South African Thoracic Society consensus statement on transbronchial lung cryobiopsy for interstitial lung disease

BackgroundTransbronchial biopsy (TBB) with a cryoprobe, also known as transbronchial lung cryobiopsy (TBLC), has become a wellestablished modality for sampling lung parenchyma. TBLC is performed under general anaesthesia in the majority of centres, utilising rigid or flexible bronchoscopy. In resource-constrained settings, however, most diagnostic bronchoscopies, including TBB, are performed under conscious sedation with flexible bronchoscopy without the presence of a specialist anaesthetist.ObjectivesGiven the paucity of evidence on TBLC performed under conscious sedation for interstitial lung diseases (ILD), specifically in a resource-constrained setting, we aimed to describe its utility in a pilot study.MethodsWe prospectively enrolled the first 20 patients who underwent TBLC for ILD at a large tertiary hospital in South Africa. All TBLCs were performed under conscious sedation using a cryoprobe. Patients were actively monitored for complications. The final diagnosis and decision regarding need for a surgical biopsy were made at a multidisciplinary meeting that included at least two specialist pulmonologists with an interest in ILD, a thoracic radiologist, and an anatomical pathologist with an interest in ILD.ResultsThree patients experienced complications. Two (10%) developed a pneumothorax (neither required any intervention). Bleeding that required 10 minutes of tamponade with the endobronchial blocker was observed in one case. This patient experienced no haemodynamic or respiratory compromise and was discharged the same day. There were no complications arising from the use of conscious sedation. A definitive diagnosis was made in 17/20 (85%) of the patients.ConclusionTBLC performed at an experienced bronchoscopy centre using a cryoprobe under conscious sedation with a dedicated sedationist was safe and well tolerated. Furthermore, it had a high diagnostic yield, and surgical lung biopsy was avoided in 85% of the patients.Study synopsisWhat the study adds. There is a paucity of evidence for the use of transbronchial lung cryobiopsy (TBLC) for the diagnosis of interstitial lung diseases (ILD) in resource-constrained settings, especially when performed under conscious sedation. In this pilot study, TBLC performed under conscious sedation was safe and well tolerated, and had a high diagnostic yield.Implications of the findings. TBLC under conscious sedation can safely be rolled out in resource-constrained settings as a first-line diagnostic procedure when lung tissue needs to be obtained in patients with ILD, as its yield is comparable to TBLC under general anaesthesia. It potentially avoids surgical lung biopsy in >80% of cases, together with the need for general anaesthesia.

Transbronchial Cryobiopsy Compared to Forceps Biopsy for Diagnosis of Acute Cellular Rejection in Lung Transplant Recipients

Background An accurate diagnosis in patients with interstitial lung diseases (ILDs) by multidisciplinary discussion (MDD) based on histopathologic information is essential for optimal treatment. Transbronchial lung cryobiopsy (TBLC) has increasingly been used as a diagnostic alternative to surgical lung biopsy. This study aimed to evaluate the appropriate methods of TBLC in patients with ILD in Korea.Methods A total of 27 patients who underwent TBLC were included. TBLC procedure details and clinical MDD diagnosis using TBLC histopathologic information were retrospectively analyzed.Results All procedures were performed under general anesthesia with the fluoroscopic guidance in the operation room using flexible bronchoscopy and endobronchial balloon blocker. The median procedure duration was less than 30 minutes, and the median number of biopsies per participant was 2. Most of the bleeding after TBLC was not severe, and the rate of pneumothorax was 25.9%. The most common histopathologic pattern was alternative (48.2%), followed by indeterminate (33.3%) and usual interstitial pneumonia (UIP)/probable UIP (18.5%). In the MDD after TBLC, the most common diagnosis was idiopathic pulmonary fibrosis (33.3%), followed by smoking-related ILD (25.9%), nonspecific interstitial pneumonia (18.6%), unclassifiable-ILD (14.8%), and others (7.4%).Conclusion This first single-center experience showed that TBLC using a flexible bronchoscopy and endobronchial balloon blocker with the fluoroscopic guidance under general anesthesia may be a safe and adequate diagnostic method for ILD patients in Korea. The diagnostic yield of MDD was 85.2%. Further studies are needed to evaluate the diagnostic yield and confidence of TBLC.

Acute Hemothorax Following Bronchoscopic Cryobiopsy: A Novel Complication.

