Transbronchial Lung Cryobiopsy Research Articles

Assessment of a randomized controlled trial on the safety of pre-placing bronchial balloons in transbronchial lung cryobiopsy for diagnosing interstitial lung disease

Rationale and objectivesBleeding is a major complication of transbronchial lung cryobiopsy (TBLC), and pre-placing a bronchial balloon is one of the clinical practices used to prevent it, but with very weak evidence, which should be confirmed. This study aimed to conduct whether pre-placing a bronchial balloon in TBLC for diagnosing interstitial lung disease (ILD) is more safety.Materials and methodsIn this prospective, single-center, randomized controlled trial, patients with suspected ILD were enrolled and randomly assigned to pre-placed balloon and none-pre-placed balloon groups. The primary outcome was incidence of moderate bleeding in each group. The secondary endpoints were the incidence of severe bleeding, pneumothorax, and other procedural complications.ResultsExactly 250 patients were enrolled between August 2019 and March 2022, with 125 in each group. There were no significant differences in severe bleeding between the none-pre-placed balloon group and pre-placed balloon group (1.6% vs. 0.8%; adjusted p = 0.520), while more moderate bleeding occurred in the none-pre-placed balloon group (26.4% vs. 6.4%, adjusted p = 0.001), as well as more use of hemostatic drug (28.0% vs. 6.4%, adjusted p = 0.001). Three patients in the none-pre-placed balloon group used the bronchial balloon. More samples could be acquired in the pre-placed balloon group than in the none-pre-placed balloon group (3.8 ± 0.9 vs. 3.1 ± 0.9, p < 0.001). There were no significant differences in multidisciplinary discussion (MDD) between the two groups (89.6% vs. 91.2%, adjusted p = 0.182).ConclusionA pre-placed bronchial balloon can reduce the incidence of moderate bleeding and increase the confidence of the bronchoscopists. However, it had no effect on increasing the diagnostic rate of MDD and reducing severe bleeding.Registration number: NCT04047667 (www.clinicaltrials.gov identifier).

Transbronchial Lung Cryobiopsies, Transbronchial Forceps Lung Biopsies, and Surgical Lung Biopsies in Mechanically Ventilated Patients with Acute Hypoxemic Respiratory Failure: A Retrospective Cohort Study.

Lung biopsies are sometimes performed in mechanically ventilated patients with acute hypoxemic respiratory failure (AHRF) of unknown etiology to guide patient management. While surgical lung biopsies (SLB) offer high diagnostic rates, they may also cause significant complications. Transbronchial forceps lung biopsies (TBLB) are less invasive but often produce non-contributive specimens. Transbronchial lung cryobiopsies (TBLC) yield specimens of potentially better quality than TBLB, but due to their novel implementation in the intensive care unit (ICU), their accuracy and safety are still unclear. Our main objective was to evaluate the risk of adverse events in patients with AHRF following the three biopsy techniques. Our secondary objectives were to assess the diagnostic yield and associated modifications of patient management of each technique. We conducted a retrospective cohort study comparing TBLC, TBLB, and SLB in mechanically ventilated patients with AHRF. The primary outcome was the proportion of patients with at least one complication, and secondary outcomes included complication rates, diagnostic yields, treatment modifications, and mortality. Of the 26 patients who underwent lung biopsies from 2018 to 2022, all TBLC and SLB patients and 60% of TBLB patients had at least one complication. TBLC patients had higher unadjusted numbers of total and severe complications, but also worse Sequential Organ Failure Assessment scores and P/F ratios. A total of 25 biopsies (25/26, 96%) provided histopathological diagnoses, 88% (22/25) of which contributed to patient management. ICU mortality was high for all modalities (63% for TBLC, 60% for TBLB and 50% for SLB). All biopsy methods had high diagnostic yields and the great majority contributed to patient management; however, complication rates were elevated. Further research is needed to determine which patients may benefit from lung biopsies and to determine the best biopsy modality.

Defining Optimal Settings for Lung Cryobiopsy in End-Stage Pulmonary Disease. A Human, Ex Vivo, Diseased Lung Clinical Trial.

