Diagnostic Performance and Safety of Endobronchial Ultrasound-guided Transbronchial Mediastinal Cryobiopsy in Diagnosing Tuberculous Mediastinal Lymphadenitis: a Randomised Controlled Trial

Diagnostic Performance and Safety of Endobronchial Ultrasound-guided Transbronchial Mediastinal Cryobiopsy in Diagnosing Tuberculous Mediastinal Lymphadenitis: a Randomised Controlled Trial

The goal of this clinical trial is to compare the diagnostic efficacy and safety of Endobronchial Ultrasound-guided Transbronchial Mediastinal Cryobiopsy (EBUS-TBMC) versus standard EBUS-guided Transbronchial Needle Aspiration (EBUS-TBNA) in adult patients with suspected mediastinal lymph node tuberculosis. The main questions it aims to answer are:

Does EBUS-TBMC provide a superior diagnostic yield for detecting granulomatous inflammation compared to EBUS-TBNA in the same target lymph node? Does the cryopreservation process affect the viability of Mycobacterium tuberculosis for culture, and does the larger tissue sample obtained via EBUS-TBMC enhance the sensitivity of molecular tests such as Xpert MTB/RIF? Is the safety profile of EBUS-TBMC, particularly regarding bleeding complications, comparable to that of EBUS-TBNA in this patient population? Researchers will compare the two biopsy techniques using a paired design within the same patient to see if EBUS-TBMC results in higher rates of positive pathology, microbiology, and molecular diagnoses.

Participants will:

Undergo both EBUS-TBNA and EBUS-TBMC procedures on the same mediastinal lymph node during a single bronchoscopy session, with the order of procedures randomized.

Provide blood and tissue samples for comprehensive testing, including histology, mycobacterial culture, and Xpert MTB/RIF assay.

Complete short-term (within 2 hours post-procedure) and 7-day follow-up assessments to monitor for any adverse events.

Participate in a 6-month clinical follow-up to establish a final diagnosis, which will serve as the reference standard for evaluating the diagnostic tests.

Inclusion Criteria:

• Age 18 years or older;
• Presence of unexplained mediastinal lymphadenopathy (short-axis diameter ≥1 cm on chest computed tomography) with clinical suspicion of tuberculosis;
• Completion of routine pre-procedural evaluations including blood tests (complete blood count, coagulation profile), electrocardiogram, and chest CT;
• Absence of contraindications for EBUS-TBNA or EBUS-TBMC procedures;
• Provision of written informed consent after being fully informed of the study purpose and procedures.

Exclusion Criteria:

• Known allergy to lidocaine or midazolam;
• Presence of bronchial artery penetration into the target lesion or high risk of bleeding as detected by contrast-enhanced CT or EBUS Doppler mode prior to the procedure;
• Unstable angina, congestive heart failure, or severe bronchial asthma;
• Evidence of significant liquefaction necrosis in the target mediastinal lymph node on pre-procedural CT or EBUS;
• Patient refusal to participate in the study;
• Participation in another clinical trial within the past three months that may interfere with the outcomes of this study;
• Any other condition that, in the opinion of the investigator, makes the patient unsuitable for study participation