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    Transbronchial cryobiopsy: a new tool for lung biopsies. Babiak Alexander,Hetzel Jürgen,Krishna Ganesh,Fritz Peter,Moeller Peter,Balli Tahsin,Hetzel Martin Respiration; international review of thoracic diseases BACKGROUND:Specimens from transbronchial lung biopsies lack sufficient quality due to crush artifact and are generally too small for diagnosis of diffuse lung diseases. Flexible cryoprobes have been shown to be useful in therapeutic bronchoscopy. We introduce a novel technique for obtaining lung biopsies bronchoscopically, using a flexible cryoprobe. OBJECTIVES:The purpose of this study was to show the feasibility of using a cryoprobe to obtain lung biopsies during flexible bronchoscopy. METHODS:Forty-one patients with radiographic signs of diffuse lung disease were selected for transbronchial biopsy. During flexible bronchoscopy, conventional transbronchial biopsies using forceps were done first. Then a flexible cryoprobe was introduced into the selected bronchus under fluoroscopic guidance. Once brought into position, the probe was cooled and then retracted with the frozen lung tissue being attached on the probe's tip. The tissue was processed for histology. After establishing a diagnosis, the specimen area was measured using a digital morphometry system. RESULTS:We evaluated the biopsy samples of 41 patients. The mean specimen area was 5.82 mm(2) (0.58-20.88 mm(2)) taken by forceps compared to 15.11 mm(2) obtained using the cryoprobe (2.15-54.15 mm(2), p < 0.01). Two patients had a pneumothorax which resolved with tube thoracostomy. Biopsy-associated bleeding did not require any intervention. Transbronchial cryobiopsy contributed in a substantial number of cases to a definitive diagnosis. CONCLUSIONS:Transbronchial cryobiopsy is a novel technique which allows to obtain large biopsy samples of lung parenchyma that exceed the size and quality of forceps biopsy samples. Prospective trials are needed to compare this technique with surgical lung biopsy for diagnosis of diffuse lung diseases. 10.1159/000203987
    Transbronchial cryobiopsy in immunocompromised patients with pulmonary infiltrates: a pilot study. Fruchter Oren,Fridel Ludmila,Rosengarten Dror,Rahman Nader Abed-el,Kramer Mordechai R Lung BACKGROUND:In immunocompromised patients with pulmonary infiltrates, transbronchial lung biopsies (TBB) obtained by forceps has been shown to increase the diagnostic yield over simple bronchoalveolar lavage. Cryo-TBB is a novel modality for obtaining lung biopsies. We aimed to evaluate for the first time the efficacy and safety of cryo-TBB in immunocompromised patients. METHODS:Fifteen immunocompromised patients with pulmonary infiltrates underwent cryo-TBB. During the procedure two to three biopsy samples were taken. Procedure characteristics, complications, and the diagnostic yield were retrospectively evaluated. RESULTS:Most patients (n = 11) were immunocompromised due to hematological malignancies. The remaining four patients were receiving chronic immunosuppressive treatment due to previous solid-organ transplantation (n = 2) or collagen-vascular disease (n = 2). No major complications occurred in the cryo-TBB group. The mean surface area of the specimen taken by cryo-TBB was 9 mm(2). The increase in surface area and quality of biopsy samples translated to a high percentage of alveolated tissue (70 %) that enabled a clear histological detection of the following diagnoses: noncaseating granulomatous inflammation (n = 2), acute interstitial pneumonitis consistent with drug reaction (n = 5), nonspecific interstitial pneumonia fibrotic variant (n = 1), diffuse alveolar damage (n = 3), organizing pneumonia (n = 3), and pulmonary cryptococcal pneumonia (n = 1). Diagnostic information obtained by cryo-TBB led to change in the management of 12 patients (80 %). CONCLUSION:Cryo-TBB in immunocompromised patients with pulmonary infiltrates provides clinically important diagnostic data with a low complication rate. These advantages should be further compared with traditional forceps TBB in a prospective randomized trial. 10.1007/s00408-013-9507-z
    [Transbronchial cryobiopsies and cryotherapy in lung diseases]. Montufar Franco,Moral Lucrecia Del,Labarca Gonzalo,Folch Erik,Majid Adnan,Fernandez-Bussy Sebastian Revista medica de Chile Bronchoscopy cryoprobes are used for palliative treatment of endobronchial obstructions caused by tumors and removal of granulation tissue or foreign bodies. Currently this technology is also used for diagnosis of diffuse interstitial lung disease (ILD). The multidisciplinary team that establishes the clinical, radiological and histopathological correlation in ILD, decides about performing a surgical lung biopsy when the characteristics of the interstitial disease are not similar to Idiopathic Pulmonary Fibrosis (IPF). Although surgical lung biopsy is the gold standard for diagnosis, treatment, and prognosis, transbronchial cryo-biopsy has a high diagnostic yield, low morbidity and mortality rate, low rate of complications and lower cost. It is the diagnostic method of choice in ILD when it is available. Technological improvements with greater freezing power and tensile strength of the cryo probes, allow their use in cryotherapy and cryo-recanalization for occlusive airway tumors. 10.4067/s0034-98872018000901033
    Lung transplant for interstitial lung disease: outcomes before and after implementation of the united network for organ sharing lung allocation scoring system. De Oliveira Nilto C,Osaki Satoru,Maloney James,Cornwell Richard D,Meyer Keith C European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery OBJECTIVES:This study was undertaken to evaluate whether the adoption of the united network for organ sharing lung allocation score (LAS) was associated with significant changes in lung transplantation (LTX) outcomes for patients with interstitial lung disease (ILD) who underwent LTX at the University of Wisconsin Hospital and Clinics. METHODS:Outcomes for 107 consecutive patients with various forms of ILD who underwent LTX between January 1993 and March 2009 were examined. Patients transplanted following the implementation of the LAS system (LAS, n = 56) were compared with those transplanted prior to LAS implementation (pre-LAS, n = 51) for whom LAS scores were calculated. RESULTS:Patients with idiopathic pulmonary fibrosis (IPF) comprised the majority of patients with ILD. Recipients transplanted after the implementation of the LAS were significantly older (pre-LAS: 50.4 vs. LAS: 56.7 years, P < 0.01), required more supplemental oxygen (3 vs. 5 l/min, P < 0.01) and displayed lower cardiac index values (3.1 vs. 2.6 l/m(2), P < 0.01). The estimated LAS was significantly increased from 38.3 (pre-LAS) to 43.3 (LAS), P < 0.01. However, waiting time decreased from 266 to 78 days (P < 0.01). The rate of bilateral vs. single LTX was lower (35 vs. 16%, P = 0.02) for the post-LAS group. Cold ischaemic time was shorter in the post-LAS group (434 vs. 299 min, P < 0.01), and the length of hospital stay decreased from 24 to 11 days (P < 0.01). Hospital mortality (11 vs. 7%, P = 0.51) and post-transplant survival did not differ between the groups. CONCLUSIONS:Post-transplant outcomes for patients with ILD or the subset of recipients with IPF were not adversely affected by the implementation of the LAS. 10.1093/ejcts/ezr079
    Histological diagnosis of interstitial lung diseases by cryo-transbronchial biopsy. Fruchter Oren,Fridel Ludmila,El Raouf Bayya Abed,Abdel-Rahman Nader,Rosengarten Dror,Kramer Mordechai R Respirology (Carlton, Vic.) BACKGROUND AND OBJECTIVE:The gold standard for the histological diagnosis of interstitial lung diseases (ILD) is an open lung biopsy (OLB). Tissue samples obtained by forceps transbronchial lung biopsies (TBB) are usually too small. We aim to evaluate the efficacy and safety of cryo-TBB for the diagnosis of ILD and to explore its role as substitute for OLB. METHODS:Seventy-five patients (mean age 56.2 years) with clinical and radiological features suggestive of ILD underwent cryo-TBB under moderate sedation. The diagnostic contribution on the work-up of suspected ILD was assessed. RESULTS:No major complications occurred during cryo-TBB procedures. The mean cross-sectional area of the biopsy specimen obtained was 9 mm2 with an average of 70% alveolated tissue. The most common pathological diagnoses were idiopathic nonspecific interstitial pneumonitis (n = 22), cryptogenic organizing pneumonia (n = 11) and usual interstitial pneumonitis (n = 7). There were three patients of pulmonary Langerhans cell histiocytosis and one patient of pulmonary lymphangioleiomyomatosis. A definite and probable clinicopathological consensus diagnosis was possible in 70% and 28% of patients, respectively. In only 2% of patients' diagnosis could not be established. CONCLUSIONS:Cryo-TBB is a safe and effective minimally invasive modality for the diagnosis of ILD. No OLB is needed in the majority of patients. 10.1111/resp.12296
    Performance of transbronchial cryobiopsy in eccentrically and adjacently orientated radial endobronchial ultrasound lesions. Kho Sze Shyang,Chan Swee Kim,Yong Mei Ching,Tie Siew Teck ERJ open research Background:Radial endobronchial ultrasound (R-EBUS) is an effective technique in the diagnosis of peripheral pulmonary lesions (PPL). However, lesion orientation with regards to the radial probe remains an important factor for effective biopsy. "Within" orientation was associated with significantly higher diagnostic yield. Cryobiopsy is a novel technique in obtaining larger tissue samples with the frozen tip allowing biopsy in a 360° direction, thus potentially achieving more effective biopsy in eccentrically and adjacently orientated lesions. We aimed to evaluate the performance and safety of transbronchial cryobiopsy forceps biopsy in eccentrically and adjacently orientated R-EBUS lesions. Methods:Retrospective review of R-EBUS transbronchial biopsy for PPL over 17 months. Results:114 R-EBUS scans were included for analysis during the study period. Forceps biopsy was performed in 76 (66.7%) cases and cryobiopsy in 38 (33.3%) cases. Baseline demographics and lesion characteristics did not differ between the two groups. Median (interquartile range) lesion size was 3.48 (2.63-4.51) cm. Overall, 41.2% of lesions were of eccentric orientation and 15.8% adjacent orientation; only 43% were concentric in orientation. Overall diagnostic yield was 67.5% (77 out of 114). Orientation remained an important factor affecting diagnostic yield. Transbronchial cryobiopsy significantly increased the diagnostic yield in eccentrically and adjacently orientated lesions to 75.0% (18 out of 24), compared to 48.8% (20 out of 41) obtained forceps biopsy (p<0.05); but not in concentric lesions. Cryobiopsy was associated with more mild and moderate bleeding complications compared to the forceps biopsy group. Conclusions:Transbronchial cryobiopsy under R-EBUS guidance is a safe procedure which potentially increases diagnostic yield in eccentrically and adjacently orientated PPLs. 10.1183/23120541.00135-2019
    The cryo-needle: a new tool for histological biopsies. A feasibility study. Franke Karl-Josef,Nilius Georg,Ruehle Karl-Heinz,Enderle Markus D,Linzenbold Walter,von Weyhern Claus Hann Lung PURPOSE:Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a standard procedure for intrathoracic lymph node biopsies. The newly developed cryo-needle operates in a similar way to the EBUS-TBNA but is able to obtain specimens for histological evaluation. The purpose of this animal study was to evaluate the feasibility, effect, and safety of the cryo-needle biopsies. METHODS:Four EBUS-guided cryo-needle biopsies were obtained from a mediastinal lymph node of a healthy pig. In an open surgery approach, cryo-needle biopsies using activation times of 1, 2, and 3 s (A1/A2/A3) and needle biopsies using a 21-gauge EBUS-TBNA needle were obtained from mesenteric lymph nodes. Cryo-needle biopsies A2 were performed with (A2+) and without (A2-) an oversheath. The size, weight, percentage of lymphatic tissue and artefact-free area of each cryobiopsy were evaluated. Smears were made with the TBNA-needle aspirates to determine the number of lymphocytes per high-power field (HPF). The bleeding duration was measured. RESULTS:We successfully obtained EBUS-guided cryo-needle biopsies. The area and weight of the biopsies A3 and A2+ were significantly larger compared with A1 (1.7 ± 0.8 and 1.4 ± 0.3 vs. 0.9 ± 0.4 mm(2); 5.2 ± 2.4 and 3.4 ± 1.8 vs. 1.5 ± 0.7 mg). The percentage of lymphatic tissue of the cryobiopsies was 90 ± 25 and 98 % of samples were artefact-free. The number of lymphocytes/HPF of TBNA-needle smears was 128 ± 54.3. There was no difference in bleeding duration between the techniques. CONCLUSIONS:The cryo-needle yields large histological specimens of high quality. 10.1007/s00408-013-9502-4
    Diagnostic Yield of Combined Pulmonary Cryobiopsies and Electromagnetic Navigation in Small Pulmonary Nodules. Taton Olivier,Bondue Benjamin,Gevenois Pierre Alain,Remmelink Myriam,Leduc Dimitri Pulmonary medicine Background:An increasing number of pulmonary nodules of unknown nature are detected as a result of screening by CT in high lung cancer risk patients. Objectives:The purposes of this study were to assess the diagnostic yield of electromagnetic navigation bronchoscopy (ENB) combined with transbronchial lung cryobiopsy (TBLC) and to compare it with standard transbronchial biopsy (TBB) in pulmonary nodules of less than 2 cm in diameter. Methods:We prospectively included 32 patients (18 men and 14 women, mean age 68 ± 9 years) with nodules of less than 2 cm in diameter and no metastasis at FDG PET-CT. The nodule position was determined by ENB, radial endobronchial ultrasonography miniprobe, and fluoroscopy. Eight samples were obtained, six by TBB and two by TBLC. Results:Nodule diameter averaged 16 ± 3 mm. Twenty-five nodules were malignant and 18 were surgically resected. Surgery was avoided in four patients as the biopsies revealed a benign disease. The samples obtained by TBLC were five times larger than those by TBB. The diagnostic yields of TBLC and TBB were 69% and 38%, respectively (=0.017). Adverse events consisted in 15 mild or moderate bleedings and one pneumothorax. Conclusions:In the setting of peripheral pulmonary lesions of less than 20 mm in diameter, ENB-combined TBLC is feasible and safe, provides larger samples, and has higher diagnostic yield than TBB. 10.1155/2018/6032974
    Diagnosis of Idiopathic Pulmonary Fibrosis: Differential Diagnosis. Aburto Myriam,Herráez Inmaculada,Iturbe David,Jiménez-Romero Ana Medical sciences (Basel, Switzerland) Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fibrotic interstitial lung disease of unknown origin with a characteristic imaging and histologic pattern called usual interstitial pneumonia (UIP). The diagnosis of IPF is a complex procedure that requires the support of various specialists, who must integrate clinical, radiological, and histological data. The multidisciplinary team (MDT) has become the new gold standard to diagnose and manage the disease, increasing the accuracy and agreement of the diagnosis between different centers. It is mandatory to exclude nonspecific interstitial pneumonia or other diseases that can cause the UIP pattern, particularly drugs or exposure diseases, including chronic hypersensitivity pneumonitis or systemic autoimmune disease. The role of the MDT is also to decide who could need a biopsy or to review patient diagnoses at regular intervals in those with additional information or unexpected evolution. This review provides updated information to achieve a proper IPF diagnosis. 10.3390/medsci6030073
    Cryobiopsies are diagnostic in Pleuroparenchymal and Airway-centered Fibroelastosis. Kronborg-White Sissel,Ravaglia Claudia,Dubini Alessandra,Piciucchi Sara,Tomassetti Sara,Bendstrup Elisabeth,Poletti Venerino Respiratory research BACKGROUND:Idiopathic pulmonary fibroelastosis (iPPFE) is a rare lung lesion characterized by pleural and subpleural parenchymal thickening due to accumulation of fibroelastotic tissue. Only recently, a few cases with a peribronchiolar distribution of fibroelastotic tissue have been reported. These lesions are more prominent in the upper lobes. Even though high resolution computed tomography (HRCT) scan features are considered characteristic, a histological confirmation is suggested, mainly when the clinical setting is not clearly defined. However, due to non-negligible complications, a surgical lung biopsy is not often recommended. The prognosis is usually poor and currently, the only effective treatment is lung transplantation. METHOD:Patients with a multidisciplinary diagnosis of iPPFE or airway-centered fibroelastosis (airway-centered FE), with histological confirmation by transbronchial cryobiopsy, were identified from an ongoing interstitial lung disease registry. Data on patient demographics, HRCT patterns, size and number of biopsies, histology patterns and complications were registered. RESULTS:Seven patients were diagnosed with iPPFE and one patient was diagnosed with airway-centered FE. Pneumothorax was documented in three cases, but none of them required a chest tube. No other complications during or after the procedure were observed. CONCLUSION:This study suggests that using cryobiopsies in the diagnostics of PPFE and airway-centered FE is safe and effective. 10.1186/s12931-018-0839-3
    Combination of 1.1 mm flexible cryoprobe with conventional guide sheath and therapeutic bronchoscope in biopsy of apical upper lobe solitary pulmonary nodule. Kho Sze Shyang,Chai Chan Sin,Nyanti Larry Ellee,Ismail Adam Malik Bin,Tie Siew Teck BMC pulmonary medicine BACKGROUND:Lung cancer is frequently situated peripherally in the upper lobes of the lung. Acquiring adequate tissue from this difficult-to-reach area remains a challenge. Transbronchial cryobiopsy (TBCB) has the ability to acquire larger specimens, but the rigidity of the standard 1.9 mm and 2.4 mm cryoprobes frequently poses challenges when used with a guide sheath (GS). The novel 1.1 mm cryoprobe, being both smaller and more flexible, may address this limitation. We describe the usage of this 1.1 mm flexible cryoprobe with GS in the biopsy of solitary pulmonary nodules (SPN) in the apical segment of the upper lobe in two cases. CASE REPORT:Both procedures were conducted with advanced airway under total intravenous anaesthesia. 2.6 mm GS was used in combination with a 2.2 mm rEBUS probe, using a therapeutic bronchoscope. Case 1 describes a SPN in the apical segment of the right upper lobe that was inconclusive by forceps biopsy due to GS displacement and inadequate biopsy depth. A steerable GS combined with the novel cryoprobe subsequently overcame this issue. Case 2 describes a SPN in the apical segment of the left upper lobe in which the standard cryoprobe failed to advance through the GS due to steep angulation. It also highlights with shorter activation time, the novel cryoprobe enable biopsied tissue to be retrieved through the GS while the bronchoscope-GS remains wedgend in the airway segment. There were no bleeding or pneumothorax complications in both cases, and histopathological examination confirmed adenocarcinoma of the lung. CONCLUSION:The 1.1 mm flexible cryoprobe in combination with GS and therapeutic bronchoscope offers an option to acquire adequate tissue in difficult-to-reach regions in the lung such as the apical segment of upper lobes. Further prospective series to evaluate its performance and safety in SPN biopsy is highly anticipated. 10.1186/s12890-020-01199-3
    Chronic Pulmonary Melioidosis Masquerading as lung malignancy diagnosed by EBUS guided sheath technique. Zaw Kyi Kyi,Wasgewatta Sanjiwika L,Kwong Kin Keung,Fielding David,Heraganahally Subash S,Currie Bart J Respiratory medicine case reports Diagnosis of pulmonary mass lesions can be challenging with several possible differentials. A 41-year-old Caucasian woman presented with intermittent non-specific chest pain on a background of 30 pack years of smoking history. A CT scan of the chest confirmed an opacity in the right lower lobe suspicious for primary pulmonary malignancy and PET scan showed moderate FDG avidity of the lesion. Conventional flexible bronchoscopy did not demonstrate an endobronchial lesion, Using Endobrochial Ultrasound (EBUS) Guide sheath technique, the lesion was localized in the posterior segment of the right lower lobe. Brushings, biopsies and washings were taken through the guide sheath, along with transbronchial cryobiopsy. Culture of bronchial brushings from the lesion on Ashdown's agar medium showed , confirming melioidosis. Treatment was with intravenous ceftazidime for 4 weeks, followed by oral sulphamethoxazole/trimethoprim for 3 months. During the follow up visits, the patient demonstrated significant improvement both clinically and radiologically. 10.1016/j.rmcr.2019.100894
    Pulmonary Parenchymal Lymphoma Diagnosed by Bronchoscopic Cryoprobe Lung Biopsy. Schiavo Dante,Batzlaff Cassandra,Maldonado Fabien Journal of bronchology & interventional pulmonology A 51-year-old man presented with progressively worsening lung infiltrates and respiratory failure. Extensive investigations including bronchoscopy with bronchoalveolar lavage and conventional transbronchial forceps biopsies failed to establish the diagnosis. After transfer to our institution, he underwent repeat bronchoscopy with transbronchial cryobiopsy, which provided large, high-quality biopsy specimens establishing the diagnosis of parenchymal diffuse large B-cell lymphoma. 10.1097/LBR.0000000000000225
    Introduction of cryobiopsies in the diagnostics of interstitial lung diseases - experiences in a referral center. Kronborg-White Sissel,Folkersen Birgitte,Rasmussen Torben Riis,Voldby Nina,Madsen Line Bille,Rasmussen Finn,Poletti Venerino,Bendstrup Elisabeth European clinical respiratory journal : Transbronchial cryobiopsies (cTBB) has emerged as a new method for obtaining lung tissue biopsies in the diagnosis of interstitial lung diseases (ILDs). Until now, it has been used in a few highly specialized interventional centers and has shown promising results in obtaining a definite diagnosis of ILDs. : All patients undergoing a cTBB between November 2015 and June 2016 were included in this case series study. Data on patient demographics, high-resolution computed tomography patterns, size and number of biopsies, histology patterns, the contribution to a confident diagnosis and complications were registered. : Thirty-eight patients underwent cTBB in the period. cTBB contributed to the diagnosis in 28 (74%) of the 38 patients. Only few complications were observed; pneumothorax was the most frequent complication (10 patients, 26%). In six patients, local bleeding occurred during the procedure and was easily controlled by a Fogarty catheter balloon and in some cases tranexamic acid. : Performing cTBB in the diagnostics of ILDs is a safe and feasible procedure. cTBB resulted in a confident diagnosis in 74% of cases. 10.1080/20018525.2016.1274099
    Critical reappraisal of underlying histological patterns in patients with suspected idiopathic pulmonary fibrosis. Rossi Giulio,Cavazza Alberto Current opinion in pulmonary medicine PURPOSE OF REVIEW:Usual interstitial pneumonia (UIP) pattern is the histologic marker of idiopathic pulmonary fibrosis (IPF), but usefulness of ancillary histologic findings may discriminate idiopathic from secondary UIP. RECENT FINDINGS:Alternative less invasive procedures may identify UIP pattern preventing conventional surgical lung biopsy, whereas genomic analysis may recognize UIP pattern from otherwise poorly diagnostic samples. SUMMARY:High-resolution computed tomography identifies a 'definite' UIP pattern in about half of cases, failing to recognize UIP in the absence of honeycombing or in limited disease. Although radiologic criteria for UIP need redefinition to improve their diagnostic yield, histologic features of UIP did not significantly change from the 1960s but continue to represent a major diagnostic tool, particularly in challenging interstitial lung diseases. A careful recognition of some histologic ancillary findings in UIP (e.g., cellular/follicular bronchiolitis with germinal centers, chronic pleuritis, interstitial granulomas/giant cells, bridging fibrosis) may be helpful in supporting secondary forms (e.g., connective tissue disease, chronic hypersensitivity pneumonia) from IPF. Cryobiopsy and awake-biopsy are promising approaches to obtain representative lung tissue preventing conventional surgical lung biopsy. Genomic techniques have recently demonstrated good-to-high sensitivity and specificity to disclose UIP pattern starting from RNA obtained in transbronchial biopsy, possibly replacing and/or flanking soon traditional histology. 10.1097/MCP.0000000000000595
    Diffuse parenchymal lung disease. Tomassetti Sara,Ravaglia Claudia,Poletti Venerino European respiratory review : an official journal of the European Respiratory Society Between September 2015 and August 2016 there were >1500 publications in the field of diffuse parenchymal lung diseases (DPLDs). For the Clinical Year in Review session at the European Respiratory Society Congress that was held in London, UK, in September 2016, we selected only five articles. This selection, made from the enormous number of published papers, does not include all the relevant studies that will significantly impact our knowledge in the field of DPLDs in the near future. This review article provides our personal view on the following topics: early diagnosis of idiopathic pulmonary fibrosis, current knowledge on the multidisciplinary team diagnosis of DPLDs and the diagnostic role of transbronchial cryobiopsy in this diagnostic setting, insights on the new entity of interstitial pneumonia with autoimmune features, and new therapeutic approaches for scleroderma-related interstitial lung disease. 10.1183/16000617.0004-2017
    Invasive diagnostic techniques in idiopathic interstitial pneumonias. Poletti Venerino,Ravaglia Claudia,Gurioli Carlo,Piciucchi Sara,Dubini Alessandra,Cavazza Alberto,Chilosi Marco,Rossi Andrea,Tomassetti Sara Respirology (Carlton, Vic.) Fibrosing interstitial lung diseases (f-ILDs) represent a heterogeneous group of disorders in which the aetiology may be identified or, not infrequently, remain unknown. Establishing a correct diagnosis of a distinct f-ILD requires a multidisciplinary approach, integrating clinical profile, physiological and laboratory data, radiological appearance and, when appropriate, histological findings. Surgical lung biopsy is still considered the most important diagnostic tool as it is able to provide lung samples large enough for identification of complex patterns such as usual interstitial pneumonitis (UIP) and nonspecific interstitial pneumonitis. However, this procedure is accompanied by significant morbidity and mortality. Bronchoalveolar lavage is still a popular diagnostic tool allowing identification of alternative diagnoses in patients with suspected idiopathic pulmonary fibrosis (IPF) when an increase in lymphocytes is detected. Conventional transbronchial lung biopsy has a very low sensitivity in detecting the UIP pattern and its role in this clinical-radiological context is marginal. The introduction of less invasive methods such as transbronchial cryobiopsy show great promise to clinical practice as they can be used to obtain samples large enough to morphologically support a diagnosis of IPF or other idiopathic interstitial pneumonias, along with fewer complications. Recent advances in the field suggest that less invasive methods of lung sampling, without significant side effects, in combination with other diagnostic methods could replace the need for surgical lung biopsy in the future. Indeed, these new multidisciplinary procedures may become the main diagnostic work-up method for patients with suspected idiopathic interstitial pneumonia. 10.1111/resp.12694
    [German Guideline for Idiopathic Pulmonary Fibrosis]. Behr J,Günther A,Bonella F,Dinkel J,Fink L,Geiser T,Geißler K,Gläser S,Handzhhiev S,Jonigk D,Koschel D,Kreuter M,Leuschner G,Markart P,Prasse A,Schönfeld N,Schupp J C,Sitter H,Müller-Quernheim J,Costabel U Pneumologie (Stuttgart, Germany) Idiopathic pulmonary fibrosis (IPF) is a severe and often fatal disease. Diagnosis of IPF requires considerable expertise and experience. Since publication of the international IPF guideline in the year 2011 and Update 2018 several studies and technical advances occurred, which made a new assessment of the diagnostic process mandatory. In view of the antifibrotic drugs which have been approved for the treatment of IPF patients, the goal of this guideline is to foster early, confident and effective diagnosis of IPF. The guideline focusses on the typical clinical setting of an IPF patient and provides tools to exclude known causes of interstitial lung disease including standardised questionnaires, serologic testing and cellular analysis of bronchoalveolar lavage. High resolution computed tomography remains crucial in the diagnostic work-up. If it is necessary to obtain specimen for histology transbronchial lung cryobiopsy is the primary approach, while surgical lung biopsy is reserved for patients who are fit for it and in whom bronchoscopic diagnosis did not provide the information needed. Despite considerable progress, IPF remains a diagnosis of exclusion and multidisciplinary discussion remains the golden standard of diagnosis. 10.1055/a-1120-3531
    Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Raghu Ganesh,Remy-Jardin Martine,Myers Jeffrey L,Richeldi Luca,Ryerson Christopher J,Lederer David J,Behr Juergen,Cottin Vincent,Danoff Sonye K,Morell Ferran,Flaherty Kevin R,Wells Athol,Martinez Fernando J,Azuma Arata,Bice Thomas J,Bouros Demosthenes,Brown Kevin K,Collard Harold R,Duggal Abhijit,Galvin Liam,Inoue Yoshikazu,Jenkins R Gisli,Johkoh Takeshi,Kazerooni Ella A,Kitaichi Masanori,Knight Shandra L,Mansour George,Nicholson Andrew G,Pipavath Sudhakar N J,Buendía-Roldán Ivette,Selman Moisés,Travis William D,Walsh Simon,Wilson Kevin C, American journal of respiratory and critical care medicine BACKGROUND:This document provides clinical recommendations for the diagnosis of idiopathic pulmonary fibrosis (IPF). It represents a collaborative effort between the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society. METHODS:The evidence syntheses were discussed and recommendations formulated by a multidisciplinary committee of IPF experts. The evidence was appraised and recommendations were formulated, written, and graded using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS:The guideline panel updated the diagnostic criteria for IPF. Previously defined patterns of usual interstitial pneumonia (UIP) were refined to patterns of UIP, probable UIP, indeterminate, and alternate diagnosis. For patients with newly detected interstitial lung disease (ILD) who have a high-resolution computed tomography scan pattern of probable UIP, indeterminate, or an alternative diagnosis, conditional recommendations were made for performing BAL and surgical lung biopsy; because of lack of evidence, no recommendation was made for or against performing transbronchial lung biopsy or lung cryobiopsy. In contrast, for patients with newly detected ILD who have a high-resolution computed tomography scan pattern of UIP, strong recommendations were made against performing surgical lung biopsy, transbronchial lung biopsy, and lung cryobiopsy, and a conditional recommendation was made against performing BAL. Additional recommendations included a conditional recommendation for multidisciplinary discussion and a strong recommendation against measurement of serum biomarkers for the sole purpose of distinguishing IPF from other ILDs. CONCLUSIONS:The guideline panel provided recommendations related to the diagnosis of IPF. 10.1164/rccm.201807-1255ST
    A Randomized Controlled Trial of a Novel Sheath Cryoprobe for Bronchoscopic Lung Biopsy in a Porcine Model. Yarmus Lonny B,Semaan Roy W,Arias Sixto A,Feller-Kopman David,Ortiz Ricardo,Bösmüller Hans,Illei Peter B,Frimpong Bernice O,Oakjones-Burgess Karen,Lee Hans J Chest BACKGROUND:Transbronchial forceps biopsy (FBx) has been the preferred method for obtaining bronchoscopic lung biopsy specimens. Cryoprobe biopsy (CBx) has been shown to obtain larger and higher quality samples, but is limited by its inability to retrieve the sample through the working channel of the bronchoscope, requiring the bronchoscope to leave the airway for sample retrieval. OBJECTIVE:We evaluated a novel device using a sheath cryobiopsy (SCBx). This method allows for specimen retrieval through the working channel of the bronchoscope, with the scope remaining inside the airway. METHODS:This prospective, randomized controlled, single-blinded porcine study compared a 1.1-mm SCBx probe, a 1.9-mm CBx probe, and 2.0-mm FBx forceps. Assessment of histologic accessibility, sample quantity and quality, number of attempts to acquire and retrieve samples, cryoprobe activation time, fluoroscopy activation time, technical feasibility, and complications were compared. RESULTS:Samples adequate for standard pathologic processing were retrieved with 82.1% of the SCBx specimens, 82.9%% of the CBx specimens, and 30% of the FBx specimens. The histologic accessibility of both SCBx (P = .0002) and CBx (P = .0003) was superior to FBx. Procedure time for FBx was faster than for both SCBx and CBx, but SCBx was significantly faster than CBx (P < .0001). Fluoroscopy time was lower for both SCBx and CBx compared with FBx. There were no significant bleeding events. CONCLUSIONS:SCBx is a feasible technique providing a higher quality lung biopsy specimen compared with FBx and can successfully be retrieved through the working channel. Human studies are needed to further assess this technique with additional safety data. 10.1016/j.chest.2016.01.018
    [Pattern of biological changes in interstitial lung diseases]. Gester F,Duysinx B,Von Frenckell C,Louis R,Guiot J Revue medicale de Liege Interstitial lung diseases (ILD) are a part of a vast and heterogeneous clinicopathological entity. The work-up have to rule out a granulomatosis or a secondary cause, before making the diagnosis of an idiopathic ILD. The etiological diagnosis is based on a multidisciplinary approach integrating a network of clinical and paraclinical datas. If the diagnosis remains unclear, a lung biopsy is suggested with a transbronchial approach (mainly cryobiopsy) or with a surgical approach (video-assisted thoracoscopy). This review article mainly describes the biological analyses that contribute to explore ILDs.
