Which Biopsy to Diagnose Interstitial Lung Disease? A Call for Evidence and Unity.

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.