A Multicenter, Single-Arm, Prospective Trial Assessing the Diagnostic Yield of Electromagnetic Bronchoscopic and Transthoracic Navigation for Peripheral Pulmonary Nodules.

Rationale: Strict adherence to procedural protocols and diagnostic definitions is critical to understand the efficacy of new technologies. Electromagnetic navigational bronchoscopy (ENB) for lung nodule biopsy has been used for decades without a solid understanding of its efficacy, but offers the opportunity for simultaneous tissue acquisition via electromagnetic navigational transthoracic biopsy (EMN-TTNA) and staging via endobronchial ultrasound (EBUS). Objective: To evaluate the diagnostic yield of EBUS, ENB, and EMN-TTNA during a single procedure using a strict a priori definition of diagnostic yield with central pathology adjudication. Methods: A prospective, single-arm trial was conducted at eight centers enrolling participants with pulmonary nodules (<3 cm; without computed tomography [CT]- and/or positron emission tomography-positive mediastinal lymph nodes) who underwent a staged procedure with same-day CT, EBUS, ENB, and EMN-TTNA. The procedure was staged such that, when a diagnosis had been achieved via rapid on-site pathologic evaluation, the procedure was ended and subsequent biopsy modalities were not attempted. A study finding was diagnostic if an independent pathology core laboratory confirmed malignancy or a definitive benign finding. The primary endpoint was the diagnostic yield of the combination of CT, EBUS, ENB, and EMN-TTNA. Measurements and Main Results: A total of 160 participants at 8 centers with a mean nodule size of 18 ± 6 mm were enrolled. The diagnostic yield of the combined procedure was 59% (94 of 160; 95% confidence interval [CI], 51-66%). Nodule regression was found on same-day CT in 2.5% of cases (4 of 160; 95% CI, 0.69-6.3%), and EBUS confirmed malignancy in 7.1% of cases (11 of 156; 95% CI, 3.6-12%). The yield of ENB alone was 49% (74 of 150; 95% CI, 41-58%), that of EMN-TTNA alone was 27% (8 of 30; 95% CI, 12-46%), and that of ENB plus EMN-TTNA was 53% (79 of 150; 95% CI, 44-61%). Complications included a pneumothorax rate of 10% and a 2% bleeding rate. When EMN-TTNA was performed, the pneumothorax rate was 30%. Conclusions: The diagnostic yield for ENB is 49%, which increases to 59% with the addition of same-day CT, EBUS, and EMN-TTNA, lower than in prior reports in the literature. The high complication rate and low diagnostic yield of EMN-TTNA does not support its routine use. Clinical trial registered with www.clinicaltrials.gov (NCT03338049).

Sedation and Analgesia in Patients Undergoing Tracheostomy in COVID-19, a Multi-Center Registry.

INTRODUCTION: Patients with COVID-19 ARDS require significant amounts of sedation and analgesic medications which can lead to longer hospital/ICU length of stay, delirium, and has been associated with increased mortality. Tracheostomy has been shown to decrease the amount of sedative, anxiolytic and analgesic medications given to patients. The goal of this study was to assess whether tracheostomy decreased sedation and analgesic medication usage, improved markers of activity level and cognitive function, and clinical outcomes in patients with COVID-19 ARDS. STUDY DESIGN AND METHODS: A retrospective registry of patients with COVID-19 ARDS who underwent tracheostomy creation at the University of Pennsylvania Health System or the Johns Hopkins Hospital from 3/2020 to 12/2020. Patients were grouped into the early (≤14 days, n = 31) or late (15 + days, n = 97) tracheostomy groups and outcome data collected. RESULTS: 128 patients had tracheostomies performed at a mean of 19.4 days, with 66% performed percutaneously at bedside. Mean hourly dose of fentanyl, midazolam, and propofol were all significantly reduced 48-h after tracheostomy: fentanyl (48-h pre-tracheostomy: 94.0 mcg/h, 48-h post-tracheostomy: 64.9 mcg/h, P = .000), midazolam (1.9 mg/h pre vs. 1.2 mg/h post, P = .0012), and propofol (23.3 mcg/kg/h pre vs. 8.4 mcg/kg/h post, P = .0121). There was a significant improvement in mobility score and Glasgow Coma Scale in the 48-h pre- and post-tracheostomy. Comparing the early and late groups, the mean fentanyl dose in the 48-h pre-tracheostomy was significantly higher in the late group than the early group (116.1 mcg/h vs. 35.6 mcg/h, P = .03). ICU length of stay was also shorter in the early group (37.0 vs. 46.2 days, P = .012). INTERPRETATION: This data supports a reduction in sedative and analgesic medications administered and improvement in cognitive and physical activity in the 48-h period post-tracheostomy in COVID-19 ARDS. Further, early tracheostomy may lead to significant reductions in intravenous opiate medication administration, and ICU LOS.

