Diagnostic yield and safety of small versus standard cryoprobes in transbronchial lung cryobiopsy for interstitial lung disease: a systematic review and meta-analysis

Background Interstitial lung diseases (ILDs) are a heterogeneous group of conditions that frequently require histopathology for a confident diagnosis. Transbronchial lung cryobiopsy (TBLC) is a minimally invasive alternative to surgical lung biopsy, but evidence comparing small-diameter and standard-diameter cryoprobes remains fragmented, with most studies being single-centre and underpowered. Objective To evaluate the diagnostic performance and safety of small-diameter (1.1–1.7 mm) versus standard-diameter (1.9 mm) cryoprobes for TBLC in patients with suspected ILD. Methods PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Scopus were searched from inception to March, 2026. Eligible studies assessed small-diameter cryoprobes for TBLC. The primary endpoint was diagnostic yield; secondary endpoints were bleeding, pneumothorax, number of biopsies, and specimen size. Random-effects meta-analyses were performed in R; single-arm proportions were pooled with a generalised linear mixed model, comparative dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD), with heterogeneity assessed by the I² statistic and certainty rated with GRADE. Results Five studies (two RCTs, three retrospective cohorts; 232 small-probe patients) were included. In the two RCTs (142 per arm), diagnostic yield did not differ between probe sizes (RR 0.95; 95% CI 0.88 to 1.03; P = 0.212; I² = 0%; moderate certainty); as this was a superiority test without a prespecified margin, equivalence was not established. Pooled single-arm yield was 88.3% (95% CI 78.2 to 94.1; four studies, n = 219; very low certainty). Bleeding (RR 0.67; 95% CI 0.32 to 1.44) and pneumothorax (RR 1.44; 95% CI 0.54 to 3.84; P = 0.463) did not differ (three studies, 155 per arm; very low certainty). More biopsies were taken with small-diameter probes (MD 0.45; 95% CI 0.14 to 0.77; P = 0.005), whereas specimen size did not differ (MD -2.02; 95% CI -4.13 to 0.08; P = 0.060; two studies, 125 per arm; very low certainty). Conclusion Small-diameter cryoprobes showed no significant difference from standard-diameter probes in diagnostic yield, bleeding, or pneumothorax, though more biopsies were required. Equivalence was not established, and certainty ranged from very low to moderate; these findings are exploratory and need confirmation in adequately powered randomised trials.