Background: Transbronchial lung cryobiopsy (TBLC) has an increased value in diagnosing interstitial lung disease (ILD). Bleeding is a major complication of TBLC, and pre-placing a balloon is one of the clinical practices used to prevent it, but with very weak evidence. However, a balloon is costly, and the safety and cost-effectiveness of pre-placing balloons in TBLC have not been confirmed.

Methods: In this prospective, single-center, randomized controlled trial, patients with suspected ILD were enrolled and randomly assigned to pre-placed-balloon and non-pre-placed-balloon groups. The primary outcome was bleeding risk in each group. The secondary endpoints were cost-effectiveness and other procedural complications.

Results: Exactly 250 patients were enrolled between August 2019 and March 2022, with 125 in each group. There were no significant differences in severe bleeding between the pre-placed-balloon group and non-pre-placed-balloon group (0.8% vs. 1.6%; adjusted p=0.847), while more moderate and above bleeding occurred in the non-pre-placed-balloon group (6.4% vs. 28.0%, adjusted p?0.001). Pneumothorax did not occur in either group. The all-in cost of TBLC with a pre-placed balloon was much higher than that without a pre-placed balloon (1429.9±15.8 USD and 708.5±131.1 USD, respectively; adjusted p<0.001).

Conclusion: The pre-placement of a balloon in TBLC for diagnosing ILD may not deal with severe bleeding and will cost patients more. Preparing a balloon with a pre-placed guidewire may be a good choice.