World Association for Bronchology and Interventional Pulmonology (WABIP) guidelines on airway stenting for malignant central airway obstruction.

Malignant Central Airway Obstruction (MCAO) encompasses significant and symptomatic narrowing of the central airways that can occur due to primary lung cancer or metastatic disease. Therapeutic bronchoscopy is associated with high technical success and symptomatic relief and includes a wide range of airway interventions including airway stents. Published literature suggests that stenting practices vary significantly across the world primarily due to lack of guidance. This document aims to address this knowledge gap by addressing relevant questions related to airway stenting in MCAO. An international group of 17 experts from 17 institutions across 11 countries with experience in using airway stenting for MCAO was convened as part of this guideline statement through the World Association for Bronchology and Interventional Pulmonology (WABIP). We performed a literature and internet search for reports addressing six clinically relevant questions. This guideline statement, consisting of recommendations addressing these six PICO questions, was formulated by a systematic and rigorous process involving the evaluation of published evidence, augmented with expert experience when necessary. Panel members participated in the development of the final recommendations using the modified Delphi technique.

Optimizing clinical outcomes for bronchoscopic lung volume reduction with Zephyr® valves.

Bronchoscopic lung volume reduction treatment with Zephyr one-way valves is an effective guideline-based treatment option for patients with severe emphysema and hyperinflation. However, in some cases the treatment response is less than anticipated or there might be a loss of initial treatment effect. Reasons for the lack of response can include incorrect assessment of collateral ventilation, improper valve placement, or patient related factors. Loss of initial benefit can be due to granulation tissue formation and subsequent valve dysfunction, or there may be side effects such as excessive coughing or infectious problems. Careful follow-up after treatment with valves is important and evaluation with a CT scan and/or bronchoscopy is helpful if there is no improvement after treatment or loss of initial benefit. This paper aims to describe the most important causes and provide a strategy of how to approach and manage these patients.

Navigational Bronchoscopy versus Computed Tomography-guided Transthoracic Needle Biopsy for the Diagnosis of Indeterminate Lung Nodules: protocol and rationale for the VERITAS multicenter randomized trial.

Background: Lung nodule incidence is increasing. Many nodules require biopsy to discriminate between benign and malignant etiologies. The gold-standard for minimally invasive biopsy, computed tomography-guided transthoracic needle biopsy (CT-TTNB), has never been directly compared to navigational bronchoscopy, a modality which has recently seen rapid technological innovation and is associated with improving diagnostic yield and lower complication rate. Current estimates of the diagnostic utility of both modalities are based largely on non-comparative data with significant risk for selection, referral, and publication biases. Methods: The VERITAS trial (na V igation E ndoscopy to R each Indeterminate lung nodules versus T ransthoracic needle A spiration, a randomized controlled S tudy) is a multicenter, 1:1 randomized, parallel-group trial designed to ascertain whether electromagnetic navigational bronchoscopy with integrated digital tomosynthesis is noninferior to CT-TTNB for the diagnosis of peripheral lung nodules 10-30 mm in diameter with pre-test probability of malignancy of at least 10%. The primary endpoint is diagnostic accuracy through 12 months follow-up. Secondary endpoints include diagnostic yield, complication rate, procedure duration, need for additional invasive diagnostic procedures, and radiation exposure. Discussion: The results of this rigorously designed trial will provide high-quality data regarding the management of lung nodules, a common clinical entity which often represents the earliest and most treatable stage of lung cancer. Several design challenges are described. Notably, all nodules are centrally reviewed by an independent interventional pulmonology and radiology adjudication panel relying on pre-specified exclusions to ensure enrolled nodules are amenable to sampling by both modalities while simultaneously protecting against selection bias favoring either modality. Conservative diagnostic yield and accuracy definitions with pre-specified criteria for what non-malignant findings may be considered diagnostic were chosen to avoid inflation of estimates of diagnostic utility. Trial registration: ClinicalTrials.gov NCT04250194.