Accuracy of Pulmonary Nodule Sampling Using Robotic Assisted Bronchoscopy with Shape Sensing, Fluoroscopy, and Radial Endobronchial Ultrasound (The ACCURACY Study).

BACKGROUND: Despite recent advances in guided bronchoscopy, the yield of bronchoscopic biopsy of a peripheral pulmonary nodule (PPN) remains highly variable. OBJECTIVE: The aim of the study was to evaluate which features of robotic assisted bronchoscopy (RAB) contribute to a successful biopsy in a cadaver model. METHODS: A preclinical, prospective, single-blinded trial using a ventilated human cadaveric model assessed the successful puncture of implanted pulmonary nodules using various localization techniques with RAB. The different approaches included positioning the robotic catheter at predefined distances from the target nodule (<10 mm, 10-20 mm, 20-30 mm), bronchoscopist correction of divergence between the software virtual map and bronchoscopic view if observed, and impact of fluoroscopy and radial endobronchial ultrasound (rEBUS). The primary endpoint was a central target hit (defined as an inner 2/3 target puncture) verified by cone-beam computed tomography. RESULTS: Thirty-eight RAB procedures were performed to target 16 PPNs. Median nodule size was 16.2 mm. All targets were located in the outer 1/3 of the lung with a bronchus sign in 31.3%. Central target hit rates were improved when the robotic catheter tip was closer to the nodule (<10 mm 68%, 10-20 mm 66%, 20-30 mm 11%, p < 0.001). Multivariable analysis confirmed the strongest predictor of a central target hit was robotic catheter distance to nodule (OR 0.89 per increase in 1 mm, p < 0.001), independent of the presence of a bronchus sign, divergence or concentric rEBUS view. CONCLUSIONS: Utilizing a RAB platform, closer proximity of the robotic catheter to the target nodule results in an increase in peripheral nodule biopsy success.

Safety and Feasibility of a Sheath Cryoprobe for Bronchoscopic Transbronchial Biopsy: The FROSTBITE Trial.

BACKGROUND: Bronchoscopic lung biopsy is typically performed using transbronchial forceps. However, this method is limited by small sample size and presence of crush artifact. Cryobiopsy offers the potential to overcome these limitations with larger artifact-free samples but has not been widely adopted due to concerns over increased rates of bleeding and pneumothorax. A new, smaller 1.1-mm cryoprobe has been developed that operates in a similar fashion to forceps, though the safety profile of this cryoprobe has not yet been prospectively studied. OBJECTIVE: The aim of this study was to investigate the safety of transbronchial biopsy using a novel 1.1-mm cryoprobe. METHODS: This prospective, single-arm study enrolled patients referred for transbronchial biopsy. All procedures were performed using the 1.1-mm cryoprobe with oversheath. The primary outcome was the composite of significant complications related to the cryobiopsy procedure (bleeding Grade ≥3, pneumothorax Grade ≥2, and respiratory failure). Bleeding and pneumothorax were graded according to previously published scales. RESULTS: Fifty participants from two academic medical centers underwent transbronchial cryobiopsy. Indications for biopsy included evaluation of lung transplant allograft (50%), diffuse lung disease (44%), and pulmonary parenchymal lesion (6%). There were two pneumothoraces (4%), neither of which required aspiration or chest tube placement. There were no Grade 3 or 4 bleeding events. Mild bleeding (Grade ≤2) was observed in 25 cases (50%). No complications occurred that met the a priori primary outcome of bleeding Grade ≥3, pneumothorax Grade ≥2, and respiratory failure. CONCLUSIONS: Transbronchial cryobiopsy using a 1.1-mm cryoprobe is feasible with an acceptable safety profile.

