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Bronchoscopic techniques in the management of patients with tuberculosis

Open AccessPublished:August 29, 2017DOI:https://doi.org/10.1016/j.ijid.2017.08.008

      Highlights

      • Bronchoscopy can be crucial for pulmonary TB diagnosis.
      • Bronchoscopic needle aspiration techniques are safe.
      • Bronchoscopic therapy can be helpful in the treatment of endobronchial TB.

      Abstract

      Tuberculosis (TB) is one of the leading causes of morbidity and mortality worldwide. Early diagnosis and treatment are key to prevent Mycobacterium tuberculosis transmission. Bronchoscopy can play a primary role in pulmonary TB diagnosis, particularly for suspected patients with scarce sputum or sputum smear negativity, and with endobronchial disease. Bronchoscopic needle aspiration techniques are accurate and safe means adopted to investigate hilar and mediastinal lymph nodes in cases of suspected TB lymphadenopathy. Tracheobronchial stenosis represents the worst complication of endobronchial tuberculosis. Bronchoscopic procedures are less invasive therapeutic strategies than conventional surgery to be adopted in the management of TB-related stenosis.
      We conducted a non-systematic review aimed at describing the scientific literature on the role of bronchoscopic techniques in the diagnosis and therapy of patients with TB.
      We focused on three main areas of interventions: bronchoscopic diagnosis of smear negative/sputum scarce TB patients, endobronchial TB diagnosis and treatment and needle aspiration techniques for intrathoracic TB lymphadenopathy. We described experiences on bronchoalveolar lavage, bronchial washing, and biopsy techniques for the diagnosis of patients with tracheobronchial and pulmonary TB; furthermore, we described the role played by conventional and ultrasound-guided transbronchial needle aspiration in the diagnosis of suspected hilar and mediastinal TB adenopathy. Finally, we assessed the role of the bronchoscopic therapy in the treatment of endobronchial TB and its complications, focusing on dilation techniques (such as balloon dilation and airway stenting) and ablative procedures (both heat and cold therapies).

      Keywords

      Introduction

      Tuberculosis (TB) is one of the most important infectious diseases worldwide (
      • World Health Organization
      Global tuberculosis report 2016.
      ). Its epidemiological burden is relevant in terms of morbidity and mortality. In particular, the last World Health Organization (WHO) Global Report on TB, published in 2016, highlighted an increased incidence (10.4 million) and mortality (1.4 million) in 2015 in comparison with the estimated figures reported in the previous year (
      • World Health Organization
      Global tuberculosis report 2016.
      ). The new public health WHO strategy (
      • WHO
      The End-TB Strategy: global strategy and targets for tuberculosis prevention, care and control after 2015.
      ,
      • D’Ambrosio L.
      • Dara M.
      • Tadolini M.
      • et al.
      European national programme representatives: Tuberculosis elimination: theory and practice in Europe.
      ,
      • Lönnroth K.
      • Migliori G.B.
      • Abubakar I.
      • et al.
      Towards tuberculosis elimination: an action framework for low-incidence countries.
      ,
      • Sotgiu G.
      • Migliori G.B.
      Is tuberculosis elimination a reality?.
      ), named End TB Strategy and aimed at eliminating TB, can achieve its goal by 2050 only if new cases of active disease are prevented (through vaccination and treatment of individuals with latent TB infection) or early detected and appropriately treated. The current diagnostic and therapeutic weapons are old and frequently ineffective (e.g., sputum smear negative patients, drug-resistant cases). Intensified research and development activities in the diagnostic, therapeutic, and preventive field could significantly address the current operational issues.
      An appropriate therapeutic prescription strongly relies on microbiologic diagnosis of the collected biological specimen (i.e., liquid or solid culture) (
      • World Health Organization
      The stop TB strategy: building on and enhancing DOTS to meet the millennium development goals.
      ).
      Several factors can hinder the collection of specimens and, then, the definitive diagnosis. In case of pulmonary TB, at least two sputum specimens are required; however, in some groups of patients (for instance, children, HIV-positive patients) the collection is difficult and alternative methods are necessary (
      • World Health Organization
      The stop TB strategy: building on and enhancing DOTS to meet the millennium development goals.
      ,
      • Dheda K.
      • Lampe F.C.
      • Johnson M.A.
      • et al.
      Outcome of HIV-associated tuberculosis in the era of highly active antiretroviral therapy.
      ). Until now, observational and experimental studies have not provided sufficient scientific evidence to recommend one specific method more than another.
      One of the medical interventions which could improve the clinical management of the TB patients is the bronchoscopy (
      • Theron G.
      • Peter J.
      • Meldau R.
      • et al.
      Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.
      ).
      Aim of the present review is to describe the most important studies on bronchoscopy in the TB field and its potential recommendations.

      Methods

      We carried out a non-systematic, narrative literature review based on a Pubmed search until June 2017. We selected only epidemiological studies performed in adult human beings and written in English. Other filters, including those related to the aim of the study, were not used.

      Bronchoscopy and diagnosis of sputum smear negative/sputum scarce TB patients

      Sputum smear microscopy is the easiest and widespread tool adopted globally to diagnose cases of pulmonary TB; however, although it has been recommended since the first WHO global TB strategy (i.e., DOTS), its sensitivity can be poor and affected by specimen processing methods and technical skills (
      • World Health Organization
      The stop TB strategy: building on and enhancing DOTS to meet the millennium development goals.
      ,
      • Steingart K.R.
      • Ng V.
      • Henry M.
      • et al.
      Sputum processing methods to improve the sensitivity of smear microscopy for tuberculosis: a systematic review.
      ). Notably, more than one third of patients with pulmonary TB cannot produce sufficient sputum or is sputum smear negative (
      • Theron G.
      • Peter J.
      • Meldau R.
      • et al.
      Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.
      ,
      • Hepple P.
      • Ford N.
      • McNerney R.
      Microscopy compared to culture for the diagnosis of tuberculosis in induced sputum samples: a systematic review.
      ). Even though sputum induction is frequently used, it fails to provide a specimen of adequate volume or quality in up to 20% of the cases (
      • Hepple P.
      • Ford N.
      • McNerney R.
      Microscopy compared to culture for the diagnosis of tuberculosis in induced sputum samples: a systematic review.
      ). Moreover, it is not allowed to explore the airways and collect samples from the low respiratory tract (
      • Theron G.
      • Peter J.
      • Meldau R.
      • et al.
      Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.
      ). Bronchoscopy with bronchial washing (BW), bronchoalveolar lavage (BAL), and biopsy can play a key role in the collection of suitable samples for TB diagnosis (
      • Lewinsohn D.M.
      • Leonard M.K.
      • LoBue P.A.
      • et al.
      Official American thoracic society/infectious diseases society of America/centers for disease control and prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children.
      ).
      Chest radiology (i.e., chest X-ray and chest computed tomography) is helpful to plan and guide the collection of bronchoscopic samples; it can show parenchymal features (e.g., consolidations, cavitations, scattered nodules, etc.) and endobronchial involvements, as well as hilar and mediastinal lymph nodes enlargements (
      • Beigelman C.
      • Sellami D.
      • Brauner M.
      CT of parenchymal and bronchial tuberculosis.
      ,
      • Skoura E.
      • Zumla A.
      • Bomanji J.
      Imaging in tuberculosis.
      ,
      • Burrill J.
      • Williams C.J.
      • Bain G.
      • et al.
      Tuberculosis: a radiologic review.
      ). On the other side, F-FDG PET/CT (18F-fluorodeoxyglucose positron emission tomography/computed tomography) may help detect active TB (
      • Skoura E.
      • Zumla A.
      • Bomanji J.
      Imaging in tuberculosis.
      ).
      Bronchoscopic diagnosis of pulmonary TB traditionally relies on acid-fast bacilli smear microscopy, nucleic acid amplification techniques (NAATs), and Mycobacterium tuberculosis cultures (
      • Theron G.
      • Peter J.
      • Meldau R.
      • et al.
      Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.
      ,
      • Jafari C.
      • Kessler P.
      • Sotgiu G.
      • et al.
      Impact of a Mycobacterium tuberculosis-specific interferon-γ release assay in bronchoalveolar lavage fluid for a rapid diagnosis of tuberculosis.
      ,
      • Jafari C.
      • Thijsen S.
      • Sotgiu G.
      • et al.
      Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a Tuberculosis Network European Trials group study.
      ,
      • Jafari C.
      • Ernst M.
      • Kalsdorf B.
      • et al.
      Rapid diagnosis of smear-negative tuberculosis by bronchoalveolar lavage enzyme-linked immunospot.
      ,
      • Tueller C.
      • Chajed P.N.
      • Buitrago-Tellez C.
      • et al.
      Value of smear and PCR in bronchoalveolar lavage fluid in culture positive pulmonary tuberculosis.
      ,
      • Mok Y.
      • Tan T.Y.
      • Tay T.R.
      • et al.
      Do we need transbronchial lung biopsy if we have bronchoalveolar lavage Xpert(®) MTB/RIF?.
      ,
      • Tamura A.
      • Shimada M.
      • Matsui Y.
      • et al.
      The value of fiberoptic bronchoscopy in culture-positive pulmonary tuberculosis patients whose pre-bronchoscopic sputum specimens were negative both for smear and PCR analyses.
      ). Transbronchial needle aspiration (
      • Reichenberger F.
      • Weber J.
      • Tamm M.
      • et al.
      The value of transbronchial needle aspiration in the diagnosis of peripheral pulmonary lesions.
      ) and transbronchial biopsy (
      • Theron G.
      • Peter J.
      • Meldau R.
      • et al.
      Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.
      ,
      • Chan A.
      • Devanand A.
      • Low S.Y.
      • et al.
      Radial endobronchial ultrasound in diagnosing peripheral lung lesions in a high tuberculosis setting.