Cystic fibrosis-related mortality in the United States from 1999 to 2020: an observational analysis of time trends and disparities.

Cystic fibrosis transmembrane conductance regulator modulators have revolutionized cystic fibrosis (CF) care in the past decade. This study explores the CF-related mortality trends in the US from 1999 to 2020. We extracted CF-related mortality data from the CDC WONDER database. CF age-standardized mortality rates (ASMRs) were identified by ICD-10 code E84 and were stratified by demographic and geographical variables. Temporal trends were analyzed using Joinpoint modeling. CF-related ASMRs decreased from 1.9 to 1.04 per million population (p = 0.013), with a greater reduction in recent years. This trend was replicated in both sexes. The median age of death increased from 24 to 37 years. CF mortality rates decreased across sex, white race, non-Hispanic ethnicity, census regions, and urbanization status. Incongruent trends were reported in non-white races and Hispanic ethnicity. A lower median age of death was observed in women, non-white races, and Hispanic ethnicity. SARS-CoV-2 infection was the primary cause of death in 1.7% of CF decedents in 2020. The national CF-related mortality rates declined and the median age of death among CF decedents increased significantly indicating better survival in the recent years. The changes were relatively slow during the earlier period of the study, followed by a greater decline lately. We observed patterns of sex, ethnic, racial, and geographical disparities associated with the worsening of the gap between ethnicities, narrowing of the gap between races and rural vs. urban counties, and closing of the gap between sexes over the study period.

Assessing a biomarker's ability to reduce invasive procedures in patients with benign lung nodules: Results from the ORACLE study.

A blood-based integrated classifier (IC) has been clinically validated to improve accuracy in assessing probability of cancer risk (pCA) for pulmonary nodules (PN). This study evaluated the clinical utility of this biomarker for its ability to reduce invasive procedures in patients with pre-test pCA ≤ 50%. This was a propensity score matching (PSM) cohort study comparing patients in the ORACLE prospective, multicenter, observational registry to control patients treated with usual care. This study enrolled patients meeting the intended use criteria for IC testing: pCA ≤ 50%, age ≥40 years, nodule diameter 8-30 mm, and no history of lung cancer and/or active cancer (except for non-melanomatous skin cancer) within 5 years. The primary aim of this study was to evaluate invasive procedure use on benign PNs of registry patients as compared to control patients. A total of 280 IC tested, and 278 control patients met eligibility and analysis criteria and 197 were in each group after PSM (IC and control groups). Patients in the IC group were 74% less likely to undergo an invasive procedure as compared to the control group (absolute difference 14%, p <0.001) indicating that for every 7 patients tested, one unnecessary invasive procedure was avoided. Invasive procedure reduction corresponded to a reduction in risk classification, with 71 patients (36%) in the IC group classified as low risk (pCA < 5%). The proportion of IC group patients with malignant PNs sent to surveillance were not statistically different than the control group, 7.5% vs 3.5% for the IC vs. control groups, respectively (absolute difference 3.91%, p 0.075). The IC for patients with a newly discovered PN has demonstrated valuable clinical utility in a real-world setting. Use of this biomarker can change physicians' practice and reduce invasive procedures in patients with benign pulmonary nodules. Trial registration: Clinical trial registration: ClinicalTrials.gov NCT03766958.

Real-world utility of a genomic classifier in establishing a diagnosis of newly identified interstitial lung disease.

