Importance: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:To evaluate the diagnostic yield of a 1.1-mm cryoprobe for transbronchial biopsy. Design, Setting, and Participants: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: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: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: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: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:ClinicalTrials.gov Identifier: NCT05751278.

BACKGROUND:Convex probe endobronchial ultrasound (EBUS) bronchoscopy-guided transbronchial needle aspiration (TBNA) is the mainstay of mediastinal and hilar lesion sampling, and EBUS-TBNA allows for the acquisition of cytologic material. However, certain clinicopathologic conditions require the acquisition of histopathologic specimens. This can be accomplished via EBUS-guided transbronchial mini-forceps biopsy (TBFB) and cryobiopsy (TBCB), but the incremental value of these -modalities in various clinicopathologic conditions has yet to be explored. OBJECTIVE:Define the incremental value of EBUS-guided TBFB and TBCB over TBNA via evaluation of diagnostic yield, tissue quality, and adequacy for ancillary assays. METHODS:All patients who underwent EBUS-TBNA supplemented by TBFB and/or TBCB across 2 large academic centers were reviewed retrospectively. Cytology and histopathology tissue specimens were scrutinized for quantity, quality, tissue diagnosis, and adequacy for immunohistochemistry, molecular assays, and flow cytometry. Comparisons were made across TBNA, TBFB, and TBCB, as well as with a control group of EBUS-TBNA-only procedures for safety and procedural duration. RESULTS:A total of 204 lesions were sampled in 156 patients. Overall diagnostic yield was similar across TBNA, TBFB, and TBCB (P = .7); however, TBFB and TBCB outperformed TBNA for the diagnosis of lymphoproliferative and inflammatory conditions (P = .03 and P < .001, respectively). Compared with TBNA and TBFB, TBCB provided higher-quality tissue for immunohistochemistry and molecular profiling assays (P = .002 and P < .001, respectively). Adequacy of TBNA for flow cytometry outperformed that of TBFB and TBCB (P < .001). Compared with TBFB, TBCB tissue specimens provided more diagnostic tissue (P < .0001) with less crush artifact (P < .0001). The rate and severity of procedure-related complications were similar across study cases and the EBUS-TBNA-only control group. CONCLUSIONS:For the sampling of mediastinal and hilar lesions, supplementation of EBUS-TBNA by TBFB or TBCB should be primarily considered when suspecting a lymphoproliferative or an inflammatory etiology or when high-quality tissue is -required for predictive immunohistochemistry and molecular assays. For accurate diagnosis and classification of lymphomas, the combination of TBNA for flow cytometry with TBCB for histopathologic interpretation appears to be optimal.

BACKGROUND:Transbronchial biopsy is a common bronchoscopic procedure that is traditionally performed with forceps. However, its diagnostic capability is limited by small specimen size and crush artifact. A 1.1 mm cryoprobe was developed to overcome these limitations utilizing rapid, controlled, freezing to retrieve larger specimens which are extractable through the bronchoscope's working channel. Whether this improves diagnostic yield remains uncertain. The 1.1 mm cryoprobe has not been directly compared to standard capacity forceps in a prospective, randomized fashion. METHODS:This multicenter randomized controlled trial evaluates whether transbronchial biopsy with a 1.1 mm cryoprobe yields superior diagnostic yield compared to standard capacity forceps in adults undergoing transbronchial biopsy for diffuse parenchymal lung disease, parenchymal pulmonary lesions, or lung allografts. Participants will be randomized 1:1 to either biopsy tool, stratified by indication. Primary outcomes include indication-specific and overall diagnostic yield, adjudicated by centralized pathology review. Secondary outcomes include histologic quality metrics and complication rates. This trial is individually powered for each indication-specific primary outcome, and can detect an 11.3% difference in overall diagnostic yield with 250 participants per arm. DISCUSSION:This trial will provide high-quality evidence to guide transbronchial biopsy tool selection to maximize diagnostic yield. Results of this trial may yield practice changing data for the evaluation of patients with diffuse parenchymal lung disease, parenchymal pulmonary lesions, and lung allografts. Unique design features include the use of a centralized histopathology core to minimize bias and interobserver variability and a pragmatic design to facilitate integration into clinical workflows and optimize recruitment.