    Usefulness of surgical lung biopsies after cryobiopsies when pathological results are inconclusive or show a pattern suggestive of a nonspecific interstitial pneumonia. Bondue Benjamin,Leduc Dimitri,Froidure Antoine,Pieters Thierry,Taton Olivier,Heinen Vincent,Alexander Patrick,Hoton Delphine,Dome Florence,Remmelink Myriam Respiratory research BACKGROUND:Although increasing data supports the use of transbronchial lung cryobiopsies (TBLCs) for the diagnosis of diffuse parenchymal lung diseases (DPLDs), its role as an alternative to surgical lung biopsy (SLB) is still under debate. The aim of this study was to assess the benefit of additional SLBs performed in selected patients after TBLCs. METHOD:We conducted a multicentric Belgian prospective trial in which SLBs were performed after TBLCs when the pathological diagnosis was uncertain or if a nonspecific interstitial pneumonia (NSIP) pattern was observed hypothesizing that SLB could provide additional information and that a co-existent UIP pattern could be missed. RESULTS:Eighty-one patients with TBLCs performed for a DPLD were included in the study between April 2015 and December 2019. A specific histological diagnosis was obtained in 52 patients (64%) whereas no pathological diagnosis following TBLCs was obtained in 13 patients (16%) and a pattern suggestive of a NSIP was observed in 16 patients (20%). Fourteen out of these 29 patients had SLBs after TBLCs. SLBs showed a UIP pattern in 11 (79%), a pattern suggestive of a hypersensitivity pneumonitis in two (14%) and a NSIP pattern in one patient (7%). Among the 16 patients with pathological NSIP following TBLCs, six underwent a SLBs showing a UIP in five and confirming a NSIP in one patient only. A retrospective pathological analysis of patients having both procedures showed a lower diagnostic confidence and agreement among pathologists for TBLCs compared to SLBs. Major factors underlying the added value of SLBs were the bigger size of the sample as well as the subpleural localization of the biopsies. CONCLUSIONS:TBLCs are useful in the setting of DPLDs with a good diagnostic yield. However, our study suggests that SLB provides critical additional information in case TBLCs are inconclusive or show a pattern suggestive of a NSIP, questioning the accuracy of TBLC to adequately identify this histological pattern. 10.1186/s12931-020-01487-w
    Morphometrical analysis of transbronchial cryobiopsies. Griff Sergej,Ammenwerth Wim,Schönfeld Nicolas,Bauer Torsten T,Mairinger Thomas,Blum Torsten-Gerriet,Kollmeier Jens,Grüning Wolfram Diagnostic pathology The recent introduction of bronchoscopically recovered cryobiopsy of lung tissue has opened up new possibilities in the diagnosis of neoplastic and non-neoplastic lung diseases in various aspects. Most notably the morphological diagnosis of peripheral lung biopsies promises to achieve a better yield with a high quality of specimens. To better understand this phenomenon, its diagnostic options and perspectives, this study morphometrically compares 15 cryobiopsies and 18 transbronchial forceps biopsies of peripheral lung tissue a priori without considering clinical hit ratio or integration of results in the clinical diagnostic processing. Cryotechnically harvested specimens were significantly larger (mean: 17.1 ± 10.7 mm2 versus 3.8 ± 4.0 mm2) and contained alveolar tissue more often. If present, the alveolar part in cryobiopsies exceeded the one of forceps biopsies. The alveolar tissue of crybiopsy specimens did not show any artefacts. Based on these results cryotechnique seems to open up new perspectives in bronchoscopic diagnosis of lung disease. 10.1186/1746-1596-6-53
    Interstitial lung disease: the diagnostic role of bronchoscopy. Kebbe Jad,Abdo Tony Journal of thoracic disease Interstitial lung diseases (ILDs) form one of the most fascinating fields in pulmonary medicine. They also pose one of the greatest challenges for accurate diagnosis and proper treatment. Even within the recommended and warranted multidisciplinary approach, differentiating between one disease and another may lead to frustration, especially when proper lung tissue is not available for adequate pathological review. A surgical lung biopsy (SLB) might render enough tissue for histopathology, but this could come at the expense of high morbidity and even mortality, as in the case of usual interstitial pneumonia (UIP). Could bronchoscopy and its various techniques offer a safer and higher yield alternative? Since the very late 19th century, efforts have been made to better examine the airways, obtain tissue and treat various conditions. This resulted in the successive emergence of bronchoalveolar lavage (BAL), endobronchial and transbronchial forceps biopsies, until recently when transbronchial cryobiopsy surfaced as a nascent technique with much promise. The use of endobronchial ultrasound revolutionized the diagnosis and staging of lung cancer, while adding to the yield of other conditions such as sarcoidosis. Ongoing research, efforts and studies have continuously scrutinized the roles of various techniques in the approach to ILDs. For example, BAL seems to serve mostly to eliminate infection as an etiology or a complicating factor in the acute worsening of a fibrotic lung disease, while a predominant cellular component might be diagnostic, such as eosinophilia in eosinophilic lung disease, or lymphocytosis in hypersensitivity pneumonitis (HP). On the other hand, endobronchial biopsy's (EBB) role appears limited to sarcoidosis. As for transbronchial biopsy by forceps, the small sample size and related artifact appear to be limiting factors in making an accurate diagnosis. Recently, however, the use of cryotherapy via employing a cryoprobe in obtaining transbronchial lung biopsies is unfolding into a refined interventional method which might transform indefinitely our approach to the pathological diagnosis of the various ILDs. 10.21037/jtd.2017.06.39
    Lung cryobiopsies: a paradigm shift in diagnostic bronchoscopy? Poletti Venerino,Casoni Gian Luca,Gurioli Carlo,Ryu Jay H,Tomassetti Sara Respirology (Carlton, Vic.) In 1963, the first bronchoscopic lung biopsy was performed. Less than 10 years later, the technique of transbronchial lung biopsy using a flexible bronchoscope was introduced into clinical practice, significantly reducing the rate of major complications and the rate of surgical lung biopsies in patients with diffuse parenchymal lung diseases. The diagnostic yield of transbronchial lung biopsy varies among various parenchymal lung diseases. In pulmonary sarcoidosis and lymphangitis carcinomatosa, a diagnosis can be obtained in up to 80% of patients. This method is considered inadequate, however, in identifying more complex histological patterns such as usual interstitial pneumonitis or nonspecific interstitial pneumonitis. Introduction of the 'jumbo forceps' and of a more 'surgically oriented' procedural setting (patients deeply sedated and intubated) allowed larger and more numerous lung specimens to be obtained without a significant increase of complications such as pneumothorax or bronchial bleeding. However, the possibility to obtain enough parenchymal tissue for a morphological diagnosis of complex patterns remained unmet. Recently, the use of cryoprobes has achieved a significant impact on this issue allowing to obtain large quantity of tissue. Recent studies document that with transbronchial cryobiopsies the diagnosis of usual interstitial pneumonitis can be made confidently by pathologists with a good inter-observer agreement. Pneumothorax is the main complication (reported in up to one fourth of cases in some series); bronchial bleeding is easily controlled using Fogarty balloon. Transbronchial cryobiopsy is a promising new technique that may become a valid alternative to surgical lung biopsy in the near feature. 10.1111/resp.12309
    Transbronchial Cryobiopsies. Oh Scott S,Wallace W Dean,Shaikh Faisal,Lynch Joseph P Seminars in respiratory and critical care medicine Transbronchial lung cryobiopsy (TBLCB) is a relatively new and promising technique for the acquisition of larger amounts of higher quality lung tissue for the diagnosis of lung diseases. There is a growing body of literature describing a diagnostic yield comparable to surgical lung biopsy with a favorable safety profile. Due to its advantages TBLCB has garnered significant interest with more institutions beginning to adopt this technique. However, several questions remain including its role in the diagnostic algorithm, indications, and technique. Herein we provide a review of the available literature describing diagnostic yield, complications, and differing techniques as well as a perspective from pathology. 10.1055/s-0038-1676645
    Are Transbronchial Cryobiopsies Ready for Prime Time?: A Systematic Review and Meta-Analysis. Sethi Jaskaran,Ali Muhammad S,Mohananey Divyanshu,Nanchal Rahul,Maldonado Fabien,Musani Ali Journal of bronchology & interventional pulmonology BACKGROUND:There is a lack of consensus regarding the yield and safety of transbronchial cryobiopsies for diagnosing diffuse parenchymal lung diseases (DPLD). The purpose of this study was to perform a systematic review and meta-analysis assessing the diagnostic yield and safety profile of transbronchial cryobiopsies in DPLD. METHODS:A literature search of MEDLINE, EMBASE databases, and Google Scholar was performed in August 2017. The quality of included studies was assessed using Quality Assessment, Data Abstraction and Synthesis-2 tool. Meta-analysis was performed using MedCalc (version 17.2). Inverse variance weighting was used to aggregate diagnostic yield proportions across studies, with the number of subjects in each study representing its weight. Random effects model was used when significant heterogeneity was observed (I>40%). RESULTS:A total of 31 studies were included in the review. Of these, 27 studies with 1443 patients reported data on the performance of cryobiopsies for diagnosing DPLD. The diagnostic yield was 72.9% [95% confidence interval (CI), 67.9%-77.7%]. The pooled mean specimen size obtained by cryobiopsies was 23.4 mm (95% CI, 9.6-37.3 mm). The overall complication rate was 23.1% with bleeding and pneumothoraces being the most commonly reported complications. The incidence of significant bleeding was 14.2% (95% CI, 7.9%-21.9%), whereas pneumothorax was seen in 9.4% (95% CI, 6.7%-12.5%) of patients. Overall reported mortality was 0.3%. CONCLUSION:Our meta-analysis shows that cryobiopsies have a good diagnostic yield but a significant risk for complications. Cryobiopsy outcomes vary markedly among different centers. Further research is needed to standardize the procedure and improve its safety profile. 10.1097/LBR.0000000000000519
    Transbronchial lung biopsy with a flexible cryoprobe: First case report from India. Dhooria Sahajal,Bal Amanjit,Sehgal Inderpaul Singh,Aggarwal Ashutosh Nath,Behera Digambar,Agarwal Ritesh Lung India : official organ of Indian Chest Society Sarcoidosis and tuberculosis are granulomatous disorders that mimic each other both clinically and radiologically. Both can present with fever and pulmonary nodules and often require the performance of transbronchial lung biopsy (TBLB) for diagnosis. In recent studies, the flexible cryoprobe for carrying out TBLB has been found to be useful in the diagnosis of disorders diffusely involving the lung parenchyma. Here, we present the case of a 29-year-old man who presented with fever and cough and was found to have multiple small nodules in both lungs. TBLB with a flexible cryoprobe helped in differentiating between sarcoidosis and tuberculosis. 10.4103/0970-2113.173066
    Ice Capades: Skating Around Current Practice of Cryobiopsy for ILD. Seashore Justin,Nishi Shawn P E Journal of bronchology & interventional pulmonology BACKGROUND:Transbronchial lung cryobiopsy (TBLC) has been proposed as a potentially safer alternative in the diagnosis of interstitial lung disease. The current practice of TBLC is unknown as most published data come from case reports, case series, and a few trials. The authors report the practice patterns of TBLC on the basis of survey responses. METHODS:The authors created an anonymous online survey to assess how proceduralists evaluate patients, perform, and manage complications of TBLC. Surveys were distributed through social media and e-mail distribution lists from the American Association of Bronchology and Interventional Pulmonology and the Society of Advanced Bronchoscopists. Aggregated responses are reported as counts, percentages, and averages. RESULTS:Surveys show significant variation in parameters providers use to assess appropriate patients for procedures, how specific aspects of TBLC are performed, and how complications and results are managed. CONCLUSION:This is the first and largest survey of providers describing the current large variation in the use of cryobiopsy for the evaluation of interstitial lung disease. The standardized practice is essential to understand the true diagnostic accuracy or rate of complications related to TBLC. 10.1097/LBR.0000000000000692
    A New Tool for Transbronchial Cryobiopsies in the Lung: An Experimental Feasibility ex vivo Study. Franke Karl-Josef,Linzenbold Walter,Nuessle Daniela,Enderle Markus,Boesmueller Hans,Nilius Georg,Hetzel Jürgen Respiration; international review of thoracic diseases BACKGROUND:Transbronchial cryobiopsy (TBCB) is a minimally invasive procedure to establish a diagnosis of interstitial lung disease though with the disadvantage that samples have to be extracted together with the bronchoscope. OBJECTIVES:The aim of the present study was to evaluate the feasibility of a new cryoprobe with which biopsy samples can be obtained through the working channel of the flexible bronchoscope. METHODS:The feasibility of obtaining transbronchial specimens with TBCB was tested and the technique was compared to transbronchial forceps biopsy (TBFB) in a prospectively randomized ex vivo animal study using a standard flexible bronchoscopy technique. The rate of successful biopsies and the duration of the sampling procedure were recorded for both methods. Size and quality of the biopsies were histologically evaluated and measured. RESULTS:Biopsy samples could be obtained in 93.3% of TBCB and in 79.0% of TBFB procedures (p = 0.182). Sampling procedure time did not differ in any clinically relevant manner between the two methods. The mean specimen area of TBCB samples was significantly higher compared to that of TBFB samples (8.08 ± 5.80 vs. 2.61 ± 2.14 mm2; p < 0.0001). TBCB specimens showed less artifacts and a significantly higher percentage of alveolar tissue (53.57 vs. 25.42%; p = 0.0285) than TBFB specimens. CONCLUSIONS:It is feasible to retrieve TBCB samples of good quality and size with the new mini cryoprobe through the working channel of the bronchoscope, while the bronchoscope remains within the central airways throughout the whole procedure. Further studies are necessary to evaluate the safety and efficacy in an in vivo setting. 10.1159/000443990
    Bilateral lung disease, extensive and diffuse. Diagnosis of pulmonary alveolar proteinosis by bronchoscopic cryobiopsy. Gando Sebastián,Duré Roberto,Violi Damián,Vazquez Bibiana,Labarca Gonzalo,Fernandez-Bussy Sebastián Respiratory medicine case reports Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the intra-alveolar accumulation of a proteinaceous phospholipid-laden material called surfactant. Clinically, this disease should be suspected with respiratory failure in association with a crazy paving pattern on high-resolution chest computed tomography. We report a 24-year-old gentleman who was referred to us for a history of respiratory failure, treatment with invasive ventilation and tracheostomy. His blood exams and biochemistry were normal. His infectious and rheumatological panel was negative for a secondary disease. A flexible bronchoscopy with a transbronchial biopsy through a CryoProbe was performed. An anatomopathological analysis was periodic acid-Schiff positive for PAP. A CryoProbe is a recently developed diagnostic tool that improves the diagnostic yield in diffuse lung diseases compared to bronchoscopy with transbronchial biopsy. This method should be considered for patients with diffuse lung disease and PAP. 10.1016/j.rmcr.2017.09.010
    Introducing transbronchial cryobiopsies in diagnosing diffuse parenchymal lung diseases in Greece: Implementing training into clinical practice. Samitas Konstantinos,Kolilekas Lykourgos,Vamvakaris Ioannis,Gkogkou Charalampos,Filippousis Petros,Gaga Mina,Zervas Eleftherios PloS one INTRODUCTION:Diffuse parenchymal lung diseases (DPLD) constitute a heterogeneous group of disorders, sometimes requiring surgical lung biopsies (SLB) to obtain a definite diagnosis. Transbronchial cryobiopsy (TBCB) is a new promising interventional bronchoscopic method of obtaining lung tissue that is gaining ground against SLB. METHODS:Fifty consecutive patients with indeterminate DPLD (definite/possible UIP excluded), after expert panel review referral, were retrospectively analyzed from January 2016 to August 2018. Patients underwent TBCB under deep sedation with endotracheal intubation and spontaneous breathing at a single, tertiary-care, reference hospital. RESULTS:A total of 110 TBCBs (2.7 per patient, range 1 to 4) were performed. Frequent complications included mild pneumothorax in 5 patients (10%), requiring only oxygen supplementation, and bleeding in 31 patients (62%) that was mild in 19 patients and moderate in 12 patients. No serious bleeding was observed. There was zero mortality and no serious adverse events. Adequate samples for diagnostic purposes were obtained in 46 patients (92%) and pathologic histologic diagnosis was reached in 40 patients (80%). The most frequent histopathological patterns were organizing pneumonia (OP) (25%) and non-specific interstitial pneumonia (NSIP) (15%). After an expert panel review of all cases a final diagnosis was achieved in 38 patients, corresponding to a diagnostic yield of 76% for TBCB. CONCLUSION:Our single center cohort demonstrates that establishing TBCBs as a new technique is safe and feasible after proper training in specialized centers, resulting in low complication rates and adequate diagnostic yields. 10.1371/journal.pone.0217554
    Safety and Feasibility of Pleural Cryobiopsy Compared to Forceps Biopsy During Semi-rigid Pleuroscopy. Pathak Vikas,Shepherd Ray W,Hussein Ehab,Malhotra Rajiv Lung BACKGROUND:Pleural biopsy is often obtained in patients with undiagnosed exudative pleural effusion during pleuroscopy. Standard forceps have been traditionally used for the biopsy. Cryoprobes are being increasingly used for transbronchial lung biopsy as they obtain larger specimens and have less crush artifact. However, the safety and feasibility of cryoprobe biopsy compared to standard forceps for pleural biopsy has not been fully assessed. OBJECTIVES:The objective of this study was to demonstrate the safety and feasibility of cryoprobe biopsy in the pleural space using semi-rigid pleuroscopy. METHODS:Patients with idiopathic exudative pleural effusions underwent pleuroscopy. The procedure was done in the endoscopy suite with full barrier precautions and moderate sedation. Pleural biopsies were initially taken with a 2.0-mm saw-toothed forceps followed by a 2.4-mm cryoprobe (ERBECRYO, ERBE, US). The freeze time for each biopsy was 3 s. RESULTS:There were a total of ten patients, five males and five females. The mean age was 69 years (SD ± 11 years). The mean number of biopsies taken from the parietal pleura using forceps was 4.5 (SD ± 1.5) vs. 3.7 (SD ± 1.4) using cryoprobe. The mean cumulative tissue volume with forceps biopsy was 80 cu. mm; the mean cumulative tissue volume with cryobiopsy was 320 cu. mm, p = 0.007. The diagnostic yields were similar in both the groups. There was no increased incidence of bleeding, chest wall injury, or pain using cryoprobe in any of the patients. CONCLUSION:The use of cryoprobe for parietal pleural biopsy via semi-rigid pleuroscopy was feasible and safe in this small pilot study. 10.1007/s00408-017-9998-0
    Cryobiopsy in the diagnosis of bronchiolitis: a retrospective analysis of twenty-three consecutive patients. Sirol Aflah Syazatul Syakirin,Piciucchi Sara,Tomassetti Sara,Ravaglia Claudia,Dubini Alessandra,Poletti Venerino Scientific reports Bronchiolitis manifests as a variety of histological features that explain the complex clinical profiles and imaging aspects. In the period between January 2011 and June 2015, patients with a cryobiopsy diagnosis of bronchiolitis were retrospectively retrieved from the database of our institution. Clinical profiles, imaging features and histologic diagnoses were analysed to identify the role of cryobiopsy in the diagnostic process. Twenty-three patients with a multidisciplinary diagnosis of small airway disease were retrieved (14 females, 9 males; age range 31-74 years old; mean age 54.2 years old). The final MDT diagnoses were post-infectious bronchiolitis (n = 5), constrictive bronchiolitis (n = 3), DIPNECH (n = 1), idiopathic follicular bronchiolitis (n = 3), Sjogren's disease (n = 1), GLILD (n = 1), smoking-related interstitial lung disease (n = 6), sarcoid with granulomatous bronchiolar disorder (n = 1), and subacute hypersensitivity pneumonitis (n = 2). Complications reported after the cryobiopsy procedure consisted of two cases of pneumothorax soon after the biopsy (8.7%), which were successfully managed with the insertion of a chest tube. Transbronchial cryobiopsy represents a robust and mini-invasive method in the characterization of small airway diseases, allowing a low percentage of complications and good diagnostic confidence. 10.1038/s41598-020-67938-y
    Bronchoscopic cryobiopsy for the diagnosis of diffuse parenchymal lung disease. Kropski Jonathan A,Pritchett Jason M,Mason Wendi R,Sivarajan Lakshmi,Gleaves Linda A,Johnson Joyce E,Lancaster Lisa H,Lawson William E,Blackwell Timothy S,Steele Mark P,Loyd James E,Rickman Otis B PloS one BACKGROUND:Although in some cases clinical and radiographic features may be sufficient to establish a diagnosis of diffuse parenchymal lung disease (DPLD), surgical lung biopsy is frequently required. Recently a new technique for bronchoscopic lung biopsy has been developed using flexible cryo-probes. In this study we describe our clinical experience using bronchoscopic cryobiopsy for diagnosis of diffuse lung disease. METHODS:A retrospective study of subjects who had undergone bronchoscopic cryobiopsy for evaluation of DPLD at an academic tertiary care center from January 1, 2012 through January 15, 2013 was performed. The procedure was performed using a flexible bronchoscope to acquire biopsies of lung parenchyma. H&E stained biopsies were reviewed by an expert lung pathologist. RESULTS:Twenty-five eligible subjects were identified. With a mean area of 64.2 mm(2), cryobiopsies were larger than that typically encountered with traditional transbronchial forceps biopsy. In 19 of the 25 subjects, a specific diagnosis was obtained. In one additional subject, biopsies demonstrating normal parenchyma were felt sufficient to exclude diffuse lung disease as a cause of dyspnea. The overall diagnostic yield of bronchoscopic cryobiopsy was 80% (20/25). The most frequent diagnosis was usual interstitial pneumonia (UIP) (n = 7). Three of the 25 subjects ultimately required surgical lung biopsy. There were no significant complications. CONCLUSION:In patients with suspected diffuse parenchymal lung disease, bronchoscopic cryobiopsy is a promising and minimally invasive approach to obtain lung tissue with high diagnostic yield. 10.1371/journal.pone.0078674
