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Interventional Pulmonology for Asthma and Emphysema: Bronchial Thermoplasty and Bronchoscopic Lung Volume Reduction Russell J. Miller, MD1

Septimiu D. Murgu, MD2

1 Divisions of Pulmonary and Critical Care Medicine, Navy Medical

Center San Diego, San Diego, California 2 Divisions of Pulmonary and Critical Care Medicine, The University of Chicago Medicine, Chicago, Illinois

Address for correspondence Septimiu Murgu, MD, Divisions of Pulmonary and Critical Care Medicine, The University of Chicago Medicine, 5841 S. Maryland Avenue, MC 6076, Chicago, IL 60637 (e-mail: [email protected]).

Abstract

Keywords

► emphysema ► asthma ► lung volume reduction ► endobronchial valve ► bronchial thermoplasty

Emphysema and asthma are responsible for economic and social burden. Altering the natural course of these diseases is a field of intense research. The National Emphysema Treatment Trial showed that lung volume reduction surgery (LVRS) could significantly reduce both morbidity and mortality in properly selected patients. LVRS is seldom performed, however, due to the high morbidity associated with the surgery. Numerous bronchoscopic interventions have been introduced with the goal of providing the clinical benefits of LVRS without the surgical complications. Thus far, these modalities have not produced the results once hoped. However, through active modification of both technique and patient selection, the role of minimally invasive modalities in the treatment of emphysema continues to evolve. Bronchial thermoplasty (BT) is a method of delivering controlled heat to airway mucosa with the goal of reducing airway smooth muscle mass and hence bronchoconstriction. In patients suffering from asthma who cannot achieve control with standard medical care, BT has been shown to be safe and improves symptoms, with long lasting benefit. BT does not seem to affect traditional markers of asthma severity such as forced expiratory volume in 1 second and questions remain regarding proper patient selection for this therapy and its true physiologic effects. This article is a review of bronchoscopic modalities for emphysema and asthma.

Chronic Obstructive Pulmonary Disease

Brief Historical Perspective: Surgical Treatment of Emphysema

Patients with severe chronic obstructive pulmonary disease (COPD) suffer from debilitating and unremitting dyspnea resulting from the excessive mechanical load caused by hyperinflation and subsequent development of muscle fatigue. Currently, medical therapies for COPD include mainly bronchodilators, corticosteroids, oxygen, and pulmonary rehabilitation. Only tobacco cessation and oxygen therapy, however, have been shown to clearly prolong life. The following sections will describe the physiologic rationale and outcomes of bronchoscopic lung volume reduction surgery (LVRS).

Surgical lung volume reduction gained widespread attention after a review of 20 patients with severe emphysema documented improved dyspnea in patients who underwent bilateral staple resection of diseased portions of the upper lobes.1 In this initial cohort, forced expiratory volume in 1 second (FEV1) increased by a mean of 82%, patients reported marked improvement in dyspnea and quality of life scores, and there was no surgical mortality after a mean follow-up of 6.4 months. The enthusiasm generated by this study led to rapid widespread adoption of LVRS. During a 17-month period between 1994 and 1996, an estimated 1,212 LVRSs were

Issue Theme Interventional Pulmonology; Guest Editors: David Feller-Kopman, MD, and Lonny Yarmus, DO, FCCP

Copyright © 2014 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.

DOI http://dx.doi.org/ 10.1055/s-0034-1395939. ISSN 1069-3424.

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performed in Medicare enrollees, with nearly half of those surgeries occurring in the last 3 months of the review period, subsequent to the release of the study discussed earlier.2 It quickly became apparent that the originally described outcomes could not be replicated nationwide. After a report revealed a 23% 12-month mortality in Medicare recipients undergoing LVRS, the Health Care Finance Organization (HCFA) halted reimbursement of surgical interventions for emphysema pending prospective evaluation.3 In response to concerns of unclear efficacy and safety of surgical treatment for emphysema, Medicare sponsored the National Emphysema Treatment Trial (NETT), which was designed to prospectively evaluate the therapeutic role of LVRS.4 Patients’ inclusion and exclusion criteria are summarized in ►Table 1. After study initiation, an interim analysis found 16% 30-day mortality in the subgroup of patients with FEV1 < 20% predicted combined with either nonheterogeneous disease or diffusing capacity for carbon monoxide (DLCO) < 20% predicted, and these patients were excluded from further enrollment.5 In total, 1,218 patients were randomized and results were published in 2003. When patients with “high risk for death” (based on the 2001 interim analysis mentioned earlier) were excluded from analysis, overall mortality was similar between surgical and medical control patients at 2 years. Overall, 16% of patients in the surgical group had an improvement in exercise capacity of > 10 W at 24 months versus only 3% in medical controls. In the subgroup of patients with a low baseline exercise capacity (< 25 W for women and 40 W for men) and predominantly upper-lobe emphysema, surgery provided the greatest benefit. In contrast, patients with homogenous emphysema and high exercise capacity did worse than medical controls (►Table 1). Postoperative complications occurred in more than 50% of patients, and 28% of patients remained hospitalized for more than 1 month after surgery. The study prompted Medicare to reapprove payment for patients deemed likely to benefit from LVRS. Because of the understanding of true morbidity and mortality related to LVRS, enthusiasm for this surgery significantly waned. In the 1990s, more than 1,000 LVRS were performed annually in the United States, but since the NETT trial, this operation is now performed less than 200 times per year.2,6

ments reducing hyperinflation. The earliest endobronchial therapies were simple detachable vascular balloons and stainless steel stents filled with occlusive sponges. In a preliminary report published in 2003, five of eight patients treated with these interventions showed improvement in dyspnea and exercise tolerance. The complication rate was high and included prosthesis migration, postobstructive pneumonia, and expectoration of devices.7 Although these airway plugs were not practical for clinical use due to complications associated with direct airway occlusion, this early work showed that endobronchial occlusion therapy could be physiologically and clinically effective in the treatment of emphysema. This prompted the development of oneway valves designed to occlude air entrance during inhalation while allowing air to escape during exhalation resulting in lobar deflation. Two devices (Zephyr-Pulmonx, Redwood City, CA and IBV-Spiration, Redmond, WA) have been studied in clinical investigations. Both of these nitinol-composed devices are placed through a flexible bronchoscope, and can be retrieved, if necessary (►Fig. 1). The Endobronchial Valve for Emphysema Palliation Trial (VENT) is the largest randomized trial performed to date evaluating the utility of unidirectional valves in the treatment of emphysema.8 This multicenter, randomized, unblinded study attempted to compare best medical therapy to endobronchial valve placement in patients with severe heterogeneous emphysema. Inclusion criteria were modeled to be similar to the NETT trial, with the hope of obtaining similar success with reduction in procedural morbidity. Study design and outcomes are summarized in ►Table 1. Although the overall improvement in 6-minute walk test distance (6MWTD) and FEV1 was minimal, subgroups of patients demonstrated dramatic clinical improvement. In total, 23.5% of patients had > 15% improvement in FEV1 6 months following intervention. When evaluating the degree of heterogeneity on high-resolution computed tomographic (HRCT) scan, those with >25% heterogeneity demonstrated a 15.3% improvement in FEV1 and 16.2% improvement in 6MWTD. Fissure integrity also seemed to greatly affect outcomes. Patients with complete fissures on HRCT had a 17.9% improvement in FEV1 at 12 months compared with 2.8% improvement in patients with incomplete fissures. Despite the response in certain subgroups, the minimal overall improvement and associated risks led to the Food and Drug Administration (FDA) denying approval for the Zephyr device. Beyond concerns of inadequate patient selection, another criticism of the VENT trial was that valves were placed unilaterally possibly underrepresenting potential clinical effect. In an attempt to address this limitation, Spiration (maker of IBV valve) sponsored a randomized, single-blinded, shamcontrolled trial to evaluate the efficacy of bilateral upper lobe endobronchial valve therapy in patients with severe heterogeneous emphysema. Another major difference in this study compared with the VENT trial was that a single segment of each target lobe was left unoccluded in an attempt to reduce the risk of pneumothorax, in exchange for potentially less volume reduction in the targeted lobes (►Table 1). The primary outcome was improvement in the St. George

