The Diagnostic Efficiency and Safety of Transbronchial Lung Cryobiopsy Using 1.1-mm Cryoprobe in Diagnosing Interstitial Lung Disease.

INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) is increasingly used to diagnose interstitial lung disease (ILD). The 1.1-mm cryoprobe has recently been available in clinical practice. The diagnostic yield and safety of TBLC using a 1.1-mm cryoprobe need to be confirmed. METHODS: A prospective, randomized controlled trial was conducted in patients with suspected ILD and randomly assigned to 1.1-mm and 1.9-mm cryoprobe groups. The primary outcome was the diagnostic yield of multidisciplinary discussion. Secondary outcomes were sample quality and incidence of complications. The tension and stress effects during TBLC onto the target lobe caused by 1.1-mm and 1.9-mm cryoprobes were also evaluated using finite element analysis. RESULTS: A total of 224 patients were enrolled. No significant differences were observed in the diagnostic yield (80.4% vs. 79.5%, p = 0.845) and sample quality scores (5.73 ± 0.64 vs. 5.66 ± 0.77; p = 0.324) between the 1.9-mm cryoprobe group and 1.1-mm cryoprobe group. The average surface areas of samples in 1.1-mm cryoprobe group were smaller, while no difference in sample weights was observed. A decreased incidence of moderate bleeding was found in the 1.1-mm cryoprobe group (17.0% vs. 6.2%, p = 0.027), while there was no difference in the incidence of the pneumothorax, there was a trend to higher rate of pneumothorax in 1.1-mm group. In finite element analysis, the 1.1-mm cryoprobe required the largest tension and produced the largest stress. CONCLUSION: Compared with a 1.9-mm cryoprobe, there was no difference in specimen quality or diagnostic rate but smaller sample size with a 1.1-mm cryoprobe. There was a decreased risk of moderate bleeding, but a trend towards increased risk for pneumothorax with 1.1-mm cryoprobe. TRAIL REGISTRATION: Clinicaltrials.gov identifier NCT04047667; registered August 4, 2019.

Transbronchial Lung Cryobiopsy Performed with Cone Beam Computed Tomography Guidance Versus Fluoroscopy: A Retrospective Cohort Review.

PURPOSE: Determining the cause of interstitial lung disease (ILD) remains challenging. While surgical lung biopsy remains the gold standard approach, risks associated with it may be prohibitive. Transbronchial lung cryobiopsy (TBLC) is a minimally invasive alternative with an improved safety profile and acceptable diagnostic accuracy. We retrospectively assessed whether the use of Cone Beam computed tomography guidance for TBLC (TBLC-CBCT) improves safety and diagnostic yield compared to performing TBLC with fluoroscopic guidance (TBLC-F). METHODS: A retrospective cohort review of 120 patients presenting for evaluation of newly diagnosed ILD was performed. Demographic data, pulmonary function test values, chest imaging pattern, procedural information, and final multidisciplinary discussion (MDD) diagnosis were recorded. RESULTS: 62 patients underwent TBLC-F and 58 underwent TBLC-CBCT. Patients undergoing TBLC-CBCT were older (67.86 ± 10.97 vs 61.45 ± 12.77 years, p = 0.004) and had a higher forced vital capacity percent predicted (73.80 ± 17.32% vs 66.00 ± 17.45%, p = 0.03) compared to the TBLC-F group. The average probe-to-pleura distance was 5.1 ± 2.3 mm in the TBLC-CBCT group with 4.0 ± 0.3 CBCT spins performed. Pneumothorax occurred more often in the TBLC-F group (n = 6, 9.7%) compared to the TBLC-CBCT group (n = 1, 1.7%, p = 0.06). Grade 2 bleeding only occurred in the TBLC-F group (n = 4, 6.5%). A final MDD diagnosis was obtained in 89% (n = 57) of TBLC-F patients and 95% (n = 57) of TBLC-CBCT patients. CONCLUSIONS: TBLC-CBCT appears to be safer compared to TBLC-F with both approaches facilitating an MDD diagnosis. Further studies from multiple institutions randomizing patients to each modality are needed to confirm these findings.

Diagnosis of leukemic lung infiltration mimicking fungal infection by transbronchial lung cryobiopsy: the first case report.

