REVIEW URRENT C OPINION

Bronchoscopic treatment of end-stage chronic obstructive pulmonary disease Edmond Cohen

Purpose of review Chronic obstructive pulmonary disease (COPD) is a progressive, debilitating disease that in its final stages cripples the patient. The disappointing results of the National Emphysema Treatment Trial study led to a decrease in the acceptance of lung volume reduction surgery as a therapy. Thus, it became clear that debilitated COPD patients would need innovative alternative nonsurgical procedures to potentially alleviate their symptoms. This review will address the various techniques of bronchoscopic lung volume reduction (BLVR). Recent findings In recent years, a variety of noninvasive BLVR procedures were developed in the hope of improving the respiratory status of these patients. BLVR aims to decrease the extent of hyperinflation due to emphysema and result in a beneficial effect similar to that from surgical resection. The most widely used BLVR devices are: endobronchial valves, foam sealant, metallic coils, airway bypass stents and vapor thermal ablation. In the USA, BLVR remains in the experimental phase. The treatment modalities should be individually tailored for each patient. Endobronchial valves are designed to exclude the most affected emphysematous regions from ventilation in order to induce lobar absorption atelectasis. Airway bypass stents target homogenous emphysema, whereas valves and thermal vapor ablation target heterogeneous emphysema. Biological sealants and endoscopic coil implants have been used in both homogenous and heterogeneous emphysema. Summary BLVR appears to be safer than surgery and presents an attractive alternative for the treatment of COPD patients. Unfortunately, the outcome data to date are inconclusive; the procedures remain experimental and any benefits unproven. However, the data that are emerging continue to appear promising. Keywords airway bypass stents, biological sealant, emphysema, endobronchial valves, endoscopic lung volume reduction, metallic coils, vapor thermal ablation

INTRODUCTION Emphysematous changes are widespread in the general population and especially common in smokers. It is estimated that in the USA 3.8 million adults are currently diagnosed with emphysema [1]. Emphysema is a progressive, debilitating disease, which in its final stages, cripples the patient and greatly impacts the patient’s quality of life, his/her family as well as the cost of medical care. It is associated with abnormal and permanent enlargement of the airspaces in the lung, loss of gas exchange surface area, air-trapping and hyperinflation. These lead to compromised lung mechanics, hypercapnea, dyspnea and hypoxia that often require oxygen therapy [2,3]. Medical therapy is often inadequate and without proven benefit. During the advanced phases of the disease, surgical and nonsurgical procedures are www.co-anesthesiology.com

performed in an attempt to alleviate the dyspnea and improve quality of life and survival.

LUNG VOLUME REDUCTION SURGERY Lung volume reduction surgery (LVRS) was initially introduced more than 50 years ago by Brantigan et al. [4]. They suggested that reducing the overall Icahn School of Medicine at Mount Sinai, New York, New York, USA Correspondence to Edmond Cohen, M.D., Professor of Anesthesiology, Director of Thoracic Anesthesia, Icahn School of Medicine at Mount Sinai, Department of Anesthesiology, Box 1010, One Gustave L. Levy Place, New York, NY 10029, USA. Tel: +1 212 241 7467; e-mail: [email protected] Curr Opin Anesthesiol 2014, 27:36–43 DOI:10.1097/ACO.0000000000000039 Volume 27  Number 1  February 2014

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KEY POINTS  The benefit from surgical treatment of emphysema, at best, is limited to a small, specific subgroup of patients. In an attempt to improve the quality of life of the majority of the patients who are not candidates for surgical treatment, noninvasive endoscopic lung volume reduction methods have been explored.  Endobronchial valves are effective in heterogeneous emphysema if there is a lobar or segmental exclusion. If collateral ventilation exists, their benefit is limited.  Biological sealants and endoscopic coil implants have been used in both homogenous and heterogeneous emphysema. Biological sealant can be effective when collateral ventilation is present.  Airway bypass stents target homogenous emphysema, whereas valves and thermal vapor ablation target heterogeneous emphysema.  These procedures are still in experimental phase in the USA, and none of them is approved by the Food and Drug Administration (FDA). However, the data that are emerging are encouraging. These techniques continue to evolve, and clinical experience is being accumulated.

[8 ]. The other two groups had similar or greater mortality with surgery. As the initial impression was that the mortality risk was higher with surgery, LVRS was met with significant skepticism by the pulmonary community. Concerns were raised relating to safety, patient selection, effectiveness, choice of surgical technique and cost. Because of these concerns, general acceptance by the medical community rapidly declined, and it is no surprise that in the 1990s more than 4000 LVRSs were performed annually in the USA compared with only some 200 reported currently [9].