Introduction:Transbronchial lung cryobiopsy (TBLC) is increasingly being used as an alternative to video-assisted thoracoscopic surgery (VATS) biopsy to establish the histopathologic pattern in interstitial lung disease (ILD).Methods:A systematic literature search of the PubMed and Embase databases, from October 2010 to October 2020, was conducted to identify studies that reported on diagnostic yield or safety of VATS or TBLC in the diagnosis of ILD.Results:43 studies were included. 23 evaluated the diagnostic yield of TBLC after multidisciplinary discussion, with a pooled diagnostic yield of 76.8% (95% confidence interval (CI) 70.6–82.1), rising to 80.7% in centres that performed ≥70 TBLC. 10 studies assessed the use of VATS and the pooled diagnostic yield was 93.5% (95% CI 88.3–96.5). In TBLC, pooled incidences of complications were 9.9% (95% CI 6.8–14.3) for significant bleeding (6.9% for centres with ≥70 TBLC), 5.6% (95% CI 3.8–8.2) for pneumothorax treated with a chest tube and 1.4% (95% CI 0.9–2.2) for acute exacerbation of ILD after TBLC. The mortality rates were 0.6% and 1.7% for TBLC and VATS, respectively.Conclusions:TBLC has a fairly good diagnostic yield, an acceptable safety profile and a lower mortality rate than VATS. The best results are obtained from more experienced centres.

Transbronchial lung cryobiopsy (TBCB) is a reliable method for obtaining histopathological findings in interstitial lung diseases. TBCB is traditionally performed during rigid bronchoscopy, positioning an endobronchial balloon blocker to facilitate bleeding management. Therefore, it can be challenging to implement in Centers without access to anesthesiologic support or dedicated beds for endoscopic procedures. We present a series of 11 patients who underwent 12 TBCBs using a flexible bronchoscope and a 5 Fr endobronchial blocker passing through an uncuffed endotracheal tube, under moderate sedation and spontaneous breathing. All procedures were carried out in an endoscopy suite, using fluoroscopy guidance but without requiring anesthesiologic assistance. TBCB was feasible in all cases, and it demonstrated similar or improved diagnostic yield (90.1%) and safety compared to rigid bronchoscopy. In 1 case, it was successfully repeated due to an inconclusive histological definition at the first attempt. The size of the samples was consistent with the literature, as it was the incidence of pneumothorax (16.6%). Four cases of moderate bleeding and 4 cases of severe bleeding were managed without further complications. To our knowledge, this is the first description of a technique allowing to perform TBCB through an artificial airway without need for either rigid bronchoscopy or general anesthesia. We believe this technique could make TBCB faster, cost-effective, and feasible even in resource-limited settings without compromising on safety. However, further studies are needed to validate these findings.

Diagnostic value of TBLC in idiopathic pulmonary fibrosis

Background:Intubation with either an endotracheal tube or a rigid bronchoscope is generally preferred to provide airway protection as well as to manage unpredictable complications during transbronchial lung cryobiopsy (TBLC). The laryngeal mask airway has been described as a safe and convenient tool for airway control during bronchoscopy.Aims and Objectives:In this study, we evaluated the safety and outcome of using a laryngeal mask airway (LMA) as a conduit for performing TBLC by flexible video bronchoscopy (FB).Methods:We retrospectively analyzed the database of the patients who underwent TBLC between November 2015 and September 2019. The procedure was performed using FB through LMA under general anesthesia. Prophylactic occlusion balloon was routinely used starting January 2017 onwards. Radial endobronchial ultrasound (R-EBUS) guidance was used for TBLC in the localized lung lesions when deemed necessary. Multidisciplinary consensus diagnostic yield was determined and periprocedural complications were recorded.Results:A total of 326 patients were analysed. The overall diagnostic yield was 81.60% (266/326) which included a positive yield of 82.98% (161/194) in patients with diffuse lung disease and 79.54% (105/132) in patients with localized disease. Serious bleeding complication occurred in 3 (0.92%) cases. Pneumothorax was encountered in 8 (2.45%) cases. A total of 9 (2.76%) cases had at least 1 major complication.Conclusion:This study demonstrates that the use of LMA during TBLC by flexible bronchoscopy allows for a convenient port of entry, adequate airway support and effective endoscopic management of intrabronchial haemorrhage especially with the use of occlusion balloon.