BACKGROUND: We here report the first case of leukemic lung infiltration diagnosed by transbronchial lung cryobiopsy (TBLC). TBLC is likely to be a superior method to transbronchial forceps biopsy because TBLC can get larger specimens, resulting in a higher chance of containing the leukemic cells infiltrated tissues. TBLC is generally considered a superior diagnostic method compared to transbronchial lung forceps biopsy (TBLB) because it utilizes cryotechnology to obtain larger specimens, increasing the likelihood of capturing tissues infiltrated with leukemic cells. CASE PRESENTATION: A 69-year-old male patient with acute myeloid leukemia presented with a fever. His initial chest CT scans revealed consolidative lesions, raising suspicion of fungal infection such as angioinvasive aspergillosis or mucormycosis. TBLC and TBLB were conducted to achieve a precise diagnosis, and eventually, leukemic lung infiltration was identified exclusively in the tissues obtained from TBLC. Two cycles of chemotherapy was administrated to patient, showing improvements in symptoms and chest CT findings. CONCLUSIONS: TBLC has greater potential as a differential diagnostic method for pulmonary lesions than TBLB in leukemia patients facing therapeutic challenges due to its higher diagnostic yield.

The accuracy of electromagnetic navigation bronchoscopy compared to fluoroscopy in navigation of transbronchial lung cryobiopsy in patients with interstitial lung disease.

BACKGROUND: Safely implementing transbronchial lung cryobiopsy (TBLC) in patients with interstitial lung disease (ILD) requires accurate navigation. Traditional fluoroscopy falls short in reducing the risk of post-procedure pneumothorax. The potential of electromagnetic navigation bronchoscopy (ENB) as a more precise navigation method warrants further exploration. METHODS: A prospective cohort study was conducted on ILD patients undergoing TBLC. Patients were assigned either fluoroscopy or ENB for cryoprobe positioning. Navigation accuracy was evaluated using cone beam computed tomography (CBCT) images as the standard. Safety and diagnostic yield were also observed. RESULTS: Seventeen patients underwent TBLC, with 10 guided by fluoroscopy and seven by ENB. Fluoroscopy-guided cryoprobe navigation required more adjustments [9/15 (60%) v.s. 1/9 (11%), p = 0.018] for subsequent TBLC compared to ENB, as confirmed by CBCT images. Clinical characteristics, post-procedure complications, and biopsy specimen size showed no significant differences between the groups. Fourteen patients obtained a pathological diagnosis, and 15 received a multidisciplinary discussion (MDD) diagnosis. In the fluoroscopy group, three patients failed to obtain a pathological diagnosis, and two failed to obtain an MDD diagnosis. CONCLUSIONS: ENB demonstrates significantly superior accuracy in TBLC navigation compared to traditional fluoroscopy when CBCT images are used as a reference. Further studies are necessary to determine the value of ENB in TBLC navigation for ILD patients.

Can transbronchial lung cryobiopsy benefit adaptive treatment strategies in connective tissue disease-associated interstitial lung disease?

BACKGROUND: Some patients with connective tissue disease (CTD)-associated interstitial lung disease (ILD) progress to pulmonary fibrosis over their disease course despite initial improvement, potentially indicating a poor prognosis. Transbronchial lung cryobiopsy (TBLC) is a new bioptic approach used in diffuse parenchymal lung diseases. This study of CTD-ILD assessed the utility of TBLC in determining therapeutic decision-making strategies. METHODS: We analyzed medical records of 31 consecutive CTD-ILD patients who underwent TBLC focusing on radio-pathological correlation and disease course. A TBLC-based usual interstitial pneumonia (UIP) score was used that assessed three morphologic descriptors: i) patchy fibrosis, ii) fibroblastic foci, and iii) honeycombing. RESULTS: Among the patients with CTD-ILD, 3 had rheumatoid arthritis, 2 systemic sclerosis, 5 polymyositis/dermatomyositis, 8 anti-synthetase syndrome, 6 Sjögren's syndrome, and 5 had microscopic polyangiitis. Pulmonary function test results showed a mean %FVC of 82.4% and %DLCO of 67.7%. Among the 10 CTD patients and TBLC-proven pathological UIP, 3 patients had prominent inflammatory cells in addition to a framework of UIP, and pulmonary function of most patients improved with anti-inflammatory agents. Six (40%) of 15 patients with TBLC-based UIP score ≥ 1 had a progressive disease course during follow-up, of whom 4 patients received anti-fibrotic agents. CONCLUSIONS: TBLC in patients with CTD-ILD can help determine an appropriate medication strategy, particularly when UIP-like lesions are present. TBLC may be useful when judging which agents to prioritize, anti-inflammatory or anti-fibrotic, is difficult. Moreover, additional information from TBLC may be beneficial when considering early intervention with anti-fibrotic agents in clinical practice.