      ,
      • Jacomelli M.
      • Silva P.R.
      • Rodrigues A.J.
      • et al.
      Bronchoscopy for the diagnosis of pulmonary tuberculosis in patients with negative sputum smear microscopy results.
      ) may support the detection of cytological and histological TB findings (i.e., necrotizing granulomatous inflammation), but a positive culture is associated with the highest diagnostic accuracy (
      • Theron G.
      • Peter J.
      • Meldau R.
      • et al.
      Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.
      ,
      • World Health Organization
      Global tuberculosis report 2015. Diagnostics and laboratory strengthening.
      ). Indeed, mycobacterial culture could provide further information on drug sensitivity (
      • World Health Organization
      Global tuberculosis report 2015. Diagnostics and laboratory strengthening.
      ).
      However, the diagnostic delay related to a time to positivity ranging from 2 to 6 weeks (
      • Theron G.
      • Peter J.
      • Meldau R.
      • et al.
      Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.
      ,
      • Mok Y.
      • Tan T.Y.
      • Tay T.R.
      • et al.
      Do we need transbronchial lung biopsy if we have bronchoalveolar lavage Xpert(®) MTB/RIF?.
      ,
      • Dheda K.
      • van Zyl-Smit R.N.
      • Meldau R.
      • et al.
      Quantitative lung T cell responses aid the rapid diagnosis of pulmonary tuberculosis.
      ) increases the probability of a poor prognosis (morbidity, mortality, and economic burden) and of Mycobacterium tuberculosis transmission (
      • Theron G.
      • Peter J.
      • Meldau R.
      • et al.
      Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.
      ,
      • Jafari C.
      • Thijsen S.
      • Sotgiu G.
      • et al.
      Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a Tuberculosis Network European Trials group study.
      ,
      • Tueller C.
      • Chajed P.N.
      • Buitrago-Tellez C.
      • et al.
      Value of smear and PCR in bronchoalveolar lavage fluid in culture positive pulmonary tuberculosis.
      ,
      • Dheda K.
      • van Zyl-Smit R.N.
      • Meldau R.
      • et al.
      Quantitative lung T cell responses aid the rapid diagnosis of pulmonary tuberculosis.
      ,
      • Le Palud P.
      • Cattoir V.
      • Malbruny B.
      • et al.
      Retrospective observational study of diagnostic accuracy of the Xpert® MTB/RIF assay on fiberoptic bronchoscopy sampling for early diagnosis of smear-negative or sputum-scarce patients with suspected tuberculosis.
      ). Smear microscopy for the identification of acid-fast bacilli is rapid (one-two days) and inexpensive (
      • Mok Y.
      • Tan T.Y.
      • Tay T.R.
      • et al.
      Do we need transbronchial lung biopsy if we have bronchoalveolar lavage Xpert(®) MTB/RIF?.
      ), but its bacillary load-related sensitivity based on bronchoscopic specimens is low (
      • Theron G.
      • Peter J.
      • Meldau R.
      • et al.
      Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.
      ,
      • Jafari C.
      • Kessler P.
      • Sotgiu G.
      • et al.
      Impact of a Mycobacterium tuberculosis-specific interferon-γ release assay in bronchoalveolar lavage fluid for a rapid diagnosis of tuberculosis.
      ,
      • Jafari C.
      • Thijsen S.
      • Sotgiu G.
      • et al.
      Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a Tuberculosis Network European Trials group study.
      ,
      • Jafari C.
      • Ernst M.
      • Kalsdorf B.
      • et al.
      Rapid diagnosis of smear-negative tuberculosis by bronchoalveolar lavage enzyme-linked immunospot.
      ,
      • Tueller C.
      • Chajed P.N.
      • Buitrago-Tellez C.
      • et al.
      Value of smear and PCR in bronchoalveolar lavage fluid in culture positive pulmonary tuberculosis.
      ,
      • Reichenberger F.
      • Weber J.
      • Tamm M.
      • et al.
      The value of transbronchial needle aspiration in the diagnosis of peripheral pulmonary lesions.
      ,
      • Chan A.
      • Devanand A.
      • Low S.Y.
      • et al.
      Radial endobronchial ultrasound in diagnosing peripheral lung lesions in a high tuberculosis setting.
      ,
      • Jacomelli M.
      • Silva P.R.
      • Rodrigues A.J.
      • et al.
      Bronchoscopy for the diagnosis of pulmonary tuberculosis in patients with negative sputum smear microscopy results.
      ,
      • Dheda K.
      • van Zyl-Smit R.N.
      • Meldau R.
      • et al.
      Quantitative lung T cell responses aid the rapid diagnosis of pulmonary tuberculosis.
      ,
      • Le Palud P.
      • Cattoir V.
      • Malbruny B.
      • et al.
      Retrospective observational study of diagnostic accuracy of the Xpert® MTB/RIF assay on fiberoptic bronchoscopy sampling for early diagnosis of smear-negative or sputum-scarce patients with suspected tuberculosis.
      ,
      • Barnard D.A.
      • Irusen E.M.
      • Bruwer J.W.
      • et al.
      The utility of Xpert MTB/RIF performed on bronchial washings obtained in patients with suspected pulmonary tuberculosis in a high prevalence setting.
      ,
      • Lee H.Y.
      • Seong M.W.
      • Park S.S.
      • et al.
      Diagnostic accuracy of Xpert® MTB/RIF on bronchoscopy specimens in patients with suspected pulmonary tuberculosis.
      ,
      • Lin S.M.
      • Ni Y.L.
      • Kuo C.H.
      • et al.
      Endobronchial ultrasound increases the diagnostic yields of polymerase chain reaction and smear for pulmonary tuberculosis.
      ). NAAT, aimed to detect Mycobacterium tuberculosis nucleic acids, and histology have a good diagnostic yield, providing a response in a few days (
      • Theron G.
      • Peter J.
      • Meldau R.
      • et al.
      Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.
      ,
      • Jafari C.
      • Kessler P.
      • Sotgiu G.
      • et al.
      Impact of a Mycobacterium tuberculosis-specific interferon-γ release assay in bronchoalveolar lavage fluid for a rapid diagnosis of tuberculosis.
      ,
      • Jafari C.
      • Thijsen S.
      • Sotgiu G.
      • et al.
      Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a Tuberculosis Network European Trials group study.
      ,
      • Jafari C.
      • Ernst M.
      • Kalsdorf B.
      • et al.
      Rapid diagnosis of smear-negative tuberculosis by bronchoalveolar lavage enzyme-linked immunospot.
      ,
      • Tueller C.
      • Chajed P.N.
      • Buitrago-Tellez C.
      • et al.
      Value of smear and PCR in bronchoalveolar lavage fluid in culture positive pulmonary tuberculosis.
      ,
      • Mok Y.
      • Tan T.Y.
      • Tay T.R.
      • et al.
      Do we need transbronchial lung biopsy if we have bronchoalveolar lavage Xpert(®) MTB/RIF?.
      ,
      • Tamura A.
      • Shimada M.
      • Matsui Y.
      • et al.
      The value of fiberoptic bronchoscopy in culture-positive pulmonary tuberculosis patients whose pre-bronchoscopic sputum specimens were negative both for smear and PCR analyses.
      ,
      • Chan A.
      • Devanand A.
      • Low S.Y.
      • et al.
      Radial endobronchial ultrasound in diagnosing peripheral lung lesions in a high tuberculosis setting.
      ,
      • Jacomelli M.
      • Silva P.R.
      • Rodrigues A.J.
      • et al.
      Bronchoscopy for the diagnosis of pulmonary tuberculosis in patients with negative sputum smear microscopy results.
      ). The combination of those techniques may significantly increase the sensitivity of bronchoscopy for the early diagnosis of pulmonary TB (
      • Theron G.
      • Peter J.
      • Meldau R.
      • et al.
      Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.
      ,
      • Tueller C.
      • Chajed P.N.
      • Buitrago-Tellez C.
      • et al.
      Value of smear and PCR in bronchoalveolar lavage fluid in culture positive pulmonary tuberculosis.
      ,
      • Mok Y.
      • Tan T.Y.
      • Tay T.R.
      • et al.
      Do we need transbronchial lung biopsy if we have bronchoalveolar lavage Xpert(®) MTB/RIF?.
      ,
      • Tamura A.
      • Shimada M.
      • Matsui Y.
      • et al.
      The value of fiberoptic bronchoscopy in culture-positive pulmonary tuberculosis patients whose pre-bronchoscopic sputum specimens were negative both for smear and PCR analyses.
      ,
      • Jacomelli M.
      • Silva P.R.
      • Rodrigues A.J.
      • et al.
      Bronchoscopy for the diagnosis of pulmonary tuberculosis in patients with negative sputum smear microscopy results.
      ). The main shortcoming of those techniques using sputum and bronchoscopic materials can be the low specificity.
      Rapid on-site evaluation (ROSE) of transbronchial needle aspirates is a well-known predictor of better yield in peripheral pulmonary lesions sampling (
      • Mondoni M.
      • Sotgiu G.
      • Bonifazi M.
      • et al.
      Transbronchial needle aspiration in peripheral pulmonary lesions: a systematic review and meta-analysis.
      ). Furthermore, for the diagnosis of endobronchial malignancies, parenchymal lesions and hilar/mediastinal lymphadenopathies, ROSE technique may allow bronchoscopists to interrupt the sampling procedure when sufficient material has been collected, avoiding further needle passes and/or useless transbronchial biopsies or brushings (
      • Mondoni M.
      • et al.
      Rapid on-site evaluation improves needle aspiration sensitivity in the diagnosis of central lung cancers: a randomized trial.
      ;
      • Mondoni M.
      • Sotgiu G.
      • Bonifazi M.
      • et al.
      Transbronchial needle aspiration in peripheral pulmonary lesions: a systematic review and meta-analysis.
      ,
      • Trisolini R.
      • Cancellieri A.
      • Tinelli C.
      • et al.
      Rapid on-site evaluation of transbronchial aspirates in the diagnosis of hilar and mediastinal adenopathy: a randomized trial.
      ,
      • Gasparini S.
      • Ferretti M.
      • Secchi E.B.
      • et al.
      Integration of transbronchial and percutaneous approach in the diagnosis of peripheral pulmonary nodules or masses Experience with 1,027 consecutive cases.
      ). In TB diagnosis ROSE may be useful to rapidly detect TB-related granulomas (
      • Gasparini S.
      • Ferretti M.
      • Secchi E.B.
      • et al.
      Integration of transbronchial and percutaneous approach in the diagnosis of peripheral pulmonary nodules or masses Experience with 1,027 consecutive cases.
      ). Unfortunately, no methods are currently available for the immediate detection of mycobacteria in respiratory samples (
      • Lewinsohn D.M.
      • Leonard M.K.
      • LoBue P.A.
      • et al.
      Official American thoracic society/infectious diseases society of America/centers for disease control and prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children.
      ).