Bronchoscopic Treatment of Emphysema The sound physiologic rationale, technical success, and physiologic improvements after LVRS prompted interest in the development of less invasive bronchoscopic options for lung volume reduction, with the goal of achieving the clinical benefit without the surgical complications. Several bronchoscopic modalities have been studied for the treatment of emphysema. There are two major categories of bronchoscopic interventions: those which aim to induce atelectasis of the hyperinflated segments and those which create extra-anatomical airways to allow expiration of trapped air.

Endobronchial Lung Volume Reduction Approaches The rationale behind bronchoscopic occlusion therapy is that mechanical blockade of selected diseased portions of lung can result in shifting of ventilation to more preserved lung segSeminars in Respiratory and Critical Care Medicine

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Trial/Study design/Intervention

Patient selection

Outcomes/Results/Comments

National Emphysema Treatment Trial (N ¼ 1,218)4,5 Study design: Open-label multicenter RCT Intervention: Bilateral resection of diseased portions of upper lobes

Inclusion criteria: CT evidence of bilateral emphysema, TLC 100% predicted, RV 150% predicted, FEV1  45% predicted, PaCO2  60 mm Hg, PaO2  45 mm Hg, BMI  31.1 (males) or  32.3 (females), not smoking, completion of pulmonary rehabilitation program Exclusion criteria: FEV1  20% predicted and either nonheterogeneous emphysema on CT scan or DLCO  20% predicted (enacted 2001), diffuse emphysema, pleural or interstitial disease which precludes surgery, giant bulla, clinically significant bronchiectasis, pulmonary nodule requiring surgery, pulmonary hypertension, recurrent pulmonary infections, daily use of >20 mg prednisone, O2 requirement > 6 L/min, 6MWTD < 140 m, unstable cardiac conditions

Efficacy: Improvement in exercise capacity > 10 W occurred in 16% surgical treatment vs. 3% in the medical-therapy group Improvement in SGRQ score > 8 points occurred in 33% surgical treatment vs. 9% medical therapy Adverse events: 29.8% major pulmonary complications within 90 d of LVRS Mortality 7.9% in LVRS vs. 1.3% in medical controls Important subgroup analysis: Patients with low exercise capacity with upper lobe predominant disease had a RR for mortality of 0.47, while those with high exercise capacity and homogeneous disease had RR for mortality 2.06 Early interim analysis: 16% 30-d mortality in the subgroup of patients with FEV1 < 20% predicted, combined with either nonheterogeneous disease or DLCO < 20% predicted; these patients were excluded from further enrollment Comments: Landmark study of surgical lung volume reduction. Significant survival and quality of life benefit in patients with predominantly upper lobe disease and low exercise capacity. Morbidity and mortality of surgical treatment was high and recovery time was long with 28% of surgical patients remaining hospitalized for more than 1 mo after surgery. Bronchoscopic therapies studied below were designed to emulate physiologic benefits of this trial without the associated surgical complications

Endobronchial Valve for Emphysema Palliation Trial (N ¼ 321)8 Study design: Open-label multicenter RCT Intervention: Unilateral endobronchial valves vs. standard medical care Device: Pulmonx Zephyr Valve

Inclusion criteria: Severe heterogeneous emphysema, FEV1 15–45% predicted, TLC 100% predicted, RV 150% predicted, BMI 31.1 (males) or 32.3 (females), PaCO2  50 mm Hg, PaO2 45 mm Hg, postrehabilitation 6MWD  140 m Exclusion criteria: DLCO < 20%, giant bullae, α1-antitrypsin deficiency, previous thoracotomy, excessive sputum production, severe pulmonary hypertension, active infection, unstable cardiac conditions

Efficacy: FEV1 increased by 4.3% (95% CI, 1.4–7.2) in the EBV group, and decreased by 2.5% in the control group 6MWTD increased by 2.5% (95% CI, 1.1 to 6.1) in the EBV group and decreased by 3.2% in the control group SGRQ increased by 2.5 in the EBV group and decreased by 3.2 in the control group Adverse events: Major complications occurred in 6.1% of the treated patients and included pneumothorax (1.4%), pneumonia (3.2%), nonmassive hemoptysis (5.6%). 6 deaths (2.3%) occurred in the treatment group compared with 0 in the control group Subgroup analysis: In patients with high heterogeneity on CT scan, FEV1 increased by 13.3% compared with 1.5% in patients with low heterogeneity at 12 mo In patients with complete fissure integrity, FEV1 increased by 17.9% compared with 2.8% in patients with incomplete fissures at 12 mo Comments: Despite the excellent response in certain subgroups of patients (compete fissures and high degree of heterogeneity), the minimal overall improvement and associated risks led to the FDA denying approval for the Zephyr device

Multicenter European study for the treatment of advanced

Inclusion criteria: Predominantly upper lobe emphysema,

Efficacy: The primary outcome was improvement in the (Continued)

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Table 1 Major clinical studies relevant to bronchoscopic lung volume reduction for emphysema

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Table 1 (Continued) Trial/Study design/Intervention

Patient selection

Outcomes/Results/Comments

emphysema with bronchial valves (N ¼ 73)9 Study design: Single blinded multicenter RCT Intervention: Bilateral upper lobe endobronchial valve therapy with single segment of each target lobe left un-occluded Device: Spiration IBV valve

severe dyspnea, FEV1 6 L/min, recurrent pulmonary infections

SGRQ score  4 points and quantitative changes in regional lung volume from upper to lower lobes of  7.5% 23% of treated patients exceeded the treatment threshold compared with 0 in sham group at 3 mo posttherapy Adverse events: Serious adverse events: 19% in treatment group vs. 11% in sham bronchoscopy group Comments: Sham bronchoscopy was performed in control group Bilateral partial lobar collapse targeted in an attempt to reduce the risk of pneumothorax in exchange for potentially less volume reduction Goal sample size not achieved (study stopped early for logistical reasons)

