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.

Interventional Pulmonology: Extending the Breadth of Thoracic Care.

Interventional pulmonary medicine has developed as a subspecialty focused on the management of patients with complex thoracic disease. Leveraging minimally invasive techniques, interventional pulmonologists diagnose and treat pathologies that previously required more invasive options such as surgery. By mitigating procedural risk, interventional pulmonologists have extended the reach of care to a wider pool of vulnerable patients who require therapy. Endoscopic innovations, including endobronchial ultrasound and robotic and electromagnetic bronchoscopy, have enhanced the ability to perform diagnostic procedures on an ambulatory basis. Therapeutic procedures for patients with symptomatic airway disease, pleural disease, and severe emphysema have provided the ability to palliate symptoms. The combination of medical and procedural expertise has made interventional pulmonologists an integral part of comprehensive care teams for patients with oncologic, airway, and pleural needs. This review surveys key areas in which interventional pulmonologists have impacted the care of thoracic disease through bronchoscopic intervention.

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.

Real-World Perspectives and Practices for Pneumonitis/Interstitial Lung Disease Associated With Trastuzumab Deruxtecan Use in Human Epidermal Growth Factor Receptor 2-Expressing Metastatic Breast Cancer.

Trastuzumab deruxtecan (T-DXd) is an antibody drug conjugate with a topoisomerase I payload that targets the human epidermal growth factor receptor 2 (HER2). T-DXd is approved for patients with previously treated HER2-positive or HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/ISH-) metastatic/unresectable breast cancer (BC). In a second-line HER2-positive metastatic BC (mBC) population (DESTINY-Breast03 [ClinicalTrials.gov identifier: NCT03529110]), T-DXd demonstrated significantly improved progression-free survival (PFS) over ado-trastuzumab emtansine (12-month rate: 75.8% v 34.1%; hazard ratio, 0.28; P < .001), and in patients with HER2-low mBC treated with one prior line of chemotherapy (DESTINY-Breast04 [ClinicalTrials.gov identifier: NCT03734029]), T-DXd demonstrated significantly longer PFS and overall survival than physician's choice chemotherapy (10.1 v 5.4 months; hazard ratio, 0.51; P < .001, and 23.4 v 16.8 months; hazard ratio, 0.64; P < .001, respectively).Interstitial lung disease (ILD) is an umbrella term used for a group of diseases characterized by lung injury including pneumonitis, which can lead to irreversible lung fibrosis. ILD is a well-described adverse event associated with certain anticancer therapies, including T-DXd. An important part of T-DXd therapy for mBC consists of monitoring for and managing ILD. Although information on ILD management strategies is included in the prescribing information, additional information on patient selection, monitoring, and treatment can be beneficial in routine clinical practice. The objective of this review is to describe real-world, multidisciplinary clinical practices and institutional protocols used for patient selection/screening, monitoring, and management related to T-DXd-associated ILD.

Impact of a Dedicated Pleural Clinic on Indwelling Pleural Catheter Related Outcomes: A Retrospective Single Center Experience.

BACKGROUND: Recurrent pleural effusions are a major cause of morbidity and frequently lead to hospitalization. Indwelling pleural catheters (IPCs) are tunneled catheters that allow ambulatory intermittent drainage of pleural fluid without repeated thoracentesis. Despite the efficacy and safety of IPCs, data supporting postplacement follow-up is limited and variable. Our study aims to characterize the impact of a dedicated pleural clinic (PC) on patient outcomes as they relate to IPCs. METHODS: Patients who underwent IPC placement between 2015 and 2021 were included in this retrospective study. Differences in outcomes were analyzed between patients with an IPC placed and managed by Interventional Pulmonology (IP) through the PC and those placed by non-IP services (non-PC providers) before and after the PC implementation. RESULTS: In total, 371 patients received IPCs. Since the implementation of the PC, there was an increase in ambulatory IPC placement (31/133 pre-PC vs. 96/238 post-PC; P =0.001). There were fewer admissions before IPC placement (18/103 vs. 43/133; P =0.01), and fewer thoracenteses per patient (2.7±2.5 in PC cohort vs. 4±5.1 in non-PC cohort; P <0.01). The frequency of pleurodesis was higher in the PC cohort (40/103 vs. 41/268; P <0.001). A Fine and Gray competing risks model indicated higher likelihood of pleurodesis in the PC cohort (adjusted subhazard ratio 3.8, 95% CI: 2.5-5.87). CONCLUSION: Our experience suggests that the implementation of a dedicated PC can lead to improved patient outcomes including fewer procedures and admissions before IPC placement, and increased rates of pleurodesis with IPC removal.

Use of tunneled pleural catheters in chronic empyema: Two case reports and brief review of the literature.