Safety and efficacy of cryobiopsy for the diagnosis of lymphangioleiomyomatosis compared with forceps biopsy and surgical lung biopsy.

BACKGROUND: Transbronchial lung forceps biopsy (TBFB) is recommended before a surgical lung biopsy (SLB) when a definitive diagnosis of lymphangioleiomyomatosis (LAM) is required for patients without any additional confirmatory features. Transbronchial lung cryobiopsy (TBCB) has been suggested as replacement test in patients considered eligible to undergo SLB for the diagnosis of interstitial lung diseases. The efficacy and safety of TBCB were compared with that of TBFB and SLB in the diagnosis of LAM. METHODS: A retrospective analysis was conducted on 207 consecutive patients suspected with LAM in the First Affiliated Hospital of Guangzhou Medical University from 2005 to 2020. RESULTS: The difference in diagnostic rate of patients suspected with LAM between TBCB (20/30, 66.7%) and TBFB (70/106, 66.0%) groups was not significant (p = 0.949). One patient performed TBCB with negative pathological results could be diagnosed exclusively after SLB. LAM diagnosis was confirmed by surgical pathological findings in 3 TBFB-negative patients. More patients with minimal cystic profusion were diagnosed with LAM by TBCB (5/19, 26.3%) and SLB (11/39, 28.2%) than by TBFB (3/61, 4.9%) (TBCB vs TBFB: p = 0.04, SLB vs TBFB, p < 0.001). The difference between the severity of cystic lung disease in patients diagnosed with LAM through TBCB and SLB was not significant (p > 0.05). One pneumothorax, 8 mild bleeding and 1 moderate bleeding were observed in TBCB. One pneumothorax, 15 mild bleeding and 1 moderate bleeding occurred after TBFB. CONCLUSION: Compared to TBFB, TBCB is safe and effective in diagnosing LAM at a higher diagnostic rate in patients with minimal cystic profusion.

Lung Involvement in Adult T-Cell Lymphoma Diagnosed Using Bronchoscopic Cryobiopsy: A Case Report and Review of the Literature.

The diagnosis of pulmonary lymphoma using small tissue samples is difficult and often requires surgical procedures; thus, a less invasive sampling method is desirable. Moreover, pulmonary involvement in adult T-cell lymphoma (ATL) is often difficult to diagnose, especially in cases without characteristic flower cells. Here, we present the case of a 78-year-old man, in whom pathological examination of the transbronchial lung biopsy (TBLB) specimen did not reveal malignant findings; therefore, transbronchial lung cryobiopsy (TBLC) in combination with endobronchial ultrasonography (EBUS) was used to diagnose ATL based on the pathological findings. A literature review identified 18 cases of pulmonary lymphomas diagnosed using TBLC. Among the 19 cases, including our own, 16 cases were of B-cell lymphoma (84.2%), and the present case is the first case of ATL diagnosed using TBLC. Eighty percent of the cases underwent a biopsy (more than two samples) of the middle or lower lobe and were diagnosed without major complications. EBUS was used with TBLC in three cases to identify the location of the pulmonary lesions. In the present case, EBUS was also useful for avoiding vascular biopsy. Although large-scale prospective studies are required to establish precise guidelines for diagnosing pulmonary lymphomas using TBLC, our case report and review contributes to a deeper understanding of the diagnosis of rare diseases.

Transbronchial lung cr onchial lung cryobiopsy for the diagnosis of diffuse obiopsy for the diagnosis of diffuse parenchymal lung disease: Pitfalls and challenges, a single center experience.

