BACKGROUND:Lung cancer is the leading cause of cancer mortality. Nonsurgical biopsies are obtained by computed tomography-guided transthoracic biopsy (CTTB) or bronchoscopically. Due to previous limitations in conventional flexible bronchoscopic techniques, the development of robotic-assisted bronchoscopy (RAB) platforms have emerged. We aim to compare the outcomes of shape-sensing RAB (ssRAB) and CTTB using a strict diagnostic yield (DY) definition. STUDY DESIGN AND METHODS:This is a single center observational study. Data was collected from adults (age ≥ 18) who underwent a lung biopsy with CTTB or ssRAB between March 21, 2023 and August 31, 2024. The primary outcome was DY. The secondary outcomes were molecular adequacy, time to treatment for new non-small cell lung cancer (NSCLC) diagnoses, procedure complications, and procedure duration. RESULTS:A total of 638 patients (ssRAB N = 489, CTTB N = 149) were included. DY for ssRAB was 84.3 % vs 80.5 % in CTTB (p = 0.347). Compared to CTTB, the ssRAB group had a lower incidence of pneumothorax (PTX) (1.4 % vs 29.5 %, p < 0.001), PTX requiring a chest tube placement (1.4 % vs 4.7 %, p = 0.039), and pulmonary hemorrhage (0.2 % vs 14.1 %, p < 0.001). Molecular adequacy was 89.6 % in ssRAB vs. 79.1 % CTTB (p = 0.022). Adjusted analysis found a similar DY between ssRAB and CTTB [adjusted OR (95 % CI): 1.14 (0.82; 1.60)] but increased molecular adequacy for ssRAB vs CTTB [adjusted OR (95 % CI): 2.21 (1.18; 4.16)], and lower incidence of PTX for ssRAB vs CTTB [adjusted OR (95 % CI): 0.04 (0.01; 0.08)]. Time from biopsy to treatment initiation for new NSCLC diagnoses was faster with ssRAB compared to CTTB [adjusted mean difference (95 % CI): -22.276 (-29.983--14.547) days]; however, a longer procedure time (adjusted mean difference (95 % CI): 10.572 [8.653; 12.491] minutes). INTERPRETATION:These findings suggest ssRAB may have a comparable diagnostic yield to CTTB but potentially provide superior quantity sufficient biopsies for molecular analysis at a lower complication rate. Adjusting for confounding variables, ssRAB may have fewer complication rates, superior molecular adequacy, and fewer days from biopsy to treatment initiation for new NSCLC diagnoses.

BACKGROUND:Robotic-assisted bronchoscopy (RAB) is limited by CT-to-body divergence. Cone-beam CT (CBCT) may enhance tool-to-lesion alignment and diagnostic yield (DY), but the benefit of integrating mobile CBCT (mCBCT) into the MonarchTM RAB remains understudied. This is the first study to evaluate diagnostic performance between Monarch alone versus Monarch plus mCBCT for peripheral pulmonary lesion (PPL) biopsy, hypothesizing improved DY with the combined approach. METHODS:This single-center retrospective study examined adults undergoing RAB biopsy for PPLs (May 2019-March 2023), applying a strict DY definition. Clinical characteristics and outcomes were evaluated in Monarch and Monarch plus mCBCT groups. RESULTS:Of 331 cases, 179 used Monarch and 152 used Monarch plus mCBCT. There was no significant difference in baseline characteristics. DY was not different (70.9 % in Monarch vs 71.7 % in Monarch plus mCBCT, p = 0.976) nor were complication rates (7.3 % in Monarch vs. 3.9 % in Monarch plus mCBCT, p = 0.291). In the Monarch group, the procedure duration was longer (77 min in Monarch vs. 69 min in Monarch plus mCBCT, p = 0.002) and the radiation dose was lower (7.4 mGy in Monarch vs. 285.9 mGy in Monarch plus mCBCT, p < 0.001). Adjusted analysis demonstrated that mCBCT was not associated with improved DY (OR [95 % CI]: 1.33[0.78-2.28]) or reduced risk for complications (OR [95 % CI]: 0.41 [0.13; 1.14]). DY increased with larger nodule size but not with lesion location. CONCLUSIONS:Evaluating outcomes across two sequential practice eras, the addition of mCBCT to Monarch RAB did not significantly improve DY or reduce complications but reduced procedure duration at the cost of increased radiation exposure. SUMMARY:- Evaluated diagnostic performance of Monarch™ vs. Monarch™ + mobile Cone-beam CT (mCBCT). - Diagnostic yield and complication rates were similar. - The mCBCT group had shorter procedure times and about 40-fold higher radiation doses. CONFERENCE PRESENTATION:The study findings have been presented in American Association for Bronchology and Interventional Pulmonology Annual Conference in 2024. The institutional review board approved all protocols (IRB 23-005284).