    Transbronchial Cryobiopsies in the Evaluation of Lung Allografts: Do the Benefits Outweigh the Risks? Roden Anja C,Kern Ryan M,Aubry Marie Christine,Jenkins Sarah M,Yi Eunhee S,Scott John P,Maldonado Fabien Archives of pathology & laboratory medicine CONTEXT:Transbronchial cryobiopsy technique yields larger biopsies with enhanced quality. The benefits and safety of cryobiopsies have not been thoroughly studied in lung allografts. OBJECTIVE:To compare size, quality, reproducibility of interpretation of rejection and complications of cryobiopsies with those of conventional biopsies from lung allografts. DESIGN:All cryobiopsies (March 2014-January 2015) of lung allografts performed at Mayo Clinic, Rochester, and medical records were reviewed. For comparison, conventional biopsies from the same patient or, if unavailable, from a random patient, were selected. Two pathologists blinded to outcome reviewed all biopsies. Specimen volume, number of alveoli, small airways, and pulmonary vessels were counted and statistically compared. RESULTS:Fifty-four biopsies (27 cryobiopsies) from 18 patients (11 men) were reviewed. A median of 3 (range, 2-5) and 10 (range, 6-12) specimens were obtained with cryobiopsies and conventional biopsies, respectively. Cryobiopsies were larger and contained more alveoli (P < .001, both) and small airways (P = .04). Conventional biopsies showed more fresh alveolar hemorrhage (procedural) and crush artifact/atelectasis (P < .001, both). Cryobiopsies contained more pulmonary veins and venules (P < .001). There was no significant difference between the types of biopsies with respect to the reviewers' agreement on grades of rejection. Complications were more frequent in the cryobiopsy group, though the difference was not statistically significant. CONCLUSIONS:Cryobiopsies of lung allografts are larger and have less artifact. However, complications occur and should be considered. Three cryobiopsy specimens appear sufficient for histopathologic evaluation of lung allografts. 10.5858/arpa.2015-0294-OA
    Transbronchial Cryobiopsy: A Cautionary Tale and Opportunities for Improvement. Lentz Robert J,Argento A Christine,Rickman Otis B,Ryu Jay H,Poletti Venerino,Hetzel Juergen,Maldonado Fabien Annals of the American Thoracic Society 10.1513/AnnalsATS.201703-193LE
    Cryoprobe transbronchial lung biopsy with flexible bronchoscope using Arndt endobronchial blocker. Madan Karan,Mittal Saurabh,Hadda Vijay,Mohan Anant Lung India : official organ of Indian Chest Society Cryoprobe transbronchial lung biopsy (TBLB)/transbronchial lung cryobiopsy (TBLC) is increasingly being described as an alternative to surgical lung biopsy and provides larger lung biopsy samples as compared with conventional TBLB in patients with diffuse parenchymal lung diseases. The technique for cryoprobe TBLB procedure has not yet been standardized, and various authors describe different modalities. However, the use of an artificial airway (rigid bronchoscope or endotracheal tube) is preferred for airway protection. In addition, the use of an occlusion balloon provides safety to prevent excessive bleeding. The exclusive use of rigid bronchoscopy may limit the widespread adoption of this diagnostic modality. We describe a method to perform cryoprobe TBLB with exclusive use of a flexible bronchoscope and utilization of Arndt endobronchial blocker as an occlusion balloon. The procedure was performed in two patients under moderate conscious sedation. Adequate lung biopsies were obtained in both the cases without any complications. This modality may allow safe performance of cryoprobe TBLB with a flexible bronchoscope. Herein, we describe the technical and procedural considerations of this modality. 10.4103/lungindia.lungindia_35_18
    Transbronchial Cryobiopsies in Lung Allograft Recipients for Surveillance Purposes: Initial Results. Mohamed Shehab,Mendogni Paolo,Tosi Davide,Carrinola Rosaria,Palleschi Alessandro,Righi Ilaria,Vaira Valentina,Ferrero Stefano,Daffrè Elisa,Bonitta Gianluca,Diotti Cristina,Pieropan Sara,Nosotti Mario,Rosso Lorenzo Transplantation proceedings Transbronchial biopsy (TBB) using standard forceps is the main procedure to establish the presence of lung allograft rejection (AR) after lung transplantation. Few studies report the use of the transbronchial cryobiopsy (TCB) as a scheduled procedure for surveillance purposes in lung allograft, despite this the technique yields larger biopsies. We aimed to analyze the diagnostic yield and potential complications of TCB compared with conventional forceps biopsy for acute rejection surveillance in lung transplantation. In our center, TCBs are performed to monitor lung allografts at 3, 6, and 12 months after transplantation. From March 2018 to September 2019 TCBs were performed in 54 lung transplanted patients for surveillance purposes. Clinical and functional data, complications, and histologic results were collected. We analyzed through a retrospective study our first 75 cases of cryobiopsies for surveillance purposes in lung allograft recipients. The diagnostic rate of AR using TCB was 100% compared with 83% using conventional TBB. Also, diagnostic rate of airway inflammation and chronic rejection was 17% and 21% higher, respectively, for TCB compared with TBB. The overall major complication rate was 9%: 1 pneumothorax case required chest tube drainage and 6 moderate bleedings. Bleeding rate in the scheduled TCB group (8%) seems to be higher if compared with scheduled TBB group (1%). TCB seems to be safe and effective for diagnosis of lung AR compared with transbronchial conventional forceps biopsy. 10.1016/j.transproceed.2020.02.052
    Bronchoscopic lung cryobiopsy: An Indian association for bronchology position statement. Dhooria Sahajal,Agarwal Ritesh,Sehgal Inderpaul Singh,Aggarwal Ashutosh Nath,Goyal Rajiv,Guleria Randeep,Singhal Pratibha,Shah Shirish P,Gupta Krishna B,Koolwal Suresh,Akkaraju Jayachandra,Annapoorni Shankar,Bal Amanjit,Bansal Avdhesh,Behera Digambar,Chhajed Prashant N,Dhamija Amit,Dhar Raja,Garg Mandeep,Gopal Bharat,Hibare Kedar R,James Prince,Jindal Aditya,Jindal Surinder K,Khan Ajmal,Kishore Nevin,Koul Parvaiz A,Kumar Arvind,Kumar Raj,Lall Ajay,Madan Karan,Mandal Amit,Mehta Ravindra M,Mohan Anant,Nangia Vivek,Nath Alok,Nayar Sandeep,Patel Dharmesh,Pattabhiraman Vallandaramam,Raghupati Narasimhan,Sarkar Pralay K,Singh Virendra,Sivaramakrishnan Mahadevan,Srinivasan Arjun,Swarnakar Rajesh,Talwar Deepak,Thangakunam Balamugesh Lung India : official organ of Indian Chest Society Background:Bronchoscopic lung cryobiopsy (BLC) is a novel technique for obtaining lung tissue for the diagnosis of diffuse parenchymal lung diseases. The procedure is performed using several different variations of technique, resulting in an inconsistent diagnostic yield and a variable risk of complications. There is an unmet need for standardization of the technical aspects of BLC. Methodology:This is a position statement framed by a group comprising experts from the fields of pulmonary medicine, thoracic surgery, pathology, and radiology under the aegis of the Indian Association for Bronchology. Sixteen questions on various technical aspects of BLC were framed. A literature search was conducted using PubMed and EMBASE databases. The expert group discussed the available evidence relevant to each question through e-mail and a face-to-face meeting, and arrived at a consensus. Results:The experts agreed that patients should be carefully selected for BLC after weighing the risks and benefits of the procedure. Where appropriate, consideration should be given to perform alternate procedures such as conventional transbronchial biopsy or subject the patient directly to a surgical lung biopsy. The procedure is best performed after placement of an artificial airway under sedation/general anesthesia. Fluoroscopic guidance and occlusion balloon should be utilized for positioning the cryoprobe to reduce the risk of pneumothorax and bleeding, respectively. At least four tissue specimens (with at least two of adequate size, i.e., ≥5 mm) should be obtained during the procedure from different lobes or different segments of a lobe. The histopathological findings of BLC should be interpreted by an experienced pulmonary pathologist. The final diagnosis should be made after a multidisciplinary discussion. Finally, there is a need for structured training for performing BLC. Conclusion:This position statement is an attempt to provide practical recommendations for the performance of BLC in DPLDs. 10.4103/lungindia.lungindia_75_18
    Transbronchial cryobiopsy in the diagnosis of desquamative interstitial pneumonia. Dias C,Mota P,Neves I,Guimarães S,Souto Moura C,Morais A Revista portuguesa de pneumologia 10.1016/j.rppnen.2016.03.006
    Protocolized Thoracic Ultrasonography in Transbronchial Lung Cryobiopsies: A Potential Role as an Exclusion Study for Pneumothorax. Matus Ismael,Raja Haroon Journal of bronchology & interventional pulmonology BACKGROUND:Widespread implementation of transbronchial lung cryobiopsy (TBLCB) in the diagnostic approach to diffuse parenchymal lung disease has prompted a call for standardization of technique to optimize safety and diagnostic yield. Thoracic ultrasound (TUS) is proving effective in detecting postconventional transbronchial biopsy pneumothorax (PTX). However, TUS does not obviate the need for chest radiography (CXR) which quantifies and guides treatment of PTX. To our knowledge, this is the first experience evaluating TUS's reliability to rule-out PTX post-TBLCB in diffuse parenchymal lung disease. METHODS:Retrospective analysis of patients undergoing TBLCB. A standardized pre-TBLCB/post-TBLCB TUS was performed to detect the presence or absence of sliding lung (SL). TUS' findings were then compared with CXR performed at 1 hour after TBLCB. RESULTS:A total of 24 patients' records reviewed. In total, 21 of 24 patients had SL in all lung zones on TUS before and after TBLCB, with a negative CXR for PTX in all 21 patients. The negative predictive value was 100% (95% confidence interval, 84%-100%). Three patients did not have SL in all lung zones on TUS, of which 2 showed the absence of SL in all lung zones on both pre-TBLCB and post-TBLCB TUS, with negative CXR for PTX. 1 of the 3 showed SL in all zones pre-TBLCB and in only 2 zones post-TBLCB. CXR confirmed PTX in this 1 patient. CONCLUSION:Our study demonstrates a 100% negative predictive value for the exclusion of PTX via TUS' verification of SL. The practical value of TUS post-TBLCB may lie in its application as a rule-out study, thereby avoiding CXR. 10.1097/LBR.0000000000000541
    Cavitary lung disease following transbronchial biopsy using cryoadhesion in a patient with diffuse parenchymal lung disease. Pathak Vikas,Zhou Christine,George Ezmin Lung India : official organ of Indian Chest Society Transbronchial lung biopsy using cryoadhesion is a diagnostic technique gaining in popularity. Several studies have been performed on its diagnostic yield and safety profile. However, definitive conclusions are limited due to the heterogeneity of results. The most common complications described in the current literature are pneumothorax and hemorrhage. This case describes a 60-year-old female who developed a cavitary lung lesion shortly after undergoing transbronchial lung cryobiopsy, highlighting the need for further research on the rarer complications that may be associated with this promising procedure. 10.4103/lungindia.lungindia_21_18
    Transbronchial Cryobiopsies for Diagnosing Interstitial Lung Disease: Real-Life Experience from a Tertiary Referral Center for Interstitial Lung Disease. Wälscher Julia,Groß Benjamin,Eberhardt Ralf,Heussel Claus Peter,Eichinger Monika,Warth Arne,Lasitschka Felix,Herth Felix J F,Kreuter Michael Respiration; international review of thoracic diseases BACKGROUND:Transbronchial cryobiopsy (cTBB) may offer an alternative to surgical lung biopsy (SLB) for histopathological diagnosis of interstitial lung diseases (ILDs). However, real-life experience is limited, although case series are increasingly reported. OBJECTIVES:We aimed to evaluate the value of cTBB performed under real-life conditions in a tertiary care center for ILDs. METHODS:Data on all patients undergoing a cTBB for evaluation of suspected ILD between October 2015 and January 2017 were included in this retrospective case series. Procedure details, complication rates, histopathological results, and diagnostic consensus reached by a multidisciplinary team (MDT) discussion were collated and evaluated. RESULTS:A total of 109 patients (mean age 64 years, range 19-85; 66% male, 38% never smokers) referred to our center with features suggestive of ILD underwent cTBB. The mean FVC% predicted was 77% (range 41-131), with a mean DLCO of 51% (range 20-86), and a 6-min walking test (6MWT) of 402 m (range 100-642). On average, 4 samples were taken from each patient (range 1-8), with a mean biopsy diameter of 5 mm (range 2-12). Complications included pneumothorax (11.9%), all treated with chest drain. Moderate bleeding occurred in 28.4% (all resolved without active measures). No acute disease exacerbations and no deaths occurred. A histopathological pattern diagnosis was possible in 80 cases (73.4%), and 26.6% of cases were considered nonspecific. An MDT consensus diagnosis was reached in 83.5% of cases. Subsequent SLB was proposed in 13 cases and performed in 8 cases. CONCLUSIONS:In the real-world setting, cTBB has a meaningful diagnostic value in the context of a MDT approach and may enable histopathological assessment even in patients with more advanced disease unsuitable for SLB. 10.1159/000493428
    Transbronchial cryobiopsy in interstitial lung disease: advantageous costs to benefits ratio. Montero Fernández M Ángeles Archivos de bronconeumologia 10.1016/j.arbres.2015.02.006
    Confocal Laser Endomicroscopy as a Guidance Tool for Transbronchial Lung Cryobiopsies in Interstitial Lung Disorder. Wijmans Lizzy,Bonta Peter I,Rocha-Pinto Rita,de Bruin Daniel M,Brinkman Paul,Jonkers René E,Roelofs Joris J T H,Poletti Venerino,Hetzel Jürgen,Annema Jouke T Respiration; international review of thoracic diseases BACKGROUND:Transbronchial cryobiopsy (TBCB) of the lung parenchyma is a minimally invasive alternative for surgical lung biopsy in interstitial lung disease (ILD) patients. Drawbacks are the nondiagnostic rate and complication risk of pneumothorax and bleeding. Fluoroscopy is the current guidance tool for TBCB, which is limited by 2D imaging and a radiation dose for the patient. Confocal laser endomicroscopy (CLE) is a high-resolution imaging technique that provides immediate feedback during bronchoscopy about the elastin fiber network of peripheral lung areas. Both the visceral pleura and fibrotic lung areas consist of elastin fibers and are therefore potentially detectable with CLE. OBJECTIVES:To investigate whether CLE is capable of (1) distinguishing fibrotic from normal alveolar areas and (2) identifying the pleura. METHODS:In and ex vivo CLE imaging obtained during bronchoscopy was compared with histology of lung biopsies in 14 ILD patients. RESULTS:CLE imaging of the alveolar compartment was feasible in all patients without adverse events. Based on CLE imaging, key characteristics that influence both diagnostic yield (dense fibrotic areas) and complication rate (pleura and subpleural space) were visualized. CONCLUSIONS:CLE seems a promising alternative to fluoroscopy as a guidance tool for TBCB procedures. 10.1159/000493271
    Efficacy and safety of cryobiopsy versus forceps biopsy for interstitial lung diseases and lung tumours: A systematic review and meta-analysis. Ganganah Oormila,Guo Shu Liang,Chiniah Manu,Li Yi Shi Respirology (Carlton, Vic.) Forceps biopsy (FB) is the most commonly used diagnostic tool for lung pathologies. FB is associated with a high diagnostic failure rate. Cryobiopsy (CB) is a novel technique providing a larger specimen size, few artefacts, more alveolar parts and superior diagnostic yield. CB, however, has drawbacks such as higher bleeding and pneumothorax rate. We conducted a meta-analysis to investigate the specimen area, diagnostic rate and bleeding severity in CB versus FB in interstitial lung diseases (ILDs) and lung tumours. A systematic literature search of PUBMED, BIOSIS PREVIEW and OVID databases was conducted using specific search terms. Eligible studies including RCTs and non-RCTs comparing cryobiopsy/cryotransbronchial biopsy (CB/CTBB) and forceps biopsy/forceps transbronchial biopsy (FB/FTBB) for specimen area, diagnostic rate and bleeding rate in ILDs and lung tumours were analysed. Two reviewers independently extracted data and evaluated the quality of the studies. Eight studies involving 916 patients were analysed. Specimen area (mm(2) ) was significantly larger in CB/CTBB than FB/FTBB (standard mean difference = 1.21, 95% confidence interval (0.94, 1.48), P < 0.00001). The diagnostic rate was significantly higher in CB/CTBB than FB/FTBB (Risk ratio 1.36, 95% confidence interval (1.16, 1.59), P = 0.0002). Three studies compared the bleeding severity with only one showing significantly more bleeding in CB. Cryobiopsy/cryotransbronchial shows superiority to FB/FTBB for specimen area and diagnostic rate. CB/CTBB has better efficacy over FB/FTBB. 10.1111/resp.12770
    Use of a molecular classifier to identify usual interstitial pneumonia in conventional transbronchial lung biopsy samples: a prospective validation study. Raghu Ganesh,Flaherty Kevin R,Lederer David J,Lynch David A,Colby Thomas V,Myers Jeffrey L,Groshong Steve D,Larsen Brandon T,Chung Jonathan H,Steele Mark P,Benzaquen Sadia,Calero Karel,Case Amy H,Criner Gerard J,Nathan Steven D,Rai Navdeep S,Ramaswamy Murali,Hagmeyer Lars,Davis J Russell,Gauhar Umair A,Pankratz Daniel G,Choi Yoonha,Huang Jing,Walsh P Sean,Neville Hannah,Lofaro Lori R,Barth Neil M,Kennedy Giulia C,Brown Kevin K,Martinez Fernando J The Lancet. Respiratory medicine BACKGROUND:In the appropriate clinical setting, the diagnosis of idiopathic pulmonary fibrosis (IPF) requires a pattern of usual interstitial pneumonia to be present on high-resolution chest CT (HRCT) or surgical lung biopsy. A molecular usual interstitial pneumonia signature can be identified by a machine learning algorithm in less-invasive transbronchial lung biopsy samples. We report prospective findings for the clinical validity and utility of this molecular test. METHODS:We prospectively recruited 237 patients for this study from those enrolled in the Bronchial Sample Collection for a Novel Genomic Test (BRAVE) study in 29 US and European sites. Patients were undergoing evaluation for interstitial lung disease and had had samples obtained by clinically indicated surgical or transbronchial biopsy or cryobiopsy for pathology. Histopathological diagnoses were made by experienced pathologists. Available HRCT scans were reviewed centrally. Three to five transbronchial lung biopsy samples were collected from all patients specifically for this study, pooled by patient, and extracted for transcriptomic sequencing. After exclusions, diagnostic histopathology and RNA sequence data from 90 patients were used to train a machine learning algorithm (Envisia Genomic Classifier, Veracyte, San Francisco, CA, USA) to identify a usual interstitial pneumonia pattern. The primary study endpoint was validation of the classifier in 49 patients by comparison with diagnostic histopathology. To assess clinical utility, we compared the agreement and confidence level of diagnosis made by central multidisciplinary teams based on anonymised clinical information and radiology results plus either molecular classifier or histopathology results. FINDINGS:The classifier identified usual interstitial pneumonia in transbronchial lung biopsy samples from 49 patients with 88% specificity (95% CI 70-98) and 70% sensitivity (47-87). Among 42 of these patients who had possible or inconsistent usual interstitial pneumonia on HRCT, the classifier showed 81% positive predictive value (95% CI 54-96) for underlying biopsy-proven usual interstitial pneumonia. In the clinical utility analysis, we found 86% agreement (95% CI 78-92) between clinical diagnoses using classifier results and those using histopathology data. Diagnostic confidence was improved by the molecular classifier results compared with histopathology results in 18 with IPF diagnoses (proportion of diagnoses that were confident or provisional with high confidence 89% vs 56%, p=0·0339) and in all 48 patients with non-diagnostic pathology or non-classifiable fibrosis histopathology (63% vs 42%, p=0·0412). INTERPRETATION:The molecular test provided an objective method to aid clinicians and multidisciplinary teams in ascertaining a diagnosis of IPF, particularly for patients without a clear radiological diagnosis, in samples that can be obtained by a less invasive method. Further prospective clinical validation and utility studies are planned. FUNDING:Veracyte. 10.1016/S2213-2600(19)30059-1
    Acute Exacerbation of Interstitial Lung Disease After Cryobiopsy. Tomic Rade,Cortes-Puentes Gustavo A,Murugan Paari,Joo Kim Hyun,Amin Khalid,Dincer H Erhan Journal of bronchology & interventional pulmonology Cryotherapy has been used in treatment of lung cancer for decades. The utility of cryotechnology in diagnosis of lung diseases is emerging and gaining popularity. Cryobiopsy (CB) of the lung, when compared with conventional transbronchial forceps lung biopsy, has proposed to have a higher diagnostic yield in interstitial lung disease by providing larger biopsy specimen and less crush artifact. Acute exacerbation of interstitial lung disease (AEILD) has been well described with surgical lung biopsies and, rarely, with conventional transbronchial forceps biopsy. The incidence of AEILD after CB is not known. Here we are presenting a case of AEILD after CB. 10.1097/LBR.0000000000000369
    Utility of Flexible Bronchoscopic Cryobiopsy for Diagnosis of Diffuse Parenchymal Lung Diseases. Lentz Robert J,Taylor Trevor M,Kropski Jonathan A,Sandler Kim L,Johnson Joyce E,Blackwell Timothy S,Maldonado Fabien,Rickman Otis B Journal of bronchology & interventional pulmonology BACKGROUND:Initial reports of transbronchial cryobiopsy for diffuse parenchymal lung disease (DPLD) suggest the diagnostic yield approaches that of surgical lung biopsy (SLB) with an excellent safety profile. Centers performing cryobiopsy differ significantly in procedure technique; an optimal technique minimizing complications but still capable of diagnosing a wide range of DPLDs has not been established. We evaluated our practice of flexible bronchoscopic cryobiopsy in a primarily outpatient setting for patients who required a tissue diagnosis for DPLD of uncertain etiology. METHODS:Consecutive patients with indeterminate DPLD who underwent bronchoscopic cryobiopsy at a large academic medical center from January 2012 to August 2015 were retrospectively analyzed. Rates of confident histopathologic diagnosis, confident multidisciplinary consensus diagnosis, management change, and complications were determined. RESULTS:One hundred four cases were identified. Confident histopathologic diagnoses were established in 44% (46/104) and confident multidisciplinary consensus diagnoses in 68% (71/104). Usual interstitial pneumonia (19/104) and idiopathic pulmonary fibrosis (22/104) were the most common histopathologic and consensus diagnoses, respectively. Five subjects proceeded to SLB after cryobiopsy which was diagnostic in 3. Results of cryobiopsies changed management in 70% (73/104). Complications occurred in 8 cases with no death. CONCLUSIONS:Cryobiopsy during outpatient flexible bronchoscopy facilitated confident multidisciplinary consensus diagnosis of DPLD in more than two thirds of cases, and appears sufficient to establish the histopathologic diagnosis of usual interstitial pneumonia, with a complication rate that compares favorably to that reported for SLB. 10.1097/LBR.0000000000000401