BACKGROUND: : Transbronchial lung cryobiopsy (TBLC) is a minimally invasive technique of the diagnosis of diffuse parenchymal lung diseases (DPLD). The aim of this study is to determine the clinical-radiological and histopathological characteristics of patients in whom cryobiopsy contributes to the diagnosis. METHODS: : In this retrospective study, we searched for the medical records of patients who underwent TBLC from July 2015 to March 2020 at the pulmonology department of our university hospital clinic. Radiological images were evaluated by a chest radiologist experienced in DPLD. Prediagnosis was indicated by clinical-radiological findings. The final diagnosis was determined by the contribution of histopathological diagnosis. The agreement of pretest/posttest diagnosis and the diagnostic yield of TBLC were calculated. RESULTS: Sixty-one patients with female predominance (59.0%) and current or ex-smoker (49.2%) made up the study population. We found the diagnostic yield of TBLC 88.5%. The most common radiological and clinical-radiological diagnosis was idiopathic pulmonary fibrosis (IPF) (n = 12, 19.6%) while the most common multidisciplinary final diagnosis was cryptogenic organizing pneumonia (COP) (n = 14, %22.9). The concordance of pre/posttests was significant (p < 0.001) with a kappa agreement = 0.485. The usual interstitial pneumonia (UIP) diagnosis was detected in six patients among 12 who were prediagnosed as IPF having also a suspicion of other DPLD by clinical-radiological evaluation (p < 0.001). After the contribution of TBLC, the multidisciplinary final diagnosis of 22(36.1) patients changed. The histopathological diagnosis in which the clinical-radiological diagnosis changed the most was nonspecific interstitial pneumonia (NSIP). DISCUSSION: We found the overall diagnostic yield of TBLC high. The pretest clinical-radiological diagnosis was often compatible with the multidisciplinary final diagnosis. However, TBLC is useful for the confirmation of clinical radiological diagnosis as well as clinical entities such as NSIP which is difficult to diagnose clinical-radiological. We also suggest that TBLC should be considered in patients whose clinicopathological IPF diagnosis is not precise.

Mucinous Adenocarcinoma of the Lung Diagnosed by Radial Endobronchial Ultrasound-guided Bronchoscopic Cryobiopsy and Presenting as Interstitial Lung Disease in a Patient with Systemic Sclerosis.

We report a patient with systemic sclerosis who was diagnosed with advanced-stage mucinous adenocarcinoma of the lungs. The clinical presentation, imaging findings, pathological results, and molecular diagnoses are presented. A 64-year-old woman with systemic sclerosis was administered prednisolone and hydroxychloroquine sulfate to control her disease. High-resolution computed tomography (HRCT) revealed an interstitial pattern in both lungs during annual imaging. Connective tissue disease-associated interstitial lung disease (CTD-ILD) was diagnosed using blood tests, pulmonary function tests, and imaging findings. One year later, the patient underwent follow-up chest HRCT, which showed progressive lung disease. The patient underwent endobronchial ultrasound (EBUS)-guided transbronchial lung cryobiopsy and computed tomography-guided biopsy for a pathological diagnosis. The pathology reports of bilateral lungs disclosed mucinous adenocarcinoma. After tumor staging and mutation testing, the patient received chemotherapy with pemetrexed and cisplatin. The bilateral lung lesions subsided after four cycles of first-line chemotherapy. Patients with CTD and lung involvement may be diagnosed with CTD-ILD. Although histopathological results are not mandatory for ILD diagnosis, EBUS-guided transbronchial lung biopsy or lung cryobiopsy should be considered when ILD has atypical or unexplained features.

The Role of Ultrasonography in the Diagnosis and Decision Algorithm for the Management of Pneumothorax after Transbronchial Lung Cryobiopsy.

BACKGROUND: Pneumothorax is one of the main complications of transbronchial lung cryobiopsy (TBLC). Chest ultrasound (CUS) is a radiation-free alternative method for pneumothorax detection. OBJECTIVE: We tested CUS diagnostic accuracy for pneumothorax and assessed its role in the decision algorithm for pneumothorax management. Secondary objectives were to evaluate the post-procedure pneumothorax occurrence and risk factors. METHODS: Eligible patients underwent TBLC, followed by chest X-ray (CXR) evaluation 2 h after the procedure, as our standard protocol. Bedside CUS was performed within 30 min and 2 h after TBLC. Pneumothorax by CUS was defined by the absence of lung sliding and comet-tail artefacts and confirmed with the stratosphere sign on M-mode. Pneumothorax size was determined through lung point projection on CUS and interpleural distance on CXR and properly managed according to clinical status. RESULTS: Sixty-seven patients were included. Nineteen pneumothoraces were detected at 2 h after the procedure, of which 8 (42.1%) were already present at the first CUS evaluation. All CXR-detected pneumothoraces had a positive CUS detection. There were 3 discordant cases (κ = 0.88, 95% CI: 0.76-1.00, p < 0.001), which were detected by CUS but not by inspiration CXR. We calculated a specificity of 97.5% (95% CI: 86.8-99.9) and a sensitivity of 100% (95% CI: 87.2-100) for CUS. Pneumothorax rate was higher when biopsies were taken in 2 lobes and if histology had pleural representation. Final diagnosis was achieved in 79.1% of patients, with the most frequent diagnosis being hypersensitivity pneumonitis. Regarding patients with large-volume pneumothorax needing drainage, the rate of detection was similar between CUS and CRX. CONCLUSION: CUS can replace CXR in detecting the presence of pneumothorax after TBLC, and the lung point site can reliably indicate its size. This useful method optimizes time spent at the bronchology unit and allows immediate response in symptomatic patients, helping to choose optimal treatment strategies, while preventing ionizing radiation exposure.