Lung cancer is the leading cause of cancer-related deaths. Earlier detection and diagnosis are crucial in improving overall survival. Limitations in conventional bronchoscopic biopsy techniques have prompted the development of robotic-assisted bronchoscopy (RAB) platforms. Among the RAB platforms, we report the first study comparing outcomes between the Ion and Monarch platforms. In this single-center retrospective study, data were collected from adults (age>18 y) who underwent a RAB biopsy with the Monarch (11/23/21 to 3/10/23) or by the Ion (3/21/23 to 12/15/23). The primary outcome was diagnostic yield (DY). The secondary outcomes were robot procedure duration, radiation time, radiation dose, and complication rate. We performed propensity score-matched analysis. A total of 365 patients (Monarch N=162, Ion N=203) were included in the analysis. DY for Ion and Monarch was 84.2% versus 71.0%, respectively (P=0.003). When compared with Monarch, Ion cases had a shorter robot procedure time [median (IQR): 37.00 (26.00, 51.00) vs. 70.00 (51.25, 87.00) min, P<0.001], shorter radiation time [median (IQR) 4.6 (3.00, 7.10) vs. 8.0 (5.80, 10.95) minutes, P<0.001], and lower radiation dose area product (DAP) [median (IQR): 22.70 (14.30, 38.35) vs. 40.00 (23.20, 67.80) Gy.cm2, P<0.001]. Pneumothorax rates were 1.0% versus 4.3% for Ion and Monarch, respectively (P=0.089). This is a retrospective study that suggests that the Ion RAB system, when compared with the Monarch RAB system, had higher DY, shorter robot procedure time and radiation time, and lower radiation dose. A randomized controlled trial is needed to confirm or refute these findings.

AimTransbronchial cryobiopsies are increasingly used for the diagnosis of interstitial lung disease (ILD), but there is a lack of published information on the features of specific ILD in cryobiopsies. Here we attempt to provide pathological guidelines for separating usual interstitial pneumonia (UIP) of idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (FHP) and connective tissue disease‐associated ILD (CTD–ILD) in cryobiopsies.MethodsWe examined 120 cryobiopsies from patients with multidisciplinary discussion (MDD)‐established CTD–ILD and compared them to a prior series of 121 biopsies from patients with MDD‐established IPF or FHP.ResultsA non‐specific interstitial pneumonia (NSIP) pattern alone was seen in 36 of 120 (30%) CTD–ILD, three of 83 (3.6%) FHP and two of 38 (5.2%) IPF cases, statistically favouring a diagnosis of CTD–ILD. The combination of NSIP + OP was present in 29 of 120 (24%) CTD–ILD, two of 83 (2.4%) FHP and none of 38 (0%) IPF cases, favouring a diagnosis of CTD–ILD. A UIP pattern, defined as fibroblast foci plus any of patchy old fibrosis/fibrosis with architectural distortion/honeycombing, was identified in 28 of 120 (23%) CTD–ILD, 45 of 83 (54%) FHP and 27 of 38 (71%) IPF cases and supported a diagnosis of FHP or IPF. The number of lymphoid aggregates/mm2 and fibroblast foci/mm2 was not different in IPF, CTD–ILD or FHP cases with a UIP pattern. Interstitial giant cells supported a diagnosis of FHP or CTD–ILD over IPF, but were infrequent.ConclusionsIn the correct clinical/radiological context the pathological findings of NSIP, and particularly NSIP plus OP, favour a diagnosis of CTD–ILD in a cryobiopsy, but CTD–ILD with a UIP pattern, FHP with a UIP pattern and IPF generally cannot be distinguished.

