Advances in the clinical diagnosis and treatment of post-tuberculosis chronic pulmonary aspergillosis

doi:10.19982/j.issn.1000-6621.20240527

Abstract

Abstract:

Tuberculosis (TB) remains the leading cause of death from infectious diseases globally. Increasing recognition has been given to the long-term consequences of post-tuberculosis lung disease (PTLD), which profoundly affect patients’ physical health, psychological well-being, and socioeconomic stability. Among these sequelae, post-tuberculosis chronic pulmonary aspergillosis (PTLD-CPA) is a persistent Aspergillus infection that arises during or after TB treatment. The substantial overlap in clinical manifestations and radiological features between CPA and TB frequently leads to misdiagnosis and inappropriate treatment, further exacerbating disease progression and associated morbidity. This underscores the critical need for early screening and timely intervention for Aspergillus infection. This review consolidates current evidence on the epidemiology, clinical characteristics, diagnostic modalities, treatment strategies, and screening protocols for PTLD-CPA. By delineating key priorities for prevention and disease management, we propose a comprehensive, life-cycle-based health management framework for TB, integrating early detection, targeted therapeutic interventions, and long-term surveillance to mitigate the enduring burden of PTLD-CPA.

Key words: Tuberculosis, pulmonary, Aspergillosis, Post-tuberculosis lung disease, Review

CLC Number:

R52
R563

Qin Lili, Yang Chengqing, Mai Hongzhen, Xu Qifeng, Xue Xinying, Lu Xiwei. Advances in the clinical diagnosis and treatment of post-tuberculosis chronic pulmonary aspergillosis[J]. Chinese Journal of Antituberculosis, 2025, 47(4): 498-504. doi: 10.19982/j.issn.1000-6621.20240527