Evaluation of Transbronchial Lung Cryobiopsy Freezing Time, Biopsy Size, Histological Quality, and Incidence of Complication: A Prospective Clinical Trial.

BACKGROUND: Transbronchial cryobiopsy (TBCB), a novel way of obtaining a specimen of lung tissue using a flexible cryoprobe, can obtain large lung biopsies without crush artifacts. The freezing time of TBCB was empirically selected from 3 to 7 s in the previous studies. However, no consensus has yet been reached regarding the optimal freezing time used in TBCB. OBJECTIVES: The primary endpoint was biopsy size in different freezing times. The secondary endpoints included sample histological quality, diagnostic confidence, and complications in different freezing times. METHODS: Patients who were suspected of DPLD requiring histopathological examination for further evaluation were enrolled in this study. Distinct biopsies were obtained by using different freezing times increased from 3 to 6 s sequentially. Samples were reviewed by 2 external expert pathologists. RESULTS: A total of 33 patients were enrolled, and 143 transbronchial cryobiopsies were taken in this trial. An average of 4.33 samples were taken from each patient. The mean biopsy size of different freezing times from 3 to 6 s was 9.10 ± 4.37, 13.23 ± 5.83, 16.26 ± 5.67, and 18.83 ± 7.50 mm2, respectively. A strong correlation between freezing time and biopsy size was observed (r = 0.99, p < 0.01). Statistically significant difference of biopsy size was detected in the freezing time of 3 s versus 4 s (p < 0.01) and 4 s versus 5 s (p = 0.02), but not in the freezing time of 5 s versus 6 s (p = 0.10). Overall bleeding in different freezing times from 3 to 6 s was 53.33%, 67.50%, 89.47%, and 77.14%, respectively. A significantly higher overall bleeding was observed when the freezing time exceeded 4 s (RR = 1.67, p < 0.01). Pneumothorax occurred in 4 cases (12.12%). One lethal case (3.03%) was noted 25 days after TBCB. Lung parenchyma was preserved well in all cryobiopsy samples. Thirty-one (93.94%) patients' histopathological findings were identified as sufficient to establish a CRP diagnosis. There was no statistical difference in diagnostic confidence between different freezing times. CONCLUSION: A longer freezing time was associated with a larger size of the biopsy sample but a higher risk of bleeding. The optimal transbronchial cryobiopsy freezing time is 3-4 s, which is easily achievable and provides an adequate biopsy size whilst creating a safety threshold from complications.

Comparison of Forceps, Cryoprobe, and Thoracoscopic Lung Biopsy for the Diagnosis of Interstitial Lung Disease - The CHILL Study.

RATIONALE: Transbronchial lung cryobiopsy (TBLC) has emerged as a less invasive method to obtain a tissue diagnosis in patients with interstitial lung disease (ILD). The diagnostic yield of TBLC compared to surgical lung biopsy (SLB) remains uncertain. OBJECTIVES: The aim of this study was to determine the diagnostic accuracy of forceps transbronchial lung biopsy (TBLB) and TBLC compared to SLB when making the final diagnosis based on multidisciplinary discussion (MDD). METHODS: Patients enrolled in the study underwent sequential TBLB and TBLC followed immediately by SLB. De-identified cases, with blinding of the biopsy method, were reviewed by a blinded pathologist and then discussed at a multidisciplinary conference. MAIN RESULTS: Between August 2013 and October 2017, we enrolled 16 patients. The raw agreement between TBLC and SLB for the MDD final diagnosis was 68.75% with a Cohen's kappa of 0.6 (95% CI 0.39, 0.81). Raw agreement and Cohen's kappa of TBLB versus TBLC and TBLB versus SLB for the MDD final diagnosis were much lower (50%, 0.21 [95% CI 0, 0.42] and 18.75%, 0.08 [95% CI -0.03, 0.19], respectively). TBLC was associated with mild bleeding (grade 1 bleeding requiring suction to clear) in 56.2% of patients. CONCLUSIONS: In patients with ILD who have an uncertain type based on clinical and radiographic data and require tissue sampling to obtain a specific diagnosis, TBLC showed moderate correlation with SLB when making the diagnosis with MDD guidance. TBLB showed poor concordance with both TBLC and SLB MDD diagnoses.

