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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

Background: Local anaesthesia of the pharynx (LAP) was introduced in the era of rigid bronchoscopy (which was initially a conscious procedure under local anaesthetic), and continued into the era of flexible bronchoscopy (FB) in order to facilitate introduction of the FB. LAP reduces cough and gagging reflex, but its post-procedural effect is unclear. This prospective multicentre trial evaluated the effect of LAP on coughing intensity/time and patient comfort after FB, and the feasibility of FB under propofol sedation alone, without LAP. Material and methods: FB was performed in 74 consecutive patients under sedation with propofol, either alone (35 patients, 47.3%) or with additional LAP (39 patients, 52.7%). A primary endpoint of post-procedural coughing duration in the first 10 min after awakening was evaluated. A secondary endpoint was the cough frequency, quality and development of coughing in the same period during the 10 min post-procedure. Finally, the ease of undertaking the FB and the patient’s tolerance and safety were evaluated from the point of view of the investigator, the assistant technician and the patient. Results: We observed a trend to a shorter cumulative coughing time of 48.6 s in the group without LAP compared to 82.8 s in the group receiving LAP within the first 10 min after the procedure, although this difference was not significant (p = 0.24). There was no significant difference in the cough frequency, quality, peri-procedural complication rate, nor patient tolerance or safety. FB, including any additional procedure, could be performed equally well with or without LAP in both groups. Conclusions: Our study suggests that undertaking FB under deep sedation without LAP does to affect post-procedural cough duration and frequency. However, further prospective randomised controlled trials are needed to further support this finding.

ZusammenfassungCOVID-19, ausgelöst durch Coronavirus SARS-CoV-2, ist eine neue, sich pandemisch ausbreitenden Infektionserkrankung, welche aktuell weltweit zu einer erheblichen Belastung der Gesundheitssysteme geführt hat. Krankenhausmitarbeiter stellen in Ländern mit hoher Krankheitsaktivität, wie China oder Italien, einen signifikanten Anteil der an COVID-19 Erkrankten und Verstorbenen dar. Bronchoskopische Untersuchungen führen beim untersuchten Patienten zu Hustenreiz und Aerosolbildung und beinhalten daher ein erhöhtes Infektionsrisiko für das Untersuchungsteam und für andere Patienten. In der aktuellen Pandemie sind daher besondere Maßnahmen bei der Durchführung bronchoskopischer Untersuchungen zu beachten, um das Infektionsrisiko zu senken.

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.

Flexible bronchoscopy (FB) is a cornerstone of modern pulmonary medicine. However, considerable heterogeneity persists with respect to education, training, and the performance of sedation during FB. Sedation administered by a non-anesthesiologist during FB has been demonstrated to be safe and effective, although comorbidities and respiratory disease severity must be taken into account regarding choice of sedation and monitoring. There is undoubtedly room for improvement concerning basic education and training in this field. In addition, current study heterogeneity complicates comparisons between various sedation regimens which in turn limit state of the art recommendations. To reach a broad acceptance of non-anesthesiologist administered sedation, future studies and guidelines must increasingly focus on education and training. Research should be performed to establish a concept of harmonized patient selection for different sedation practices.

IntroductionThe 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 is the current recommended tissue sampling technique according to the most recent guidelines. Transbronchial lung cryobiopsy (TBLC) has been proposed as an alternative to surgical lung biopsy.MethodsThis prospective, multicentre, international study analysed the impact of TBLC on the diagnostic assessment of 128 patients with suspected idiopathic interstitial pneumonia by a central MDTD board (two clinicians, two radiologists, two pathologists). The level of confidence for the first-choice diagnoses were evaluated in four steps, as follows: 1) clinicoradiological data alone; 2) addition of bronchoalveolar lavage (BAL) findings; 3) addition of TBLC interpretation; and 4) surgical lung biopsy findings (if available). We evaluated the contribution of TBLC to the formulation of a confident first-choice MDTD diagnosis.ResultsTBLC 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 patients nondiagnostic 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% of patients, and moderate or severe bleeding in 15.7% of patients. No deaths were observed within 30 days.InterpretationTBLC increases diagnostic confidence in the majority of ILD patients with an uncertain noninvasive diagnosis, with manageable side-effects. These data support the integration of TBLC into the diagnostic algorithm for ILD.