      Bronchoalveolar lavage and bronchial washing aspirate

      Smear microscopy shows a sensitivity ranging between 4.7% and 58.0% on BAL and BW (
      • Theron G.
      • Peter J.
      • Meldau R.
      • et al.
      Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.
      ,
      • Jafari C.
      • Thijsen S.
      • Sotgiu G.
      • et al.
      Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a Tuberculosis Network European Trials group study.
      ,
      • Tueller C.
      • Chajed P.N.
      • Buitrago-Tellez C.
      • et al.
      Value of smear and PCR in bronchoalveolar lavage fluid in culture positive pulmonary tuberculosis.
      ,
      • Dheda K.
      • van Zyl-Smit R.N.
      • Meldau R.
      • et al.
      Quantitative lung T cell responses aid the rapid diagnosis of pulmonary tuberculosis.
      ,
      • Le Palud P.
      • Cattoir V.
      • Malbruny B.
      • et al.
      Retrospective observational study of diagnostic accuracy of the Xpert® MTB/RIF assay on fiberoptic bronchoscopy sampling for early diagnosis of smear-negative or sputum-scarce patients with suspected tuberculosis.
      ,
      • Barnard D.A.
      • Irusen E.M.
      • Bruwer J.W.
      • et al.
      The utility of Xpert MTB/RIF performed on bronchial washings obtained in patients with suspected pulmonary tuberculosis in a high prevalence setting.
      ,
      • Lee H.Y.
      • Seong M.W.
      • Park S.S.
      • et al.
      Diagnostic accuracy of Xpert® MTB/RIF on bronchoscopy specimens in patients with suspected pulmonary tuberculosis.
      ,
      • Lin S.M.
      • Ni Y.L.
      • Kuo C.H.
      • et al.
      Endobronchial ultrasound increases the diagnostic yields of polymerase chain reaction and smear for pulmonary tuberculosis.
      ,
      • Ko Y.
      • Lee H.K.
      • Lee Y.S.
      • et al.
      Accuracy of Xpert(®) MTB/RIF assay compared with AdvanSure™ TB/NTM real-time PCR using bronchoscopy specimens.
      ,
      • Agrawal M.
      • Bajaj A.
      • Bhatia V.
      • et al.
      Comparative study of GeneXpert with ZN stain and culture in samples of suspected pulmonary tuberculosis.
      ,
      • Khalil K.F.
      • Butt T.
      Diagnostic yield of bronchoalveolar lavage gene Xpert in smear-negative and sputum-scarce pulmonary tubrculosis.
      ).
      The NAAT sensitivity significantly varies when carried out on BW (51.9%-97.2%) (
      • Tamura A.
      • Shimada M.
      • Matsui Y.
      • et al.
      The value of fiberoptic bronchoscopy in culture-positive pulmonary tuberculosis patients whose pre-bronchoscopic sputum specimens were negative both for smear and PCR analyses.
      ,
      • Lee J.E.
      • Lee B.J.
      • Roh E.Y.
      • et al.
      The diagnostic accuracy of tuberculosis real-time polymerase chain reaction analysis of computed tomography-guided bronchial wash samples.
      ,
      • Min J.W.
      • Yoon H.I.
      • Park K.U.
      • et al.
      Real-time polymerase chain reaction in bronchial aspirate for rapid detection of sputum smear-negative tuberculosis.
      ,
      • Wong C.F.
      • Yew W.W.
      • Chan C.Y.
      • et al.
      Rapid diagnosis of smear-negative pulmonary tuberculosis via fibreoptic bronchoscopy: utility of polymerase chain reaction in bronchial aspirates as an adjunct to transbronchial biopsies.
      ,
      • Chen N.H.
      • Liu Y.C.
      • Tsao T.C.
      • et al.
      Combined bronchoalveolar lavage and polymerase chain reaction in the diagnosis of pulmonary tuberculosis in smear-negative patients.
      ,
      • Boehme C.
      • Nabeta P.
      • Hillemann D.
      • et al.
      Rapid molecular detection of tuberculosis and rifampin resistance.
      ) and BAL (31.3-83.8%) (
      • Jafari C.
      • Kessler P.
      • Sotgiu G.
      • et al.
      Impact of a Mycobacterium tuberculosis-specific interferon-γ release assay in bronchoalveolar lavage fluid for a rapid diagnosis of tuberculosis.
      ,
      • Jafari C.
      • Thijsen S.
      • Sotgiu G.
      • et al.
      Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a Tuberculosis Network European Trials group study.
      ,
      • Tueller C.
      • Chajed P.N.
      • Buitrago-Tellez C.
      • et al.
      Value of smear and PCR in bronchoalveolar lavage fluid in culture positive pulmonary tuberculosis.
      ,
      • Mondoni M.
      • Sotgiu G.
      • Bonifazi M.
      • et al.
      Transbronchial needle aspiration in peripheral pulmonary lesions: a systematic review and meta-analysis.
      ,
      • Chen N.H.
      • Liu Y.C.
      • Tsao T.C.
      • et al.
      Combined bronchoalveolar lavage and polymerase chain reaction in the diagnosis of pulmonary tuberculosis in smear-negative patients.
      ), whereas the specificity is higher than 70% (73.2-100.0%) on BW (
      • Tamura A.
      • Shimada M.
      • Matsui Y.
      • et al.
      The value of fiberoptic bronchoscopy in culture-positive pulmonary tuberculosis patients whose pre-bronchoscopic sputum specimens were negative both for smear and PCR analyses.
      ,
      • Lee J.E.
      • Lee B.J.
      • Roh E.Y.
      • et al.
      The diagnostic accuracy of tuberculosis real-time polymerase chain reaction analysis of computed tomography-guided bronchial wash samples.
      ,
      • Min J.W.
      • Yoon H.I.
      • Park K.U.
      • et al.
      Real-time polymerase chain reaction in bronchial aspirate for rapid detection of sputum smear-negative tuberculosis.
      ,
      • Wong C.F.
      • Yew W.W.
      • Chan C.Y.
      • et al.
      Rapid diagnosis of smear-negative pulmonary tuberculosis via fibreoptic bronchoscopy: utility of polymerase chain reaction in bronchial aspirates as an adjunct to transbronchial biopsies.
      ,
      • Chen N.H.
      • Liu Y.C.
      • Tsao T.C.
      • et al.
      Combined bronchoalveolar lavage and polymerase chain reaction in the diagnosis of pulmonary tuberculosis in smear-negative patients.
      ) and 92.4-98.2% on BAL (
      • Jafari C.
      • Kessler P.
      • Sotgiu G.
      • et al.
      Impact of a Mycobacterium tuberculosis-specific interferon-γ release assay in bronchoalveolar lavage fluid for a rapid diagnosis of tuberculosis.
      ,
      • Jafari C.
      • Thijsen S.
      • Sotgiu G.
      • et al.
      Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a Tuberculosis Network European Trials group study.
      ,
      • Tueller C.
      • Chajed P.N.
      • Buitrago-Tellez C.
      • et al.
      Value of smear and PCR in bronchoalveolar lavage fluid in culture positive pulmonary tuberculosis.
      ,
      • Dheda K.
      • van Zyl-Smit R.N.
      • Meldau R.
      • et al.
      Quantitative lung T cell responses aid the rapid diagnosis of pulmonary tuberculosis.
      ,
      • Ko Y.
      • Lee H.K.
      • Lee Y.S.
      • et al.
      Accuracy of Xpert(®) MTB/RIF assay compared with AdvanSure™ TB/NTM real-time PCR using bronchoscopy specimens.
      ,
      • Chen N.H.
      • Liu Y.C.
      • Tsao T.C.
      • et al.
      Combined bronchoalveolar lavage and polymerase chain reaction in the diagnosis of pulmonary tuberculosis in smear-negative patients.
      ), respectively. The mismatch between sensitivity and specificity might be partially explained from the reference to different standards in the retrieved studies (single or combined use of microbiological, clinical and histological data) (
      • Jafari C.
      • Kessler P.
      • Sotgiu G.
      • et al.
      Impact of a Mycobacterium tuberculosis-specific interferon-γ release assay in bronchoalveolar lavage fluid for a rapid diagnosis of tuberculosis.
      ,
      • Jafari C.
      • Thijsen S.
      • Sotgiu G.
      • et al.
      Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a Tuberculosis Network European Trials group study.
      ,
      • Tueller C.
      • Chajed P.N.
      • Buitrago-Tellez C.
      • et al.
      Value of smear and PCR in bronchoalveolar lavage fluid in culture positive pulmonary tuberculosis.
      ,
      • Tamura A.
      • Shimada M.
      • Matsui Y.
      • et al.
      The value of fiberoptic bronchoscopy in culture-positive pulmonary tuberculosis patients whose pre-bronchoscopic sputum specimens were negative both for smear and PCR analyses.
      ,
      • Ko Y.
      • Lee H.K.
      • Lee Y.S.
      • et al.
      Accuracy of Xpert(®) MTB/RIF assay compared with AdvanSure™ TB/NTM real-time PCR using bronchoscopy specimens.
      ,
      • Lee J.E.
      • Lee B.J.
      • Roh E.Y.
      • et al.
      The diagnostic accuracy of tuberculosis real-time polymerase chain reaction analysis of computed tomography-guided bronchial wash samples.
      ,
      • Min J.W.
      • Yoon H.I.
      • Park K.U.
      • et al.
      Real-time polymerase chain reaction in bronchial aspirate for rapid detection of sputum smear-negative tuberculosis.
      ,
      • Wong C.F.
      • Yew W.W.
      • Chan C.Y.
      • et al.
      Rapid diagnosis of smear-negative pulmonary tuberculosis via fibreoptic bronchoscopy: utility of polymerase chain reaction in bronchial aspirates as an adjunct to transbronchial biopsies.
      ,
      • Chen N.H.
      • Liu Y.C.
      • Tsao T.C.
      • et al.
      Combined bronchoalveolar lavage and polymerase chain reaction in the diagnosis of pulmonary tuberculosis in smear-negative patients.
      ).
      Xpert®MTB/RIF (Cepheid Inc, Sunnyvale, California, USA) assay, a single cartridge-based NAAT, can simultaneously detect Mycobacterium tuberculosis nucleic acids and its genetic rifampicin (RMP) resistence within 2–3 hours (
      • Boehme C.
      • Nabeta P.
      • Hillemann D.
      • et al.
      Rapid molecular detection of tuberculosis and rifampin resistance.
      ,
      • World Health Organization
      Policy statement: automated real-time nucleic acid amplification technology for rapid and simultaneous detection of tuberculosis and rifampicin resistance. Xpert MTB/RIF. Policy statement.
      ). In comparison with the other commercially available NAATs, it is based on a fully-automated process (
      • Theron G.
      • Peter J.
      • Meldau R.
      • et al.
      Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.
      ,
      • Le Palud P.
      • Cattoir V.
      • Malbruny B.
      • et al.
      Retrospective observational study of diagnostic accuracy of the Xpert® MTB/RIF assay on fiberoptic bronchoscopy sampling for early diagnosis of smear-negative or sputum-scarce patients with suspected tuberculosis.
      ,
      • Boehme C.
      • Nabeta P.
      • Hillemann D.
      • et al.
      Rapid molecular detection of tuberculosis and rifampin resistance.
      ,
      • World Health Organization
      Policy statement: automated real-time nucleic acid amplification technology for rapid and simultaneous detection of tuberculosis and rifampicin resistance. Xpert MTB/RIF. Policy statement.
      ,
      • Sharma S.K.
      • Kohli M.
      • Yadav R.N.
      • et al.
      Evaluating the diagnostic accuracy of Xpert MTB/RIF assay in pulmonary tuberculosis.
      ,
      • Albert H.
      • Nathavitharana R.R.
      • Isaacs C.
      • et al.
      Development, roll-out and impact of Xpert MTB/RIF for tuberculosis: what lessons have we learnt and how ca we do better?.
      ). Its diagnostic accuracy was widely confirmed on sputum specimens; however, in recent years its performance was successfully assessed on bronchoscopic specimens such as BW (
      • Le Palud P.
      • Cattoir V.
      • Malbruny B.
      • et al.
      Retrospective observational study of diagnostic accuracy of the Xpert® MTB/RIF assay on fiberoptic bronchoscopy sampling for early diagnosis of smear-negative or sputum-scarce patients with suspected tuberculosis.
      ,
      • Barnard D.A.
      • Irusen E.M.
      • Bruwer J.W.
      • et al.
      The utility of Xpert MTB/RIF performed on bronchial washings obtained in patients with suspected pulmonary tuberculosis in a high prevalence setting.
      ,
      • Lee H.Y.
      • Seong M.W.
      • Park S.S.
      • et al.
      Diagnostic accuracy of Xpert® MTB/RIF on bronchoscopy specimens in patients with suspected pulmonary tuberculosis.
      ,
      • Ko Y.
      • Lee H.K.
      • Lee Y.S.
      • et al.
      Accuracy of Xpert(®) MTB/RIF assay compared with AdvanSure™ TB/NTM real-time PCR using bronchoscopy specimens.
      ,
      • Sharma S.K.
      • Kohli M.
      • Yadav R.N.
      • et al.
      Evaluating the diagnostic accuracy of Xpert MTB/RIF assay in pulmonary tuberculosis.
      ,
      • Jo Y.S.
      • Park J.H.
      • Lee J.K.
      • et al.
      Discordance between MTB/RIF and real-time tuberculosis-Specific polymerase chain reaction assay in bronchial washing specimen and its clinical implications.
      ), BAL (
      • Theron G.
      • Peter J.
      • Meldau R.
      • et al.
      Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.
      ,
      • Mok Y.
      • Tan T.Y.
      • Tay T.R.
      • et al.
      Do we need transbronchial lung biopsy if we have bronchoalveolar lavage Xpert(®) MTB/RIF?.
      ,
      • Le Palud P.
      • Cattoir V.
      • Malbruny B.
      • et al.
      Retrospective observational study of diagnostic accuracy of the Xpert® MTB/RIF assay on fiberoptic bronchoscopy sampling for early diagnosis of smear-negative or sputum-scarce patients with suspected tuberculosis.
      ,
      • Lee H.Y.
      • Seong M.W.
      • Park S.S.
      • et al.
      Diagnostic accuracy of Xpert® MTB/RIF on bronchoscopy specimens in patients with suspected pulmonary tuberculosis.
      ,
      • Ko Y.
      • Lee H.K.
      • Lee Y.S.
      • et al.
      Accuracy of Xpert(®) MTB/RIF assay compared with AdvanSure™ TB/NTM real-time PCR using bronchoscopy specimens.
      ,
      • Agrawal M.
      • Bajaj A.
      • Bhatia V.
      • et al.
      Comparative study of GeneXpert with ZN stain and culture in samples of suspected pulmonary tuberculosis.
      ,
      • Khalil K.F.
      • Butt T.
      Diagnostic yield of bronchoalveolar lavage gene Xpert in smear-negative and sputum-scarce pulmonary tubrculosis.
      ,
      • Sharma S.K.
      • Kohli M.
      • Yadav R.N.
      • et al.
      Evaluating the diagnostic accuracy of Xpert MTB/RIF assay in pulmonary tuberculosis.
      ,
      • Ullah I.
      • Javaid A.
      • Masud H.
      • et al.
      Rapid detection of Mycobacterium tuberculosis and rifampicin resistance in extrapulmonary tuberculosis and sputum smear-negative pulmonary suspects using Xpert MTB/RIF.
      ), and endobronchial ultrasound guided-transbronchial needle aspiration (EBUS-TBNA) (
      • Dhasmana D.J.
      • Ross C.
      • Bradley C.J.
      • et al.
      Performance of Xpert MTB/RIF in the diagnosis of tuberculous mediastinal lymphadenopathy by endobronchial ultrasound.
      ,
      • Dhooria S.
      • Gupta N.
      • Bal A.
      • et al.
      Role of Xpert MTB/RIF in differentiating tuberculosis from sarcoidosis in patients with mediastinal lymphadenopathy undergoing EBUS-TBNA: a study of 147 patients.
      ,
      • Lee J.
      • Choi S.M.
      • Lee C.H.
      • et al.
      The additional role of Xpert MTB/RIF in the diagnosis of intrathoracic tuberculous lymphadenitis.
      ) (Table 1).
      Table 1Summary of studies evaluating the diagnostic performance of Xpert®MTB/RIF on bronchoscopic specimens.
      Author/yearCountryStudy designPatients numberBronchoscopic specimenSensitivitySpecificityReference standard
      • Theron G.
      • Peter J.
      • Meldau R.
      • et al.
      Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.
      South AfricaPCS27BAL92.6%96%Culture
      • Lee H.Y.
      • Seong M.W.
      • Park S.S.
      • et al.
      Diagnostic accuracy of Xpert® MTB/RIF on bronchoscopy specimens in patients with suspected pulmonary tuberculosis.
      Republic of KoreaRCS38BAL and BW81.6%100%Culture
      • Le Palud P.
      • Cattoir V.
      • Malbruny B.
      • et al.
      Retrospective observational study of diagnostic accuracy of the Xpert® MTB/RIF assay on fiberoptic bronchoscopy sampling for early diagnosis of smear-negative or sputum-scarce patients with suspected tuberculosis.
      FranceRCS23BAL and BW80%98.6%Culture
      • Dhasmana D.J.
      • Ross C.
      • Bradley C.J.
      • et al.
      Performance of Xpert MTB/RIF in the diagnosis of tuberculous mediastinal lymphadenopathy by endobronchial ultrasound.
      Great BritainRCS84EBUS-TBNA72.6%NRCulture
      • Barnard D.A.
      • Irusen E.M.
      • Bruwer J.W.
      • et al.
      The utility of Xpert MTB/RIF performed on bronchial washings obtained in patients with suspected pulmonary tuberculosis in a high prevalence setting.
      South AfricaRCS39BW92.3%87.7%Culture
      • Khalil K.F.
      • Butt T.
      Diagnostic yield of bronchoalveolar lavage gene Xpert in smear-negative and sputum-scarce pulmonary tubrculosis.
      PakistanRCS85BAL91.8%71.4%Culture
      • Agrawal M.
      • Bajaj A.
      • Bhatia V.
      • et al.
      Comparative study of GeneXpert with ZN stain and culture in samples of suspected pulmonary tuberculosis.
      IndiaRCS27BAL81.4%93.4%Culture
      • Ko Y.
      • Lee H.K.
      • Lee Y.S.
      • et al.
      Accuracy of Xpert(®) MTB/RIF assay compared with AdvanSure™ TB/NTM real-time PCR using bronchoscopy specimens.
      Republic of KoreaRCS105BAL and BW92.4%91.7%Culture
      • Sharma S.K.
      • Kohli M.
      • Yadav R.N.
      • et al.
      Evaluating the diagnostic accuracy of Xpert MTB/RIF assay in pulmonary tuberculosis.
      IndiaPCSBAL: 127

