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Abstract Rationale Technological advances have improved the ability of bronchoscopists to access peripheral pulmonary lesions for tissue sampling. Radial probe endobronchial ultrasound (EBUS) provides real-time feedback to guide biopsies of peripheral lesions, thereby potentially improving diagnostic yield over conventional bronchoscopy. Objectives We assessed the overall diagnostic yield of peripheral bronchoscopy using radial probe EBUS for peripheral pulmonary lesions, as well as factors that might influence the diagnostic yield, such as radial ultrasound view, lesion size, and ability to locate the peripheral lesion. Methods We conducted a retrospective review of peripheral bronchoscopy cases in which radial probe EBUS was utilized to diagnose peripheral pulmonary lesions at a tertiary care university hospital. Measurements and Main Results Our study cohort comprised 496 patients who underwent bronchoscopies between January 2008 and December 2012 for the diagnosis of peripheral pulmonary lesions. Radial probe EBUS was used alone for diagnostic purposes in 467 patients. A diagnosis was made on that basis in 321 (69%) of 467 patients. A diagnosis was obtained for 83 of 144 (58%) of nodules 1–2 cm in diameter, 99 of 137 (72%) of nodules 2.1–3 cm, 54 of 70 (77%) of nodules 3.1–4 cm, 41 of 47 (87%) of nodules 4.1–5 cm, and 35 of 40 (88%) of nodules larger than 5.1 cm. Of all 467 nodules, 446 (96%) were successfully identified using radial probe EBUS. When the radial probe position was within the target lesion, the diagnostic yield was 84% compared with 48% when the probe was positioned adjacent to the lesion. Conclusions Radial probe EBUS can be used to guide biopsy during peripheral bronchoscopy. This technique provides real-time ultrasound-based confirmation of target lesion localization prior to biopsy. Using radial probe EBUS, the vast majority of peripheral pulmonary nodules can be identified. Radial EBUS probe position relative to the target lesion significantly affects the diagnostic yield.

Background Targeted lung denervation (TLD), a novel bronchoscopic procedure which attenuates pulmonary nerve input to the lung to reduce the clinical consequences of neural hyperactivity, may be an important emerging treatment for COPD. While procedural safety and impact on clinical outcomes have recently been reported, the mechanism of action has not been reported. We explored the long-term pathologic and histopathologic effects in a sheep model of ablation of bronchial branches of the vagus nerve using a novel dual-cooled radiofrequency ablation catheter. Methods Nineteen sheep underwent circumferential ablation of both main bronchi with simultaneous balloon surface cooling using a targeted lung denervation system (Nuvaira, Inc., USA). Animals were followed over an extended time course (30, 365, and 640 days post procedure). At each time point, lung denervation (axonal staining in bronchial nerves), and effect on peribronchial structures near the treatment site (histopathology of bronchial epithelium, bronchial cartilage, smooth muscle, alveolar parenchyma, and esophagus) were quantified. One way analysis of variance (ANOVA) was performed to reveal differences between group means on normal data. Non-parametric analysis using Kruskal-Wallis Test was employed on non-normal data sets. Results No adverse clinical effects were observed in any sheep. Nerve axon staining distal to the ablation site was decreased by 60% at 30 days after TLD and efferent axon staining was decreased by >70% at 365 and 640 days. All treated airways exhibited 100% epithelial integrity. Effect on peribronchial structures was strictly limited to lung tissue immediately adjacent to the ablation site. Tissue structure 1 cm proximal and distal to the treatment area remained normal, and the pulmonary veins, pulmonary arteries, and esophagus were unaffected. Conclusions The denervation of efferent axons induced by TLD therapy is durable and likely a contributing mechanism through which targeted lung denervation impacts clinical outcomes. Further, long term lung denervation did not alter the anatomy of the bronchioles or lung, as evaluated from both a gross and histologic perspective.

Background Targeted lung denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung reducing clinical consequences of cholinergic hyperactivity. The AIRFLOW-1 study assessed safety and TLD dose in patients with moderate-to-severe, symptomatic COPD. This analysis evaluated the long-term impact of TLD on COPD exacerbations, pulmonary function, and quality of life over 3 years of follow up. Methods TLD was performed in a prospective, energy-level randomized (29 W vs 32 W power), multicenter study (NCT02058459). Additional patients were enrolled in an open label confirmation phase to confirm improved gastrointestinal safety after procedural modifications. Durability of TLD was evaluated at 1, 2, and 3 years post-treatment and assessed through analysis of COPD exacerbations, pulmonary lung function, and quality of life. Results Three-year follow-up data were available for 73.9% of patients (n = 34). The annualized rate of moderate to severe COPD exacerbations remained stable over the duration of the study. Lung function (FEV 1 , FVC, RV, and TLC) and quality of life (SGRQ-C and CAT) remained stable over 3 years of follow-up. No new gastrointestinal adverse events and no unexpected serious adverse events were observed. Conclusion TLD in COPD patients demonstrated a positive safety profile out to 3 years, with no late-onset serious adverse events related to denervation therapy. Clinical stability in lung function, quality of life, and exacerbations were observed in TLD treated patients over 3 years of follow up.