Sex differences in M2 polarization, chemokine and IL-4 receptors in monocytes and macrophages from asthmatics.

Allergic asthma affects more women than men. It is mediated partially by IL-4/IL-13-driven polarization of monocyte-derived macrophages in the lung. We tested whether sex differences in asthma are due to differential IL-4 responsiveness and/or chemokine receptor expression in monocytes and monocyte-derived macrophages from healthy and allergic asthmatic men and women. We found female cells expressed M2 genes more robustly following IL-4 stimulation than male cells, as did cells from asthmatics than those from healthy controls. This likely resulted from increased expression ofγC, part of the type I IL-4 receptor, and reduced IL-4-induced SOCS1, a negative regulator of IL-4 signaling, in asthmatic compared to healthy macrophages. Monocytes from asthmatic women expressed more CX3CR1, which enhances macrophage survival. Our findings highlight how sex differences in IL-4 responsiveness and chemokine receptor expression may affect monocyte recruitment and macrophage polarization in asthma, potentially leading to new sex-specific therapies to manage the disease.

Safety and diagnostic performance of pulmonologists performing electromagnetic guided percutaneous lung biopsy (SPiNperc).

BACKGROUND AND OBJECTIVE: Percutaneous lung biopsy for diagnostic sampling of peripheral lung nodules has been widely performed by interventional radiologists under computed tomography (CT) guidance. New technology allows pulmonologists to perform percutaneous lung biopsies using electromagnetic (EM) guided technology. With the adoption of this new technique, the safety, feasibility and diagnostic yield need to be explored. The goal of this study was to determine the safety, feasibility and diagnostic yield of EM-guided percutaneous lung biopsy performed by pulmonologists. METHODS: We conducted a retrospective, multicentre study of 129 EM-guided percutaneous lung biopsies that occurred between November 2013 and March 2017. The study consisted of seven academic and three community medical centres. RESULTS: The average age of participants was 65.6 years, BMI was 26.3 and 50.4% were females. The majority of lesions were in the right upper lobe (37.2%) and left upper lobe (31.8%). The mean size of the lesions was 27.31 mm and the average distance from the pleura was 13.2 mm. Practitioners averaged two fine-needle aspirates and five core biopsies per procedure. There were 23 (17.8%) pneumothoraces, of which 16 (12.4%) received small-bore chest tube placement. The diagnostic yield of percutaneous lung biopsy was 73.7%. When EM-guided bronchoscopic sampling was also performed during the same procedural encounter, the overall diagnostic yield increased to 81.1%. CONCLUSION: In this large multicentred series, the use of EM guidance for percutaneous lung biopsies was safe and feasible, with acceptable diagnostic yield in the hands of pulmonologists. A prospective multicentre trial to validate these findings is currently underway (NCT03338049).

First-in-Human Use of a Hybrid Real-Time Ultrasound-Guided Fine-Needle Acquisition System for Peripheral Pulmonary Lesions: A Multicenter Pilot Study.

BACKGROUND: The ability to successfully perform a biopsy on pulmonary lesions by means of bronchoscopy varies widely due to anatomic and technological limitations. One major limitation is the lack of the ability to utilize real-time guidance during tissue sampling in the periphery. A novel system has been developed that enables real-time visualization and sampling of peripheral lesions by displaying an ultrasound image of the lesion and needle simultaneously. METHODS: We performed a multicenter, prospective pilot in patients with peripheral pulmonary lesions undergoing a clinically indicated bronchoscopy. The purpose of this study was to demonstrate the feasibility of visualizing, accessing, and obtaining specimens adequate for the cytology of lung lesions when using a novel hybrid real-time ultrasound-guided fine-needle aspiration system for peripheral pulmonary lesions. RESULTS: Twenty-three patients underwent bronchoscopic sampling of a peripheral pulmonary lesion with the study device. Mean lesion size was 3.6 (range 1.7-5.7) cm. Targeted lesions were located in all lobes of the lung. All lesions were successfully visualized and sampled under real-time visualization with specimens adequate for cytological evaluation. The needle was visualized in all lesions throughout targeting and sampling. There were no incidents of pneumothorax or moderate-to-severe bleeding. CONCLUSION: In this feasibility study, we report the first-in-human use of a continuous real-time endobronchial ultrasound guidance system to sample peripheral pulmonary lesions. Future generations of this device may improve usability and further studies are needed to determine the true diagnostic capabilities of this novel technique.