The incidence of empyema is increasing worldwide, which, coupled with the aging global population, makes the non-surgical management of pleural space infections increasingly important. Despite this, there remains no consensus for management of chronic empyema in those patients who are not surgical candidates and do not get adequate source control with chest tube and intra-pleural lytic therapy, particularly for patients with non-expandable lungs. We reviewed the literature regarding non-surgical management of chronic empyema and present two cases that support the use of pleuroscopy in conjunction with tunneled pleural catheters for management of chronic empyema in non-surgical candidates.

Bleeding Risk With Combination Intrapleural Fibrinolytic and Enzyme Therapy in Pleural Infection: An International, Multicenter, Retrospective Cohort Study.

BACKGROUND: Combination intrapleural fibrinolytic and enzyme therapy (IET) has been established as a therapeutic option in pleural infection. Despite demonstrated efficacy, studies specifically designed and adequately powered to address complications are sparse. The safety profile, the effects of concurrent therapeutic anticoagulation, and the nature and extent of nonbleeding complications remain poorly defined. RESEARCH QUESTION: What is the bleeding complication risk associated with IET use in pleural infection? STUDY DESIGN AND METHODS: This was a multicenter, retrospective observational study conducted in 24 centers across the United States and the United Kingdom. Protocolized data collection for 1,851 patients treated with at least one dose of combination IET for pleural infection between January 2012 and May 2019 was undertaken. The primary outcome was the overall incidence of pleural bleeding defined using pre hoc criteria. RESULTS: Overall, pleural bleeding occurred in 76 of 1,833 patients (4.1%; 95% CI, 3.0%-5.0%). Using a half-dose regimen (tissue plasminogen activator, 5 mg) did not change this risk significantly (6/172 [3.5%]; P = .68). Therapeutic anticoagulation alongside IET was associated with increased bleeding rates (19/197 [9.6%]) compared with temporarily withholding anticoagulation before administration of IET (3/118 [2.6%]; P = .017). As well as systemic anticoagulation, increasing RAPID score, elevated serum urea, and platelets of < 100 × 109/L were associated with a significant increase in bleeding risk. However, only RAPID score and use of systemic anticoagulation were independently predictive. Apart from pain, non-bleeding complications were rare. INTERPRETATION: IET use in pleural infection confers a low overall bleeding risk. Increased rates of pleural bleeding are associated with concurrent use of anticoagulation but can be mitigated by withholding anticoagulation before IET. Concomitant administration of IET and therapeutic anticoagulation should be avoided. Parameters related to higher IET-related bleeding have been identified that may lead to altered risk thresholds for treatment.

Erector Spinae Plane Block: A Novel Anesthetic Approach for Pleuroscopy.

BACKGROUND: Anesthesia and analgesia for thoracic procedures, specifically pleuroscopy, present unique challenges given the spectrum of underlying pulmonary disease and susceptibility to respiratory complications. This study describes efforts to reduce postoperative pain and minimize opioid analgesia after thoracoscopic procedures through the use of erector spinae plane block (ESPB). METHODS: This is a single center, retrospective case series of all patients who underwent rigid pleuroscopy with ESPB plus monitored anesthesia care (MAC) from November 2018 through September 2020. The primary outcome measures were postoperative pain scores and analgesic medication requirements. RESULTS: Twenty-six patients underwent pleuroscopy with ESPB plus MAC. Average intraoperative and postoperative opioid consumption in oral morphine equivalents were 18.4±15.8 and 11.2±19.6 mg, respectively. There was no significant difference between average preoperative and postoperative subjective numerical pain scores (P=0.221). There were no complications associated with ESPB. CONCLUSION: This case series demonstrates the feasibility of utilizing single shot ESPB in combination with MAC as the primary anesthetic for thoracoscopic procedures.

A retrospective observational study of benign anthracotic lymphadenitis and its association with PET avid lymph nodes in patients undergoing cancer evaluation.

BACKGROUND: Accurate staging of newly diagnosed or recurrent malignancy is essential for effective treatment. An important first step in staging involves the use of PET/CT to identify areas of FDG avidity. PET/CT however has limitations, including false positive FDG uptake from benign causes. In this paper we characterize an uncommon yet clinically important cause of false positive PET/CTs, that of benign anthracotic lymphadenitis (BAL). We examine the clinical, radiographic and histologic characteristics of BAL in patients referred for endobronchial ultrasound (EBUS) guided biopsies and discuss its context in relation to existing literature. METHODS: We performed a retrospective observational case series of 20 patients who were referred for EBUS guided biopsies of PET positive mediastinal and hilar lymph nodes during the work-up or treatment of suspected malignancy. RESULTS: To be included, all patients received PET imaging as well as an EBUS guided biopsy of FDG avid lymph nodes which demonstrated anthracotic pigment as the only histologic abnormality. The key findings were that 90% of patients in this cohort were born outside of the US, 90% had bilateral FDG avid lymph nodes with an average standardized uptake value (SUV) of 7.9±2.2. Most patients, based on their history, had a likely exposure to biomass fuel or urban pollution. CONCLUSIONS: BAL may be an underrecognized cause for PET positive lymph nodes in patients undergoing work-up for malignancy. These findings support the importance of sampling mediastinal and hilar lymph nodes even when SUVs are highly suggestive of malignancy.

