Assessment of Advanced Diagnostic Bronchoscopy Outcomes for Peripheral Lung Lesions: A Delphi Consensus Definition of Diagnostic Yield and Recommendations for Patient-centered Study Designs. An Official American Thoracic Society/American College of Chest Physicians Research Statement.

Background: Advanced diagnostic bronchoscopy targeting the lung periphery has developed at an accelerated pace over the last two decades, whereas evidence to support introduction of innovative technologies has been variable and deficient. A major gap relates to variable reporting of diagnostic yield, in addition to limited comparative studies. Objectives: To develop a research framework to standardize the evaluation of advanced diagnostic bronchoscopy techniques for peripheral lung lesions. Specifically, we aimed for consensus on a robust definition of diagnostic yield, and we propose potential study designs at various stages of technology development. Methods: Panel members were selected for their diverse expertise. Workgroup meetings were conducted in virtual or hybrid format. The cochairs subsequently developed summary statements, with voting proceeding according to a modified Delphi process. The statement was cosponsored by the American Thoracic Society and the American College of Chest Physicians. Results: Consensus was reached on 15 statements on the definition of diagnostic outcomes and study designs. A strict definition of diagnostic yield should be used, and studies should be reported according to the STARD (Standards for Reporting Diagnostic Accuracy Studies) guidelines. Clinical or radiographic follow-up may be incorporated into the reference standard definition but should not be used to calculate diagnostic yield from the procedural encounter. Methodologically robust comparative studies, with incorporation of patient-reported outcomes, are needed to adequately assess and validate minimally invasive diagnostic technologies targeting the lung periphery. Conclusions: This American Thoracic Society/American College of Chest Physicians statement aims to provide a research framework that allows greater standardization of device validation efforts through clearly defined diagnostic outcomes and robust study designs. High-quality studies, both industry and publicly funded, can support subsequent health economic analyses and guide implementation decisions in various healthcare settings.

Medical thoracoscopy for pleural diseases.

PURPOSE OF REVIEW: The purpose of this review is to elaborate on the role of medical thoracoscopy for various diagnostic and therapeutic parietal pleural interventions. The renewed interest in medical thoracoscopy has been boosted by the growth of the field of interventional pulmonology and, possibly, well tolerated and evolving anesthesia. RECENT FINDINGS: Medical thoracoscopy to obtain pleural biopsies is established largely as a safe and effective diagnostic procedure. Recent data suggest how a pragmatic biopsy-first approach in specific cancer scenarios may be patient-centered. The current scope of medical thoracoscopy for therapeutic interventions other than pleurodesis and indwelling pleural catheter (IPC) placement is limited. In this review, we discuss the available evidence for therapeutic indications and why we must tread with caution in certain scenarios. SUMMARY: This article reviews contemporary published data to highlight the best utility of medical thoracoscopy as a diagnostic procedure for undiagnosed exudative effusions or effusions suspected to be secondary to cancers or tuberculosis. The potentially therapeutic role of medical thoracoscopy in patients with pneumothorax or empyema warrants further research focusing on patient-centered outcomes and comparisons with video-assisted thoracoscopic surgery.

Safety and utility of indwelling pleural catheters in lung transplant recipients.

INTRODUCTION: The safety and efficacy of indwelling pleural catheters (IPCs) in lung allograft recipients is under-reported. METHODS: We performed a multicenter, retrospective analysis between 1/1/2010 and 6/1/2022 of consecutive IPCs placed in lung transplant recipients. Outcomes included incidence of infectious and non-infectious complications and rate of auto-pleurodesis. RESULTS: Seventy-one IPCs placed in 61 lung transplant patients at eight centers were included. The most common indication for IPC placement was recurrent post-operative effusion. IPCs were placed at a median of 59 days (IQR 40-203) post-transplant and remained for 43 days (IQR 25-88). There was a total of eight (11%) complications. Infection occurred in five patients (7%); four had empyema and one had a catheter tract infection. IPCs did not cause death or critical illness in our cohort. Auto-pleurodesis leading to the removal of the IPC occurred in 63 (89%) instances. None of the patients in this cohort required subsequent surgical decortication. CONCLUSIONS: The use of IPCs in lung transplant patients was associated with an infectious complication rate comparable to other populations previously studied. A high rate of auto-pleurodesis was observed. This work suggests that IPCs may be considered for the management of recurrent pleural effusions in lung allograft recipients.

