First-in-human use of a new robotic electromagnetic navigation bronchoscopic platform with integrated Tool-in-Lesion Tomosynthesis (TiLT) technology for peripheral pulmonary lesions: The FRONTIER study.

BACKGROUND AND OBJECTIVE: As the presentation of pulmonary nodules increases, the importance of a safe and accurate method of sampling peripheral pulmonary nodules is highlighted. First-generation robotic bronchoscopy has successfully assisted navigation and improved peripheral reach during bronchoscopy. Integrating tool-in-lesion tomosynthesis (TiLT) may further improve yield. METHODS: We performed a first-in-human clinical trial of a new robotic electromagnetic navigation bronchoscopy system with integrated digital tomosynthesis technology (Galaxy System, Noah Medical). Patients with moderate-risk peripheral pulmonary nodules were enrolled in the study. Robotic bronchoscopy was performed using electromagnetic navigation with TiLT-assisted lesion guidance. Non-specific results were followed up until either a clear diagnosis was achieved or repeat radiology at 6 months demonstrated stability. RESULTS: Eighteen patients (19 nodules) were enrolled. The average lesion size was 20 mm, and the average distance from the pleura was 11.6 mm. The target was successfully reached in 100% of nodules, and the biopsy tool was visualized inside the target lesion in all cases. A confirmed specific diagnosis was achieved in 17 nodules, 13 of which were malignant. In one patient, radiological monitoring confirmed a true non-malignant result. This translates to a yield of 89.5% (strict) to 94.7% (intermediate). Complications included one pneumothorax requiring observation only and another requiring an overnight chest drain. There was one case of severe pneumonia following the procedure. CONCLUSION: In this first-in-human study, second-generation robotic bronchoscopy using electromagnetic navigation combined with integrated digital tomosynthesis was feasible with an acceptable safety profile and demonstrated a high diagnostic yield for small peripheral lung nodules.

Tracheobronchial stents: an expanding prospect.

The first dedicated tracheobronchial silicone stent was designed by the French pulmonologist Jean-Paul Dumon. The most common indications for stenting are to minimise extrinsic airway compression from mass effect, maintain airway patency due to intrinsic obstruction or treat significant nonmalignant airway narrowing or fistulae. Silicone stents require rigid bronchoscopy for insertion; however, they are more readily repositioned and removed compared with metallic stents. Metallic stents demonstrate luminal narrowing when loads are applied to their ends, therefore stents should either be reinforced at the ends or exceed the area of stenosis by a minimum of 5 mm. Nitinol, a nickel-titanium metal alloy, is currently the preferred material used for airway stents. Airway stenting provides effective palliation for patients with severe symptomatic obstruction. Drug-eluting and three-dimensional printing of airway stents present promising solutions to the challenges of the physical and anatomical constraints of the tracheobronchial tree. Biodegradable stents could also be a solution for the treatment of nonmalignant airway obstruction.

Reversal of collateral ventilation using endoscopic polymer foam in COPD patients undergoing endoscopic lung volume reduction with endobronchial valves: A controlled parallel group trial.

BACKGROUND AND OBJECTIVE: We have previously described reversal of collateral ventilation (CV) in a severe chronic obstructive pulmonary disease (COPD) patient with endoscopic polymer foam (EPF), prior to endoscopic lung volume reduction (ELVR) with valves. The aim of this study was to investigate the efficacy of this in a larger cohort and compare outcomes with a similar cohort with no CV. METHODS: Patients with severe COPD, with the left upper lobe (LUL) targeted for ELVR, were assessed for CV with high resolution computed tomography (HRCT). If fissure completeness was >95% they were enrolled as controls for valves alone (endobronchial valve control group [EBV-CTRL]). If fissure completeness was 80%-95%, defects were mapped to the corresponding segment, where EPF was instilled following confirmation of CV with CHARTIS. EBVs were inserted 1 month afterwards. RESULTS: Fourteen patients were enrolled into both arms. After 6 months, there were significant improvements in both groups in forced expiratory volume in 1 s (FEV1; +19.7% EPF vs. +27.7% EBV-CTRL, p < 0.05); residual volume (RV; -16.2% EPF vs. -20.1% EBV-CTRL, p = NS); SGRQ (-15.1 EPF vs. -16.6 EBV-CTRL p = NS) and 6 min walk (+25.8% EPF [77.2 m] vs. +28.4% [82.3 m] EBV-CTRL p = NS). Patients with fissural defects mapped to the lingula had better outcomes than those mapped to other segments (FEV1 +22.9% vs. +16.3% p < 0.05). There were no serious adverse reactions to EPF. CONCLUSION: EPF successfully reverses CV in severe COPD patients with a left oblique fissure that is 80%-95% complete. Following EBV, outcomes are similar to patients with complete fissures undergoing ELVR with EBV alone. EPF therapy to reverse CV potentially increases the number of COPD patients suitable for ELVR with minimal adverse reactions.