Transbronchial cryobiopsies (TBCB) have recently been introduced as a promising and safer alternative to surgical lung biopsy in the diagnostic approach to diffuse parenchymal lung diseases (DPLD). Despite a substantial and expanding body of literature, the technique has not yet been standardized and its place in the diagnostic algorithm of DPLD remains to be defined. In part, this reflects concerns over the diagnostic yield and safety of the procedure, together with the rapid spread of the technique without competency and safety standards; furthermore, there is a substantial procedural variability among centers and interventional pulmonologists. We report this expert statement proposed during the third international conference on “Transbronchial Cryobiopsy in Diffuse Parenchymal Lung Disease” (Ravenna, October 27–28, 2016), which formulates evidence- and expert-based suggestions on the indications, contraindications, patient selection, and procedural aspects of the procedure. The following 5 domains were reviewed: (1) what is the role of TBCB in the diagnostic evaluation of DPLD: patient selection; (2) pathological considerations; (3) contraindications and safety considerations; (4) how should TBCB be performed and in what procedural environment; and (5) who should perform TBCB. Finally, the existence of white paper recommendations may also reassure local hospital credentialing committees tasked with endorsing an adoption of the technique.

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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

Objectives: Bronchoscopy is an integral part of pulmonary medicine. In recent years, a series of new technologies have evolved. It is to assume that significant changes have also occurred in clinical practice. We conducted a nationwide survey to evaluate the current status of care and to compare it with earlier reports. Methods: A standard questionnaire was sent to 1875 institutions to assess the clinical practice of bronchoscopy in Germany with respect to general issues, education, sedation/anaesthesia and technical aspects. Results: The returned questionnaires cover 301,965 bronchoscopies, performed by 2158 physicians over 12 months, making it the largest survey to date. The proportion of rigid bronchoscopies has decreased and amounts to 7.3 % at present. Atropine as a premedication is hardly used any more. Sedation is routinely applied in 88 % of flexible bronchoscopies, for which a combination of propofol and midazolam is preferred by most institutions (41.3 %), followed by propofol monotherapy (28.3 %). 74.4 % of institutions accept aspirin for transbronchial biopsy, 8.1 % dual platelet inhibition. 62.4 % of all institutions perform airway recanalisation, favouring cryotherapy and argon plasma coagulation. 9.1 % of bronchoscopies are supported by endobronchial ultrasound. Conclusion: Compared to preceding surveys, the experience of bronchoscopists, especially regarding interventional procedures, has increased. Endobronchial ultrasound has become a standard of care, as has patient sedation with propofol.

Flexible bronchoscopy is a standard examination today and is conducted not only in nearly every hospital but also in privately owned practices. The vast majority of patients want sedation for this examination. Such a procedure is nearly always necessary in complex and interventional procedures, irrespective of the patient's wish. The recommendation at hand to use sedation measures for flexible bronchoscopy is based on the results of numerous clinical studies and also takes account of individual experiences in this area. The structural and procedural requirements and the requirements for staff training are defined and should describe the minimum standard when it comes to conducting a bronchoscopy under sedation. Furthermore the drugs recommended for sedation are discussed and their methods of application shown. Finally the recommendations also include suggestions for patient clarification, monitoring and discharge. They should provide the examiner with concrete operating options and therefore above all increase patient safety.

Bronchoscopic training courses are an essential part of the education in bronchoscopy for all kinds of specialisations and professions performing such investigations. All aspects of the application should be mentioned during a course. These recommendations are necessary because the number of bronchoscopies performed in the last years has increased due to the increasing number of patients, improved equipment and better availability. Courses should provide the basic knowledge including main points of indications, preconditions for the procedure and decisions of consequence after bronchoscopy. Participants should be trained in the skills of correct handling and performing flexible bronchoscopies in training dummies. Necessary competence requirements on the course instructor are adequate professional qualifications, paedagogic skills and the availability of appropriate teaching material. Quality assurance of the course should be achieved by consequent evaluation. A widely spread field of bronchoscopic applications can improve patient care in many medical specialisations.