Bronchial valve treatment of emphysema: lung volume reduction in a double-blind randomized trial (N ¼ 277)10–12 Study design: Open-label multicenter RCT Intervention: Bilateral upper lobe endobronchial valve therapy with single segment of each target lobe left un-occluded Device: Spiration IBV valve

N/A at the time of this writing

Partial results published in abstract form: Efficacy: SGRQ score not clinically different in treatment vs. control In treated patients, CT-measured lobar volume decreased by 6.4% in upper lobes and increased by 7.4% in lower lobes No differences in lung function or exercise capacity in treatment vs. control Adverse events: Serious adverse events: 27% in treatment group vs. 13% in sham bronchoscopy group Death occurred in 4.2% in treatment group vs. 0.74% in sham bronchoscopy group Comments: Bilateral partial lobar collapse targeted in an attempt to reduce the risk of pneumothorax in exchange for potentially less volume reduction Primary endpoint achieved; however, total effect was minimal

Radiological and clinical outcomes of using Chartis to plan endobronchial valve treatment (N ¼ 80)17 Study design: Prospective case series Intervention: Unilateral Pulmonx valve occlusion of lobe with the greatest disease with intraprocedural Chartis assessment to determine presence of CV Device: Pulmonx Zephyr Valve

Inclusion criteria: Severe heterogeneous emphysema Exclusion criteria: Active pulmonary infection, FEV1 50% predicted

Efficacy: In those with significant CV, there was only a 98.6 mL average reduction in total lung volume posttreatment vs. 752.7 mL in the patients without CV By defining “responders” as patients who achieved > 350 mL reduction in total lung volume after endobronchial valve placement, presence of significant CV had an 83% NPV, while the absence of CV had a 71% PPV Adverse events: Serious adverse events occurred in 20% of patients Most common AEs included pneumothorax (8.3%) and COPD exacerbation (7.3%) Comments: This study demonstrated the relevance of measuring CV in predicting response to EBV placement

Evaluation of the IBV valve for Emphysema to Improve Lung Function (EMPROVE) Currently enrolling19

Inclusion criteria: Severe heterogeneous emphysema with complete fissure integrity by CT, FEV1  45% of predicted, RV  150% of

Results pending trial completion Comments: Study designed to evaluate treatment response

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659

Trial/Study design/Intervention

Patient selection

Outcomes/Results/Comments

Study design: Open-label multicenter RCT Reported intervention: Unilateral IBV valve inserted into lobe with the greatest disease Device: Spiration IBV valve

predicted, TLC  100% of predicted, 6MWTD  140 m, not smoking Exclusion criteria: BMI < 15 kg/m2 or > 35 kg/m2, PCO2 > 50 mm Hg, PO2 < 45 mm Hg on RA, diffuse emphysema, α1-antitrypsin deficiency, excessive sputum production, daily use of >15 mg prednisone, giant bulla, pulmonary hypertension, prior major lung surgery, recent hospitalization for COPD exacerbation or respiratory infection

of IBV placement in patients with complete fissure integrity on CT scan

Pulmonx Endobronchial Valves Used in Treatment of Emphysema Currently enrolling18 Study design: Open-label multicenter RCT Reported intervention: Unilateral Pulmonx valve occlusion of lobe with the greatest disease in patients with minimal CV on preprocedural Chartis assessment Device: Pulmonx Zephyr valve

Inclusion criteria: Clinical and radiological evidence of emphysema, stable on current medication regimen, FEV1 15–45% predicted, not smoking Exclusion criteria: 2 hospitalizations over the last year for a COPD exacerbation, 2 hospitalizations over the last year for pneumonia, prior lung transplant, lung volume reduction surgery, bullectomy or lobectomy, MI or CHF failure within the last 6 mo, cardiac arrhythmia, α1-antitrypsin deficiency

Results pending trial completion Comments: Similar to EMPROVE; however, CV is evaluated with Chartis system and only patients with minimal CV undergo EBV placement

Abbreviations: 6MWTD, 6-minute walk test distance; BMI, body mass index; COPD, chronic obstructive pulmonary disease; CT, computed tomography; CV, collateral ventilation; DLCO, diffusing capacity for carbon monoxide; EBV, endobronchial valve; FDA, Food and Drug Administration; FEV1, forced expiratory volume in 1 second; IBV, intrabronchial valve; LVRS, lung volume reduction surgery; N, number; N/A, not available; RCT, randomized clinical trial; RR, relative risk; RV, residual volume; SGRQ, St. George’s Respiratory Questionnaire; TLC, total lung capacity; W, watts.

Respiratory Questionnaire (SGRQ) score  4 points and quantitative changes in regional lung volume from upper to lower lobes of  7.5%. In this small study, 23% of treated patients exceeded the treatment threshold (compared with 0 in sham group) at 3 months posttherapy.9 This was followed by a similar larger multicenter study, which did not achieve clinically significant improvements in primary endpoints.10–12 It remains unclear whether unilateral complete lobar occlusion or bilateral incomplete lobar occlusion is more efficacious, although in one small study of 22 patients with severe bilateral heterogeneous emphysema, unilateral com-

plete occlusion was found to be superior to bilateral incomplete occlusion.13 Neither the VENT nor the IBV trial addressed the role of collateral ventilation (CV) in predicting outcomes. CV in normal individuals is typically minimal or absent with inspired air leaving lung units through the same pathways.14 In patients with emphysema, however, collateral pathways often allow air to backfill the occluded segments.15 It has been postulated that patients who lack significant CV in targeted lung segments would experience the greatest benefit from endobronchial valve therapy. With the goal of

Fig. 1 (A) IBV endobronchial valve (Spiration). (B) Zephyr valve (Pulmonx). (C) Chartis system (Pulmonx). Images courtesy of Spiration Inc. and Pulmonx Inc. Seminars in Respiratory and Critical Care Medicine

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improving patient selection, Pulmonx created the Chartis system to predict CV before intervention. This device consists of a balloon tipped catheter, which allows for isolation of a target lung segment, and a console, which measures the pressure and flow from the isolated segment, allowing for indirect measurement of CV by estimating collateral resistance (►Fig. 1). Within the console, there is a one-way valve which works in a similar manner to the unidirectional endobronchial valves16. When CV is insignificant, the resistance to airflow increases as segmental volume declines. In segments with significant CV, air continues to enter occluded segments and resistance to flow remains low. This technology has provided hope that with proper pretreatment assessment, one can better predict the subgroup of patients who will benefit from unidirectional endobronchial valve therapy. In a European trial, 80 patients underwent Chartis assessment before bronchoscopic LVR17 (►Table 1). A larger prospective U.S. study (LIBERATE) is reportedly evaluating outcome of LVR in patients who are found to have minimal CV on preprocedural Chartis assessment.18 In addition, another ongoing U.S. trial (EMPROVE) is reportedly testing LVR through unilateral deployment of IBV valves in patients with fissure integrity on preprocedure CT.19 The rationale for this study is that the presence of intact fissures indicates a low likelihood of significant CV and hence would potentially increase responder rates. A similar approach is being used by UK investigators,20 but their protocol also includes CV measurements using the Chartis system both in the control and the treatment arms. For patients with homogenous emphysema and/or significant CV, endobronchial valve therapy is currently not a viable option. An alternative bronchoscopic modality designed to achieve LVR in these subsets of patients involves the endoscopic introduction of biological agents into the lung parenchyma. The goal of biological therapy is to produce regional atelectasis. This is accomplished by inducing a local inflammatory response and subsequent remodeling of a target lung segment over a period of weeks to months. A unique advantage of this therapy is that it is designed to work not at the airway level but rather to exert its effect on alveolar tissue, inducing scar formation of small distal collateral channels. Early work in animals led to the development of a biological agent that promotes fibroblast attachment and collagen synthesis. This formulation was designed to produce scar formation without the typically inflammatory response associated with tissue injury. In a sheep model, parenchymal scarring with associated tissue contraction was successfully achieved in 91% of treatment sites without development of granulation tissue, infection, or allergic reactions.21 In an open-label phase II human study of patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage III and stage IV COPD, this compound was bronchoscopically instilled into four segments of each lung. Patients were randomized to either “low dose” instillation (10 mL per segment) or “high dose” instillation (20 mL per segment). In both groups, there was a significant reduction in the ratio of residual volume (RV) to total lung capacity (TLC) and improvement in FEV1 and dyspnea scores at 3 months. In