Introduction. Pathologies included in the diffuse paren-chymal lung disease group are numerous, differential di-agnosis between them is difficult and requires morpho-logical verification. There are minimally invasive methods of morphological verification, such as transbronchial forceps lung biopsy, which is less traumatic compared to surgical biopsy, but is accompanied by a smaller vol-ume of biological material, which often contains artifacts due to damaging with forceps. In 2008, for the first time, a method of transbronchial lung cryobiopsy was pro-posed for morphological verification of lung diseases. The effectiveness of cryobiopsy for diagnosing diffuse parenchymal lung diseases differs according to different sources, however, based on the data of meta-analyses, it can be said that the effectiveness of cryobiopsy is ap-proaching the “gold standard” of surgical lung biopsy. In Russia, however, the use of cryotechniques is limited to single clinical centers, which may be due to the lack of a sufficient number of publications in the domestic lit-erature. The aim of the study was to evaluate the effi-cacy of transbronchial cryobiopsy versus transbronchial forceps biopsy in patients with diffuse parenchymal lung disease. Materials and methods. Inclusion criteria: pres-ence of diffuse parenchymal lung disease of unknown etiology, need for invasive diagnostics. Exclusion criteria: FEV1 less than 40%. Transbronchial forceps lung biop-sy and transbronchial lung cryobiopsy were performed simultaneously. Results. Of 21 patients included in the study, the process was verified in 17 (80.95%). Lung sar-coidosis was detected in 12 (57.14%) cases, pulmonary tuberculosis — in 3 (14.28%), pulmonary mycobacterio-sis — in 2 (9.52%). The diagnosis was verified according to cryobiopsy in 15 patients (71.42%), according to for-ceps lung biopsy in 10 (47.61%). Conclusion. Transbron-chial cryobiopsy of the lung shows better efficacy in com-parison with transbronchial forceps biopsy. Cryobiopsy can be combined with transbronchial forceps biopsy if there is a pathology in the apex of the lungs and/or if it is impossible to place the cryoprobe in the “safe” zone. Further research is needed to confirm the findings on a larger clinical material.

Diagnostic accuracy of transbronchial lung cryobiopsy for interstitial lung disease diagnosis (COLDICE): a prospective, comparative study

BackgroundThe usefulness and safety of transbronchial lung cryobiopsy (TBLC) for reassessment of diffuse parenchymal lung disease (DPLD) with progression is still unknown. Our purpose was to clarify the usefulness and safety of TBLC for reassessment of DPLD with progression.MethodsThis retrospective study included 31 patients with DPLD diagnosed by surgical lung biopsy who progressed in the clinical course and underwent TBLC for reassessment between January 2017 and September 2019 at Kanagawa Cardiovascular & Respiratory Center. Two pulmonologists independently selected the clinical diagnosis, treatment strategy, and confidence level of the treatment strategy based on clinical and radiological information with and without pathological information from TBLC. A consensus was reached among the pulmonologists regarding the clinical diagnosis, treatment strategy, and confidence level of the treatment strategy. Complications of TBLC were also examined.ResultsSeven (22.6%), 5 (16.1%), and 6 (19.4%) of clinical diagnosis was changed after TBLC for Pulmonologist A, for Pulmonologist B, and for consensus, respectively. The treatment strategy was changed in 7 (22.6%), 8 (25.9%), and 6 (19.4%) cases after TBLC for Pulmonologist A, for Pulmonologist B and for consensus, respectively. The definite or high confidence level of the consensus treatment strategy was 54.8% (17/31) without TBLC and 83.9% (26/31) with TBLC. There were 6 cases of moderate bleeding, but no other complications were noted.ConclusionsPathological information from TBLC may contribute to decision-making in treatment strategies for the progression of DPLD, and it may be safely performed.

