Advancements in airway stents: a comprehensive update.

PURPOSE OF REVIEW: This review provides an overview of the evolving field of airway stenting (AS), highlighting its relevance in the management of central airway obstruction (CAO). It discusses recent advancements, including 3D-printed silicone stents (3DPSS), metallic stents, biodegradable stents (BS), and drug-eluting stents (DES), which are transforming clinical practice. The review underscores the ongoing challenges in patient selection, stent choice, and long-term management in the context of an evolving landscape. RECENT FINDINGS: Innovations, particularly 3DPSS, have shown promise in providing patient-specific solutions. These stents offer improved symptom relief, enhanced quality of life, and lower complication rates, especially for complex airway diseases. The use of BS and DES is explored, raising prospects for future applications. SUMMARY: The evolution of AS reflects a deepening understanding of airway obstructions. Recent innovations, such as 3DPSS, BS, and DES, show considerable promise in addressing the limitations of conventional stents. However, challenges related to complications, patient selection, and long-term management persist, demanding further research. Wide practice variations in the management of AS highlight the need for more clinical data and standardized guidelines. The search for the ideal stent continues, driven by the pursuit of better outcomes for patients with CAO.

Malignant Central Airway Obstruction: What's New?

Malignant central airway obstruction (MCAO) is a debilitating and life-limiting complication that occurs in an unfortunately large number of individuals with advanced intrathoracic cancer. Although the management of MCAO is multimodal and interdisciplinary, the task of providing patients with prompt palliation falls increasingly on the shoulders of interventional pulmonologists. While a variety of tools and techniques are available for the management of malignant obstructive lesions, advancements and evolution in this therapeutic venue have been somewhat sluggish and limited when compared with other branches of interventional pulmonary medicine (e.g., the early diagnosis of peripheral lung nodules). Indeed, one pragmatic, albeit somewhat uncharitable, reading of this article's title might suggest a wry smile and shug of the shoulders as to imply that relatively little has changed in recent years. That said, the spectrum of interventions for MCAO continues to expand, even if at a less impressive clip. Herein, we present on MCAO and its endoscopic and nonendoscopic management-that which is old, that which is new, and that which is still on the horizon.

Prospective cohort of cryobiopsy in interstitial lung diseases: a single center experience.

RATIONALE: Transbronchial cryobiopsy has been increasingly used to diagnose interstitial lung diseases. However, there is uncertainty regarding its accuracy and risks, mainly due to a paucity of prospective or randomized trials comparing cryobiopsy to surgical biopsy. OBJECTIVES: To evaluate the diagnostic yield and complications of cryobiopsy in patients selected by multidisciplinary discussion. METHODS: This was a prospective cohort from 2017 to 2019. We included consecutive patients with suspected interstitial lung diseases being considered for lung biopsy presented at our multidisciplinary meeting. MEASUREMENTS AND MAIN RESULTS: Of 112 patients, we recommended no biopsy in 31, transbronchial forceps biopsy in 16, cryobiopsy in 54 and surgical biopsy in 11. By the end of the study, 34 patients had had cryobiopsy and 24 patients, surgical biopsy. Overall pathologic and multidisciplinary diagnostic yield of cryobiopsy was 47.1% and 61.8%, respectively. The yield increased over time for both pathologic (year 1: 28.6%, year 2: 54.5%, year 3: 66.7%, p = 0.161) and multidisciplinary (year 1: 50%, year 2: 63.6%, year 3: 77.8%, p = 0.412) diagnosis. Overall rate of grade 4 bleeding after cryobiopsy was 11.8%. Cryobiopsy required less chest tube placement (11.8% vs 100%, p < 0.001) and less hospitalizations compared to surgical biopsy (26.5% vs 95.7%, p < 0.001), but hospitalized patients had a longer median hospital stay (2 days vs 1 day, p = 0.004). CONCLUSIONS: Diagnostic yield of cryobiopsy increased over time but the overall grade 4 bleeding rate was 11.8%.

A Prediction Model to Help with Oncologic Mediastinal Evaluation for Radiation: HOMER.

