Faculty Bibliography

IMPORTANCE/UNASSIGNED:Bronchoscopic biopsy is conventionally performed with forceps, which can result in small specimen sizes and poor specimen quality due to crush artifact. Cryoprobe use localizes freezing at the probe tip, enabling retrieval of larger, more intact biopsy specimens. OBJECTIVE/UNASSIGNED:To evaluate the diagnostic yield of a 1.1-mm cryoprobe for transbronchial biopsy. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This open-label, outcome assessor-masked, multicenter randomized clinical trial included 500 patients aged 18 years or older scheduled to undergo transbronchial biopsy for lung nodules or masses, lung transplant, or diffuse parenchymal lung disease. The trial was conducted in 9 US medical centers and enrolled patients between February 27, 2023, and September 11, 2024. The date of last follow-up was October 12, 2024. INTERVENTION/UNASSIGNED:Patients were randomized 1:1 to transbronchial biopsy using a 1.1-mm cryoprobe (n = 250) or 2.0-mm forceps (n = 250). MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was diagnostic yield, defined as the percentage of patients for whom the transbronchial biopsy sample led to a specific diagnosis based on histologic examination. Of the 8 prespecified secondary analyses, key secondary analyses were the diagnostic yield for each of the 3 conditions (lung nodules or masses, lung transplant, and diffuse parenchymal lung disease) and complication rates. RESULTS/UNASSIGNED:Of 774 patients assessed for eligibility, 609 provided consent, 500 were randomized, and 490 were included in the primary analysis; the mean age was 62.6 years (SD, 12.7 years) and 252 of 500 (50.4%) were male. The primary outcome of diagnostic yield was significantly higher in patients randomized to transbronchial biopsy with cryoprobes vs forceps (217 of 245 [88.6%] vs 193 of 245 [78.8%]; absolute difference, 9.8%; 95% CI, 3.3%-16.3%; P = .003). For the key secondary analyses, compared with that of forceps, the diagnostic yield of cryoprobes was significantly higher among patients with pulmonary nodules or masses (79 of 95 [83.2%] vs 68 of 97 [70.1%]; absolute difference, 13.1%; 95% CI, 1.0%-24.6%; P = .04) and lung transplant (120 of 125 [96.0%] vs 110 of 124 [88.7%]; absolute difference, 7.3%; 95% CI, 0.6%-14.4%; P = .03) but did not differ significantly in diffuse parenchymal lung disease (18 of 25 [72.0%] vs 15 of 24 [62.5%]; absolute difference, 9.5%; 95% CI, -16.0% to 33.6%; P = .55). For the secondary safety analysis, there were 4 pneumothoraces requiring chest tube placement in the forceps group (1.6%) vs none in the cryoprobe group; no patients experienced significant bleeding or respiratory failure events. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Transbronchial lung biopsy performed with a 1.1-mm cryoprobe had a significantly higher diagnostic yield compared with 2.0-mm forceps in a group of patients with lung nodules or masses, lung transplant, and diffuse parenchymal lung disease. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT05751278.

Recent advances have furthered our understanding of the role of the tumor draining lymph node (TDLN) in the immune response to thoracic malignancies. This review synthesizes the rapidly expanding evidence that tumor draining lymph nodes (TDLNs) are not passive conduits of metastasis but dynamic immunologic organs that shape anti-tumor immunity in non-small cell lung cancer (NSCLC). Across cytokine, cellular, genomic, transcriptomic, and metabolic domains, the TDLN microenvironment becomes progressively remodeled towards immune suppression. These changes influence tumor growth and early metastasis, and may dictate responsiveness to various treatment modalities. The TDLN is also a practical and clinically relevant site for biomarker discovery and therapeutic innovation as a target of drug delivery and immunomodulation.