BACKGROUND: Diagnosing interstitial lung disease (ILD) remains challenging. Guidelines recommend utilizing a multidisciplinary discussion (MDD) to review clinical and radiographic data and if diagnostic uncertainty persists, then to obtain histopathology. Surgical lung biopsy and transbronchial lung cryobiopsy (TBLC) are acceptable methods, but risks of complications may be prohibitive. The Envisia genomic classifier (EGC) represents another option to determine a molecular usual interstitial pneumonia (UIP) signature to facilitate an ILD diagnosis at MDD with high sensitivity and specificity. We evaluated the concordance between TBLC and EGC at MDD and the safety of this procedure. METHODS: Demographic data, pulmonary function values, chest imaging pattern, procedural information, and MDD diagnosis were recorded. Concordance was defined as agreement between the molecular EGC results and histopathology from TBLC in the context of the patient's High Resolution CT pattern. RESULTS: 49 patients were enrolled. Imaging demonstrated a probable (n = 14) or indeterminate (n = 7) UIP pattern in 43% and an alternative pattern in 57% (n = 28). EGC results were positive for UIP in 37% (n = 18) and negative in 63% (n = 31). MDD diagnosis was obtained in 94% (n = 46) with fibrotic hypersensitivity pneumonitis (n = 17, 35%) and IPF (n = 13, 27%) most common. The concordance between EGC and TBLC at MDD was 76% (37/49) with discordant results seen in 24% (12/49) of patients. CONCLUSIONS: There appears to be reasonable concordance between EGC and TBLC results at MDD. Efforts clarifying the contributions of these tools to an ILD diagnosis may help identify specific patient populations that may benefit from a tailored diagnostic approach.

Reclassification of risk of malignancy with Percepta Genomic Sequencing Classifier following nondiagnostic bronchoscopy.

INTRODUCTION: Bronchoscopic sampling of pulmonary lesions suspicious for lung cancer is frequently nondiagnostic. A genomic sequencing classifier utilizing bronchial brushings obtained at the time of the bronchoscopy has been shown to provide an accurate reclassification of the risk of malignancy (ROM) based on pre-procedure risk. Our objectives for this study were to determine the frequency with which the classifier up- or down-classifies risk in regular clinical practice and to model the potential clinical utility of that reclassification. METHODS: This observational study retrospectively assessed data from four clinical sites that regularly use the genomic classifier in the bronchoscopic evaluation of indeterminate lesions. Demographics and pre-bronchoscopy ROM were recorded. The frequency of up- and down-classification was calculated. Modeling based on reclassification rates and the performance characteristics of the classifier was performed to demonstrate the potential clinical utility of the result. RESULTS: 86 patients who underwent classifier testing following a nondiagnostic bronchoscopy were included. 45% of patients with high ROM prior to bronchoscopy were reclassified very high-risk. 38% of patients with intermediate ROM were up-or down-classified. 56% of patients with low ROM were reclassified to very low-risk. Overall, 42% of patients had a change in classification. 35% of the study cohort could potentially have avoided additional unnecessary procedures with subsequent guideline-adherent management. CONCLUSIONS: The classifier can guide decision-making following a nondiagnostic bronchoscopy, reclassifying risk in a significant percentage of cases. Use of the classifier should allow more patients with early-stage cancer to proceed directly to curative therapy while helping more patients with benign disease avoid further unnecessary procedures.

Does transbronchial lung cryobiopsy improve diagnostic yield of digital tomosynthesis-assisted electromagnetic navigation guided bronchoscopic biopsy of pulmonary nodules? A pilot study.

INTRODUCTION: Bronchoscopic biopsies have limited sensitivity for small, peripheral lung nodules. Electromagnetic navigation guided bronchoscopy (ENB) with fluoroscopic digital tomosynthesis and a 1.1 mm cryoprobe for transbronchial lung cryobiopsy (TBLC) may improve diagnostic yield. We evaluated the diagnostic yield and safety of this approach. METHODS: 42 patients (45 nodules) underwent sequential biopsies by transbronchial needle aspiration (TBNA), then forceps biopsy (FB), and finally TBLC. Demographic data, nodule characteristics, biopsy results, and procedural complications were recorded. RESULTS: Nodules were predominantly solid (n = 35, 78%), without a bronchus sign (n = 30, 67%), and 33% (n = 15) were <2 cm in all dimensions (mean axial: 25.7 ± 15.3 mm, coronal: 21.0 ± 10.1 mm, sagittal 25.5 ± 16.5 mm). TBNA was the most informative biopsy modality (31/45 diagnoses total, five unique, 69% modality diagnostic yield (MDY)) compared to FB (27/45, one unique, 60% MDY) or TBLC (27/45, six unique, 60% MDY). FB contributed four additional diagnoses, improving diagnostic yield to 80% (36/45). TBLC contributed six additional diagnoses for a final diagnostic yield of 93% (42/45). No bleeding that required intervention or pneumothoraxes occurred. In unadjusted logistic regression models, solid nodules had increased odds of obtaining a diagnosis with TBNA (OR: 5.06; 95% CI: 1.14-22.49) and increased axial dimension nodule size had increased odds of obtaining a diagnosis with TBLC (OR: 1.10; 95% CI: 1.02-1.19). CONCLUSION: ENB guided TBLC of lung nodules appears safe and may increase the final diagnostic yield when combined with other modalities. Future studies identifying nodule characteristics and comparing biopsy tools may clarify the most efficacious approach to maximize yield and minimize risk.