Transbronchial lung cryobiopsy (TBLC) with flexible bronchoscope represents an encouraging modality to obtain a larger-sized specimen without crush artifact and a higher diagnostic yield in patients with diffuse parenchymal lung lesions/diseases as compared to conventional transbronchial lung biopsy, and fewer complications as opposed to surgical lung biopsy. An artificial airway is preferred as it provides better airway protection in cases of severe bleeding. Although various researchers have published data on different modalities, the data is not sufficient to standardize a single technique. This study describes the procedural technique, safety, and yield of TBLC using a flexible bronchoscope with an endobronchial blocker. We performed a retrospective analysis of 100 consecutive patients who underwent TBLC using flexible bronchoscopy from May 2018 to June 2022. TBLC samples were obtained under moderate sedation without the use of an artificial airway or fluoroscopy. Among the 100 patients, the majority were male (63%). The mean age of the enrolled patients was 44.43±15.92 years. The predominant diagnoses in our study were hypersensitivity pneumonitis (27%), followed by sarcoidosis (12%) and tuberculosis (10%). We obtained alveolated lung tissue in 90 out of 100 cases with a median biopsy size of 5 mm (in greatest dimension, interquartile range 5-4 mm), resulting in a specific histopathological diagnosis in 82 cases. The most frequent complications were bleeding and pneumothorax (13%). Mild bleeding occurred in 58% of the patients, and moderate bleeding occurred in 20%. There was no episode of severe/life-threatening bleeding. None of the patients required intensive care unit admission or endotracheal intubation. In conclusion, the use of TBLC through flexible bronchoscopy with an endobronchial blocker emerges as a minimally invasive, secure, time-efficient, and readily reproducible technique. Significantly, this procedure can be seamlessly executed in the bronchoscopy suite, eliminating the requirement for an artificial airway or general anesthesia.

BackgroundIncreasing evidence indicates the utility of transbronchial lung cryobiopsy (TBLC) for the diagnosis of interstitial lung disease (ILD). However, only one study has compared TBLC and surgical lung biopsy (SLB) performed on the same patients.MethodsWe identified seven patients with ILD with TBLC and SLB. We evaluated the clinical characteristics and made a pathological diagnosis based on the official ATS/ERS/JRS/ALAT clinical practice guideline of idiopathic pulmonary fibrosis with both TBLC and SLB.ResultsSix cases were diagnosed as Usual interstitial pneumonia (UIP) in both TBLC and SLB. One case was diagnosed as indeterminate for UIP with TBLC and probable UIP with SLB. Etiological diagnosis with TBLC and SLB were concordant in 2 cases of idiopathic pulmonary fibrosis (IPF) but discordant for other diagnoses. Major histological findings of UIP including dense fibrosis, peripheral distribution, and fibroblastic foci showed high concordance between TBLC and SLB, which implies that TBLC can reliably detect these features. In contrast, loose fibrosis, cellular infiltration, and airway disease showed poor concordance between the two methods.ConclusionOur study showed that TBLC is useful for UIP diagnosis but not for other ILD. With a multidisciplinary approach, diagnosis of IPF may be determined by TBLC, whereas ILD other than IPF may require SLB.

