Interstitial lung disease (ILD) often requires histopathological confirmation when high-resolution computed tomography (HRCT) findings are inconclusive. Transbronchial lung cryobiopsy has emerged as a less invasive alternative to surgical lung biopsy, but diagnostic yield remains variable and dependent on biopsy location and procedural precision.

Robotic-assisted bronchoscopy (RAB) combined with cone-beam computed tomography (CBCT) may allow more precise navigation to target lung segments and potentially improve biopsy quality and diagnostic yield.

This multi-center, investigator-initiated randomized controlled trial will compare conventional bronchoscopy with 2D fluoroscopy guidance versus robotic-assisted bronchoscopy with CBCT guidance for transbronchial lung cryobiopsy in patients undergoing diagnostic evaluation for suspected interstitial lung disease.

Participants will be randomized in a 1:1 ratio to undergo either conventional bronchoscopy or robotic-assisted bronchoscopy. In both groups, four cryobiopsies will be obtained from two lung lobes using a 1.7 mm cryoprobe (en-bloc removal for both study arms).

The primary endpoint is the rate of definitive histological diagnosis as determined by a blinded multidisciplinary ILD board.

Histopathologic evaluation remains a key component in the diagnosis of many interstitial lung diseases when radiological and clinical findings are inconclusive. Transbronchial lung cryobiopsy (TBLC) has increasingly replaced surgical lung biopsy due to its lower morbidity, but diagnostic yield varies widely depending on procedural technique and sampling accuracy.

Robotic-assisted bronchoscopy (RAB) offers improved catheter stability and precise navigation to peripheral lung regions. When combined with cone-beam CT (CBCT), RAB allows real-time confirmation of biopsy location, potentially improving sampling of diagnostically relevant lung parenchyma while avoiding bronchial structures.

However, the incremental diagnostic value of RAB combined with CBCT compared with conventional bronchoscopy using fluoroscopy guidance has not yet been evaluated in a randomized controlled trial.

This investigator-initiated trial aims to determine whether robotic-assisted bronchoscopy with CBCT improves the rate of definitive histological diagnosis compared with conventional bronchoscopy.

Participants will be randomized 1:1 to either:

• Conventional bronchoscopy with fluoroscopy-guided cryobiopsy
• Robotic-assisted bronchoscopy with CBCT-guided cryobiopsy

In both arms, four biopsies will be obtained from two different lung lobes using a 1.7 mm cryoprobe.

Histological specimens will be evaluated by a blinded multidisciplinary ILD board.

Inclusion Criteria:

• Age ≥18 years
• Clinical suspicion of interstitial lung disease requiring histological confirmation
• Non-diagnostic HRCT pattern (e.g. probable UIP or indeterminate pattern)
• Candidate for transbronchial lung cryobiopsy
• Ability to provide informed consent

Exclusion Criteria:

• Definite UIP pattern on HRCT
• Severe pulmonary hypertension
• Severe hypoxemia contraindicating bronchoscopy
• Coagulopathy or contraindication to biopsy
• Pregnancy
• Inability to provide informed consent