References 57

[1]	胡鑫洋, 高静韬. 世界卫生组织《2024年全球结核病报告》解读. 结核与肺部疾病杂志, 2024, 5(6): 500-504. doi:10.19983/j.issn.2096-8493.2024164.
[2]	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): 820-828. doi:10.5588/ijtld.20.0067. pmid: 32912387
[3]	Neuböck MJ, Günther G, Barac A, et al. Chronic pulmonary aspergillosis as a considerable complication in post-tuberculosis lung disease. Semin Respir Crit Care Med, 2024, 45(1): 102-113. doi:10.1055/s-0043-1776913. pmid: 38196060
[4]	Denning DW, Riniotis K, Dobrashian R, et al. Chronic cavitary and fibrosing pulmonary and pleural aspergillosis: case series, proposed nomenclature change, and review. Clin Infect Dis, 2003, 37 Suppl 3: S265-S280. doi:10.1086/376526.
[5]	Lowes D, Al-Shair K, Newton PJ, et al. Predictors of mortality in chronic pulmonary aspergillosis. Eur Respir J, 2017, 49(2): 1601062. doi:10.1183/13993003.01062-2016.
[6]	Lakoh S, Kamara JB, Orefuwa E, et al. Prevalence and predictors of aspergillus seropositivity and chronic pulmonary aspergillosis in an urban tertiary hospital in Sierra Leone: A cross-sectional study. PLoS Negl Trop Dis, 2023, 17(7): e0011284. doi:10.1371/journal.pntd.0011284.
[7]	Denning DW, Pleuvry A, Cole DC. Global burden of chronic pulmonary aspergillosis as a sequel to pulmonary tuberculosis. Bull World Health Organ, 2011, 89(12): 864-872. doi:10.2471/BLT.11.089441.
[8]	Denning DW, Cole DC, Ray A. New estimation of the prevalence of chronic pulmonary aspergillosis (CPA) related to pulmonary TB-a revised burden for India. IJID Reg, 2023, 6: 7-14. doi:10.1016/j.ijregi.2022.11.005.
[9]	Setianingrum F, Rozaliyani A, Syam R, et al. Evaluation and comparison of automated and manual ELISA for diagnosis of chronic pulmonary aspergillosis (CPA) in Indonesia. Diagn Microbiol Infect Dis, 2020, 98(3): 115124. doi:10.1016/j.diagmicrobio.2020.115124.
[10]	Denning DW. Global incidence and mortality of severe fungal disease. Lancet Infect Dis, 2024, 24(7): e428-e438. doi:10.1016/S1473-3099(23)00692-8.
[11]	Nguyen NTB, Le Ngoc H, Nguyen NV, et al. Chronic pulmonary aspergillosis situation among post tuberculosis patients in Vietnam: an observational study. J Fungi (Basel), 2021, 7(7): 532. doi:10.3390/jof7070532.
[12]	Mohamed A, Obanda BA, Njeri HK, et al. Serological evidence of chronic pulmonary aspergillosis in tuberculosis patients in Kenya. BMC Infect Dis, 2022, 22(1): 798. doi:10.1186/s12879-022-07782-9.
[13]	周萌, 梅春林, 曹探赜, 等. 尘肺并发慢性肺曲霉病误诊为肺结核一例. 中国防痨杂志, 2021, 43(5): 526-528. doi:10.3969/j.issn.1000-6621.2021.05.021.
[14]	Rozaliyani A, Setianingrum F, Azahra S, et al. Performance of LDBio Aspergillus WB and ICT antibody detection in chronic pulmonary aspergillosis. J Fungi (Basel), 2021, 7(4): 311. doi:10.3390/jof7040311.
[15]	Denning DW, Cadranel J, Beigelman-Aubry C, et al. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management. Eur Respir J, 2016, 47(1): 45-68. doi:10.1183/13993003.00583-2015. pmid: 26699723
[16]	杨澄清, 陈淑芳, 梅春林, 等. 220例肺结核合并慢性肺曲霉病患者的临床特征. 中国防痨杂志, 2024, 46(7): 770-777. doi:10.19982/j.issn.1000-6621.20240129.
[17]	Davies AA, Adekoya AO, Balogun OJ, et al. Prevalence of chronic pulmonary aspergillosis in two (2) tuberculosis treatment clinics in Lagos, Nigeria: a prospective longitudinal study. Open Forum Infect Dis, 2024, 11(4): ofae090. doi:10.1093/ofid/ofae090.
[18]	Page ID, Byanyima R, Hosmane S, et al. Chronic pulmonary aspergillosis commonly complicates treated pulmonary tuberculosis with residual cavitation. Eur Respir J, 2019, 53(3): 1801184. doi:10.1183/13993003.01184-2018.
[19]	Anan K, Kataoka Y, Okabayashi S, et al. Diagnostic accuracy of Aspergillus-specific antibodies for chronic pulmonary aspergillosis: A systematic review and meta-analysis. Mycoses, 2021, 64(7): 701-715. doi:10.1111/myc.13253. pmid: 33594774
[20]	Sehgal IS, Choudhary H, Dhooria S, et al. Diagnostic cut-off of Aspergillus fumigatus-specific IgG in the diagnosis of chronic pulmonary aspergillosis. Mycoses, 2018, 61(10): 770-776. doi:10.1111/myc.12815. pmid: 29920796