Rationale: When stereotactic ablative radiotherapy is an option for patients with non-small cell lung cancer (NSCLC), distinguishing between N0, N1, and N2 or N3 (N2|3) disease is important.Objectives: To develop a prediction model for estimating the probability of N0, N1, and N2|3 disease.Methods: Consecutive patients with clinical-radiographic stage T1 to T3, N0 to N3, and M0 NSCLC who underwent endobronchial ultrasound-guided staging from a single center were included. Multivariate ordinal logistic regression analysis was used to predict the presence of N0, N1, or N2|3 disease. Temporal validation used consecutive patients from 3 years later at the same center. External validation used three other hospitals.Measurements and Main Results: In the model development cohort (n = 633), younger age, central location, adenocarcinoma, and higher positron emission tomography-computed tomography nodal stage were associated with a higher probability of having advanced nodal disease. Areas under the receiver operating characteristic curve (AUCs) were 0.84 and 0.86 for predicting N1 or higher (vs. N0) disease and N2|3 (vs. N0 or N1) disease, respectively. Model fit was acceptable (Hosmer-Lemeshow, P = 0.960; Brier score, 0.36). In the temporal validation cohort (n = 473), AUCs were 0.86 and 0.88. Model fit was acceptable (Hosmer-Lemeshow, P = 0.172; Brier score, 0.30). In the external validation cohort (n = 722), AUCs were 0.86 and 0.88 but required calibration (Hosmer-Lemeshow, P < 0.001; Brier score, 0.38). Calibration using the general calibration method resulted in acceptable model fit (Hosmer-Lemeshow, P = 0.094; Brier score, 0.34).Conclusions: This prediction model can estimate the probability of N0, N1, and N2|3 disease in patients with NSCLC. The model has the potential to facilitate decision-making in patients with NSCLC when stereotactic ablative radiotherapy is an option.

Accuracy of a Robotic Endoscopic System in Cadaver Models with Simulated Tumor Targets: ACCESS Study.

BACKGROUND: Bronchoscopy for the diagnosis of peripheral pulmonary lesions continues to present clinical challenges, despite increasing experience using newer guided techniques. Robotic bronchoscopic platforms have been developed to potentially improve diagnostic yields. Previous studies in cadaver models have demonstrated increased reach into the lung periphery using robotic systems compared to similarly sized conventional bronchoscopes, although the clinical impact of additional reach is unclear. OBJECTIVES: This study was performed to evaluate the performance of a robotic bronchoscopic system's ability to reach and access artificial tumor targets simulating peripheral nodules in human cadaveric lungs. METHODS: Artificial tumor targets sized 10-30 mm in axial diameter were implanted into 8 human cadavers. CT scans were performed prior to procedures and all cadavers were intubated and mechanically ventilated. Electromagnetic navigation, radial probe endobronchial ultrasound, and fluoroscopy were used for all procedures. Robotic-assisted bronchoscopy was performed on each cadaver by an individual bronchoscopist to localize and biopsy peripheral lesions. RESULTS: Sixty-seven nodules were evaluated in 8 cadavers. The mean nodule size was 20.4 mm. The overall diagnostic yield was 65/67 (97%) and there was no statistical difference in diagnostic yield for lesions <20 mm compared with lesions measuring 21-30 mm, the presence of a concentric or eccentric radial ultrasound image, or relative distance from the pleura. CONCLUSIONS: The robotic bronchoscopic system was successful at biopsying 97% of peripheral pulmonary lesions 10-30 mm in size in human cadavers. These findings support further exploration of this technology in prospective clinical trials in live human subjects.

Application of 3D Printing for Patient-Specific Silicone Stents: 1-Year Follow-Up on 2 Patients.