External beam radiation therapy combined with airway stenting leads to better survival in patients with malignant airway obstruction.

BACKGROUND AND OBJECTIVE: Malignant airway obstruction (MAO), a common complication of patients with advanced lung cancer, causes debilitating dyspnoea and poor quality of life. Two common interventions used in the treatment of MAO include bronchoscopy with airway stenting and external beam radiotherapy (EBRT). Data are limited regarding their clinical effectiveness and overall effect on survival. METHODS: A retrospective chart review of patients treated with airway stenting and/or EBRT at the Johns Hopkins Hospital for MAO between July 2010 and January 2017 was reviewed. Demographics, performance status, cancer histology, therapeutic intervention and date of death were recorded. Survival was calculated using cox regression analysis. RESULTS: Of the 606 patients who were treated for MAO, 237 were identified as having MAO and included in the study. Sixty-eight patients underwent rigid bronchoscopy and stenting, 102 EBRT and 67 a combined approach. Patients who underwent stenting hand an increased hazard ratio (HR) of death in comparison to those who received combination therapy (HR: 2.12, 95% CI: 1.02, 4.39), while there was a trend towards significance in the EBRT alone group in comparison to the combination therapy group (HR: 1.62, 95% CI: 0.93, 2.83). CONCLUSION: In this retrospective analysis, combination therapy with stenting and EBRT led to better survival in comparison to stenting or EBRT alone. Prospective cohort trials are needed to confirm these results.

Understanding the Social Risk Factors That Avert Equitable Lung Cancer Care.

BACKGROUND: Lung cancer remains the leading cause of cancer death in the United States. There is an association between certain social determinants of health (SDOH) and adverse cancer outcomes. These include Black race and low-income, which are associated with poorer adherence to lung cancer screening and presentation at a later stage of disease. METHODS: We conducted a retrospective review of all patients with a diagnosis of lung cancer at a single urban, academic center from 2015 to 2021. Demographic data including race and clinical data including time taken to progress through various checkpoints (ie, concerning CT scan to diagnosis, diagnosis to treatment) were collected. Income data was approximated based on population medians at patient's home address zip code. RESULTS: A total of 550 patients were included in the final analysis. The study population was 57.4% Black and 61.2% of patients presenting with a household income of $40,000 US Dollars or lower based on approximated median household income. The time from CT scan to first treatment for the entire cohort was 121.3 days with no statistically significant variance by race. However, among patients presenting at stage IV, 72.7% were black and 76.0% resided in a zip code with a median income < $40,000. CONCLUSIONS: This study demonstrated no significant delays in progressing through checkpoints of lung cancer diagnosis and treatment on the basis of race or income approximation. Black patients and patients in low-income households were diagnosed with lung cancer at a more advanced stage. Efforts to close the gap in lung cancer disparities should be focused on targeting screening and early identification toward social groups that may be at highest risk of late presentation. Institutional focus on patient navigation through these stages should be paramount. TWEETABLE ABSTRACT: There were no delays in progression to lung cancer diagnostic and therapeutic milestones based on race or income approximation. Black race and residing in a low-income area are predictors for presenting at stage IV.

Resistin Pathway as Novel Mechanism of Post-lung Transplantation Bronchial Stenosis.

BACKGROUND: Bronchial stenosis remains a significant source of morbidity among lung transplant recipients. Though infection and anastomotic ischemia have been proposed etiologies of the development of bronchial stenosis, the pathophysiologic mechanism has not been well elucidated. METHODS: In this single-centered prospective study, from January 2013 through September 2015, we prospectively collected bronchoalveolar lavage (BAL) and endobronchial epithelial brushings from the direct anastomotic site of bronchial stenosis of bilateral lung transplant recipients who developed unilateral post-transplant bronchial stenosis. Endobronchial epithelial brushings from the contralateral anastomotic site without bronchial stenosis and BAL from bilateral lung transplant recipients who did not develop post-transplant bronchial stenosis were used as controls. Total RNA was isolated from the endobronchial brushings and real-time polymerase chain reaction reactions were performed. Electrochemiluminescence biomarker assay was used to measure 10 cytokines from the BAL. RESULTS: Out of 60 bilateral lung transplant recipients, 9 were found to have developed bronchial stenosis with 17 samples adequate for analysis. We observed a 1.56 to 70.8 mean-fold increase in human resistin gene expression in the anastomotic bronchial stenosis epithelial cells compared with nonstenotic airways. Furthermore, IL-1ß (21.76±10.96 pg/mL; control 0.86±0.44 pg/mL; P <0.01) and IL-8 levels (990.56±326.60 pg/mL; control 20.33±1.17 pg/mL; P <0.01) were significantly elevated in the BAL of the lung transplant patients who developed anastomotic bronchial stenosis. CONCLUSION: Our data suggest that the development of postlung transplantation bronchial stenosis may be in part mediated through the human resistin pathway by IL-1ß induced transcription factor nuclear factor-κß activation and downstream upregulation of IL-8 in alveolar macrophages. Further study is needed in the larger patient cohorts and to determine its potential therapeutic role in the management of post-transplant bronchial stenosis.