Development of a Bronchoscopy-Radiologic Skills and Task Assessment Tool (BRadSTAT): A Tool for Evaluating the Radiological Skills of Bronchoscopists with Different Experience.

BACKGROUND: Competency using radiologic images for bronchoscopic navigation is presumed during subspecialty training, but no assessments objectively measure combined knowledge of radiologic interpretation and ability to maneuver a bronchoscope into peripheral airways. OBJECTIVES: The objectives of this study were (i) to determine whether the Bronchoscopy-Radiology Skills and Tasks Assessment Tool (BRadSTAT) discriminates between bronchoscopists of various levels of experience and (ii) to improve construct validity using study findings. METHODS: BRadSTAT contains 10 questions that assess chest X-ray and CT scan interpretation using multiple images per question and 2 technical skill assessments. After administration to 33 bronchoscopists (5 Beginners, 9 Intermediates, 10 Experienced, and 9 Experts), discriminative power was strengthened using differential weighting on CT-related questions, producing the BRadSTAT-CT score. Cut points for both scores were determined via cross-validation. RESULTS: Mean BRadSTAT scores for Beginner, Intermediate, Experienced, and Expert were 74 (±13 SD), 78 (±14), 86 (±9), and 88 (±8), respectively. Statistically significant differences were noted between Expert and Beginner, Expert and Intermediate, and Experienced and Beginner (all p ≤ 0.05). Mean BRadSTAT-CT scores for Beginner, Intermediate, Experienced, and Expert were 63 (±14), 74 (±15), 82 (±13), and 90 (±9), respectively, all statistically significant (p ≤ 0.03). Cut points for BRadSTAT-CT had lower sensitivity but greater specificity and accuracy than for BRadSTAT. CONCLUSION: BRadSTAT represents the first validated assessment tool measuring knowledge and skills for bronchoscopic access to peripheral airways, which discriminates between bronchoscopists of various experience levels. Refining BRadSTAT produced the BRadSTAT-CT, which had higher discriminative power. Future studies should focus on their usefulness in competency-based bronchoscopy programs.

Cryobiopsy for Identification of Usual Interstitial Pneumonia and Other Interstitial Lung Disease Features. Further Lessons from COLDICE, a Prospective Multicenter Clinical Trial.

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 radiologic asymmetry. 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).

Interventional bronchoscopy for chronic obstructive pulmonary disease: more than a pipe dream.

Endoscopic lung volume reduction (ELVR) is recognised in both national and international expert guidelines as one of the few additive treatments to benefit patients with advanced chronic obstructive pulmonary disease (COPD) who are otherwise receiving optimal medical and supportive care. Despite these recommendations and a growing evidence base, these procedures are not widely offered across Australia and New Zealand, and general practitioner and physician awareness of this therapy can be improved. ELVR aims to mitigate the impact of hyperinflation and gas trapping on dyspnoea and exercise intolerance in COPD. Effective ELVR is of proven benefit in improving symptoms, quality of life, lung function and survival. Several endoscopic techniques to achieve ELVR have been developed, with endobronchial valve placement to collapse a single lobe being the most widely studied and commonly practised. This review describes the physiological rationale underpinning lung volume reduction, highlights the challenges of patient selection, and provides an overview of the evidence for current and investigational endoscopic interventions for COPD.

Bronchial Rheoplasty for Treatment of Chronic Bronchitis. Twelve-Month Results from a Multicenter Clinical Trial.