Managing complex benign airway disease is a major challenge in interventional pulmonology. Airway stent placement can result in complications due to a variety of factors, including poor fit of the stent in the airway. We report the 1-year outcome of 2 patients with airway disease caused by granulomatosis with polyangiitis (Wegener's) affecting the left main bronchus and secondary carina. These patients had not responded to systemic therapy or standard bronchoscopic techniques and had complications with commercially available airway stents. We describe a first-in-human, clinical experience to address these issues. Using computed tomography (CT) imaging and 3D printing technology, we generated and implanted patient-specific silicone airway stents to address airway disease. 3D patient-specific stent prescription was created using a CT scan of the patient's chest and a proprietary software package originally developed for orthopedic surgical planning. Silicone stents were manufactured and implanted. Observation for > 1 year after implantation compared to the 6 months prior to patient-specific stent implant were compared for the number, clinically required stent changes, procedure time, and general clinical improvement per usual standard of care after airway stenting. Patients showed improved durability, a shorter procedure time, and improvement of patient-reported symptoms leading to a reduced need for stent changes and modifications. The use of 3D printing technology to make patient-specific silicone stents is feasible with early clinical proof of concept noting a durable improvement over 1 year of follow-up.

A Prediction Model to Help with the Assessment of Adenopathy in Lung Cancer: HAL.

RATIONALE: Estimating the probability of finding N2 or N3 (prN2/3) malignant nodal disease on endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients with non-small cell lung cancer (NSCLC) can facilitate the selection of subsequent management strategies. OBJECTIVES: To develop a clinical prediction model for estimating the prN2/3. METHODS: We used the AQuIRE (American College of Chest Physicians Quality Improvement Registry, Evaluation, and Education) registry to identify patients with NSCLC with clinical radiographic stage T1-3, N0-3, M0 disease that had EBUS-TBNA for staging. The dependent variable was the presence of N2 or N3 disease (vs. N0 or N1) as assessed by EBUS-TBNA. Univariate followed by multivariable logistic regression analysis was used to develop a parsimonious clinical prediction model to estimate prN2/3. External validation was performed using data from three other hospitals. MEASUREMENTS AND MAIN RESULTS: The model derivation cohort (n = 633) had a 25% prevalence of malignant N2 or N3 disease. Younger age, central location, adenocarcinoma histology, and higher positron emission tomography-computed tomography N stage were associated with a higher prN2/3. Area under the receiver operating characteristic curve was 0.85 (95% confidence interval, 0.82-0.89), model fit was acceptable (Hosmer-Lemeshow, P = 0.62; Brier score, 0.125). We externally validated the model in 722 patients. Area under the receiver operating characteristic curve was 0.88 (95% confidence interval, 0.85-0.90). Calibration using the general calibration model method resulted in acceptable goodness of fit (Hosmer-Lemeshow test, P = 0.54; Brier score, 0.132). CONCLUSIONS: Our prediction rule can be used to estimate prN2/3 in patients with NSCLC. The model has the potential to facilitate clinical decision making in the staging of NSCLC.

Electromagnetic navigation bronchoscopy to access lung lesions in 1,000 subjects: first results of the prospective, multicenter NAVIGATE study.

BACKGROUND: Electromagnetic navigation bronchoscopy (ENB) is an image-guided, minimally invasive approach that uses a flexible catheter to access pulmonary lesions. METHODS: NAVIGATE is a prospective, multicenter study of the superDimension™ navigation system. A prespecified 1-month interim analysis of the first 1,000 primary cohort subjects enrolled at 29 sites in the United States and Europe is described. Enrollment and 24-month follow-up are ongoing. RESULTS: ENB index procedures were conducted for lung lesion biopsy (n = 964), fiducial marker placement (n = 210), pleural dye marking (n = 17), and/or lymph node biopsy (n = 334; primarily endobronchial ultrasound-guided). Lesions were in the peripheral/middle lung thirds in 92.7%, 49.7% were <20 mm, and 48.4% had a bronchus sign. Radial EBUS was used in 54.3% (543/1,000 subjects) and general anesthesia in 79.7% (797/1,000). Among the 964 subjects (1,129 lesions) undergoing lung lesion biopsy, navigation was completed and tissue was obtained in 94.4% (910/964). Based on final pathology results, ENB-aided samples were read as malignant in 417/910 (45.8%) subjects and non-malignant in 372/910 (40.9%) subjects. An additional 121/910 (13.3%) were read as inconclusive. One-month follow-up in this interim analysis is not sufficient to calculate the true negative rate or diagnostic yield. Tissue adequacy for genetic testing was 80.0% (56 of 70 lesions sent for testing). The ENB-related pneumothorax rate was 4.9% (49/1,000) overall and 3.2% (32/1,000) CTCAE Grade ≥2 (primary endpoint). The ENB-related Grade ≥2 bronchopulmonary hemorrhage and Grade ≥4 respiratory failure rates were 1.0 and 0.6%, respectively. CONCLUSIONS: One-month results of the first 1,000 subjects enrolled demonstrate low adverse event rates in a generalizable population across diverse practice settings. Continued enrollment and follow-up are required to calculate the true negative rate and delineate the patient, lesion, and procedural factors contributing to diagnostic yield. TRIAL REGISTRATION: ClinicalTrials.gov NCT02410837 . Registered 31 March 2015.