Intrapleural Anticancer Therapy for Malignant Pleural Diseases: Facts or Fiction?

Malignant pleural diseases involves both primary pleural malignancies (e.g., mesothelioma) as well as metastatic disease involving the pleura. The management of primary pleural malignancies remains a challenge, given their limited response to conventional treatments such as surgery, systemic chemotherapy, and immunotherapy. In this article, we aimed to review the management of primary pleural malignancy as well as malignant pleural effusion and assess the current state of intrapleural anticancer therapies. We review the role intrapleural chemotherapy, immunotherapy, and immunogene therapy, as well as oncolytic viral, therapy and intrapleural drug device combination. We further discuss that while the pleural space offers a unique opportunity for local therapy as an adjuvant option to systemic therapy and may help decrease some of the systemic side effects, further patient outcome-oriented research is needed to determine the exact role of these treatments within the armamentarium of currently available options.

Tracheostomy for COVID-19 Respiratory Failure: Multidisciplinary, Multicenter Data on Timing, Technique, and Outcomes.

OBJECTIVE: The aim of this study was to assess the outcomes of tracheostomy in patients with COVID-19 respiratory failure. SUMMARY BACKGROUND DATA: Tracheostomy has an essential role in managing COVID-19 patients with respiratory failure who require prolonged mechanical ventilation. However, limited data are available on how tracheostomy affects COVID-19 outcomes, and uncertainty surrounding risk of infectious transmission has led to divergent recommendations and practices. METHODS: It is a multicenter, retrospective study; data were collected on all tracheostomies performed in COVID-19 patients at 7 hospitals in 5 tertiary academic medical systems from February 1, 2020 to September 4, 2020. RESULT: Tracheotomy was performed in 118 patients with median time from intubation to tracheostomy of 22 days (Q1-Q3: 18-25). All tracheostomies were performed employing measures to minimize aerosol generation, 78.0% by percutaneous technique, and 95.8% at bedside in negative pressure rooms. Seventy-eight (66.1%) patients were weaned from the ventilator and 18 (15.3%) patients died from causes unrelated to tracheostomy. No major procedural complications occurred. Early tracheostomy (≤14 days) was associated with decreased ventilator days; median ventilator days (Q1-Q3) among patients weaned from the ventilator in the early, middle and late groups were 21 (21-31), 34 (26.5-42), and 37 (32-41) days, respectively with P = 0.030. Compared to surgical tracheostomy, percutaneous technique was associated with faster weaning for patients weaned off the ventilator [median (Q1-Q3): 34 (29-39) vs 39 (34-51) days, P = 0.038]; decreased ventilator-associated pneumonia (58.7% vs 80.8%, P = 0.039); and among patients who were discharged, shorter intensive care unit duration [median (Q1-Q3): 33 (27-42) vs 47 (33-64) days, P = 0.009]; and shorter hospital length of stay [median (Q1-Q3): 46 (33-59) vs 59.5 (48-80) days, P = 0.001]. CONCLUSION: Early, percutaneous tracheostomy was associated with improved outcomes compared to surgical tracheostomy in a multi-institutional series of ventilated patients with COVID-19.

Variable Learning Curve of Basic Rigid Bronchoscopy in Trainees.