To evaluate optimal settings of probe size, freezing time, and distance to the pleura that influence the size and quality of biopsy specimens during transbronchial lung cryobiopsies in ESPD. We prospectively recruited 17 patients undergoing lung transplantation. We created a nonperfused ex vivo bronchoscopy setting to perform multiple cryobiopsies with different probe sizes (1.7, 1.9, and 2.4mm), freezing times (3, 5, 7, 10, 20, 30 seconds), and probe distance from pleura (5, 10, and 20mm). Alveolated pulmonary parenchyma area≥50% in histology was considered a good quality biopsy, with a minimum procedural artifact. We used logistic regression to identify independent parameters as risk factors for histologic adequacy. A total of 545 cryobiopsies were obtained from 34 explanted lungs after pneumonectomy for lung transplantation. The mean maximum diameter of the specimen achieved with the 1.7 probe was larger (13.5mm) than those obtained with 1.9 and 2.4mm probes (11.3 and 10.7mm, P= 0.07). More pleural macroscopic damage and pleural tissue in histology occurred with the 2.4mm probe ( P <0.001). There was no difference in the quality of specimens between the different freezing times and the distance from the pleura. Freezing time and distance from the pleura did not affect the histologic quality for diagnosing ESPD in severely damaged lungs. Smaller cryoprobe size did not negatively affect sample adequacy.

Assessing the effectiveness and safety of transbronchial lung cryobiopsy utilizing a flexible bronchoscope with an endobronchial blocker in diffuse parenchymal lung lesions.

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

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

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

Low bleeding rates following transbronchial lung cryobiopsy in unclassifiable interstitial lung disease.

Bronchoscopic transbronchial lung cryobiopsy (TBLC) is a guideline-endorsed alternative to surgical lung biopsy for tissue diagnosis in unclassifiable interstitial lung disease (ILD). The reported incidence of post-procedural bleeding has varied widely. We aimed to characterize the incidence, severity and risk factors for clinically significant bleeding following TBLC using an expert-consensus airway bleeding scale, in addition to other complications and diagnostic yield. A retrospective cohort study of consecutive adult outpatients with unclassifiable ILD who underwent TBLC following multidisciplinary discussion at a single centre in the UK between July 2016 and December 2021. TBLC was performed under general anaesthesia with fluoroscopic guidance and a prophylactic endobronchial balloon. One hundred twenty-six patients underwent TBLC (68.3% male; mean age 62.7 years; FVC 86.2%; DLCO 54.5%). Significant bleeding requiring balloon blocker reinflation for >20 min, admission to ICU, packed red blood cell transfusion, bronchial artery embolization, resuscitation or procedural abandonment, occurred in 10 cases (7.9%). Significant bleeding was associated with traction bronchiectasis on HRCT (OR 7.1, CI 1.1-59.1, p = 0.042), a TBLC histological pattern of UIP (OR 4.0, CI 1.1-14, p = 0.046) and the presence of medium-large vessels on histology (OR 37.3, CI 6.5-212, p < 0.001). BMI ≥30 (p = 0.017) and traction bronchiectasis on HRCT (p = 0.025) were significant multivariate predictors of longer total bleeding time (p = 0.017). Pneumothorax occurred in nine cases (7.1%) and the 30-day mortality was 0%. Diagnostic yield was 80.6%. TBLC has an acceptable safety profile in experienced hands. Radiological traction bronchiectasis and obesity increase the risk of significant bleeding following TBLC.

Histopathological significance of connective tissue disease-associated interstitial lung disease in transbronchial lung cryobiopsy specimens

Differentiating between idiopathic interstitial pneumonia (IIP) and secondary interstitial pneumonia, particularly connective tissue disease-associated interstitial lung disease (CTD-ILD), can be challenging histopathologically, and there may be discrepancies among pathologists. While surgical lung biopsy has traditionally been considered the gold standard for diagnosing interstitial pneumonia, the usefulness of transbronchial lung cryobiopsy (TBLC) has been reported. If TBLC could effectively distinguish between primary and secondary diseases, it would provide a less invasive option for patients. The aim of this study was to identify specific pathologic findings in TBLC specimens that could assist in distinguishing CTD-ILD from IIP. A total of 93 underwent TBLC at Tenri Hospital between 2018 and 2022. We retrospectively reviewed cases of CTD-ILD exhibiting a nonspecific interstitial pneumonia (NSIP) pattern (CTD-NSIP) and cases of NSIP with an unknown etiology (NSIP-UE), as determined through multidisciplinary discussion. Nineteen patients with CTD-NSIP and 26 patients with NSIP-UE were included in the study for clinicopathological analysis. The CTD-NSIP group had a significantly higher proportion of female patients compared to the NSIP-UE group (79% vs. 31%; p = 0.002). The presence of both fresh and old intraluminal fibrosis within the same TBLC specimen was significantly more frequent in CTD-NSIP group than in the NSIP-UE group (p = 0.023). The presence of an NSIP pattern with co-existing fresh and old intraluminal fibrosis in TBLC specimens raised suspicion for CTD-ILD.

