aimed at improving long-term post-TB outcomes. This review systematically synthesizes recent advancements in international research on PTLD by analyzing systematic reviews, expert consensuses, and clinical studies. It aims to provide an integrated framework of PTLD by elucidating its clinical characteristics, diagnostic criteria, and pathogenic mechanisms. Furthermore, this review discusses current clinical management strategies and future research directions to offer evidence-based insights for precision clinical decision-making and long-term chronic disease management for TB survivors.

Key words: Tuberculosis, Lung diseases, Pathology, clinical, Health promotion

中图分类号:

R521

杨欢, 彭奥辉, 江心雨, 陈园园. 结核后肺疾病:被忽视的全球健康负担、发病机制及临床管理研究进展[J]. 中国防痨杂志, 2026, 48(5): 723-630. doi: 10.19982/j.issn.1000-6621.20250486

Yang Huan, Peng Aohui, Jiang Xinyu, Chen Yuanyuan. Post-tuberculosis lung disease (PTLD): research progress on a neglected global health burden, pathogenesis, and clinical management[J]. Chinese Journal of Antituberculosis, 2026, 48(5): 723-630. doi: 10.19982/j.issn.1000-6621.20250486

图/表 2

参考文献 70

[1]	屈燕, 李涛, 马文斌, 等. 世界卫生组织《2025年全球结核病报告》解读. 结核与肺部疾病杂志, 2025, 6 (6): 613-623. doi:10.19983/j.issn.2096-8493.20250178.
[2]	Dodd PJ, Yuen CM, Jayasooriya SM, et al. Quantifying the global number of tuberculosis survivors: a modelling study. Lancet Infect Dis, 2021, 21(7): 984-992. doi:10.1016/S1473-3099(20)30919-1. URL pmid: 33640076
[3]	Allwood BW, van der Zalm MM, Amaral AFS, et al. Post-tuberculosis lung health: perspectives from the First International Symposium. Int J Tuberc Lung Dis, 2020, 24(8): 820-8. doi:10.5588/ijtld.20.0067. URL pmid: 32912387
[4]	Taylor J, Bastos ML, Lachapelle-Chisholm S, et al. Residual respiratory disability after successful treatment of pulmonary tuberculosis: a systematic review and meta-analysis. EClinical Medicine, 2023, 59: 101979. doi:10.1016/j.eclinm.2023.101979.
[5]	Bisson GP, Allwood B, Byrne A, et al. Post-tuberculosis lung disease: a case definition for use in research studies. Lancet Infect Dis, 2025: S1473- 3099(25)00548-1. doi:10.1016/S1473-3099(25)00548-1.
[6]	Cupido G, Günther G. Post tuberculosis lung disease and tuberculosis sequelae: A narrative review. Indian J Tuberc, 2024, 71(1): 64-72. doi:10.1016/j.ijtb.2023.04.001. URL pmid: 38296392
[7]	Allwood BW, Byrne A, Meghji J, et al. Post-Tuberculosis Lung Disease: Clinical Review of an Under-Recognised Global Challenge. Respiration, 2021, 100(8): 751-763. doi:10.1159/000512531.
[8]	Auld SC, Barczak AK, Bishai W, et al. Pathogenesis of Post-Tuberculosis Lung Disease: Defining Knowledge Gaps and Research Priorities at the Second International Post-Tuberculosis Symposium. Am J Respir Crit Care Med, 2024, 210(8): 979-993. doi:10.1164/rccm.202402-0374SO.
[9]	Meghji J, Auld SC, Bisson GP, et al. Post-tuberculosis lung disease: towards prevention, diagnosis, and care. Lancet Respir Med, 2025, 13(5): 460-472. doi:10.1016/S2213-2600(24)00429-6.
[10]	Yadav S, Rawal G. Understanding the Spectrum and Management of Post-Tuberculosis Lung Disease: A Comprehensive Review. Cureus, 2024, 16(6): e63420. doi:10.7759/cureus.63420.
[11]	Yadav S. Understanding the complexities of post-tuberculosis lung disease: Implications for global health. P Indian J Immunol Respir Med, 2024, 9(1): 1-2. doi:10.7759/cureus.49542.
