Transbronchial Lung Cryobiopsy for Diagnosing Interstitial Lung Diseases and Peripheral Pulmonary Lesions - A Stepwise Approach

Summary

Transbronchial lung cryobiopsy (TBLC) for diagnosing interstitial lung disease and peripheral pulmonary lesions is a high-yield diagnostic and safe procedure. We describe a stepwise approach to conduct TBLC for the different indications mentioned with a flexible bronchoscope, which might be helpful for novice bronchoscopists performing TBLC.

Abstract

Transbronchial lung cryobiopsy (TBLC) is an invasive procedure increasingly implemented during the last decade as an alternative to video-assisted thoracic surgery lung biopsy (SLB) for diagnosing interstitial lung diseases (ILDs). The indication for TBLC has primarily been to sub-classify a specific ILD subtype when this cannot be achieved on the basis of a preceding multidisciplinary team discussion. Although SLB is considered the gold standard for establishing a histological diagnosis, TBLC has been gradually suggested as the first-choice histological diagnostic modality in patients with unclassified ILDs due to a comparable diagnostic yield with SLB, but superior to SLB in terms of complications, including mortality. During recent years, radial endobronchial ultrasound (R-EBUS) and electromagnetic navigation bronchoscopy (ENB)-guided TBLC for peripheral pulmonary lesions have also been described as safe procedures, which may improve the diagnostic yield compared to forceps biopsies. Still, the diagnostic properties of TBLC rely on the quality of the procedure's performance. This article aims to describe the stepwise approach to conducting TBLC with a flexible bronchoscope for the different indications mentioned, which might be helpful for novice bronchoscopists performing TBLC.

Introduction

Interstitial lung diseases (ILDs) constitute a group of both acute and chronic lung diseases that affect one or more of all the lung parenchymal components forming the interstitium such as bronchi, alveoli, connective tissue, and blood- and lymphatic vessels. Despite being rare diseases, the more than 200 different subtypes of ILDs represent a heterogeneous disease category with different clinical, radiological, and cyto-histological characteristics. ILDs typically manifest as inflammation, fibrosis, or a combination of both, which are the underlying causes for the patients' usual perceived symptoms as dry cough, dyspnea on exertion, and fatigue^1,2.

ILDs are categorized as idiopathic interstitial pneumonia (IIP), interstitial pneumonia of known etiology (e.g., connective tissue disease interstitial lung disease, drug-induced ILD, and work-related pneumoconiosis), granulomatous interstitial affection (e.g., sarcoidosis and hypersensitivity pneumonia), and orphan ILDs (e.g., multiple cystic lung diseases and eosinophilic pneumonia)¹. This categorization and further diagnostic subtyping are fundamental to determining optimal treatment and follow-up, and allow prognostication. However, as the diagnostic puzzle may be challenging, interpretation of available clinical (including anamnesis, disposition, and potential exposures) and paraclinical information as chest high-resolution computed tomography (HRCT), lung physiology, and autoimmunology obtained on the basis of a multidisciplinary team discussion (MDD) is recommended^3,4,5. If a confident MDD diagnosis is not obtainable^6,7, histological sampling to increase the likelihood of a definite ILD subtype diagnosis is indicated by the use of transbronchial lung cryobiopsy (TBLC)^8,9. In well-selected patients, TBLC is considered a safe invasive procedure with a diagnostic accuracy close to that of video-assisted thoracic surgery lung biopsy (SLB), which is still regarded as the histological gold standard for histological ILD diagnostics^{10,11,12,13,14}. The TBLC procedure is performed as a systematic bronchoscopy, applying special cryoprobes for histological sampling and with recommended fluoroscopic guidance. It is recommended that TBLC is performed in tertiary ILD centers using an MDD setting and by interventional pulmonologists familiar with the management of TBLC complications, who have undergone training in a dedicated center with TBLC expertise^{9,10,11,15,16,17}.

TBLC has also recently gained attention as a procedure to be combined with radial endobronchial ultrasound (R-EBUS) for ILD diagnostics^18,19. Furthermore, TBLC has been combined with both R-EBUS and electromagnetic navigation bronchoscopy (ENB) for diagnosing peripheral pulmonary lesions (PPL) to improve the diagnostic yield when compared to conventional transbronchial forceps biopsies^20,21. However, this relatively novel approach for PPL diagnostics has not yet been implemented as a standard procedure and thus, warrants further evidence in this specific area. The aim of the present report is to describe a stepwise approach to conducting TBLC with a flexible bronchoscope in a clinical setting for the indications mentioned.

Protocol

The authors come from two Danish TBLC centers (Odense University Hospital and Aarhus University Hospital) that both conduct research in accordance with the principles of the Declaration of Helsinki. Ethics approval was not necessary as the study was observational in nature. All patients included for research purposes gave written informed consent. It is important to emphasize that the described stepwise approach for TBLC conductance relates to the use of a flexible bronchoscope and is based on a combination of recommenda…

Representative Results

Based on the observations from the authors from two TBLC centers, the described stepwise procedure for TBLC with a flexible bronchoscope allowed histological sampling in well-selected Danish patients with yet undiagnosed ILD subtypes despite preceding MDD. Detailed observations from these cohorts are reported in two recently published studies23,25 and for the center of the first author summarized in Table 2. <table border="1" fo:keep-together…

Discussion

Regardless of the indication for TBLC, its diagnostic properties rely on the quality of the procedure's performance and the selected criteria for undergoing the procedure. This emphasizes the recommendation of implementing a formal and certified training program to acquire the competences required to perform a standardized TBLC procedure. Despite the fact that no official TBLC education is currently obtainable, the recent European Respiratory Society guideline on TBLC for ILD suggests that interventional pulmonologis…

Materials

"Chimney" for tube
CO2 gas bottle adapter
CO2 gas tank	Erbe
Endoscopy column
Endotracheal tube, size 7.5-8.5 mm	Erbe
Erbecryo pedal footswitch	Erbe
Erbecryo2 workstation	Erbe
Flexible bronchoscope
Flexible gas hose	Mediland
Flexible single use cryoprobe, OD 1.1 mm	Erbe
Flexible single use cryoprobe, OD 1.7 mm	Erbe
Flexible single use cryoprobe, OD 2.4 mm
Fluoroscope
Fogarty balloon catheter
Formalin glasses in closed system
NaCl incl. cold NaCl
Pean for fixating Fogarty balloon
Sterile disposable cup
Sterile suction tube
Sterile tweesers
Syringe for Fogarty balloon inflation/deflation
Table bag for flouroscope
Three way tap for Fogarty balloon syringe
Tracheal suction
Ultrasound machine	Erbe
Valve for biopsy chanel
Valve to suction duct