Yield and safety of different biopsy types in interstitial lung disease: a systematic review and meta-analysis

Lung biopsy remains an important consideration in the management of interstitial lung disease (ILD). Transbronchial lung cryobiopsy (TBLC) offers an alternative to traditional surgical lung biopsy (SLB) and transbronchial forceps biopsy (TBB); however, up-to-date comparisons between these methods in ILD, particularly fibrotic ILD, remain limited.

A comprehensive literature search of Medline, Embase and Evidence-Based Medicine Reviews was performed for studies published between January 2000 and September 2025 to identify all citations reporting yield and complications of the three main lung biopsy methods for ILD.

A total of 143 studies were included. Pooled multidisciplinary yield (following multidisciplinary discussion) in TBB, TBLC and SLB was 35.3% (95% CI 21.3-52.5), 84.3% (95% CI 81.7-86.5) and 88.6% (95% CI 83.4-92.3), respectively. For fibrotic ILD, the multidisciplinary yield was 12.5% (only one eligible study), 87.6% (95% CI 83.5-90.7) and 87.3% (95%CI 80.5-92.0), respectively. Meta-regression showed an increasing multidisciplinary yield of TBLC with more recent years of patient recruitment and an increasing percentage of fibrotic ILD in each study. The multidisciplinary yield of both TBLC and SLB was 85-90%, suggesting a biopsy "ceiling effect". All evaluated complications were more frequent in TBLC compared to TBB and some were more frequent in SLB compared to TBLC. Several complications were more frequent in fibrotic ILD compared to all ILD.

The multidisciplinary yield of TBLC and SLB is equivalent, with both offering an acceptable safety profile. TBB has low yield, particularly in fibrotic ILD. These findings support using either TBLC or SLB as an initial diagnostic tool in fibrotic ILD, mainly based on patient-physician shared decision-making.