A systematic review of procedural and sampling techniques for cryobiopsy in interstitial lung disease

Background Transbronchial lung cryobiopsy (TBLC) is an alternative to surgical lung biopsy for histopathological evaluation of unclassifiable interstitial lung disease (ILD) or ILD diagnosed with low confidence. This meta-analysis synthesised current literature regarding cryobiopsy diagnostic performance and safety, focusing on procedural and sampling techniques. Methods Medline and Embase were searched on 11 April 2022. Studies included adults with unclassifiable ILD, reporting diagnostic yield, complications and methodological techniques of TBLC. Meta-analyses were performed for diagnostic yield, pneumothorax and bleeding. Subgroup analyses and meta-regression assessed methodological variables. PROSPERO registration: CRD42022312386. Results 70 studies were included with 6183 participants. Diagnostic yield of TBLC was 81% (95% CI 79-83%, - 83%, I-2=97%), with better yield being observed with general anaesthesia (p=0.007), ILD multidisciplinary meeting prior to cryobiopsy (p=0.02), 2.4 mm cryoprobe (p=0.04), higher mean forced vital capacity (p=0.046) and higher mean diffusing capacity for carbon monoxide (p=0.023). Pneumothorax rate was 5% (95% CI 4-5%, - 5%, I-2=91%), with higher rates associated with a 2.4 mm cryoprobe (p<0.00001), routine post-procedure imaging (p<0.00001), multiple lobe sampling (p<0.0001), reduced mean diffusing capacity for carbon monoxide (p=0.028) and general anaesthesia (p=0.05). Moderate-to-severe bleeding rate was 12% (11-14%, - 14%, I-2=95%) and higher rates were associated with a 2.4 mm cryoprobe (p=0.001) and bleeding score selection (p=0.04). Interpretation Patient characteristics and modifiable factors, including procedural methods and anaesthetic techniques, impacted diagnostic yield and safety outcomes of TBLC in people with unclassifiable ILD and contributed to heterogeneity of clinical outcomes. These variables should be considered for individualised clinical decision making and guideline development and warrant routine reporting in future research.