Cost effectiveness of bronchial thermoplasty in patients with severe uncontrolled asthma.

RATIONALE: Based on its clinical effectiveness, bronchial thermoplasty (BT) was approved by the Food and Drug Administration in 2010 for the treatment of severe persistent asthma in patients 18 years and older whose asthma is not well-controlled with inhaled corticosteroids and long-acting beta-agonist medicines. OBJECTIVE: Assess the 10 year cost-effectiveness of BT for individuals with severe uncontrolled asthma. METHODS: Using a Markov decision analytic model, the cost-effectiveness of BT was estimated. The patient population involved a hypothetical cohort of 41-year-old patients comparing BT to usual care over a 10-year time frame. The main outcome measure was cost in 2013 dollars per additional quality adjusted life year (QALY). RESULTS: Treatment with BT resulted in 6.40 QALYs and $7512 in cost compared to 6.21 QALYs and $2054 for usual care. The incremental cost-effectiveness ratio for BT at 10 years was $29,821/QALY. At a willingness to pay per QALY of $50,000, BT continues to be cost effective unless the probability of severe asthma exacerbation drops below 0.63 exacerbation per year or the cost of BT rises above $10,384 total for all three bronchoscopic procedures needed to perform thermoplasty and to cover the entire bronchial tree (baseline = $6690). CONCLUSIONS: BT is a cost-effective treatment for asthmatics at high risk of exacerbations. Continuing to follow asthmatics treated with BT beyond 5 years will help inform longer efficacy and support its cost-effectiveness.

Design of a prospective, multicenter, global, cohort study of electromagnetic navigation bronchoscopy.

BACKGROUND: Electromagnetic navigation bronchoscopy (ENB) procedures allow physicians to access peripheral lung lesions beyond the reach of conventional bronchoscopy. However, published research is primarily limited to small, single-center studies using previous-generation ENB software. The impact of user experience, patient factors, and lesion/procedural characteristics remains largely unexplored in a large, multicenter study. METHODS/DESIGN: NAVIGATE (Clinical Evaluation of superDimension™ Navigation System for Electromagnetic Navigation Bronchoscopy) is a prospective, multicenter, global, cohort study. The study aims to enroll up to 2,500 consecutive subjects presenting for evaluation of lung lesions utilizing the ENB procedure at up to 75 clinical sites in the United States, Europe, and Asia. Subjects will be assessed at baseline, at the time of procedure, and at 1, 12, and 24 months post-procedure. The pre-test probability of malignancy will be determined for peripheral lung nodules. Endpoints include procedure-related adverse events, including pneumothorax, bronchopulmonary hemorrhage, and respiratory failure, as well as quality of life, and subject satisfaction. Diagnostic yield and accuracy, repeat biopsy rate, tissue adequacy for genetic testing, and stage at diagnosis will be reported for biopsy procedures. Complementary technologies, such as fluoroscopy and endobronchial ultrasound, will be explored. Success rates of fiducial marker placement, dye marking, and lymph node biopsies will be captured when applicable. Subgroup analyses based on geography, demographics, investigator experience, and lesion and procedure characteristics are planned. DISCUSSION: Study enrollment began in April 2015. As of February 19, 2016, 500 subjects had been enrolled at 23 clinical sites with enrollment ongoing. NAVIGATE will be the largest prospective, multicenter clinical study on ENB procedures to date and will provide real-world experience data on the utility of the ENB procedure in a broad range of clinical scenarios. TRIAL REGISTRATION: ClinicalTrials.gov NCT02410837 . Registered 31 March 2015.

