Defining Optimal Settings for Transbronchial Lung Cryobiopsy II: An Ex-Vivo Human Lungs Model Study for Improvement of Specimen Quality

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Description

Transbronchial lung cryobiopsy (TBLC) is a less invasive procedure than surgical lung biopsy (SLB) to establish the diagnosis of interstitial lung disease (ILD) and as an endoscopic intervention can be done as an outpatient procedure. This technology has also being used for cryoadhesion to remove ti...

Transbronchial lung cryobiopsy (TBLC) is a less invasive procedure than surgical lung biopsy (SLB) to establish the diagnosis of interstitial lung disease (ILD) and as an endoscopic intervention can be done as an outpatient procedure. This technology has also being used for cryoadhesion to remove tissue from the airway. The freeze lung tissue provides bigger samples than the conventional transbronchial lung biopsy (TBB), less crush artifacts with more alveolar structures which gives better quality specimens and diagnostic yield for ILDs that usually has a complex morphologic pattern like unusual interstitial pneumonia and nonspecific interstitial pneumonia compared by TBB forceps biopsy. A recent trial showed that the histological diagnosis was obtained in only 34.1% of patients who had a TBB and the diagnostic yield of this technique was 29.1%. Lung cryobiopsy is associated with higher diagnostic yield (up to 83%) than TBBs and because of this, TBB is not recommended for ILD diagnosis in the current guidelines. The diagnostic algorithm for ILD etiology definition is complex and has been born out of the necessity for diagnosis in patients where gold standard lung biopsy is associated with significant risk and therefore is typically saved as a last resort. Currently, SLB is indicated in only about 4 to 5% of the new cases suspected to have ILD. If TBLC is shown to be associated with lower complication rates, the investigator may be able to obtain definitive histological diagnoses in a great majority of cases and forego complex, inefficient and inaccurate methods of disease diagnosis. However, in order to replace SLB, TBLC should provide a similar diagnostic yield and better safety profile. Compared to SLB, retrospective data has shown that TBLC is associated with fewer complications, lower mortality, and better patient tolerance and recently one multicentric prospective trial (COLDICE) was designed to compare both techniques and guide the diagnostic accuracy for TBLC, not yet known. Several groups have published retrospective series of TBLC in ILD with promising results and diagnostic yields, however, the different technical components for performing a TBLC are very heterogeneous among the published series. Probe size, freezing time and distance from the probe to pleura are all parameters that may influence the size and quality of the samples. As a technique recently applied to obtain adequate lung tissue for ILD differential diagnosis, its use was first described in 2009, there is no standard way to perform TBLC, and very limited data on how these parameters can influence biopsy quality. It is not clear which settings or parameters could affect the results. A few animal studies documented positive correlation between freezing time and biopsy size in TBLC. Published series on humans have used 4 and 6 seconds with a mini-cryoprobe probe and between 1 to 2 cm from the visceral pleura. One of the limitations from the previous studies was that the lung specimens were obtained from healthy animal lungs. The lungs from patients undergoing transplant are affected by diffuse parenchymal pathologies and should offer a good predictor of how to obtain the best specimens for highest diagnostic yield in human lungs. The ex-vivo human model also has the advantage of performing multiple lung biopsies without any risks related with the procedure in in-vivo patients.

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