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Diagnostic performance analysis of transbronchial lung biopsy using cryoprobes (cryobiopsy) in diffuse lung diseases

Report of the Spanish Network of Agencies for Assessing National Health System Technologies and Performance.

The use of cryoprobes in transbronchial lung biopsy (TBLB) has greatly improved the diagnostic yield of this procedure and obtains larger, higherquality tissue samples than the use of conventional forceps. This technique may modify the diagnostic algorithm and may benefit many patients as a possible alternative to surgical lung biopsy (SLB).

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Available in Spanish.


To analyse the scientific evidence of the diagnostic yield, safety and costeffectiveness of cryobiopsy in the diagnosis of diffuse interstitial lung diseases (DILD) compared with SLB and conventional TBLB. “Diagnostic yield” is defined as the percentage of patients in whom a sample can be obtained and used to produce a diagnosis.


Systematic review of clinical practice guidelines (CPG), health technology assessment reports (HTA), systematic reviews (SR) and original articles on the usefulness of cryobiopsy in the diagnosis of DILD. Comprehensive literature search (until June 2016) of CPG repositories and HTA reports (NICE Evidence Search and the AHRQ Guidelines Clearinghouse) and the MEDLINE, EMBASE and Cochrane Library bibliographic databases. Evaluation of the methodological quality of the documents selected, using AMSTAR for SRs and an adaptation of the QUADAS-2 questionnaire for original studies.


As a starting point, an SR was chosen that reported a diagnostic yield for cryobiopsy of 76.9% (95% CI: 67.2-85.3) to 85.9% (95% CI: 78.2-92.2) depending on whether the diagnosis was considered definitive or probabledefinitive. The SR was updated with three studies.

Comparison of cryobiopsy with surgical lung biopsy
There is a single study that describes the diagnostic yield of cryobiopsy compared with surgical biopsy guided by video-assisted thoracoscopic surgery (VATS), and shows the yield of cryobiopsy to be lower (83% [95% CI: 78% -87%] vs. 99% [95% CI: 95% -100%]). VATS mortality was higher (2.7% vs. 0.3%, p = 0.045) as was the number of exacerbations (3.3% vs. 0.3%). The mean time to the first adverse event after surgical biopsy was 27.5 ± 73.9 days, versus 0.6 ± 2 days after cryobiopsy. Hospital length of stay was significantly shorter for cryobiopsy (2.6 days [0-17] vs. 6.1 days [3-48]). In Dhooria’s SR, the rate of patients needing a SLB to confirm diagnosis after a cryobiopsy ranged from 3.6% to 28% (based on four studies). A cost study included in the review5 concluded that cryobiopsy can save 953 to 1,925 euros per patient compared to SLB.

Comparison of cryobiopsy with conventional transbronchial lung biopsy
Dhooria reported a significantly higher diagnostic yield with cryobiopsy than with conventional TBLB (86.3% [95% CI: 80.2%-90.8%] vs. 56.5% [95% CI: 27.5%-83.2%]), as well as an odds ratio for reaching a diagnosis of 6.7 (95% CI: 3.6-12.4). The size of the tissue sample obtained with the cryobiopsy procedure was significantly larger than with conventional TBLB (20.4 vs. 4.3 mm2, p = 0.005). The findings of the additional studies identified were consistent with those of the review. 


The conclusions of this report are based on fundamentally retrospective observational evidence of limited quality.

  1. The diagnostic yield of surgical lung biopsy by VATS is superior to that of cryobiopsy, but this comes at the cost of increased mortality and an increase in the number of exacerbations of the disease.
  2. The diagnostic yield of cryobiopsy is superior to that of conventional transbronchial lung biopsy; the procedure obtains tissue samples of larger size and higher quality.
  3. Cryobiopsy is a safe test that is associated with few complications or adverse effects. These safety results are limited to the populations included in the studies, and may not be representative of the test’s safety in patients with greater morbidity and mortality due to reduced lung function, hemodynamic instability, and so on.
  4. Initial use of cryobiopsy might avoid the need to perform surgical biopsies in a significant number of patients. However, multicentre clinical trials are necessary to confirm these results in different scenarios and in the various entities that comprise diffuse interstitial lung disease.
  5. The use of cryobiopsy is expected to reduce the costs associated with a surgical lung biopsy. However, further studies are necessary to evaluate its possible cost-effectiveness or cost-utility in more detail.
Update:  15.06.2018