      BW: 4
      BAL and BWBAL: 90%

      BW: 100%
      BAL: 100%

      BW: 100%
      Culture
      • Mok Y.
      • Tan T.Y.
      • Tay T.R.
      • et al.
      Do we need transbronchial lung biopsy if we have bronchoalveolar lavage Xpert(®) MTB/RIF?.
      SingaporeRCS44BAL68%98%Culture
      • Jo Y.S.
      • Park J.H.
      • Lee J.K.
      • et al.
      Discordance between MTB/RIF and real-time tuberculosis-Specific polymerase chain reaction assay in bronchial washing specimen and its clinical implications.
      Republic of KoreaRCS64BW92.2.4%81.6%Culture
      • Dhooria S.
      • Gupta N.
      • Bal A.
      • et al.
      Role of Xpert MTB/RIF in differentiating tuberculosis from sarcoidosis in patients with mediastinal lymphadenopathy undergoing EBUS-TBNA: a study of 147 patients.
      IndiaRCS53EBUS-TBNA49.1%97.9%AFB microscopy or culture or histology and clinico-radiological presentation and responses to treatment
      • Lee J.
      • Choi S.M.
      • Lee C.H.
      • et al.
      The additional role of Xpert MTB/RIF in the diagnosis of intrathoracic tuberculous lymphadenitis.
      Republic of KoreaRCS10EBUS-TBNA100%NRCulture or histology or NAAT (Xpert)
      • Ullah I.
      • Javaid A.
      • Masud H.
      • et al.
      Rapid detection of Mycobacterium tuberculosis and rifampicin resistance in extrapulmonary tuberculosis and sputum smear-negative pulmonary suspects using Xpert MTB/RIF.
      PakistanPCS98BAL80%87.5%Culture
      PCS: prospective cohort study; RCS: retrospective cohort study; TB: tuberculosis; BAL: bronchoalveolar lavage; BW: bronchial washing; EBUS-TBNA: endobronchial ultrasounds-transbronchial needle aspiration; NR: not reported.
      Theron et al. firstly demonstrated the high diagnostic accuracy of Xpert®MTB/RIF on BAL (
      • Theron G.
      • Peter J.
      • Meldau R.
      • et al.
      Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.
      ). In a high TB incidence country (South Africa), the Authors prospectively enrolled 160 sputum scarce or smear-negative patients with suspected pulmonary TB, who underwent bronchoscopy with BAL. Out of 27 patients with BAL culture positive for Mycobacterium tuberculosis, Xpert®MTB/RIF showed a sensitivity of 97%, significantly higher than that of smear microscopy performed on the same specimen (58%). Definite diagnosis was done in more than 80% of sputum smear negative patients. HIV/TB co-infection (35% of patients) did not affect sensitivity and specificity (
      • Theron G.
      • Peter J.
      • Meldau R.
      • et al.
      Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.
      ). In contrast with the findings of Ko et al. (
      • Ko Y.
      • Lee H.K.
      • Lee Y.S.
      • et al.
      Accuracy of Xpert(®) MTB/RIF assay compared with AdvanSure™ TB/NTM real-time PCR using bronchoscopy specimens.
      ), they failed to demonstrate a significantly shorter treatment delay in patients with positive BAL Xpert.
      Similar findings were shown by other Authors (
      • Barnard D.A.
      • Irusen E.M.
      • Bruwer J.W.
      • et al.
      The utility of Xpert MTB/RIF performed on bronchial washings obtained in patients with suspected pulmonary tuberculosis in a high prevalence setting.
      ,
      • Lee H.Y.
      • Seong M.W.
      • Park S.S.
      • et al.
      Diagnostic accuracy of Xpert® MTB/RIF on bronchoscopy specimens in patients with suspected pulmonary tuberculosis.
      ,
      • Agrawal M.
      • Bajaj A.
      • Bhatia V.
      • et al.
      Comparative study of GeneXpert with ZN stain and culture in samples of suspected pulmonary tuberculosis.
      ,
      • Khalil K.F.
      • Butt T.
      Diagnostic yield of bronchoalveolar lavage gene Xpert in smear-negative and sputum-scarce pulmonary tubrculosis.
      ,
      • Sharma S.K.
      • Kohli M.
      • Yadav R.N.
      • et al.
      Evaluating the diagnostic accuracy of Xpert MTB/RIF assay in pulmonary tuberculosis.
      ,
      • Jo Y.S.
      • Park J.H.
      • Lee J.K.
      • et al.
      Discordance between MTB/RIF and real-time tuberculosis-Specific polymerase chain reaction assay in bronchial washing specimen and its clinical implications.
      ,
      • Ullah I.
      • Javaid A.
      • Masud H.
      • et al.
      Rapid detection of Mycobacterium tuberculosis and rifampicin resistance in extrapulmonary tuberculosis and sputum smear-negative pulmonary suspects using Xpert MTB/RIF.
      ) who retrospectively demonstrated a high sensitivity (81-100%) of Xpert®MTB/RIF in both BW and BAL (Table 1).
      Interestingly,
      • Le Palud P.
      • Cattoir V.
      • Malbruny B.
      • et al.
      Retrospective observational study of diagnostic accuracy of the Xpert® MTB/RIF assay on fiberoptic bronchoscopy sampling for early diagnosis of smear-negative or sputum-scarce patients with suspected tuberculosis.
      confirmed a high sensitivity (80%) of the assay also in a low TB incidence country (France), enrolling 23 culture-positive patients who underwent bronchoscopy with BAL and BW for suspected pulmonary TB.
      However,
      • Barnard D.A.
      • Irusen E.M.
      • Bruwer J.W.
      • et al.
      The utility of Xpert MTB/RIF performed on bronchial washings obtained in patients with suspected pulmonary tuberculosis in a high prevalence setting.
      reported on a lower specificity (87.7%): 9 patients resulted Xpert positive and culture negative (with a very low cycle threshold value), with three of them previously treated for pulmonary TB and one infected by Mycobacterium avium intracellulare. They highlight the importance of culture confirmation, as well as the medical history of a previous TB diagnosis and treatment (
      • Barnard D.A.
      • Irusen E.M.
      • Bruwer J.W.
      • et al.
      The utility of Xpert MTB/RIF performed on bronchial washings obtained in patients with suspected pulmonary tuberculosis in a high prevalence setting.
      ,
      • Ko Y.
      • Lee H.K.
      • Lee Y.S.
      • et al.
      Accuracy of Xpert(®) MTB/RIF assay compared with AdvanSure™ TB/NTM real-time PCR using bronchoscopy specimens.
      ,
      • Khalil K.F.
      • Butt T.
      Diagnostic yield of bronchoalveolar lavage gene Xpert in smear-negative and sputum-scarce pulmonary tubrculosis.
      ).
      Ko et al. compared the accuracy of Xpert®MTB/RIF with AdvanSure™, a conventional real-time polymerase chain reaction (PCR) in 105 culture-confirmed pulmonary TB patients for whom both PCR techniques were available on BAL and BW. Xpert®MTB/RIF sensitivity was significantly higher than that of the conventional assay (92.4% vs. 83.8%, respectively) in smear negative patients, without any significant differences in smear positive subjects (
      • Ko Y.
      • Lee H.K.
      • Lee Y.S.
      • et al.
      Accuracy of Xpert(®) MTB/RIF assay compared with AdvanSure™ TB/NTM real-time PCR using bronchoscopy specimens.
      ). Similar findings were also demonstrated by
      • Jo Y.S.
      • Park J.H.
      • Lee J.K.
      • et al.
      Discordance between MTB/RIF and real-time tuberculosis-Specific polymerase chain reaction assay in bronchial washing specimen and its clinical implications.
      .
      Several studies demonstrated a high sensitivity (83.3-100.0%) and specificity (97.7-100.0%) of Xpert in diagnosing RMP resistance on both BAL and BW (
      • Theron G.
      • Peter J.
      • Meldau R.
      • et al.
      Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.
      ,
      • Barnard D.A.
      • Irusen E.M.
      • Bruwer J.W.
      • et al.
      The utility of Xpert MTB/RIF performed on bronchial washings obtained in patients with suspected pulmonary tuberculosis in a high prevalence setting.
      ,
      • Lee H.Y.
      • Seong M.W.
      • Park S.S.
      • et al.
      Diagnostic accuracy of Xpert® MTB/RIF on bronchoscopy specimens in patients with suspected pulmonary tuberculosis.
      ,
      • Sharma S.K.
      • Kohli M.
      • Yadav R.N.
      • et al.
      Evaluating the diagnostic accuracy of Xpert MTB/RIF assay in pulmonary tuberculosis.
      ,
      • Ullah I.
      • Javaid A.
      • Masud H.
      • et al.
      Rapid detection of Mycobacterium tuberculosis and rifampicin resistance in extrapulmonary tuberculosis and sputum smear-negative pulmonary suspects using Xpert MTB/RIF.
      ).
      Interferon-gamma release assays (IGRAs) are being used increasingly for the detection of an immune response against Mycobacterium tuberculosis antigens. However, their diagnostic accuracy (sub-optimal sensitivity and low specificity) for active TB has been disappointing when performed on blood specimens, especially in high TB incidence areas (
      • Sester M.
      • Sotgiu G.
      • Lange C.
      • et al.
      Interferon-γ release assays for the diagnosis of active tuberculosis: a systematic review and meta-analysis.
      ,
      • Cattamanchi A.
      • Ssewenyana I.
      • Nabatanzi R.
      • et al.
      Bronchoalveolar lavage enzyme-linked immunospot for diagnosis of smear-negativetuberculosis in HIV-infected patients.
      ). The identification of a TB-specific immune response at the site of disease (i.e. the lungs) might improve IGRA performance, favouring an early diagnosis in AFB smear negative/sputum scarce patients (
      • Sester M.
      • Sotgiu G.
      • Lange C.
      • et al.
      Interferon-γ release assays for the diagnosis of active tuberculosis: a systematic review and meta-analysis.
      ,
      • Cattamanchi A.
      • Ssewenyana I.
      • Nabatanzi R.
      • et al.
      Bronchoalveolar lavage enzyme-linked immunospot for diagnosis of smear-negativetuberculosis in HIV-infected patients.
      ).
      Only a few studies have assessed the IGRAs on BAL specimens: the first ones, performed in low TB burden countries (Europe) with a lowest HIV infection prevalence, demonostrated a sensitivity and a specificity ranging from 91.0 to 100.0% and from 80.0-100.0%, respectively, with a low rate of indeterminate results (5-9%) (
      • Jafari C.
      • Kessler P.
      • Sotgiu G.
      • et al.
      Impact of a Mycobacterium tuberculosis-specific interferon-γ release assay in bronchoalveolar lavage fluid for a rapid diagnosis of tuberculosis.
      ,
      • Jafari C.
      • Thijsen S.
      • Sotgiu G.
      • et al.
      Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a Tuberculosis Network European Trials group study.
      ,
      • Jafari C.
      • Ernst M.
      • Kalsdorf B.
      • et al.
      Rapid diagnosis of smear-negative tuberculosis by bronchoalveolar lavage enzyme-linked immunospot.
      ). Studies performed in high HIV/TB incidence countries showed a lower accuracy and a higher rate of indeterminate results (up to 34%) (
      • Dheda K.
      • van Zyl-Smit R.N.
      • Meldau R.
      • et al.
      Quantitative lung T cell responses aid the rapid diagnosis of pulmonary tuberculosis.
      ,
      • Cattamanchi A.
      • Ssewenyana I.
      • Nabatanzi R.
      • et al.
      Bronchoalveolar lavage enzyme-linked immunospot for diagnosis of smear-negativetuberculosis in HIV-infected patients.
      ,
      • Jafari C.
      • Ernst M.
      • Kalsdorf B.
      • et al.
      Comparison of molecular and immunological methods for the rapid diagnosis of smear-negative tuberculosis.
      ). To date, its suboptimal accuracy in BAL is limiting its scale-up (
      • Sester M.
      • Sotgiu G.
      • Lange C.
      • et al.
      Interferon-γ release assays for the diagnosis of active tuberculosis: a systematic review and meta-analysis.
      ,
      • Cattamanchi A.
      • Ssewenyana I.
      • Nabatanzi R.
      • et al.
      Bronchoalveolar lavage enzyme-linked immunospot for diagnosis of smear-negativetuberculosis in HIV-infected patients.
      ,
      • Jafari C.
      • Ernst M.
      • Kalsdorf B.
      • et al.
      Comparison of molecular and immunological methods for the rapid diagnosis of smear-negative tuberculosis.
      ).