Rationale: Chronic bronchitis (CB) is characterized by productive cough with excessive mucus production, resulting in quality-of-life impairment and increased exacerbation risk. Bronchial rheoplasty uses an endobronchial catheter to apply nonthermal pulsed electrical fields to the airways. Preclinical studies have demonstrated epithelial ablation followed by regeneration of normalized epithelium.Objectives: To evaluate the feasibility, safety, and initial outcomes of bronchial rheoplasty in patients with CB.Methods: Pooled analysis of two separate studies enrolling 30 patients undergoing bilateral bronchial rheoplasty was conducted. Follow-up through 6 months (primary outcome) and 12 months included assessment of adverse events, airway histology, and changes in symptoms using the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test and St. George's Respiratory Questionnaire (SGRQ).Measurements and Main Results: Bronchial rheoplasty was performed in all 30 patients (63% male; mean [SD] age, 67 [7.4]; mean [SD] postbronchodilator FEV1, 65% [21%]; mean [SD] COPD Assessment Test score 25.6 [7.1]; mean [SD] SGRQ score, 59.6 [15.3]). There were no device-related and four procedure-related serious adverse events through 6 months, and there were none thereafter through 12 months. The most frequent nonserious, device- and/or procedure-related event through 6 months was mild hemoptysis in 47% (14 of 30) patients. Histologically, the mean goblet cell hyperplasia score was reduced by a statistically significant amount (P < 0.001). Significant changes from baseline to 6 months in COPD Assessment Test (mean, -7.9; median, -8.0; P = 0.0002) and SGRQ (mean, -14.6; median, -7.2; P = 0.0002) scores were observed, with similar observations through 12 months.Conclusions: This study provides the first clinical evidence of the feasibility, safety, and initial outcomes of bronchial rheoplasty in symptomatic patients with CB.Clinical trial registered with www.anzctr.org.au (ACTRN 12617000330347) and clinicaltrials.gov (NCT03107494).

Training in interventional pulmonology: What we have learned and a way forward.

IP encompasses a complex list of procedures requiring knowledge, technical skills and competence. Modern, learner-centric educational philosophies and an explosion of multidimensional educational tools including manikins, simulators, online resources, social media and formal programs can foster learning in IP, promoting professionalism and a culture of lifelong learning. This paper provides background and guidance to a structured, multidimensional and learner-centric strategy for medical procedural education. Focusing on our experience in IP, we describe how competency-based measures, simulation technology and various teaching modalities contribute to a more uniform learning environment in which patients do not suffer the burdens of procedure-related training.

Outcomes of an initiative to improve inpatient safety of small bore thoracostomy tube insertion.

BACKGROUND: Intercostal chest catheter (ICC) insertion is a common hospital procedure with attendant risks including life-threatening complications such as pneumothorax and visceral damage. AIM: To investigate the effect of a quality improvement (QI) initiative on complications associated with inpatient thoracostomy tube insertion. METHODS: Following an audit of ICC complications in inpatients over a 2-year period we implemented a comprehensive QI programme. This involved formal training in and mandatory use of thoracic ultrasound, standardisation of the procedure and documentation, a dedicated procedure room with nurses trained in assisting ICC insertion and senior supervision for medical staff. An audit over 2 years post-implementation of the QI protocol was compared with pre-implementation results. RESULTS: A total of 103 cases were reviewed pre-implementation and 105 cases were reviewed post-implementation of the QI programme. All procedures following the QI initiative were image guided compared to 23.3% of cases pre-implementation. The rate of developing a pneumothorax requiring intervention post-implementation was less than pre-implementation (1.9% vs 5.8% (P = 0.023). Post-implementation, there were no instances of dry taps, viscera perforation, clinically significant bleeding or wrong side ICC insertion and documentation improved. CONCLUSION: QI initiative applied to thoracostomy tube insertion in hospital inpatients can reduce complications and improve procedure documentation.

Thoracic ultrasound recognition of competence: A position paper of the Thoracic Society of Australia and New Zealand.

The ability to perform bedside thoracic ultrasound is increasingly recognized as an essential skill for thoracic clinicians, extending the clinical examination and aiding diagnostic and therapeutic procedures. Thoracic ultrasound reduces complications and increases success rates when used prior to thoracentesis or intercostal chest tube insertion. It is increasingly difficult to defend performing these procedures without real or near-real time image guidance. To assist thoracic physicians and others achieve and demonstrate thoracic ultrasound competence, the Interventional Pulmonology Special Interest Group (IP-SIG) of the Thoracic Society of Australia and New Zealand (TSANZ) has developed a new pathway with four components: (i) completion of an approved thoracic ultrasound theory and hands-on teaching course. (ii) A log of at least 40 relevant scans. (iii) Two formative assessments (following 5-10 scans and again after 20 scans) using the Ultrasound-Guided Thoracentesis Skills and Tasks Assessment Tool (UG-STAT). (iv) A barrier assessment (UG-STAT, pass score of 90%) by an accredited assessor not directly involved in the candidate's training. Upon completion of these requirements a candidate may apply to the TSANZ for recognition of competence. This pathway is intended to provide a regional standard for thoracic ultrasound training.

Evaluation of Transbronchial Lung Cryobiopsy Size and Freezing Time: A Prognostic Animal Study.