BACKGROUND: Appropriate risk stratification of indeterminate pulmonary nodules (IPNs) is necessary to direct diagnostic evaluation. Currently available models were developed in populations with lower cancer prevalence than that seen in thoracic surgery and pulmonology clinics and usually do not allow for missing data. We updated and expanded the Thoracic Research Evaluation and Treatment (TREAT) model into a more generalized, robust approach for lung cancer prediction in patients referred for specialty evaluation.RESEARCH QUESTION: Can clinic-level differences in nodule evaluation be incorporated to improve lung cancer prediction accuracy in patients seeking immediate specialty evaluation compared with currently available models?STUDY DESIGN AND METHODS: Clinical and radiographic data on patients with IPNs from six sites (N = 1,401) were collected retrospectively and divided into groups by clinical setting: pulmonary nodule clinic (n = 374; cancer prevalence, 42%), outpatient thoracic surgery clinic (n = 553; cancer prevalence, 73%), or inpatient surgical resection (n = 474; cancer prevalence, 90%). A new prediction model was developed using a missing data-driven pattern submodel approach. Discrimination and calibration were estimated with cross-validation and were compared with the original TREAT, Mayo Clinic, Herder, and Brock models. Reclassification was assessed with biascorrected clinical net reclassification index and reclassification plots.RESULTS: Two-thirds of patients had missing data; nodule growth and fluorodeoxyglucose-PET scan avidity were missing most frequently. The TREAT version 2.0 mean area under the receiver operating characteristic curve across missingness patterns was 0.85 compared with that of the original TREAT (0.80), Herder (0.73), Mayo Clinic (0.72), and Brock (0.68) models with improved calibration. The bias-corrected clinical net reclassification index was 0.23. INTERPRETATION: The TREAT 2.0 model is more accurate and better calibrated for predicting lung cancer in high-risk IPNs than the Mayo, Herder, or Brock models. Nodule calculators such as TREAT 2.0 that account for varied lung cancer prevalence and that consider missing data may provide more accurate risk stratification for patients seeking evaluation at specialty nodule evaluation clinics. CHEST 2023; 164(5):1305-1314

Background Appropriate risk stratification of indeterminate pulmonary nodules (IPNs) is necessary to direct diagnostic evaluation. Currently available models were developed in populations with lower cancer prevalence than that seen in thoracic surgery and pulmonology clinics and usually do not allow for missing data. We updated and expanded the Thoracic Research Evaluation and Treatment (TREAT) model into a more generalized, robust approach for lung cancer prediction in patients referred for specialty evaluation. Research Question Can clinic-level differences in nodule evaluation be incorporated to improve lung cancer prediction accuracy in patients seeking immediate specialty evaluation compared with currently available models? Study Design and Methods Clinical and radiographic data on patients with IPNs from six sites (N = 1,401) were collected retrospectively and divided into groups by clinical setting: pulmonary nodule clinic (n = 374; cancer prevalence, 42%), outpatient thoracic surgery clinic (n = 553; cancer prevalence, 73%), or inpatient surgical resection (n = 474; cancer prevalence, 90%). A new prediction model was developed using a missing data-driven pattern submodel approach. Discrimination and calibration were estimated with cross-validation and were compared with the original TREAT, Mayo Clinic, Herder, and Brock models. Reclassification was assessed with bias-corrected clinical net reclassification index and reclassification plots. Results Two-thirds of patients had missing data; nodule growth and fluorodeoxyglucose-PET scan avidity were missing most frequently. The TREAT version 2.0 mean area under the receiver operating characteristic curve across missingness patterns was 0.85 compared with that of the original TREAT (0.80), Herder (0.73), Mayo Clinic (0.72), and Brock (0.68) models with improved calibration. The bias-corrected clinical net reclassification index was 0.23. Interpretation The TREAT 2.0 model is more accurate and better calibrated for predicting lung cancer in high-risk IPNs than the Mayo, Herder, or Brock models. Nodule calculators such as TREAT 2.0 that account for varied lung cancer prevalence and that consider missing data may provide more accurate risk stratification for patients seeking evaluation at specialty nodule evaluation clinics.