Survey of Clinical Knowledge and Procedural Readiness of Pulmonary Fellows to Start Interventional Pulmonary Fellowship: A Survey of Interventional Pulmonary Fellowship Directors.

BACKGROUND: Entry into the interventional pulmonary (IP) fellowship requires prerequisite training in pulmonary and critical care medicine (PCCM) fellowship in the United States. IP fellowship has become standardized, but the prerequisite training may be quite variable depending on the learner's exposure to IP during their PCCM fellowship. A survey study was conducted to identify potential foundational knowledge and/or skills gaps of new fellows entering IP fellowships. This may help both PCCM and IP fellowship directors to identify common knowledge gaps within PCCM training specific to IP. METHODS: Based on components of the ACGME's common program requirements for PCCM fellowships, a survey was developed and categorized into 5 domains: nonprocedural skills, didactic knowledge, diagnostic bronchoscopy, pleural procedures, and airway/percutaneous procedures. The survey was then sent to 42 IP fellowship directors after the content validity review and approval by the Association of Interventional Pulmonary Program Directors. RESULTS: The survey response rate was 88.1% (37/42). The overall mean scores in all 5 domains were perceived as below competent (<3). The highest mean domain was nonprocedural skills, and the lowest was airway/percutaneous procedures. Within the domains, there were 4/ 30 topics that were considered competent with a score of ≥3 as competent or higher; bronchoscopy lavage (mean: 3.5/5, SD: 0.87), interpersonal skills (mean: 3.03/5, SD: 0.76), thoracentesis (mean: 3.14/5, SD: 0.89), and ultrasound for pleural effusion (mean: 3.19/5, SD: 0.84). CONCLUSION: There are perceived gaps in PCCM training pertaining to IP fellowship readiness.

Acquisition and Handling of Endobronchial Ultrasound Transbronchial Needle Samples: An American College of Chest Physicians Clinical Practice Guideline.

BACKGROUND: Endobronchial ultrasound-guided transbronchial aspiration (EBUS-TBNA) has become the standard for initial lung cancer diagnosis and staging. Previous guidelines have generally focused on the "when" and "how" of EBUS-TBNA; however, little guidance is available on handling and processing specimens during and after acquisition to help optimize both diagnostic yield and tissue integrity for ancillary studies. This document examines the available literature on EBUS-TBNA specimen processing and handling. STUDY DESIGN AND METHODS: Rigorous methodology was applied to provide a trustworthy evidence-based guideline and expert panel report. Panelists developed key clinical questions utilizing the Population, Intervention, Comparator, and Outcome (PICO) format, addressing specific topics in EBUS-TBNA specimen processing. MEDLINE (via PubMed) and the Cochrane Library were systematically searched to identify relevant literature, supplemented by manual searches. References were screened for inclusion with document evaluation tools to assess the quality of included studies, extract meaningful data, and grade the level of evidence to support each recommendation or suggestion. RESULTS: Our systematic review and critical analysis of the literature of the 9 PICO questions related to handling and processing EBUS-TBNA specimens resulted in 9 evidence-based statements. INTERPRETATION: Evidence of the handling and processing of EBUS-TBNA specimens varies in strength but is satisfactory in some areas to guide clinicians in certain aspects of specimen handling. Additional research in many aspects of specimen handling and processing is needed to help improve our knowledge base.