Transbronchial Lung Cryobiopsy is Safe and Effective for Diagnosing Acutely Ill Hospitalized Patients with New Diffuse Parenchymal Lung Disease.

INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) is an accepted alternative to surgical lung biopsy (SLB) for diagnosing diffuse parenchymal lung disease (DPLD) that is less invasive and results in comparable diagnostic yields. Performing lung biopsies on hospitalized patients, however, has increased risk due to the patient's underlying disease severity. Data evaluating the safety and efficacy of TBLC in hospitalized patients are limited. We present a comparison of TBLC for hospitalized and outpatients and provide the safety and diagnostic yields in these populations. METHODS: Demographic data, pulmonary function values, chest imaging pattern, procedural information, and diagnosis were recorded from enrolled patients. Complications from the procedure were the primary outcomes and diagnostic yield was the secondary outcome. RESULTS: 77 patients (n = 22 hospitalized vs n = 55 outpatient) underwent TBLC during the study period. Comparing adverse events between hospitalized and outpatients revealed no statistically significant differences in pneumothorax (9%, n = 2 vs 5%,n = 3), tube thoracostomy placement (5%, n = 1 vs 2%, n = 1), grade 2 bleeding (9%, n = 2 vs 0%, n = 0), escalation in level of care (5%, n = 1 vs 0%, n = 0), 30-day mortality (9%, n = 2 vs 2%, n = 1), and 60-day mortality (9%, n = 2 vs 4%, n = 2) (p > 0.05 for all). No deaths were attributed to the procedure. 95% of cases received a multidisciplinary conference diagnosis (hospitalized 100%, n = 22 vs outpatients 93%, n = 51, p = 0.32). CONCLUSION: Our experience supports that TBLC may be a safe and effective modality for acutely ill-hospitalized patients with DPLD. Further efforts to enhance procedural safety and to determine the impact of an expedited tissue diagnosis on patient outcomes are needed.

Usefulness and safety of transbronchial lung cryobiopsy for reassessment of treatment in the clinical course of diffuse parenchymal lung disease.

BACKGROUND: The 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. METHODS: This 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. RESULTS: Seven (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. CONCLUSIONS: Pathological information from TBLC may contribute to decision-making in treatment strategies for the progression of DPLD, and it may be safely performed.

Evaluation of large airway specimens obtained by transbronchial lung cryobiopsy in diffuse parenchymal lung diseases.

BACKGROUND: The difference in diagnostic yield between surgical lung biopsy and transbronchial lung cryobiopsy (TBLC) in diffuse parenchymal lung diseases (DPLD) has been reported to be due to differences in the rate of interpathologist agreement, specimen size, and specimen adequacy. In TBLC, the specimens containing large airway components are generally believed as inadequate specimens for histological evaluation, but the detailed characteristics of TBLC specimens including the large airway and the impact on histological diagnostic rates of DPLD have not been investigated. METHODS: We retrospectively reviewed the specimen characteristics of patients with DPLD who underwent TBLC. RESULTS: Between February 2018 and January 2020, 74 patients and 177 specimens were included. There were 85 (48.0%) large airway specimens (LAS) that contained bronchial gland or bronchial cartilage. The ideal specimen ratio was significantly lower in the LAS-positive group than that in the LAS-negative group (5.8% vs. 45.6%), and the proportion of bronchioles, alveoli, and perilobular area were similarly lower in the LAS-positive group. The presence of traction bronchiectasis and diaphragm overlap sign on high-resolution computed tomography (HRCT) were also significantly higher in the LAS-positive group than those in the LAS-negative group. We observed a statistically significant trend in histological diagnostic yield (40.7% in LAS positive group; 60.8% in LAS positive and negative group; 91.6% in LAS negative group) (Cochran-Armitage trend test). CONCLUSION: LAS is a specimen often collected in TBLC and contains a low percentage of bronchioles, alveoli, and perilobular area. Since the histological diagnostic yield tends to be higher in cases that do not contain LAS, it may be important to determine the biopsy site that reduces the frequency of LAS collection by referring to the HRCT findings in TBLC.