the low-dose group, much of this benefit was lost by 6 months, while the high-dose group retained significant (and likely clinically meaningful) improvement at 6 months, with a 16.8% improvement in FEV1.22 A similar pilot study conducted on patients with homogenous disease showed encouraging results, although efficacy was less significant than with heterogeneous disease.23 The manufacturer subsequently shifted to a hydrogel foam polymer without biological activity. This polymer worked by directly adhering to the alveolar wall, resulting in gas absorption and subsequent segmental collapse. To evaluate the safety of the new hydrogel foam, a small, open-label, pilot study was conducted in Germany in 25 patients with severe heterogeneous emphysema. Although there were only small improvements in pulmonary function at 6 months, the treatment was well tolerated. The most common adverse event following treatment was development of flu-like symptoms, which occurred to some degree in all treated patients, typically in the first 24 hours postprocedure. COPD exacerbations and pneumonia occurred in 40 and 12% of patients respectively.24 A phase III randomized trial of this device, which began enrolling patients in June 2012, was recently terminated and further details have not yet been disclosed.25 A similar technique aiming to induce localized inflammation and regional lung collapse is bronchoscopic application of heated water vapor to diseased airways. The application of steam was evaluated in the VAPOR trial and showed promise with an average FEV1 improvement of 17% at 6 months. The therapy, however, is limited by a high rate of systemic inflammatory reactions, which can last between 8 and 12 weeks after application.26 Currently, a larger prospective trial of this system (STEP-UP) is underway, to determine safety and efficacy of this technology in patients with severe upper lobe predominant emphysema.27 Lung volume reduction can also be achieved through the placement of mechanical coiling devices. These devices are deployed while flattened and resume a predetermined coiled shape in the lung parenchyma. The coils are supposed to pull lung tissue together, improve lung elastic recoil, and reshape the diaphragm into a more advantageous position for breathing. A pilot study of 16 patients with severe heterogeneous emphysema treated with coils showed significant improvements in SGRQ scores, pulmonary function tests, and 6MWTD at 6 months with an acceptable safety profile. Adverse events included mild hemoptysis, pneumothorax, pneumonia, and COPD exacerbations.28 A prospective phase III trial is currently evaluating the safety and efficacy of this device for treatment of both homogenous and heterogeneous emphysema.29

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Extra-Anatomical Airways Creation: Airway Bypass Approaches All of the previously discussed devices work by inducing atelectasis of hyperinflated lung segments. In patients with significant CV, the creation of bypass tracks between hyperinflated parenchyma and more proximal airways has been explored as a therapeutic option. The goal of this therapy is to alter flow dynamics and facilitate expiration of trapped air. This has been performed through the use of

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Asthma Prevalence of asthma continues to rise, increasing from 7.4% in 2001 to 8.4% in 2010 within the United States. Currently, an estimated 25.7 million Americans have a diagnosis of asthma.34 Management of asthma typically occurs in a stepwise manner, and with standard medical care most patients’ disease can be controlled. A small subset (likely < 5%) of asthma patients continue to have symptoms despite maximal therapy.35 This group of patients, refractory to conventional therapy, represents a population that consumes a significant economic cost and has a large societal impact resulting from missed work and school.

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Brief Historical Perspective: Medical Use of Radiofrequency Ablation Radiofrequency ablation is commonly used to ablate abnormal tissue in tumors and for the treatment of abnormal electrical pathways in the heart, for which it has been shown to be safe and effective.36,37 The technology works through the application of a high-frequency, low-voltage alternating currents, which travel from an electrode applicator to a remote grounding pad. Frictional heat is generated at tissue interfaces where the flow of current meets resistance. An advantage of this therapy is that the frequency of the waves does not induce neuromuscular reactions.38 The initial hypothesis regarding the potential role of radiofrequency in the treatment of asthma was that low-thermal energy applied to airway mucosa could selectively ablate airway smooth muscle.39

Bronchoscopic Treatment of Asthma Bronchoconstriction results from abnormal contraction of bronchial smooth muscle in response to environmental stimulus.40,41 An important pathologic feature of asthma is hypertrophy of airway smooth muscle. This finding is even more pronounced in fatal asthma.42 Bronchial thermoplasty (BT) was developed to reduce airway smooth muscle mass in patients with difficult to control asthma and hence reduce bronchoconstriction and airway narrowing. This section will review the technical aspects of BT, as well as the role BT has in the treatment of refractory asthma patients based on the current published literature. BT reduces airway smooth muscle mass through application of controlled heat to the airway mucosa. The device currently used (Boston Scientific, Marlborough, MA) works through an expandable wire array catheter which is inserted into the working channel of a diagnostic flexible bronchoscope.43 When the wires contact the airway wall, monopolar radiofrequency energy is applied and converted to heat (►Fig. 2). The radiofrequency energy disrupts the normal airway smooth muscle resulting in destruction and atrophy.39 BT is performed in three sessions approximately 3 weeks apart. Ablations are performed starting in the distal airways and working more proximally in a contiguous fashion (►Fig. 2). This procedure can be performed under either moderate sedation or general anesthesia. The earliest study evaluating the effects of BT on bronchial smooth muscle was in a series of 11 healthy canines.39 In this experiment, lungs were divided into four regions. BT was performed in three regions at temperatures 55, 65, or 75°C, and the fourth untreated region served as a control. All activations were performed during a single bronchoscopy with therapy applied to airways distal to the carina and greater than 3 mm in diameter. Pretreatment methacholine challenge was performed and repeated at a preselected interval posttherapy. The canines were then euthanized at 1, 6, 12, or 157 weeks following therapy. Local airway responsiveness to methacholine which was determined through bronchoscopic visualization was significantly reduced in the lung segments that received BT at 65 or 75°C compared with controls up to 157 weeks after treatment. In Seminars in Respiratory and Critical Care Medicine