Size and vision: Impact of fluoroscopic navigation, digital tomosynthesis, and continuous catheter tip tracking on diagnostic yield of small, bronchus sign negative lung nodules.

INTRODUCTION: Accurate biopsies of lung nodules, including small (<2 cm), bronchus sign negative lesions, remain challenging. Technological advances, however, may improve outcomes. We describe our experience using a novel system combining fluoroscopic navigation with digital tomosynthesis and continuous catheter tip tracking to guide lung nodule biopsies. METHODS: Demographic data, procedural characteristics, and biopsy results from prospectively enrolled patients were collected. RESULTS: 159 nodules (144 patients) were biopsied. Average nodule size was 22.2 ± 15.2 mm (axial), 21.7 ± 13.9 mm (coronal), and 33.2 ± 20.5 mm (sagittal), with 45% (n = 72) <2 cm in all dimensions and 66% (n = 105) without a bronchus sign. Diagnostic yield was 84% (134/159), with malignancy (n = 75, 47%) most common. A diagnosis was obtained in 75% (n = 54/72) of lesions that were <2 cm in all dimensions and 79% (n = 83/105) of bronchus sign negative lesions. Unadjusted generalized mixed-effects logistic regression models showed that nodule size as a categorical variable (>2 cm in any dimension) and as a continuous variable in the coronal dimension, the presence of a bronchus sign, and a concentric radial EBUS view had an increased odds ratio for diagnosis. A concentric radial EBUS view also had an increased OR for diagnosis in a fully adjusted mixed-effects logistic regression model. CONCLUSION: Fluoroscopic navigation with digital tomosynthesis and continuous catheter tip tracking shows an overall improved diagnostic accuracy compared to historical controls, including for small, bronchus sign negative lesions. Future studies clarifying the optimal modality for patients with different nodules will be of importance to provide the most appropriate procedure tailored to each individual lesion's unique characteristics.

Efficacy and Safety of Cone-Beam CT Augmented Electromagnetic Navigation Guided Bronchoscopic Biopsies of Indeterminate Pulmonary Nodules.

Bronchoscopic biopsy results for indeterminate pulmonary nodules remain suboptimal. Electromagnetic navigation bronchoscopy (ENB) coupled with cone beam computed tomography (CBCT) for confirmation has the potential to improve diagnostic yield. We present our experience using this multimodal approach to biopsy 17 indeterminate nodules in 14 consecutive patients from April to August 2021. Demographic information, nodule characteristics, and biopsy results were recorded. Procedures were performed in a hybrid operating room equipped with a Siemens Artis Q bi-plane CBCT (Siemens, Munich, Germany). After ENB using the superDimension version 7.1 (Medtronic, Plymouth, MN, USA) to target the lesion, radial endobronchial ultrasound was used as secondary confirmation. Next, transbronchial needle aspiration was performed prior to CBCT to evaluate placement of the biopsy tool in the lesion. The average nodule size was 21.7+/−15 mm with 59% (10/17) < 2 cm in all dimensions and 35% (6/17) showing a radiographic bronchus sign. The diagnostic yield of CBCT-guided ENB was 76% (13/17). No immediate periprocedural or postprocedural complications were identified. Our experience with CBCT-guided ENB further supports the comparable efficacy and safety of this procedure compared to other mature biopsy modalities. Studies designed to optimize the lung nodule biopsy process and to determine the contributions from different procedural aspects are warranted.