The diagnostic value of transbronchial lung cryobiopsy combined with rapid on-site evaluation in diffuse lung diseases: a prospective and self-controlled study.

BACKGROUND: The etiology of interstitial lung diseases (ILDs) is varied. Early diagnosis and a specific pathological type could significantly improve the prognosis. Mostly, it is difficult to make the etiology diagnosis of ILD through traditional biopsy methods. It will be of great significance to explore an effective biopsy method. METHODS: The prospective study was designed to evaluate the diagnostic value of transbronchial lung cryobiopsy (TBCB) combined with rapid on-site evaluation (ROSE), compared with conventional transbronchial lung biopsy (TBLB), in a large sample of ILD patients. All patients enrolled will undergo both TBLB and TBCB procedures. The study will observe the differences in the diagnostic efficiency of pathological typing and incidence of operation-related complications between TBCB and TBLB. Besides, it will analyze the relationship between the time of biopsy and the incidence of complications, the relationship between freezing time, size of specimen, and complications. And it will evaluate the consistency of pathological, clinical, and radiology. DISCUSSION: It may be the first time that ROSE technique will be used in the diagnosis of ILD. The results of this study will clarify the value of TBCB in the diagnosis of ILD and confirm its safety and effectiveness, which is expected to significantly improve the efficiency of diagnosis in ILD patients. TRAIL REGISTRATION: The trial was registered on the Chinese Clinical Trial Registry website ( http://www.chictr.org.cn/showproj.aspx?proj=57834 ) (Registration number: ChiCTR2000035492).

Cone Beam CT Guidance Improves Transbronchial Lung Cryobiopsy Safety.

INTRODUCTION: Determining the cause of diffuse parenchymal lung disease (DPLD) is challenging. While surgical lung biopsy has been the standard approach, transbronchial lung cryobiopsy (TBLC) represents a minimally invasive alternative with an acceptable safety profile and reasonable accuracy. In this study, we prospectively assessed whether the use of cone beam CT (CBCT) coupled with a novel bronchoscope holder and prophylactic administration of vasoconstricting medications decreases potential complications and improves diagnostic accuracy when performing TBLC. METHODS: 33 patients presenting for evaluation of newly diagnosed DPLD were enrolled. Demographic data, pulmonary function values, chest imaging pattern, procedural information, and diagnosis were recorded. RESULTS: Mean patient age was 67, with the majority Caucasian (n = 26, 79%) and male (n = 20, 61%). Mean pulmonary function values revealed restrictive lung disease (76 ± 14% predicted) and diffusing capacity impairment (52 ± 16%). A non-usual interstitial pneumonia imaging pattern was commonly seen (n = 20, 61%). CBCT guided TBLC was performed in one lobe (n = 29, 88%) or two lobes (n = 4, 12%) with mean probe-to-pleura distance of 4.2 ± 1.3 mm. No peri or post procedural complications occurred. 32 patients (97%) received a histological diagnosis with a final multidisciplinary conference diagnosis possible for 32 (97%). CONCLUSION: CBCT guided TBLC coupled with a novel articulating scope holder and prophylactic phenylephrine administration has the potential to increase safety and diagnostic yield for patients with newly identified DPLD. Future studies comparing different aspects of this approach in isolation and with other modalities have the potential to refine this procedure to improve patient care.

Implementation of transbronchial lung cryobiopsy in a tertiary referral center for interstitial lung diseases: a cohort study on diagnostic yield, complications, and learning curves.