      Transbronchial biopsy techniques

      Fluoroscopy-guided transbronchial forceps biopsy (TBB) has long been used in diagnosing pulmonary TB in sputum-scarce or smear negative patients with peripheral pulmonary lesions (Figure 1). The histological feature of necrotizing granulomas on transbronchial samples in adjunction with AFB examination can shorten the TB diagnostic delay (
      • Mok Y.
      • Tan T.Y.
      • Tay T.R.
      • et al.
      Do we need transbronchial lung biopsy if we have bronchoalveolar lavage Xpert(®) MTB/RIF?.
      ,
      • Tamura A.
      • Shimada M.
      • Matsui Y.
      • et al.
      The value of fiberoptic bronchoscopy in culture-positive pulmonary tuberculosis patients whose pre-bronchoscopic sputum specimens were negative both for smear and PCR analyses.
      ,
      • Chan A.
      • Devanand A.
      • Low S.Y.
      • et al.
      Radial endobronchial ultrasound in diagnosing peripheral lung lesions in a high tuberculosis setting.
      ,
      • Jacomelli M.
      • Silva P.R.
      • Rodrigues A.J.
      • et al.
      Bronchoscopy for the diagnosis of pulmonary tuberculosis in patients with negative sputum smear microscopy results.
      ,
      • Willcox P.A.
      • Benatar S.R.
      • Potgieter P.D.
      Use of the flexible fibreoptic bronchoscope in diagnosis of sputum-negative pulmonary tuberculosis.
      ). In case of missing contraindications, it was recommended by several Authors to add on TBB to BAL in order to increase bronchoscopy sensitivity (
      • Mok Y.
      • Tan T.Y.
      • Tay T.R.
      • et al.
      Do we need transbronchial lung biopsy if we have bronchoalveolar lavage Xpert(®) MTB/RIF?.
      ,
      • Tamura A.
      • Shimada M.
      • Matsui Y.
      • et al.
      The value of fiberoptic bronchoscopy in culture-positive pulmonary tuberculosis patients whose pre-bronchoscopic sputum specimens were negative both for smear and PCR analyses.
      ,
      • Jacomelli M.
      • Silva P.R.
      • Rodrigues A.J.
      • et al.
      Bronchoscopy for the diagnosis of pulmonary tuberculosis in patients with negative sputum smear microscopy results.
      ,
      • Lin S.M.
      • Ni Y.L.
      • Kuo C.H.
      • et al.
      Endobronchial ultrasound increases the diagnostic yields of polymerase chain reaction and smear for pulmonary tuberculosis.
      ,
      • Charoenratanakul S.
      • Dejsomritrutai W.
      • Chaiprasert A.
      Diagnostic role of fiberoptic bronchoscopy in suspected smear negative pulmonary tuberculosis.
      ).
      Figure 1
      Figure 1Chest computed tomography (A) and PET/CT scan (B) of a cavitated lesion in a patient with tuberculosis; conventional fluoroscopy-guided transbronchial biopsy (C) and needle aspiration (D) of the lesion.
      Several studies showed a TBB sensitivity of 16-77% in association with a good safety profile. Pneumothorax and bleeding are the most frequently reported complications (
      • Theron G.
      • Peter J.
      • Meldau R.
      • et al.
      Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.
      ,
      • Mok Y.
      • Tan T.Y.
      • Tay T.R.
      • et al.
      Do we need transbronchial lung biopsy if we have bronchoalveolar lavage Xpert(®) MTB/RIF?.
      ,
      • Tamura A.
      • Shimada M.
      • Matsui Y.
      • et al.
      The value of fiberoptic bronchoscopy in culture-positive pulmonary tuberculosis patients whose pre-bronchoscopic sputum specimens were negative both for smear and PCR analyses.
      ,
      • Chan A.
      • Devanand A.
      • Low S.Y.
      • et al.
      Radial endobronchial ultrasound in diagnosing peripheral lung lesions in a high tuberculosis setting.
      ,
      • Jacomelli M.
      • Silva P.R.
      • Rodrigues A.J.
      • et al.
      Bronchoscopy for the diagnosis of pulmonary tuberculosis in patients with negative sputum smear microscopy results.
      ,
      • Willcox P.A.
      • Benatar S.R.
      • Potgieter P.D.
      Use of the flexible fibreoptic bronchoscope in diagnosis of sputum-negative pulmonary tuberculosis.
      ,
      • Charoenratanakul S.
      • Dejsomritrutai W.
      • Chaiprasert A.
      Diagnostic role of fiberoptic bronchoscopy in suspected smear negative pulmonary tuberculosis.
      ,
      • Wallace J.M.
      • Deutsch A.L.
      • Harrell J.H.
      • et al.
      Bronchoscopy and transbronchial biopsy in evaluation of patients with suspected active tuberculosis.
      ,
      • Willcox P.A.
      • Potgieter P.D.
      • Bateman E.D.
      • et al.
      Rapid diagnosis of sputum negative miliary tuberculosis using the flexible fibreoptic bronchoscope.
      ,
      • Danek S.J.
      • Bower J.S.
      Diagnosis of pulmonary tuberculosis by flexible fiberoptic bronchoscopy.
      ,
      • Stenson W.
      • Aranda C.
      • Bevelaqua F.A.
      Transbronchial biopsy culture in pulmonary tuberculosis.
      ,
      • Lai R.S.
      • Lee S.S.
      • Ting Y.M.
      • et al.
      Diagnostic value of transbronchial lung biopsy under fluoroscopic guidance in solitary pulmonary nodule in an endemic area of tuberculosis.
      ).
      The wide inter-study variability of the diagnostic accuracy might be explained by the heterogeneous TB diagnostic criteria (i.e., histology, bacteriology, or their combination), lesions size, and radiological features of the parenchymal lesions (
      • Theron G.
      • Peter J.
      • Meldau R.
      • et al.
      Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.
      ,
      • Mok Y.
      • Tan T.Y.
      • Tay T.R.
      • et al.
      Do we need transbronchial lung biopsy if we have bronchoalveolar lavage Xpert(®) MTB/RIF?.
      ,
      • Tamura A.
      • Shimada M.
      • Matsui Y.
      • et al.
      The value of fiberoptic bronchoscopy in culture-positive pulmonary tuberculosis patients whose pre-bronchoscopic sputum specimens were negative both for smear and PCR analyses.
      ,
      • Chan A.
      • Devanand A.
      • Low S.Y.
      • et al.
      Radial endobronchial ultrasound in diagnosing peripheral lung lesions in a high tuberculosis setting.
      ,
      • Jacomelli M.
      • Silva P.R.
      • Rodrigues A.J.
      • et al.
      Bronchoscopy for the diagnosis of pulmonary tuberculosis in patients with negative sputum smear microscopy results.
      ,
      • Willcox P.A.
      • Benatar S.R.
      • Potgieter P.D.
      Use of the flexible fibreoptic bronchoscope in diagnosis of sputum-negative pulmonary tuberculosis.
      ,
      • Charoenratanakul S.
      • Dejsomritrutai W.
      • Chaiprasert A.
      Diagnostic role of fiberoptic bronchoscopy in suspected smear negative pulmonary tuberculosis.
      ,
      • Wallace J.M.
      • Deutsch A.L.
      • Harrell J.H.
      • et al.
      Bronchoscopy and transbronchial biopsy in evaluation of patients with suspected active tuberculosis.
      ,
      • Willcox P.A.
      • Potgieter P.D.
      • Bateman E.D.
      • et al.
      Rapid diagnosis of sputum negative miliary tuberculosis using the flexible fibreoptic bronchoscope.
      ,
      • Danek S.J.
      • Bower J.S.
      Diagnosis of pulmonary tuberculosis by flexible fiberoptic bronchoscopy.
      ,
      • Stenson W.
      • Aranda C.
      • Bevelaqua F.A.
      Transbronchial biopsy culture in pulmonary tuberculosis.
      ,
      • Lai R.S.
      • Lee S.S.
      • Ting Y.M.
      • et al.
      Diagnostic value of transbronchial lung biopsy under fluoroscopic guidance in solitary pulmonary nodule in an endemic area of tuberculosis.
      ), with lesions sized >2 cm (
      • Lai R.S.
      • Lee S.S.
      • Ting Y.M.
      • et al.
      Diagnostic value of transbronchial lung biopsy under fluoroscopic guidance in solitary pulmonary nodule in an endemic area of tuberculosis.
      ) and miliary TB (
      • Willcox P.A.
      • Potgieter P.D.
      • Bateman E.D.
      • et al.
      Rapid diagnosis of sputum negative miliary tuberculosis using the flexible fibreoptic bronchoscope.
      ,
      • Burk J.R.
      • Viroslav J.
      • Bynum L.J.
      Miliary tuberculosis diagnosed by fibreoptic bronchoscopy and transbronchial biopsy.
      ) associated with an improved yield.
      Chan et al. described the highest sensitivity of TBB (77%) with the guidance of radial probe endobronchial ultrasounds (
      • Chan A.
      • Devanand A.
      • Low S.Y.
      • et al.
      Radial endobronchial ultrasound in diagnosing peripheral lung lesions in a high tuberculosis setting.
      ), whereas Lin et al. showed that EBUS-guided TBB is associated with a higher sensitivity than conventional fluoroscopically-guided samples (32.9% vs. 4.2%). Furthermore, in the subgroup of lesions detected with EBUS probes, AFB smears and cultures on BAL showed a higher sensitivity than in the control group (
      • Lin S.M.
      • Ni Y.L.
      • Kuo C.H.
      • et al.
      Endobronchial ultrasound increases the diagnostic yields of polymerase chain reaction and smear for pulmonary tuberculosis.
      ) (Table 2).
      Table 2Factors potentially affecting the sensitivity of transbronchial biopsy in diagnosing pulmonary tuberculosis.
      Lesion size
      Presence of miliary tuberculosis
      Radial probe endobronchial ultrasounds-guidance
      More recently, Mok et al. reported on the results of an observational, retrospective study conducted in a tertiary hospital in Singapore, where the diagnostic role of BAL Xpert on sputum scarce and smear negative patients with pulmonary TB was assessed (
      • Mok Y.
      • Tan T.Y.
      • Tay T.R.
      • et al.
      Do we need transbronchial lung biopsy if we have bronchoalveolar lavage Xpert(®) MTB/RIF?.
      ). They confirmed the good sensitivity of Xpert assay on BAL (68%) and stated that when Xpert® assay is added to routine BAL analysis TBLB did not significantly increase early and overall diagnostic yield. However, TBLB has a higher yield than BAL in diagnosing both interstitial lung diseases and pulmonary cancers, i.e. in cases showing clinical and radiological features that can closely resemble pulmonary TB. This technical characteristic may be relevant in countries with a low TB incidence, where the diagnosis of interstitial and malignant diseases is more frequent than TB. Then, the replacement of TBLB might lead to underdiagnosis of rapidly progressive and life-threatening medical conditions (
      • Mok Y.
      • Tan T.Y.
      • Tay T.R.
      • et al.
      Do we need transbronchial lung biopsy if we have bronchoalveolar lavage Xpert(®) MTB/RIF?.
      ,
      • Jacomelli M.
      • Silva P.R.
      • Rodrigues A.J.
      • et al.
      Bronchoscopy for the diagnosis of pulmonary tuberculosis in patients with negative sputum smear microscopy results.
      ,
      • Lin S.M.
      • Ni Y.L.
      • Kuo C.H.
      • et al.
      Endobronchial ultrasound increases the diagnostic yields of polymerase chain reaction and smear for pulmonary tuberculosis.
      ,
      • Mondoni M.
      • Fois A.
      • Centanni S.
      • et al.
      Could BAL Xpert(®) MTB/RIF replace transbronchial lung biopsy everywhere for suspected pulmonary TB patients?.
      ).
      Other Authors reported on the utility of cytological specimens containing typical granulomas collected through fluoroscopically-guided brushing and transbronchial needle aspiration in the diagnosis of TB-related peripheral pulmonary nodules and masses (
      • Tamura A.
      • Shimada M.
      • Matsui Y.
      • et al.
      The value of fiberoptic bronchoscopy in culture-positive pulmonary tuberculosis patients whose pre-bronchoscopic sputum specimens were negative both for smear and PCR analyses.
      ,
      • Reichenberger F.
      • Weber J.
      • Tamm M.
      • et al.
      The value of transbronchial needle aspiration in the diagnosis of peripheral pulmonary lesions.
      ,
      • Gasparini S.
      • Ferretti M.
      • Secchi E.B.
      • et al.
      Integration of transbronchial and percutaneous approach in the diagnosis of peripheral pulmonary nodules or masses Experience with 1,027 consecutive cases.
      ,
      • Jafari C.
      • Ernst M.
      • Kalsdorf B.
      • et al.
      Comparison of molecular and immunological methods for the rapid diagnosis of smear-negative tuberculosis.
      ,
      • Franzen D.
      • Diacon A.H.
      • Freitag L.
      • et al.
      Ultrathin bronchoscopy for solitary pulmonary lesions in a region endemic for tuberculosis: a randomised pilot trial.
      ) (Figure 1). Franzen et al., who carried out a randomized controlled trial in a high TB incidence country, failed to demonstrate a higher yield of brushing and TBLB performed with an ultrathin bronchocope versus samplings obtained with a standard bronchoscope (
      • Franzen D.
      • Diacon A.H.
      • Freitag L.
      • et al.
      Ultrathin bronchoscopy for solitary pulmonary lesions in a region endemic for tuberculosis: a randomised pilot trial.
      ).
      To date only one case report has described the utility and safety of transbronchial cryoprobes in diagnosing pulmonary TB and discriminating it from other diffuse lung diseases (such as sarcoidosis) in a high TB incidence setting (
      • Dhooria S.
      • Bal A.
      • Shegal I.S.
      • et al.
      Transbronchial lung biopsy with a flexible cryoprobe.First case report from India.
      ). Cryoprobes might further enhance the diagnostic performance of bronchoscopy in early and overall diagnosis of TB and diseases closely resembling TB (
      • Mondoni M.
      • Fois A.
      • Centanni S.
      • et al.
      Could BAL Xpert(®) MTB/RIF replace transbronchial lung biopsy everywhere for suspected pulmonary TB patients?.
      ,
      • Dhooria S.
      • Bal A.
      • Shegal I.S.
      • et al.
      Transbronchial lung biopsy with a flexible cryoprobe.First case report from India.
      ) but future, controlled studies are needed.