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bronchoscopically placed bypass stents. Initially, this modality was studied in excised emphysematous human lungs removed during lung transplantation. In this in vitro experiment, a radiofrequency catheter was passed through the working channel of a flexible bronchoscope to create passages between three separate segmental bronchi and adjacent lung parenchyma. Within these passages, expandable metal stents were deployed to maintain the neo-airways. There was significant improvement in expiratory flow in the excised lungs.30 The introduction of these bypass stents in live animals was performed in canines. Extra-anatomical airway passages were formed by insertion of a needle tipped catheter with an integrated 2.5-mm balloon through the walls of segmental and subsegmental airways into lung parenchyma. After the airways were created, 3 mm  3 mm siliconecoated metal stents were inserted into the airways. Although the device placement was technically feasible and safe in this animal model, the stents would typically occlude within the first week after placement.31 The investigators subsequently created a paclitaxel-impregnated stent. The patency rate improved compared with the silicone-coated metal stents, but still only 65% of the stents remained patent at 12 weeks.32 The feasibility of these devices for use in humans with severe homogenous emphysema was evaluated in the double-blinded, sham-controlled Exhale Airway Stents for Emphysema (EASE) trial. At 1-month postintervention, patients showed significant improvement in FEV1, reduction in RV, and improvement in SGRQ score. These benefits were short lived and at 12 months, no significant improvement in endpoints were seen when compared with controls.33 Similar to the animal model, the stents would not maintain their patency long after deployment. Improved modalities for maintaining stent patency would be necessary before these devices will have a role in the bronchoscopic management of emphysema. In summary, the ability to bronchoscopically achieve the benefits of LVRS without the surgical morbidity has not yet been achieved. At the time of writing this article, none of the therapies mentioned above are approved for clinical use in the United States. By applying sound physiologic rationale, refining techniques, and improving patient selection through clinical trials, however, bronchoscopy may soon become a valuable tool in the treatment of emphysema.

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Fig. 2 (A) BT catheter in the subsegmental airway. (B) BT catheter in the segmental airway. BT, bronchial thermoplasty.

the 55°C segments, the airway responsiveness declined at 1-week posttherapy, but that reduction was not sustained. Histologically, there was a reduction in airway smooth muscle, which occurred as early as 1 week posttreatment, with the extent of smooth muscle degeneration increasing in the segments treated at higher temperatures. Smooth muscle remained atrophied without regeneration over the 3-year follow-up. With the exception of mild cough, there was no evidence to suggest injury in the treated animals. The first human study of BT was conducted on eight nonasthmatic patients with known or suspected lung cancer before planned lung resection.44 One to 3 weeks before surgery, BT was performed with activations of either 55 or 65°C targeting airways within the area of lung which was to be surgically removed. At the time of resection, a repeat bronchoscopy was performed for visual inspection of treated airways. Following surgery, histologic specimens were examined for tissue effect. In the airways treated at 55°C, only small alterations in smooth muscle were noted in histological specimens. In the airways treated at 65°C, approximately 50% of the treated tissue had significant alterations in smooth muscle architecture. Patients tolerated the procedure well. Following the feasibility study, the first prospective observational study of humans with stable, mild-to-moderate asthma was performed in 16 adult subjects.45 Patients were treated in three separate sessions 3 weeks apart. The lower lobes were treated each in dedicated sessions and the bilateral upper lobes were treated in a single session. The right middle lobe was left untreated due to theoretical concern for development of right middle lobe collapse. Systemic corticosteroids were given the day before, day of, and day after treatment with the goal of minimizing periprocedural edema and inflammation. Short-term side effects occurred in all patients with the most common treatment-related side effects being cough, dyspnea, wheezing, and bronchospasm. All events were considered to be “mild or moderate” and occurred within 1 week of treatment. No patients required hospitalization and symptoms resolved at a mean time of 4.6 days after treatment. Patients were then followed up for up to 2 years after BT and no long-term side effects were observed (►Table 2). Despite the improvement in symptom-free days, airway hyperresponsiveness, and peak flow, there was no significant reduction in rescue medication use or improvement in FEV1 at 2-year follow-up. Seminars in Respiratory and Critical Care Medicine

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The first prospective randomized trial evaluating the efficacy of BT in patients with moderate to severe asthma was the Asthma Intervention Research Trial (AIR)46 (►Table 2). Patients who underwent treatment reported approximately fewer than 10 mild exacerbations and 86 additional symptom-free days per year when compared with controls. Peak expiratory flow rate (PEFR), rescue medication use, and scores on both asthma quality of life questionnaire (AQLQ) and asthma control questionnaire improved in the treatment group. Early worsening of symptoms following BT occurred commonly, with the majority of treated patients reporting worsening of dyspnea, cough, and wheezing. Severe worsening of asthma requiring hospitalization occurred in four patients (7.6%). The early worsening of symptoms generally resolved within 7 days and there was no difference in adverse events between the treatment group and control group 6 weeks to 12 months after therapy. Following the AIR trial, the Research in Severe Asthma (RISA) trial was conducted to evaluate the safety and efficacy of BT in the treatment of severe asthmatics that remained symptomatic despite high-dose inhaled corticosteroid/long acting bronchodilator with or without daily oral prednisone (< 30 mg/day)47 (►Table 2). Thirty-four patients were enrolled (17 BT patients and 17 controls). During the stable steroid period, there was a significant reduction in rescue inhaler use, improvement in FEV1, and AQLQ score in the BTtreated group compared with controls. These improvements continued after steroid reduction. In addition, absolute reduction in steroid dose and complete elimination of oral steroid use occurred more often in the treatment group. Adverse events were significantly more common in the patients treated with BT. Seven hospitalizations occurred in four of the seventeen treated patients (23%). Two of these hospitalizations were secondary to development of segmental lobar collapse, with one patient requiring therapeutic bronchoscopy for mucus aspiration. Although the results of the AIR and RISA trials were promising, these studies were unblinded and the potential for placebo effect was high. To address this concern, the double-blinded, sham-controlled AIR-2 trial was developed.48 This study was designed in a 2:1 randomized fashion of BT versus sham bronchoscopy. Two hundred ninety-seven patients were enrolled at 30 centers (►Table 2). Regarding the primary outcome of AQLQ score, both the treatment group

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Trial/Study design/Intervention

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Outcomes/Results/Comments

Trial: A prospective feasibility study of bronchial thermoplasty in the human airway (N ¼ 9)44 Study design: Prospective single-center cohort Intervention: BT performed during pre-op bronchoscopy 1–3 wk prior to scheduled lung resection Activations of either 55°C or 65°C performed in targeting airways within area of lung which was to be surgically removed

Inclusion criteria: Patients scheduled to undergo lung resection for suspected or proven lung cancer Exclusion criteria: Not specified

Efficacy: In the airways treated at 55°C, only small alterations in smooth muscle were noted in histological specimens In airways treated at 65°C, 50% (16–71) of the treated tissue had significant alterations in smooth muscle architecture Adverse events: All patients tolerated the procedure well and were able to proceed with planned surgery Comments: First feasibility study which showed early safety and treatment effect in humans. Study also showed significant increased effect in segments treated at 65 vs. 55°C