BACKGROUND: Despite increased use of rigid bronchoscopy (RB) for therapeutic indications and recommendations from professional societies to use performance-based competency, an assessment tool has not been utilized to measure the competency of trainees to perform RB in clinical settings. OBJECTIVES: The aim of the study was to evaluate a previously developed assessment tool - Rigid Bronchoscopy Tool for Assessment of Skills and Competence (RIGID-TASC) - for determining the RB learning curve of interventional pulmonary (IP) trainees in the clinical setting and explore the variability of learning curve of trainees. METHODS: IP fellows at 4 institutions were enrolled. After preclinical simulation training, all RBs performed in patients were scored by faculty using RIGID-TASC until competency threshold was achieved. Competency threshold was defined as unassisted RB intubation and navigation through the central airways on 3 consecutive patients at the first attempt with a minimum score of 89. A regression-based model was devised to construct and compare the learning curves. RESULTS: Twelve IP fellows performed 178 RBs. Trainees reached the competency threshold between 5 and 24 RBs, with a median of 15 RBs (95% CI, 6-21). There were differences among trainees in learning curve parameters including starting point, slope, and inflection point, as demonstrated by the curve-fitting model. Subtasks that required the highest number of procedures (median = 10) to gain competency included ability to intubate at the first attempt and intubation time of <60 s. CONCLUSIONS: Trainees acquire RB skills at a variable pace, and RIGID-TASC can be used to assess learning curve of IP trainees in clinical settings.

Malignant Pleural Effusion at Presentation in Patients with Small-Cell Lung Cancer.

BACKGROUND: Malignant pleural effusion (MPE) is commonly seen in patients with non-small cell lung cancer. However, the prevalence of MPE at presentation in small-cell lung cancer (SCLC) is not reported and the clinical impact of MPE at presentation on patients with SCLC remains largely unknown. OBJECTIVE: The objective of this study is to assess the occurrence rate of MPE and its prognostic implications at presentation in patients with SCLC. METHOD: We used the Surveillance Epidemiology and End Results (SEER) registry to extract data from patients with SCLC diagnosed between 2004 and 2014. The Kaplan-Meier method was used to estimate the overall survival and the Cox proportional hazard model was used to evaluate whether MPE was an independent risk for outcome. RESULTS: Among the 68,443 patients with SCLC, MPE was present in 7,639 (11.16%). The probability of MPE was higher in older patients with larger tumors and mediastinal lymph node involvement at presentation. Median overall survival (3 vs. 7 months), estimated 1-year survival (17 vs. 30%), and 2-year survival (6 vs. 14%) were significantly lower in patients with MPE than without MPE, respectively (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.41-1.50, p< 0.001). MPE was also an independent factor for worse survival in multivariate analysis (HR 1.36, 95% CI 1.32-1.41, p < 0.001). CONCLUSIONS: MPE is common at presentation (11%) in patients with SCLC and may be associated with decreased survival. Additional studies are required to assess the treatment-adjusted survival rate in the setting of MPE.

Repeat Thoracentesis in Hepatic Hydrothorax and Non-Hepatic Hydrothorax Effusions: A Case-Control Study.

BACKGROUND: Repeat thoracentesis for symptom control is offered to patients with refractory hepatic hydrothorax (HH) but the risk profile for this management strategy remains unclear. OBJECTIVES: This study aimed to compare complication frequency and nature during repeat thoracentesis in patients with and without HH. METHODS: Complication rates in patients undergoing repeat thoracentesis for symptom relief was compared between patients with HH and a control group (non-HH group) at a single center from 2010 to 2015. Records were reviewed for demographics, laboratory values, number of thoracentesis, and associated complications with each procedure. RESULTS: 82 patients with HH (274 thoracenteses) and 100 control patients (188 thoracenteses) were included. A complication was noted in 17/462 (0.03%) procedures in the entire cohort. There was a higher overall complication rate with repeat thoracentesis in the HH group (8 vs. 0%, p = 0.016, 95% CI = 1.5-14.6). In the HH group, the cumulative risk of complications increased with sequential thoracenteses; a complication occurring in the preceding intervention was the strongest predictor for subsequent complication (OR = 17.1, p = 0.0013) and more than 1 previous complication was associated with a 15-fold increased risk of a subsequent complication (p < 0.001). In multivariate analysis within the HH group, the Model for End-Stage Liver Disease (MELD) score was an independent predictor of hemothorax (OR = 1.19, 95% CI = 1.03-1.36, p = 0.012). CONCLUSIONS: Repeat thoracentesis is an overall low-risk procedure, although a higher complication rate is observed in HH compared with non-HH patients. The presence of a previous complication significantly increases the risk of future complications in the HH population.