    Transbronchial cryobiopsy in diffuse parenchymal lung disease. A new star in the horizon. Poletti Venerino,Benzaquen Sadia Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG
    Metastatic pulmonary calcification diagnosed by transbronchial cryobiopsy. Samolski Daniel,Duré Roberto,Bentolila Gonzalo,Castiglioni Teresa Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace Metastatic pulmonary calcification is a rare disease characterized by calcium deposits in the lung. We describe a case where this pathology is observed associated with bone lithic lesions and kidney failure and it was diagnosed with transbronchial cryobiopsy. 10.4081/monaldi.2020.1430
    Comparing Transbronchial Cryobiopsy and Surgical Biopsy in Idiopathic Pulmonary Fibrosis. Quadrelli Silvia,Enghelmayer Juan Ignacio,Otaola Maria,Sobrino Edgardo American journal of respiratory and critical care medicine 10.1164/rccm.201905-1058LE
    Transbronchial Cryobiopsy Leading to Transient Pulmonary Cavitations. Jacobs Blake,Youness Houssein,Kebbe Jad Journal of bronchology & interventional pulmonology 10.1097/LBR.0000000000000597
    Cryobiopsy in the diagnosis of diffuse interstitial lung disease: yield and cost-effectiveness analysis. Hernández-González Fernanda,Lucena Carmen M,Ramírez José,Sánchez Marcelo,Jimenez María José,Xaubet Antoni,Sellares Jacobo,Agustí Carlos Archivos de bronconeumologia BACKGROUND:Assessment of patients with suspected interstitial lung disease (ILD) includes surgical lung biopsy (SLB) when clinical and radiological data are inconclusive. However, cryobiopsy is acquiring an important role in the ILD diagnostic process. The objective of this study was to evaluate the diagnostic yield, safety and economic costs of the systematic use of cryobiopsy in the assessment of patients with suspected ILD. METHODS:This was a retrospective observational study of patients who had undergone transbronchial cryobiopsy for evaluation of ILD from January 2011 to January 2014. The procedures were performed with a video bronchoscope using a cryoprobe for the collection of lung parenchyma specimens, which were analyzed by pathologists. Diagnostic yield, complications and economic costs of this technique were analyzed. RESULTS:Criobiopsy specimens from a total of 33 patients were included. A specific diagnosis was obtained in 26, producing a diagnostic yield of 79%. In 5 patients, SLB was required for a histopathological confirmation of disease, but the procedure could not be performed in 4, due to severe comorbidities. The most frequent complications were pneumothorax (12%) and gradei (9%) or gradeii (21%) bleeding. There were no life-threatening complications. The systematic use of cryobiopsy saved up to €59,846. CONCLUSION:Cryobiopsy is a safe and potentially useful technique in the diagnostic assessment of patients with ILD. Furthermore, the systematic use of cryobiopsy has an important economic impact. 10.1016/j.arbres.2014.09.009
    Increasing Diagnostic Value of Transbronchial Lung Cryobiopsy. Poletti Venerino Respiration; international review of thoracic diseases 10.1159/000445123
    Radial Endobronchial Ultrasound-guided Transbronchial Cryobiopsy. Abdelghani Ramsy,Thakore Sanket,Kaphle Upendra,Lasky Joseph A,Kheir Fayez Journal of bronchology & interventional pulmonology BACKGROUND:Transbronchial lung cryobiopsy (TBLC) is a novel technique that has proved its diagnostic value in various diffuse parenchymal lung diseases (DPLD). However, there is substantial variability among interventional pulmonologists in procedural technique, diagnostic yield, and complication rate. Radial endobronchial ultrasound (R-EBUS) is useful for identification of ground-glass opacity lesions and can help identify target lung parenchyma. We aim to evaluate R-EBUS in TBLC histopathologic diagnosis for patients with DPLD. METHODS:This was a prospective observational study of patients with clinical and radiologic features suggestive of DPLD who underwent TBLC. The R-EBUS probe was initially advanced to the desired lobe under fluoroscopic guidance until reaching 1 cm from the pleura. R-EBUS images were identified looking for either blizzard or mixed blizzard signs. TBLC samples were sent to pathology and microbiology laboratories for diagnostic analysis. Procedural complications were recorded. RESULTS:In total, 40 patients (16 women/24 men) with a mean age of 63 years were included. The mean area of the samples was 36.2 mm (9 to 189 mm) with mean number of samples per procedure of 3.45 (1 to 6). Definitive diagnosis was obtained in 37 patients (92.5%). The most frequent histopathologic patterns were: usual interstitial pneumonia (37.5%), nonspecific interstitial pneumonia (17.5%), and pulmonary infection (7.5%). There were 2 pneumothoraces (5%) and 5 cases of moderate bleeding (12.5%). CONCLUSION:The use of R-EBUS to locate and select target lung biopsy site before TBLC might increase diagnostic yield. Randomized studies comparing TBLC histopathologic diagnosis with and without R-EBUS are needed to ascertain its clinical value. 10.1097/LBR.0000000000000566
    Diagnostic yield and safety of transbronchial cryobiopsy in sarcoidosis. Jacob Maria,Bastos Hélder Novais,Mota Patrícia Caetano,Melo Natália,Cunha Rui,Pereira José Miguel,Guimarães Susana,Souto Moura Conceição,Morais António ERJ open research Introduction:Transbronchial lung cryobiopsy (TBLC) is an endoscopic technique proven to be useful in diagnostic approach to interstitial lung disease (ILD), but its role in sarcoidosis is not fully established. The aim of the present study was to assess the diagnostic yield of TBLC in sarcoidosis and its safety profile. Methods:Retrospective analysis of patients, evaluated in a tertiary hospital ILD outpatient clinic, who underwent TBLC in the diagnostic work-up. TBLC was performed in accordance with the 2018 expert statement from the Cryobiopsy Working Group. Results:32 patients were included (mean±sd age 47.7±12.6 years, 59.4% male) and divided into three groups: highly likely sarcoidosis (n=21), possible sarcoidosis (n=6) and unlikely sarcoidosis (n=5). A mean of 2.8±0.8 TBLCs were performed. The definitive diagnosis was established by TBLC in 20 out of 27 patients with suspected sarcoidosis. Two patients were diagnosed with sarcoidosis by other methods performed afterwards. TBLC leaded to other diagnosis as well, such as fungal infection (n=1), hypersensitivity pneumonitis (n=1) and silicosis (n=3), making the diagnostic yield for suspected sarcoidosis of TBLC of 92.6%. TBLC was also able to show compatible histological features in five patients whom sarcoidosis was not previously considered. The complications reported overall were pneumothorax in five (15.6%) patients and moderate bleeding in one (3.1%) case. Conclusion:In this cohort, TBLC was a safe, reliable and useful procedure in sarcoidosis diagnosis. These results suggest that TBLC can be used successfully in those cases where a definitive diagnosis could not be reached with the usual and less-invasive diagnostic tools. 10.1183/23120541.00203-2019
    Diagnostic yield of transbronchial lung cryobiopsy in interstitial lung diseases. Marçôa R,Linhas R,Apolinário D,Campainha S,Oliveira A,Nogueira C,Loureiro A,Almeida J,Costa F,Wen X,Neves S Revista portuguesa de pneumologia 10.1016/j.rppnen.2017.07.002
    Transbronchial Lung Cryobiopsy: New Options for a New Reality. Torrego Alfonso,Shah Pallav L Respiration; international review of thoracic diseases 10.1159/000444265
    Transbronchial cryobiopsy: a new way to assess lung disease in rheumatic disorders. Sousa-Neves Joana,Mota Patrícia,Melo Natália,Santos-Faria Daniela,Bernardes Miguel,Morais António Acta reumatologica portuguesa
    Diagnostic yield of transbronchial cryobiopsy in non-neoplastic lung disease: a retrospective case series. Griff Sergej,Schönfeld Nicolas,Ammenwerth Wilhelm,Blum Torsten-Gerriet,Grah Christian,Bauer Torsten T,Grüning Wolfram,Mairinger Thomas,Wurps Henrik BMC pulmonary medicine BACKGROUND:Due to the small amount of alveolar tissue in transbronchial biopsy (TBB) by forceps, the diagnosis of diffuse, parenchymal lung diseases (DPLD) is inherently problematic, with an overall low yield. The use of cryotechnique in bronchoscopy, including TBB by cryoprobe, has revealed new opportunities in the endoscopical diagnosis of malignant and non-malignant lung diseases. METHODS:To evaluate TBB by cryotechnique for non-neoplastic lung diseases, we analyzed 52 patients (mean age 63 ± 13 years) with unclear DPLD. These individuals underwent bronchoscopy with TBB by cryoprobe. Thereafter histopathological results were compared with the clinically evaluated diagnosis. RESULTS:No major complications were seen. Mean specimen diameter in the histological biopsies was 6.9 ± 4.4 mm (Range 2 - 22 mm). A correlation between clinical and histopathological diagnoses was found in 79% of cases (41/52). In the case of UIP (usual interstitial pneumonia) pattern, the concordance was 10/15 (66%). CONCLUSION:Based on these results TBB by cryotechnique would appear to be a safe and useful method that reveals new perspectives for the endoscopical diagnosis of DPLD. 10.1186/1471-2466-14-171
    Bronchial Laceration as a Complication of Transbronchial Lung Cryobiopsy. Machado Daniela,Vaz Daniel,Neves Sofia,Campainha Sérgio Archivos de bronconeumologia 10.1016/j.arbres.2018.01.027
    Transbronchial Lung Cryobiopsy: A Meticulous Technique. Dhillon Sarbroop S,Harryanto Hilman,Randhawa Sharan,Rosell Antoni,Salamonsen Matthew Journal of bronchology & interventional pulmonology 10.1097/LBR.0000000000000660
    Safety and diagnostic efficacy of cone beam computed tomography-guided transbronchial cryobiopsy for interstitial lung disease: a cohort study. Zhou Guowu,Ren Yanhong,Li Jun,Yang Ting,Su Nan,Zhao Ling,Wang Dan,Li Ying,Tian Zheng,Liu Ruihong,Dai Huaping,Wang Chen The European respiratory journal 10.1183/13993003.00724-2020
    Transbronchial lung cryobiopsy in the diagnosis of fibrotic interstitial lung diseases. Casoni Gian Luca,Tomassetti Sara,Cavazza Alberto,Colby Thomas V,Dubini Alessandra,Ryu Jay H,Carretta Elisa,Tantalocco Paola,Piciucchi Sara,Ravaglia Claudia,Gurioli Christian,Romagnoli Micaela,Gurioli Carlo,Chilosi Marco,Poletti Venerino PloS one BACKGROUND:Histology is a key element for the multidisciplinary diagnosis of fibrotic diffuse parenchymal lung diseases (f-DPLD) when the clinical-radiological picture is nondiagnostic. Transbronchial lung cryobiopsy (TBLC) have been shown to be useful for obtaining large and well-preserved biopsies of lung parenchyma, but experience with TBLC in f-DPLD is limited. OBJECTIVES:To evaluate safety, feasibility and diagnostic yield of TBLC in f-DPLD. METHOD:Prospective study of 69 cases of TBLC using flexible cryoprobe in the clinical-radiological setting of f-DPLD with nondiagnostic high resolution computed tomography (HRCT) features. RESULTS: SAFETY:pneumothorax occurred in 19 patients (28%). One patient (1.4%) died of acute exacerbation. Feasibility: adequate cryobiopsies were obtained in 68 cases (99%). The median size of cryobiopsies was 43.11 mm(2) (range, 11.94-76.25). Diagnostic yield: among adequate TBLC the pathologists were confident ("high confidence") that histopathologic criteria sufficient to define a specific pattern in 52 patients (76%), including 36 of 47 with UIP (77%) and 9 nonspecific interstitial pneumonia (6 fibrosing and 3 cellular), 2 desquamative interstitial pneumonia/respiratory bronchiolitis-interstitial lung disease, 1 organizing pneumonia, 1 eosinophilic pneumonia, 1 diffuse alveolar damage, 1 hypersensitivity pneumonitis and 1 follicular bronchiolitis. In 11 diagnoses of UIP the pathologists were less confident ("low confidence"). Agreement between pathologists in the detection of UIP was very good with a Kappa coefficient of 0.83 (95% CI, 0.69-0.97). Using the current consensus guidelines for clinical-radiologic-pathologic correlation 32% (20/63) of cases were classified as Idiopathic Pulmonary Fibrosis (IPF), 30% (19/63) as possible IPF, 25% (16/63) as other f-DPLDs and 13% (8/63) were unclassifiable. CONCLUSIONS:TBLC in the diagnosis of f-DPLD appears safe and feasible. TBLC has a good diagnostic yield in the clinical-radiological setting of f-DPLD without diagnostic HRCT features of usual interstitial pneumonia. Future studies should consider TBLC as a potential alternative to SLBx in f-DPLD. 10.1371/journal.pone.0086716
    Acute Exacerbation and Progression of Interstitial Lung Disease After Transbronchial Lung Cryobiopsy. Kodati Rakesh,Sehgal Inderpaul S,Prasad Kuruswamy T,Bal Amanjit,Agarwal Ritesh,Dhooria Sahajal Journal of bronchology & interventional pulmonology 10.1097/LBR.0000000000000612
    Evaluation of Efficacy of a New Cryoprobe for Transbronchial Cryobiopsy: A Randomized, Controlled in vivo Animal Study. Hetzel Jürgen,Linzenbold Walter,Boesmueller Hans,Enderle Markus,Poletti Venerino Respiration; international review of thoracic diseases BACKGROUND:Forceps biopsy (FB) is still the most popular procedure for the bronchoscopic sampling of lung tissue. However, it has limitations like inadequate sample size and crush artifacts. Cryobiopsy (CB) has been introduced to obtain bronchoscopic biopsies with improved diagnostic yield compared to FB. Limitations of CB are the need to retract the cryoprobe en bloc with bronchoscope because samples are larger than the working channel and the variations of the freezing power of the reusable CB (rCB). Therefore, 3 new disposable cryoprobes (dCB) have been developed with different outer diameters: 1.1 mm (CB11-S) that can be retracted through the working channel of the bronchoscope, 1.7 mm (CB17) and 2.4 mm (CB24n), respectively. OBJECTIVES:The aim was to evaluate the new cryoprobes with regard to feasibility, specimen area, specimen quality and complications. METHODS:We compared biopsy samples of the new probes with those obtained by FB and by rCB in an in vivo (porcine) model. A flexible bronchoscope was used to perform biopsy at 4 different locations at the upper and lower lobes of the right and left lung, respectively. The biopsies were taken under fluoroscopic control. The biopsy tool and activation times were allocated randomly. Altogether 204 biopsy procedures were performed. RESULTS:The sample quality of the dCB was superior to that of FB (all p < 0.05) and not significantly different to the rCB sample quality. Mean specimen sample area of all CB was significantly larger compared to FB (p < 0.05). The sample area of the small cryoprobe (CB11-S) was significantly smaller compared to the other CB probes (p < 0.05). No severe bleedings occurred. Pneumothoraces were detected in 3 of the 7 pigs. CONCLUSION:We conclude that CB with the new single-use instruments are feasible and represent a viable option to improve the diagnostic accuracy of histopathological evaluation compared to FB. 10.1159/000506017
    Transbronchial Lung Cryobiopsy With 2 Bronchoscopes: nec novum nec magna. Dhooria Sahajal,Sehgal Inderpaul S,Prasad Kuruswamy T,Agarwal Ritesh Journal of bronchology & interventional pulmonology 10.1097/LBR.0000000000000419
    A Single US Center Experience of Transbronchial Lung Cryobiopsy for Diagnosing Interstitial Lung Disease With a 2-Scope Technique. Sriprasart Thitiwat,Aragaki Alejandro,Baughman Robert,Wikenheiser-Brokamp Kathryn,Khanna Gaurav,Tanase Daniel,Kirschner Michelle,Benzaquen Sadia Journal of bronchology & interventional pulmonology BACKGROUND:Transbronchial lung cryobiopsy (TBLC) has been used to establish the diagnosis of interstitial lung disease (ILD) in recent years. The technique and diagnostic yield vary among institutions. We report a new 2-scope technique and the results of TBLC in our institution. METHODS:This is a retrospective chart review of patients who underwent TBLC for evaluation of ILD. Bronchoscopy with TBLC was performed by a board-certified interventional pulmonologist with a 2-scope technique under general anesthesia. RESULTS:A total of 74 patients underwent TBLC with a 2-scope technique. Their mean age was 54±14 years. The mean tissue surface area was 63.54±6.76 mm. The average anesthesia time was 80.66 minutes. The diagnostic yield was 87.84%. The most common diagnosis was sarcoidosis pneumothorax, which occurred in 5 cases (7%). There was 1 case with bronchoscopic-related respiratory failure associated with significant bleeding. Death occurred in 3 cases (4%), which is comparable to recent mortality data for "elective" surgical lung biopsy for ILD (1.7% to 4.2%). CONCLUSION:TBLC with a 2-scope technique could be an alternative method for diagnosing various types of ILD in patients unfit for surgical lung biopsy. Further prospective studies should clarify its role in the diagnostic armamentarium for undiagnosed ILDs. 10.1097/LBR.0000000000000366
    Transbronchial cryobiopsy in interstitial lung disease: experience in 106 cases - how to do it. Bango-Álvarez Antonio,Ariza-Prota Miguel,Torres-Rivas Hector,Fernández-Fernández Luis,Prieto Amador,Sánchez Inmaculada,Gil Maria,Pando-Sandoval Ana ERJ open research Transbronchial biopsy using forceps (TBB) is the first diagnostic technique performed on patients with interstitial lung disease (ILD). However, the small size of the samples and the presence of artefacts in the tissue obtained make the yield variable. Our objectives were 1) to attempt to reproduce transbronchial cryobiopsy under the same conditions with which we performed conventional TBB, that is, in the bronchoscopy unit without intubating the patient and without fluoroscopy or general anaesthesia; 2) to describe the method used for its execution; and 3) to analyse the diagnostic yield and its complications. We carried out a prospective study that included 106 patients with clinical and radiological features suggestive of ILD who underwent cryo-transbronchial lung biopsy (cryo-TBB) under moderate sedation without endotracheal intubation, general anaesthesia or use of fluoroscopy. We performed the procedure using two flexible bronchoscopes connected to two video processors, which we alternated until obtaining the number of desired samples. A definitive diagnosis was obtained in 91 patients (86%). As for complications, there were five pneumothoraces (4.7%) and in no case was there severe haemorrhage or exacerbation of the underlying interstitial disease. Cryo-TBB following our method is a minimally invasive, rapid, safe and economic technique that can be performed in a bronchoscopy suite under moderate sedation without the need for intubating the patient or using fluoroscopy and without requiring general anaesthesia. 10.1183/23120541.00148-2016
    Usefulness of an angioplasty balloon as selective bronchial blockade device after transbronchial cryobiopsy. Echevarria-Uraga José Javier,Pérez-Izquierdo Julio,García-Garai Nerea,Gómez-Jiménez Estíbaliz,Aramburu-Ojembarrena Amaia,Tena-Tudanca Luis,Miguélez-Vidales José L,Capelastegui-Saiz Alberto Respirology (Carlton, Vic.) BACKGROUND AND OBJECTIVE:Transbronchial cryobiopsy (TBCB) is a technique in which frozen samples of lung are obtained using a probe inserted through a bronchoscope. We performed a retrospective study to assess the performance of the TBCB procedure complemented by segmental bronchial blockade using an angioplasty balloon, in terms of diagnostic yield and safety in diffuse parenchymal lung disease (DPLD). METHODS:Data from 100 patients with suspected DPLD (clinical and radiological findings), who underwent TBCB in our institution to establish a definitive diagnosis, were reviewed. In our institution, TBCB is monitored with fluoroscopy and performed under general anaesthesia by a multidisciplinary team (an anaesthesiologist, a pulmonologist and an interventional radiologist). In each patient, four samples were collected using a 2.4-mm distal diameter cryoprobe. To control bleeding, the biopsied segmental bronchus was blocked with a 6-mm diameter angioplasty balloon, inserted over a 0.035-inch angled hydrophilic guidewire. After the cryoextraction, the balloon was inflated for 3 min intervals until bleeding stopped. RESULTS:Overall, 98% of samples had diagnostic value. In 85% of cases, DPLD was confirmed, while in 7%, cancer was diagnosed. Complications were observed in 16% of the patients: 13 patients developed moderate haemorrhage, and 3 developed pneumothorax. CONCLUSION:Transbronchial cryobiopsy had a high diagnostic yield for DPLD. Performing the procedure under fluoroscopy guidance and using angioplasty balloon for selective bronchial blockade achieved a low rate of iatrogenic complications directly associated with the technique. 10.1111/resp.12827
    Supraglottic Airway Device for Transbronchial Lung Cryobiopsy. Gelzinis Theresa A Journal of cardiothoracic and vascular anesthesia 10.1053/j.jvca.2017.03.021
    Validation of transbronchial cryobiopsy in interstitial lung disease - interim analysis of a prospective trial and critical review of the literature. Hagmeyer Lars,Theegarten Dirk,Treml Marcel,Priegnitz Christina,Randerath Winfried Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG BACKGROUND:Transbronchial Cryobiopsy (Cryo-TBB) represents a new approach for sampling lung tissue in interstitial lung disease (ILD). OBJECTIVES:Comparing the reliability of Cryo-TBB results and the procedure's complication rates with the procedure of surgical lung biopsy (SLB). METHODS:ILD subjects with the need of lung tissue sampling are analyzed in this prospective trial. To determine the relevance of procedure-related complications the pooled data from the ongoing and previous Cryo-TBB studies were compared with pooled data from previous SLB studies in an interim analysis. In our own cohort we analyzed how often Cryo-TBB results lead to a definite diagnosis without the need for a SLB. In subjects who underwent both procedures it was determined how often SLB confirmed Cryo-TBB findings. RESULTS:Analyzing the pooled data of the ongoing study (19 subjects) and our own retrospective study (32 subjects), in 38/51 subjects (75%) SLB was deemed to be unnecessary following Cryo-TBB. In 12/13 subjects an SLB was performed confirming Cryo-TBB results in 92%. 30 day-mortality was 1.9%, bleeding occurred in 78%, pneumothorax in 22%. 2 subjects showed a myocardial infarction. Complication rates are comparable to previous Cryo-TBB studies. Analysis of the pooled data from the literature showed an overall 30-day mortality of 0.7% for Cryo-TBB and 3.3% for SLB. CONCLUSIONS:Cryo-TBB may be a reliable diagnostic tool in ILD, dispensing the need for a SLB in most cases. Severe complications may occur less frequently than in SLB. Modifications of the procedure may lead to further risk reduction.
