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Background The Robotic Endoscopic System (Auris Health, Inc., Redwood City, CA) has the potential to overcome several limitations of contemporary guided-bronchoscopic technologies for the diagnosis of lung lesions. Our objective is to report on the initial post-marketing feasibility, safety and diagnostic yield of this technology. Methods We retrospectively reviewed data on consecutive cases in which robot-assisted bronchoscopy was used to sample lung lesions at four centers in the US (academic and community) from June 15th, 2018 to December 15th, 2018. Results One hundred and sixty-seven lesions in 165 patients were included in the analysis, with an average follow-up of 185 ± 55 days. The average size of target lesions was 25.0 ± 15.0 mm. Seventy-one percent were located in the peripheral third of the lung. Pneumothorax and airway bleeding occurred in 3.6 and 2.4% cases, respectively. Navigation was successful in 88.6% of cases. Tissue samples were successfully obtained in 98.8%. The diagnostic yield estimates ranged from 69.1 to 77% assuming the cases of biopsy-proven inflammation without any follow-up information ( N  = 13) were non-diagnostic and diagnostic, respectively. The yield was 81.5, 71.7 and 26.9% for concentric, eccentric and absent r-EBUS views, respectively. Diagnostic yield was not affected by lesion size, density, lobar location or centrality. Conclusions RAB implementation in community and academic centers is safe and feasible, with an initial diagnostic yield of 69.1–77% in patients with lung lesions that require diagnostic bronchoscopy. Comparative trials with the existing bronchoscopic technologies are needed to determine cost-effectiveness of this technology.

Background The increasing use of low-dose CT (LDCT) screening has significantly enhanced the detection of pulmonary nodules, particularly in early-stage lung cancer. However, diagnosing peripheral pulmonary nodules (PPNs) presents unique challenges due to their distal location, rendering traditional methods like CT-guided biopsy less effective and associated with higher complication risks. Robotic-assisted bronchoscopy (RAB) has emerged as a promising minimally invasive technology that offers improved diagnostic accuracy and safety. Methods This review explores recent advancements in RAB technology for PPN diagnosis, focusing on the integration of multimodal imaging innovations. These include shape-sensing technology, electromagnetic navigation bronchoscopy (ENB), radial endobronchial ultrasound (rEBUS), cone-beam CT (CBCT), and needle-based confocal laser endomicroscopy (nCLE). Additionally, advanced biopsy techniques such as transbronchial cryobiopsy (TBCB) are discussed for their contributions to improving diagnostic yield. Results The integration of multimodal imaging technologies has significantly enhanced the precision of navigation and biopsy, reducing the risk of complications associated with traditional methods. Comparative studies show that RAB achieves similar or superior diagnostic outcomes compared to conventional approaches, with improved lesion targeting and tissue sampling. The use of techniques like TBCB has further improved the diagnostic yield and quality of tissue samples. Conclusions RAB represents a safer and more accurate alternative to conventional biopsy methods for diagnosing peripheral pulmonary nodules. The combined use of advanced imaging and biopsy techniques has solidified RAB’s clinical utility, making it a promising tool for current and future developments in pulmonary nodule diagnosis.

The single pulmonary nodule evaluation is a complex problem. In particular, attempts to biopsy peripheral nodules with bronchoscopy have been hampered by difficulty navigating to the correct airway and then confirming the instruments' proximity to the nodule. Virtual systems in use do not provide real-time feedback of a live image of the nodule in question. Fluoroscopy has traditionally offered limited assistance as often the nodule is not visible and provides no information on airways/pathways to the nodule. We describe the use of LungVision augmented fluoroscopy to aid in real-time navigation assistance to peripheral lung nodules.

Asthma is a heterogeneous, complex syndrome, and identifying asthma endotypes has been challenging. We hypothesize that distinct endotypes of asthma arise in disparate genetic variation and life-time environmental exposure backgrounds, and that disease comorbidity patterns serve as a surrogate for such genetic and exposure variations. Here, we computationally discover 22 distinct comorbid disease patterns among individuals with asthma (asthma comorbidity subgroups) using diagnosis records for >151 M US residents, and re-identify 11 of the 22 subgroups in the much smaller UK Biobank. GWASs to discern asthma risk loci for individuals within each subgroup and in all subgroups combined reveal 109 independent risk loci, of which 52 are replicated in multi-ancestry meta-analysis across different ethnicity subsamples in UK Biobank, US BioVU, and BioBank Japan. Fourteen loci confer asthma risk in multiple subgroups and in all subgroups combined. Importantly, another six loci confer asthma risk in only one subgroup. The strength of association between asthma and each of 44 health-related phenotypes also varies dramatically across subgroups. This work reveals subpopulations of asthma patients distinguished by comorbidity patterns, asthma risk loci, gene expression, and health-related phenotypes, and so reveals different asthma endotypes. Asthma is a heterogeneous, complex syndrome that arises in individuals with various genetic and exposure variations. Here, the authors show that disease comorbidity patterns can serve as a surrogate for these variations, and identify asthma endotypes distinguished by comorbidity patterns, asthma risk loci, gene expression, and health-related phenotypes.