Effects of a web-based patient activation intervention to overcome clinical inertia on blood pressure control: cluster randomized controlled trial.

BACKGROUND: Only approximately half of patients with hypertension have their blood pressure controlled, due in large part to the tendency of primary care providers (PCPs) not to intensify treatment when blood pressure values are elevated. OBJECTIVE: This study tested the effect of an intervention designed to help patients ask questions at the point of care to encourage PCPs to appropriately intensify blood pressure treatment. METHODS: PCPs and their patients with hypertension (N=500) were recruited by letter and randomized into 2 study groups: (1) intervention condition in which patients used a fully automated website each month to receive tailored messages suggesting questions to ask their PCP to improve blood pressure control, and (2) control condition in which a similar tool suggested questions to ask about preventive services (eg, cancer screening). The Web-based tool was designed to be used during each of the 12 study months and before scheduled visits with PCPs. The primary outcome was the percentage of patients in both conditions with controlled blood pressure. RESULTS: Of 500 enrolled patients (intervention condition: n=282; control condition: n=218), 418 (83.6%) completed the 12-month follow-up visit. At baseline, 289 (61.5%) of participants had controlled blood pressure. Most (411/500, 82.2%) participants used the intervention during at least 6 of 12 months and 222 (62.5%) reported asking questions directly from the Web-based tool. There were no group differences in asking about medication intensification and there were no differences in blood pressure control after 12 months between the intervention condition (201/282, 71.3%) and control condition (143/218, 65.6%; P=.27) groups. More intervention condition participants discussed having a creatinine test (92, 52.6% vs 49, 35.5%; P=.02) and urine protein test (81, 44.8% vs 21, 14.6%; P<.001), but no group differences were observed in the rate of testing. The control condition participants reported more frequent discussions about tetanus and pneumonia vaccines and reported more tetanus (30, 13.8% vs 15, 5.3%; P=.02) and pneumonia (25, 11.5% vs 16, 5.7%; P=.02) vaccinations after 12 months. CONCLUSIONS: The use of an interactive website designed to overcome clinical inertia for hypertension care did not lead to improvements in blood pressure control. Participant adherence to the intervention was high. The control intervention led to positive changes in the use of preventive services (eg, tetanus immunization) and the intervention condition led to more discussions of hypertension-relevant tests (eg, serum creatinine and urine protein). By providing patients with individually tailored questions to ask during PCP visits, this study demonstrated that participants were likely to discuss the questions with PCPs. These discussions did not, however, lead to improvements in blood pressure control. TRIAL REGISTRATION: ClinicalTrials.gov NCT00377208; http://clinicaltrials.gov/ct2/show/NCT00377208 (Archived by WebCite at http://www.webcitation.org/6IqWiPLon).

Bronchoalveolar Lavage (BAL) and Pathologic Assessment of Electronic Cigarette or Vaping Product Use-associated Lung Injury (EVALI): The EVALI-BAL Study, A Multicenter Cohort.

BACKGROUND: E-cigarette or vaping-use related acute lung injury (EVALI) is a spectrum of radiographic and histologic patterns consistent with acute to subacute lung injury. However, limited data exist characterizing bronchoalveolar lavage (BAL) findings. The goal of this study is to further define the pathologic findings from BAL and biopsy samples of subjects with EVALI across 7 institutions. METHODS: A multicentered registry of patients admitted with EVALI who underwent flexible bronchoscopy with BAL+/-transbronchial biopsy from July 2019 to April 2021 was compiled for retrospective evaluation from 7 academic institutions throughout the United States. Radiographic and cytopathologic findings and frequencies were correlated with the substance vaped. RESULTS: Data from 21 subjects (42.9% women) who were predominantly White (76.2%) with a median age of 25 years (range, 16 to 68) with EVALI were included in this study. Sixteen patients (76.2%) reported use of tetrahydrocannabinol; the remainder used nicotine. BAL was performed in 19 of the 21 subjects, and transbronchial lung biopsy was performed in 7 subjects. BAL findings revealed neutrophilic predominance (median, 59.5%, range, 3.1 to 98) in most cases. Ten BAL samples demonstrated pulmonary eosinophilia ranging from 0.2% to 49.1% with one subject suggesting a diagnosis of acute eosinophilic pneumonia associated with the use of e-cigarettes. Lipid-laden macrophages were noted in 10 of 15 reports (66.7%). Transbronchial biopsy most frequently demonstrated patterns of organizing pneumonia (57.1%). CONCLUSION: EVALI-associated BAL findings typically demonstrate a spectrum of nonspecific inflammatory changes, including neutrophilia, lipid-laden macrophages, and in some cases eosinophilia.