BACKGROUND:Transbronchial cryobiopsy has expanded beyond its established role in interstitial lung disease, driven by release of single-use cryoprobes, most notably the 1.1-mm cryoprobe. As use of transbronchial cryobiopsy accelerates across non-interstitial lung disease diagnostic contexts, practice variability has outpaced evidence generation and formal guidance. RESEARCH QUESTION/OBJECTIVE:Our objective was to formulate clinical consensus statements regarding indications, tools, techniques, specimen handling, safety considerations, and requisite procedural expertise for the use of the 1.1mm cryoprobe in non-interstitial lung disease transbronchial cryobiopsy, including convex-probe endobronchial ultrasound guided, and peripheral pulmonary lesion, sampling. STUDY DESIGN AND METHODS/METHODS:An international panel of bronchoscopy experts was assembled through the Interventional Pulmonology Outcomes Group. Following a structured evidence review, a modified Delphi methodology was conducted, consisting of an initial round of open-ended questions followed by three rounds in which panelists rated their agreement with statements on a 5-point Likert scale. Consensus was defined a priori as ≥80% agreement. Domains included: (1) peripheral transbronchial cryobiopsy, (2) convex-probe endobronchial ultrasound guided cryobiopsy, (3) airway, anesthesia, and complication management, and (4) specimen handling and processing. RESULTS:A total of 32 physicians participated in this project. The modified Delphi process consisted of four survey rounds conducted between May and November 2025. Consensus was obtained on 31 statements. No consensus was obtained on 17 statements. INTERPRETATION/CONCLUSIONS:This Delphi statement represents the first expert guidance for non-interstitial lung disease applications of both endobronchial ultrasound-guided and peripheral transbronchial cryobiopsy. The consensus statements delineate contemporary best practice, bridge critical gaps in standardization, and outline domains where further research is needed.

Therapeutic bronchoscopy is well established for palliative treatment of advanced malignancies, including for recanalization of malignant central airway obstruction. Although less common in clinical practice, bronchoscopic treatments (including thermal ablation) may also be considered for curative endobronchial treatment in several clinical scenarios including benign or occasionally low-grade purely endoluminal neoplasms. In this article, we highlight evidence for where endobronchial therapies for curative intent may be considered based on clinical experience over several decades. Although treatment of peripheral lung malignancies remains investigational at this time, advantages and disadvantages of several ablative techniques and potential immunostimulatory therapies are also discussed.

INTRODUCTION/UNASSIGNED:Outcomes for NSCLC remain suboptimal. Recent data suggest that cryoablation can generate antitumor immune effects. In this first-in-human phase I clinical trial, we investigated the safety and feasibility of bronchoscopic cryoimmunotherapy (BCI) delivered during standard-of-care bronchoscopy and explored associated systemic immune responses. METHODS/UNASSIGNED:Subjects with known or suspected advanced-stage NSCLC were recruited. BCI was delivered in dose-escalated freeze-thaw cycles to determine maximum dose tolerance. Feasibility assessment was determined with a pre-set goal of achieving successful BCI in more than or equal to 80% of subjects. Safety was assessed by review of BCI-related complications, including grades 2 to 3 bleeding, pneumothorax requiring intervention, and National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 to 5 adverse events. Pre- and post-BCI blood samples were collected to explore changes in the systemic immune profile. RESULTS/UNASSIGNED:Subjects with predominantly clinical TNM stage 3 or 4 adenocarcinoma or squamous cell carcinoma were enrolled. We reached the maximum dose of 30 seconds with 100% feasibility and no BCI-related adverse events. In peripheral blood analysis, we observed a significant decrease in derived neutrophil-to-lymphocyte ratio in the high-dose BCI group in comparison to the low-dose BCI cohort. We also observed increases in inflammatory cytokines-GM-CSF, IFN-γ, IL-1β, IL-17A, and IL-2-and effector memory T cells post-BCI. CONCLUSION/UNASSIGNED:BCI is safe and feasible. In addition, we provide preliminary evidence that at higher dose levels there is a systemic immune response consistent with a cytotoxic profile. Further immune analyses will determine the potential of BCI as an adjunctive therapy in combination with immune checkpoint inhibition in NSCLC treatment.