Diagnostic Value of Transbronchial Lung Cryobiopsy Using an Ultrathin Cryoprobe and Guide Sheath for Peripheral Pulmonary Lesions.

The addition of cryobiopsy to conventional biopsy methods improves the diagnostic yield of peripheral pulmonary lesions. Moreover, cryobiopsy with a guide sheath (GS) provides additional diagnostic benefits. Semi-real-time biopsy can be repeatedly performed using conventional biopsy devices and a GS, and subsequent cryobiopsy can be easily performed at the same location. Recently, a disposable 1.1mm-diameter ultrathin cryoprobe has been developed and can be used with a 1.95mm GS in a 2.0mm working channel. In this study, we evaluated the diagnostic performance of transbronchial lung cryobiopsy (TBLC) with the 1.1mm cryoprobe and a GS in patients with peripheral pulmonary lesions. We retrospectively reviewed the medical records of patients who underwent endobronchial ultrasound transbronchial lung biopsy with a guide sheath and TBLC from July 23, 2021 to April 30, 2022 at Chungnam National University Hospital. Of a consecutive series of 229 patients, 199 were included. The diagnostic yields of forceps biopsy and cryobiopsy were 65.3% (130/199) and 84.4% (168/199), respectively, and the total diagnostic yield was 91.5% (182/199) ( P <0.001 vs. forceps biopsy). Multivariate analysis showed that solid lesion morphology [adjusted odds ratio (OR) 3.659, P =0.002] was associated with a significantly greater diagnostic yield of cryobiopsy, whereas a lesion diameter >20mm ( P =0.026; adjusted OR 3.816) and 'within' orientation ( P =0.004; adjusted OR 6.174) were associated with a significantly greater overall diagnostic yield. TBLC using an ultrathin cryoprobe and GS markedly improves the diagnostic yield.

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

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

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

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

The efficacy and safety of radial endobronchial ultrasound-guided transbronchial lung cryobiopsy in the diagnosis of lung disease.

Transbronchial lung cryobiopsy (TBLC) is a novel technology in which a cryoprobe is used to obtain large tissue samples from the lungs of patients with interstitial lung diseases (ILDs) and peripheral pulmonary lesions (PPLs). We aimed to determine the efficacy and safety of TBLC in the diagnosis of peripheral lung diseases in the Endoscopy Center of Shanghai Pulmonary Hospital. Further, the application value of radial endobronchial ultrasound (R-EBUS) used to determine the optimal area for cryobiopsy was evaluated in this study. In this retrospective study, the data of patients with unclarified ILDs or PPLs who underwent TBLC guided by R-EBUS between April 2020 and December 2021 at Shanghai Pulmonary Hospital in China were analyzed. A total of 137 patients [72 men, 65 women; median age, 52 years (range, 24-76 years)] were enrolled in the study. Out of the 137 patients included in the study, 123 (89.8%) were diagnosed after multidisciplinary discussions (MDDs), including 105 (85.4%) with ILD, 10 (8.1%) with tuberculosis, and 8 (6.5%) with a malignant tumor. Sixty-five (47.4%) patients had a definitive pathologic diagnosis through TBLC, including 54 (83.1%) with ILD, 5 (7.7%) with tuberculosis and 6 (9.2%) with malignant tumors. The overall pathological diagnosis rate was 47.4%. In addition to clarifying the blood supply situation of the candidate target, R-EBUS detected lesions in 44 (32.1%) patients. Mild and moderate bleeding occurred in 75.2% and 24.8% of patients, respectively. No cases of severe bleeding were observed. Pneumothorax occurred in 6 (4.4%) patients, of which 2 recovered without additional treatment, and 4 (66.7%) needed closed thoracic drainage. Hydropneumothorax and mediastinal emphysema occurred in one patient each. No patients died due to TBLC. R-EBUS-guided TBLC is safe and effective for the diagnosis of lung diseases, including ILDs and other PPLs. R-EBUS can guide cryobiopsy and avoid the potential risk of severe bleeding as well as radiation exposure. The pathological diagnosis rate of ILDs is relatively low, and MDD plays an important role in the diagnosis of ILDs.