Trial: Bronchial Thermoplasty for Asthma (N ¼ 16)45 Study design: Prospective single-center cohort Intervention: Standard BT protocol

Inclusion criteria: 18 y or older, stable asthma with no change in asthma condition or medication needs in previous 6 wk Exclusion criteria: Respiratory tract infection within 6 wk, history of  2 LRTI per year requiring antibiotics, use of > 4 puffs SABA per day

Efficacy: During 12-wk follow-up period, 67% of patients reported an increase in symptom-free days (mean symptom-free days increased from 50 to 73%) Morning and evening PEFR increased significantly PC20 changed from 0.92 mg/dL pretreatment to 3.40 mg/dL 2 y following treatment Rescue medication use was not significantly changed Pre-BD FEV1 did not changed baseline at 1 y follow-up Adverse events: A total of 312 AEs reported over 2-y period with 74% considered mild, 25% moderate, and 1% severe Most common side effects included cough, 94%; dyspnea, 69%; wheeze, 50%; bronchospasm, 63%; fever, 44%; chest discomfort, 56%; mucus production, 50%; throat irritation, 25%; headache, 25%; congestion, 13%; hemoptysis, 19% All procedure-related side effects presented within 1 wk of BT with 58% resolving spontaneously, and 42% managed with medications such as albuterol, acetaminophen, antibiotic, and steroids Comments: Initial pilot study of BT in stable asthmatic patients Showed general safety with self-limiting posttreatment side effects Significant improvement in symptom-free days and BHR to methacholine challenge

Trial: Asthma Intervention Research Trial (AIR) (N ¼ 112)46 Study design: Open-label multicenter RCT Intervention: Standard BT protocol. Following BT, LABA dose was stepped down at 3, 6, and 12 mo

Inclusion criteria: FEV1 60–85% predicted, airway hyper-responsiveness (PC20) < 8 mg/mL, stable asthma during the 6 wk before enrollment, worsening asthma control after abstention from LABA for 2 wk Exclusion criteria: 3 or more LRTIs requiring antibiotics during the previous 12 mo, LRTI within the previous 6 wk

Efficacy: Morning PEFR improved at 12 mo compare with controls (39.3  48.7 vs. 8.5  44.2 LPM) AQLQ score was improved at 12 mo compared with controls (1.3  1.0 vs. 0.6  1.1) ACQ score was improved at 12 mo compared with controls (reduction, 1.2  1.0 vs. 0.5  1.0) Percentage of symptom-free days increased at 12 mo compare with controls (40.6  39.7 vs. 17.0  37.9) FEV1% predicted was unchanged at 12 mo vs. control group (Continued)

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Table 2 Clinical studies of bronchial thermoplasty

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Table 2 (Continued) Trial/Study design/Intervention

Patient selection

Outcomes/Results/Comments Airway responsiveness was not significantly changed at 12 mo (PC20): BT group (0.61 mg/ mL from 0.24 mg/mL at baseline) vs. control group (0.5 mg/mL from 0.32 mg/dL at baseline) Adverse events: Clinically significant side effects occurring within 6 wk of treatment period included dyspnea (70.9 vs. 33.3%), wheezing 61.8 vs. 13.0%), cough (52.7 vs. 18.5%), night awakenings (40.0 vs. 9.3%), productive cough (40.0 vs. 11.1%) Severe worsening of asthma requiring hospitalization occurred in 4 patients in treatment group (7.6%) vs. 2 patients (4.08%) in control group Comments: Showed safety (with exception of early worsening of symptoms) and improvement in asthma symptoms following BT in moderate asthma with 12-mo follow-up. Placebo effect could not be accounted for in this study (controls received no procedural intervention)

Trial: Research in Severe Asthma (RISA) Trial (N ¼ 34)47 Study design: Open-label multicenter RCT Intervention: Standard BT protocol. Following treatment period, patients entered 16-wk period of stable dose steroid use. This was followed by a 14-wk protocoled reduction of oral or inhaled corticosteroids and then a 16-wk period of observation

Inclusion criteria: Age 18–65, requirement of high-dose ICS and LABA with or without oral prednisone ( 50% of predicted, airway hyperresponsiveness by methacholine (not performed if baseline FEV1 reduced or reversible BC, uncontrolled asthma symptoms despite taking maintenance medication, non-smoking and < 10 pack-year history Exclusion criteria: Immunosuppressant therapy other than CS, current LRTI, LRTI within 6 wk, history of > 3 LRTIs requiring ABX in previous 3 mo, DLCO < 70% predicted, uncontrolled sinus disease, uncontrolled GERD, implanted electronic device, post-BD FEV1 < 55% predicted

Efficacy: BT subjects had significant improvement at 22 wk in rescue medication use (26.6 puffs/7 d  40.1) vs. controls (–1.5 6 puffs/ 7 d  11.7) BT subjects had significant improvement at 22 wk in pre-BD FEV1 (14.9% improvement  17.4) vs. controls (0.94% reduction  22.3) BT subjects had significant improvement at 22 wk in AQLQ score (-1.04  1.03) vs. controls (-0.13  1.00) Adverse events: Clinically significant (p < 0.05) side effects occurring within treatment period included wheezing (73.3 vs. 23.5%), cough (73.3 vs. 35.3), chest discomfort (40.0 vs. 5.9%) 7 hospitalizations occurred in 4/17 treated patients (23%); 2 of these hospitalizations were secondary to development of segmental lobar collapse, with 1 patient requiring bronchoscopic aspiration of mucous Comments: Trial was conducted to evaluate the safety and efficacy of BT in the treatment of severe asthmatics that remained symptomatic despite high-dose ICS/LABA with or without daily oral prednisone In this small study, there was a short-term increase in asthma-related morbidity; however, significant long-term benefit was observed As in the AIR1 trial, placebo effect could not be accounted for in this study (controls received no procedural intervention)

Trial: Effectiveness and Safety of Bronchial Thermoplasty in the Treatment of Severe Asthma (AIR2) (N ¼ 297)48 Study design:

Inclusion criteria: Age 18–65, asthma requiring regular maintenance medications, stable maintenance asthma medications for 4 wk before entry, baseline AQLQ score

Efficacy: Change in AQLQ score was significantly improved in the BT-treated patients (1.35  1.10) compared with sham bronchoscopy (1.16  1.23). Although

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multicenter, randomized, doubleblind, sham-controlled trial with 2:1 randomization Intervention: Standard BT protocol