BACKGROUND: Anxiety and emotional distress have not been studied in large, diverse samples of patients with pulmonary nodules.RESEARCH QUESTION: How common are anxiety and distress in patients with newly identified pulmonary nodules, and what factors are associated with these outcomes?STUDY DESIGN AND METHODS: This study surveyed participants in the Watch the Spot Trial, a large, pragmatic clinical trial of more vs less intensive strategies for radiographic surveillance of patients with small pulmonary nodules. The survey included validated instruments to measure patient-centered outcomes such as nodule-related emotional distress (Impact of Event Scale-Revised) and anxiety (Six-Item State Anxiety Inventory) 6 to 8 weeks following nodule identification. Mixed-effects models were used to compare outcomes between study arms following adjustment for potential confounders and clustering within enrollment site, while also examining a limited number of prespecified explanatory factors, including nodule size, mode of detection, type of ordering clinician, and lack of timely notification prior to contact by the study team.RESULTS: The trial enrolled 34,699 patients; 2,049 individuals completed the baseline survey (5.9%). Respondents and nonrespondents had similar demographic and nodule character-istics, although more respondents were non-Hispanic and White. Impact of Event Scale -Revised scores indicated mild, moderate, or severe distress in 32.2%, 9.4%, and 7.2% of re-spondents, respectively, with no difference in scores between study arms. Following adjust-ment, greater emotional distress was associated with larger nodule size and lack of timely notification by a clinician; distress was also associated with younger age, female sex, ever smoking, Black race, and Hispanic ethnicity. Anxiety was associated with lack of timely notification, ever smoking, and female sex.INTERPRETATION: Almost one-half of respondents experienced emotional distress 6 to 8 weeks following pulmonary nodule identification. Strategies are needed to mitigate the burden of distress, especially in younger, female, ever smoking, and minoritized patients, and those with larger nodules.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02623712; URL: www. clinicaltrials.gov CHEST 2023; 164(6):1560-1571

Background: Clinical differentiation of fibrotic hypersensitivity pneumonitis (f-HP) remains challenging given variable and overlapping presentations with other fibrotic interstitial lung disease (f-ILD). Objective: We derived a multivariable model for predicting histopathologic f-HP to better inform multidisciplinary team discussion (MDD) diagnosis, particularly when biopsy may be unsafe or cannot be achieved. Methods: Patients with histopathologically-defined f-HP and other overlapping f-ILD were reviewed for distinguishing clinical and radiological variables. Using elastic net logistic regression, a penalized regression approach to minimize overfitting, a clinical model built on non-invasive assessments was derived for the prediction of histopathologic f-HP. This model was then validated in an independently derived external cohort from three sites. Results: The derivation and validation cohorts consisted of 248 (84 cHP and 164 other f-ILD) and 157 (82 f-HP and 75 other f-ILD) histopathologically-defined patients, respectively (total study N = 405). Variables retained from the elastic net model included age in years (regression coefficient 0.033), male sex (-1.109), positive exposure history (1.318), percent predicted forced vital capacity (-0.021), radiologic peribronchovascular axial ILD distribution (0.199), mid (-0.22) or lower lobe (-0.839) craniocaudal or patchy (0.287) ILD distribution, upper (1.188) or equivalent upper and lower lobe (0.237) traction bronchiectasis, mosaic attenuation (1.164), and centrilobular nodules (2.045). Bias corrected AUC was 0.84 (standard error = 0.02) for the derivation cohort and 0.80 (CI 0.73-0.87) for the validation cohort. Conclusions: This multivariable model demonstrated good predictive performance for delineating histopathologically-defined f-HP from other f-ILD as a means of avoiding or justifying biopsy and supporting MDD diagnostic confidence.

"Trends in Intrabronchial Valve Implantation in Patients with Persistent Air Leak: Analysis of a Nationwide Database over a 10-Year Period." Annals of the American Thoracic Society, 17(12), pp. 1642–1645

Oguz Karcioglu, MD* Rıza Dogan, MD† Omrum Uzun, MD‡ Fatma Tokat, MD§ Dolunay Gülmez, MD∥ Sevtap Arikan-Akdagli, MD∥ Ziya T. Selcuk, MD¶ *Department of Chest Diseases Çubuk Halil Şıvgın State Hospital, Çubuk Departments of †Thoracic Surgery ‡Infectious Diseases and Clinical Microbiology ∥Medical Microbiology ¶Chest Diseases, Hacettepe University Faculty of Medicine Ankara §Department of Pathology, Acibadem Mehmet Ali Aydinlar University İstanbul Turkey

Pathology of Vaping-Associated Lung Injury This letter describes findings in 17 patients with a history of vaping who had lung biopsies after presenting with symptoms and bilateral pulmonary opacit...