[12]	Allwood BW, Nightingale R, Agbota G, et al. Perspectives from the 2nd International Post-Tuberculosis Symposium: mobilising advocacy and research for improved outcomes. IJTLD Open, 2024, 1(3): 111-123. doi:10.5588/ijtldopen.23.0619. URL pmid: 38966406
[13]	Meghji J, Lesosky M, Joekes E, et al. Patient outcomes associated with post-tuberculosis lung damage in Malawi: a prospective cohort study. Thorax, 2020, 75(3): 269-278. doi:10.1136/thoraxjnl-2019-213808. URL pmid: 32102951
[14]	Nkereuwem E, Agbla S, Sallahdeen A, et al. Reduced lung function and health-related quality of life after treatment for pulmonary tuberculosis in Gambian children: a cross-sectional comparative study. Thorax, 2023, 78(3): 281-287. doi:10.1136/thorax-2022-219085.
[15]	Nightingale R, Chinoko B, Lesosky M, et al. Respiratory symptoms and lung function in patients treated for pulmonary tuberculosis in Malawi: a prospective cohort study. Thorax, 2022, 77(11): 1131-1139. doi:10.1136/thoraxjnl-2021-217190.
[16]	Mbatchou Ngahane BH, Nouyep J, Nganda Motto M, et al. Post-tuberculous lung function impairment in a tuberculosis reference clinic in Cameroon. Respir Med, 2016, 114: 67-71. doi:10.1016/j.rmed.2016.03.007. URL pmid: 27109813
[17]	Singh S, Allwood BW, Chiyaka TL, et al. Immunologic and imaging signatures in post tuberculosis lung disease. Tuberculosis (Edinb), 2022, 136: 102244. doi:10.1016/j.tube.2022.102244.
[18]	王秀芬, 罗莉, 宋美娟, 等. 进阶式呼吸康复训练在中青年结核后肺疾病患者中的应用效果分析. 结核与肺部疾病杂志, 2026, 7(1):92-100. doi:10.19983/j.issn.2096-8493.20250131.
[19]	Gai X, Cao W, Rao Y, et al. Risk factors and biomarkers for post-tuberculosis lung damage in a Chinese cohort of male smokers and non-smokers: protocol for a prospective observational study. BMJ Open, 2023, 13(10): e065990. doi:10.1136/bmjopen-2022-065990.
[20]	Allwood BW, Stolbrink M, Baines N, et al. Persistent chronic respiratory symptoms despite TB cure is poorly correlated with lung function. Int J Tuberc Lung Dis, 2021, 25(4): 262-270. doi:10.5588/ijtld.20.0906. URL pmid: 33762069
[21]	Migliori GB, Marx FM, Ambrosino N, et al. Clinical standards for the assessment, management and rehabilitation of post-TB lung disease. Int J Tuberc Lung Dis, 2021, 25(10): 797-813. doi:10.5588/ijtld.21.0425. URL pmid: 34615577
[22]	Mkoko P, Naidoo S, Mbanga LC, et al. Chronic lung disease and a history of tuberculosis (post-tuberculosis lung disease): Clinical features and in-hospital outcomes in a resource-limited setting with a high HIV burden. S Afr Med J, 2019, 109(3): 169-173. doi:10.7196/SAMJ.2019.v109i3.13366.
[23]	Ivanova O, Hoffmann VS, Lange C, et al. Post-tuberculosis lung impairment: systematic review and meta-analysis of spirometry data from 14 621 people. Eur Respir Rev, 2023, 32(168): 220221. doi:10.1183/16000617.0221-2022.
[24]	Johnson DH, Via LE, Kim P, et al. Nuclear imaging: a powerful novel approach for tuberculosis. Nucl Med Biol, 2014, 41(10): 777-784. doi:10.1016/j.nucmedbio.2014.08.005. URL pmid: 25195017
[25]	Thomson H, Baines N, Huisamen T, et al. A new understanding of clinical patterns in post-TB lung disease. Int J Tuberc Lung Dis, 2024, 28(3): 115-121. doi:10.5588/ijtld.23.0327. URL pmid: 38454184
[26]	Salgame P. MMPs in tuberculosis: granuloma creators and tissue destroyers. J Clin Invest, 2011, 121(5): 1686-1688. doi:10.1172/JCI57423. URL pmid: 21519148