Ultrasound-guided pleural access.

Ultrasonography of the thorax has become a more recognized tool in pulmonary medicine, thanks to continuing clinical research that has proven its many valuable roles in the day-to-day management of pulmonary and pleural diseases. Ultrasound examination is a cost-effective imaging modality that permits the pulmonologist to obtain information about the pathologies in the thorax without the risk of exposure to ionizing radiation, providing the examiner with real-time and immediate results. Its ease of use and training along with its portability to the patient's bedside and accurate examination of the pleural space has allowed for safer pleural procedures such as thoracentesis, chest tube placement, tunneled pleural catheter placement, and medical thoracoscopy. In this review, we summarize the technique of chest ultrasonography, compare ultrasound to other frequently used thoracic imaging modalities, and focus on its use in obtaining pleural access while performing invasive pleural procedures.

Palliative interventional pulmonology procedures in the incarcerated population with cancer: a case series.

RATIONALE: Cancer is the second most common cause of death in incarcerated population and lung cancer is the most common cause of cancer death in this group. Inmates are excluded from most published surveys and research,thus the effectiveness of lung cancer palliation in this population is not known. OBJECTIVE: To report the feasibility and safety of palliative interventional pulmonary procedures in inmates with cancer. STUDY DESIGN: Retrospective review of registry data from a single center. MATERIALS AND METHODS: Inmate data on prospectively enrolled data registry (2009­2012) from the interventional pulmonology procedural registry at Virginia Commonwealth University was extracted and analyzed for safety and efficacy. Inmates with lung cancer and advanced malignancies with pleural or airway metastasis requiring airway debulking (mechanical/thermal), airway stenting, and tunneled pleural catheter (TPC) placement were included in the analysis. RESULTS: A total of 16 procedures were performed in 12 incarcerated patients. These included six TPC placements in six patients. Ten procedures were performed in seven patients with airway obstruction. These procedures included rigid and flexible bronchoscopy with mechanical (rigid and balloon dilation) and thermal (laser, argon plasma coagulation, and cautery) tumor debulking and dilation,airway stenting, and tracheostomy in one case. All six TPCpatients had immediate symptomatic relief and improved lung aeration on chest radiograph. Three of six patients had successful auto-pleurodesis. In the seven patients with airway obstruction, three patients reported symptomatic relief and one had resolution of post-obstructive pneumonia. No immediate- or long-term procedure-related complications were reported. CONCLUSION: Incarcerated patients with advanced malignancy may benefit from interventional pulmonology procedures with low complications. Palliative interventional pulmonology procedures in inmates should not be withheld solely on their incarceration status.

The effect of pleural drainage on pulse oximetry in a post-operative thoracic surgery population.

BACKGROUND: Pleural effusions in post-operative thoracic surgery patients are common. Effusions can result in prolonged hospitalizations or readmissions, with prior studies suggesting mixed effects of pleural drainage on hypoxia. We aimed to define the impact of pleural drainage on pulse oximetry (SpO2) in post-thoracic surgery patients. METHODS: A retrospective study of post-operative thoracic surgery patients undergoing pleural drainage was performed. SpO2 and supplemental oxygen (FiO2) values were recorded at pre- and post-procedure. The primary outcome was difference in pre-procedural and post-procedural SpO2. RESULTS: We identified 95 patients with a mean age of 65 (SD - 13.8) years undergoing 122 pleural drainage procedures. Mean drainage volume was 619 (SD-423) mL and the majority of procedures (88.5 %) included a drainage of <1000 mL. SpO2 was associated with an increase from 94.0 % (SD-2.6) to 97.3 % (SD-2.0) at 24-h (p < 0.0001). FiO2 was associated with a decrease from 0.31 (SD-0.15) to 0.29 (SD-0.12) at 24-h (p = 0.0081). SpO2/FiO2 was associated with an increase from 344.5 (SD-99.0) to 371.9 (SD-94.7) at 24-h post-procedure (p < 0.0001). CONCLUSIONS: Pleural drainage within post-operative thoracic surgery patients offers statistically significant improvements in oxygen saturation by peripheral pulse oximetry and oxygen supplementation; however the clinical significance of these changes remains unclear. Pleural drainage itself may be requested for numerous reasons, including diagnostic (fevers, leukocytosis, etc.) or therapeutic (worsening dyspnea) evaluation. However, pleural drainage may offer minimal clinical impact on pulse oximetry in post-operative thoracic surgery patients.