Scimitar syndrome is a rare constellation of congenital conditions pertaining to partial anomalous pulmonary venous return. Radiographically, these anomalous pulmonary veins can resemble a scimitar, and have heterogeneous clinical presentations. We present an unusual case of scimitar syndrome with associated recurrent pneumonia. We will briefly review the literature on scimitar syndrome as well as discuss how a predisposition to recurrent pneumonia may develop in this unusual variant of a rare clinical entity.

PURPOSE: Sighing dyspnea is an uncomfortable awareness of feeling unable to take a deep, satisfying breath, often while sighing or yawning. We developed a breathing technique to alleviate this symptom and evaluated it in a cohort of such patients. METHODS: We enrolled patients who presented to the Mayo Clinic for evaluation of breathlessness, and who underwent cardiopulmonary evaluations that failed to establish a distinct cause for the dyspnea. The demographic and clinical data were abstracted from the medical record. Patients were taught a breathing technique focused on prolonged exhalation to control symptoms. The severity and frequency of dyspnea symptoms before and after the breathing training were assessed with a survey. RESULTS: 36 patients (6 males) met inclusion criteria. Median (interquartile range) age was 51 (45-57) years. BMI was 26.9 (23.4-32), the left-ventricle ejection fraction was 64 (59-66)%, with FEV1/FVC 103 (96-106)%, FVC 92 (85-104)% and RV 105 (99-115)% of predicted. Post-exercise O2 saturation 96% (95-97)%. Chest imaging was non-contributory in all cases. 30 patients also had symptoms of hyperventilation. 17 patients returned the questionnaires. Mean symptom severity decreased from 3.71 (out of 5) to 3.12 (p=0.01), and frequency ecreased from 4.47 (of 6) to 3.94 (p=0.008) with the breathing technique. CONCLUSIONS: Patients who present with dyspnea with sighing or yawning and negative initial diagnostic testing may benefit symptomatically from breathing maneuvers focused on prolonged exhalation CLINICAL IMPLICATIONS: Patients with symptoms of sighing dyspnea may be reassured the condition is benign and controllable through education and a breathing technique

Small pulmonary nodules are most often managed by surveillance imaging with computed tomography (CT) of the chest, but the optimal frequency and duration of surveillance are unknown. The Watch the Spot Trial is a multicenter, pragmatic, comparative-effectiveness trial with cluster randomization by hospital or health system that compares more- versus less-intensive strategies for active surveillance of small pulmonary nodules. The study plans to enroll approximately 35,200 patients with a small pulmonary nodule that is newly detected on chest CT imaging, either incidentally or by screening. Study protocols for more- and less-intensive surveillance were adapted from published guidelines. The primary outcome is the percentage of cancerous nodules that progress beyond American Joint Committee on Cancer seventh edition stage T1a. Secondary outcomes include patient-reported anxiety and emotional distress, nodule-related health care use, radiation exposure, and adherence with the assigned surveillance protocol. Distinctive aspects of the trial include: 1) the pragmatic integration of study procedures into existing clinical workflow; 2) the use of cluster randomization by hospital or health system; 3) the implementation and evaluation of a system-level intervention for protocol-based care; 4) the use of highly efficient, technology-enabled methods to identify and (passively) enroll participants; 5) reliance on data collected as part of routine clinical care, including data from electronic health records and state cancer registries; 6) linkage with state cancer registries for complete ascertainment of the primary study outcome; and 7) intensive engagement with a diverse group of patient and nonpatient stakeholders in the design and execution of the study.