Background: Targeted lung denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung. Parasympathetic input to the heart originating from the lungs contributes to respiratory sinus arrhythmia (RSA) and disruption of pulmonary nerves via TLD may impact RSA. Objective: The aim of this study was to assess the potential of TLD to affect RSA in sheep and humans. Methods: TLD was performed in 5 sheep and 9 humans using a novel lung denervation system (Nu­vaira Inc., Minneapolis, MN, USA) with an electrocardiogram collected before and after the procedure. Frequency domain analysis of heart rate variability was performed in 5 sheep and 6 humans with presence of RSA approximated as high-frequency power (HF power). Results: HF power decreased in 3 of 5 sheep with 1 animal reaching less than 7% of its baseline HF power 30 days after TLD. The average treatment location was more distal in the remaining 2 animals, which did not exhibit RSA attenuation, suggesting diminished denervation. HF power decreased in 5 of 6 humans, with 3 subjects reaching less than 50% of their baseline HF power 90 days after TLD. Conclusions: TLD appeared to attenuate RSA in both sheep and human cohorts of this sub-study. Further confirmation in humans is necessary to allow for RSA attenuation to be used as a marker of successful lung denervation via TLD.

An amendment to this paper has been published and can be accessed via the original article.

To evaluate the safety and efficacy of bronchoscopic balloon dilation (BBD) without fluoroscopy for relief of tracheobronchial obstruction. We performed a retrospective study of all adult patients who underwent BBD without fluoroscopy at the Tulane University Hospital and Clinic between July 1, 1997, and June 30, 2002. Twenty-four patients (mean [± SD] age, 58 ± 14 years; 80% men) underwent 59 BBD procedures without fluoroscopy for the following conditions: iatrogenic tracheal stenosis (80%); saber-sheath trachea (4%); bronchial stenosis resulting from lung transplantation (4%); sarcoidosis (4%); Wegener granulomatosis (4%); and idiopathic stenosis (4%). All BBD procedures were performed via a rigid bronchoscope (61%) or a flexible bronchoscope (39%) without fluoroscopy. BBD was often combined with mechanical debridement (64%), stent placement (47%), or laser photoresection (19%), although in 26% of cases BBD was the only intervention. During the 59 procedures, 71 different balloon catheters were deployed a total of 112 times (deployment was defined as any use of balloon dilation in a different location, for a different purpose, or to a different inflation diameter). These 112 deployments were performed for primary dilation (49%), dilation prior to stent placement (28%), and stent seating (22%). Improvement in stenosis was achieved immediately postprocedure in all 59 procedures (100%). One balloon ruptured during inflation without clinically significant effect, and no other complications occurred. BBD without fluoroscopy for the relief of nonmalignant tracheobronchial obstruction can be safely performed through a rigid or flexible bronchoscope. It can be used alone or as an adjunct to other therapeutic modalities. In this series, 100% of airway obstructions were improved, and there were no clinically significant complications. BBD of a tracheobronchial obstruction without fluoroscopy is safe, efficacious, and cost-effective.

Patients with malignant pleural effusions have significant dyspnea and shortened life expectancy. Indwelling pleural catheters allow patients to drain pleural fluid at home and can lead to autopleurodesis. The optimal drainage frequency to achieve autopleurodesis and freedom from catheter has not been determined. To determine whether an aggressive daily drainage strategy is superior to the current standard every other day drainage of pleural fluid in achieving autopleurodesis. Patients were randomized to either an aggressive drainage (daily drainage; n = 73) or standard drainage (every other day drainage; n = 76) of pleural fluid via a tunneled pleural catheter. The primary outcome was the incidence of autopleurodesis following the placement of the indwelling pleural catheters. The rate of autopleurodesis, defined as complete or partial response based on symptomatic and radiographic changes, was greater in the aggressive drainage arm than the standard drainage arm (47% vs. 24%, respectively; P = 0.003). Median time to autopleurodesis was shorter in the aggressive arm (54 d; 95% confidence interval, 34-83) as compared with the standard arm (90 d; 95% confidence interval, 70 to nonestimable). Rate of adverse events, quality of life, and patient satisfaction were not significantly different between the two arms. Among patients with malignant pleural effusion, daily drainage of pleural fluid via an indwelling pleural catheter led to a higher rate of autopleurodesis and faster time to liberty from catheter. Clinical trial registered with www.clinicaltrials.gov (NCT 00978939).