Background Endobronchial microwave ablation via flexible catheter offers the potential for local therapy for inoperable peripheral lung cancer. The study aimed to evaluate the feasibility and safety of navigation bronchoscopy‐guided water‐cooled microwave ablation catheter for nonsurgical peripheral lung cancer. Methods This was a prospective single arm pilot study. Patients with early stage or multiple primary peripheral lung cancer who were nonsurgical candidates for surgery were enrolled in the study. Bronchoscopic microwave ablation was performed via a flexible water‐cooled microwave ablation antenna under the guidance of navigation bronchoscopy. Radial probe endobronchial ultrasound combined with fluoroscopy was used to confirm the position. Treatment outcomes were evaluated based on follow‐up chest CT and positron emission tomography scans. Primary endpoints were technical success and safety. Secondary endpoints were complete ablation rate, 2‐year local control rate, and progression‐free survival. Results Thirteen patients were enrolled in the study from April 2018 to July 2019. A total of 19 sessions of microwave ablation were performed on 14 tumors under the guidance of navigation bronchoscopy. The technical success was 100%. Treatment‐related complications occurred in two patients. The complete ablation rate was 78.6% (11/14). The 2‐year local control rate was 71.4%. Median progression‐free survival was 33 months for all patients. Conclusions In this pilot study, bronchoscopic microwave ablation appears to be feasible with acceptable occurrence of complication in the treatment of peripheral lung cancer under the guidance of navigation bronchoscopy. Thirteen patients with early stage or multiple primary nonsurgical peripheral lung cancer underwent navigation bronchoscopy‐guided water‐cooled microwave ablation. Technical success was 100%. Treatment‐related complications occurred in two patients. The study demonstrated that bronchoscopic microwave ablation was feasible in the treatment of peripheral lung cancer.

Bronchial thermoplasty is an alternative treatment for patients with severe, uncontrolled asthma in which the airway smooth muscle is eliminated using radioablation. Although this emerging therapy shows promising outcomes, little is known about its effects on airway inflammation. We examined the presence of bronchoalveolar lavage cytokines and expression of smooth muscle actin in patients with severe asthma before and in the weeks after bronchial thermoplasty. Endobronchial biopsies and bronchoalveolar lavage samples from 11 patients with severe asthma were collected from the right lower lobe before and 3 and 6 weeks after initial bronchial thermoplasty. Samples were analyzed for cell proportions and cytokine concentrations in bronchoalveolar lavage and for the presence of α-SMA in endobronchial biopsies. α-SMA expression was decreased in endobronchial biopsies of 7 of 11 subjects by Week 6. In bronchoalveolar lavage fluid, both transforming growth factor-β1 and regulated upon activation, normal T-cell expressed and secreted (RANTES)/CCL5 were substantially decreased 3 and 6 weeks post bronchial thermoplasty in all patients. The cytokine tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL), which induces apoptosis in several cell types, was increased in concentration both 3 and 6 weeks post bronchial thermoplasty. Clinical improvement and reduction in α-SMA after bronchial thermoplasty in severe, uncontrolled asthma is associated with substantial changes in key mediators of inflammation. These data confirm the substantial elimination of airway smooth muscle post thermoplasty in the human asthmatic airway and represent the first characterization of significant changes in airway inflammation in the first weeks after thermoplasty.

