ISSN: 2581-36842581-3684
Archives of Pulmonology and Respiratory Care
Mini Review       Open Access      Peer-Reviewed

Usefulness of Transbronchial Cryobiopsy in Interstitial Lung Disease

Umair A Gauhar*

University of Louisville, KY, USA
*Corresponding author: Umair Gauhar, MBBS Director, Interventional Pulmonary Program University of Louisville, KY, USA, Email:
Received: 29 May, 2017 | Accepted: 08 June, 2017 | Published: 09 June, 2017

Cite this as

Gauhar UA (2017) Usefulness of Transbronchial Cryobiopsy in Interstitial Lung Disease. Arch Pulmonol Respir Care 3(1): 050-051. DOI: 10.17352/aprc.000025


Interstitial lung disease (ILD) is a term that describes a group of more than 200 lung disorders that show varying degrees of inflammation and fibrosis of the pulmonary interstitium. The etiology and pathophysiology of many of these disorders still remains poorly understood and is the topic of ongoing research and debate. The diagnostic approach to ILD can be complex and often requires a multidisciplinary team approach with involvement of a pulmonologist, radiologist and pathologist. A lung biopsy is often needed to determine the particular subcategory of interstitial lung disease. Unfortunately, conventional transbronchial biopsy with forceps has a very poor diagnostic yield in ILD. A large review of 801 patients showed a diagnostic yield of less than 30% [1]. Surgical lung biopsy is considered the “gold standard” but has a high mortality with several studies showing a mortality of 1.7% to 4.2% in elective cases and 16% to 17.5% in urgent cases [2-6]. In the last several years, the introduction of bronchoscopic transbronchial cryobiopsy has been an exciting development in this regard. This particular diagnostic intervention has the potential to provide diagnosis in ILD with a safety profile closer to conventional transbronchial biopsy and a diagnostic yield approaching surgical lung biopsy.

The cryobiopsy apparatus consists of a cryo-generator that contains Nitric Oxide or Nitrous Oxide gas. Cryo-generators with Carbon Dioxide as the cyogen are also available and are less costly than Nitric Oxide or Nitrous Oxide based systems. A flexible cryoprobe ranging in diameter from 1.9 to 2.6 mm is connected to the generator. A foot paddle allows the operator to release the gas from the generator to exit at the tip of the probe. Utilizing Joule-Thompson effect of fluids, the rapid expansion of gas exiting at the tip of the probe causes a rapid drop in temperature and freezes the tissue surrounding the tip of the probe. Freezing times from 3-6 seconds are generally considered adequate. Care is taken to keep the probe 5-10 mm away from the pleural lining on the fluoroscopic view to avoid advertent freezing of the visceral pleura which could cause a pneumothorax. The probe and scope are then pulled back gently removing the frozen tissue attached at the tip of the cryoprobe. An endobronchial blocker has been used by some operators to control bleeding but its use is not universal or standardized [7]. As opposed to conventional transbronchial biopsy with forceps, cryobiopsy provides a larger specimen with the area of sample ranging from 11.11 mm2 to 64.2 mm2 as compared to 0.58 mm2 to 20.88 mm2 for conventional transbronchial biopsy sample size [8-12]. Moreover, there is avoidance of crush artifact leading to better preservation of tissue architecture.

The larger sample size and preservation of tissue architecture translates into a better diagnostic yield as well. A systematic review and meta-analysis of 11 studies (731 patients), showed a diagnostic yield from 74 to 98% when transbronchial cryobiopsy findings were interpreted in isolation, with a pooled estimate of 83%. Diagnostic yield ranged from 51 to 98% when the results were reviewed within a multidisciplinary discussion with a pooled estimate of 79%13.

The safety profile of transbronchial cryobiopsy seems to be favorable, although the risk of pneumothorax and bleeding are higher than conventional transbronchial biopsy. In the systematic review and meta-analysis published by Johnson KA et al., the pooled estimate for pneumothorax and moderate to severe bleeding were 12% and 39% respectively [13].

Ranaswamy A et al., published a retrospective review comparing conventional transbronchial biopsy and cryobiopspy [14]. Fifty six patients underwent flexible bronchoscopy under conscious sedation and had conventional transbronchial biopsies followed by transbronchial cryobiopsy. Forty five patients (80.4%) had a definitive pathologic diagnosis. In twenty six patients (46.4%), both types of biopsies yielded the same diagnosis. Transbronchial cryobiopsy added a diagnosis in 11 patients (19.6%) while only 4 patients (7.1%) had a diagnosis established only by conventional biopsy. The diagnostic yield of cryobiopsy was higher in hypersensitivity pneumonitis (HP) and non-specific pneumonitis (NSIP) when compared to conventional biopsy. Only two patients needed subsequent surgical biopsy.

A retrospective analysis of 447 cases with ILD undergoing transbronchial cryobiopsy and/or surgical lung biopsy showed no significant difference between the diagnostic yield of cryobiopsy vs video-assisted thoracoscopic (VATS) lung biopsy (82.8% vs 98.7%, p=0.013) [15]. There was a significant decrease in number of hospital days with cryobiopsy when compared to VATS lung biopsy (2.6 d vs 6.1 d, p<0.0001). The mortality rates were 2.7% for surgical biopsy as opposed to 0.3% for cryobiopsy.