Convex probe endobronchial ultrasound (EBUS) bronchoscopy-guided transbronchial needle aspiration (TBNA) is the mainstay of mediastinal and hilar lesion sampling. EBUS-TBNA allows for the acquisition of cytologic material. However, certain clinicopathologic conditions require the acquisition of histopathologic specimens. This can be accomplished via EBUS-guided transbronchial mini-forceps biopsy (TBFB) and cryobiopsy (TBCB), but the incremental value of these modalities in various clinicopathologic conditions has yet to be explored. Define the incremental value of EBUS-guided TBFB and TBCB over TBNA via evaluation of diagnostic yield, tissue quality, and adequacy for ancillary assays. All patients who underwent EBUS-TBNA supplemented by TBFB and/or TBCB across two large academic centers were reviewed retrospectively. Cytology and histopathology tissue specimens were scrutinized for quantity, quality, tissue diagnosis, and adequacy for immunohistochemistry, molecular, and flow cytometry assays. Comparisons were made across TBNA, TBFB, and TBCB, as well as with a control group of EBUS-TBNA-only procedures for safety and procedural duration. A total of 204 lesions were sampled in 156 patients. Overall diagnostic yield was similar across TBNA, TBFB, and TBCB (P = 0.7); however, TBFB and TBCB outperformed TBNA for the diagnosis of lymphoproliferative and inflammatory conditions (P = 0.03 and P < 0.001, respectively). Compared with TBNA and TBFB, TBCB provided higher quality tissue for immunohistochemistry and molecular profiling assays (P = 0.002 and P < 0.001, respectively). TBNA adequacy for flow cytometry outperformed that of TBFB and TBCB (P < 0.001). Compared with TBFB, TBCB tissue specimens provided more diagnostic tissue (P < 0.0001) with less crush artifact (P < 0.0001). The rate and severity of procedure-related complications were similar across study cases and the EBUS-TBNA-only control group. For the sampling of mediastinal and hilar lesions, supplementation of EBUS-TBNA by TBFB or TBCB should be primarily considered when suspecting a lymphoproliferative or an inflammatory etiology or when high-quality tissue is required for predictive immunohistochemistry, and molecular assays. For accurate diagnosis and classification of lymphomas, the combination of TBNA for flow cytometry with TBCB for histopathologic interpretation appears to be optimal.

QuestionIs the diagnostic yield of transbronchial lung biopsy higher with use of a 1.1-mm cryoprobe compared with 2.0-mm forceps?FindingsIn this randomized clinical trial of 500 patients undergoing transbronchial biopsy for pulmonary nodules or masses, evaluation after lung transplant, or diffuse parenchymal lung disease, the diagnostic yield was 88.6% with cryobiopsy vs 78.8% with forceps (absolute difference, 9.8%).MeaningThe diagnostic yield of transbronchial lung biopsy was significantly higher with use of a 1.1-mm cryoprobe vs 2.0-mm forceps in a group of patients with pulmonary nodules or masses, lung transplant, and diffuse parenchymal lung disease. ImportanceBronchoscopic 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.ObjectiveTo evaluate the diagnostic yield of a 1.1-mm cryoprobe for transbronchial biopsy.Design, Setting, and ParticipantsThis 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.InterventionPatients 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 MeasuresThe 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.ResultsOf 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 RelevanceTransbronchial 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 RegistrationClinicalTrials.gov Identifier: NCT05751278 This trial investigates the diagnostic yield of transbronchial lung biopsy with a 1.1-mm cryoprobe vs 2.0-mm forceps.

Application of guidelines to the day-to-day clinical practice of clinicians is not always straightforward. Guidelines often provide a structure to the thought process demanded during clinical decision-making, which requires the application of evidence as best suited for each individual patient. These guidelines provide recommendations and suggestions, and the weight of these recommendations relies heavily on the quality of evidence and the vote of experts in the field, when evidence is lacking or insufficient. The following document elaborates on our approach to benign and malignant central airway obstruction, applying the principles of recently published central airway obstruction American College of Chest Physicians (CHEST) guidelines.