Management of Central Airway Obstruction. An American College of Chest Physicians Clinical Practice Guideline.

BACKGROUND: Central airway obstruction (CAO), seen in a variety of malignant and non-malignant airway disorders, is associated with a poor prognosis. The management of CAO is dependent on provider training and local resources, which may make the clinical approach and outcomes highly variable. We reviewed the current literature and provided evidence-based recommendations for the management of CAO. METHODS: A multidisciplinary expert panel developed key questions using the PICO (Patient, Intervention, Comparator, and Outcomes) format and conducted a systematic literature search using MEDLINE (PubMed) and the Cochrane Library. The panel screened references for inclusion and used vetted evaluation tools to assess the quality of included studies and extract data, and graded the level of evidence supporting each recommendation. A modified Delphi technique was used to reach consensus on recommendations. RESULTS: Nine thousand, six hundred and eighty-eight abstracts were reviewed, 150 full-text articles were assessed, and 31 studies were included in the analysis. One good practice statement and ten graded recommendations were developed. The overall certainty of evidence was very low. CONCLUSIONS: Therapeutic bronchoscopy can improve the symptoms, quality of life, and survival of patients with malignant and non-malignant CAO. Multi-modality therapeutic options, including rigid bronchoscopy with general anesthesia, tumor/tissue debridement, ablation, dilation, and stent placement should be utilized when appropriate. Therapeutic options and outcomes are dependent on the underlying etiology of CAO. A multidisciplinary approach and shared decision-making with the patient are strongly encouraged.

Robotic versus Electromagnetic bronchoscopy for pulmonary LesIon AssessmeNT: the RELIANT pragmatic randomized trial.

BACKGROUND: Robotic-assisted bronchoscopy has recently emerged as an alternative to electromagnetic navigational bronchoscopy for the evaluation of peripheral pulmonary lesions. While robotic-assisted bronchoscopy is proposed to have several advantages, such as an easier learning curve, it is unclear if it has comparable diagnostic utility as electromagnetic navigational bronchoscopy. METHODS: Robotic versus Electromagnetic bronchoscopy for pulmonary LesIon AssessmeNT (RELIANT) is an investigator-initiated, single-center, open label, noninferiority, cluster randomized controlled trial conducted in two operating rooms at Vanderbilt University Medical Center. Each operating room (OR) is assigned to either robotic-assisted or electromagnetic navigational bronchoscopy each morning, with each OR day considered one cluster. All patients undergoing diagnostic bronchoscopy for evaluation of a peripheral pulmonary lesion in one of the two operating rooms are eligible. Schedulers, patients, and proceduralists are blinded to daily group allocations until randomization is revealed for each operating room each morning. The primary endpoint is the diagnostic yield defined as the proportion of cases yielding lesional tissue. Secondary and safety endpoints include procedure duration and procedural complications. Enrolment began on March 6, 2023, and will continue until 202 clusters have been accrued, with expected enrolment of approximately 400 patients by the time of completion in March of 2024. DISCUSSION: RELIANT is a pragmatic randomized controlled trial that will compare the diagnostic yield of the two most commonly used bronchoscopic approaches for sampling peripheral pulmonary lesions. This will be the first known cluster randomized pragmatic trial in the interventional pulmonology field and the first randomized controlled trial of robotic-assisted bronchoscopy. TRIAL REGISTRATION: ClinicalTrials.gov registration (NCT05705544) on January 30, 2023.