An 80-year-old woman with myelofibrosis and diffuse mosaic attenuation on chest computed tomography.

An 80-year-old woman with myelofibrosis sought evaluation for progressive dyspnea. Her past medical history included essential thrombocytosis, which transformed to myelofibrosis. Inspiratory computed tomography of chest showed diffuse mosaic attenuation with lymphadenopathy. Flexible bronchoscopy with lymph node and pulmonary parenchymal cryo biopsy revealed nodular deposits of extramedullary hematopoiesis in lung parenchyma and moderate to severe vascular medial and intimal thickening of pulmonary vasculature consistent with pulmonary parenchymal extramedullary hematopoiesis associated with pulmonary hypertension (a rare compensatory mechanism in myeloproliferative disorders). In this report, we explore the manifestations, pathogenesis, treatment, and prognosis of pulmonary extramedullary hematopoiesis reported in the literature.

A wolf in sheep's clothing: Dogs confer an unrecognized risk for their immunocompromised master.

Bordetella bronchiseptica is a pleomorphic gram-negative coccobacillus that commonly causes respiratory tract infections in canines, felines, and swine. Human infections are rare. We report a case of Bordetella bronchiseptica pneumonia in a 67-year-old immunocompromised host. His past medical history included multiple myeloma treated with autologous bone marrow transplant followed by a chimeric antigen receptor cell therapy for relapse. He was admitted with unrelenting diarrhea due to HHV-6 pancolitis. During the hospital course he developed high-grade fever (102.3°F), cough and respiratory failure requiring mechanical ventilation. Chest imaging demonstrated bilateral opacities most pronounced at lung bases and worsening mediastinal lymphadenopathy. Bronchoalveolar lavage cultures grew Bordetella bronchiseptica. He was treated with piperacillin/tazobactam, but developed progressive multiorgan failure, transitioned to comfort care, and expired in the hospital. Bordetella bronchiseptica is an organism that do not cause serious infection in immunocompetent persons but can sometimes cause serious illness in immunocompromised populations. It causes "kennel cough" in dogs and spready by respiratory droplets. Dogs and cats are not uniformly vaccinated against this pathogen. Therefore, transmission through animal contact is becoming increasingly common. Realize that unlike other Bordetella spp, this pathogen is not typically responsive to erythromycin and is often resistant to ampicillin and cephalosporins so the typical neutropenic fever coverage with an antipseudomonal cephalosporin and azithromycin might not be effective. Given the increasing recognition of this zoonosis as a threat to the immunocompromised, it is essential to educate immunocompromised patients to minimize zoonotic exposure, as immunization of pets might not confer protection to humans.

Photodynamic therapy for treatment of recurrent adenocarcinoma of the lung with tracheal oligometastasis.

Introduction: Tracheal neoplasms account for less than 0.1% of all malignancies. The majority of tracheal malignancies are secondary neoplasms from direct tracheal invasion from adjacent structures and less commonly from hematogenous or lymphatic spread from distal malignancies. Evidence-based guidelines for management are lacking. Less invasive bronchoscopic ablation modalities are an option for non-operable patients. We report a case of endotracheal oligometastatic adenocarcinoma successfully treated with photodynamic therapy. Case: A 59-year-old man with past medical history of stage 1 right upper and left upper lobe neoplasm treated with right lobectomy 2 years ago and wedge resection of the lingula ten months ago presented with cough and hemoptysis. Flexible bronchoscopy revealed a 10 mm endoluminal exophytic lesion of the mid-trachea confirmed as lung adenocarcinoma on biopsy. Considering the lack of extra-cartilaginous spread and the small size, a multidisciplinary team recommended local treatment using photodynamic therapy. Surveillance biopsies out to 2 years confirmed lack of disease recurrence. The patient did not experience any adverse effects. Conclusion: PDT as first line therapy for a 10 mm oligometastatic endotracheal adenocarcinoma from recurrent pulmonary malignancy with no extra-cartilaginous spread is an effective modality that is well tolerated and produces a durable response, which in our patient led to complete response without recurrence at 24 months and with no adverse effects or complications. Determining depth of tumor penetration is paramount if the treatment is with curative intent. PDT should be considered as part of a multidisciplinary approach for endotracheal malignant disease.