AABIP Evidence-informed Guidelines and Expert Panel Report for the Management of Indwelling Pleural Catheters.

BACKGROUND: While the efficacy of Indwelling pleural catheters for palliation of malignant pleural effusions is supported by relatively robust evidence, there is less clarity surrounding the postinsertion management. METHODS: The Trustworthy Consensus-Based Statement approach was utilized to develop unbiased, scientifically valid guidance for the management of patients with malignant effusions treated with indwelling pleural catheters. A comprehensive electronic database search of PubMed was performed based on a priori crafted PICO questions (Population/Intervention/Comparator/Outcomes paradigm). Manual searches of the literature were performed to identify additional relevant literature. Dual screenings at the title, abstract, and full-text levels were performed. Identified studies were then assessed for quality based on a combination of validated tools. Appropriateness for data pooling and formation of evidence-based recommendations was assessed using predetermined criteria. All panel members participated in development of the final recommendations utilizing the modified Delphi technique. RESULTS: A total of 7 studies were identified for formal quality assessment, all of which were deemed to have a high risk of bias. There was insufficient evidence to allow for data pooling and formation of any evidence-based recommendations. Panel consensus resulted in 11 ungraded consensus-based recommendations. CONCLUSION: This manuscript was developed to provide clinicians with guidance on the management of patients with indwelling pleural catheters placed for palliation of malignant pleural effusions. Through a systematic and rigorous process, management suggestions were developed based on the best available evidence with augmentation by expert opinion when necessary. In addition, these guidelines highlight important gaps in knowledge which require further study.

Characterizing smoking-induced transcriptional heterogeneity in the human bronchial epithelium at single-cell resolution.

The human bronchial epithelium is composed of multiple distinct cell types that cooperate to defend against environmental insults. While studies have shown that smoking alters bronchial epithelial function and morphology, its precise effects on specific cell types and overall tissue composition are unclear. We used single-cell RNA sequencing to profile bronchial epithelial cells from six never and six current smokers. Unsupervised analyses led to the characterization of a set of toxin metabolism genes that localized to smoker ciliated cells, tissue remodeling associated with a loss of club cells and extensive goblet cell hyperplasia, and a previously unidentified peri-goblet epithelial subpopulation in smokers who expressed a marker of bronchial premalignant lesions. Our data demonstrate that smoke exposure drives a complex landscape of cellular alterations that may prime the human bronchial epithelium for disease.

Cryoprobe retrieval of an airway foreign body: A case report and literature review.

We report a case of a 7-year-old boy with clinical and radiographic evidence of foreign body (FB) aspiration with a 2-week delay in diagnosis. The retrieval of the pushpin with traditional bronchoscopic instrumentation was made difficult by granulation tissue formation. A cryoprobe through a flexible bronchoscope was used to successfully remove the FB. To our knowledge, this is the first report of interventional bronchoscopy with a cryoprobe to remove a pushpin in a child under suspension laryngoscopy and spontaneous ventilation. A high index of suspicion is crucial for identifying FBs early and minimizing granulation tissue development which complicates FB removal.

Evaluations of Implementation at Early-Adopting Lung Cancer Screening Programs: Lessons Learned.

BACKGROUND: Guidelines recommend lung cancer screening (LCS), and it is currently being adopted nationwide. The American College of Chest Physicians advises inclusion of specific programmatic components to ensure high-quality screening. However, little is known about how LCS has been implemented in practice. We sought to evaluate the experience of early-adopting programs, characterize barriers faced, and identify strategies to achieve successful implementation. METHODS: We performed qualitative evaluations of LCS implementation at three Veterans Administration facilities, conducting semistructured interviews with key staff (n = 29). Guided by the Promoting Action on Research Implementation in Health Services framework, we analyzed transcripts using principals of grounded theory. RESULTS: Programs successfully incorporated most recommended elements of LCS, although varying in approaches to patient selection, tobacco treatment, and quality audits. Barriers to implementation included managing workload to ensure appropriate evaluation of pulmonary nodules detected by screening and difficulty obtaining primary care "buy-in." To manage workload, programs used nurse coordinators to actively maintain screening registries, held multidisciplinary conferences that generated explicit management recommendations, and rolled out implementation in a staged fashion. Successful strategies to engage primary care providers included educational sessions, audit and feedback of local outcomes, and assisting with and assigning clear responsibility for nodule evaluation. Capitalizing on pre-existing relationships and including a designated program champion helped facilitate intradisciplinary communication. CONCLUSIONS: Lung cancer screening implementation is a complex undertaking requiring coordination at many levels. The insight gained from evaluation of these early-adopting programs may inform subsequent design and implementation of LCS programs.