BACKGROUND:Incidental pulmonary nodules (IPNs) are frequently identified on computed tomography (CT) scans but are often associated with poor rates of patient notification and follow-up, limiting opportunities for early lung cancer detection. OBJECTIVE:To evaluate whether implementation of an artificial intelligence (AI)-supported workflow improves patient notification and follow-up of IPNs detected in the emergency department (ED). METHODS:We conducted a retrospective pre-post cohort study at an academic-affiliated community hospital. The pre-intervention cohort included ED patients undergoing chest CT between January and March 2023. The post-intervention cohort included ED patients undergoing chest CT between June and August 2025, in which an AI-based natural language processing system identified potential IPNs from radiology reports, and patients were contacted to facilitate follow-up. Primary outcomes were rates of patient notification about their IPN and nodule-specific follow-up. RESULTS:With implementation of the AI-supported workflow, patient notification increased from 171/228 (75%) to 223/252 (88.4%) p = 0.0001, and nodule-specific follow-up increased from 122/228 (53.5%) to 171/252 (67.9%) p = 0.0012. Inability to reach patients by phone after their ED visit was identified as a significant barrier to follow-up. There was no significant difference in lung cancer stage at diagnosis between cohorts. CONCLUSIONS:An AI-supported IPN identification and outreach workflow improved patient notification and follow-up. Proactive communication strategies, facilitated by AI, represent a feasible approach to addressing care gaps and enhancing early lung cancer detection.

The field of pediatric bronchoscopy is rapidly expanding and enables diagnostic tests and therapeutic maneuvers, benefiting many children suffering from respiratory disease. However, due to a paucity of pediatric providers trained in bronchoscopy, many institutions rely on adult interventionalists collaborating with pediatric care teams to complete these procedures. In this article, we address the adult interventionalist taking on these cases and offer insight into key differences in pediatric anatomy and physiology, unique challenges encountered in this population and explore the equipment available in pediatric sizes. We also consider the future of the field, including broadening pediatric training to enhance capacity to complete these necessary procedures.

Foreign body aspiration during endoscopic procedures is a rare but serious complication. Examples of these include instrumentation failure resulting in inadvertent dislodging of a stone or procedure item. Here we present a case of a patient who underwent successful endoscopic retrograde cholangiopancreatography (ERCP) complicated by a single-use cap dislodging into the trachea, which was ultimately retrieved by rigid bronchoscopy. A 92-year-old man underwent successful ERCP for an obstructing gallstone. Unfortunately, a removeable component (Figure A) of the scope became dislodged during the procedure and fell into his upper airway, becoming stuck against the left tracheal wall and the endotracheal tube (ETT). Immediate retrieval of the device was attempted by flexible bronchoscopy, but the scope could not be advanced due to the combination of extrinsic compression of the ETT by the foreign body and localized airway swelling. The patient was transferred to our facility for retrieval of the dislodged piece. Steroids were administered beforehand to reduce airway swelling, after which a second attempt was pursued by flexible bronchoscopy with an alligator clamp in addition to synchronized retraction of the ETT. The foreign body was again dislodged during removal and fell into the airway, now to the level of the vocal cords. (Figure B) Ultimately, a rigid scope was introduced into the airway and the foreign body was retrieved using biopsy forceps. (Figure C) Foreign body aspiration in adults is a rare phenomenon with the preferred initial method of retrieval being flexible bronchoscopy. Among adults these aspirates tend to be biologic or metallic in origin and are typically retrieved by alligator or shark-tooth forceps. Iatrogenic aspirates have been documented and may account for nearly one third of all aspirates in adults; with teeth, dental equipment, and pills representing most reported cases. A gallstone dislodged during procedure has been reported but to our knowledge we report the first ERCP component to fall into a patient's airway. The component was an FDA approved single-use distal end cap used to improve device sanitation efficiency, patient safety, and infection control. Here we highlight an unintentional harm of using these devices. These cases are associated with higher morbidity and mortality, which was seen in our patient with bleeding and mucosal damage at the site of the dislodged component, upper airway and laryngeal edema, and prolonged intubation time.

Red blood cells (RBCs), which are enucleated and mitochondria-deficient, have traditionally been considered essential for gas exchange and systemic metabolic regulation. Here, an unrecognized role for RBCs in promoting lung cancer progression is identified. In a cohort of 226 lung cancer patients and 239 healthy controls, significantly elevated levels of miR-93-5p are observed in RBCs and RBC-derived exosomes, but not in plasma, with higher levels correlating with advanced stage and poor prognosis. Functional assays demonstrate that RBC-derived exosomal miR-93-5p is transferred to tumor cells, where it suppresses PTEN and enhances proliferation, migration, and invasion. Conversely, exosomes released by lung cancer cells deliver miR-93-5p to RBCs, thereby augmenting its abundance within RBCs. Inhibition of miR-93-5p or restoration of PTEN abrogates these effects. In both subcutaneous and orthotopic mouse models, RBC-derived exosomal miR-93-5p accelerates tumor growth and reduces survival, whereas therapeutic delivery of antisense oligonucleotides targeting miR-93-5p suppresses tumor burden, reduces metastasis, and prolongs survival. Together, the novel function of RBCs as active participants in tumorigenesis is reported through exosomal transfer of oncogenic miR-93-5p, establishing a bidirectional tumor-RBC-tumor communication axis that promotes malignancy and offers new diagnostic and therapeutic opportunities in lung cancer.

