Yield and safety of different biopsy types in interstitial lung disease: a systematic review and meta-analysis

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

Transbronchial Lung Cryobiopsy for Interstitial Lung Disease Diagnosis: Results of the COLDICE Study

Transbronchial lung cryobiopsy (TBLC) is a novel technique for sampling lung tissue for interstitial lung disease (ILD) diagnosis. Despite increasing use, the diagnostic accuracy of TBLC compared to surgical lung biopsy (SLB) remains unclear. Methods: We conducted a prospective, multicenter study investigating agreement between TBLC and SLB. ILD patients referred for lung biopsy after central screening underwent sequential TLBC and SLB, under one anesthetic. Blinded analysis of samples was conducted by 3 pathologists, individually and by consensus. At multidisciplinary discussion (MDD), deidentified cases were discussed twice with either TBLC or SLB along with clinical and radiology data, in random non-consecutive order. Primary endpoints were agreement of TBLC and SLB for 1) “definite/probable usual interstitial pneumonia (UIP)”, “indeterminate for UIP” and “alternative diagnosis” histopathologic patterns; and for 2) MDD diagnoses. Concordance and kappa values were calculated. Results: 65 patients (30 males; age 66±9yrs; FVC 84±14%; DLCO 63±13%) were enrolled. TBLC (7.1±1.9mm) and SLB samples (47±15mm) were 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); agreement at MDD was 76.9%, κ 0.62 (95%CI 0.47-0.78). For TBLC with high/definite diagnostic confidence at MDD (39/65, 60% cases), 94.9% were concordant with SLB diagnoses. In the 26 with low-confidence/unclassifiable TBLC diagnoses, SLB reclassified only 6 to alternative high/definite MDD diagnoses. Conclusion: High agreement between TBLC and SLB for pathologic and MDD diagnoses support the clinical utility of TBLC in ILD diagnostic algorithms.

Prognostic value of transbronchial lung cryobiopsy for the multidisciplinary diagnosis of idiopathic pulmonary fibrosis: a retrospective validation study

Transbronchial Cryobiopsy Is Superior to Forceps Biopsy for Diagnosing both Fibrotic and Non-Fibrotic Interstitial Lung Diseases

Acute Hemothorax Following Bronchoscopic Cryobiopsy: A Novel Complication.

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

Rationale: Interstitial lung disease (ILD) can be challenging to diagnose, and frequently relies on multidisciplinary discussion of representative histopathology. Transbronchial lung cryobiopsy (TBLC) is accepted as a reasonable alternative to surgical lung biopsy due to its favorable safety profile and acceptable diagnostic accuracy. While imaging guidance with cone beam computed tomography (CBCT) has recently been shown to improve the safety profile of TBLC, its use is limited by cost and logistical burdens. 3D mobile fluorosocpy may represent an alternative to CBCT. We performed a retrospective analysis of the safety profile and radiation dose of TBLC using 3D mobile fluoroscopy guidance. Methods: A retrospective single center analysis of patients undergoing TBLC with 3D mobile fluoroscopy guidance using the Cios Spin (Siemens Healthineers USA, Malvern, PA) for ILD evaluation from August 2023 to March 2024 was performed. Safety, defined as the incidence of pulmonary hemorrhage or pneumothorax, was the primary endpoint. Radiation dose was the secondary endpoint. Procedures were performed under general anesthesia through a 9.0mm endotracheal tube with endobronchial blocker placement. After airway inspection and bronchoalveolar lavage were performed, a 1.7mm single use cryoprobe with CO2 as the cryogen (Erbe Medizintechnik GmbH, Tübingen, Germany) was used for TBLC. A bronchoscope holder (Mediflex bronchoscope stabilization system, Mediflex, Islandia, NY, USA) was used to stabilize the cryoprobe during the 3D fluoroscopy spin. If clinically indicated, transbronchial lung forceps biopsy was performed after TBLC. Results: 51 patients underwent TBLC during the study period. An average of 2.8 specimens (range 2-4; n=2 (6), n=3 (41), n=4 (4)) were collected for each patient. All patients had samples collected from the right lower lobe and two patients had additional samples collected from the right upper lobe. One patient experienced pneumothorax (n=1, 2%) after transbronchial forceps biopsy and did not require a chest tube with same day discharge. No patients experienced bleeding requiring intervention beyond routine suctioning. Two patients were hospitalized within 30 days (n=2, 4%), one for pneumomediastinum that developed ∼12 hours after discharge and one for pneumonia secondary to seasonal coronavirus that developed five days post-procedure. No deaths occurred within 30 days. The average procedure time was 62±13 minutes, and the average radiation dose was 137±57 mGy. Conclusions: Compared to 2D-fluoroscopic guidance, TBLC using 3D fluoroscopy may offer an improved safety profile with comparable radiation exposure. 3D mobile fluoroscopy guidance may offer a similar safety profile to TBLC under fixed CBCT guidance with reduced radiation exposure.