With a diagnostic yield approaching that of surgical lung biopsy and an acceptable safety profile, it is possible that bronchoscopic transbronchial cryobiopsy will obviate the need for surgical biopsy in many cases of interstitial lung diseases. An interim analysis of a prospective trial found that in 38 out of 51 patients (75%), a surgical biopsy was deemed unnecessary following a cryobiopsy [16].

With further studies showing the feasibility and usefulness of transbronchial cryobiopsy, it is hoped that this diagnostic intervention will become an integral part of the diagnostic algorithm of interstitial lung diseases. Transbronchial cryobiopsy is still an evolving diagnostic modality that requires development of a standardized procedural technique and protocols to manage complications, particularly bleeding. This is especially important as variations in technique as well as the target patient population can result in widely different diagnostic yields and complications rates. These questions can be explored with a prospective randomized clinical trial [17].

  1. Poletti V, Patelli M, Poggi S, Bertanti T, Spiga L, et al. (1998) Transbronchial lung biopsy and bronchoalveolar lavage in diagnosis of diffuse infiltrative lung diseases. Respiration 54:66-72. Link:
  2. Kreider ME, Hansen-Flaschen J, Ahmad NN, Joseph B. Shrager, et al. (2007) Complications of video-assisted thoracoscopic lung biopsy in patients with interstitial lung disease. Ann Thorac Surg. 83:1120-1145. Link:
  3. Park JH, Kim DK, Kim DS, Y Koh, D S Lee, et al. (2007) Mortality and risk factors for surgical lung biopsy in patients with idiopathic interstitial pneumonia. Eur J Cardiothorac Surg. 31:1115-1119. Link:
  4. Lettieri CJ, Veerappan GR, Helman DL, Charles R, Andrew F, et al. (2005) Outcomes and safety of surgical lung biopsy for interstitial lung disease. Chest 127:1600-1605. Link:
  5. Kayatta MO, Ahmed S, Hammel JA, Allan Pickens, Daniel Miller, et al. (2013) Surgical biopsy of suspected interstitial lung disease is superior to radiographic diagnosis. AnnThorac Surg. 2013;96:399-402 Link:
  6. Hutchinson JP, Fogarty AW, McKeever, TM, Richard B. Hubbard, et al. (2016) In-hospital mortality after surgical lung biopsy for interstitial lung disease in the United States 2000 to 2011. Am J Respir Crit Care Med. 193:1161-1167 Link:
  7. Hohberger LA, DePew ZS, Utz JP, Maldonado F, Edell E S, et al. (2014) Utilizing an Endobronchial Blocker and a Flexible Bronchoscope for Transbronchial Cryobiopsies in Diffuse Parenchymal Lung Disease. Respiration. 88:521-522. Link:
  8. Sriprasart T, Aragaki A, Baughman R, K W Brokamp, G Khanna, et al. (2017) A Single US Center Experience of Transbronchial Lung Cryobiopsy for Diagnosing Interstitial Lung Disease with a 2-Scope Technique. J Bronchol Intervent Pulmonol. 24:131-135. Link:
  9. Babiak A, Hetzel J, Krishna G, Fritz P, Moeller P, et al. (2009) Transbronchial cryobiopsy: a new tool for lung biopsies. Respiration 78:203-208. Link:
  10. Frutcher O, Fridel L, El Raouf BA, N A Rahman, M R Kramer, et al. (2014) Histological diagnosis of interstitial lung diseases by cryo-transbronchial biopsy. Respirology. 19:683. Link:
  11. Casoni GL, Tomassetti S, Cavazza A, Thomas V Colby, Jay H Ryu, et al.(2014) Transbronchial lung cryobiopsy in the diagnosis of fibrotic interstitial lung diseases. PLoS One. 9:86716. Link:
  12. Hagmeyer L, Theegarten D, Wohlschläger J, et al. Clin Respir J. 2016;10:589.
  13. Johnson KA, Marcoux VS, Ronksley PE, Christopher J Ryerson (2016) Diagnostic Yield and Complication of TransbronchialLung Cryobiopsy for Interstitial Lung Disease. A Systematic Review and Metaanalysis. Ann Am Thorac Soc. 13: 1828-1838. Link:
  14. Ranaswamy A, Homer R, Killam J, Murph , Araujo, et al. (2016) Comparison of Transbronchial and Cryobiopsies in Evaluation of Diffuse Parenchymal Lung Disease. J Broncholgy Interv Pulmonol. January 23:14-21 Link:
  15. Ravaglia C, Bonifazi M, Well AU, Tomassetti S. Tomassetti S, Gurioli C, et al. (2016) Safety and Diagnostic Yield of Transbronchial Lung Cryobiopsy in Diffuse Parenchymal Lung Diseases: A Comparative Study versus Video-Assisted Thoracoscopic Lung Biopsy and a Systematic Review of the Literature. Respiration. 91: 215-217 Link:
  16. Hagmeyer L, Theegarten D, Tremi M, et al. (2016) Sarcoidosis Vasc Diffuse Lung Dis. 29;33:2-9.
  17. Chen AC, Feller-Kopman D. Cryobiopsy (2017) A Work in Progress. Ann Am Thorac Soc. 14: 827-828 Link:
© 2017 Gauhar UA. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.