    How might transbronchial cryobiopsy improve diagnosis and treatment of diffuse parenchymal lung disease patients? Poletti Venerino,Ravaglia Claudia,Dubini Alessandra,Piciucchi Sara,Rossi Giulio,Kronborg-White Sissel,Tomassetti Sara Expert review of respiratory medicine 10.1080/17476348.2017.1395283
    Learning curve for transbronchial lung cryobiopsy in diffuse lung disease. Almeida L M,Lima B,Mota P C,Melo N,Magalhães A,Pereira J M,Moura C S,Guimarães S,Morais A Revista portuguesa de pneumologia INTRODUCTION:Transbronchial lung cryobiopsy (TBLC) is increasingly used in the diagnosis of diffuse lung disease (DLD), but no data have yet been published on the learning curve associated with this technique. AIM:To evaluate diagnostic yield, lung tissue sample length and area, and procedure-related complications in a cohort of TBLC procedures to define the learning curve and threshold for proficiency. METHODS:Retrospective analysis of the first 100 TBLCs performed in different segments of the same lobe in patients with suspected DLD. We compared diagnostic yield, sample length and area, and complications between consecutive groups of patients. RESULTS:The overall diagnostic yield for TBLC was 82%. Median sample length was 5.4mm (IQR, 5-6) and median area was 19.5mm (IQR, 13.3-25). Pneumothorax was the most common complication (18%). On comparing the two groups of 50 consecutive patients, a significant difference was found for diagnostic yield (74% vs 90%; p=0.04), sample length (5.0mm [2.5-16] vs 6.0mm [4-12;] p<0.01) and area (17.5mm [6-42] vs 21.5mm [10-49]; p<0.01). Logarithm regression was applied to median diagnostic yield and sample length and area for groups of 10 consecutive patients to define the learning curve, which plateaued after approximately 70 procedures. CONCLUSIONS:Our findings suggest that proficiency in TBLC is achieved at approximately the 70th procedure; however they need to be validated in more series and cohorts. 10.1016/j.rppnen.2017.09.005
    Cryobiopsy versus open lung biopsy in the diagnosis of interstitial lung disease (COLDICE): protocol of a multicentre study. Troy Lauren K,Grainge Christopher,Corte Tamera,Williamson Jonathan P,Vallely Michael P,Cooper Wendy,Mahar Annabelle M,Lai Simon,Mulyadi Ellie,Torzillo Paul J,Salamonsen Matthew,Don Garrick,Myers Jeffrey,Raghu Ganesh,Lau Edmund M T, BMJ open respiratory research Introduction:Transbronchial lung cryobiopsy (TBLC) is a novel, minimally invasive technique for obtaining lung tissue for histopathological assessment in interstitial lung disease (ILD). Despite its increasing popularity, the diagnostic accuracy of TBLC is not yet known. The COLDICE Study (Cryobiopsy versus Open Lung biopsy in the Diagnosis of Interstitial lung disease allianCE) aims to evaluate the agreement between TBLC and surgical lung biopsy sampled concurrently from the same patients, for both histopathological and multidisciplinary discussion (MDD) diagnoses. Methods and analysis:This comparative, multicentre, prospective trial is enrolling patients with ILD requiring surgical lung biopsy to aid with their diagnosis. Participants are consented for both video-assisted thoracoscopic surgical (VATS) biopsy and TBLC within the same anaesthetic episode. Specimens will be blindly assessed by three expert pathologists both individually and by consensus. Each tissue sample will then be considered in conjunction with clinical and radiological data, within a centralised MDD. Each patient will be presented twice in random order, once with TBLC data and once with VATS data. Meeting participants will be blinded to the method of tissue sampling. The accuracy of TBLC will be assessed by agreement with VATS at (1) histopathological analysis and (2) MDD diagnosis. Data will be collected on interobserver agreement between pathologists, interobserver agreement between MDD participants, and detailed clinical and procedural characteristics. Ethics and dissemination:The study is being conducted in accordance with the International Conference on Harmonisation Guideline for Good Clinical Practice and Australian legislation for the ethical conduct of research. Trial registration number:ACTRN12615000718549. 10.1136/bmjresp-2019-000443
    Transbronchial lung cryobiopsy may be of value for nonresolving acute respiratory distress syndrome: case series and systematic literature review. Zhou Guowu,Feng Yingying,Wang Shiyao,Zhang Yi,Tian Ye,Wu Xiaojing,Zhao Ling,Wang Dan,Li Ying,Tian Zheng,Zhan Qingyuan BMC pulmonary medicine BACKGROUND:Identification of pathologic features is helpful for the management of nonresolving acute respiratory distress syndrome (ARDS). Transbronchial lung cryobiopsy (TBLC) is a novel biopsy technique that may have comparable utility to surgical biopsy. The aim of this study was to assess the value of TBLC in patients with nonresolving ARDS. METHODS:All patients with nonresolving ARDS who underwent TBLC from January 2019 to August 2019 in a tertiary medical ICU were included. In addition, a literature search of TBLC for ARDS was performed by searching PubMed, EMBASE, ATS/ERS/APSR meeting abstracts, ClinicalTrials.gov , and Google Scholar. Data on complications, histologic diagnosis, management changes, and outcomes were analysed. RESULTS:Five patients (three women and two men) underwent TBLC. None of the patients developed pneumothorax, although two patients developed massive bleeding, which was controlled by continuous occlusion using bronchial blockers. There were no procedure-related deaths. Diffuse alveolar damage (DAD) and alternative histologic patterns were found in two and three patients, respectively, resulting in management changes in all cases. The literature search yielded four studies, which together with the present study comprised data from 25 cases in which TBLC was used in nonresolving ARDS. The summary diagnostic yield was 92% (23/25). Only 44% (11/25) of cases were proven to be DAD. TBLC contributed to management changes in 80% of patients (20/25). Procedure-related complications consisted of pneumothorax (16%, 4/25), significant bleeding (12%, 3/25), and persistent air leaks (8%, 2/25). There were no procedure-related deaths. The follow-up survival rate was 61.9% (13/21). CONCLUSIONS:The complications of TBLC in selected patients with nonresolving ARDS may be acceptable. The procedure may have a high diagnostic yield and can lead to a re-evaluation of the diagnosis as well as changes in patient management. Further investigations with larger sample sizes are required. 10.1186/s12890-020-01203-w
    Pleural Emphysema after Transbronchial Lung Cryobiopsy. Asaoka Masato,Baba Tomohisa,Ogura Takashi Internal medicine (Tokyo, Japan) 10.2169/internalmedicine.4698-20
    Transbronchial cryobiopsy in diffuse parenchymal lung diseases. Poletti Venerino,Ravaglia Claudia,Tomassetti Sara Current opinion in pulmonary medicine PURPOSE OF REVIEW:The diagnostic yield of conventional transbronchial lung biopsy varies among various parenchymal lung diseases: in pulmonary sarcoidosis and lymphangitis carcinomatosa, a diagnosis can be obtained in up to 80% of patients; this method is considered inadequate, however, in identifying more complex histological patterns such as usual interstitial pneumonitis or nonspecific interstitial pneumonitis, mainly because the specimens are tiny and the interpretation is confounded by crush artifacts. Recently, the use of cryoprobes has achieved a significant impact on this issue. This review is about this promising application of cryobiopsy in the diagnostic process of diffuse parenchymal lung diseases. RECENT FINDINGS:Recent studies document that with transbronchial cryobiopsies, the diagnosis of usual interstitial pneumonitis can be made confidently by pathologists with a good interobserver agreement. Pneumothorax is the main complication (reported in up to one-quarter of cases in some series); bronchial bleeding is usually controlled using Fogarty balloon. SUMMARY:Transbronchial cryobiopsy is a promising new technique that may become a valid alternative to surgical lung biopsy in the near feature. 10.1097/MCP.0000000000000272
    Diagnostic yield of transbronchial cryobiopsy in interstitial lung disease: a randomized trial. Pajares Virginia,Puzo Carmen,Castillo Diego,Lerma Enrique,Montero M Angeles,Ramos-Barbón David,Amor-Carro Oscar,Gil de Bernabé Angels,Franquet Tomás,Plaza Vicente,Hetzel Jürgen,Sanchis Joaquin,Torrego Alfons Respirology (Carlton, Vic.) BACKGROUND AND OBJECTIVE:Transbronchial lung biopsy (TBLB) is required for evaluation in selected patients with interstitial lung disease (ILD). The diagnostic yield of histopathologic assessment is variable and is influenced by factors such as the size of samples and the presence of crush artefacts left by conventional biopsy forceps. We compared the diagnostic yield and safety of TBLB with cryoprobe sampling versus conventional forceps sampling. METHODS:This randomized clinical trial analysed data for 77 patients undergoing TBLB for evaluation of ILD; patients were assigned to either a conventional-forceps group or a cryoprobe group. Two pathologists assessed the tissue samples and agreed on histopathologic diagnoses. We also compared the duration of procedures, complications and sample-quality variables. RESULTS:The most frequent diagnosis observed in the cryoprobe group was non-specific interstitial pneumonia. Histopathologic diagnoses were identified in more cases in the cryoprobe group (74.4%) than in the conventional-forceps group (34.1%) (P < 0.001), and the diagnostic yield was higher in the cryoprobe group (51.3% vs 29.1% in the conventional forceps group; P = 0.038). A larger mean area of tissue was harvested by cryoprobe (14.7 ± 11 mm(2) ) than by conventional forceps (3.3 ± 4.1 mm(2)) (P < 0.001). More grade 2 bleeding (not statistically significant) occurred in the cryoprobe group (56.4%) than in the conventional-forceps group (34.2%). No differences in other complications were observed. CONCLUSIONS:TBLB by cryoprobe is safe and potentially useful in the diagnosis of ILD. Larger multisite randomized trials are required to confirm the potential benefits of this procedure. Clinical trial registration at ClinicalTrials.gov: NCT01064609. 10.1111/resp.12322
    Report Standardization in Transbronchial Lung Cryobiopsy. Ravaglia Claudia,Rossi Giulio,Tomassetti Sara,Dubini Alessandra,Piciucchi Sara,Chilosi Marco,Cavazza Alberto,Bendstrup Elisabeth,Kronborg-White Sissel Brix,Folkersen Birgitte,Colella Sara,Madsen Line Bille,Poletti Venerino Archives of pathology & laboratory medicine 10.5858/arpa.2018-0438-LE
    Transbronchial Cryobiopsy in Diffuse Parenchymal Lung Disease: Retrospective Analysis of 74 Cases. Ussavarungsi Kamonpun,Kern Ryan M,Roden Anja C,Ryu Jay H,Edell Eric S Chest BACKGROUND:Diagnostic evaluation of patients with diffuse parenchymal lung disease (DPLD) is best achieved by a multidisciplinary team correlating clinical, radiological, and pathologic features. Surgical lung biopsy remains the gold standard for histopathologic diagnosis of idiopathic interstitial pneumonias. Emerging data suggest an increasing role for transbronchial cryobiopsy (TBC) in DPLD evaluation. We describe our experience with TBC in patients with DPLD. METHODS:We retrospectively reviewed medical records of patients with radiographic features of DPLD who underwent TBC at Mayo Clinic in Rochester, Minnesota from June 2013 to September 2015. RESULTS:Seventy-four patients (33 women [45%]) with a mean age of 63 years (SD, 13.8) were included. The mean maximal diameter of the samples was 9.2 mm (range, 2-20 mm [SD, 3.9]). The median number of samples per procedure was three (range, one to seven). Diagnostic yield was 51% (38 of 74 specimens). The most frequent histopathologic patterns were granulomatous inflammation (12 patients) and organizing pneumonia (OP) (11 patients), resulting in the final diagnoses of hypersensitivity pneumonitis (six patients), cryptogenic OP (six patients), connective tissue disease-associated OP (three patients), drug toxicity (three patients), infection-related OP (two patients), sarcoidosis (two patients), and aspiration (one patient). Other histopathologic patterns included respiratory bronchiolitis (three patients), acute fibrinous and organizing pneumonia (two patients), desquamative interstitial pneumonia (1 patient), diffuse alveolar damage (one patient), pulmonary alveolar proteinosis (one patient), amyloidosis (one patient), eosinophilic pneumonia (one patient), necrotizing vasculitis (one patient), bronchiolitis with food particles (one patient), and malignancy (three patients). Pneumothorax developed in one patient (1.4%), and bleeding occurred in 16 patients (22%). CONCLUSIONS:Our single-center cohort demonstrated a 51% diagnostic yield from TBC; the rates of pneumothorax and bleeding were 1.4% and 22%, respectively. The optimal use of TBC needs to be determined. 10.1016/j.chest.2016.09.002
    Transbronchial cryobiopsy for diffuse parenchymal lung disease: a state-of-the-art review of procedural techniques, current evidence, and future challenges. Lentz Robert J,Argento A Christine,Colby Thomas V,Rickman Otis B,Maldonado Fabien Journal of thoracic disease Transbronchial lung biopsy with a cryoprobe, or cryobiopsy, is a promising new bronchoscopic biopsy technique capable of obtaining larger and better-preserved samples than previously possible using traditional biopsy forceps. Over two dozen case series and several small randomized trials are now available describing experiences with this technique, largely for the diagnosis of diffuse parenchymal lung disease (DPLD), in which the reported diagnostic yield is typically 70% to 80%. Cryobiopsy technique varies widely between centers and this predominantly single center-based retrospective literature heterogeneously defines diagnostic yield and complications, limiting the degree to which this technique can be compared between centers or to surgical lung biopsy (SLB). This review explores the broad range of cryobiopsy techniques currently in use, their rationale, the current state of the literature, and suggestions for the direction of future study into this promising but unproven procedure. 10.21037/jtd.2017.06.96
    Role of Transbronchial Cryobiopsy in Interstitial Lung Diseases: An Ongoing Tale. Wand Ori,Unterman Avraham,Shochet Gali Epstein,Shitrit David American journal of respiratory and critical care medicine 10.1164/rccm.201908-1559LE
    Reply to Wand : Role of Transbronchial Cryobiopsy in Interstitial Lung Diseases: An Ongoing Tale. Bourdin Arnaud,Suehs Carey M,Colby Thomas V,Vachier Isabelle,Molinari Nicolas,Romagnoli Micaela American journal of respiratory and critical care medicine 10.1164/rccm.201909-1736LE
    Transbronchial cryobiopsy validity in diagnosing diffuse parenchymal lung diseases in Egyptian population. Shafiek Hanaa,Elbialy Shaimaa,El Achy Samar Nabil,Gad Ahmed Youssef Shaaban Journal of multidisciplinary healthcare Objectives:We aimed to evaluate the efficacy, safety, and diagnostic utility of transbronchial cryobiopsy (TBCB) in diagnosing diffuse parenchymal lung diseases (DPLDs) in an Egyptian population and to identify common DPLD pathologies among them. Methods:This prospective interventional study enrolled 25 Egyptian patients presenting to the Main Alexandria University Hospital who had clinical and radiological features of DPLD, but insufficient elements to achieve definite features of usual interstitial pneumonia on chest high-resolution computed tomography. Twelve patients were subjected to TBCB and 13 to forceps transbronchial lung biopsy (TBLB). Results:The diagnostic yield was significantly higher among the TBCB group (83.3%), and increased to 100% with clinicopathological correlation vs the TBLB group (38.5%, =0.041). Granulomatous diseases (24%, either sarcoidosis or hypersensitivity pneumonitis) were the commonest pathology, followed by malignancy (12%) in both groups. TBCB sizes were 2.5-5 mm vs 1-3 mm in TBLB (<0.001), with preserved tissue architecture (91.7% vs 38.5%, respectively; =0.011). Only 8.3% were complicated by insignificant bleeding grade 2 after TBCB, but no pneumothorax was detected. Conclusion:TBCB is a safe, tolerable procedure with high diagnostic yield for evaluating DPLD with indefinite usual interstitial pneumonia pattern on high-resolution computed tomography. 10.2147/JMDH.S208824
    Transbronchial lung cryobiopsy in ILD: the data we've been waiting for. Ryerson Christopher J,Johannson Kerri A The Lancet. Respiratory medicine 10.1016/S2213-2600(19)30344-3
    Transbronchial cryobiopsy for diffuse parenchymal lung disease: 30- and 90-day mortality. Pannu Jasleen,Roller Lance J,Maldonado Fabien,Lentz Robert J,Chen Heidi,Rickman Otis B The European respiratory journal 10.1183/13993003.00337-2019
    Poor Concordance between Sequential Transbronchial Lung Cryobiopsy and Surgical Lung Biopsy in the Diagnosis of Diffuse Interstitial Lung Diseases. Romagnoli Micaela,Colby Thomas V,Berthet Jean-Philippe,Gamez Anne Sophie,Mallet Jean-Pierre,Serre Isabelle,Cancellieri Alessandra,Cavazza Alberto,Solovei Laurence,Dell'Amore Andrea,Dolci Giampiero,Guerrieri Aldo,Reynaud Paul,Bommart Sébastien,Zompatori Maurizio,Dalpiaz Giorgia,Nava Stefano,Trisolini Rocco,Suehs Carey M,Vachier Isabelle,Molinari Nicolas,Bourdin Arnaud American journal of respiratory and critical care medicine The diagnostic concordance between transbronchial lung cryobiopsy (TBLC)-versus surgical lung biopsy (SLB) as the current gold standard-in interstitial lung disease (ILD) cases requiring histology remains controversial. To assess diagnostic concordance between TBLC and SLB sequentially performed in the same patients, the diagnostic yield of both techniques, and subsequent changes in multidisciplinary assessment (MDA) decisions. A two-center prospective study included patients with ILD with a nondefinite usual interstitial pneumonia pattern (on high-resolution computed tomography scan) confirmed at a first MDA. Patients underwent TBLC immediately followed by video-assisted thoracoscopy for SLB at the same anatomical locations. After open reading of both sample types by local pathologists and final diagnosis at a second MDA (MDA2), anonymized TBLC and SLB slides were blindly assessed by an external expert pathologist (T.V.C.). Kappa-concordance coefficients and percentage agreement were computed for: TBLC versus SLB, MDA2 versus TBLC, MDA2 versus SLB, and blinded pathology versus routine pathology. Twenty-one patients were included. The median TBLC biopsy size (longest axis) was 7 mm (interquartile range, 5-8 mm). SLB biopsy sizes averaged 46.1 ± 13.8 mm. Concordance coefficients and percentage agreement were: TBLC versus SLB: κ = 0.22 (95% confidence interval [CI], 0.01-0.44), percentage agreement = 38% (95% CI, 18-62%); MDA2 versus TBLC: κ = 0.31 (95% CI, 0.06-0.56), percentage agreement = 48% (95% CI, 26-70)%; MDA2 versus SLB: κ = 0.51 (95% CI, 0.27-0.75), percentage agreement = 62% (95% CI, 38-82%); two pneumothoraces (9.5%) were recorded during TBLC. TBLC would have led to a different treatment if SLB was not performed in 11 of 21 (52%) of cases. Pathological results from TBLC and SLB were poorly concordant in the assessment of ILD. SLBs were more frequently concordant with the final diagnosis retained at MDA. 10.1164/rccm.201810-1947OC
    Transbronchial Lung Cryobiopsy in Diffuse Interstitial Lung Diseases . . . Bent but Not Broken. Agarwal Ritesh,Dhooria Sahajal,Sehgal Inderpaul S,Mehta Ravindra,Pattabhiraman Vallandaraman,Aggarwal Ashutosh N,Bal Amanjit,Srinivasan Arjun,Madan Karan,Mohan Anant,Chhajed Prashant,Goyal Rajiv,Akkaraju Jayachandra,Patel Dharmesh American journal of respiratory and critical care medicine 10.1164/rccm.201904-0785LE
    Transbronchial cryobiopsy increases diagnostic confidence in interstitial lung disease: a prospective multicenter trial. Hetzel Jürgen,Wells Athol U,Costabel Ulrich,Colby Thomas V,Walsh Simon L F,Verschakelen Johny,Cavazza Alberto,Tomassetti Sara,Ravaglia Claudia,Böckeler Michael,Spengler Werner,Kreuter Michael,Eberhardt Ralf,Darwiche Kaid,Torrego Alfons,Pajares Virginia,Muche Rainer,Musterle Regina,Horger Marius,Fend Falko,Warth Arne,Heußel Claus Peter,Piciucchi Sara,Dubini Alessandra,Theegarten Dirk,Franquet Tomas,Lerma Enrique,Poletti Venerino,Häntschel Maik The European respiratory journal INTRODUCTION:The accurate diagnosis of individual interstitial lung diseases (ILD) is often challenging, but is a critical determinant of appropriate management. If a diagnosis cannot be made after multidisciplinary team discussion (MDTD) surgical lung biopsy (SLB) is the current recommended tissue sampling technique according to the most recent guidelines. Transbronchial lung cryobiopsy (TBLC) has been proposed as an alternative to SLB. METHODS:This prospective, multicenter, international study analysed the impact of TBLC on the diagnostic assessment of 128 patients with suspected idiopathic intersitital pneumonia by a central MDTD board (two both clinicians, radiologists, pathologists). The level of confidence for the first-choice diagnoses were evaluated in four steps: 1. clinicoradiological data alone, 2. addition of BAL findings, 3. addition of TBLC interpretation, and 4. SLB findings (if available). We evaluated the contribution of TBLC to the formulation of a confident first-choice MDTD diagnosis. RESULTS:TBLC led to a significant increase in the percentage of cases with confident diagnoses or provisional diagnoses with high confidence (likelihood ≥70%) from 60.2% to 81.2%. In 32 out of 52 nondiagnostic patients after BAL TBLC provided a diagnosis with a likelihood≥70%. The percentage of confident diagnoses (likelihood≥90%) increased from 22.7% after BAL to 53.9% after TBLC. Pneumothoraces occurred in 16.4%, moderate or severe bleeding in 15.7% of patients. No deaths were observed within 30 days. INTERPRETATION:TBLC increases diagnostic confidence in the majority of ILD patients with an uncertain non-invasive diagnosis, with manageable side effects. These data support the integration of TBLC in the diagnostic algorithm for ILD. 10.1183/13993003.01520-2019
    Safety and Diagnostic Yield of Transbronchial Lung Cryobiopsy in Diffuse Parenchymal Lung Diseases: A Comparative Study versus Video-Assisted Thoracoscopic Lung Biopsy and a Systematic Review of the Literature. Ravaglia Claudia,Bonifazi Martina,Wells Athol U,Tomassetti Sara,Gurioli Carlo,Piciucchi Sara,Dubini Alessandra,Tantalocco Paola,Sanna Stefano,Negri Eva,Tramacere Irene,Ventura Valentina Anna,Cavazza Alberto,Rossi Andrea,Chilosi Marco,La Vecchia Carlo,Gasparini Stefano,Poletti Venerino Respiration; international review of thoracic diseases BACKGROUND:A diagnosis of interstitial lung diseases (ILDs) may include surgical lung biopsy (SLB), which is associated with significant morbidity and mortality and also appreciable costs. Transbronchial lung cryobiopsy (TBLC) is adopting an important role. OBJECTIVES:The aim of this study was to compare the diagnostic yield (DY) and safety of TBLC and SLB in a large cohort of patients and to perform a systematic review of the literature as well as a meta-analysis. METHODS:We performed a retrospective analysis of 447 cases with ILD undergoing TBLC and/or SLB and a systematic review of the literature (MEDLINE and Embase for all original articles on the DY and safety of TBLC in ILDs up to July 2015). RESULTS:A total of 150 patients underwent SLB and 297 underwent TBLC. The median time of hospitalization was 6.1 days (SLB) and 2.6 days (TBLC; p < 0.0001). Mortality due to adverse events was observed for 2.7% (SLB) and 0.3% (TBLC) of the patients. Pneumothorax was the most common complication after TBLC (20.2%). No severe bleeding was observed. TBLC was diagnostic for 246 patients (82.8%), SLB for 148 patients (98.7%, p = 0.013). A meta-analysis of 15 investigations including 781 patients revealed an overall DY of 0.81 (0.75-0.87); the overall pooled probability of developing a pneumothorax, as retrieved from 15 studies including 994 patients, was 0.06 (95% CI 0.02-0.11). CONCLUSION:Cryobiopsy is safe and has lower complication and mortality rates compared to SLB. TBLC might, therefore, be considered the first diagnostic approach for obtaining tissue in ILDs, reserving the surgical approach for cases in which TBLC is not diagnostic. 10.1159/000444089
    Transbronchial lung cryobiopsy in idiopathic acute fibrinous and organizing pneumonia. Shintani Ryota,Oda Tsuneyuki,Niwa Takashi,Sekine Akimasa,Hagiwara Eri,Okudela Koji,Takemura Tamiko,Ogura Takashi Respiratory medicine case reports A 53-year-old Japanese female was admitted to our hospital with 3-week history of cough and worsening dyspnea. Chest computed tomography revealed unilateral focal consolidation in the right lower lobe. She underwent transbronchial lung cryobiopsy (TBLC) and histology showed acute fibrinous and organizing pneumonia (AFOP). High-dose methylprednisolone treatment improved her respiratory condition and radiological findings. AFOP is a rare histologic interstitial pneumonia pattern and has been diagnosed by surgical lung biopsy or autopsy in most cases. To our knowledge, this is the first detailed report of AFOP diagnosed by TBLC. TBLC can be performed safely with less invasion and be a useful diagnostic technique for rapidly progressive diffuse lung disease such as AFOP. 10.1016/j.rmcr.2019.100888
    Transbronchial Biopsy and Cryobiopsy in the Diagnosis of Hypersensitivity Pneumonitis among Patients with Interstitial Lung Disease. Chami Hassan A,Diaz-Mendoza Javier,Chua Abigail,Duggal Abhijit,Jenkins Alex R,Knight Shandra,Patolia Setu,Tamae-Kakazu Maximiliano,Raghu Ganesh,Wilson Kevin C Annals of the American Thoracic Society RATIONALE:Hypersensitivity Pneumonitis (HP) is an interstitial lung disease (ILD) whose diagnosis is based on clinical, radiological, and pathological findings. The evidence supporting transbronchial forceps lung biopsy (TBBx) and transbronchial lung cryobiopsy (TBLC) as sampling techniques to diagnose HP in patients with newly detected ILD has not been reviewed systematically. OBJECTIVE:A systematic review was performed to assess the diagnostic yield and complication rates of TBBx or TBLC in patients with newly detected ILD whose differential diagnosis includes HP and to inform the development of the American Thoracic Society (ATS), Japanese Respiratory Society (JRS), and Asociación Latinoamericana del Tórax (ALAT) clinical practice guideline on the diagnosis of HP. METHODS:Medline, EMBASE and the Cochrane Library were searched through October 2019. Studies that enrolled patients with ILD and reported the diagnostic yield of TBBx or TBLC were selected for inclusion. Data related to diagnostic yield and safety outcomes were extracted and then pooled across studies via meta-analysis. The quality of the evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS:Histopathologic diagnostic yield (number of procedures that yielded a histopathologic diagnosis divided by the total number of procedures performed) of TBBx and TBLC were 37% (95% CI 32-42%) and 82% (95% CI 78-86%) respectively among patients with ILD. Among those diagnosed by TBBx, the proportion with HP could not be determined. However, among those diagnosed by TBLC, 13.4% had HP. TBBx was complicated by moderate to severe bleeding, severe bleeding, and pneumothorax in 4% (95% CI 0-8%), 0% (95% CI 0-1%), and 7% (95% 2-13%) of patients, respectively. TBLC was complicated by any bleeding, severe bleeding, and pneumothorax in 11% (95% CI 7-15%), 0% (95% CI 0-1%), and 11% (95% 9-14%) of patients, respectively. The quality of the evidence was very low due to the uncontrolled study designs, lack of consecutive enrollment, and inconsistent results. CONCLUSION:Very low quality evidence indicated that TBLC had a higher diagnostic yield than TBBx among patients with ILD, although complications were more common with TBLC. 10.1513/AnnalsATS.202005-421OC