BACKGROUND: Transbronchial lung biopsy using a cryoprobe is a novel way of sampling lung parenchyma. Correlation of freezing time with biopsy size and complications has not been evaluated in vivo. OBJECTIVES: The primary aim of the study is to evaluate the correlation between transbronchial cryobiopsy freezing time and size. The secondary aims are to evaluate histological quality of the biopsy and evaluate procedure-associated complications. METHODS: Transbronchial lung cryobiopsies were obtained from two anaesthetised sheep using a 1.9-mm cryoprobe inserted into a flexible bronchoscope under fluoroscopic guidance. Freezing times ranged from 1 to 6 s (n = 49). The cryobiopsies were evaluated histologically with respect to their size and quality. Complications of bleeding and pneumothorax were recorded. RESULTS: The mean cross-sectional area of the cryobiopsy ranged from 4.7 ± 2.1 to 15.7 ± 15.3 mm2. There was a significant positive correlation between increasing freezing time and cryobiopsy cross-sectional area (p = 0.028). All biopsies contained lung tissue with preserved parenchyma. Crush and freeze artefacts were not observed and tissue architecture was intact in all specimens. Small blood vessels and terminal bronchioles were observed in 88% of specimens. All cryobiopsies caused nil or mild haemorrhage with the exception of only 1 episode of severe haemorrhage at 6 s freezing time. Pneumothoraces occurred at 2, 5 and 6 s freezing time and required chest tube insertion. The most significant haemorrhage and pneumothoraces occurred at 5 and 6 s. Our results suggest an initial freezing time of 3 s can provide the maximal biopsy size while minimising major complications. CONCLUSION: The optimal transbronchial cryobiopsy freezing time is initially 3 s. This time is associated with minimal complications and large artefact-free biopsies.

Evaluation of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) Samples from Advanced Non-Small Cell Lung Cancer for Whole Genome, Whole Exome and Comprehensive Panel Sequencing.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is often the only source of tumor tissue from patients with advanced, inoperable lung cancer. EBUS-TBNA aspirates are used for the diagnosis, staging, and genomic testing to inform therapy options. Here we extracted DNA and RNA from 220 EBUS-TBNA aspirates to evaluate their suitability for whole genome (WGS), whole exome (WES), and comprehensive panel sequencing. For a subset of 40 cases, the same nucleic acid extraction was sequenced using WGS, WES, and the TruSight Oncology 500 assay. Genomic features were compared between sequencing platforms and compared with those reported by clinical testing. A total of 204 aspirates (92.7%) had sufficient DNA (100 ng) for comprehensive panel sequencing, and 109 aspirates (49.5%) had sufficient material for WGS. Comprehensive sequencing platforms detected all seven clinically reported tier 1 actionable mutations, an additional three (7%) tier 1 mutations, six (15%) tier 2-3 mutations, and biomarkers of potential immunotherapy benefit (tumor mutation burden and microsatellite instability). As expected, WGS was more suited for the detection and discovery of emerging novel biomarkers of treatment response. WGS could be performed in half of all EBUS-TBNA aspirates, which points to the enormous potential of EBUS-TBNA as source material for large, well-curated discovery-based studies for novel and more effective predictors of treatment response. Comprehensive panel sequencing is possible in the vast majority of fresh EBUS-TBNA aspirates and enhances the detection of actionable mutations over current clinical testing.

Central airway squamous metaplasia following radiation therapy mimicking local tumour recurrence.

Radiation therapy can result in injury to the lung parenchyma and central airways; the latter is less well documented in the literature. Here, we describe a 65-year-old Caucasian male, who developed focal endobronchial nodules and right main bronchial stenosis suggesting tumour recurrence, 32 months following curative intent concurrent chemoradiation therapy for Stage 3B squamous cell carcinoma of the lung. Computed tomography and positron emission tomography results are detailed. Flexible bronchoscopy with bronchial biopsies revealed squamous metaplasia rather than malignant tumour recurrence, with ongoing observation planned.

Central airway squamous metaplasia following radiation therapy mimicking local tumour recurrence.

Radiation therapy can result in injury to the lung parenchyma and central airways; the latter is less well documented in the literature. Here, we describe a 65-year-old Caucasian male, who developed focal endobronchial nodules and right main bronchial stenosis suggesting tumour recurrence, 32 months following curative intent concurrent chemoradiation therapy for Stage 3B squamous cell carcinoma of the lung. Computed tomography and positron emission tomography results are detailed. Flexible bronchoscopy with bronchial biopsies revealed squamous metaplasia rather than malignant tumour recurrence, with ongoing observation planned.