      Bronchoscopy and endobronchial tuberculosis

      Endobonchial TB (EBTB) is a TB form involving the tracheobronchial tree (microbiological and histopathological evidence), regardless of a parenchymal involvement (
      • Kashyap S.
      • Solanki A.
      Challenges in endobonchial tuberculosis: from diagnosis to management.
      ,
      • Sahin F.
      • Yildiz P.
      Characteristics of endobronchial tuberculosis patients with negative sputum acid-fast bacillus.
      ). The estimated incidence of EBTB was equal to 5.8%-50% (
      • Altin S.
      • Cikrikçioglu S.
      • Morgül M.
      • et al.
      50 endobronchial tuberculosis cases based on bronchoscopic diagnosis.
      ,
      • Chung H.S.
      • Lee J.H.
      Bronchoscopic assessment of the evolution of endobronchial tuberculosis.
      ,
      • Lee J.Y.
      • Yi C.A.
      • Kim T.S.
      • et al.
      CT scan features as predictors of patient outcome after bronchial intervention in endobronchial TB.
      ,
      • Kurasawa T.
      • Kuze F.
      • Kawai M.
      • et al.
      Diagnosis and management of endobronchial tuberculosis.
      ,
      • Jung S.S.
      • Park H.S.
      • Kim J.O.
      • et al.
      Incidence and clinical predictors of endobronchial tuberculosis in patients with pulmonary tuberculosis.
      ) among all pulmonary TB cases. However, since bronchoscopy is not routinely performed in all TB patients, its true incidence is likely underestimated (
      • Kashyap S.
      • Solanki A.
      Challenges in endobonchial tuberculosis: from diagnosis to management.
      ,
      • Ozkaya S.
      • Bilgin S.
      • Findik S.
      • et al.
      Endobronchial tuberculosis: histopathological subsets and microbiological results.
      ). Bronchoscopy can be relevant for its diagnosis. In this context the role of endoscopy is complementary to chest CT, which evaluates the bronchial involvement length and peribronchial thickness, as well as the luminal patency. Furthermore, CT scans may detect indirect signs of bronchial stenosis (i.e., atelectasis, cavities, hyperinflation, obstructive pneumonias) and predict patient outcome after bronchoscopic re-expansion procedures (
      • Beigelman C.
      • Sellami D.
      • Brauner M.
      CT of parenchymal and bronchial tuberculosis.
      ,
      • Skoura E.
      • Zumla A.
      • Bomanji J.
      Imaging in tuberculosis.
      ,
      • Burrill J.
      • Williams C.J.
      • Bain G.
      • et al.
      Tuberculosis: a radiologic review.
      ,
      • Kashyap S.
      • Solanki A.
      Challenges in endobonchial tuberculosis: from diagnosis to management.
      ,
      • Chung H.S.
      • Lee J.H.
      Bronchoscopic assessment of the evolution of endobronchial tuberculosis.
      ,
      • Lee J.H.
      • Chung H.S.
      Bronchoscopic, radiologic and pulmonary function evaluation of endobronchial tuberculosis.
      ). Since severe complications have been described in patients with EBTB, bronchoscopic examination of the tracheobronchial wall should be prompt in case of persistent cough, haemoptysis, clinical signs of bronchostenosis (such as wheezing and stridor), and radiological suspicion of endobronchial micobacterial invasion (
      • Kashyap S.
      • Solanki A.
      Challenges in endobonchial tuberculosis: from diagnosis to management.
      ,
      • Lee J.Y.
      • Yi C.A.
      • Kim T.S.
      • et al.
      CT scan features as predictors of patient outcome after bronchial intervention in endobronchial TB.
      ,
      • Hou G.
      • Zhang T.
      • Kang D.H.
      Efficacy of real-time polymerase chain reaction for rapid diagnosis of endobronchial tuberculosis.
      ).
      On the basis of the bronchoscopic characteristics, endobronchial TB may be classified into seven categories, which are closely related to pathological changes (
      • Chung H.S.
      • Lee J.H.
      Bronchoscopic assessment of the evolution of endobronchial tuberculosis.
      ,
      • Xue Q.
      • Wang N.
      • Xue X.
      • et al.
      Endobronchial tuberculosis: an overview.
      ) (Table 3).
      Table 3Bronchoscopic features of endobronchial tuberculosis (EBTB) subtypes according to Chung classification (
      • Chung H.S.
      • Lee J.H.
      Bronchoscopic assessment of the evolution of endobronchial tuberculosis.
      ).
      EBTB SubtypeBronchoscopic features
      Non specific bronchiticmildly swollen and/or hyperemic mucosa
      Edematous-hyperemicseverely swollen and hyperemic mucosal surface
      Actively caseatingedematous and hyperemic tracheobronchial mucosa covered with a large amount of whitish cheese-like material. Usual luminal narrowing.
      Granularseverely inflamed mucosa with scattered rice-like nodules on the surface
      Tumorousendobronchial mass whose surface is often covered with caseous material and may totally occlude the bronchial lumen
      Ulcerativeulcerate tracheobronchial mucosa
      Fibrostenotictracheobronchial narrowing of the bronchial lumen due to fibrosis
      Edematous-hyperemic, granular, and actively caseating subtypes are the most frequently detected (
      • Sahin F.
      • Yildiz P.
      Characteristics of endobronchial tuberculosis patients with negative sputum acid-fast bacillus.
      ,
      • Chung H.S.
      • Lee J.H.
      Bronchoscopic assessment of the evolution of endobronchial tuberculosis.
      ,
      • Ozkaya S.
      • Bilgin S.
      • Findik S.
      • et al.
      Endobronchial tuberculosis: histopathological subsets and microbiological results.
      ,
      • Qingliang X.
      • Jianxin W.
      Investigation of endobronchial tuberculosis diagnoses in 22 cases.
      ,
      • Um S.W.
      • Yoon Y.S.
      • Lee S.M.
      Predictors of persistent airway stenosis in patients with endobronchial tuberculosis.
      ) but different subtypes may coexist in the same patient and one subtype may change into another (
      • Chung H.S.
      • Lee J.H.
      Bronchoscopic assessment of the evolution of endobronchial tuberculosis.
      ,
      • Xue Q.
      • Wang N.
      • Xue X.
      • et al.
      Endobronchial tuberculosis: an overview.
      ). Bronchoscopic follow-up studies demonstrated that the evolution of EBTB depends on initial findings, which are closely related to the formation of granulation tissue (
      • Chung H.S.
      • Lee J.H.
      Bronchoscopic assessment of the evolution of endobronchial tuberculosis.
      ,
      • Kim Y.H.
      • Kim H.T.
      • Lee K.S.
      • et al.
      Serial fiberoptic bronchoscopic observations of endobronchial tuberculosis before and early after antituberculosis chemotherapy.
      ,
      • Lee J.H.
      • Park S.S.
      • Lee D.H.
      • et al.
      Endobronchial tuberculosis. Clinical and bronchoscopic features in 12 cases.
      ). Fibrostenotic, actively caseating, edematous-hyperemic and tumorous EBTB are associated with the worst prognosis (Figure 2); however, while the fibrostenotic subtype is not associated with a worsening of the bronchial narrowing until complete fibrotic bronchial obstruction, the other three subtypes result in fibrostenosis in the majority of the patients (
      • Kashyap S.
      • Solanki A.
      Challenges in endobonchial tuberculosis: from diagnosis to management.
      ,
      • Chung H.S.
      • Lee J.H.
      Bronchoscopic assessment of the evolution of endobronchial tuberculosis.
      ,
      • Shim Y.S.
      Endobronchial tuberculosis.
      ). Furthermore, because changes of endoscopic findings can occur within the first three months of treatment without any further significant variations, therapeutic outcomes can be estimated by follow-up bronchoscopy performed during the first three months of therapy, with the only exception of the tumourous type. This group of lesions, which is mainly due to an intrathoracic tuberculous lymph node erosion and protrusion into the bronchus (Figure 3), deserves a close and long-term follow-up because its evolution may be unpredictable and bronchial stenosis may occur in a late phase of the disease (
      • Chung H.S.
      • Lee J.H.
      Bronchoscopic assessment of the evolution of endobronchial tuberculosis.
      ,
      • Kim Y.H.
      • Kim H.T.
      • Lee K.S.
      • et al.
      Serial fiberoptic bronchoscopic observations of endobronchial tuberculosis before and early after antituberculosis chemotherapy.
      ,
      • Lee J.H.
      • Park S.S.
      • Lee D.H.
      • et al.
      Endobronchial tuberculosis. Clinical and bronchoscopic features in 12 cases.
      ). Unfortunately, antibiotics play a limited role in preventing bronchostenosis (
      • Um S.W.
      • Yoon Y.S.
      • Lee S.M.
      Predictors of persistent airway stenosis in patients with endobronchial tuberculosis.
      ). Therefore, prompt diagnosis and mechanical treatment are of paramount importance in EBTB, in order to minimize the resultant bronchial strictures (
      • Chung H.S.
      • Lee J.H.
      Bronchoscopic assessment of the evolution of endobronchial tuberculosis.
      ).
      Figure 2
      Figure 2Tumorous endobronchial tuberculosis: endobronchial lesions covered with caseous material (A); fibrostenotic endobronchial tuberculosis: severe pinpoint lobar stenosis (B).
      Figure 3
      Figure 3Tumorous lesion at the level of the main carina due to a subcarinal lymph node protrusion into the bronchial tree. Chest computed tomography view at the top.