    Bronchoscopic Cryobiopsy and Forceps Biopsy for the Diagnostic Evaluation of Diffuse Parenchymal Lung Disease in Clinical Practice. Koslow Matthew,Edell Eric S,Midthun David E,Mullon John J,Kern Ryan M,Nelson Darlene R,Sakata Kenneth K,Moua Teng,Roden Anja C,Yi Eunhee S,Reisenauer Janani S,Decker Paul A,Ryu Jay H Mayo Clinic proceedings. Innovations, quality & outcomes Objective:To assess the contribution and safety of bronchoscopic cryobiopsy vs traditional forceps biopsy used in clinical practice for diagnosing diffuse parenchymal lung disease (DPLD). Patients and Methods:We identified 271 patients who underwent bronchoscopic biopsy for DPLD at Mayo Clinic, MN (June 1, 2013, through September 30, 2017). Medical records were reviewed including prebiopsy clinical and radiographic impressions. was assessed in terms of a specific histologic pattern resulting in a diagnosis when combined with the clinical-radiologic context. was defined as a biopsy result deemed useful in patient management. Results:The cohort included 120 cryobiopsy and 151 forceps biopsy cases with mean age 61±14 years and 143 (53%) men. Diagnostic yield (55% vs 41%; odds ratio [OR], 1.73; 95% CI, 1.07 to 2.83; =.026) and clinical utility (60% vs 40%; OR, 2.21; 95% CI, 1.36 to 3.63; =.001) were higher for the cryobiopsy group, and the association remained after control for prebiopsy clinical impressions (OR, 2.21; 95% CI, 1.22 to 4.08; =.010 and OR, 3.23; 95% CI, 1.76 to 6.10; <.001, respectively). However, pneumothorax (5.4% vs 0.7%; =.022) and serious bleeding (7.1% vs 0%; =.001) rates were higher for the cryobiopsy group. Thirty-day mortality was 1.6% in the cryobiopsy group vs 0% for the forceps biopsy group (=.20). Conclusion:Bronchoscopic cryobiopsy revealed higher diagnostic yield and clinical utility than did forceps biopsy. However, procedure-related complications were higher in the cryobiopsy group. The choice of bronchoscopic biopsy procedure for patients with DPLD depends on the clinicalradiologic context. 10.1016/j.mayocpiqo.2020.05.005
    Transbronchial Cryobiopsy in Interstitial Lung Disease: Safety of a Standardized Procedure. She Shelley,Steinfort Daniel P,Ing Alvin J,Williamson Jonathan P,Leong Paul,Irving Louis B,Jennings Barton R,Saghaie Tajalli Journal of bronchology & interventional pulmonology BACKGROUND:Transbronchial lung cryobiopsy (TBCB) plays an increasing role in the evaluation of diffuse parenchymal lung disease with acceptable diagnostic yield and safety profile compared with that of video-assisted thoracoscopic surgical lung biopsy on most reports. However, published outcomes with regard to safety and complication rates vary. We aim to determine the safety profile of TBCB when performed using a standardized protocol consistent with recently published expert guidelines. MATERIALS AND METHODS:We reviewed prospectively maintained databases from 5 Australian tertiary referral centers. The procedures were performed in accordance with a recent expert statement recommending standardization of TBCB procedures, in particular with fluoroscopy, a secured airway, and prophylactic bronchial blockers. Periprocedural complications were assessed along with clinical outcomes. RESULTS:A total of 121 patients underwent TBCB between August 2013 and August 2017 following a standardized protocol using general anesthesia. Of them, 84 patients (66.7%) were discharged on the day of the procedure. Pneumothorax occurred in 18 patients (14.9%), 13 (10.7%) of whom required chest tube drainage. Moderate bleeding occurred in 15 patients (13.2%) and severe bleeding in 1 (0.83%). Histopathologic diagnosis was made in 80 patients (66.1%). CONCLUSION:Pooled outcomes from Australian tertiary centers indicate that TBCB is safe when performed in a protocolized fashion. Active measures to anticipate and manage bleeding and to direct biopsy position result in low rates of major complications. 10.1097/LBR.0000000000000633
    The role of transbronchial cryobiopsy and surgical lung biopsy in the diagnostic algorithm of interstitial lung disease. Hagmeyer Lars,Theegarten Dirk,Wohlschläger Jeremias,Treml Marcel,Matthes Sandhya,Priegnitz Christina,Randerath Winfried J The clinical respiratory journal BACKGROUND AND AIMS:It is not yet known if transbronchial cryobiopsy (TCB) is a reliable and safe diagnostic tool in the investigation of interstitial lung disease (ILD). To date, there have been no studies directly comparing the value of TCB with that of surgical lung biopsy (SLB). The study was initiated to determine whether the samples taken by TCB lead to a reliable diagnosis and whether SLB can be avoided in a relevant percentage of cases. METHODS:We analyzed 32 subjects with suspected ILD who underwent a TCB. Subjects' baseline characteristics, pathological findings after TCB and SLB, and complication rates were analyzed. The pathological inter-rater agreement was quantified statistically. RESULTS:The overall inter-rater agreement concerning TCB sample evaluation was good with a kappa value of 0.80. In 23/32 cases (72%), the findings from the TCB showed a strong congruence with all other clinical data, thereby enabling a definitive diagnosis. Eight of the remaining nine subjects gave their consent for an SLB, which led to a definitive histological diagnosis in six cases (75%). Following TCB, pneumothorax occurred in 6/32 subjects (19%) and endobronchial bleeding was moderate in 8/32 (25%) and was severe in 17/32 cases (53%). CONCLUSION:This is the first study to correlate histological results and complications following TCB and SLB in ILD subjects, some of whom underwent both procedures. TCB is a suitable diagnostic tool in ILD, potentially completely dispensing with the need for an SLB in some cases. In all cases, an interdisciplinary case evaluation is necessary as a final step. 10.1111/crj.12261
    [Efficacy and safety of transbronchial cryobiopsy in the etiologic diagnosis of diffuse lung disease]. Li Y S,Guo S L,Yi X H,Xiao M L,Jin X X,Xiao Y,Zhu X Y,Li X,Dai L W,Ao Z,Liu X Z,Ding M Zhonghua yi xue za zhi To assess the efficacy and safety of transbronchial cryobiopsy (TBCB) for the etiologic evaluation of diffuse lung disease (DLD). Between December 2015 to April 2017, a total of 38 patients with DLD met the inclusion criteria for TBCB in the First Affiliated Hospital of Chongqing Medical University, and 35 of them consented to undergo the procedure under rigid or flexible bronchoscopy. On the tissues obtained from the 35 patients, histopathologic and microbiological evaluations were performed, and together with clinical and radiological manifestations, diagnoses were made and the efficacy of TBCB in the diagnosis of DLD was confirmed, and then therapies were planned accordingly. Complications of the biopsy procedures were recorded. Of the 35 patients who were enrolled, 24 underwent TBCB under rigid bronchoscopy and 11 under flexible bronchoscopy. Another 3 patients refused the procedure due to disinclination to invasive examinations. One single procedure of TBCB took (51.8±19.2) min on average, the median number of tissues obtained was 6 (5, 8), and the median area of tissues was 15 (9, 20) mm(2).Definite diagnoses were reached in 33 patients, including idiopathic nonspecific interstitial pneumonia (=8), connective tissue disease-interstitial lung disease (=8), occupational lung disease (=4), idiopathic pulmonary fibrosis (=3), interstitial pneumonia with autoimmune features (=3), tuberculosis (=2), cryptogenic organization pneumonia (=1), acute interstitial pneumonia (=1), pulmonary infection (=1), hypersensitivity pneumonia (=1) and sarcoidosis (=1). Diagnostic yield was 94.3% (33 out of 35 cases diagnosed). Pneumothorax occurred in 3 patients (1 patients with mild pneumothorax , 1 moderate and 1 severe), and were resolved with thoracic puncture or pleural drainage. Bleeding occurred in all 24 patients who received TBCB under rigid bronchoscopy (11 patients with mild bleeding, 12 moderate and 1 severe) and was controlled after coagulation measures. After one month of treatment according to the diagnoses acquired with cryobiopsy, the condition was cured in 1 patient (3.0%), alleviated in 17 (51.5%), stable in 11 (33.3%), and deteriorated in 4 (12.1%). TBCB yields reliable diagnoses with a good safety profile. 10.3760/cma.j.issn.0376-2491.2017.46.004
    Utility of Transbronchial Lung Cryobiopsy in Non-Interstitial Diseases. Sánchez-Cabral Olivia,Martínez-Mendoza Dina,Fernandez-Bussy Sebastián,López-González Berenice,Perea-Talamantes Carolina,Rivera-Rosales Rosa María,Luna-Rivero César,Martínez-Orozco José Arturo,Flores-Suárez Luis Felipe,Santillán-Doherty Patricio,Reyes-Terán Gustavo Respiration; international review of thoracic diseases BACKGROUND:Transbronchial lung cryobiopsy (TLCB), performed with a flexible cryoprobe, is an interventional pulmonology procedure that has proved its diagnostic value for interstitial pulmonary disease. However, it has not been explored extensively as a diagnostic tool for patients with non-interstitial lung pathology, including infectious and malignant diseases. OBJECTIVE:To evaluate the diagnostic yield and safety of an interventional pulmonology approach that integrates TLCB and bronchoalveolar lavage (BAL) for the diagnosis of non-interstitial pulmonary disease. METHODS:TLCB and BAL were performed under general anesthesia through the same bronchoscopic access on 103 adult patients (including immunocompromised HIV+ individuals) with clinical/radiological evidence of non-interstitial lung disease admitted to the Interventional Pulmonology Service between May 2015 and April 2016. Samples obtained were sent to pathology and microbiology laboratories for standard diagnostic analysis. RESULTS:Samples of TLCB allowed the diagnosis of 75.7% of patients, while 39.8% were diagnosed from BAL. The global diagnostic yield from the dual sampling was 92.2%. TLCB allowed the diagnosis of 94.7% of cancer cases and 60.0% of infectious cases, while BAL samples identified 77.5% of infectious cases and 21.2% of malignant lesions. The incidence of complications was 4.9% with full recovery in all cases. CONCLUSIONS:Simultaneous TLCB and BAL constitute a safe and useful diagnostic procedure for non-interstitial pulmonary disease, with a global diagnostic yield of 92.2%. Complementary advantages of samples obtained by each technique result in a robust diagnostic strategy for infectious and malignant disease in adults, including HIV+ individuals. 10.1159/000478786
    Diagnostic yield and risk/benefit analysis of trans-bronchial lung cryobiopsy in diffuse parenchymal lung diseases: a large cohort of 699 patients. Ravaglia Claudia,Wells Athol U,Tomassetti Sara,Gurioli Carlo,Gurioli Christian,Dubini Alessandra,Cavazza Alberto,Colby Thomas V,Piciucchi Sara,Puglisi Silvia,Bosi Marcello,Poletti Venerino BMC pulmonary medicine BACKGROUND:Standardization of trans-bronchial lung cryobiopsy in diffuse parenchymal lung diseases is imminent; however, the majority of published series on cryobiopsy include a limited number of patients and are characterized by several differences in procedural technical details. METHODS:This is an observational, retrospective cohort study. Aim of the study was to suggest some sampling strategies related to transbronchial cryobiopsy in the diagnostic work-up of patients with diffuse parenchymal lung diseases. RESULTS:Six hundred ninety-nine patients with suspected diffuse parenchymal lung disease were recruited. A specific pathological diagnosis was achieved in 614/699 cases (87.8%) and a multidisciplinary diagnosis was obtained in 630/699 cases (90.1%). Diagnostic yield was significantly influenced by the number of samples taken (1 vs ≥ 2 biopsies, p < 0.005). In 60.4% of patients, biopsies were taken from one site and in 39.6% from different sites (in the same lobe or in two different lobes), with a significant increase in diagnostic yield, specifically in patients with fibrotic lung diseases (65.5% vs 93.4%, p < 0.0001). The 2.4 mm or 1.9 mm probes were used, with no differences in terms of diagnostic yield. Regarding safety, pneumothorax occurred in 19.2% and was influenced by baseline lung function; in all patients Fogarty balloon has been used and severe haemorrhage occurred in 0.7% of cases. Three patients (0.4% of cases) died within 30 days after the procedure. CONCLUSIONS:We propose some sampling strategies of cryobiopsy which seem to be associated with a higher diagnostic yield and a favorable risk/benefit ratio: sampling at least two samples in different sites, using either the 2.4 mm or the 1.9 mm probe, intubating the patients and using bronchial blockers/catheters. 10.1186/s12890-019-0780-3
    Transbronchial cryobiopsy in fibrosing interstitial lung disease: modifications of the procedure lead to risk reduction. Hagmeyer Lars,Theegarten Dirk,Wohlschläger Jeremias,Hager Thomas,Treml Marcel,Herkenrath Simon Dominik,Hekmat Khosro,Heldwein Matthias,Randerath Winfried J Thorax Sixty-one subjects with fibrosing interstitial lung disease were prospectively analysed to determine the efficacy of transbronchial cryobiopsy (CryoTBB) and the effect of procedural modifications which were introduced after an interim analysis of the first 19 subjects. The modifications significantly reduced complication rates from 84% to 14% (p<0.001). 30-day-mortality was 2%. The algorithm with initial CryoTBB and surgical lung biopsy (SLB) as optional step-up procedure was feasible. CryoTBB led to a confident diagnosis in 46/61 subjects (75%). Only 21% out of all subjects were forwarded for SLB. As the modified CryoTBB reduced but not eliminated the risk of severe complications, tissue sampling should be limited to patients where confident diagnosis enables life prolonging therapy. Trial registration number: NCT01714518. 10.1136/thoraxjnl-2018-212095
    Transbronchial lung cryobiopsy in the diagnosis of interstitial lung disease. Keenan Joseph,Backer Elliot,Gibson Heidi,Cho Roy,Dinçer H Erhan Tuberkuloz ve toraks Transbronchial cryoprobe lung biopsy (TBCLB) have recently been introduced as a safe diagnostic tool in the diagnosis of interstitial lung diseases. While we do not enough evidence its role and place as a diagnostic procedure, the technique has been adopted by many centers. In spite of expanding body of literature, there are variations in patient selection and procedural aspect of the procedure. It has been established as a safe procedure if safety measures are practiced. Diagnosis of interstitial lung diseases continuous to be challenging. Surgical lung biopsy considered as gold standard but its morbidity and mortality limit its utilization in every case. Multidisciplinary medical decision is a validated team work effort when approaching patients with interstitial lung disease. 10.5578/tt.69078
    [The efficacy and safety of transbronchial lung cryobiopsy in interstitial lung disease: a prospective study]. Chen X B,Luo Q,Chen Y,Han Q,Zhong C H,Xiao W Q,Su Z Q,Yao Y,Li S Y Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases To evaluate the efficacy and safety of transbronchial lung cryobiopsy (TBCB) and conventional transbronchial lung biopsy (TBLB) in the diagnosis of interstitial lung diseases(ILD). A prospective, self-control study was conducted during January 2017 and April 2017 in First Affiliated Hospital of Guangzhou Medical University. A total of 25 patients [male 16, female 9; mean age (51±13) years, range 24 to 70 years] with inconclusive diagnosis of interstitial lung diseases were sequentially enrolled. In the study, TBCB (TBCB group) and TBLB (TBLB group) were performed successively under general anesthesia in all patients. The size of biopsy specimens, the duration of procedures, complications and pathological results were recorded. Gaussian distribution data were compared between 2 groups by using Student's test, while abnormal distribution data were compared by using Wilcoxon rank sum test. The incidences of bleeding and pathologic diagnostic yield between the 2 groups were compared by using Pearson chi-square test. A -value< 0.05 was assumed to be statistically significant. The specimen sizes of TBCB group and TBLB group were (12.3+ 4.9) and (3.1+ 1.9) mm(2) respectively (=-18.268, =0.000). The duration of procedures was (7.8±3.2) and (5.4±2.1)min respectively (=-3.001, =0.003). In TBCB group, the diagnostic yield was 72% (18/25), with valuable pathological results in 2 cases (8%), but in 5 cases (20%) it failed to provide valuable pathological results. In TBLB group, the diagnostic yield was 12% (3/25). There were no useful pathological results in other 22 cases. The difference in the rate of useful pathological results between TBCB group and TBLB group was significant (χ(2)=20.779, =0.000). There was no pneumothorax or severe bleeding. The rate of mild to moderate bleeding in TBCB group and TBLB group was 47.2%(50/106) and 18.9%(20/106) (χ(2)=19.195, =0.000) respectively. TBCB is superior to TBLB for lung biopsy as indicated by larger sample size, higher diagnostic yield and less complication. TBCB is valuable for the diagnosis of ILD. 10.3760/cma.j.issn.1001-0939.2018.06.007
    Feasibility and utility of transbronchial cryobiopsy in precision medicine for lung cancer: Prospective single-arm study. Udagawa Hibiki,Kirita Keisuke,Naito Tomoyuki,Nomura Shogo,Ishibashi Masayuki,Matsuzawa Reiko,Hisakane Kakeru,Usui Yuko,Matsumoto Shingo,Yoh Kiyotaka,Niho Seiji,Ishii Genichiro,Goto Koichi Cancer science Cryoprobe is a novel transbronchial biopsy (TBB) tool that yields larger tissue samples than forceps. Pathological diagnosis and biomarker analysis, such as genetic alterations and programmed death-ligand 1 (PD-L1) expression, are paramount for precision medicine against lung cancer. We evaluated the safety and usefulness of cryoprobe TBB for lung cancer diagnosis and biomarker analysis. In this single-center, prospective single-arm study, patients suspected of having or diagnosed with primary lung cancer underwent cryoprobe TBB using flexible bronchoscopy after conventional forceps TBB from the same lesion. Cryoprobe TBB was performed in 121 patients. The incidence rate of severe bleeding and serious adverse events (4% [90% confidence interval: 2%-9%]) was significantly lower than the expected rate (20% with 30% threshold, P < 0.01). Combining both central and peripheral lesions, the diagnostic yield rate of cryoprobe samples was 76% and that of forceps samples was 84%. Compared with forceps TBB samples, cryoprobe TBB samples were larger (cryoprobe 15 mm vs forceps 2 mm ) and resulted in a larger proportion of definite histomorphological diagnosis (cryoprobe 86% vs forceps 74%, P < 0.01), larger amounts of DNA extracted from samples (median: cryoprobe, 1.60 µg vs forceps, 0.58 µg, P = 0.02) and RNA (median: cryoprobe, 0.62 µg vs forceps, 0.17 µg, P < 0.01) extracted from samples, and tended to yield greater rates of PD-L1 expression >1% (51% vs 42%). In conclusion, cryoprobe is a safe and useful tool for obtaining lung cancer tissue samples of adequate size and quality, which allow morphological diagnosis and biomarker analysis for precision medicine against lung cancer. 10.1111/cas.14489
    Transbronchial Lung Cryobiopsy in the Diagnosis of Interstitial Lung Disease: A Retrospective Single-center Experience. Cho Roy,Zamora Felix,Gibson Heidi,Dincer H Erhan Journal of bronchology & interventional pulmonology BACKGROUND:Surgical lung biopsy (SLB) is the gold standard to aid diagnosis of interstitial lung disease (ILD). Complication rates are restrictive as routine approach for all patients with ILD. Transbronchial lung cryobiopsy (TBLC) is presumed to be a safe, less invasive alternative to assist multidisciplinary discussions regarding the diagnosis of ILD. Varying practice patterns and lack of consistent guidelines prohibit wide support of this technique. The purpose of this study was to evaluate safety and diagnostic yield of TBLC, with highlight of distinct technical features, in ILD. METHODS:Retrospective study of patients with ILD on the basis of high-resolution chest computed tomography who underwent TBLC. RESULTS:Of 121 TBLC, 40 patients (mean age, 57.2±13 y; 28 men) with ILD were referred for biopsy. Procedures were performed in endoscopy suite (60%) or operating room by using 1.9-mm cryoprobe. Biopsies were performed in 2 lobes with at least 3 to 5 specimens >5 mm in diameter. The average diameter and area of specimens were 5.7±2 mm and 40±2 mm, respectively. The most common diagnosis was nonspecific interstitial pneumonitis; usual interstitial pneumonia was diagnosed in 1 patient. Of 6 nondiagnostic specimens, 2 underwent SLB with subsequent diagnoses. Final histopathologic diagnostic rate was 85%. Bleeding was the most frequent complication. CONCLUSION:We provided a detailed description of our TLBC technique and highlighted areas of similarity and differences among comparative studies and attest that TBLC is a safe alternative to SLB in the diagnosis of ILD. Our data also indicated the tendency for moderate-to-severe bleeding occurred more in the endoscopy suite. 10.1097/LBR.0000000000000514
    The role of transbronchial cryobiopsy in lung transplantation. Montero M Angeles,de Gracia Javier,Culebras Amigo Mario,Mugnier Jacqueline,Álvarez Antonio,Berastegui Cristina,Ortiz-Villalón Cristian Histopathology AIMS:Lung transplant monitoring is usually performed with forceps transbronchial biopsies. These types of biopsy show limited reliability and a high degree of variability, owing to insufficient material and compression artefact, which lead to misinterpretation and, eventually, inappropriate treatment of the transplanted patients. The following study was undertaken to assess the diagnostic yield, histological quality and safety of cryobiopsy (CB) in comparison with conventional forceps biopsy (FB) for sampling lung tissue in transplant recipients. METHODS AND RESULTS:From January to December 2011, 81 consecutive transbronchial biopsies (41 FBs and 40 CBs) were indicated in single or bilateral lung transplantation recipients with clinical acute or chronic lung injury. Lung samples obtained by CB were larger (8.5 ± 6.5 mm in the FB group versus 22.1 ± 12.5 mm in the CB group; P < 0.0001) and had no crush artefacts (P = 0.002), allowing us to increase the diagnostic yield of acute (P = 0.0657) and chronic (P = 0.0053) cellular rejection. DISCUSSION:Transbronchial cryoprobe bronchoscopy allows the harvesting of larger and more expanded lung tissue samples, increasing the diagnostic yield in the monitoring of the lung allograft by means of a safe procedure. 10.1111/his.13656
    Transbronchial Cryobiopsy in Interstitial Lung Diseases: State-of-the-Art Review for the Interventional Pulmonologist. Avasarala Sameer K,Wells Athol U,Colby Thomas V,Maldonado Fabien Journal of bronchology & interventional pulmonology Interstitial lung diseases are a heterogenous group of disorders that are often difficult to diagnose precisely. Clinical, laboratory, radiographic, and histologic information may be needed to arrive at the correct diagnosis. The multidisciplinary discussion has been proven to be useful in this patient group. Transbronchial cryobiopsy has become a popular method for obtaining tissue samples. Over the course of the last decade, there has been a significant amount of research assessing the feasibility, safety, and diagnostic endpoints of transbronchial cryobiopsy in patients with interstitial lung disease. Data continues to mount to support its use, which has been reflected in guidelines and expert panel reports. Patient selection, procedural performance, and appropriate specimen handling are critical factors for success. A coordinated approach by pulmonologists with expertise in interstitial lung diseases, interventional pulmonologists, and thoracic pathologists is essential. In this evidence-based narrative review, we address transbronchial cryobiopsies from these three distinct perspectives. In addition, the current literature was used to address nine common procedural questions. 10.1097/LBR.0000000000000716
    Transbronchial Cryobiopsy for the Diagnosis of Interstitial Lung Diseases: CHEST Guideline and Expert Panel Report. Maldonado Fabien,Danoff Sonye K,Wells Athol U,Colby Thomas V,Ryu Jay H,Liberman Moishe,Wahidi Momen M,Frazer Lindsy,Hetzel Juergen,Rickman Otis B,Herth Felix J F,Poletti Venerino,Yarmus Lonny B Chest BACKGROUND:Transbronchial cryobiopsy (TBC) is increasingly recognized as a potential alternative to surgical lung biopsy (SLB) for the diagnosis of interstitial lung disease (ILD). The goal of this analysis was to examine the literature on TBC as it relates to diagnostic utility and safety to provide evidence-based and expert guidance to clinicians. METHODS:Approved panelists developed key questions regarding the diagnostic utility and safety of TBC for the evaluation of ILD using the PICO (Population, Intervention, Comparator, Outcome) format. MEDLINE (via PubMed) and the Cochrane Library were systematically searched for relevant literature, which was supplemented by manual searches. References were screened for inclusion, and vetted evaluation tools were used to assess the quality of included studies, to extract data, and to grade the level of evidence supporting each recommendation or statement. Graded recommendations and ungraded consensus-based statements were drafted and voted on using a modified Delphi technique to achieve consensus. RESULTS:The systematic review and critical analysis of the literature based on four PICO questions resulted in six statements: two evidence-based graded recommendations and four ungraded consensus-based statements. CONCLUSIONS:Evidence of the utility and safety of TBC for the diagnosis of ILD is limited but suggests TBC is safer than SLB, and its contribution to the diagnosis obtained via multidisciplinary discussion is comparable to that of SLB, although the histological diagnostic yield appears higher with SLB (approximately 80% for TBC vs 95% for SLB). Additional research is needed to enhance knowledge regarding utility and safety of TBC, its role in the diagnostic algorithm of ILD, and the impact of technical aspects of the procedure on diagnostic yield and safety. 10.1016/j.chest.2019.10.048
    Transbronchial Lung Cryobiopsy in Diffuse Parenchymal Lung Disease: Comparison between Biopsy from 1 Segment and Biopsy from 2 Segments - Diagnostic Yield and Complications. Ravaglia Claudia,Wells Athol U,Tomassetti Sara,Dubini Alessandra,Cavazza Alberto,Piciucchi Sara,Sverzellati Nicola,Gurioli Carlo,Gurioli Christian,Costabel Ulrich,Tantalocco Paola,Ryu Jay H,Chilosi Marco,Poletti Venerino Respiration; international review of thoracic diseases BACKGROUND:Transbronchial lung cryobiopsy is an innovative method of obtaining samples from the parenchyma of patients with diffuse parenchymal lung diseases. However, the technique is not yet standardized, and uncertainty exists about the optimal protocol, including the number of samples, the biopsy size, and the choice of the biopsy site. OBJECTIVES:To compare the diagnostic yield and complications of cryobiopsy with different strategies adopted to sample lung tissue (number of samples, biopsy site, and sample size). METHODS:We prospectively enrolled 46 patients with suspected diffuse parenchymal lung diseases for the diagnosis of which a biopsy was deemed useful. All patients underwent transbronchial lung cryobiopsy, and they were randomly assigned to group A (4 samples obtained from the same segment) or group B (2 samples obtained from one segment and 2 samples obtained from a different segment of the same lobe). Analysis of the samples was performed sequentially (from the first to the last sample), and pathologists reformulated their histopathologic diagnosis with the addition of each sample. RESULTS:The mean diagnostic yield of the procedure combining the 2 groups and performing only the first sampling was 69%. When a second biopsy was performed as well, the mean diagnostic yield improved, but this increase was significant only when the 2 samples were obtained from 2 different segments (96%, group B). CONCLUSIONS:This study suggests that the strategy of performing 2 biopsies with a cryoprobe may be associated with an increased diagnostic yield in diffuse parenchymal lung diseases if these samples are obtained from 2 different segments within the same lobe. 10.1159/000456671