Elastic properties of the central airways in obstructive lung diseases measured using anatomical optical coherence tomography.

RATIONALE: Our understanding of how airway remodeling affects regional airway elastic properties is limited due to technical difficulties in quantitatively measuring dynamic, in vivo airway dimensions. Such knowledge could help elucidate mechanisms of excessive airway narrowing. OBJECTIVES: To use anatomical optical coherence tomography (aOCT) to compare central airway elastic properties in control subjects and those with obstructive lung diseases. METHODS: After bronchodilation, airway lumen area (Ai) was measured using aOCT during bronchoscopy in control subjects (n = 10) and those with asthma (n = 16), chronic obstructive pulmonary disease (COPD) (n = 9), and bronchiectasis (n = 8). Ai was measured in each of generations 0 to 5 while airway pressure was increased from -10 to 20 cm H(2)O. Airway compliance (Caw) and specific compliance (sCaw) were derived from the transpulmonary pressure (Pl) versus Ai curves. MEASUREMENTS AND MAIN RESULTS: Caw decreased progressively as airway generation increased, but sCaw did not differ appreciably across the generations. In subjects with asthma and bronchiectasis, Caw and sCaw were similar to control subjects and the Pl-Ai curves were left-shifted. No significant differences were observed between control and COPD groups. CONCLUSIONS: Proximal airway elastic properties are altered in obstructive lung diseases. Although central airway compliance does not differ from control subjects in asthma, bronchiectasis, or COPD, Ai is lower in asthma and the Pl-Ai relationship is left-shifted in both asthma and bronchiectasis, suggesting that airways are maximally distended at lower inflating pressures. Such changes reflect alteration in the balance between airway wall distensibility and radial traction exerted on airways by surrounding lung parenchyma favoring airway narrowing. Clinical trial registered with Australian New Zealand Clinical Trials Registry (ACTRN12607000624482).

Phenotyping airway disease with optical coherence tomography.

Airway diseases are a major concern around the world. However, the pace of new drug and biomarker discovery has lagged behind those of other common disorders such as cardiovascular diseases and diabetes. One major barrier in airway research has been the inability to accurately visualize large or small airway remodelling or dysplastic/neoplastic (either pre or early cancerous) changes using non- or minimally invasive instruments. The advent of optical coherence tomography (OCT) has the potential to revolutionize airway research and management by allowing investigators and clinicians to visualize the airway with resolution approaching histology and without exposing patients to harmful effects of ionizing radiation. Thus, with the aid of OCT, we may be able to accurately determine and quantify the extent of airway remodelling in asthma and chronic obstructive pulmonary disease, detect early pre-cancerous lesions in smokers for chemoprevention, study the upper airway anatomy of patients with obstructive sleep apnea in real time while they are asleep and facilitate optimal selection of stents for those with tracheal obstruction. In this paper, we review the current state of knowledge of OCT and its possible application in airway diseases.

Localized tracheobronchial amyloidosis: A rare case presentation and tailored management approaches.

Localized tracheobronchial amyloidosis (TBA) is a rare manifestation of pulmonary amyloid disease, and can result in central airway obstruction. The nature of presentation is variable and there may be a delayed diagnosis. TBA has a variable prognosis and the most commonly used strategy for management is airway recanalization. Here, we describe the tailored management approach for a 64-year-old Caucasian female presenting with localized TBA of the left main bronchus. Pulmonary function testing, computed tomography and positron emission tomography results are detailed. Rigid bronchoscopy was utilized for diagnostic and therapeutic intervention, which involved debulking and stent insertion. Amyloid deposition and localized inflammation were identified through histopathology. Focal external beam radiation therapy was administered following multidisciplinary discussion and review of the literature, with no evidence of active disease at 6 months follow-up.

Con: Bronchoscopy is essential for pulmonary infections in patients with haematological malignancies.

Whilst some patients with haematological malignancy and pulmonary infection may benefit from a bronchoscopy, this uniform approach is not justified by the literature and more studies are required to fill the void in our understanding of this area https://bit.ly/3bfUfs7.

A foreign body experience.

Foreign body inhalation (FBI) is an uncommon clinical entity in adults. Despite this, FBI is an under-recognized, serious, and easily treatable condition. The authors report a case of a 31-year-old female asthmatic who presented with wheeze and cough not responding to therapy. Chest computed tomography and bronchoscopy confirmed a foreign body distal to the left upper lobe vestibule. The non-organic material was removed with rigid bronchoscopy and cryoprobe with resolution of symptoms. FBI remains an important differential in those presenting with respiratory symptoms in the absence of other diagnoses.