< 6.25, FEV1 >60% of predicted, airway hyperresponsiveness (PC20 8 mg/mL), 2 or more days of asthma symptoms during 4-wk baseline period, non-smoking and < 10 pack-year history Exclusion criteria: Life-threatening asthma, OCS > 10 mg/d, chronic sinus disease, respiratory diseases such as emphysema, use of immunosuppressants, β-blocking agents, or anticoagulants, history of  3 hospitalizations for asthma in previous year, 3 or more LRTIs in previous year, 4 or more pulses of OCS for asthma in previous year

improvement was significant, the change was only minimal and fell below the threshold for clinically meaningful difference (change in AQLQ score of > 0.5) Percent of subjects with AQLQ change >0.5 was significantly different in the BT-treated patients (78.9%) compared with sham bronchoscopy (64.3%) Pre-BD FEV1 was not significantly improved in BT subjects (77.8%  15.65 at baseline and 76.6%  17.74 at 12 mo) vs. sham bronchoscopy subjects (79.78%  15.14 at baseline and 79.1%  15.98 at 12 mo) Rescue medication use (puffs/7 d) was not significantly improved in BT subjects (13.4  19.17 at baseline and 7.4  15.01 at 12 mo) vs. sham bronchoscopy subjects (11.8  11.24 at baseline and 7.5  12.60 at 12 mo) Difference in morning PERF was not significantly improved in BT subjects Severe exacerbations were significantly reduced during the 12-mo flow-up period in the BT subjects (0.48  0.067) vs. sham bronchoscopy subjects (0.70  0.122) Days lost from work, school, or other activities due to asthma were significantly reduced during the 12-mo flow-up period in the BT subjects (1.315  0.361) vs. sham bronchoscopy subjects (3.915  1.553) Adverse events: During treatment period, respiratory-related adverse events occurred more frequently in BT (85% with 8.4% requiring hospitalization) vs. sham bronchoscopy subjects (76% with 2.0% requiring hospitalization) Comments: Double-blind sham controlled study of BT showed reduction in severe exacerbations and days of missed school/work but did not show difference in morning PEFR, rescue medication use, FEV1 or significant improvement in quality of life score There was a very strong placebo effect in the sham treated subjects

Trial: A prospective observational study of biopredictors of Bronchial Thermoplasty Response in Patients with Severe Refractory Asthma (BTR Study) Currently enrolling55 Study design: Prospective observational cohort Intervention: Standard BT protocol

Inclusion criteria: Age 18–65, asthma requiring regular maintenance medications, airway hyperresponsiveness (PC20 8 mg/mL), FEV1 > 50% of predicted, at least 2 d or 1 night of asthma symptoms during previous 2 wk, non-smoking and < 10 pack-year history Exclusion criteria: Asthma exacerbation within previous 4 wk, 3 or more hospitalizations or at least 1 ICU admission for asthma in previous year, respiratory infection in past 4 wk, other respiratory disease including ABPA, significant comorbid disease

Results pending trial completion Comments: Study goal to assess relationship between baseline clinical, physiologic, biologic, and imaging markers and response to bronchial thermoplasty

(Continued)

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Table 2 (Continued)

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Table 2 (Continued) Trial/Study design/Intervention

Patient selection

Outcomes/Results/Comments

Trial: Bronchial Thermoplasty in Severe Persistent Asthma (PAS2) Enrollment recently completed52 Study design: Prospective postapproval observational study Intervention: Standard BT protocol

Inclusion criteria: Age 18–65, asthma requiring regular maintenance medications, baseline AQLQ score < 6.25, FEV1 >60% of predicted, 2 or more days of asthma symptoms during 4-wk baseline period, non-smoking and < 10 pack-year history Exclusion criteria: Regular use of rescue medications, history of life-threatening asthma, history of  3 hospitalizations for asthma in previous year, 4 or more LRTTs in previous year, 4 or more pulses of OCS for asthma in previous year, other respiratory disease including ABPA, significant comorbid disease

Results pending publication Comments: FDA mandated postapproval study of longterm safety and efficacy of the system in the intended use population

Abbreviations: AE, adverse event; AQLQ, Asthma Quality of Life Questionnaire; BC, bronchoconstriction; BD, bronchodilator; BHR, bronchial hyperresponsiveness; BT, bronchial thermoplasty; C, Celsius; DLCO, diffusing capacity for carbon monoxide; FDA, Food and Drug Administration; FEV1, forced expiratory volume in 1 second; GERD, gastroesophageal reflux disease; ICS, inhaled corticosteroid; LABA, long acting bronchodilator; LRTI, lower respiratory tract infection; N, number; OCS, oral corticosteroid; PEFR, peak expiratory flow rate; PC20, provocative concentration of methacholine causing a 20% drop in FEV1; RCT, randomized clinical trial; SABA, short acting bronchodilator.

and sham bronchoscopy group reported clinically meaningful improvements in AQLQ scores, highlighting the strong placebo effect. Although the improvement was significant in the BT group compared with controls, the change was only minimal and fell below the threshold for clinically meaningful difference (change in AQLQ score of > 0.5). There was also no difference seen in morning PEFR, rescue medication use, or FEV1. Interestingly, additional outcomes not included in the original protocol, including reduction in severe exacerbations, emergency department visits, and days of missed school/work, were significantly improved in the BT group.49,50 This benefit persisted through the 1-year follow-up period. Regarding adverse events, more patients were hospitalized for treatment-related complications in the BT group compared with the sham group (8.4 vs. 2.0%, respectively). In the complete follow-up period, however, there were fewer total respiratory adverse events in those who received BT than those who received sham bronchoscopy (27 vs. 43%). Five-year follow-up data have been published and findings indicate a lasting benefit. Patients who underwent BT reported a 44% reduction in severe asthma exacerbations and 78% reduction in emergency department visits when compared with the year before treatment with BT.51 In addition, CT did not show evidence of new structural abnormalities such as bronchiectasis or pulmonary fibrosis. Despite not meeting the primary endpoint, the FDA conditionally approved BT for use in patients with uncontrolled severe persistent asthma based on secondary endpoints including reduction in severe exacerbations, decreased emergency department visits, and fewer days of missed school/work. Currently, a postapproval FDA mandated study is underway to evaluate treatment effect and safety of BT in the intended use population.52 There are still many questions that remain unanswered regarding the role of BT in the treatment of asthma. Asthma Seminars in Respiratory and Critical Care Medicine

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experts question the validity and clinical significance of the published trails, especially the AIR-2 data. A recent critical analysis of the available literature noted that many of the outcomes, touted as indicative of success, were not mutually exclusive (i.e., patients with more hospitalizations will also likely have more emergency department visits). In addition, these outcomes were highly influenced by the presence of outliers, which were not excluded from analysis, and that one patient, in particular, in the sham group, had nine hospitalizations. Exclusion of this individual from analysis would have potentially impacted the statistical significance of the study.53 Even if the clinical endpoints achieved in the AIR-2 trial are valid, it remains unclear why a therapy designed to reduce smooth muscle, and thus bronchoconstriction, does not affect FEV1. Mechanistically, it would make more sense that reduction of exacerbations, without improvement in pulmonary function, would be related to alterations in inflammatory response to asthma triggers and not simple reduction in airway wall smooth muscle mass. In addition, there is a growing realization that asthma is not a single disease and that multiple asthma phenotypes with different clinical and physiological characteristics exist which have very different responses to specific pharmacologic therapies.39,44,54 Current patient identification strategies for BT are focused on severity of disease without consideration of the phenotypic subsets which would most likely benefit from treatment and more research is needed to define characteristics predictive of successful BT. The use of biomarkers to predict response to BT is being evaluated in an ongoing clinical trial.55 Endobronchial biopsy has been shown to be useful in identifying asthma phenotypes most likely to respond to specific medical therapy.56 One small study has used endobronchial biopsy performed before and after BT to better define histology and treatment response.57 It is not practical or safe, however, to

