To the Editor:
We read with great interest the recent article by Romagnoli and coworkers (1). This first-of-its-kind, prospective, blinded study compared the diagnostic impact of two biopsy modalities, transbronchial lung cryobiopsy (TBLC) and surgical lung biopsy, and found that they provide poor diagnostic agreement (κ = 0.22). The reasons for the low concordance between TBLC and surgical lung biopsy are unknown; however, we speculate that the unique study design, the relative size of the biopsies, technical differences in sampling methods and locations, and the impact of freezing are potential contributors.
These findings are preliminary—the sample size was small and the diagnostic process atypical—but if confirmed, they could have major clinical implications. Although previous studies have evaluated the diagnostic certainty of TBLC in patients with interstitial lung disease (ILD) (2), Romagnoli and colleagues’ study demonstrates that questions remain regarding its diagnostic accuracy (3). We agree that these findings underscore the risk of early, widespread adoption of TBLC in ILD without more robust evidence (4).
What are the next steps? First, we need funding agencies and international societies to support high-quality research on the diagnostic value and safety of TBLC. Second, we need collaboration among members of the international scientific community to work toward consensus and avoid the production of discordant recommendations that poorly serve patients and providers. Lastly, we believe it is important to continue to explore the diagnostic “gold standard” for patients with ILD, including the best methodology to obtain tissue for histopathology and new diagnostic paradigms such as the use of molecular profiling of transbronchial biopsy samples (5) and behavioral classifications (6, 7). As this study shows, we need to use a deliberative process when investigating novel approaches to improve our diagnostic methods.
While we await additional data, the current study should give clinicians pause before they consider further implementation of TBLC in ILD. Despite the frustration inherent in this approach, increasing diagnostic confidence, minimizing adverse outcomes, and lowering barriers against substantive progress will remain our community’s common goals.
Supplementary Material
Footnotes
Originally Published in Press as DOI: 10.1164/rccm.201905-0932LE on August 23, 2019
Author disclosures are available with the text of this letter at www.atsjournals.org.
References
- 1.Romagnoli M, Colby TV, Berthet JP, Gamez AS, Mallet JP, Serre I, et al. Poor concordance between sequential transbronchial lung cryobiopsy and surgical lung biopsy in the diagnosis of diffuse interstitial lung diseases. Am J Respir Crit Care Med. 2019;199:1249–1256. doi: 10.1164/rccm.201810-1947OC. [DOI] [PubMed] [Google Scholar]
- 2.Tomassetti S, Wells AU, Costabel U, Cavazza A, Colby TV, Rossi G, et al. Bronchoscopic lung cryobiopsy increases diagnostic confidence in the multidisciplinary diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2016;193:745–752. doi: 10.1164/rccm.201504-0711OC. [DOI] [PubMed] [Google Scholar]
- 3.Patel NM, Borczuk AC, Lederer DJ. Cryobiopsy in the diagnosis of interstitial lung disease: a step forward or back? Am J Respir Crit Care Med. 2016;193:707–709. doi: 10.1164/rccm.201511-2313ED. [DOI] [PubMed] [Google Scholar]
- 4.Raghu G, Lederer DJ, Rabe KF. Cryobiopsy for interstitial lung disease: the heat is on. Am J Respir Crit Care Med. 2019;199:1183–1184. doi: 10.1164/rccm.201903-0682ED. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Raghu G, Flaherty KR, Lederer DJ, Lynch DA, Colby TV, Myers JL, et al. Use of a molecular classifier to identify usual interstitial pneumonia in conventional transbronchial lung biopsy samples: a prospective validation study. Lancet Respir Med. 2019;7:487–496. doi: 10.1016/S2213-2600(19)30059-1. [DOI] [PubMed] [Google Scholar]
- 6.Travis WD, Costabel U, Hansell DM, King TE, Jr, Lynch DA, Nicholson AG, et al. ATS/ERS Committee on Idiopathic Interstitial Pneumonias. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2013;188:733–748. doi: 10.1164/rccm.201308-1483ST. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Flaherty KR, Brown KK, Wells AU, Clerisme-Beaty E, Collard HR, Cottin V, et al. Design of the PF-ILD trial: a double-blind, randomised, placebo-controlled phase III trial of nintedanib in patients with progressive fibrosing interstitial lung disease. BMJ Open Respir Res. 2017;4:e000212. doi: 10.1136/bmjresp-2017-000212. [DOI] [PMC free article] [PubMed] [Google Scholar]
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