Diagnosis of lung cancer at advanced stages can result in missed treatment opportunities, worse outcomes, and higher health care costs. This study evaluated the wait time to diagnose non-small-cell lung cancer (NSCLC) and the cost of diagnosis and treatment based on the stage at diagnosis. Adult patients diagnosed with NSCLC between January 2007 and September 2011 were identified from a proprietary oncology registry and linked to health insurance claims from a large US health insurance company. Continuous enrollment in the health plan was required for at least 12 months prediagnosis (baseline) and at least 3 months postdiagnosis (follow-up). Use of diagnostic tests and time to diagnosis were examined. The rates of health care utilization and per-patient per-month (PPPM) health care costs were calculated. A total of 1,210 patients with NSCLC were included in the analysis. Most patients (93.6%) had evidence of diagnostic tests beginning 5 to 6 months prior to diagnosis, and most were diagnosed at an advanced stage (23% Stage IIIb and 46% Stage IV). The PPPM total health care costs in USD pre- and postdiagnosis were $2,407±$3,364 (mean±standard deviation) and $16,577±$33,550, respectively. PPPM total health care costs and utilization after lung cancer diagnosis were significantly higher among patients diagnosed at Stage IV disease and lowest among patients diagnosed at Stage I disease ($7,239 Stage I, $9,484 Stage II, $11,193 Stage IIIa, $17,415 Stage IIIb, and $21,441 Stage IV). This study showed that most patients experienced long periods of delay between their first diagnostic test for lung cancer and a definitive diagnosis, and the majority were diagnosed at advanced stages of disease. Costs associated with the management of lung cancer increased substantially with higher stages at diagnosis. Procedures that diagnose lung cancer at earlier stages may allow for less resource use and costs among patients with lung cancer.

Defects in the innate immune system in the lung with attendant bacterial infections contribute to lung tissue damage, respiratory insufficiency, and ultimately death in the pathogenesis of cystic fibrosis (CF). Professional phagocytes, including alveolarmacrophages (AMs), have specialized pathways that ensure efficient killing of pathogens in phagosomes. Phagosomal acidification facilitates the optimal functioning of degradative enzymes, ultimately contributing to bacterial killing. Generation of low organellar pH is primarily driven by the V-ATPases, proton pumps that use cytoplasmic ATP to load H⁺ into the organelle. Critical to phagosomal acidification are various channels derived from the plasma membrane, including the anion channel cystic fibrosis transmembrane conductance regulator, which shunt the transmembrane potential generated by movement of protons. Here we show that the transient receptor potential canonical-6 (TRPC6) calcium-permeable channel in the AMalso functions to shunt the transmembrane potential generated by proton pumping and is capable of restoring microbicidal function to compromised AMs in CF and enhancement of function in non-CF cells. TRPC6 channel activity is enhanced via translocation to the cell surface (and then ultimately to the phagosome during phagocytosis) in response to G-protein signaling activated by the small molecule (R)-roscovitine and its derivatives. These data show that enhancing vesicular insertion of the TRPC6 channel to the plasma membrane may represent a general mechanism for restoring phagosome activity in conditions, where it is lost or impaired.

A 36-year-old woman with rheumatoid arthritis who was receiving systemic immunotherapy died from disseminated histoplasmosis while participating in a gene-therapy trial of a tumor necrosis factor α antagonist delivered through an adeno-associated viral vector delivery system and administered by intraarticular injection. A 36-year-old woman with rheumatoid arthritis who was receiving systemic immunotherapy died from disseminated histoplasmosis while participating in a gene-therapy trial of a tumor necrosis factor α antagonist. Rheumatoid arthritis is a chronic inflammatory disease that is characterized by autoimmune destruction of multiple joints, causing substantial pain, swelling, and loss of mobility. 1 TNF-α inhibitors have represented a dramatic improvement in the treatment of rheumatoid arthritis; they include the two antibodies infliximab and adalimumab, as well as etanercept, a dimeric fusion protein that combines an immunoglobulin domain with a TNF-receptor domain (TNFR:Fc). 2 , 3 Trials of TNF-α inhibitors delivered with the use of gene-therapy methods in patients with rheumatoid arthritis are increasing in number. 4 The most common vectors used in models of rheumatoid arthritis are viral vectors such as lentivirus, . . .

Bronchial thermoplasty (BT) is a novel therapy for patients with severe asthma. Using radio frequency thermal energy, it aims to reduce the airway smooth muscle mass. Several clinical trials have demonstrated improvements in asthma-related quality of life and a reduction in the number of exacerbations following treatment with BT. In addition, recent data has demonstrated the long-term safety of the procedure as well as sustained improvements in rates of asthma exacerbations, reduction in health care utilization, and improved quality of life. Further study is needed to elucidate the underlying mechanisms that result in these improvements. In addition, improved characterization of the asthma subphenotypes likely to exhibit the largest clinical benefit is a critical step in determining the precise role of BT in the management of severe asthma.