[21]	Takazono T, Ito Y, Tashiro M, et al. Evaluation of aspergillus-specific lateral-flow device test using serum and bronchoalveolar lavage fluid for diagnosis of chronic pulmonary aspergillosis. J Clin Microbiol, 2019, 57(5): e00095-19. doi:10.1128/JCM.00095-19.
[22]	Kitasato Y, Tao Y, Hoshino T, et al. Comparison of Aspergillus galactomannan antigen testing with a new cut-off index and Aspergillus precipitating antibody testing for the diagnosis of chronic pulmonary aspergillosis. Respirology, 2009, 14(5): 701-708. doi:10.1111/j.1440-1843.2009.01548.x.
[23]	Park SY, Lee SO, Choi SH, et al. Serum and bronchoalveolar lavage fluid galactomannan assays in patients with pulmonary aspergilloma. Clin Infect Dis, 2011, 52(7): e149-e152. doi:10.1093/cid/cir027.
[24]	Sehgal IS, Dhooria S, Choudhary H, et al. Efficiency of a fumigatus-specific IgG and galactomannan testing in the diagnosis of simple aspergilloma. Mycoses, 2019, 62(12): 1108-1115. doi:10.1111/myc.12987. pmid: 31408547
[25]	Chowdhury M, Singh G, Pandey M, et al. The utility of galactomannan and polymerase chain reaction assays in bronchoalveolar lavage for diagnosis of chronic pulmonary aspergillosis. Mycopathologia, 2023, 188(6): 1041-1053. doi:10.1007/s11046-023-00797-z. pmid: 37857979
[26]	de Oliveira VF, Silva GD, Taborda M, et al. Systematic review and meta-analysis of galactomannan antigen testing in serum and bronchoalveolar lavage for the diagnosis of chronic pulmonary aspergillosis: defining a cutoff. Eur J Clin Microbiol Infect Dis, 2023, 42(9): 1047-1054. doi:10.1007/s10096-023-04639-0.
[27]	Tarrand JJ, Lichterfeld M, Warraich I, et al. Diagnosis of invasive septate mold infections. A correlation of microbiological culture and histologic or cytologic examination. Am J Clin Pathol, 2003, 119(6): 854-858. doi:10.1309/EXBV-YAUP-ENBM-285Y. pmid: 12817433
[28]	Li H, Rui Y, Zhou W, et al. Role of the aspergillus-specific IgG and IgM test in the diagnosis and follow-up of chronic pulmonary aspergillosis. Front Microbiol, 2019, 10: 1438. doi:10.3389/fmicb.2019.01438.
[29]	Ma X, Wang K, Zhao X, et al. Prospective study of the serum Aspergillus-specific IgG, IgA and IgM assays for chronic pulmonary aspergillosis diagnosis. BMC Infect Dis, 2019, 19(1): 694. doi:10.1186/s12879-019-4303-x. pmid: 31387539
[30]	Zhou W, Li H, Zhang Y, et al. Diagnostic value of galactomannan antigen test in serum and bronchoalveolar lavage fluid samples from patients with nonneutropenic invasive pulmonary aspergillosis. J Clin Microbiol, 2017, 55(7): 2153-2161. doi:10.1128/JCM.00345-17. pmid: 28446576
[31]	张尧, 缪青, 金文婷, 等. 宏基因二代测序技术对慢性肺曲霉病病原学诊断的价值. 中国临床医学, 2020, 27(4): 563-566. doi:10.12025/j.issn.1008-6358.2020.20201183.
[32]	Denning DW, Page ID, Chakaya J, et al. Case definition of chronic pulmonary aspergillosis in resource-constrained settings. Emerg Infect Dis, 2018, 24(8): e171312. doi:10.3201/eid2408.171312.
[33]	中华医学会呼吸病学分会. 慢性阻塞性肺疾病伴肺曲霉病诊治和管理专家共识. 中华结核和呼吸杂志, 2024, 47(7):604-622. doi:10.3760/cma.j.cn112147-20231228-00399.
[34]	Sehgal IS, Dhooria S, Muthu V, et al. Efficacy of 12-months oral itraconazole versus 6-months oral itraconazole to prevent relapses of chronic pulmonary aspergillosis: an open-label, randomised controlled trial in India. Lancet Infect Dis, 2022, 22(7): 1052-1061. doi:10.1016/S1473-3099(22)00057-3. pmid: 35429465
[35]	Im Y, Jhun BW, Kang ES, et al. Impact of treatment duration on recurrence of chronic pulmonary aspergillosis. J Infect, 2021, 83(4): 490-495. doi:10.1016/j.jinf.2021.07.030.
[36]	Bongomin F, Asio LG, Olum R, et al. Intravenous therapy for chronic pulmonary aspergillosis: A systematic review and meta-analysis. Mycoses, 2020, 63(9): 921-927. doi:10.1111/myc.13131. pmid: 32542771
[37]	Jhun BW, Jeon K, Eom JS, et al. Clinical characteristics and treatment outcomes of chronic pulmonary aspergillosis. Med Mycol, 2013, 51(8): 811-817. doi:10.3109/13693786.2013.806826. pmid: 23834282
[38]	Ohba H, Miwa S, Shirai M, et al. Clinical characteristics and prognosis of chronic pulmonary aspergillosis. Respir Med, 2012, 106(5): 724-729. doi:10.1016/j.rmed.2012.01.014. pmid: 22349065