[27]	Wang CH, Lin HC, Lin SM, et al. MMP-1(-1607G) polymorphism as a risk factor for fibrosis after pulmonary tuberculosis in Chinese Taiwan. Int J Tuberc Lung Dis, 2010, 14(5): 627-634. doi:10.5588/ijtld.09.0293. URL pmid: 20392358
[28]	Elkington P, Shiomi T, Breen R, et al. MMP-1 drives immunopathology in human tuberculosis and transgenic mice. J Clin Invest, 2011, 121(5): 1827-1833. doi:10.1172/JCI45666. URL pmid: 21519144
[29]	Shanmugasundaram K, Talwar A, Madan K, et al. Pulmonary Functions and Inflammatory Biomarkers in Post-Pulmonary Tuberculosis Sequelae. Tuberc Respir Dis (Seoul), 2022, 85(2): 175-184. doi:10.4046/trd.2021.0127.
[30]	Sathyamoorthy T, Sandhu G, Tezera LB, et al. Gender-dependent differences in plasma matrix metalloproteinase-8 elevated in pulmonary tuberculosis. PLoS One, 2015, 10(1): e0117605. doi:10.1371/journal.pone.0117605.
[31]	Walker NF, Clark SO, Oni T, et al. Doxycycline and HIV infection suppress tuberculosis-induced matrix metalloproteinases. Am J Respir Crit Care Med, 2012, 185(9): 989-997. doi:10.1164/rccm.201110-1769OC.
[32]	Muefong CN, Owolabi O, Donkor S, et al. Major Neutrophil-Derived Soluble Mediators Associate With Baseline Lung Pathology and Post-Treatment Recovery in Tuberculosis Patients. Front Immunol, 2021, 12: 740933. doi:10.3389/fimmu.2021.740933.
[33]	Nwongbouwoh Muefong C, Owolabi O, Donkor S, et al. Neutrophils Contribute to Severity of Tuberculosis Pathology and Recovery From Lung Damage Pre- and Posttreatment. Clin Infect Dis, 2022, 74(10): 1757-1766. doi:10.1093/cid/ciab729.
[34]	Ndlovu LN, Peetluk L, Moodley S, et al. Increased Neutrophil Count and Decreased Neutrophil CD15 Expression Correlate With TB Disease Severity and Treatment Response Irrespective of HIV Co-infection. Front Immunol, 2020, 11: 1872. doi:10.3389/fimmu.2020.01872. URL pmid: 32983107
[35]	Hilda JN, Das S, Tripathy SP, et al. Role of neutrophils in tuberculosis: A bird’s eye view. Innate Immun, 2020, 26(4): 240-247. doi:10.1177/1753425919881176.
[36]	Meirisandy S, Tabri NA. Nutritional status affects serum interleukin-8 level in active pulmonary tuberculosis and latent tuberculosis patients. Int J Med Rev Case Rep, 2019, 3(9): 572-577.
[37]	Christine T, Tarigan AP, Ananda FR. The Correlation between Levels of Transforming Growth Factor-β with Pulmonary Fibrosis in Post Pulmonary Tuberculosis in Medan, North Sumatera-Indonesia. Open Access Maced J Med Sci, 2019, 7(13): 2075-2078. doi:10.3889/oamjms.2019.544. URL pmid: 31456828
[38]	Louw E, Baines N, Maarman G, et al. The prevalence of pulmonary hypertension after successful tuberculosis treatment in a community sample of adult patients. Pulm Circ, 2023, 13(1): e12184. doi:10.1002/pul2.12184.
[39]	Ernst JD. Macrophage receptors for Mycobacterium tuberculosis. Infect Immun, 1998, 66(4): 1277-1281. doi:10.1128/IAI.66.4.1277-1281.1998.
[40]	Stefanescu S, Cocoş R, Turcu-Stiolica A, et al. Prediction of Treatment Outcome with Inflammatory Biomarkers after 2 Months of Therapy in Pulmonary Tuberculosis Patients: Preliminary Results. Pathogens, 2021, 10(7): 789. doi:10.3390/pathogens10070789.
[41]	Malefane L, Maarman G. Post-tuberculosis lung disease and inflammatory role players: can we characterise the myriad inflammatory pathways involved to gain a better understanding?. Chem Biol Interact, 2024, 387: 110817. doi:10.1016/j.cbi.2023.110817.