Transbronchial cryobiopsy using an ultrathin cryoprobe with a guide sheath for the diagnosis of pulmonary mucosa-associated lymphoid tissue lymphoma.

Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma is difficult to diagnose and relatively rare. Tissue sampling through transbronchial biopsy is often inadequate, necessitating surgical lung biopsy. However, a recently developed technique, transbronchial lung cryobiopsy (TBLC), has shown promise for obtaining larger specimens. A 1.1 mm cryoprobe has recently become available, and its usefulness has been increasingly reported. Use of a conventional cryoprobe for TBLC in diagnosing pulmonary MALT lymphoma has been previously reported; however, there are no reports on the use of a 1.1 mm ultrathin cryoprobe and guide sheath (GS). We aimed to assess the effectiveness and safety of using a 1.1 mm ultrathin cryoprobe in combination with a GS for diagnosing pulmonary MALT lymphoma using a simpler and safer method. We retrospectively analyzed the findings for four patients showing characteristic computed tomography (CT) findings of MALT lymphoma, including peripheral pulmonary lesions, air bronchogram nodules, and bronchiectasis, at our hospital. Each patient underwent endobronchial ultrasound (EBUS) with a GS, followed by TBLC using a 1.1 mm cryoprobe. Morphological diagnosis, immunohistochemical examination, and molecular testing were performed on the biopsy specimens to establish the diagnosis. Complications during the procedure were also monitored. We obtained 8-16 biopsy specimens in all four cases using a cryoprobe. Histopathological analysis of two cases revealed the infiltration of small lymphocytes with numerous lymphoepithelial lesions, confirming MALT lymphoma. Immunohistochemical examination further demonstrated B-cell lymphocyte proliferation and light-chain restriction, confirming monoclonality and providing a definitive diagnosis. In the remaining two cases, histopathological evidence of pulmonary MALT lymphoma was lacking. However, molecular testing using polymerase chain reaction to analyze immunoglobulin gene rearrangements revealed B-cell clonality, which supported the diagnosis. Molecular testing proved particularly useful when histopathological diagnosis alone was inconclusive. No complications such as pneumothorax or hemorrhage occurred during the procedure. The combination of a GS and EBUS facilitated specimen collection at the same location as EBUS, with the GS providing compression hemostasis and eliminating the need for an additional hemostatic device. Therefore, TBLC with a GS is a useful and safe method for diagnosing pulmonary MALT lymphomas and reproducibly yielded sufficient quantities of good-quality biopsy specimens.

Aspirin use is safe in patients undergoing transbronchial lung cryobiopsy

BackgroundAspirin has been shown to be safe for patients undergoing certain diagnostic bronchoscopy procedures, such as transbronchial biopsies and endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration. However, there are no studies documenting the safety of aspirin in patients undergoing trans-bronchial lung cryobiopsy (TBLC). ObjectiveTo determine whether aspirin increases the risk of bleeding during or following TBLC. Methods172 consecutive patients undergoing TBLC were included in this retrospective cohort study. Data on demographic characteristics, comorbidities etc. were collected. Bleeding severity was defined by the intervention needed to stop the bleeding: mild-cold saline injection, moderate-adrenalin/hexakarpon injection, or severe - Intensive Care Unit admission after bronchoscopy. ResultsFifty-one patients (29.6 %) were under aspirin treatment at the time of TBLC. Overall, there was no significant difference between the aspirin and the control groups regarding the incidence of moderate-severe bleeding (41.2 % vs. 33.1 %, respectively, p.0.31). the Clopidogrel was found as a risk factor for increased bleeding when taken together with aspirin (Odds ratio = 9.8 (1.1–86), p = 0.013). When taken alone, clopidogrel was also found as a risk factor to increased bleeding, yet these results didn't reach significance due to low number of patients (fig. 1, N = 5, Odds ratio = 2.8 (0.46–17.35), p = 0.245). No difference was observed between the groups regarding additional post-procedural complications, including pneumothorax, hospitalizations, and mortality. ConclusionTo the best of our knowledge, this is the first study examining bleeding risk of cryobiopsy under aspirin treatment. Based on our results, it seems safe to perform TBLC under aspirin treatment, except for patients who are concurrently treated with clopidogrel. Further research should be conducted to substantiate this conclusion.