[39]	Monk EJM, Harris C, Döffinger R, et al. Interferon gamma replacement as salvage therapy in chronic pulmonary aspergillosis: effects on frequency of acute exacerbation and all-cause hospital admission. Thorax, 2020, 75(6): 513-516. doi:10.1136/thoraxjnl-2019-213606. pmid: 32229542
[40]	Ahmad T, Ahmed SW, Hussain N, et al. Clinical profile and postoperative outcome in patients with simple and complex aspergilloma of lung. J Coll Physicians Sur Pak, 2010, 20(3): 190-193.
[41]	Akbari JG, Varma PK, Neema PK, et al. Clinical profile and surgical outcome for pulmonary aspergilloma: a single center experience. Ann Thorac Surg, 2005, 80(3): 1067-1072. doi:10.1016/j.athoracsur.2005.03.078. pmid: 16122488
[42]	Chen QK, Jiang G N, Ding JA. Surgical treatment for pulmonary aspergilloma: a 35-year experience in the Chinese population. Interact Cardiovasc Thorac Surg, 2012, 15(1): 77-80. doi:10.1093/icvts/ivs130.
[43]	El Hammoumi MM, Slaoui O, El Oueriachi F, et al. Lung resection in pulmonary aspergilloma: experience of a Moroccan center. BMC Surg, 2015, 15: 114. doi:10.1186/s12893-015-0103-4. pmid: 26475478
[44]	Endo S, Sohara Y, Murayama F, et al. Surgical outcome of pulmonary resection in chronic necrotizing pulmonary aspergillosis. Ann Thorac Surg, 2001, 72(3): 889-894. doi:10.1016/s0003-4975(01)02884-3. pmid: 11565676
[45]	Shen C, Qiao G, Wang C, et al. Outcomes of surgery for different types of chronic pulmonary aspergillosis: results from a single-center, retrospective cohort study. BMC Pulm Med, 2022, 22(1): 40. doi:10.1186/s12890-022-01836-z. pmid: 35045860
[46]	Farid S, Mohamed S, Devbhandari M, et al. Results of surgery for chronic pulmonary Aspergillosis, optimal antifungal therapy and proposed high risk factors for recurrence--a National Centre’s experience. J Cardiothorac Surg, 2013, 8:180. doi:10.1186/1749-8090-8-180.
[47]	Muniappan A, Tapias LF, Butala P, et al. Surgical therapy of pulmonary aspergillomas: a 30-year North American experience. Ann Thorac Surg, 2014, 97(2): 432-438. doi:10.1016/j.athoracsur.2013.10.050. pmid: 24365218
[48]	Ullmann AJ, Aguado JM, Arikan-Akdagli S, et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect, 2018, 24 Suppl 1: e1-e38. doi:10.1016/j.cmi.2018.01.002.
[49]	两性霉素B脱氧胆酸盐临床合理应用专家共识编写组, 中国医药教育协会感染疾病专业委员会, 中华医学会细菌感染与耐药防控专业委员会. 两性霉素B脱氧胆酸盐临床合理应用专家共识(2022). 中华医学杂志, 2023, 103(16): 1173-1183. doi:10.3760/cma.j.cn112137-20221206-02578.
[50]	中华医学会呼吸病学分会感染学组. 成人抗感染药物下呼吸道局部应用专家共识. 中华结核和呼吸杂志, 2021, 44(4): 322-339. doi:10.3760/cma.j.cn112147-20200531-00656.
[51]	中华医学会呼吸病学分会. 支气管镜诊疗操作相关大出血的预防和救治专家共识. 中华结核和呼吸杂志, 2016, 39(8):588-591. doi:10.3760/cma.j.issn.1001-0939.2016.08.007.
[52]	He G, Liu W, Gao Z, et al. Intervention treatment on massive hemoptysis of pulmonary aspergilloma. Exp Ther Med, 2017, 13(5): 2259-2262. doi:10.3892/etm.2017.4230. pmid: 28565835
[53]	Corr P. Management of severe hemoptysis from pulmonary aspergilloma using endovascular embolization. Cardiovasc Intervent Radiol, 2006, 29(5): 807-810. doi:10.1007/s00270-005-0329-0.
[54]	Shimohira M, Ohta K, Nagai K, et al. Bronchial arterial embolization using a gelatin sponge for hemoptysis from pulmonary aspergilloma: comparison with other pulmonary diseases. Emerg Radiol, 2019, 26(5): 501-506. doi:10.1007/s10140-019-01695-y. pmid: 31129737
[55]	Shin B, Koh WJ, Shin SW, et al. Outcomes of bronchial artery embolization for life-threatening hemoptysis in patients with chronic pulmonary aspergillosis. PLoS One, 2016, 11(12): e0168373. doi:10.1371/journal.pone.0168373.
[56]	Ando T, Kawashima M, Masuda K, et al. Exacerbation of chronic pulmonary aspergillosis was associated with a high rebleeding rate after bronchial artery embolization. Respir Investig, 2019, 57(3): 260-267. doi:10.1016/j.resinv.2018.12.009. pmid: 30692051
[57]	Bongomin F, Olum R, Kibone W, et al. Prevalence of chronic pulmonary aspergillosis along the continuum of pulmonary tuberculosis care: a protocol for a living systematic review and meta-analysis. PLoS One, 2023, 18(12): e0294634. doi:10.1371/journal.pone.0294634.