[42]	Fan JM, Huang XR, Ng YY, et al. Interleukin-1 induces tubular epithelial-myofibroblast transdifferentiation through a transforming growth factor-beta1-dependent mechanism in vitro. Am J Kidney Dis, 2001, 37(4): 820-831. doi:10.1016/s0272-6386(01)80132-3. URL pmid: 11273883
[43]	Guiedem E, Pefura-Yone EW, Ikomey GM, et al. Cytokine profile in the sputum of subjects with post-tuberculosis airflow obstruction and in those with tobacco related chronic obstructive pulmonary disease. BMC Immunol, 2020, 21(1): 52. doi:10.1186/s12865-020-00381-w. URL pmid: 32998687
[44]	Martin CJ, Carey AF, Fortune SM. A bug’s life in the granuloma. Semin Immunopathol, 2016, 38(2): 213-220. doi:10.1007/s00281-015-0533-1.
[45]	Davis JM, Ramakrishnan L. The role of the granuloma in expansion and dissemination of early tuberculous infection. Cell, 2009, 136(1): 37-49. doi:10.1016/j.cell.2008.11.014. URL pmid: 19135887
[46]	Evans S, Butler JR, Mattila JT, et al. Systems biology predicts that fibrosis in tuberculous granulomas may arise through macrophage-to-myofibroblast transformation. PLoS Comput Biol, 2020, 16(12): e1008520. doi:10.1371/journal.pcbi.1008520.
[47]	Gideon HP, Phuah J, Myers AJ, et al. Variability in tuberculosis granuloma T cell responses exists, but a balance of pro- and anti-inflammatory cytokines is associated with sterilization. PLoS Pathog, 2015, 11(1): e1004603. doi:10.1371/journal.ppat.1004603.
[48]	Diaz PT, Clanton TL, Pacht ER. Emphysema-like pulmonary disease associated with human immunodeficiency virus infection. Ann Intern Med, 1992, 116(2): 124-128. doi:10.7326/0003-4819-116-2-124. URL pmid: 1727615
[49]	Bigna JJ, Kenne AM, Asangbeh SL, et al. Prevalence of chronic obstructive pulmonary disease in the global population with HIV: a systematic review and meta-analysis. Lancet Glob Health, 2018, 6(2): e193-e202. doi:10.1016/S2214-109X(17)30451-5.
[50]	Kajogoo VD, Twebaze C, Said B, et al. Post tuberculosis chronic lung disease in tuberculosis HIV coinfected and non-HIV individuals in Sub-Saharan Africa: A systematic review and meta-analysis. Int J Mycobacteriol, 2022, 11(2): 139-144. doi:10.4103/ijmy.ijmy_66_22. URL pmid: 35775545
[51]	Smith SG, Bowness R, Cliff JM. Host-directed therapy in diabetes and tuberculosis comorbidity toward global tuberculosis elimination. Int J Infect Dis, 2025, 155: 107877. doi:10.1016/j.ijid.2025.107877.
[52]	Gai X, Allwood B, Sun Y. Post-tuberculosis lung disease and chronic obstructive pulmonary disease. Chin Med J (Engl), 2023, 136(16): 1923-1928. doi:10.1097/CM9.0000000000002771.
[53]	Rehm J, Samokhvalov AV, Neuman MG, et al. The association between alcohol use, alcohol use disorders and tuberculosis (TB). A systematic review. BMC Public Health, 2009, 9: 450. doi:10.1186/1471-2458-9-450. URL pmid: 19961618
[54]	Lönnroth K, Williams BG, Cegielski P, et al. A consistent log-linear relationship between tuberculosis incidence and body mass index. Int J Epidemiol, 2010, 39(1): 149-155. doi:10.1093/ije/dyp308. URL pmid: 19820104
[55]	Ji DX, Witt KC, Kotov DI, et al. Role of the transcriptional regulator SP140 in resistance to bacterial infections via repression of type I interferons. Elife, 2021, 10: e67290. doi:10.7554/eLife.67290.