Concordance between transbronchial lung cryobiopsy and surgical lung biopsy in patients with idiopathic multicentric Castleman disease: A report of four cases

BackgroundIdiopathic multicentric Castleman disease (iMCD) is a rare polyclonal lymphoproliferative disease often associated with pulmonary involvement. Recently, transbronchial lung cryobiopsy (TBLC) has been reported to be useful for the diagnosis of diffuse interstitial lung disease. However, there have been no reports of pathological assessment of TBLC for iMCD. MethodTo clarify the efficacy of TBLC in the diagnosis of iMCD, we retrospectively reviewed four iMCD patients who had undergone both TBLC and surgical lung biopsy (SLB). ResultsThe median age was 44 years; 2 males and 2 females. Two or three TBLC specimens were taken from each patient. All patients had no complications other than minimal bleeding. The size of the TBLC specimens was approximately 5–6 × 3–4 mm, and the alveolar region, and centrilobular and perilobular areas were adequately sampled. As with SLB, the extent of lung lesions and inflammatory cell infiltration could be sufficiently evaluated by TBLC. The presence of lymphoid follicles could also be assessed by TBLC; however, the germinal centers with lymphoid follicles were difficult to evaluate. The TBLC specimens could also be evaluated for immunostaining, especially IgG4 immunostaining, to rule out IgG4-related lung disease. Pulmonary pathological grading showed a high concordance rate between major pathological findings of TBLC and SLB. The pathologist's confidence level of TBLC for the diagnosis of iMCD was high in all cases. ConclusionsTBLC exhibits a high concordance rate with SLB in the pathological evaluation of iMCD, which may be useful for the diagnosis of iMCD.

Diagnostic Approaches for Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia with a very poor prognosis. Accurate diagnosis of IPF is essential for good outcomes but remains a major medical challenge due to variability in clinical presentation and the shortcomings of existing diagnostic tests. Medical history collection is the first and most important step in the IPF diagnosis process; the clinical probability of IPF is high if the suspected patient is 60 years or older, male, and has a history of cigarette smoking. Systemic assessment for connective tissue disease is essential in the initial evaluation of patients with suspected IPF to identify potential causes of interstitial lung disease (ILD). Radiologic examination using high-resolution computed tomography plays a pivotal role in the evaluation of patients with ILD, and prone and expiratory computed tomography images can be considered. If additional tests such as surgical lung biopsy or transbronchial lung cryobiopsy are needed, transbronchial lung cryobiopsy should be considered as an alternative to surgical lung biopsy in medical centers with experience performing this procedure. Diagnosis through multidisciplinary discussion (MDD) is strongly recommended as MDD has become the cornerstone for diagnosis of IPF, and the scope of MDD has expanded to monitoring of disease progression and suggestion of appropriate treatment options.

Comparison of the diagnostic yield of transbronchial lung biopsies by forceps and cryoprobe in diffuse parenchymal lung disease.

Transbronchial lung cryobiopsy (TBLC) in the diagnosis of diffuse parenchymal lung disease (DPLD) has shown a promising yield in recent times, with low post-procedural mortality and morbidity. To compare the yield of TBLC and conventional transbronchial forceps lung biopsy (TBLB). A prospective study was carried out in patients with DPLD over a period of 1 year in a tertiary respiratory care institute in New Delhi, India. All 87 patients enrolled underwent both TBLB and TBLC. The procedures were performed in the bronchoscopy suite under conscious sedation and local anaesthesia, with an attempt to take a minimum of three biopsy specimens by conventional TBLB followed by TBLC. A 1.9 mm cryoprobe with a freezing time of 4 - 5 seconds was used. An Arndt endobronchial blocker was used to control bleeding along with locally administered medications. TBLB and TBLC led to a definitive diagnosis in 27 (31.0%) and 69 (79.3%) cases, respectively. The commonest diagnoses were hypersensitivity pneumonitis, sarcoidosis and pulmonary tuberculosis. TBLC led to additional diagnoses in 42 cases (48.3%). Pneumothorax was observed in 12 cases (13.8%), and moderate bleeding occurred in 63 (72.4%). There were no procedure-related deaths. TBLC had a better diagnostic yield than conventional TBLB in DPLD. It has the potential to become a safe day-care procedure in a resource-limited setting, if certain precautions are taken. What the study adds. Compared with transbronchial forceps lung biopsy, transbronchial lung cryobiopsy (TBLC) led to additional diagnoses in 42 (48.3%) of 87 patients with clinicoradiological features of diffuse parenchymal lung disease. Pneumothorax was observed in 12 cases (13.8%) and moderate bleeding in 63 (72.4%). TBLC without rigid bronchoscopy or advanced airway devices under conscious sedation had a good diagnostic yield with an acceptable adverse events profile.Implications of the findings. TBLC under conscious sedation is not resource intensive and can be carried out in settings with limited resources.