A randomised trial of lung sealant versus medical therapy for advanced emphysema.

Uncontrolled pilot studies demonstrated promising results of endoscopic lung volume reduction using emphysematous lung sealant (ELS) in patients with advanced, upper lobe predominant emphysema. We aimed to evaluate the safety and efficacy of ELS in a randomised controlled setting.Patients were randomised to ELS plus medical treatment or medical treatment alone. Despite early termination for business reasons and inability to assess the primary 12-month end-point, 95 out of 300 patients were successfully randomised, providing sufficient data for 3- and 6-month analysis.57 patients (34 treatment and 23 control) had efficacy results at 3 months; 34 (21 treatment and 13 control) at 6 months. In the treatment group, 3-month lung function, dyspnoea, and quality of life improved significantly from baseline when compared to control. Improvements persisted at 6 months with >50% of treated patients experiencing clinically important improvements, including some whose lung function improved by >100%. 44% of treated patients experienced adverse events requiring hospitalisation (2.5-fold more than control, p=0.01), with two deaths in the treated cohort. Treatment responders tended to be those experiencing respiratory adverse events.Despite early termination, results show that minimally invasive ELS may be efficacious, yet significant risks (probably inflammatory) limit its current utility.

Tracheobronchial smooth muscle atrophy and separation.

We report a case series involving 4 patients with chronic obstructive pulmonary disease who were on an appropriate medical regimen including a high dose of inhaled corticosteroids (ICS). During bronchoscopy, patients were found to have an excessive dynamic collapse of the posterior wall and its separation from the ends of the adjacent cartilaginous rings. This was causing a near-total occlusion of the tracheal and bronchial lumen during exhalation, thereby presenting with an obstructive pattern on the pulmonary functions. We suspect that this was caused by the atrophy of the smooth muscles of the tracheobronchial wall. We reviewed the literature to explore the mechanisms causing atrophy of the bronchial smooth muscle, focusing on the potential role of long-term ICS use.

The natural history of lung function after lung transplantation for α(1)-antitrypsin deficiency.

RATIONALE: Lung transplantation (LT) is an established treatment for end-stage lung diseases, including chronic obstructive pulmonary disease (COPD) associated with α1-antitrypsin deficiency (AATD). OBJECTIVES: We sought to compare the post-transplantation course of patients with AATD and AAT-replete COPD. METHODS: Between June 1991 and January 2008, a total of 231 patients with AAT-replete COPD and 45 with AATD underwent LT at Cleveland Clinic. Data reviewed included baseline recipient, donor, and surgical data; all spirometry evaluations; acute cellular rejection (ACR) events; and survival data. Endpoints included temporal change in FEV1, severity of ACR, and survival. A longitudinal temporal decomposition model was used for analysis. MEASUREMENTS AND MAIN RESULTS: Comparison of overall rates of FEV1 decline in AATD and AAT-replete patients with COPD showed no significant differences (P > 0.09). However, although the single LT patients had similar trends in FEV1 in both groups, patients with AATD with double LT declined faster (P < 0.002) than the AAT-replete patients. No differences in the frequency or severity of ACR episodes were observed (P = 0.32). Furthermore, there was no difference in early or late mortality between patients with AATD and patients with AAT-replete COPD (P > 0.09). CONCLUSIONS: Although overall the post-LT FEV1 slope, severity of ACR, and survival among patients with AATD is similar to that of AAT-replete patients with COPD, patients with AATD with double LT have a faster rate of FEV1 decline. These findings support the eligibility of patients with AATD for LT, and suggest the need for additional studies to better understand the difference between single and double LT in AATD.

Patient-specific airway stent using three-dimensional printing: a review.

The primary function of an airway stent is to reestablish patency, impeding restenosis, supporting the tracheobronchial wall, or occluding fistulas. But stent-related complications are prevalent and can have devastating consequences. For this reason, stents are considered a last resort when there are no alternatives in treatment. Additionally, commercially available airway stents often poorly fit patients with complex airways, and they can cause various complications. At the end of the 20th century, three-dimensional (3D) printing technology was created. It has been transformative in healthcare and has been used in several applications. One of its first utilizations was the anatomical modeling of body structures that helps preoperative planning. In respiratory medicine, this technology has been essentially used in central airway diseases to produce 3D airway models and to create airway splints and prostheses. In the last decade, it has led to a transformation and allowed progress in personalized medicine, making patient-specific stents for individuals with complex airway problems. A patient-specific stent using 3D printing may minimize complications, improve quality of life, and reduce the need for repeated procedures. This review describes the recent advances in 3D printing technology, its use for developing airway prostheses to treat complex airway diseases, and the current evidence that supports its use.