Diagnostic Yield vs Diagnostic Accuracy for Peripheral Lung Biopsy Evaluation: Evidence Supporting a Future Pragmatic End Point.

BACKGROUND: Diagnostic yield and accuracy endpoints have been used inconsistently in the evaluation of advanced diagnostic bronchoscopy devices and techniques, limiting between-study comparisons. In addition, diagnostic accuracy can be adjudicated only after prolonged clinical follow-up, which delays reporting on the performance of novel devices. RESEARCH QUESTION: Will a conservative diagnostic yield definition result in few false-negative initial results to closely approximate diagnostic accuracy and represent a useful outcome for future studies of diagnostic utility? METHODS: Commonly used definitions of diagnostic yield were applied to a prospective data set of consecutive peripheral pulmonary lesions sampled by navigational bronchoscopy from 2017 to 2019. All consider malignancy to be diagnostic but differ in their classification of nonmalignant biopsy findings, which were subcategorized as specific benign, nonspecific benign, or normal lung. Diagnostic yield calculations were also compared with diagnostic accuracy, defined as the proportion of biopsy specimens deemed diagnostic by each definition that were confirmed accurate through 2 years of follow-up. RESULTS: A total of 450 biopsy specimens of lesions were analyzed. The prevalence of malignancy was 60.9% (274 of 450). On initial bronchoscopy pathology, there were 227 malignant diagnoses (50.4%), with a single false positive (0.4%). Among 104 biopsy specimens with specific benign findings, only two were false negative for malignancy (1.9%). There were 119 nonspecific benign biopsy specimens, with 46 false negatives for malignancy (38.7%). The discrepancy between diagnostic yield and accuracy was 0.7% for the conservative definition, which only considered malignant or specific benign findings as diagnostic. INTERPRETATION: A conservative diagnostic yield definition excluding nonspecific benign diagnoses closely approximated diagnostic accuracy through 2 years' follow-up, with a less than 1% discrepancy. Using this conservative yield definition may allow for dissemination of reliable diagnostic utility data without protracted delays needed for follow-up data in this era of rapid technological change in advanced diagnostic bronchoscopy.

Spray Cryotherapy for Benign Large Airway Stenosis: A Multicenter Retrospective Cohort Study of Safety and Practice Patterns.

BACKGROUND: Benign airway stenosis (BAS) represents a significant burden on patients, providers, and healthcare systems. Spray cryotherapy (SCT) has been proposed as an adjunctive treatment to reduce BAS recurrence. We sought to examine safety and practice variations of the latest SCT system when used for BAS. METHODS: We conducted a retrospective multicenter cohort study in seven academic institutions within the Interventional Pulmonary Outcomes Group. All patients who underwent at least one SCT session with a diagnosis of BAS at the time of procedure at these institutions were included. Demographics, procedure characteristics, and adverse events were captured through each center's procedural database and electronic health record. RESULTS: A total of 102 patients underwent 165 procedures involving SCT from 2013 to 2022. The most frequent etiology of BAS was iatrogenic (n = 36, 35%). In most cases, SCT was used prior to other standard BAS interventions (n = 125; 75%). The most frequent SCT actuation time per cycle was five seconds. Pneumothorax complicated four procedures, requiring tube thoracostomy in two. Significant post-SCT hypoxemia was noted in one case, with recovery by case conclusion and no long-term effects. There were no instances of air embolism, hemodynamic compromise, or procedural or in-hospital mortality. CONCLUSION: SCT as an adjunctive treatment for BAS was associated with a low rate of complications in this retrospective multicenter cohort study. SCT-related procedural aspects varied widely in examined cases, including actuation duration, number of actuations, and timing of actuations relative to other interventions.