Utility and Safety of Bronchoscopic Cryotechniques-A Comprehensive Review.

Cryosurgical techniques are employed for diagnostic and therapeutic bronchoscopy and serve as important tools for the management of pulmonary diseases. The diagnosis of interstitial lung disease requires multidisciplinary team discussions after a thorough assessment of history, physical exam, computed tomography, and lung-function testing. However, histological diagnosis is required in selected patients. Surgical lung biopsy has been the gold standard but this can be associated with increased morbidity and mortality. Transbronchial lung cryobiopsy is an emerging technique and multiple studies have shown that it has a high diagnostic yield with a good safety profile. There is wide procedural variability and the optimal technique for cryobiopsy is still under investigation. There is emerging data that demonstrate that cryobiopsy is safe and highly accurate in the diagnosis of thoracic malignancies. Furthermore, cryorecanalization procedures are a useful adjunct for the palliation of tumors in patients with central airway obstruction. One should keep in mind that these procedures are not free from complications and should be carried out in a specialized center by a trained and experienced bronchoscopy team. We present a review of the literature on the diagnostic and therapeutic utility of bronchoscopy-guided cryosurgical procedures and their safety profile.

Concordance between transbronchial lung cryobiopsy and surgical lung biopsy for interstitial lung disease in the same patients

BackgroundThe diagnostic accuracy and safety of transbronchial lung cryobiopsy (TBLC) via a flexible bronchoscope under sedation compared with that of surgical lung biopsy (SLB) in the same patients is unknown.MethodsRetrospectively the data of fifty-two patients with interstitial lung diseases (median age: 63.5 years; 21 auto-antibody positive) who underwent TBLC followed by SLB (median time from TBLC to SLB: 57 days) was collected. The samples from TBLC and SLB were randomly labelled to mask the relationship between the two samples. Diagnosis was made independently by pathologists, radiologists, and pulmonary physicians in a stepwise manner, and a final diagnosis was made at multidisciplinary discussion (MDD). In each diagnostic step the specific diagnosis, the diagnostic confidence level, idiopathic pulmonary fibrosis (IPF) diagnostic guideline criteria, and treatment strategy were recorded.ResultsWithout clinical and radiological information, the agreement between the histological diagnoses by TBLC and SLB was 42.3% (kappa [κ] = 0.23, 95% confidence interval [CI]: 0.08–0.39). However, the agreement between the TBLC-MDD and SLB-MDD diagnoses and IPF/non-IPF diagnosis using the two biopsy methods was 65.4% (κ = 0.57, 95% CI: 0.42–0.73) and 90.4% (47/52), respectively. Out of 38 (73.1%) cases diagnosed with high or definite confidence at TBLC-MDD, 29 had concordant SLB-MDD diagnoses (agreement: 76.3%, κ = 0.71, 95% CI: 0.55–0.87), and the agreement for IPF/non-IPF diagnoses was 97.4% (37/38). By adding the pathological diagnosis, the inter-observer agreement of clinical diagnosis improved from κ = 0.22 to κ = 0.42 for TBLC and from κ = 0.27 to κ = 0.38 for SLB, and the prevalence of high or definite diagnostic confidence improved from 23.0% to 73.0% and from 17.3% to 73.0%, respectively. Of all 383 TBLC performed during the same period, pneumothorax occurred in 5.0% of cases, and no severe bleeding, acute exacerbation of interstitial lung disease, or fatal event was observed.ConclusionsTBLC via a flexible bronchoscope under deep sedation is safely performed, and the TBLC-MDD diagnosis with a high or definite confidence level is concordant with the SLB-MDD diagnosis in the same patients.

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

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

Pulmonary Artery Pseudoaneurysm as a Complication of Transbronchial Lung Cryobiopsy.

"Pulmonary Artery Pseudoaneurysm as a Complication of Transbronchial Lung Cryobiopsy." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.