We report a 12-year-old boy who underwent stent implantation into the left main bronchus at the age of 9.5 years for palliation of severe bronchial stenosis. He had developed complete obstruction of the stent by granulation tissue resulting in respiratory deterioration and the requirement of mechanical ventilation. The stent obstruction was treated at the age of 11.5 years by cryorecanalization. In this technique, cooling of the tip of the cryoprobe is used to induce adherence of the obstructing tissue allowing the subsequent removal of tissue particles by retraction of the probe. Under general anesthesia, a miniaturized cryoprobe was advanced via the working channel of a flexible bronchoscope. Repeat maneuvers of freezing and retraction resulted in complete recanalization of the stent. Repeat bronchoscopies 4 and 12 weeks later revealed recurrent formation of some granulation tissue which was removed by repeat cryorecanalization. Seven months after the initial procedure there was a complete patency of the stent. According to our experience, cryorecanalization is a safe and effective alternative for the treatment of stent obstruction by granulation tissue. Due to the introduction of a miniaturized probe, this method is well applicable in children since it can be performed via the working channel of a flexible pediatric bronchoscope.

Objective In addition to use of a laser, argon plasma coagulation, electrocautery, or coring with a rigid bronchoscope, tumor debulking with a flexible cryoprobe is used for therapeutic bronchoscopy with an immediate effect for endobronchial pathologies. We performed this analysis to determine the usefulness, efficacy, and safety of the flexible cryorecanalization in a large population under routine conditions. Methods We identified 225 bronchoscopic interventions that were done as cryorecanalization with a flexible cryoprobe. All patients had symptomatic airway stenosis. We determined the endoscopic success rate and safety (bleeding and perforation) of the procedure. Results Successful cryorecanalization was achieved in 205 (91.1%) of 225 patients. The flexible cryoprobe was used with all patients, in most patients in combination with flexible bronchoscopy and only in a minority (n = 31, 13.8%) in combination with a rigid bronchoscope. Additional interventional techniques used were endobronchial stents (n = 11, 4.9%) and argon plasma coagulation (n = 37, 16.4%). Mild bleeding (if ice-cold NaCl or epinephrine solution was necessary) occurred in 9 (4.0%) patients, moderate bleeding (if argon plasma coagulation or a bronchus blocker was required) occurred in 18 (8.0%) patients, and severe bleeding (events with hemodynamic instability) never occurred. Conclusions Cryorecanalization with the flexible cryoprobe for treatment of symptomatic endobronchial tumor stenosis is a safe technique with a high success rate and immediate treatment effect.

Background: Cryoextraction is a procedure used for the recanalization of obstructed airways caused by visible exophytic endobronchial tumor. Biopsy samples obtained by this technique have been shown to be useful for histological assessment. Objectives: The aim of the present animal study was to systematically evaluate biopsy size, histological quality and bleeding risk after cryobiopsy with new, flexible cryoprobes in comparison with forceps biopsy, serving as the gold standard. Methods: Biopsies were obtained from anesthetized pigs with the flexible bronchoscopy technique, and evaluated histologically with respect to their size and quality. Bleeding frequency, bleeding duration and histological changes in the biopsy bed were also recorded. Results: Cryobiopsies were significantly larger than forceps biopsies. The size of cryobiopsies was dependent on the freezing time. The histological quality of the cryobiopsy specimenswas not impaired by the freezing process, whereas forceps biopsies showed typical crush artifacts. Despite the larger defects left in the tracheobronchial system after cryobiopsy, bleeding frequency and duration were not higher compared to forceps biopsy. Conclusions: Since cryobiopsy sampling is not associated with a higher bleeding risk compared with forceps biopsy, this new biopsy technique offers – in addition to a good specimen quality – a safe and valuable tool with the potential of improving the outcome of diagnostic endoscopy.

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 mm2 (0.58–20.88 mm2) taken by forceps compared to 15.11 mm2 obtained using the cryoprobe (2.15–54.15 mm2, 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.