      Bronchoscopic diagnostic techniques for patients with endobronchial tuberculosis

      Bronchoscopy may provide support for bacteriological and histological diagnosis of EBTB, since sputum examinations show a low diagnostic yield in the majority of the cases (
      • Sahin F.
      • Yildiz P.
      Characteristics of endobronchial tuberculosis patients with negative sputum acid-fast bacillus.
      ,
      • Chung H.S.
      • Lee J.H.
      Bronchoscopic assessment of the evolution of endobronchial tuberculosis.
      ,
      • Hou G.
      • Zhang T.
      • Kang D.H.
      Efficacy of real-time polymerase chain reaction for rapid diagnosis of endobronchial tuberculosis.
      ,
      • Kim Y.H.
      • Kim H.T.
      • Lee K.S.
      • et al.
      Serial fiberoptic bronchoscopic observations of endobronchial tuberculosis before and early after antituberculosis chemotherapy.
      ,
      • Lee J.H.
      • Park S.S.
      • Lee D.H.
      • et al.
      Endobronchial tuberculosis. Clinical and bronchoscopic features in 12 cases.
      ,
      • Aggarwal A.N.
      • Gupta D.
      • Joshi K.
      • et al.
      Endobronchial involvement in tuberculosis: a report of 24 cases diagnosed by flexible bronchoscopy.
      ). Furthermore, because endobronchial tuberculosis may mimic endobronchial neoplasms, in this context endoscopy plays a key role to rule out the presence of malignancies (
      • Altin S.
      • Cikrikçioglu S.
      • Morgül M.
      • et al.
      50 endobronchial tuberculosis cases based on bronchoscopic diagnosis.
      ,
      • Ozkaya S.
      • Bilgin S.
      • Findik S.
      • et al.
      Endobronchial tuberculosis: histopathological subsets and microbiological results.
      ,
      • Shim Y.S.
      Endobronchial tuberculosis.
      ).
      Endobronchial biopsy (EBB) is the most reliable sampling method for EBTB diagnosis, with a sensitivity of 72.2-100.0% in the detection of granulomas (
      • Altin S.
      • Cikrikçioglu S.
      • Morgül M.
      • et al.
      50 endobronchial tuberculosis cases based on bronchoscopic diagnosis.
      ,
      • Ozkaya S.
      • Bilgin S.
      • Findik S.
      • et al.
      Endobronchial tuberculosis: histopathological subsets and microbiological results.
      ,
      • Lee J.H.
      • Chung H.S.
      Bronchoscopic, radiologic and pulmonary function evaluation of endobronchial tuberculosis.
      ,
      • Hou G.
      • Zhang T.
      • Kang D.H.
      Efficacy of real-time polymerase chain reaction for rapid diagnosis of endobronchial tuberculosis.
      ,
      • Xue Q.
      • Wang N.
      • Xue X.
      • et al.
      Endobronchial tuberculosis: an overview.
      ,
      • Qingliang X.
      • Jianxin W.
      Investigation of endobronchial tuberculosis diagnoses in 22 cases.
      ,
      • Lee J.H.
      • Park S.S.
      • Lee D.H.
      • et al.
      Endobronchial tuberculosis. Clinical and bronchoscopic features in 12 cases.
      ,
      • Aggarwal A.N.
      • Gupta D.
      • Joshi K.
      • et al.
      Endobronchial involvement in tuberculosis: a report of 24 cases diagnosed by flexible bronchoscopy.
      ,
      • Hoheisel G.
      • Chan B.K.
      • Chan C.H.
      • et al.
      Endobronchial tuberculosis: diagnostic features and therapeutic outcome.
      ).
      Altin et al. demonstrated a significantly better histological yield of EBB than endobronchial needle aspiration (respectively 84.0% vs 19.0%, respectively) in 42 subjects with EBTB (
      • Altin S.
      • Cikrikçioglu S.
      • Morgül M.
      • et al.
      50 endobronchial tuberculosis cases based on bronchoscopic diagnosis.
      ). On the other side, smear and culture of bioptic tissues shows a wide sensitivity (8.0-100.0%), but few studies are available on their diagnostic performance (
      • Ozkaya S.
      • Bilgin S.
      • Findik S.
      • et al.
      Endobronchial tuberculosis: histopathological subsets and microbiological results.
      ,
      • Hou G.
      • Zhang T.
      • Kang D.H.
      Efficacy of real-time polymerase chain reaction for rapid diagnosis of endobronchial tuberculosis.
      ,
      • Aggarwal A.N.
      • Gupta D.
      • Joshi K.
      • et al.
      Endobronchial involvement in tuberculosis: a report of 24 cases diagnosed by flexible bronchoscopy.
      ,
      • Hoheisel G.
      • Chan B.K.
      • Chan C.H.
      • et al.
      Endobronchial tuberculosis: diagnostic features and therapeutic outcome.
      ). Beside the most frequently used forceps biopsies, cryobioprobes have been described to successfully diagnose TB endobronchial masses (
      • Chou C.L.
      • Wang C.W.
      • Lin S.M.
      • et al.
      Role of flexible bronchoscopic cryotechnology in diagnosing endobronchial masses.
      ).
      Real-time PCR can reduce the time to diagnosis, improving patient prognosis (bronchial stenosis), showing a high sensitivity and specificity. Hou et al. reported on a sensitivity of 89.2% in a cohort of 74 patients with EBTB, significantly higher than that of sputum (4.1%) and bronchial brush smear microscopy (39.2%). Furthermore, employing the ABI PRISM 7500HT real-time PCR (Applied Biosystems, Foster City, CA, USA), the Authors showed a higher PCR sensitivity in granular, caseating and ulcerative EBTB than in edematous-hyperemic and fibrostenotic subtypes (
      • Hou G.
      • Zhang T.
      • Kang D.H.
      Efficacy of real-time polymerase chain reaction for rapid diagnosis of endobronchial tuberculosis.
      ).
      Studies based on traditional bacteriology on BW and BAL revealed a diagnostic yield of 10.0-37.0% and 12.5%-62.5% for smear microscopy and culture, respectively (
      • Sahin F.
      • Yildiz P.
      Characteristics of endobronchial tuberculosis patients with negative sputum acid-fast bacillus.
      ,
      • Altin S.
      • Cikrikçioglu S.
      • Morgül M.
      • et al.
      50 endobronchial tuberculosis cases based on bronchoscopic diagnosis.
      ,
      • Ozkaya S.
      • Bilgin S.
      • Findik S.
      • et al.
      Endobronchial tuberculosis: histopathological subsets and microbiological results.
      ,
      • Aggarwal A.N.
      • Gupta D.
      • Joshi K.
      • et al.
      Endobronchial involvement in tuberculosis: a report of 24 cases diagnosed by flexible bronchoscopy.
      ). Ozkaya et al. demonstrated in a group of 21 patients that the highest smear and culture positivity was found in granular subtype (75%), while both resulted negative in patients with non specific bronchitic and fibrostenotic EBTB (
      • Ozkaya S.
      • Bilgin S.
      • Findik S.
      • et al.
      Endobronchial tuberculosis: histopathological subsets and microbiological results.
      ).

      Bronchoscopic treatment for patients with endobronchial tuberculosis

      TB tracheobronchial stenosis, which is the commonest cause of benign stenosis in high TB incidence countries, represents the worst complication of EBTB. Different degrees of tracheobronchial strictures can occur, from slight luminal narrowing to complete obliteration, thus determining segmental, lobar or whole lung atelectasis despite the administration of effective TB therapy (
      • Um S.W.
      • Yoon Y.S.
      • Lee S.M.
      Predictors of persistent airway stenosis in patients with endobronchial tuberculosis.
      ). Left-side bronchi are more frequently involved because they are anatomically compressed by the aortic arch and TB is more often located in the left-sided lymph nodes (
      • Lee J.Y.
      • Yi C.A.
      • Kim T.S.
      • et al.
      CT scan features as predictors of patient outcome after bronchial intervention in endobronchial TB.
      ,
      • Lim S.Y.
      • Park H.K.
      • Jeon K.
      • et al.
      Factors predicting outcome following airway stenting for post-tuberculosis tracheobronchial stenosis.
      ,
      • Verma A.
      • Park H.Y.
      • Lim S.Y.
      • et al.
      Posttuberculosis tracheobronchial stenosis: use of CT to optimize the time of silicone stent removal.
      ,
      • Iwamoto Y.
      • Miyazawa T.
      • Kurimoto N.
      • et al.
      Interventional bronchoscopy in the management of airway stenosis due to tracheobronchial tuberculosis.
      ). These clinical conditions, which may cause respiratory failure, deserve an immediate endoscopic evaluation and management (
      • Aggarwal A.N.
      • Gupta D.
      • Joshi K.
      • et al.
      Endobronchial involvement in tuberculosis: a report of 24 cases diagnosed by flexible bronchoscopy.
      ,
      • Verma A.
      • Park H.Y.
      • Lim S.Y.
      • et al.
      Posttuberculosis tracheobronchial stenosis: use of CT to optimize the time of silicone stent removal.
      ,
      • Iwamoto Y.
      • Miyazawa T.
      • Kurimoto N.
      • et al.
      Interventional bronchoscopy in the management of airway stenosis due to tracheobronchial tuberculosis.
      ).
      Bronchoscopic procedures (ablation and dilation techniques) represent an alternative and less invasive strategy than conventional surgery in the management of stenosis resulting from endobronchial disease, particularly when surgical treatment is contraindicated or in case of multi-level stenosis (
      • Kashyap S.
      • Solanki A.
      Challenges in endobonchial tuberculosis: from diagnosis to management.
      ,
      • Lim S.Y.
      • Park H.K.
      • Jeon K.
      • et al.
      Factors predicting outcome following airway stenting for post-tuberculosis tracheobronchial stenosis.
      ,
      • Verma A.
      • Park H.Y.
      • Lim S.Y.
      • et al.
      Posttuberculosis tracheobronchial stenosis: use of CT to optimize the time of silicone stent removal.
      ,
      • Iwamoto Y.
      • Miyazawa T.
      • Kurimoto N.
      • et al.
      Interventional bronchoscopy in the management of airway stenosis due to tracheobronchial tuberculosis.
      ) (Table 4).
      Table 4Summary of bronchoscopic treatment options described in literature.
      TherapyTechniqueBronchoscope usedScientific evidence levelIndicationsAdverse events
      DilationRigid bronchoscope (
      • Iwamoto Y.
      • Miyazawa T.
      • Kurimoto N.
      • et al.
      Interventional bronchoscopy in the management of airway stenosis due to tracheobronchial tuberculosis.
      ,
      • Low S.Y.
      • Hsu A.
      • Eng P.
      Interventional bronchoscopy for tuberculous tracheobronchial stenosis.
      ,
      • Ryu Y.J.
      • Kim H.
      • Yu C.M.
      • et al.
      Use of silicone stents for the management of post-tuberculosis tracheobronchial stenosis.
      )
      RigidRCSsFibrostenotic EBTB dilationNR
      Metal bougie (
      • Lim S.Y.
      • Park H.K.
      • Jeon K.
      • et al.
      Factors predicting outcome following airway stenting for post-tuberculosis tracheobronchial stenosis.
      ,
      • Ryu Y.J.
      • Kim H.
      • Yu C.M.
      • et al.
      Use of silicone stents for the management of post-tuberculosis tracheobronchial stenosis.
      )
      RigidRCSsFibrostenotic EBTB dilationNR
      Balloon (
      • Iwamoto Y.
      • Miyazawa T.
      • Kurimoto N.
      • et al.
      Interventional bronchoscopy in the management of airway stenosis due to tracheobronchial tuberculosis.
      ,
      • Ryu Y.J.
      • Kim H.
      • Yu C.M.
      • et al.
      Use of silicone stents for the management of post-tuberculosis tracheobronchial stenosis.
      ,
      • Shitrit D.
      • Kuchuk M.
      • Zismanov V.
      • et al.
      Bronchoscopic balloon dilatation of tracheobronchial stenosis: long-term follow-up.
      ,
      • Ferretti G.
      • Jouvan F.B.
      • Thony F.
      • et al.
      Benign noninflammatory bronchial stenosis: treatment with balloon dilation.
      ,
      • Lee K.W.
      • Im J.G.
      • Han J.K.
      • et al.
      Tuberculous stenosis of the left main bronchus: results of treatment with balloons and metallic stents.
      ,
      • Cho Y.C.
      • Kim J.H.
      • Park J.H.
      • et al.
      Tuberculous tracheobronchial strictures treated with balloon dilation: a single-center experience in 113 patients during a 17-year period.
      )
      Rigid and flexibleRCSsFibrostenotic EBTB dilation (particularly in presence of annular cicatricial stenosis)Mild haemoptysis, transient fever
      Stents placement

      (silicone and metallic)

      (
      • Lim S.Y.
      • Park H.K.
      • Jeon K.
      • et al.
      Factors predicting outcome following airway stenting for post-tuberculosis tracheobronchial stenosis.
      ,
      • Verma A.
      • Park H.Y.
      • Lim S.Y.
      • et al.
      Posttuberculosis tracheobronchial stenosis: use of CT to optimize the time of silicone stent removal.
      ,
      • Iwamoto Y.
      • Miyazawa T.
      • Kurimoto N.
      • et al.
      Interventional bronchoscopy in the management of airway stenosis due to tracheobronchial tuberculosis.
      ,
      • Low S.Y.
      • Hsu A.
      • Eng P.
      Interventional bronchoscopy for tuberculous tracheobronchial stenosis.
      ,
      • Ryu Y.J.
      • Kim H.
      • Yu C.M.
      • et al.
      Use of silicone stents for the management of post-tuberculosis tracheobronchial stenosis.
      ,
      • Bolliger C.T.
      • Sutedja T.G.
      • Strausz J.
      • et al.
      Therapeutic bronchoscopy with immediate effect: laser, electrocautery, argon plasma coagulation and stents.
      ,
      • Cavaliere S.
      • Foccoli P.
      • Farina P.L.
      Nd:YAG laser bronchoscopy. A five-year experience with 1,396 applications in 1,000 patients.
      )
      Rigid (silicone)