Off-label use of intrabronchial valves for persistent air leak is safe and effective: a retrospective case analysis.

Background: Persistent air leak (PAL) is a challenging clinical problem associated with prolonged hospital stay and increased morbidity. Historically, treatment options were limited to thoracostomy tube drainage, pleurodesis, and surgical repair. The development of one-way airway valves has represented a paradigm shift in PAL management. We present our experience using intrabronchial valves (IBVs) for PAL management looking at both on-label (post-thoracic surgery) and off-label (all other) indications. Methods: We performed a retrospective review of our single-center experience. Data collected included demographics, primary pathology leading to PAL, comorbidities, time to chest tube removal, complications, mortality, need for any additional procedure, and time to IBV removal. Results: During the study period, 15 patients underwent IBV insertion for PAL. The on-label cohort contained three patients (post lobectomy or segmentectomy). The off-label cohort had 12 patients (6 empyema, 4 secondary spontaneous pneumothorax, 1 penetrating trauma, and 1 post percutaneous lung nodule biopsy). In the on-label cohort, chest tube was removed after a mean duration of 4.0±1.0 days for all patients. In the off-label cohort, 83.3% (10/12) had chest tube removal 16.2±5.7 days (P=0.396) after IBV placement. One patient developed hypoxic respiratory failure shortly after IBV insertion, necessitating removal of 2 out of 5 valves. Conclusions: IBVs are a minimally invasive, well tolerated treatment modality for patients with PAL and a viable alternative to invasive surgical interventions. Procedure or valve-related complications are uncommon. Valves can be removed and do not preclude surgical intervention. Updated guidelines are necessary to formalize PAL management.

A 39-Year-Old Woman With Synchronous Endobronchial and Adrenal Tumors.

CASE PRESENTATION: A 39-year-old woman with systemic lupus erythematosus that was complicated by end-stage renal disease that had required a deceased donor renal transplant 16 years ago was referred for evaluation of chronic, nonproductive cough for 2 years. She was a lifetime nonsmoker whose condition was maintained on prednisone 5 mg daily, tacrolimus 3 mg twice day, mycophenolate mofetil 500 mg twice a day for her immunosuppression regimen, valacyclovir 500 mg twice a day for prophylaxis, and clonidine 0.1 mg daily and metoprolol succinate 100 mg twice daily for hypertension.

Venovenous Extracorporeal Membrane Oxygenation to Facilitate Removal of Endobronchial Tumors.

Short-term extracorporeal membrane oxygenation is a useful adjunct to thoracic procedures. We report the cases of 2 middle-aged men who were supported with venovenous extracorporeal membrane oxygenation to facilitate tumor debulking and recanalization of the carina and mainstem bronchi. Neither patient had major complications or adverse events. These cases suggest that short-term extracorporeal membrane oxygenation is safe in patients undergoing complex resection or debulking of endobronchial lesions.

A Woman in Her Late 40s with Hypersensitivity Pneumonitis and Recurrent Pleural Effusions.

CASE PRESENTATION: A woman in her late 40s with a history of recurrent deep vein thromboses and hypersensitivity pneumonitis (HP) presented to the ED with progressive exertional dyspnea and productive cough. She recently had started oral corticosteroids after HP was confirmed via transbronchial lung cryobiopsy from both the right upper and lower lobes, which showed poorly formed granulomas with mild interstitial and perivascular lymphocytic infiltrates. A causative antigen for her HP was never clearly identified.