    High Complication Rate after Introduction of Transbronchial Cryobiopsy into Clinical Practice at an Academic Medical Center. DiBardino David M,Haas Andrew R,Lanfranco Anthony R,Litzky Leslie A,Sterman Daniel,Bessich Jamie L Annals of the American Thoracic Society RATIONALE:Transbronchial cryobiopsy is an emerging technique for obtaining biopsies of lung parenchyma. Despite limited evidence of its safety and efficacy in direct comparison with other available biopsy procedures, pulmonologists are integrating this technique into clinical practice with the hope of avoiding the risks of surgical lung biopsy. OBJECTIVES:To report the rate of severe complications and diagnostic outcomes immediately after introduction of transbronchial cryobiopsy into the clinical practice of a single-center, high-volume, interventional pulmonary group at a large academic medical center in the United States. METHODS:We conducted a retrospective review of a case series. RESULTS:Twenty-five consecutive patients underwent transbronchial cryobiopsy for a variety of indications over a period of 14 weeks. In the absence of a strict protocol, a variety of techniques were employed by four attending interventional pulmonologists and one advanced interventional pulmonology fellow to plan and complete the procedures. Three patients (12%) experienced serious hemorrhage immediately after biopsy, including one patient who survived a life-threatening bleed. Two procedures were complicated by an iatrogenic pneumothorax. One patient experienced hypercapnic respiratory failure shortly after the procedure. A definitive diagnosis was made with 14 cryobiopsies (56%). Another five biopsies (20%) contributed to a presumptive diagnosis achieved by multidisciplinary consensus. CONCLUSIONS:Transbronchial cryobiopsy may have diagnostic and safety limitations that are not yet well appreciated, given the state of the published medical literature. Major questions remain regarding the safest procedural protocol to be used when performing transbronchial cryobiopsy. Thorough planning and a high degree of caution are encouraged on first introduction of this technique into a clinical practice. 10.1513/AnnalsATS.201610-829OC
    Transbronchial lung cryobiopsy: Associated complications. Linhas R,Marçôa R,Oliveira A,Almeida J,Neves S,Campainha S Revista portuguesa de pneumologia INTRODUCTION:Transbronchial lung cryobiopsy (TBC) has emerged as a diagnostic alternative to surgical lung biopsy in interstitial lung disease (ILD). Despite its less invasive nature, some associated complications have been described. OBJECTIVE:To evaluate complications of TBC and associated factors. METHODS:Prospective evaluation of all patients with ILD submitted to TBC in our centre. Clinicodemographic variables and factors associated to TBC complications were analyzed. The effect of the variables on the complication risk was evaluated by a logistic regression model. RESULTS:Ninety patients were included (mean age 60±13 years; 58.9% male). Twenty-two patients presented pneumothorax, 18 (81.8%) of which were treated with chest tube drainage [median air leak time: 1 day (IQR=2)]. Grade 2 and 3 bleeding was observed in 13 (14.4%) cases. Presence of visceral pleura in the sample accounted for almost more than 10 times the odds of pneumothorax (OR=9.59, 95% CI 2.95-31.17, p<0.001). Increased body mass index (BMI) was associated with bleeding (16% additional odds for each BMI unit increase (OR=1.16, 95% CI 1.01-1.34, p=0.049). CONCLUSION:The most frequent complication of TBC was pneumothorax, although rapidly reversible. There was a positive association between pneumothorax and the presence of pleura in the biopsy samples as well as between bleeding and increased BMI. More studies about TBC complications are needed to improve the selection of the candidates for this procedure. 10.1016/j.rppnen.2017.07.001
    A Multidisciplinary Proposal for a Diagnostic Algorithm in Idiopathic Pulmonary Fibrosis: The Role of Transbronchial Cryobiopsy. Castillo Diego,Sánchez-Font Albert,Pajares Virginia,Franquet Tomás,Llatjós Roger,Sansano Irene,Sellarés Jacobo,Centeno Carmen,Fibla Juan J,Sánchez Marcelo,Ramírez José,Moreno Amalia,Trujillo-Reyes Juan Carlos,Barbeta Enric,Molina-Molina María,Torrego Alfons, Archivos de bronconeumologia The diagnosis of idiopathic pulmonary fibrosis (IPF) is a complex process that requires the multidisciplinary integration of clinical, radiological, and histological variables. Due to its diagnostic yield, surgical lung biopsy has been the recommended procedure for obtaining samples of lung parenchyma, when required. However, given the morbidity and mortality of this technique, alternative techniques which carry a lower risk have been explored. The most important of these is transbronchial cryobiopsy -transbronchial biopsy with a cryoprobe- which is useful for obtaining lung tissue with less comorbidity. Yield may be lower than surgical biopsy, but it is higher than with transbronchial biopsy with standard forceps. This option has been discussed in the recent clinical guidelines for the diagnosis of IPF, but the authors do not go so far as recommend it. The aim of this article, the result of a multidisciplinary discussion forum, is to review current evidence and make proposals for the use of transbronchial cryobiopsy in the diagnosis of IPF. 10.1016/j.arbres.2019.07.001
    Transbronchial lung cryobiopsy for the diagnosis of lepidic-predominant lung adenocarcinoma. Pathak Vikas,Zhou Christine Lung India : official organ of Indian Chest Society Lung cancer is one of the most common malignancies globally with lung adenocarcinoma as the most common type of lung cancer. With new classification of lung cancers in 2011, it has become pertinent that adequate tissue is obtained for the diagnosis and subtyping of lung adenocarcinoma particularly for prognostication. Transbronchial cryobiopsy is a minimally invasive procedure which helps obtain adequate tissue and avoid surgical lung biopsy. 10.4103/lungindia.lungindia_325_18
    The safety and efficacy of different methods for obtaining transbronchial lung cryobiopsy in diffuse lung diseases. Dhooria Sahajal,Mehta Ravindra M,Srinivasan Arjun,Madan Karan,Sehgal Inderpaul Singh,Pattabhiraman Vallandramam,Yadav Pavan,Sivaramakrishnan Mahadevan,Mohan Anant,Bal Amanjit,Garg Mandeep,Agarwal Ritesh The clinical respiratory journal INTRODUCTION:Most data on transbronchial lung cryobiopsy (TBLC) are from single centers, with little evidence on the outcome of different methods for performing TBLC. OBJECTIVE:To report the diagnostic yield and safety of TBLC with different procedural techniques. MATERIALS AND METHODS:Retrospective multicenter study of subjects who underwent TBLC for the diagnosis of diffuse parenchymal lung diseases (DPLDs). The procedure was performed using various methods: flexible or rigid bronchoscopy, with or without the use of fluoroscopy or occlusion balloon. RESULTS:In total, 128 subjects (59% women) with a mean age of 48.9 years were included. The overall diagnostic yield of TBLC was 78.1%, with a definite diagnosis on multidisciplinary discussion made in 57 (44.5%) subjects. On a multivariate analysis, the diagnostic yield was associated with the number of biopsies taken {ajdusted odds ratio [AOR] [95% confidence interval (CI)], 2.17 [1.29-3.67]}. The incidence of pneumothorax was lower in subjects who underwent TBLC with fluoroscopic guidance (5.9% vs 20.9%), [AOR (95% CI), 0.26 (0.07-0.94)]. Moderate-to-severe bleeding occurred less frequently when an occlusion balloon was used [1.8% vs 35.7%; AOR (95% CI), 0.02 (0.001-0.18)], after adjusting for age, use of fluoroscopy, number of biopsies obtained and number of lobes sampled. Four deaths occurred; 2 because of acute exacerbation of idiopathic pulmonary fibrosis. CONCLUSIONS:Transbronchial lung cryobiopsy was found to offer a reasonable yield in the diagnosis of DPLDs. The incidence of pneumothorax and moderate-to-severe bleeding was lower with the use of fluoroscopy and an occlusion balloon, respectively. 10.1111/crj.12734
    The complimentary role of transbronchial lung cryobiopsy and endobronchial ultrasound fine needle aspiration in the diagnosis of sarcoidosis. Aragaki-Nakahodo Alejandro Adolfo,Baughman Robert P,Shipley Ralph T,Benzaquen Sadia Respiratory medicine PURPOSE:Transbronchial lung cryobiopsy (TBLC) is a novel technique that has proved to be useful in diagnosing various interstitial lung diseases (ILD). The use of TBLC to diagnose sarcoidosis in an unselected patient population is unknown, and could be complimentary to endobronchial ultrasound fine needle aspiration (EBUS-FNA). METHODS:A retrospective analysis of 36 patients in a single, tertiary-care, academic medical center was conducted to describe the yield of both EBUS-FNA and TBLC in the diagnosis of suspected sarcoidosis over a three year period. A grading system to evaluate the presence and extent of specific radiographic features on computed tomography chest imaging studies was compared to the results of EBUS-FNA and TBLC. Complications associated with the procedures were also noted. RESULTS:The overall diagnostic yield in our cohort (all pathologic diagnosis considered) was 80.6% (29 out of 36 patients had a definite pathologic diagnosis). Eighteen patients referred for possible sarcoidosis had a positive bronchoscopic specimen confirming the diagnosis of sarcoidosis. For those patients with a pathologic diagnosis of sarcoidosis, the diagnostic yield for EBUS-FNA and TBLC was 66.7% each (12 out of 18 patients), while the combined diagnostic yield for EBUS-FNA and TBLC increased to 100%. For all cases, the pneumothorax rate was 11.1%. CONCLUSIONS:TBLC appears to be a safe and complimentary technique to diagnose sarcoidosis and could be considered part of the diagnostic armamentarium in bronchoscopic centers. 10.1016/j.rmed.2017.08.003
    Granulomatous and lymphocytic interstitial lung disease diagnosed by transbronchial lung cryobiopsy. Doan John,Rao Nagarjun,Kurman Jonathan S,Routes John M,Benn Bryan S Cryobiology Granulomatous and lymphocytic interstitial lung disease is a pulmonary complication of common variable immune deficiency with significant morbidity and increased mortality. Diagnosis has historically been obtained by surgical lung biopsy as transbronchial biopsy typically yields insufficient tissue for definitive diagnosis from a disease process with a patchy distribution. However, the potential for significant morbidity and mortality with surgical lung biopsy exists, necessitating the development of alternative diagnostic approaches. We present a case of granulomatous and lymphocytic interstitial lung disease confirmed through minimally invasive transbronchial lung cryobiopsy and discuss the role of this modality in diagnosing interstitial lung disease. 10.1016/j.cryobiol.2020.08.004
    Transbronchial cryobiopsy: an effective tool in the diagnosis of lymphoproliferative disorders of the lung. Bianchi Rita,Dubini Alessandra,Asioli Silvia,Ravaglia Claudia,Tomassetti Sara,Puglisi Silvia,Piciucchi Sara,Gurioli Christian,Gurioli Carlo,Fiocca Roberto,Poletti Venerino ERJ open research Introduction:Malignant lymphoproliferative disorders are rarely observed in the lung and, considering their clinical and radiological heterogeneity, diagnosis is often difficult and may require invasive methods. Transbronchial cryobiopsy has been confirmed as a new tool in the diagnosis of interstitial lung diseases, given its fewer risks and costs compared to surgical approach. This study is aimed at assessing the effectiveness of cryobiopsy in the diagnosis of lymphoproliferative disorders. Materials and methods:Among 970 consecutive cryobiopsies, performed between January 2011 and June 2018 at Morgagni Hospital of Forlì, Italy, 13 cases of lymphoproliferative disorders were collected. Results:In 12 out of 13 cases a precise pathological diagnosis could be reached with the support of immunohistochemistry (IHC) and molecular ancillary studies. In the only case in which cryobiopsy did not lead to a definitive diagnosis, the subsequent surgical biopsy also did not help to clarify the diagnosis. Severe bleeding or pneumothorax did not occur in any case. On average, five biopsies were obtained per case, with a mean total area of 1161 mm, and only 5 out of 65 specimens were inadequate for diagnosis. Instant freezing did not produce tissue artefacts nor did it affect IHC and molecular tests. In all cases the amount of available tissue was sufficient for all ancillary studies. Conclusions:Transbronchial lung cryobiopsy is safe and effective for diagnosis in patients with suspected pulmonary involvement by lymphoproliferative disorders and it should therefore be considered a valid alternative to surgical biopsy in such cases. 10.1183/23120541.00260-2019
    Transbronchial biopsy results according to diffuse interstitial lung disease classification. Cryobiopsy versus forceps: MULTICRIO study. Pajares Virginia,Núñez-Delgado Manuel,Bonet Gloria,Pérez-Pallarés Javier,Martínez Raquel,Cubero Noelia,Zabala Txomin,Cordovilla Rosa,Flandes Javier,Disdier Carlos,Torrego Alfons, PloS one BACKGROUND:In recent years, transbronchial cryobiopsy (TBCB) has come to be increasingly used in interventional pulmonology units as it obtains larger and better-quality samples than conventional transbronchial lung biopsy (TBLB) with forceps. No multicenter studies have been performed, however, that analyse and compare TBCB and TBLB safety and yield according to the interstitial lung disease (ILD) classification. OBJECTIVES:We compared the diagnostic yield and safety of TBCB with cryoprobe sampling versus conventional TBLB forceps sampling in the same patient. METHOD:Prospective multicenter clinical study of patients with ILD indicated for lung biopsy. Airway management with orotracheal tube, laryngeal mask and rigid bronchoscope was according to the protocol of each centre. All procedures were performed using fluoroscopy and an occlusion balloon. TBLB was followed by TBCB. Complications were recorded after both TBLB and TBCB. RESULTS:Included were 124 patients from 10 hospitals. Airway management was orotracheal intubation in 74% of cases. Diagnostic yield according to multidisciplinary committee results for TBCB was 47.6% and for TBLB was 19.4% (p<0.0001). Diagnostic yield was higher for TBCB compared to TBLB for two groups: idiopathic interstitial pneumonias (IIPs) and ILD of known cause or association (OR 2.5; 95% CI: 1.4-4.2 and OR 5.8; 95% CI: 2.3-14.3, respectively). Grade 3 (moderate) bleeding after TBCB occurred in 6.5% of patients compared to 0.8% after conventional TBLB. CONCLUSIONS:Diagnostic yield for TBCB was higher than for TBLB, especially for two disease groups: IIPs and ILD of known cause or association. The increased risk of bleeding associated with TBCB confirms the need for safe airway management and prophylactic occlusion-balloon use. TRIAL REGISTRATION:clinicaltrials.gov identifier: NCT02464592. 10.1371/journal.pone.0239114
    Transbronchial lung cryobiopsy: a novel confirmatory tool to diagnose asbestos-related pulmonary fibrosis. Zajaczkowska Marta,Johnson Anthony,Gallur Luis,Shin Joo,Henderson Christopher,Williamson Jonathan Respirology case reports Asbestosis is diagnosed with a combination of historical, clinical and radiological findings in the absence of another cause. Histology is required when uncertainty exists, with lung biopsy via VATs being gold standard. Transbronchial cryobiopsy is becoming increasingly popular for diagnosing interstitial lung disease and may provide sufficient lung sample to demonstrate asbestosis. A 73 year old man presented with dyspnoea on a background of rheumatoid arthritis, previous methotrexate use and asbestos exposure. Examination revealed fine crackles in the mid and lower zones bilaterally without signs of pulmonary hypertension. The presence of pleural plaques and basal interstitial reticulation on HRCT was suggestive of asbestosis but histology was required to differentiate this from rheumatoid or methotrexate associated ILD. Samples of lung tissue were obtained via transbronchial cryobiopsy, demonstrating fibrosis and asbestos fibres consistent with asbestosis. Transbronchial cryobiopsy appears effective in obtaining sufficient parenchymal lung samples to diagnose asbestosis when clinical uncertainty exists. 10.1002/rcr2.380
    Prognostic value of transbronchial lung cryobiopsy for the multidisciplinary diagnosis of idiopathic pulmonary fibrosis: a retrospective validation study. Tomassetti Sara,Ravaglia Claudia,Wells Athol U,Cavazza Alberto,Colby Thomas V,Rossi Giulio,Ley Brett,Ryu Jay H,Puglisi Silvia,Arcadu Antonella,Marchi Martina,Sultani Fabio,Martinello Sabrina,Donati Luca,Gurioli Carlo,Gurioli Christian,Tantalocco Paola,Hetzel Jurgen,Dubini Alessandra,Piciucchi Sara,Klersy Catherine,Lavorini Federico,Poletti Venerino The Lancet. Respiratory medicine BACKGROUND:Transbronchial lung cryobiopsy (TBLC) has been introduced recently in the diagnosis of interstitial lung diseases. We aimed to evaluate the prognostic significance of the distinction between idiopathic pulmonary fibrosis and other interstitial lung diseases with the use of TBLC data in multidisciplinary team (MDT) diagnosis. METHODS:In this single-centre, retrospective, investigator-initiated comparative study, we evaluated consecutive patients without a definite usual interstitial pneumonia pattern on high-resolution CT, who presented to the GB Morgagni Hospital (Forlì, Italy), and who underwent TBLC (Jan 1, 2011, to Dec 31, 2014) or surgical lung biopsy (SLB; Jan 1, 2002, to Dec 31, 2016). Three pathologists reviewed the specimens, masked to clinical information. MDT evaluation was done before and after biopsy. The primary endpoint was the prognostic significance of the MDT diagnostic separation between idiopathic pulmonary fibrosis and other interstitial lung diseases in patients undergoing TBLC. Mortality was evaluated by means of Cox regression analysis. FINDINGS:We evaluated 500 consecutive cases, 426 of which were included: 266 had TBLC and 160 had SLB. 189 patients had idiopathic pulmonary fibrosis, 143 had other fibrotic interstitial lung diseases, and 94 had non-fibrotic interstitial lung diseases. Patients undergoing TBLC had more comorbidities and better preserved lung function compared with those undergoing SLB; among patients with a final MDT diagnosis of idiopathic pulmonary fibrosis, patients undergoing TBLC were older, had more comorbidities, and had a different post-biopsy treatment profile than those who received SLB. The distinction between idiopathic pulmonary fibrosis and other interstitial lung diseases made by MDT diagnosis on the basis of TBLC biopsy had clear prognostic significance, with a 5-year transplant-free survival of 68% (95% CI 57-76) in patients with an MDT idiopathic pulmonary fibrosis diagnosis based on TBLC compared with 93% (87-96) in patients without an idiopathic pulmonary fibrosis diagnosis based on TBLC (hazard ratio 5·28, 95% CI 2·72-10·04; p<0·0001). This distinction remained statistically significant in a multivariate analysis controlling for age, sex, smoking status, comorbidities, pulmonary function, and high-resolution CT patterns (p=0·02). INTERPRETATION:TBLC makes an important diagnostic contribution in interstitial lung disease, on the basis of the prognostic distinction between idiopathic pulmonary fibrosis and other interstitial lung diseases when TBLC findings are included in multidisciplinary diagnosis. FUNDING:None. 10.1016/S2213-2600(20)30122-3
    [Transbronchial cryobiopsy in diffuse interstitial lung diseases]. Camuset J,Naccache J M,Dhalluin X,Febvre M,Wallyn F,Ouennoure O,Copin M-C,Assouad J,Antoine M,Cadranel J,Fournier C Revue des maladies respiratoires INTRODUCTION:In the diagnostic approach to interstitial lung disease (ILD), the use of transbronchial cryobiopsy (TBC) may offer an alternative to surgical lung biopsy (SLB). We report the diagnostic effectiveness and the safety of TBC in ILD based on the preliminary experience in two French university centers. METHODS:Twenty four patients underwent TBC for the diagnosis of ILD in the operating room between 2014 and 2017. All the histological diagnoses obtained were then reviewed and validated during multidisciplinary discussions (MDD). RESULTS:Patients had an average of 3 TBC.TBC samples were analyzable in 22/24 (91.7%) patients. In these, samples allowed a histological diagnosis to be made in 14/22 (63.6%) patients and a diagnosis with certainty in 13/22 (59%) after MDD. The overall diagnostic yield from TBC was 13/24 (54.2%). Nine (37.5%) patients had a pneumothorax. Five (20.8%) patients had a bleeding. There were no deaths. Taking into account a possible initial learning curve and considering only the 15 patients who had their TBC after 2015, we note that a diagnosis could be made after MDD for 12 of them, that is, 80%. CONCLUSION:A prospective randomized study is needed to evaluate the technique in France in order to specify its diagnostic performance and its safety profile in comparison to SLB. 10.1016/j.rmr.2018.10.618
    Diagnostic accuracy of transbronchial lung cryobiopsy for interstitial lung disease diagnosis (COLDICE): a prospective, comparative study. Troy Lauren K,Grainge Christopher,Corte Tamera J,Williamson Jonathan P,Vallely Michael P,Cooper Wendy A,Mahar Annabelle,Myers Jeffrey L,Lai Simon,Mulyadi Ellie,Torzillo Paul J,Phillips Martin J,Jo Helen E,Webster Susanne E,Lin Qi T,Rhodes Jessica E,Salamonsen Matthew,Wrobel Jeremy P,Harris Benjamin,Don Garrick,Wu Peter J C,Ng Benjamin J,Oldmeadow Christopher,Raghu Ganesh,Lau Edmund M T, The Lancet. Respiratory medicine BACKGROUND:Transbronchial lung cryobiopsy (TBLC) is a novel technique for sampling lung tissue for interstitial lung disease diagnosis. The aim of this study was to establish the diagnostic accuracy of TBLC compared with surgical lung biopsy (SLB), in the context of increasing use of TBLC in clinical practice as a less invasive biopsy technique. METHODS:COLDICE was a prospective, multicentre, diagnostic accuracy study investigating diagnostic agreement between TBLC and SLB, across nine Australian tertiary hospitals. Patients with interstitial lung disease aged between 18 and 80 years were eligible for inclusion if they required histopathological evaluation to aid diagnosis, after detailed baseline evaluation. After screening at a centralised multidisciplinary discussion (MDD), patients with interstitial lung disease referred for lung biopsy underwent sequential TBLC and SLB under one anaesthetic. Each tissue sample was assigned a number between 1 and 130, allocated in a computer-generated random sequence. Encoded biopsy samples were then analysed by masked pathologists. At subsequent MDD, de-identified cases were discussed twice with either TBLC or SLB along with clinical and radiological data, in random non-consecutive order. Co-primary endpoints were agreement of histopathological features in TBLC and SLB for patterns of definite or probable usual interstitial pneumonia, indeterminate for usual interstitial pneumonia, and alternative diagnosis; and for agreement of consensus clinical diagnosis using TBLC and SLB at MDD. Concordance and κ values were calculated for each primary endpoint. This study is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12615000718549. FINDINGS:Between March 15, 2016, and April 15, 2019, we enrolled 65 patients (31 [48%] men, 34 [52%] women; mean age 66·1 years [SD 9·3]; forced vital capacity 83·7% [SD 14·2]; diffusing capacity for carbon monoxide 63·4% [SD 12·8]). TBLC (7·1 mm, SD 1·9) and SLB (46·5 mm, 14·9) samples were each taken from two separate ipsilateral lobes. Histopathological agreement between TBLC and SLB was 70·8% (weighted κ 0·70, 95% CI 0·55-0·86); diagnostic agreement at MDD was 76·9% (κ 0·62, 0·47-0·78). For TBLC with high or definite diagnostic confidence at MDD (39 [60%] of 65 cases), 37 (95%) were concordant with SLB diagnoses. In the 26 (40%) of 65 cases with low-confidence or unclassifiable TBLC diagnoses, SLB reclassified six (23%) to alternative high-confidence or definite MDD diagnoses. Mild-moderate airway bleeding occurred in 14 (22%) patients due to TBLC. The 90-day mortality was 2% (one of 65 patients), following acute exacerbation of idiopathic pulmonary fibrosis. INTERPRETATION:High levels of agreement between TBLC and SLB for both histopathological interpretation and MDD diagnoses were shown. The TBLC MDD diagnoses made with high confidence were particularly reliable, showing excellent concordance with SLB MDD diagnoses. These data support the clinical utility of TBLC in interstitial lung disease diagnostic algorithms. Further studies investigating the safety profile of TBLC are needed. FUNDING:University of Sydney, Hunter Medical Research Institute, Erbe Elektromedizin, Medtronic, Cook Medical, Rymed, Karl-Storz, Zeiss, and Olympus. 10.1016/S2213-2600(19)30342-X
    Concordance between sequential transbronchial lung cryobiopsy and surgical lung biopsy in patients with diffuse interstitial lung disease. Zaizen Yoshiaki,Kohashi Yasuo,Kuroda Kishio,Tabata Kazuhiro,Kitamura Yuka,Hebisawa Akira,Saito Yuji,Fukuoka Junya Diagnostic pathology BACKGROUND:Increasing 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. METHODS:We 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. RESULTS:Six 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. CONCLUSION:Our 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. 10.1186/s13000-019-0908-z
    Transbronchial Lung Cryobiopsy in Interstitial Lung Diseases: Best Practice. Colella Sara,Haentschel Maik,Shah Pallav,Poletti Venerino,Hetzel Jürgen Respiration; international review of thoracic diseases The lung biopsy in interstitial lung disease (ILD) represents an important diagnostic step when the clinical and radiological data are insufficient for a firm diagnosis. A growing body of evidence suggests the utility of transbronchial lung cryobiopsy (TBLC) in the diagnostic algorithm of ILD as it allows, compared to transbronchial lung biopsy with conventional forceps, a better identification of complex histological patterns - such as usual interstitial pneumonia - and can provide information which has a clinical impact on the multidisciplinary discussion similar to that provided by surgical lung biopsy. Performed correctly, it appears to have a better safety profile than surgery. The decision to perform a lung biopsy should be a multidisciplinary decision process where it is felt that there is sufficient diagnostic doubt after a careful clinical evaluation including review of the computed tomograms of the thorax. The presence of severe pulmonary hypertension (> 50 mm Hg), poor lung function (FVC < 50%), or dismissed gas transfer (DLCO of < 35%) are considered relative contraindications for TBLC. Anticoagulants and antiplatelet drugs should be discontinued for the minimum period required for the specific drugs. The greatest consideration should be given to ensure the biopsy is performed safely and we recommend the use of either an endotracheal tube or rigid bronchoscopy. Deep sedation or general anesthesia allow better control of the procedure and a better patient experience. Prophylactic balloon blockers should be used to tamponade any bleeding and also to prevent overspill of blood from the segment that is being sampled. The procedure should be performed under fluoroscopy to ensure that samples are ideally obtained about 10 mm from the pleural edge. The cryoprobe is activated for about 5 s for the first biopsy and then adjusted according to the sample size obtained. With a careful standardized approach it is possible to obtain good-quality lung specimens for diagnosis in a safe manner. 10.1159/000488910
    Diagnostic utility of transbronchial lung cryobiopsy: Two cases of anti-aminoacyl-tRNA synthetase syndrome with respiratory failure. Yoshimura Hanako,Awano Nobuyasu,Inomata Minoru,Kuse Naoyuki,Tone Mari,Jo Tatsunori,Takemura Tamiko,Kumasaka Toshio,Izumo Takehiro Respiratory investigation Transbronchial lung cryobiopsy (TBLC) is a useful and safe method for the diagnosis of interstitial lung disease (ILD). Herein, we describe the cases of two patients who developed ILD from anti-aminoacyl-tRNA synthetase syndrome with respiratory failure. TBLC was performed instead of surgical lung biopsy. There were no complications, and sufficient specimens were harvested to make the precise histopathological diagnosis. TBLC should be considered as a critical approach for the histopathological diagnosis of ILD in patients who cannot undergo surgical lung biopsy because of respiratory failure. 10.1016/j.resinv.2019.03.002