      Rigid and flexible (metallic)
      RCSsFibrostenotic EBTB dilation (particularly in presence of tracheo-bronchial malacia)Granulation tissue growth, mucostasis, stent migration
      Mitomycin-C application

      (
      • Cary C.
      • Jhajj M.
      • Cinicola J.
      • et al.
      A rare case of fibrostenotic endobronchial tuberculosis of trachea.
      ,
      • Faisal M.
      • Harun H.
      • Hassan T.M.
      Treatment of multiple-level tracheobronchial stenosis secondary to endobronchial tuberculosis using bronchoscopic balloon dilatation with topical mitomycin-C.
      ,
      • Penafiel A.
      • Lee P.
      • Hsu A.
      Topical mitomycin-C for obstructing endobronchial granuloma.
      )
      Rigid and flexibleCRsFibrostenotic EBTB relapse prevention after dilationNone
      AblationNd-YAG laser (
      • Lim S.Y.
      • Park H.K.
      • Jeon K.
      • et al.
      Factors predicting outcome following airway stenting for post-tuberculosis tracheobronchial stenosis.
      ,
      • Low S.Y.
      • Hsu A.
      • Eng P.
      Interventional bronchoscopy for tuberculous tracheobronchial stenosis.
      ,
      • Ryu Y.J.
      • Kim H.
      • Yu C.M.
      • et al.
      Use of silicone stents for the management of post-tuberculosis tracheobronchial stenosis.
      ,
      • Bolliger C.T.
      • Sutedja T.G.
      • Strausz J.
      • et al.
      Therapeutic bronchoscopy with immediate effect: laser, electrocautery, argon plasma coagulation and stents.
      ,
      • Cavaliere S.
      • Foccoli P.
      • Farina P.L.
      Nd:YAG laser bronchoscopy. A five-year experience with 1,396 applications in 1,000 patients.
      )
      Rigid and flexibleRCSsFibrostenotic EBTB treatmentNR
      KTP laser (
      • Qiu-Sheng J.
      • Cai-Ping L.
      Efficacy of KTP laser in the treatment of severe obstructive tracheobronchial tuberculosis: report of two cases.
      )
      FlexibleCRsTumorous EBTB treatmentNone
      Carbon dioxide laser (
      • Cary C.
      • Jhajj M.
      • Cinicola J.
      • et al.
      A rare case of fibrostenotic endobronchial tuberculosis of trachea.
      ,
      • Tong M.C.
      • Van Hasselt C.A.
      Tuberculous tracheobronchial strictures: clinicopathological features and management with the bronchoscopic carbon dioxide laser.
      )
      RigidCSFibrostenotic EBTB treatmentNone
      Electrocautery (
      • Shim Y.S.
      Endobronchial tuberculosis.
      ,
      • Amat B.
      • Esselmann A.
      • Reichle G.
      • et al.
      The electrosurgical knife in an optimized intermittent cutting mode for the endoscopic treatment of benign web-like tracheobronchial stenosis.
      )
      RigidCSFibrostenotic (web-like stenosis) and tumorous EBTB treatmentNone
      APC (
      • Jin F.
      • Mu D.
      • Xie Y.
      • et al.
      Application of bronchoscopic argon plasma coagulation in the treatment of tumorous endobronchial tuberculosis: historical controlled trial.
      )
      FlexibleRCSTumorous EBTB treatment in stenosis preventionMild bleeding, laryngeal spasm, cough
      Cryotherapy (
      • Marasso A.
      • Gallo E.
      • Massaglia G.M.
      • et al.
      Cryosurgery in bronchoscopic treatment of tracheobronchial stenosis.
      ,
      • Mu D.
      • Nan D.
      • Li W.
      • et al.
      Efficacy and safety of bronchoscopic cryotherapy for granular endobronchial tuberculosis.
      )
      Rigid and flexibleRCSsFibrostenotic EBTB treatment and granular EBTB treatment in stenosis preventionMild bleeding
      RCS: retrospective cohort study; CS: case series; CR: case report; NR: not reported; EBTB: endobronchial tuberculosis; Nd-YAG: neodymium:yttrium aluminium garnet; KTP: potassium titanyl phosphate; APC: Argon Plasma Coagulation.
      To date, only one case series has described TB cavity collapse performed by a bronchoscopy (
      • Corbetta L.
      • Tofani A.
      • Montinaro F.
      Lobar collapse therapy using endobronchial valves as a new complementary approach to treat cavities in multidrug-resistant tuberculosis and difficult-to-treat tuberculosis: A case series.
      ). Interestingly, Corbetta et al. described a minimally invasive lung collapse therapy recommended for emphysema-associated hyperinflation, characterized by the placement of endobronchial one-way valves (EBVs) in four TB patients (with multi-drug resistant and difficult-to-treat extensive disease) and in one patient with atypical mycobacteriosis (
      • Sciurba F.C.
      • Ernst A.
      • Herth F.J.
      • et al.
      A randomized study of endobronchial valves for advanced emphysema.
      ). The patients were considered not eligible for surgery owing to a large pulmonary involvement or serious clinical conditions. EBVs and medical therapy resulted in cavity collapse in all patients (partial in one and complete in four), and sputum smear became negative within 3-5 months after EBVs implantation.
      No complications occurred and the valves were removed in 3 out of 5 patients after 8 months and no relapses were recorded after 15 months of follow-up (
      • Corbetta L.
      • Tofani A.
      • Montinaro F.
      Lobar collapse therapy using endobronchial valves as a new complementary approach to treat cavities in multidrug-resistant tuberculosis and difficult-to-treat tuberculosis: A case series.
      ).

      Dilation techniques for tuberculosis patients with TB-related stenosis

      Bronchoscopic airway dilation may be accomplished through rigid or flexible bronchoscopes.
      The rigid bronchoscope itself provides dilation with the shear mechanics of the scope (
      • Xue Q.
      • Wang N.
      • Xue X.
      • et al.
      Endobronchial tuberculosis: an overview.
      ,
      • Shim Y.S.
      Endobronchial tuberculosis.
      ,
      • Iwamoto Y.
      • Miyazawa T.
      • Kurimoto N.
      • et al.
      Interventional bronchoscopy in the management of airway stenosis due to tracheobronchial tuberculosis.
      ,
      • Watanabe Y.
      • Murakami S.
      • Iwa T.
      Bronchial stricture due to endobronchial tuberculosis.
      ,
      • Low S.Y.
      • Hsu A.
      • Eng P.
      Interventional bronchoscopy for tuberculous tracheobronchial stenosis.
      ,
      • Ryu Y.J.
      • Kim H.
      • Yu C.M.
      • et al.
      Use of silicone stents for the management of post-tuberculosis tracheobronchial stenosis.
      ). Metal bougie dilators provide the same effect but dilation performed by this technique, described only in a few studies (
      • Lim S.Y.
      • Park H.K.
      • Jeon K.
      • et al.
      Factors predicting outcome following airway stenting for post-tuberculosis tracheobronchial stenosis.
      ,
      • Ryu Y.J.
      • Kim H.
      • Yu C.M.
      • et al.
      Use of silicone stents for the management of post-tuberculosis tracheobronchial stenosis.
      ), may damage the mucosa (
      • Xue Q.
      • Wang N.
      • Xue X.
      • et al.
      Endobronchial tuberculosis: an overview.
      ,
      • Shim Y.S.
      Endobronchial tuberculosis.
      ). Balloon dilation is a minimally invasive and safe technique that can be performed with flexible bronchoscopes, by gentle balloon inflation through the stricture. It is particularly appropriate for annular cicatricial stenosis, since the balloon dilates the stenotic bronchus by expanding radially. As suggested by Shitrit et al., fibrotic process with fixed stenosis may be more responsive to a successful balloon dilation than those with active inflammation, calcification, or in whom the surrounding cartilage is destroyed (malacia). This approach is frequently the first treatment for tracheobronchial stenosis, with long term successful results ranging from to 6.3% to 73.0%. The wide effectiveness range depends on different conditions of the treated tracheobronchial walls among studies (
      • Iwamoto Y.
      • Miyazawa T.
      • Kurimoto N.
      • et al.
      Interventional bronchoscopy in the management of airway stenosis due to tracheobronchial tuberculosis.
      ,
      • Ryu Y.J.
      • Kim H.
      • Yu C.M.
      • et al.
      Use of silicone stents for the management of post-tuberculosis tracheobronchial stenosis.
      ,
      • Ferretti G.
      • Jouvan F.B.
      • Thony F.
      • et al.
      Benign noninflammatory bronchial stenosis: treatment with balloon dilation.
      ,
      • Lee K.W.
      • Im J.G.
      • Han J.K.
      • et al.
      Tuberculous stenosis of the left main bronchus: results of treatment with balloons and metallic stents.
      ,
      • Cho Y.C.
      • Kim J.H.
      • Park J.H.
      • et al.
      Tuberculous tracheobronchial strictures treated with balloon dilation: a single-center experience in 113 patients during a 17-year period.
      ). When balloon dilation fails and more than one dilation is required, stent procedures are needed.
      Airway stenting is an important strategy for managing tracheobronchial stenosis. Stenting is usually performed after balloon dilatation when the patient has a bacteriological conversion (
      • Iwamoto Y.
      • Miyazawa T.
      • Kurimoto N.
      • et al.
      Interventional bronchoscopy in the management of airway stenosis due to tracheobronchial tuberculosis.
      ). The major indications for the placement of airway stents are: patency of the central airways, racheobronchial malacia, fistulas due to TB erosion. Because stent-related complications are frequently observed in patients with benign stenosis caused by TB, and airway remodelling usually follows brochoscopic interventions, a removable stent should be selected (e.g., silicone stents such as Dumon stents (
      • Dumon J.F.
      • Cavaliere S.
      • Diaz-Jimenez J.P.
      Seven-year experience with the dumon prothesis.
      )). Furthermore, the dynamic properties of self-expandable metallic stents (such as Ultraflex and Gianturco stents) may lead to their fracture due to metal fatigue with severe repeated coughing (
      • Iwamoto Y.
      • Miyazawa T.
      • Kurimoto N.
      • et al.
      Interventional bronchoscopy in the management of airway stenosis due to tracheobronchial tuberculosis.
      ,
      • Madden B.P.
      • Loke T.K.
      • Sheth A.C.
      Do expandable metallic airway stents have a role in the management of patients with benign tracheobronchial disease?.
      ,
      • Chung F.T.
      • Chen H.C.
      • Chou C.L.
      • et al.
      An outcome analysis of self-expandable metallic stents in central airway obstruction: a cohort study.
      ,
      • Gottlieb J.
      • Fuehner T.
      • Dierich M.
      • et al.
      Are metallic stents really safe? A long-term analysis in lung transplant recipients.
      ).
      Iwamoto et al. reported successful long-term outcomes of six patients treated with Dumon stents (both tubular and Y-shaped) to re-establish the patency of the central airway, without any severe complications in comparison with cases treated with expandable metallic stent (Ultraflex). They described the growth of granulation tissue more frequently in Ultraflex stent patients (between the mesh of uncovered Ultraflex stents and at the edges of the covered ones) than in those treated with silicone stents (
      • Iwamoto Y.
      • Miyazawa T.
      • Kurimoto N.
      • et al.
      Interventional bronchoscopy in the management of airway stenosis due to tracheobronchial tuberculosis.
      ). Interestingly, the Authors employed radial EBUS probes to assess the condition of the bronchial wall and to diagnose cartilaginous bronchomalacia.
      Low et al. described an immediate and long-term clinical recovery in 7/11 (63.6%) patients treated with Dumon stents (
      • Low S.Y.
      • Hsu A.
      • Eng P.
      Interventional bronchoscopy for tuberculous tracheobronchial stenosis.
      ); similar successful findings were observed by Ryu et al. for 75 patients with tracheobronchial tuberculous stenosis (
      • Ryu Y.J.
      • Kim H.
      • Yu C.M.
      • et al.
      Use of silicone stents for the management of post-tuberculosis tracheobronchial stenosis.
      ): they placed silicon stents (both Dumon and Natural stents) which provided immediate symptomatic relief and improved lung function in 88% of the cases. After airway stabilization, stents were successfully removed in 49/75 (65%) patients after a median of 14 months. The most common complications were late and included migration (51%), granuloma formation (49%), mucostasis (19%), and restenosis (40%) (