Applications of cryobiopsy in airway, pleural, and parenchymal disease.

INTRODUCTION: Cryobiopsy is a novel diagnostic technique for thoracic diseases, which has been extensively investigated over the past 20 years. It was originally proposed for the diagnosis of endobronchial lesions and diffuse parenchymal lung disease due to limitations of conventional sampling techniques including small size and presence of artifacts. AREAS COVERED: We review recent evidence related to the expanding use of cryobiopsy in thoracic diseases. To identify references, the MEDLINE database was searched from database inception until May 2022 for case series, cohort studies, randomized controlled trials, systematic reviews, and meta-analyses related to cryobiopsy. EXPERT OPINION: Cryobiopsy has expanding applications in the field of thoracic diseases. Evidence to support transbronchial cryobiopsy as an alternative to surgical lung biopsy is increasing and was recently endorsed as a conditional recommendation by the latest American Thoracic Society guideline update for Idiopathic Pulmonary Fibrosis. Developments in technology and technique, in particular the availability of a 1.1 mm flexible cryoprobe, have extended applications to pulmonary diseases, including diagnosis of interstitial lung diseases, peripheral pulmonary lesions, and lung transplant rejection.

Predictive performance of selected breath volatile organic carbon compounds in stage 1 lung cancer.

Background: Lung cancer remains the leading cause of cancer deaths accounting for almost 25% of all cancer deaths. Breath-based volatile organic compounds (VOCs) have been studied in lung cancer but previous studies have numerous limitations. We conducted a prospective matched case to control study of the ability of preidentified VOC performance in the diagnosis of stage 1 lung cancer (S1LC). Methods: Study participants were enrolled in a matched case to two controls study. A case was defined as a patient with biopsy-confirmed S1LC. Controls included a matched control, by risk factors, and a housemate control who resided in the same residence as the case. We included 88 cases, 88 risk-matched, and 49 housemate controls. Each participant exhaled into a Tedlar® bag which was analyzed using gas chromatography-mass spectrometry. For each study participant's breath sample, the concentration of thirteen previously identified VOCs were quantified and assessed using area under the curve in the detection of lung cancer. Results: Four VOCs were above the limit of detection in more than 10% of the samples. Acetoin was the only compound that was significantly associated with S1LC. Acetoin concentration below the 10th percentile (0.026 µg/L) in the training data had accuracy of 0.610 (sensitivity =0.649; specificity =0.583) in the test data. In multivariate logistic models, the best performing models included Acetoin alone (AUC =0.650). Conclusions: Concentration of Acetoin in exhaled breath has low discrimination performance for S1LC cases and controls, while there was not enough evidence for twelve additional published VOCs.

Direct Visualization and Quantitative Imaging of Small Airway Anatomy In Vivo Using Deep Learning Assisted Diffractive OCT.

OBJECTIVE/BACKGROUND: In vivo imaging and quantification of the microstructures of small airways in three dimensions (3D) allows a better understanding and management of airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). At present, the resolution and contrast of the currently available conventional optical coherence tomography (OCT) imaging technologies operating at 1300 nm remain challenging to directly visualize the fine microstructures of small airways in vivo. METHODS: We developed an ultrahigh-resolution diffractive endoscopic OCT at 800 nm to afford a resolving power of 1.7 µm (in tissue) with an improved contrast and a custom deep residual learning based image segmentation framework to perform accurate and automated 3D quantification of airway anatomy. RESULTS: The 800-nm diffractive OCT enabled the direct delineation of the structural components in the small airway wall in vivo. We further first demonstrated the 3D anatomic quantification of critical tissue compartments of small airways in sheep using the automated segmentation method. CONCLUSION: The deep learning assisted diffractive OCT provides a unique ability to access the small airways, directly visualize and quantify the important tissue compartments, such as airway smooth muscle, in the airway wall in vivo in 3D. SIGNIFICANCE: These pilot results suggest a potential technology for calculating volumetric measurements of small airways in patients in vivo.