    Competence in transbronchial cryobiopsy. Barisione Emanuela,Salio Mario,Romagnoli Micaela,Praticò Alessia,Bargagli Elena,Corbetta Lorenzo Panminerva medica Over the last decade transbronchial lung cryobiopsy (TBLC) has proven to be an "innovative application" of an "old procedure" for the histologic diagnosis of diffuse interstitial lung diseases (DILDs). Thus, the technique of TBL cryobiopsy is now adopted for diagnostic purposes, transbronchially in peripheral airways to sample lung parenchyma, whereas this same technique was traditionally employed in the past for therapeutic purposes, essentially for the management of malignant obstruction of central airways. When patients with interstitial lung diseases (ILDs) need histopathological data in their diagnostic pathway, this bioptic approach could be a valid alternative to surgical lung biopsy, that is still the gold standard at the moment. TBL cryobiopsy has a good safety profile, its sensitivity and specificity appear good overall in idiopathic pulmonary fibrosis. In the last ten years, many papers have been published about this procedure defining modalities by which cryobiopsy should be performed. These studies have shown that TBL cryobiopsy is feasible, it allows to obtain larger lung parenchymal specimens (3 times larger than "classic" transbronchial biopsies), characterized by unaltered and artefact-free morphology, and it represents a safe and poorly invasive diagnostic tool for the histologic diagnosis of ILDs. The technical aspects are really important, and they still need a complete standardization. TBL cryobiopsy should be part of an equipment of the modern interventional pulmonologist, who should know indications and contraindications of this methodic and the technical aspects of the procedure. This is a complex procedure requiring to be performed by endoscopists working in specialized centers with specific knowledge of DILDs, and a multidisciplinary approach, which represent pre-requisites for admission to training in this procedure. 10.23736/S0031-0808.18.03567-X
    Transbronchial Lung Cryobiopsy for Interstitial Lung Disease Diagnosis: A Perspective From Members of the Pulmonary Pathology Society. Raparia Kirtee,Aisner Dara L,Allen Timothy Craig,Beasley Mary Beth,Borczuk Alain,Cagle Philip T,Capelozzi Vera,Dacic Sanja,Hariri Lida P,Kerr Keith M,Lantuejoul Sylvie,Mino-Kenudson Mari,Rekhtman Natasha,Roden Anja C,Roy-Chowdhuri Sinchita,Sholl Lynette,Smith Maxwell L,Thunnissen Eric,Tsao Ming Sound,Yatabe Yasushi Archives of pathology & laboratory medicine Transbronchial lung cryobiopsy involves using a cryoprobe rather than forceps to obtain a bronchoscopic biopsy. Recent studies have shown that transbronchial cryobiopsy provides a larger specimen than conventional transbronchial forceps biopsy, and that the interobserver agreement in the interpretation of cryobiopsy specimens is comparable to that of a surgical lung biopsy. This is encouraging, and transbronchial lung cryobiopsy clearly has a role in the workup and diagnosis of interstitial lung diseases. However, very few patients who have been studied underwent both transbronchial lung cryobiopsy and surgical lung biopsy, and the available data suggest that the diagnostic accuracy of cryobiopsy may not be similar to that of surgical lung biopsy. Further study is needed before transbronchial lung biopsy can be recommended as a replacement for surgical lung biopsy. 10.5858/arpa.2016-0258-SA
    Safety of performing transbronchial lung cryobiopsy on hospitalized patients with interstitial lung disease. Cooley Joseph,Balestra Rick,Aragaki-Nakahodo Alejandro A,Caudell Stamper Danielle N,Sriprasart Thitiwat,Swank Zulma,Baughman Robert P,Benzaquen Sadia Respiratory medicine INTRODUCTION:Transbronchial lung cryobiopsy (TBLC) has become a popular option for tissue diagnosis of interstitial lung disease (ILD), however reports vary regarding the safety of this procedure. Herein, we evaluate the safety of transbronchial cryobiopsy in hospitalized patients, comparing adverse events to outpatient procedures. METHODS AND MEASUREMENTS:This is a single center, retrospective chart review of all TBLC performed for suspected ILD between November 2013 and March 2017. Biopsies were performed by a board certified interventional pulmonologist or interventional pulmonology fellow using a two-scope technique. RESULTS:One hundred fifty-nine cryobiopsies were performed for the diagnosis of ILD. Rates of adverse events are as follows: pneumothorax 11%, persistent air leak 1.3%, moderate-severe bleeding 3.8%, ICU transfer within 48 h 3.1%, and all cause 30-day mortality 1.9%. No deaths were attributed to the procedure. Comparing adverse events between hospitalized patients and outpatients, rates of pneumothorax were 24% vs 9.9%, persistent air leak 5.9% vs 0.7%, ICU transfer 12% vs 2.1%, and 30-day mortality 5.9% vs 1.4%. However, no differences were statistically significant. CONCLUSION:Practitioners should recognize that while cryobiopsies are a high-yield, safe, and cost-effective alternative to surgical lung biopsy, not all procedures carry the same risk profiles. Hospitalized patients may have a greater propensity for pneumothorax, persistent air leak, transfer to the ICU, and 30-day mortality. 10.1016/j.rmed.2018.05.019
    Management and utility of transbronchial lung cryobiopsy in Japan. Kuse Naoyuki,Inomata Minoru,Awano Nobuyasu,Yoshimura Hanako,Jo Tatsunori,Tone Mari,Moriya Atsuko,Bae Yuan,Kumasaka Toshio,Takemura Tamiko,Izumo Takehiro Respiratory investigation BACKGROUND:Transbronchial lung cryobiopsy (TBLC), which is transbronchial lung biopsy performed using a cryoprobe, has emerged as a new method for obtaining lung tissue specimens for diagnosing pulmonary diseases. TBLC has been widely performed, and many reports have documented its safety and feasibility in diagnosing pulmonary diseases such as lung cancer and diffuse parenchymal lung disease. However, to date, no reports have yet been published from Japan. Therefore, the purpose of this study was to describe our experience with TBLC in daily practice in Japan and compare it with those reported in previous studies from other countries. We also evaluated the efficacy and feasibility of TBLC. METHODS:We retrospectively evaluated the clinical records of 50 consecutive patients who had undergone TBLC between November 2017 and May 2018 at the Japanese Red Cross Medical Center. Demographic data, procedure details, and the diagnostic yield were analyzed. RESULTS:We analyzed the records of 50 patients who underwent diagnostic TBLC. Their median age was 71 years, and they included 34 men (68%). The median maximal diameter of the cryobiopsy specimens was 5.3 mm (range, 2.0-23.0 mm), and the median area of the cryobiopsy specimens was 15.5 mm (range, 3.0-136.5 mm). The rate of obtaining adequate specimens was 91%, and the pathological diagnostic yield was 76%. No complications were observed, except for one case of pneumonia. CONCLUSIONS:This is the first report from Japan analyzing the efficacy and feasibility of TBLC in daily clinical practice. TBLC was considered efficacious, safe, and feasible for Japanese patients with various lung diseases. 10.1016/j.resinv.2018.12.011
    Idiopathic pulmonary fibrosis: prognostic impact of histologic honeycombing in transbronchial lung cryobiopsy. Ravaglia Claudia,Bosi Marcello,Wells Athol U,Gurioli Carlo,Gurioli Christian,Dubini Alessandra,Piciucchi Sara,Puglisi Silvia,Mascetti Susanna,Arcadu Antonella,Tomassetti Sara,Poletti Venerino Multidisciplinary respiratory medicine Background:Prognostic evaluation in idiopathic pulmonary fibrosis (IPF) may be important as it can guide management decisions, but the potential role of honeycomb changes in providing information about outcome and survival of patients with IPF, particularly if diagnosed using cryobiopsy, has not been evaluated. Aim of this study was to determinate whether a relationship exists between honeycombing on cryobiopsy and clinical/radiological picture and outcome in patients with IPF and to assess whether the same pathologic criteria that have been used to define the UIP pattern (usual interstitial pneumonia) for surgical biopsy can also be applied to cryobiopsy. Methods:Sixty-three subjects with a multidisciplinary diagnosis of IPF and a UIP pattern on cryobiopsy were evaluated. Patients were classified into two sub-groups depending on the presence of honeycombing on histology. Results:The presence of honeycombing on cryobiopsy did not identify a specific phenotype of patients as it did not correlate with radiological and clinical picture and it was not associated neither with the risk of death ( = 0.1192) or with the event-free survival ( = 0.827); a higher number of samples and the presence of pleura on biopsy were instead associated with an increase in the finding of honeycombing. Conclusions:The same pathologic criteria that have been used to define the UIP pattern in surgical biopsies (with honeycombing changes considered as non-mandatory for the definition of the pattern itself) can be applied to cryobiopsy samples, as the presence of these changes do not define different clinical or radiological phenotypes of patients with IPF. 10.1186/s40248-019-0170-y
    [Transbronchial lung cryobiopsy in diffuse lung disease: a pathological analysis of 173 cases]. Liu C P,Gu Y Y,Li S Y,Chen X B,Li L G,Jiang J J,Zhao J,Fu L,Li M S,Chen Z C Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases To evaluate the value of transbronchial lung cryobiopsy (TBCB) in pathological diagnosis for diffuse lung disease. The clinicopathological data of 173 patients from the first affiliated hospital of Guangzhou medical university between Jaunary 2017 and June 2019 with transbronchial lung cryobiopsy of diffuse lung disease were retrospectively analyzed and summarized with review. Among 173 cases, TBCB and conventional transbronchial lung biopsy (TBLB) were performed in 54 patients. The size of biopsy samples and diagnostic yield were compared. Among 173 cases, the diagnostic yield was 85.54% (148/173) , 160 (92.49%) cases provided definite diagnosis and valuable pathological results, according to age, sex, occupation, past history, contact history, smoking history, laboratory serology and imaging findings. Among 160 cases, there were 72 cases of known etiology (45.00%), 27 cases of idiopathic interstitial pneumonia (16.88%), 7 cases of granulomatous lesions (4.38%) and 54 cases of other types (33.75%). With TBCB and TBLB in 54 patients, the specimens sizes of TBCB and TBLB were (3.3±1.3) mm(2) and (1.0±0.3) mm(2) respectively ('=12.67 0.01) . The diagnostic yields of TBCB and TBLB were 81.48% (44/54) and 42.59% (23/54) respectively (χ(2)=17.33, 0.01) . The diagnostic yields of TBCB and TBLB for interstitial lung diseases were 48.15% (26/54) and 5.56% (3/54) respectively (χ(2)=24.94, 0.01) . However, the diagnostic yields of TBCB and TBLB for the other diffuse lung disease except interstitial lung diseases were 33.33% (18/54) and 37.04% (20/54) respectively, with no significant difference (χ(2)=0.1624, 0.687). Compared with TBLB, TBCB has obvious advantages and application value in the diagnosis of diffuse pulmonary diseases, especially interstitial pulmonary diseases. 10.3760/cma.j.issn.1001-0939.2020.03.018
    Transbronchial Cryobiopsy in the Diagnosis of Fibrotic Interstitial Lung Disease. Mehrad Mitra,Colby Thomas V,Rossi Giulio,Cavazza Alberto Archives of pathology & laboratory medicine CONTEXT.—:Transbronchial cryobiopsy is an emerging procedure to obtain lung tissue for diagnosis of interstitial lung disease and has gained popularity because it is less invasive and has a lower rate of complications compared with nonselective surgical lung biopsy. OBJECTIVE.—:To provide an overview of the status of the medical literature regarding transbronchial cryobiopsy . DATA SOURCES.—:A literature search was performed using PubMed search engine. The terms "cryobiopsy" or "cryoprobe" and "interstitial lung disease" or "diffuse parenchymal lung disease" or "pulmonary fibrosis" were used, with the search concluding at the end of November 2019. CONCLUSIONS.—:While the diagnostic yield of transbronchial cryobiopsy is slightly lower than surgical lung biopsy, a growing literature suggests that with a multidisciplinary approach cryobiopsy provides diagnostic and prognostic information approaching that of surgical lung biopsy with lower morbidity and mortality. 10.5858/arpa.2020-0007-RA
    Transbronchial Cryobiopsy in the Diagnosis of Diffuse Lung Disease. Cavazza Alberto,Colby Thomas V,Dubini Alessandra,Tomassetti Sara,Ravaglia Claudia,Poletti Venerino,Mengoli Maria Cecilia,Tagliavini Elena,Rossi Giulio Surgical pathology clinics Transbronchial cryobiopsy, a new diagnostic procedure in patients with diffuse lung disease, provides larger and better-preserved lung specimens compared to forceps biopsy. The diagnostic yield of cryobiopsy is much better than that of forceps biopsy and slightly lower than that of surgical lung biopsy, but with a lower complication rate compared to the latter. Literature suggests that in the multidisciplinary approach to patients with diffuse lung disease cryobiopsy provides diagnostic and prognostic information similar to surgical lung biopsy. Cryobiopsy can also be performed in some patients unsuitable for surgical biopsy, yet in whom histologic input is needed. 10.1016/j.path.2019.11.004
    Transbronchial Cryobiopsy in Diffuse Lung Disease: Update for the Pathologist. Colby Thomas V,Tomassetti Sara,Cavazza Alberto,Dubini Alessandra,Poletti Venerino Archives of pathology & laboratory medicine CONTEXT:- Transbronchial cryobiopsy has recently been proposed as an alternative to surgical biopsy in the diagnosis of diffuse lung disease. OBJECTIVE:- To familiarize pathologists with transbronchial cryobiopsy, including what it is, how it is performed, how it compares to other techniques of lung biopsy in diffuse lung disease, what are the technical issues relating to it, what the complications are, how cryobiopsies should be interpreted, and the clinical usefulness of cryobiopsy. DATA SOURCES:- All the available literature on cryobiopsy in diffuse lung disease through May 2016, primarily in the last 5 years, was reviewed, and some unpublished data known to the authors were included. CONCLUSIONS:- Cryobiopsies are considerably larger than forceps biopsies and allow pattern recognition approaching that of a surgical lung biopsy in many cases. Artifacts associated with cryobiopsy are minimal. In comparison with surgical lung biopsies, the diagnosis rate with cryobiopsies is lower, in the neighborhood of 80%, versus higher than 90% for surgical lung biopsies. Cryobiopsy is proposed as an alternative to surgical lung biopsy and a technique that may appreciably decrease the number of patients who require surgical lung biopsy for diagnosis. This is important because the mortality from cryobiopsy is very small (0.1% to date) compared with surgical lung biopsy (1.7% for elective procedures and considerably higher for nonelective procedures). 10.5858/arpa.2016-0233-RA
    Transbronchial Lung Cryobiopsy in Idiopathic Pulmonary Fibrosis: A State of the Art Review. Lodhi Taha,Hughes Gareth,Stanel Stefan,Chaudhuri Nazia,Hayton Conal Advances in therapy Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease associated with significant morbidity and mortality. The diagnosis of IPF involves a combination of clinical history, radiological imaging and examination of histopathological samples in appropriate cases. Historically, transbronchial biopsy (TBB) has been used to obtain histological samples; however this lacks diagnostic accuracy. At present, surgical lung biopsy (SLB) is the gold standard technique for obtaining specimen samples; however this carries a significant mortality risk. Transbronchial lung cryobiopsy (TBLC) is a new technique that has been pioneered in the management of lung malignancy and offers a potential alternative to SLB. The technique employs a freezing probe, which is used to obtain lung tissue samples that are larger and better quality than traditional TBB samples. This affords TBLC an estimated diagnostic yield of 80% in interstitial lung disease. However, with limited evidence directly comparing TBLC to SLB, the diagnostic accuracy of the procedure has been uncertain. Common complications of TBLC include pneumothorax and bleeding. Mortality in TBLC is low compared with SLB, with exacerbation of IPF frequently reported as the cause. TBLC represents an exciting potential option in the diagnostic pathway in IPF; however its true value has yet to be determined. 10.1007/s12325-019-01036-y
    High Diagnostic Accuracy of Transbronchial Cryobiopsy in Fibrotic Interstitial Lung Diseases Compared to Final Explant Diagnosis. Unterman Avraham,Wand Ori,Fridel Ludmila,Edelstein Evgeny,Pertzov Barak,Kramer Mordechai R Respiration; international review of thoracic diseases BACKGROUND:A diagnostic lung biopsy may be required in some cases of fibrotic interstitial lung diseases (ILD). Transbronchial cryobiopsy has been suggested as a possible alternative to surgical lung biopsy. However, previous estimates of its diagnostic yield were not validated compared to the definitive diagnosis in explanted lungs. OBJECTIVES:We aimed to assess the diagnostic accuracy of cryobiopsy in fibrotic ILD patients who subsequently had lung transplantation. METHODS:All 197 patients who underwent lung transplantation at our Center due to fibrotic ILD from January 2010 to May 2018, were screened for the presence of a pre-transplant cryobiopsy. Fourteen patients who underwent cryobiopsy before transplantation were identified. Two expert lung pathologists blindedto the explant diagnoses, independently examined these cryobiopsy specimens to decide if they match guideline criteria for usual interstitial pneumonia (UIP) pattern or an alternative diagnosis. The primary measure was the diagnostic accuracy of cryobiopsy to detect or refute a UIP pattern, as compared to the final explant diagnosis. RESULTS:Median time between cryobiopsy and transplantation was 1.4 years. All 14 cryobiopsy samples contained adequate alveolar tissue. The explant diagnosis of 13/14 patients was UIP. The two pathologists correctly diagnosed or refuted UIP in the cryobiopsy specimen in 12/14 cases (85.7%) and 11/14 cases (78.6%), respectively. The level of diagnostic agreement between pathologists was good (kappa 0.59, p = 0.016). CONCLUSIONS:Compared to the final explant diagnosis, transbronchial cryobiopsy had high diagnostic accuracy and good inter-observer agreement for UIP pattern. These findings support a potential diagnostic role for cryobiopsy in experienced centers. 10.1159/000502893
    Use of transbronchial cryobiopsy in the diagnosis of interstitial lung disease-a systematic review and cost analysis. Sharp C,McCabe M,Adamali H,Medford A R QJM : monthly journal of the Association of Physicians Background:Histological diagnosis by surgical lung biopsy for interstitial lung disease (ILD) is currently limited. Transbronchial cryobiopsy via flexible bronchoscope may this for more patients. The relative costs, diagnostic yields and safety of this approach and more traditional approaches have not been determined. Objectives:To perform a systematic review and meta-analysis of transbronchial cryobiopsy, forceps transbronchial biopsy and video assisted (VATS) surgical lung biopsy assessing their relative diagnostic yields and safety. To perform a cost analysis to demonstrate any savings through change to the newer technique. Methods:We performed a systematic review of the literature using MEDLINE and EMBASE for all original articles on the diagnostic yield and safety of transbronchial cryobiopsy, forceps transbronchial biopsy and VATS-biopsy in ILD up to February 2016. Data were extracted on yield and complication rates, in addition to study characteristics. Theoretical cost analysis was performed from local institution financial data, 2015-16 reimbursement tariffs and results of the systematic review. Results:A meta-analysis of 11 investigations for transbronchial cryobiopsy, 11 for forceps transbronchial biopsy and 24 for VATS-biopsy revealed diagnostic yields of 84.4% (75.9-91.4%), 64.3% (52.6-75.1%) and 91.1% (84.9-95.7%), respectively. Pneumothorax occurred in 10% (5.4-16.1%) of transbronchial cryobiopsy procedures, moderate bleeding in 20.99% (5.6-42.8%), with three deaths reported. Surgical mortality was 2.3% (1.3-3.6%). Cost analysis demonstrated potential savings of £210 per patient in the first year and £647 in subsequent years. Conclusions:Transbronchial cryobiopsy represents a potentially cost-saving approach to improve histological diagnosis in ILD, however is accompanied by a significant risk of moderate bleeding. 10.1093/qjmed/hcw142
    Transbronchial Lung Cryobiopsy and Video-assisted Thoracoscopic Lung Biopsy in the Diagnosis of Diffuse Parenchymal Lung Disease. A Meta-analysis of Diagnostic Test Accuracy. Iftikhar Imran H,Alghothani Lana,Sardi Alejandro,Berkowitz David,Musani Ali I Annals of the American Thoracic Society RATIONALE:Transbronchial lung cryobiopsy is increasingly being used for the assessment of diffuse parenchymal lung diseases. Several studies have shown larger biopsy samples and higher yields compared with conventional transbronchial biopsies. However, the higher risk of bleeding and other complications has raised concerns for widespread use of this modality. OBJECTIVES:To study the diagnostic accuracy and safety profile of transbronchial lung cryobiopsy and compare with video-assisted thoracoscopic surgery (VATS) by reviewing available evidence from the literature. METHODS:Medline and PubMed were searched from inception until December 2016. Data on diagnostic performance were abstracted by constructing two-by-two contingency tables for each study. Data on a priori selected safety outcomes were collected. Risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool. Random effects meta-analyses were performed to obtain summary estimates of the diagnostic accuracy. RESULTS:The pooled diagnostic yield, pooled sensitivity, and pooled specificity of transbronchial lung cryobiopsy were 83.7% (76.9-88.8%), 87% (85-89%), and 57% (40-73%), respectively. The pooled diagnostic yield, pooled sensitivity, and pooled specificity of VATS were 92.7% (87.6-95.8%), 91.0% (89-92%), and 58% (31-81%), respectively. The incidence of grade 2 (moderate to severe) endobronchial bleeding after transbronchial lung cryobiopsy and of post-procedural pneumothorax was 4.9% (2.2-10.7%) and 9.5% (5.9-14.9%), respectively. CONCLUSIONS:Although the diagnostic test accuracy measures of transbronchial lung cryobiopsy lag behind those of VATS, with an acceptable safety profile and potential cost savings, the former could be considered as an alternative in the evaluation of patients with diffuse parenchymal lung diseases. 10.1513/AnnalsATS.201701-086SR
    Diagnostic Yield and Complications of Transbronchial Lung Cryobiopsy for Interstitial Lung Disease. A Systematic Review and Metaanalysis. Johannson Kerri A,Marcoux Veronica S,Ronksley Paul E,Ryerson Christopher J Annals of the American Thoracic Society RATIONALE:The diagnostic usefulness and safety of transbronchial lung cryobiopsy for the evaluation of interstitial lung disease remain unclear. OBJECTIVES:This systematic review and metaanalysis aims to establish the diagnostic accuracy and yield of transbronchial cryobiopsy for interstitial lung diseases. METHODS:We searched MedLine, EMBASE, Cochrane Central Register of Controlled Trials, and conference proceedings to identify studies assessing the diagnostic accuracy (compared with surgical biopsy) or yield of transbronchial lung cryobiopsy for interstitial lung disease (from database inception to January 2016). The diagnostic accuracy and yield were quantified and stratified by the method of diagnosis determination (histologic interpretation in isolation vs. incorporation within a multidisciplinary discussion). The frequency of procedure-related complications was also assessed from these reports. For full-text studies, random-effects models were used to calculate pooled estimates of diagnostic accuracy, yield, and complication frequency. MEASUREMENTS AND MAIN RESULTS:Of 900 citations, 11 studies were selected for inclusion in this systematic review (7 full text, 4 abstracts). The selected studies reported on a total of 731 patients. No studies reported the diagnostic accuracy of transbronchial cryobiopsy. Diagnostic yield ranged from 74 to 98% when transbronchial cryobiopsy findings were interpreted in isolation, with a pooled estimate of 83% (95% confidence interval [CI], 73-94). Diagnostic yield ranged from 51 to 98% when transbronchial cryobiopsy was reviewed within a multidisciplinary discussion, with a pooled estimate of 79% (95% CI, 65-93). Pooled estimates for pneumothorax and moderate/severe bleeding were 12% (95% CI, 3-21) and 39% (95% CI, 3-76), respectively. CONCLUSIONS:The diagnostic accuracy of transbronchial lung cryobiopsy cannot be determined given the absence of studies directly comparing cryobiopsy diagnoses with diagnoses derived from surgical lung biopsies interpreted within multidisciplinary discussions. The histopathological and multidisciplinary discussion-based diagnostic yield of transbronchial cryobiopsy appears high, but with variable frequencies of complications dominated by pneumothorax and moderate-to-severe hemorrhage. 10.1513/AnnalsATS.201606-461SR
    Bleeding risk of transbronchial cryobiopsy compared to transbronchial forceps biopsy in interstitial lung disease - a prospective, randomized, multicentre cross-over trial. Hetzel Juergen,Eberhardt Ralf,Petermann Christoph,Gesierich Wolfgang,Darwiche Kaid,Hagmeyer Lars,Muche Rainer,Kreuter Michael,Lewis Richard,Ehab Ahmed,Boeckeler Michael,Haentschel Maik Respiratory research BACKGROUND:Bronchoscopic cryobiopsy is a new method of bronchoscopic tissue sampling in interstitial lung disease. In case of transbronchial biopsies, the resultant tissue samples are of high quality, and the lung parenchyma seen in the samples is adequate for a histological diagnosis in most cases. Bleeding after transbronchial biopsy is the most important procedure- associated complication and may be life threatening. This study addresses the risk of bleeding of transbronchial cryobiopsy. METHODS:In this prospective, randomized, controlled multicentre study 359 patients with interstitial lung disease requiring diagnostic bronchoscopic tissue sampling were included. Both conventional transbronchial forceps biopsy and transbronchial cryobiopsy were undertaken in each patient. The sequence of the procedures was randomized. Bleeding severity was evaluated semi-quantitatively as "no bleeding", "mild" (suction alone), "moderate" (additional intervention) or "severe" (prolonged monitoring necessary or fatal outcome), for each intervention. RESULTS:In 359 patients atotal of 1160 cryobiopsies and 1302 forceps biopsies were performed. Bleeding was observed after forceps biopsy in 173 patients (48.2%) and after cryobiopsy in 261 patients (72.7%). Bleeding was significantly greater in the cryobiopsy group (cryobiopsy/forceps biopsy: no bleeding 27.3%/51.8%; mild 56.5%/44.0%; moderate 15.0%/4.2%; severe 1.2%/0%; p < 0.001). The rate of clinically relevant bleeding (moderate or severe) was higher after the cryobiopsy procedures compared to the forceps biopsies (16.2% vs. 4.2%, p < 0.05). No fatal bleeding complications occurred. CONCLUSIONS:Compared to transbronchial forceps biopsy, transbronchial cryobiopsy was associated with an increased risk of bleeding which is of clinical relevance. Therefore training and additional precautions for bleeding control should be considered. TRIAL REGISTRATION:The study was registered with clinicaltrials.gov ( NCT01894113 ). 10.1186/s12931-019-1091-1
    Before Freezing Out Cryobiopsy, We Need to Thaw Out Flaws in the Diagnosis of Interstitial Lung Disease. Maldonado Fabien,Wells Athol,Danoff Sonye,Colby Thomas,Ryu Jay,Poletti Venerino,Rickman Otis,Herth Felix,Wahidi Momen,Hetzel Juergen,Liberman Moishe,Yarmus Lonny American journal of respiratory and critical care medicine 10.1164/rccm.201903-0699LE