Background: Endobronchial forceps biopsies are often small and are associated with a relevant extent of artifacts. To overcome these limitations is an important task. Especially when considering predictive factors for pharmacological therapies of lung cancer (ERCC1, RRM1) a development of biopsy techniques seems to be essential. This is the first report on a new endobronchial biopsy technique called cryobiopsy. Objectives: In this study the feasibility and the potential advantages of applying cryoprobes for harvesting samples for histological examination in flexible bronchoscopies will be focused on. Methods: In 12 patients suffering from exophytic endobronchial malignancies, a modified flexible cryoprobe was used for immediate recanalization. The extracted tissue was examined histologically regarding sample quality and sample size. Results: Tissue samples obtained using the cryoprobe showed an extraordinary good quality in terms of size (median diameter of 6.7 mm, range 4.2–13 mm) and artifact-free sample area (75% of the samples showed an artifact-free sample area of more than 75%). Additionally molecular markers were shown to be well preserved. Conclusions: The new technique termed cryobiopsy might widen the chest physician’s range of tools for diagnostic bronchoscopies.

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.

To assess the impact of endobronchial coiling on the segment bronchus cross-sectional area and volumes in patients with lung emphysema using quantitative chest-CT measurements. Thirty patients (female = 15; median age = 65.36 years) received chest-CT before and after endobronchial coiling for lung volume reduction (LVR) between January 2010 and December 2014. Thin-slice (0.6 mm) non-enhanced image data sets were acquired both at end-inspiration and end-expiration using helical technique and 120 kV/100–150 mAs. Clinical response was defined as an increase in the walking distance (Six-minute walk test; 6MWT) after LVR-therapy. Additionally, pulmonary function test (PFT) measurements were used for clinical correlation. In the treated segmental bronchia, the cross-sectional lumen area showed significant reduction (p 0.05). In the ipsilateral lobes, the lumina showed no significant changes. In the contralateral lung, we found tendency towards increased cross-sectional area in inspiration (p = 0.06). Volumes of the treated segments correlated with the treated segmental bronchial lumina in expiration (r = 0.80, p

Forceps, brushes or needles are currently the standard tools used during flexible bronchoscopy when diagnosing endobronchial malignancies. The new biopsy technique of cryobiopsy appears to provide better diagnostic samples. The aim of this study was to evaluate cryobiopsy over conventional endobronchial sampling. A total of 600 patients in eight centres with suspected endobronchial tumours were included in a prospective, randomised, single-blinded multicentre study. Patients were randomised to either sampling using forceps or the cryoprobe. After obtaining biopsy samples, a blinded histological evaluation was performed. According to the definitive clinical diagnosis, the diagnostic yield for malignancy was evaluated by a Chi-squared test. A total of 593 patients were randomised, of whom 563 had a final diagnosis of cancer. 281 patients were randomised to receive endobronchial biopsies using forceps and 282 had biopsies performed using a flexible cryoprobe. A definitive diagnosis was achieved in 85.1% of patients randomised to conventional forceps biopsy and 95.0% of patients who underwent cryobiopsy (p

Cryoextraction is a procedure for recanalization of obstructed airways caused by exophytic growing tumors. Biopsy samples obtained with this method can be used for histological diagnosis. The objective of this study was to evaluate the parameters influencing the size of cryobiopsies in an in vitro animal model. New flexible cryoprobes with different diameters were used to extract biopsies from lung tissue. These biopsies were compared with forceps biopsy (gold standard) in terms of the biopsy size. Tissue dependency of the biopsy size was analyzed by comparing biopsies taken from the lung, the liver, and gastric mucosa. The effect of contact pressure exerted by the tip of the cryoprobe on the tissue was analyzed on liver tissue separately. Biopsy size was estimated by measuring the weight and the diameter. Weight and diameter of cryobiopsies correlated positively with longer activation times and larger diameters of the cryoprobe. The weight of the biopsies was tissue dependent: lung < liver < stomach. Only little tissue dependency was found for the biopsy diameter. The biopsy size increased when the probe was pressed on the tissue during cooling. Cryobiopsies can be taken from different tissue types with flexible cryoprobes. The size of the samples depends on tissue type, probe diameter, application time, and pressure exerted by the probe on the tissue. Even the cryoprobe with the smallest diameter can provide larger biopsies than a forceps biopsy in lung. It can be expected that the same parameters influence the sample size of biopsies in vivo.