Transbronchial lung cryobiopsy (TBLC) is an applicable technique that can provide a histologic diagnosis of interstitial lung disease(ILD). The general sample size of TBLC is much smaller than that of surgical lung biopsy (SLB), which raises more concerns about the procedure's diagnostic accuracy. A guiding consensus and guidelines on the pathological procedure of ILD with TBLC are required to better guide pathologists in diagnostic practice. The Respiratory Pathology Working Group of the Respiratory Physicians Branch of the Chinese Medical Doctor Association and the Thoracic Diseases Group of the Pathological Branch of the Chinese Medical Association, jointly organized by experts, have worked together to discuss and formulated the consensus. The consensus is based on literature review, clinical practice, collection of clinical issues, and discussion during a series of meetings. Experts approved the final proposed consensus with more than 70% of votes in favor (Delphi). The consensus summarized the delivery requirements, quality evaluation and artificial phenomena of TBLC specimens. It also proposed the diagnostic principles and procedures, types of ILD corresponding to major pathological changes, and major corresponding differential diagnoses of TBLC specimens. Finally, the consensus formed 14 recommendations for clinical diagnosis and multidisciplinary discussion.The recommendations are addressed as follows.Recommendation 1: We suggest that the TBLC clinical manipulators should observe and measure the size of the specimen in time. The specimen size should be greater than 5 mm in diameter, and multiple pieces(3 to 5 pieces)are recommended.Recommendation 2: Pathologists should record the number of blocks of tissue submitted for examination and the volume, color, and texture of each specimen. Evaluation of the proportion of alveolar parenchyma/airway components under the microscope, analysis of the type and distribution of lesions will facilitate making diagnostic suggestions.Recommendation 3: The size of TBLC specimens is significantly smaller than SLB and may not show sufficient features of ILD or secondary changes. It is more necessary to combine the evaluation of clinical changes and lesion distribution assessed by HRCT for a comprehensive diagnosis.Recommendation 4: Common microscopic artefacts of TBLC specimen are mass of red blood cells, proteinaceous fluid and fibrin exudation. In the absence of hemosiderin cells or clinical signs of hemoptysis symptoms, the diagnosis of pulmonary hemorrhagic disease should be considered with caution.Recommendation 5: TBLC is not a suggested diagnosis when the pathological changes are mainly located in the pleural or subpleural lung tissues, e.g., pleuroparenchymal fibroelastosis.Recommendation 6: The principle of pathological diagnosis of ILD in TBLC is consistent with SLB, with a description of the main pathological morphological change and a tendentious pathological diagnosis; if the lesion is not fully shown, only a pathological description is given.Recommendation 7: A well-sampled TBLC specimen may show patchy fibrosis and fibroblast foci in UIP, supporting a pathological diagnosis of a probable UIP pattern. TBLC may not display sufficient features of the distribution of subpleural and peripheral lung lesions in UIP, as well as secondary lesions.Recommendation 8: TBLC specimens show diffuse inflammation and fibrosis with well-preserved lung tissue structure, which may support a pathological diagnosis of NSIP; if the distribution of lesions and lung tissue structure are difficult to evaluate, it is recommended that a pathological diagnosis of fibrotic ILD or cellular ILD be made.Recommendation 9: TBLC specimens may show pathological features of NSIP accompanied by organization, but it is difficult to accurately evaluate the proportion of organization area. In this scenario, a descriptive diagnosis of NSIP accompanied by organization is suggested.Recommendation 10: It is recommended to diagnose organizing pneumonia if only distal airway organization is present in TBLC; in addition to organization, if pathological histology is accompanied by obvious interstitial fibrosis and lung tissue remodelling, granuloma formation, obvious neutrophil infiltration or accompanied with abscess formation, obvious eosinophil infiltration, tissue necrosis, hyaline membrane formation or vasculitis, secondary OP should be considered.Recommendation 11: It is recommended to diagnose acute fibrinous and organizing pneumonia (AFOP) if lesions on TBLC show features of organizing pneumonia and fibrin balls.Recommendation 12: A diagnosis of smoking-related ILD (RB-ILD or DIP) is suggested when a good sampling of TBLC shows a significant accumulation of histocytes or smoker's macrophages in the alveolar spaces, and without specific changes sufficient for other diagnoses. If the lesions are confined to the lumen of respiratory bronchioles and the immediate peribronchiolar airspaces, RB-ILD is supported; if the distribution is diffuse, DIP should be considered. If it is difficult to determine the distribution of the lesions, it is necessary to integrate clinical and chest CT imaging findings to differentiate RB-ILD from DIP.Recommendation 13: A well-sampled TBLC specimen can display the pathological features of DAD and then also support such a pathological diagnosis.Recommendation 14: Lymphoid interstitial pneumonia (LIP) should show diffuse lymphocyte infiltration and lymphoid follicle formation in the lung interstitium in TBLC specimens. It is recommended that chest CT imaging be combined to determine whether the lesion is diffuse to differentiate from other lymphoproliferative diseases.

Background: Transbronchial lung forceps biopsy (TBLF) is of limited value for the diagnosis of interstitial lung disease (ILD). However, in cases with predominantly peribronchial pathology, such as sarcoidosis, TBLF is considered to be diagnostic in most cases. The present study examines whether transbronchial lung cryobiopsy (TBLC) is superior to TBLF in terms of diagnostic yield in cases of sarcoidosis. Methods: In this post hoc analysis of a prospective, randomized, controlled, multicentre study, 359 patients with ILD requiring diagnostic bronchoscopic tissue sampling were included. TBLF and TBLC were both used for each patient in a randomized order. Histological assessment was undertaken on each biopsy and determined whether sarcoid was a consideration. Results: A histological diagnosis of sarcoidosis was established in 17 of 272 cases for which histopathology was available. In 6 out of 17 patients, compatible findings were seen with both TBLC and TBLF. In 10 patients, where the diagnosis of sarcoidosis was confirmed by TBLC, TBLF did not provide a diagnosis. In one patient, TBLF but not TBLC confirmed the diagnosis of sarcoidosis. Conclusions: In this post hoc analysis, the histological diagnosis of sarcoidosis was made significantly more often by TBLC than by TBLF. As in other idiopathic interstitial pneumonias (IIPs), the use of TBLC should be considered when sarcoidosis is suspected.