This study aimed to evaluate if integrating diverse molecular biomarkers in plasma and sputum could improve the diagnosis of lung cancer. The study analyzed miRNAs in plasma and bacterial DNA in sputum from 58 lung cancer patients and 62 cancer-free smokers using droplet digital PCR. The individual plasma miRNA and sputum bacterial biomarkers had sensitivities of 62–71% and specificities of 61–79% for diagnosing lung cancer. A panel of plasma miRNA or sputum bacterial biomarkers produced sensitivities of 79–85% and specificities of 74–82%. An integromic signature consisting of two miRNAs in plasma and three bacterial biomarkers in sputum had a higher sensitivity (87%) and specificity (89%) compared to individual biomarkers. The signature’s diagnostic value was confirmed in a validation cohort of 56 lung cancer patients and 59 controls, independent of tumor stage, histological type, and demographic factors. Integrating diverse molecular biomarkers in plasma and sputum could improve the diagnosis of lung cancer.

African American (AA) populations present with notably higher incidence and mortality rates from lung cancer in comparison to other racial groups. Here, we elucidated the contribution of long non-coding RNAs (lncRNAs) in the racial disparities and their potential clinical applications in both diagnosis and therapeutic strategies. AA patients had elevated plasma levels of MALAT1 and PVT1 compared with cancer-free smokers. Incorporating these lncRNAs as plasma biomarkers, along with smoking history, achieved 81% accuracy in diagnosis of lung cancer in AA patients. We observed a rise in MALAT1 expression, correlating with increased levels of monocyte chemoattractant protein-1 (MCP-1) and CD68, CD163, CD206, indicative of tumor-associated macrophages in lung tumors of AA patients. Forced MALAT1 expression led to enhanced growth and invasiveness of lung cancer cells, both in vitro and in vivo, accompanied by elevated levels of MCP-1, CD68, CD163, CD206, and KI67. Mechanistically, MALAT1 acted as a competing endogenous RNA to directly interact with miR-206, subsequently affecting MCP-1 expression and macrophage activity, and enhanced the tumorigenesis. Targeting MALAT1 significantly reduced tumor sizes in animal models. Therefore, dysregulated MALAT1 contributes to lung cancer disparities in AAs by modulating the tumor immune microenvironment through its interaction with miR-206, thereby presenting novel diagnostic and therapeutic targets.

Rationale: Follow-up of patients with emphysema treated with endobronchial valves is limited to 3-12 months after treatment in prior reports. To date, no comparative data exist between treatment and control subjects with a longer follow-up. Objectives: To assess the durability of the Spiration Valve System (SVS) in patients with severe heterogeneous emphysema over a 24-month period. Methods: EMPROVE, a multicenter randomized controlled trial, presents a rigorous comparison between treatment and control groups for up to 24 months. Lung function, respiratory symptoms, and quality-of-life (QOL) measures were assessed. Results: A significant improvement in forced expiratory volume in 1 second was maintained at 24 months in the SVS treatment group versus the control group. Similarly, significant improvements were maintained in several QOL measures, including the St. George's Respiratory Questionnaire and the COPD Assessment Test. Patients in the SVS treatment group experienced significantly less dyspnea than those in the control group, as indicated by the modified Medical Research Council dyspnea scale score. Adverse events at 24 months did not significantly differ between the SVS treatment and control groups. Acute chronic obstructive pulmonary disease exacerbation rates in the SVS treatment and control groups were 13.7% (14 of 102) and 15.6% (7 of 45), respectively. Pneumothorax rates in the SVS treatment and control groups were 1.0% (1 of 102) and 0.0% (0 of 45), respectively. Conclusions: SVS treatment resulted in statistically significant and clinically meaningful durable improvements in lung function, respiratory symptoms, and QOL, as well as a statistically significant reduction in dyspnea, for at least 24 months while maintaining an acceptable safety profile. Clinical trial registered with www.clinicaltrials.gov (NCT01812447).