Determination of patient-specific airway stent fit using novel 3D reconstruction measurement techniques: a 4-year follow-up of a patient.

Managing complex benign airway disease is a major challenge in interventional pulmonology. With the introduction of additive manufacturing in the medical field, patient-specific (PS) implants are an innovate prospect for airway management. Historically, stents were oversized to resist migration. However, the optimal degree and impact of stent oversizing remains unclear. The ability to design stents based on computed tomography (CT) invites opportunity to understand sizing. Here, we report a novel three-dimensional (3D) image reconstruction tool to quantify fit repeatedly over time. Analysis of CT imaging before and after successive stent implants in a single patient with different areas of stenosis and malacia was done. Nine PS airway stents over 4 years (five left mainstem and four right mainstem) were studied. The distance between the airway model and stent was calculated. The CT images were correlated to stent designs in CloudCompare software (v2.10-alpha) for novel analysis. Heat map was exported depicting the distances between the airway and the stent to the clinician's prescribed stent model. Corresponding histograms containing distances, mean, and standard deviation were reported. It is possible to measure stent fit based on heat map quantification on patient imaging. Observation of the airway over time and stent change suggests that the airway became more open over time requiring increased stent diameters. The ability to design and measure stent fit over time can help quantify the utility and impact of PS silicone airway stent. The airway appears to display plasticity such that there is notable change in stent prescription over time.

Ergonomics of bronchoscopy: good advice or a pain in the neck?

Interventional pulmonologists require a unique set of skills including precise motor abilities and physical endurance, but surprisingly the application of ergonomic principles in the field of bronchoscopy remains limited. This is particularly intriguing when considering the significant impact that poor ergonomics can have on diagnostic aptitude, income potential and overall health. It is therefore imperative to provide comprehensive education to physicians regarding the significance of ergonomics in their work, especially considering the introduction of advanced diagnostic and therapeutic procedures. By implementing simple yet effective measures (e.g. maintaining neutral positions of the wrist, neck and shoulder; adjusting the height of tables and monitors; incorporating scheduled breaks; and engaging in regular exercises), the risk of injuries can be substantially reduced. Moreover, objective tools are readily available to assess ergonomic postures and estimate the likelihood of work-related musculoskeletal injuries. This review aims to evaluate the current literature on the impact of procedure-related musculoskeletal pain on practising pulmonologists and identify modifiable factors for future research.

Innovation in rigid bronchoscopy-past, present, and future.

German laryngologist Gustav Killian performed the first "Direkte Bronchoskopie" using a rigid bronchoscope to extract a foreign airway body from the right main bronchus over a hundred years ago, transforming the practice of respiratory medicine. The procedure instantaneously became popular throughout the world. Chevalier Jackson Sr from the United States further advanced the instrument, technique, safety, and application. In the 1960s, Professors Harold H. Hopkins and N.S. Kapany introduced optical rods as well as fiberoptics that led Karl Storz to develop the cold light system improving endoluminal illumination, achievements that ushered in the modern era of flexible endoscopy. Several diagnostic and therapeutic procedures became possible such as transbronchial needle biopsy, transbronchial lung biopsy, airway electrosurgery, or cryotherapy. Dr. Jean-François Dumon from France advanced the use of Nd-YAG laser in the endobronchial tree and created the dedicated Dumon silicone stent introducing the whole new field of interventional pulmonology (IP). This major milestone revitalized interest in rigid bronchoscopy (RB). Now, advancements are being made in stenting, instrumentation, and education. RB robotic technology advancements are currently anticipated and can potentially revolutionize the practice of pulmonary medicine. In this review, we describe some of the most substantial advances related to RB from its beginning to the modern era.