[56]	Bhattacharya B, Xiao S, Chatterjee S, et al. The integrated stress response mediates necrosis in murine Mycobacterium tuberculosis granulomas. J Clin Invest, 2021, 131(3): e130319. doi:10.1172/JCI130319.
[57]	Krug S, Prasad P, Xiao S, et al. Adjunctive Integrated Stress Response Inhibition Accelerates Tuberculosis Clearance in Mice. mBio, 2023, 14(2): e0349622. doi:10.1128/mbio.03496-22.
[58]	Walter K, Kokesch-Himmelreich J, Treu A, et al. Interleukin-13-Overexpressing Mice Represent an Advanced Preclinical Model for Detecting the Distribution of Antimycobacterial Drugs within Centrally Necrotizing Granulomas. Antimicrob Agents Chemother, 2022, 66(6): e0158821. doi:10.1128/AAC.01588-21.
[59]	Awaisu A, Nik Mohamed MH, Mohamad Noordin N, et al. The SCIDOTS Project: evidence of benefits of an integrated tobacco cessation intervention in tuberculosis care on treatment outcomes. Subst Abuse Treat Prev Policy, 2011, 6: 26. doi:10.1186/1747-597X-6-26. URL pmid: 21943384
[60]	Meghji J, Simpson H, Squire SB, et al. A Systematic Review of the Prevalence and Pattern of Imaging Defined Post-TB Lung Disease. PLoS One, 2016, 11(8): e0161176. doi:10.1371/journal.pone.0161176.
[61]	Venkitakrishnan R, Ramachandran D, Augustine J, et al. Inhaled corticosteroids and risk of tuberculosis-How bad is the risk?. Indian J Tuberc, 2022, 69(2): 128-130. doi:10.1016/j.ijtb.2021.06.010. URL pmid: 35379390
[62]	You Y, Ni Y, Shi G. Inhaled Corticosteroids and Mycobacterial Infection in Patients with Chronic Airway Diseases: A Systematic Review and Meta-Analysis. Respiration, 2022, 101(10): 970-980. doi:10.1159/000525980.
[63]	Bongomin F. Post-tuberculosis chronic pulmonary aspergillosis: An emerging public health concern. PLoS Pathog, 2020, 16(8): e1008742. doi:10.1371/journal.ppat.1008742.
[64]	Bongomin F, Harris C, Hayes G, et al. Twelve-month clinical outcomes of 206 patients with chronic pulmonary aspergillosis. PLoS One, 2018, 13(4): e0193732. doi:10.1371/journal.pone.0193732.
[65]	Silva DR, Santos AP, Visca D, et al. Brazilian Thoracic Association recommendations for the management of post-tuberculosis lung disease. J Bras Pneumol, 2024, 49(6): e20230269. doi:10.36416/1806-3756/e20230269.
[66]	Nasiri MJ, Silva DR, Rommasi F, et al. Vaccination in post-tuberculosis lung disease management: A review of the evidence. Pulmonology, 2025, 31(1): 2416801. doi:10.1016/j.pulmoe.2023.07.002.
[67]	Visca D, Centis R, D’Ambrosio L, et al. The need for pulmonary rehabilitation following tuberculosis treatment. Int J Tuberc Lung Dis, 2020, 24(7): 720-722. doi:10.5588/ijtld.20.0030. URL pmid: 32718406
[68]	Silva DR, Mello FCQ, Galvão TS, et al. Pulmonary Rehabilitation in Patients With Post-Tuberculosis Lung Disease: A Prospective Multicentre Study. Arch Bronconeumol, 2025, 61(10): 603-609. doi:10.1016/j.arbres.2025.02.007.
[69]	Igbokwe V, Ruby LC, Sultanli A, et al. Post-tuberculosis sequelae in children and adolescents: a systematic review. Lancet Infect Dis, 2023, 23(4): e138-e150. doi:10.1016/S1473-3099(23)00004-X. URL pmid: 36963920
[70]	马志明. 结核后肺疾病的研究进展和临床挑战. 结核与肺部疾病杂志, 2026, 7(2): 156-164. doi:10.19983/j.issn.2096-8493.20260008.

功能/结构受损区域	病理生理表现	潜在的临床后果
气道型
中央气道和大支气管	支气管阻塞/扭曲	慢性阻塞性肺疾病、不可逆性气流受限
	支气管扩张	反复呼吸道感染、持续性咳嗽、咯血
小气道	小气道疾病/闭塞	阻塞性通气功能障碍、通气-血流失衡
肺实质损伤	容积损失	限制性通气功能障碍
	肺纤维化	肺顺应性下降、肺一氧化碳弥散量降低
	空洞	真菌感染、细菌感染
肺血管系统	血管损伤/重塑	肺动脉高压
胸膜	胸膜增厚/钙化	胸膜疼痛、限制性通气功能障碍
其他	不符合上述标准的其他病理表现,持续炎症感染、恶病质、营养不良