BACKGROUND: Transbronchial lung cryobiopsy (TBLC) has been introduced as an alternative to surgical lung biopsy (SLB) in the diagnostics of interstitial lung diseases (ILD). Despite controversy on safety, TBLC is increasingly implemented in ILD centers with an apparent diagnostic yield comparable to SLB. The aim of this study was to assess TBLC implementation experiences from a tertiary Danish ILD center regarding diagnosis, complications, and learning curves for TBLC performance. METHODS: TBLC was prospectively performed in a cohort of patients with unclassifiable ILD based on a preceding multidisciplinary clinical and radiological revision. TBLC was performed as an outpatient procedure with the patients in general anesthesia using a flexible bronchoscope with 1.9 or 2.4 mm cryoprobes. Learning curves for TBLC performance were calculated using cumulated sum (CUSUM) scores for diagnostic yield, pneumothorax, and bleeding. RESULTS: From February 2017 to March 2020 141 patients (86 (61%) men, median age 69 years [IQR, 60-74 years]) had TBLC performed. A histological and confirmative diagnosis was made in 101 patients (75.2%) and 124 patients (87.9%, i.e. clinical diagnostic yield), respectively, in whom idiopathic interstitial pneumonias constituted the majority (67.3%) of the clinical diagnoses. We observed 2 deaths (1.4%) within 30 days of TBLC, but no procedure-related mortality or severe bleeding. Moderate bleeding occurred in 23 patients (16.3%), pneumothorax in 21 patients (14.9%) with only 14 patients (9.9%) requiring a pleural drain. Based on the CUSUM score analysis, the diagnostic yield obtained was satisfactory throughout the period. CONCLUSION: This study reports experiences of outpatient TBLC implementation in a tertiary referral ILD center from the largest investigated TBLC cohort in Scandinavia The diagnostic yield and prevalence of complications obtained by TBLC from this single center study on unclassifiable ILD support outpatient TBLC as a valuable and safe alternative to SLB to diagnose ILD in well-selected patients. The learning curves for TBLC were acceptable in the hands of experienced bronchoscopists.

Evaluation of lymphocytic infiltration in the bronchial glands of Sjögren's syndrome in transbronchial lung cryobiopsy.

BACKGROUND: Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by deteriorated exocrine gland function with associated lymphocytic infiltration. However, there are few pathological studies on bronchial glands in SS. In this study, we aimed to clarify pathological features of bronchial glands in SS. METHODS: We retrospectively evaluated infiltration of lymphocytes in the bronchial glands incidentally collected by transbronchial lung cryobiopsy (TBLC), which were performed for the diagnosis of diffuse lung diseases. The degrees of lymphocyte infiltration in the bronchial glands were classified into four grades (grade 0-3). We compared the degrees of infiltration of SS with those of other diffuse lung diseases. RESULTS: TBLC for diagnosis of diffuse lung diseases were performed on 432 cases during the study period. The samples of 50 cases included bronchial glands. Of those, 20 cases were excluded due to insufficient size or influence of therapy. The remaining 30 cases included 17 of idiopathic interstitial pneumonias, 5 of chronic hypersensitivity pneumonia, 6 of connective tissue disease (SS; n = 4, systemic sclerosis; n = 1, dermatomyositis; n = 1) and 2 of other diseases. In SS, infiltration of lymphocytes was observed in all cases; grade 1 in one, grade 2 in one, and grade 3 in two cases. In contrast, 11 of 26 in other diseases showed no lymphocytes infiltration, with the remaining 15 of grade 1 infiltration. Grade 2 or more infiltration were found only in SS but not in other diseases. CONCLUSION: Our results suggested that high-grade lymphocytic infiltration of bronchial glands is a distinct characteristics in SS.

Diagnostic approach in parenchymal lung diseases: transbronchial lung biopsy or cryobiopsy?

Background/aim: Diagnosis of interstitial lung diseases requires a multidisciplinary approach, and a gold standard for histological diagnosis is open lung biopsy. Transbronchial lung biopsy (TBLB) and in recent years an alternative method, cryobiopsy (TBLC), are used for the diagnosis of parenchymal lung lesions. The aim of this study is to compare the efficacy of concomitant conventional TBLB and TBLC. Materials and methods: A total of 82 patients who underwent TBLC for diagnosis of diffuse parenchymal lung diseases at Dr. Suat Seren Chest Diseases and Surgery Training and Research Hospital between 2015 and 2018 were screened retrospectively and included in the study. Of the patients, 53.7% (n: 44) were male, and 46.4% (n:38) of them were female. The mean age was 58.37 (±9.33) years. First TBLB and then TBLC were performed to all patients in the same session and their diagnostic performances were compared. Results: Although both procedures were done in the same session, 45 patients (54.9%) were diagnosed with TBLB and 75 patients (91.5%) were diagnosed with TBLC (P ˂ 0.001). Hemorrhage was observed in 39 patients (47.6%), but only one had a massive hemorrhage. Pneumothorax was observed in 6 patients (7.3%) and none of them required tube drainage. Conclusion: Transbronchial lung cryobiopsy is a promising technique for the diagnosis of parenchymal lung diseases compared to transbronchial lung biopsy.