1) Transbronchial cryobiopsy is a bronchoscopic technique that uses extreme cold to obtain biopsy samples and has potential as a safer alternative to surgical lung biopsy for diagnosing interstitial lung diseases. 2) Results from studies show the diagnostic yield of cryobiopsy is around 73% with an overall complication rate of 23%, including pneumothorax in 9.4% of patients and significant bleeding in 14.2%. 3) Guidelines now recommend considering cryobiopsy for suspected idiopathic pulmonary fibrosis when a multidisciplinary team reviews clinical, radiological, and pathological findings.

1. Mahmoud Elhusseiny Abolmagd MSc, MD
lecturer of Pulmonary & Critical Care Medicine
Mansoura University
Transbronchial Cryo-biopsy in ILD:
The Journey From Practice to Guidelines

2. Introduction
• Bronchoscopic cryo techniques are available that
employ extremely low temperatures by Cooling
agents (cryogen) to freeze tissue for:
- Destruction (cryoablation)
- Adhesion (cryoadhesion)
- Biopsy (cryobiopsy)

4. Question
• Which of the following is the gold standard of
diagnosis of ILD?
1) HRCT
2) MDT
3) SLB
4) TBLCB

5. Question
• Which of the following is the gold standard of
diagnosis of fibrosing ILD?
1) HRCT
2) MDT
3) SLB
4) TBLCB

6. Scope of the problem

7. Lung Biopsy
• Diagnostic algorithm in interstitial lung disease (ILD).
• required in up to 30% of patients.
• In the absence of a pulmonary biopsy, the diagnosis
of IPF is underestimated, since the typical
radiological pattern of IPF is found only in 50% of
cases, while in the remaining cases the HRCT picture
is rather atypical and does not allow for a reliable
diagnosis.

8. Lung Biopsy in ILD
•SLB
•TBLFB •TBLCB

9. Guidelines 2018
• The updated American Thoracic Society, European
Respiratory Society, Japanese Respiratory Society,
and Latin American Thoracic Society idiopathic
pulmonary fibrosis guidelines recommend for TBLC in
suspected idiopathic pulmonary fibrosis cases.

11. Introduction
• Historically, surgical lung biopsy (SLB) has been
considered as the definitive means of obtaining
adequate biopsy specimens. However, in many
patients, the risk/benefit ratio of the procedure is
unacceptable. Morbidity and mortality related to SLB
are substantial, particularly in older subjects, in
patients with significant comorbidities or severe
respiratory impairment, and in cases with a final
diagnosis of IPF.

12. Introduction
• Available data indicate pneumothorax to be a complication associated
with TBCB. However, the rate varies considerably between different
studies: from less than 1% to almost 30%. In a meta-analysis that included
15 studies comprising 994 patients, the average rate was 10% . the same
results were confirmed by a more recent meta-analysis of 13
studies with an incidence of postprocedural pneumothorax of 9.5% (5.9–
14.9%) .
The risk of pneumothorax increases with UIP histology, fibrotic reticulation
on HRCT scan, and with biopsies taken close to the pleura

13. Key points ‫كله‬ ‫في‬ ‫حلوة‬

14. Introduction
• Conversely, biopsies obtained too
proximally from the middle third of the lung increase
the risk of severe bleeding due to the fact that in this
region, medium-sized arterial vessels that
accompany the bronchi lack the protective shield
afforded by complete cartilage plates present in
more central airways

21. Results

22. Diagnostic Accuracy

24. Pneumothorax

26. Bleeding

28. (30 days) Mortality

30. Results

31. Results

33. Introduction
• Clinical information, radiological features and biopsy
results were then reviewed by clinicians, radiologist
and pathologists and a multidisciplinary diagnosis
was made, with cryobiopsy considered diagnostic if
additional evaluation, including surgical lung biopsy,
was considered to be unnecessary.

34. Results

35. Introduction
• bleeding was defined as:
- “No bleeding”
- “Mild” if requiring just endoscopic suction.
- “Moderate” if requiring further endoscopic procedures (bronchial
occlusion and/or instillation of ice-cold saline).
- “Severe” if requiring surgical interventions, transfusions and/or admission
to intensive care unit for hemodynamic or respiratory instability.
- There is no generally accepted bleeding severity scale and therefore
comparability of different papers is difficult. However,

36. Results

37. Results
35 %
6.4 %
4 %
35 %
7 %
5.6 %

38. Results

39. Results

40. Results

42. COLDICE

44. Results
• A total of 27 studies were included in the review
with 1443 patients reported data on the
performance of cryobiopsies for diagnosing DPLD.
• The diagnostic yield was 72.9%.
• The overall complication rate was 23.1%.
• The incidence of significant bleeding was 14.2%.
• Pneumothorax was seen in 9.4% of patients.
• Overall reported mortality was 0.3%.

48. Introduction
• Exclusion criteria for TBCBs vary substantially across studies:
- FEV1 < 50% predicted.
- FVC < 50% predicted.
- DLCOr < 50% predicted.
- Echo to exclude those with estimated PASP >40 mm Hg.
- Significant hypoxemia, PaO2 <55–60 mm Hg on room air.
- Bleeding diathesis and anticoagulant therapy, treatment with
antiplatelet drugs and thrombocytopenia with platelets <50 ×
109 /L.

49. Technique

51. • Finally, a smaller 1.1 mm cryoprobe used in
conjunction with an oversheath is in development. This system
permits the bronchoscope to remain wedged in the
biopsied segment as the smaller cryobiopsy is extracted
through the working channel, which is protected by the
oversheath. To date, this probe has only been tested in two
in vivo animal studies, and it is unclear whether biopsies will
be of sufficient size to diagnose DPLDs (

52. Guidelines 2025
• The updated American Thoracic Society,
European Respiratory Society, Japanese
Respiratory Society, and Latin American
Thoracic Society idiopathic pulmonary
fibrosis guidelines recommend for TBLC in
suspected idiopathic pulmonary fibrosis
cases.

53. Closing Comments
• Indications for TBLCB in the diagnosis of ILD within
the context of a multidisciplinary discussion are
currently under evaluation.
• The recent introduction of TBLCB as a promising and
safer alternative to SLB is generating considerable
interest in the pulmonary community.
• Patients with DPLD without a diagnosis after
integration of clinical profile, laboratory tests, and
HRCT features could be submitted to TBCB instead of
SLB in centers with an established experience in the
MDD and TBCB.

54. Closing Comments
• Indications for transbronchial lung cryobiopsy in the
diagnosis of diffuse parenchymal lung diseases
within the context of a multidisciplinary discussion
are currently under evaluation.

55. Pulmonologist
Thoracic Radiologist
Thoracic Pathologist
Multidisciplinary Collaboration
Rheumatologist

56. Thank You..