Appropriate risk-stratification of indeterminate pulmonary nodules (IPNs) is necessary to estimate the best diagnostic strategy. Validated models for patients with high-risk IPNs are poorly calibrated. We sought to expand our previous Thoracic Research Evaluation And Treatment (TREAT) model into a more generalized, robust model for lung cancer prediction, the TREAT 2.0. A total of 1402 patients with known or suspected lung cancer were used to recalibrate the TREAT 1.0 model. Clinical data and patient demographics were retrospectively collected from six clinics located in four U.S. states. Six datasets were divided into 3 clinical groups: patients who presented to a pulmonary nodule clinic (n=375), patients who presented to an outpatient thoracic surgery clinic (n=553) and patients who presented for surgical resection (n=474). A logistic regression model using multiple imputation was developed and validated. Model variables included age, body mass index, gender, smoking pack-years, size of nodule, spiculation, growth over time, location in upper lobe, prior cancer history, pre-operative FEV1, pre-operative symptoms, FDG-PET positivity, and clinical group. The discrimination and calibration of the TREAT 2.0 model was estimated and compared to two other common models for lung nodules, the Mayo Clinic and Herder models. Lung cancer prevalence was as follows: pulmonary nodule clinic 42%, thoracic surgery clinic 73%, and surgical resection cohort 90%. The strongest predictors of cancer were clinical group, age, nodule growth, PET positivity, and smoking pack-years. The median TREAT 2.0 area under the receiver operating curve (AUC) for the imputed dataset was 0.86 (95% confidence interval (CI), 0.86-0.87) and the Brier score was 0.13. The TREAT 2.0 model had better accuracy (p < 0.001) (Figure 1) and calibration than the Mayo Clinic (AUC =0.74 95% CI: 0.74-0.75; Brier score=0.21) or Herder models (AUC=0.75; 95%CI: 0.74-0.75 and Brier score=0.19). The TREAT 2.0 model is more accurate and better calibrated than the Mayo Clinic or Herder models in patients presenting with nodules at high risk for lung cancer. Nodule calculators such as the TREAT 2.0 that account for variation in lung cancer prevalence with a variable for clinical group may improve generalizability and increase use in clinical practice.

Diagnostic imaging plays a prominent role in the evaluation of numerous medical conditions, ranging from suspected infections to assessment of the acutely injured patient to staging malignancies and numerous other conditions, both common and rare. Imaging can be a very powerful tool in the diagnosis of medical disorders and plays a major role in the assessment of therapeutic response as well. It is common in practice for imaging studies to provide findings that may corroborate the clinical or laboratory impression of a disorder, allowing a presumptive diagnosis and institution of therapy, often circumventing the morbidity and even mortality that could be associated with an invasive tissue confirmation of a suspected diagnosis. Furthermore, imaging may occasionally detect entirely unsuspected disorders in minimally symptomatic, or even entirely asymptomatic, patients, the latter typically in the context of screening for malignancies. However, on occasion, imaging may fail to disclose a condition that “should be there” on the basis of findings at clinical and/or laboratory examination; this situation is particularly true when imaging fails to reveal abnormalities in the context of a suspected paraneoplastic syndrome. In this circumstance, there may be few, if any, alternatives to approach diagnosing such patients, and the appropriate treatment of these patients becomes exceedingly difficult. Such a situation can even lead to unnecessary, perhaps even inappropriate, interventions. In this circumstance, careful reconsideration of the imaging findings is paramount for correct patient management.

The use of venovenous extracorporeal membrane oxygenation (VV-ECMO) has traditionally been limited to a narrow set of clinical circumstances, such as acute hypoxic respiratory failure, submassive pulmonary embolism, and cardiopulmonary collapse. Within the pediatric population, there have been cases of VV-ECMO in the context of extrinsic airway compression by a mediastinal mass, typically in the setting of either a lymphoma or germ cell tumors. However, the use of VV-ECMO for adults with extrinsic airway compression is comparatively limited. More specifically, VV-ECMO has been used as a bridge for tracheal reconstruction in both children and adults. Although, it has not been used in adults in the context of palliative endobronchial stent placement. We present a case of a 49-year-old woman with refractory multiple myeloma and extramedullary plasmacytoma presenting with acute hypoxic respiratory failure from extrinsic airway compression by a mediastinal plasmacytoma. We were able to use VV-ECMO to assist with endobronchial stent placement, followed by radiation therapy, and ultimately hospital discharge. In this article, we also review the literature surrounding VV-ECMO for extrinsic airway compression.