New therapies are needed for patients with severe persistent asthma who cannot achieve control with current therapy of inhaled corticosteroids and long-acting β2-agonists. Bronchial thermoplasty is a novel intervention for asthma that delivers controlled thermal energy to the airway wall during a series of bronchoscopies, resulting in a prolonged reduction in airway smooth muscle mass. We review the method of performing bronchial thermoplasty with the Alair System, how to appropriately select and manage patients undergoing bronchial thermoplasty, and the clinical experience to date with this treatment. Randomized, controlled clinical trials with bronchial thermoplasty in subjects with severe asthma have resulted in improvements in overall asthma control as demonstrated by significant improvement in quality of life, asthma symptoms, severe exacerbations requiring corticosteroids, days lost from work/school/other daily activities due to asthma, and healthcare utilization.

Background Parasympathetic pulmonary nerves release acetylcholine that induces smooth muscle constriction. Disruption of parasympathetic pulmonary nerves improves lung function and COPD symptoms. Aims To evaluate ‘targeted lung denervation’ (TLD), a novel bronchoscopic therapy based on ablation of parasympathetic pulmonary nerves surrounding the main bronchi, as a potential therapy for COPD. Methods This 1-year, prospective, multicentre study evaluated TLD in patients with COPD forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) (FEV1/FVC <0.70; FEV1 30%–60% predicted). Patients underwent staged TLD at 20 watts (W) or 15 W following baseline assessment off bronchodilators. Assessments were repeated on tiotropium before treatment and off bronchodilators at 30, 90, 180, 270 and 365 days after TLD. The primary endpoint was freedom from documented and sustained worsening of COPD directly attributable to TLD to 1 year. Secondary endpoints included technical feasibility, change in pulmonary function, exercise capacity, and quality of life. Results Twenty-two patients were included (n=12 at 20 W, n=10 at 15 W). The procedures were technically feasible 93% of the time. Primary safety endpoint was achieved in 95%. Asymptomatic bronchial wall effects were observed in 3 patients at 20 W. The clinical safety profiles were similar between the two energy doses. At 1 year, changes from baseline in the 20 W dose compared to the 15 W dose were: FEV1 (+11.6%±32.3 vs +0.02%±15.1, p=0.324), submaximal cycle endurance (+6.8 min±12.8 vs 2.6 min±8.7, p=0.277), and St George's Respiratory Questionnaire (−11.1 points ±9.1 vs −0.9 points ±8.6, p=0.044). Conclusions Bronchoscopic TLD, based on the concept of ablating parasympathetic pulmonary nerves, was feasible, safe, and well tolerated. Further investigation of this novel therapy is warranted. Trial registration number NCT01483534.

Targeted lung denervation (TLD) is a novel bronchoscopic therapy for COPD which ablates parasympathetic pulmonary nerves running along the outside of the two main bronchi with the intent of inducing permanent bronchodilation. The goal of this study was to evaluate the feasibility and long-term safety of bilateral TLD during a single procedure. This prospective, multicenter study evaluated 15 patients with moderate-to-severe COPD (forced expiratory volume in 1 s [FEV ] 30%-60%) who underwent bilateral TLD treatment following baseline assessment without bronchodilators. The primary safety end point was freedom from documented and sustained worsening of COPD directly attributable to TLD up to 1 year. Secondary end points included technical feasibility, change in pulmonary function tests, exercise capacity, and health-related quality of life. Follow-up continued up to 3 years for subjects who reconsented for longer-term follow-up. A total of 15 patients (47% male, age 63.2±4.0 years) underwent TLD with a total procedure time of 89±16 min, and the total fluoroscopy time was 2.5±2.7 min. Primary safety end point of freedom from worsening of COPD was 100%. There were no procedural complications reported. Results of lung function analysis and exercise capacity demonstrated similar beneficial effects of TLD without bronchodilators, when compared with long-acting anticholinergic therapy at 30 days, 180 days, 365 days, 2 years, and 3 years post-TLD. Five of the 12 serious adverse events that were reported through 3 years of follow-up were respiratory related with no events being related to TLD therapy. TLD delivered to both lungs in a single procedure is feasible and safe with few respiratory-related adverse events through 3 years.