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sal and submucosal airway wall during bronchoscopy.58 In a feasibility study, OCT has been used to assess response to BT.59 Radial probe balloon-based endobronchial ultrasound is a readily available technology that has successfully been used to measure airway wall thickness in patients with asthma and also might be useful in selecting patients for BT and monitoring treatment response.60 Recent studies show that CFM may have a role in identifying some remodeling changes in asthma because elastic fibers (which represent a major component of

routinely obtain airway biopsies in all patients eligible for BT. There may also be a high likelihood of obtaining inadequate (crush artifacts, limited cellularity) or nonrepresentative samples. Thus, biopsy surrogates such as optical coherence tomography (OCT) and confocal microscopy (CFM) with or without high-resolution radial balloon-based endobronchial ultrasonography have been proposed to study airway remodeling but need further exploration. OCT, for instance, allows real-time, near-microscopic resolution imaging of the muco-

BRONCHIAL THERMOPLASTY SKILLS AND TASKS 10 point ASSESSMENT TOOL BT-STAT

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Learner _____________________________________

training______________________ Faculty______________________________________ Date_______________________________

Items 1-10 each scored separately

Satisfactory Yes / No

1. Patient correctly identified (3 points each, target 6 points): [] Patient’s identity confirmed [] Consent obtained

Yes / No Score___/6

2. Patient is appropriate for BT (1 points each, target 10 points):

Yes / No

[] NPO status reviewed [] Prednisone intake reviewed [] No signs of active respiratory infection [] No asthma attack within the past 2 weeks [] No dose change of systemic steroids in the past 2 weeks [] No known bleeding disorder [] Anticoagulant and antiplatelet therapy reviewed [] O2 sat > 90% on room air [] No increase in asthma symptoms requiring more than 4 rescue puffs [] Post bronchodilator FEV1 > 85% of patient’s baseline

Score___/10

3. Contraindications reviewed (3 points each, target 9 points):

Yes / No

[] implantable pacemaker, defibrillator or other electronic device [] sensitivity to drugs necessary for bronchoscopy [] previous treatment with Alair system

Score___/9 Yes / No

4. Equipment and supplies (2 points each, target 6 points): [] functioning RF generator [] Alair catheters [] Diagnostic bronchoscope 5. Pre procedure patient management (2 points each, target 6 points):

Score___/6 Yes / No

[] lidocaine nebulization administered [] bronchodilators nebulization administered [] patient is a candidate for moderate sedation or general anesthesia 6. BT treatment sessions (15 points each session, no partial points given): [] Session 1 (RLL): includes [] RB6 [] RB7

Score___/6 Yes / No

[] RB8 [] RB9 [] RB10

Fig. 3 Bronchial thermoplasty assessment tool.

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[] Session 2 (LLL): includes [] LB6 [] LB7+8

Miller, Murgu

[] LB9 [] LB10

[] Session 3 (RUL and LUL): includes [] RB1 [] RB2 [] RB3 [] LB1+2 [] LB3

[]

Score___/15

LB4 [] LB5 7. BT systematic approach in each segment (5 points each, target 20 points):

Yes / No

[] work from distal (subsubsegmental) to proximal (subsegmental) airways [] treat all visible airways [] use a dedicated airway map to track the treated airways [] avoid double treatment in the same airway

Score___/20

8. Reasons to terminate the procedure (2 points, target 8 points)

Yes / No

[] airway edema [] bronchoconstriction [] tenacious mucus /mucus plugging Score___/8

[] inability to access the target airways 9. Post procedure care (3 points each, target 12 points):

Yes / No

[] discharge home if post bronchodilator FEV1 > 80% of pre-procedure value and patient has no respiratory symptoms [] assure patient takes Prednisone 50 mg po on post procedure day 1 [] follow up phone calls Q 12 hrs X 2; then at 48 hrs and 1 week Score___/12

[] schedule outpatient visit in 2 -3 weeks 10. Post procedure hospital admission (1 points each, target 8 points):

Yes / No

[] significant cough persisting beyond 2 hours [] post-BD FEV1 < 80% of preprocedure value [] persistent hypoxia 130 bpm [] unexpected altered mental status during or after procedure [] significant hemoptysis [] requirement for bronchodilator every 2 hours on more than 3 occasions [] unexpected absence of a companion or caretaker at home FINAL GRADE:

PASS

Score___/8

FAIL

SCORE:________/100 Fig. 3 (Continued)

the extracellular matrix in the airway wall) and their disruption can be identified with bronchoscopic CFM.61 These optical and acoustic modalities will require further studies to develop a better understanding of the true mechanistic effect of BT (or competing technology for that matter) and the phenotypic characteristics of patients most likely to achieve clinical benefit.

Education Emerging technologies can turn experienced bronchoscopists into novices. Even basic bronchoscopy training is fundamentally changing as low fidelity and virtual reality simulators make bronchoscopy training much less of an apprenticeship and more of a predictable discipline. Both procedures described in this article are currently taught as part of structured curricula at national and international courses. Endobronchial valve placement, for example, requires technical skills to ensure proper placement and removal. For BT, Seminars in Respiratory and Critical Care Medicine

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assessment of quality of intervention is challenging because there are no long-term changes seen with conventional imaging (i.e., CT) or white light bronchoscopy, which would potentially indicate procedure quality. In the AIR-2 trial, for instance, a mean of 151 activations were performed in the three treatment sessions.51 In clinical practice, however, there is a wide variability in the number of activations performed depending on the patient’s anatomy, level of sedation, and the patience of the operator. The use of standardized assessments of targeted criteria has been shown to improve operating room performance in surgical trainees62 and validated assessment tools have been shown to be useful in the evaluation of fundamental bronchoscopy skills.63 Development and implementation of validated competency-based metrics specific to advanced bronchoscopic interventions, to assure competency before credentialing, is crucial in ensuring maximal success and safety, even for operators experienced in other bronchoscopic

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14 Menkes H, Traystman R, Terry P. Collateral ventilation. Fed Proc

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modalities. Checklists and assessment tools for IBV placement and BT (►Fig. 3) have been developed and implemented at national and international congresses, but validation studies are required before their implementation in fellowship training programs. Assessment tools are increasingly relevant instruments for the objective and standardized evaluation of bronchoscopy trainees. Bronchoscopic treatment for emphysema and asthma may be incorporated in clinical practice in the near future. If this happens, there will be a need for widespread implementation in the fellowship training programs of structured curricula including validated assessment tools, problem-based learning exercises, low and high fidelity simulation. Targeted, curriculum-specific, faculty development programs will assure competent and learner-centric educators for the newly developed bronchoscopic technologies.64

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Interventional pulmonology for asthma and emphysema: bronchial thermoplasty and bronchoscopic lung volume reduction.

Emphysema and asthma are responsible for economic and social burden. Altering the natural course of these diseases is a field of intense research. The...
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