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

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

Rationale: 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. Objectives: 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. Methods: 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. Measurements and Main Results: 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. Conclusions: 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.

Introduction: Transbronchial lung cryobiopsies (TBLCs) are useful in the setting of diffuse parenchymal lung diseases (DPLDs). However, no direct comparison with surgical lung biopsy (SLB) is available. The aim of this study was therefore to evaluate the benefit of SLBs performed in selected patients after TBLCs. Method: We conducted a multicentric Belgian prospective trial in which SLBs were performed after TBLCs if the pathological diagnosis was uncertain or if a nonspecific interstitial pneumonia (NSIP) pattern was observed hypothesizing that a co-existent UIP pattern could be missed. Results: Between April 2015 and January 2018, TBLCs were performed in 67 patients with DPLDs. The diagnostic yield was 69%. Among these 67 patients, no pathological diagnosis following TBLCs was noticed in 11 patients (16%) and a pattern suggestive of a NSIP observed in 10 patients (15%). 12 of these patients had SLBs after TBLCs. Interestingly, SLBs showed a UIP pattern in ten, a pattern suggestive of a hypersensitivity pneumonitis in one and a NSIP pattern in one patient. Moreover, among patients with pathological NSIP following TBLCs, six benefited from SLBs showing a UIP in five and confirming a NSIP in only one patient. Conclusion: TBLCs are useful in the setting of DPLDs with a good diagnostic yield. However, when pathological results are inconclusive or show a NSIP pattern, SLBs seem to provide additional information. Our data are preliminary and based on a relatively small number of patients. Therefore, further studies are required to definitely assess the indication of SLBs after TBLCs.

Rationale: Transbronchial lung cryobiopsy (TBLC) is an emerging technique for interstitial lung disease diagnosis. Good histopathologic agreement between TBLC and surgical lung biopsy (SLB) was demonstrated in the COLDICE (Cryobiopsy versus Open Lung Biopsy in the Diagnosis of Interstitial Lung Disease Alliance) study; however, diagnostic confidence was frequently lower for TBLC than SLB. Objectives: To characterize specific features of TBLC predictive of usual interstitial pneumonia (UIP) in corresponding SLB and to identify clinical indices predictive of biopsy concordance. Methods: The COLDICE study was a prospective, multicenter study investigating diagnostic agreement between TBLC and SLB. The participants underwent both procedures with blinded pathologist analysis of specimens, applying international guideline criteria. The TBLC features predictive of UIP in the paired SLB and predictive features of overall concordance were analyzed. Measurements and Main Results: A total of 65 patients (66.1 ± 9.3 yr; FVC, 84.7 ± 14.2%; DlCO, 63.4 ± 13.8%) participated in the COLDICE study. UIP was identified in 33/65 (50.8%) SLB, and 81.5% were concordant with corresponding TBLC (κ, 0.61; 95% confidence interval [CI], 0.38-0.77). The UIP guideline criteria of "predominantly subpleural or paraseptal fibrosis" was infrequently reported in TBLC (8/33, 24.2%), whereas "patchy fibrosis," "fibroblast foci," and the "absence of alternative diagnostic features" were frequently observed in TBLC. The combination of these three features strongly predicted UIP in paired SLB (odds ratio [OR], 23.4; 95% CI, 6.36-86.1; P < 0.0001). Increased numbers of TBLC samples predicted histopathologic concordance with SLB (OR,1.8; 95% CI, 1.08-3.01; P = 0.03). The predictors of discordance included older age, family history, and radiologicasymmetry. Conclusions: Subpleural and/or paraseptal fibrosis were not essential for diagnosing UIP in TBLC, provided that other guideline criteria features were present. The diagnostic accuracy of TBLC was strengthened when increased numbers of samples were taken. Clinical trial registered with www.anzctr.org.au (ACTRN12615000718549).

Diagnostic value of TBLC in idiopathic pulmonary fibrosis

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