The field of Interventional Pulmonology suffers from a paucity of methodologically robust studies to inform patient care, often relying on retrospective, single-center, non-comparative cohorts of commercialized products. The Interventional Pulmonary Outcomes Group (IPOG) was established to address the critical need for increased scientific rigor within the Interventional Pulmonology community. IPOG convened a meeting to assess the current state and future needs for minimally invasive lung cancer diagnostics and treatment. The goals of this meeting were to review the current landscape, and identify gaps and barriers in lung cancer diagnostics and therapeutics research. From this discussion short- and long-term research goals and priorities were identified. Nineteen international experts from various institutions and disciplines participated. The top short-term priorities identified were: 1) harmonization of core outcome measures in interventional pulmonology trials, 2) validation of a pathway/structure for the introduction of new technology, 3) establishment of a patient advisory board with focus on patient centered outcomes, 4) early engagement with industry partnerships during clinical trial design. The top long-term priorities identified were: 1) characterize the development, implementation, and role of bronchoscopic ablation, 2) validation and clinical utility of biomarker use and artificial intelligence, 3) implement research training skills for junior investigators in interventional pulmonology, 4) deliver 5 prospective, large clinical trials, with at least one adaptive trial, 5) develop a biorepository accessible to investigators. This perspective reviews the colloquium discussions, the identified priorities and the plans to help address those priorities as well as progress made in the year since its inception. Keywords: Interventional Pulmonology Outcomes Group; Interventional Pulmonology; Lung Cancer; Research; Outcomes.

Pleural effusions are commonly encountered in the practice of pulmonary medicine, and their clinical evaluation is usually straightforward. However, up to 20% of pleural effusions are not diagnosed despite clinical evaluation and pleural fluid analysis. Further investigation of the undiagnosed pleural effusion requires a systematic evaluation using clues from a patient's history, physical examination, imaging, and pleural fluid analysis help narrow down the differential diagnosis. Occasionally, pleural biopsy may be necessary via several minimally invasive techniques, especially if malignancy is considered.

Despite remarkable advances in tumor response and patient survival in the past decade, systemic immunotherapies for lung cancer result in an objective response in only around half of patients treated. On the basis of this limitation, combination strategies are being investigated to improve response rates. Cryoablation has been proposed as one such technique to induce immunogenic cell death and synergize with systemic immunotherapies, including immune checkpoint inhibitors. Cryoablation has been traditionally delivered percutaneously with imaging guidance although recent technological advances allow for bronchoscopic delivery. Herein, we review the pre-clinical and clinical evidence for the use of cryoablation in non-small cell lung cancer and potential induction of anti-tumor immunity. We highlight ongoing studies involving this approach and propose areas of future investigation.

PURPOSE OF REVIEW:Percutaneous tracheostomy and gastrostomy are minimally invasive procedures among the most common performed in intensive care units. Practices across centres vary considerably, and questions remain about the optimal timing, performance and postoperative care related to these procedures. RECENT FINDINGS:The COVID-19 pandemic has triggered a reevaluation of the practice of percutaneous tracheostomy and gastrostomy in the ICU. Combined percutaneous tracheostomy and gastrostomy at the bedside has potential benefits, including improved nutrition, decreased exposure to anaesthetics, decreased patient transport and decreased hospital costs. Percutaneous ultrasound gastrostomy is a novel technique that eliminates the need for an endoscope that may allow intensivists to perform gastrostomy at the bedside. SUMMARY:Multidisciplinary care is essential to the follow up of critically ill patients receiving tracheostomy and gastrostomy. Combined tracheostomy and gastrostomy has numerous potential benefits to patients and hospital systems. Interventional pulmonologists are uniquely qualified to perform both procedures and serve on a tracheostomy and gastrostomy team.