BRONCHOSCOPIC LUNG VOLUME REDUCTION PROCEDURES Emphysema is a chronic progressive disease. Other than bilateral lung transplant, an option available to only a few patients, no procedure can cure the disease. It became clear that these sick debilitated patients would need some innovative alternative nonsurgical procedure to potentially alleviate their symptoms. In the recent years, a variety of noninvasive endoscopic lung volume reduction procedures were developed with the hope of improving the respiratory status of these patients [10 ]. The common principle underlying bronchoscopic lung volume reduction (BLVR) is the reduction of the hyperinflation due to emphysema via a flexible bronchoscope that would result in a beneficial effect similar to that of surgical resection [11,12]. The most widely used BLVR devices are: endobronchial valves, foam sealant, metallic coils, airway bypass stents and vapor thermal ablation. At the present time in the USA, none of these treatments has been approved by the FDA. In Europe, both the valves and the foam sealant are CE approved (that is, they have received certification approval in the European Union) for BLVR treatment, whereas thermal vapor ablation and coils have yet to be approved. &

lung volume, by means of multiple wedge excisions, would restore the elastic ‘pull’ on the small airways, and thereby improve pulmonary mechanics. As surgical staplers had not yet been introduced, surgery resulted in a high incidence of persistent air leaks, a significant mortality rate, and therefore did not gain wide acceptance. Interest in the Brantigan proposal was renewed by Cooper et al. [5], following their experience with lung transplantation. They noticed that the lung recipient’s distended chest reconfigured to the smaller volume of the donor lung. They suggested that by reducing the large residual volume, the diaphragm resumes its normally curved shape and lengthened configuration, improving lung function. LVRS gained in popularity despite evidence of limited short-term beneficial effects [6,7]. In an attempt to determine potential beneficial outcome of the procedure, the National Institutes of Health proposed the ‘National Emphysema Treatment Trial’ (NETT). This was a randomized multicenter prospective clinical trial of medical versus surgical treatments of patients with severe bilateral emphysema. The NETT study results were reported in 2003 and were somewhat disappointing. Out of 1228 randomized patients divided into four groups, depending on the extent of the emphysema and their exercise capacity, only the group with upper lobe emphysema and a low exercise capacity showed a significant reduction in mortality with surgery

PATIENT SELECTION AND ANESTHETIC MANAGEMENT Patients selected for BLVR are essentially pulmonary cripples with progressive dyspnea despite maximal medical treatment. They are at high risk for general anesthesia and represent a great challenge to the anesthesiologist. The typical patient has a forced expiratory volume in one second (FEV1) less than 0.5, L, arterial oxygen partial pressure (PaO2) less than 55 mmHg and arterial carbon dioxide partial pressure (PaCO2) more than 50 mmHg. Chest radiographs show hyperinflation and a residual volume of more than 150% of predicted. Cessation of

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Thoracic anesthesia

smoking is mandatory, and the patient must enroll in a rehabilitation program that includes an adequate 6-minute walk. The ideal candidate presents with a 30–40% reduction in perfusion to the upper lobes. The least favorable candidates by computed tomography (CT) scanning are those with a patchy, mottled pattern, uniformly affecting the lung [13]. Unlike LVRS, which must be performed under general anesthesia, these procedures can be managed under sedation in the spontaneously breathing patient. The ability to perform these procedures under sedation is a major advantage as general anesthesia, endotracheal intubation and paralysis may often necessitate postoperative ventilatory support. The procedures present a challenge because the line between deep sedation and respiratory depression in these patients is rather thin. Should general anesthesia be required, it can be performed through a laryngeal mask airway, which allows closer control of ventilation and enables the use of potent inhaled anesthetic agents. Placement of an arterial line for close hemodynamic monitoring and arterial blood sampling is recommended. There is no need for a large bore intravenous cannula as there are rarely large fluid shifts or major blood loss. Sedation can be achieved by infusion of remifentanil, dexmedetomidine or low doses of propofol. Close attention should be paid to end-tidal gas monitoring and the oxygen flow rate so as not to depress the hypoxic respiratory drive.

Endobronchial valves Endobronchial valves are unidirectional valves designed to reduce airflow during inspiration. They are placed in the most affected emphysematous regions of the lung. Patients with heterogeneous emphysema are ideal candidates for endobronchial valve therapy to achieve an end result of segmental or lobar reabsorption atelectasis, similar physiologically to surgical lung volume reduction. The most important factor determining successful treatment with endobronchial valves is the achievement of a ‘complete lobar exclusion’, that is the entire targeted segment would be excluded without collateral communication with other segments; otherwise that segment will fail to collapse [14,15]. Two types of valves are available: endobronchial valves (EBV, Zephyr, Pulmonx, Inc., Palo Alto, California, USA) and intrabronchial valves (IBV, Spiration, Olympus Medical Co., Tokyo, Japan), duck-billed (EBV) and umbrella-shaped (IBV) valves.

Endobronchial valves (Zephyr) The endobronchial valve has a duck-billed shape supported by a nickel-titanium (nitinol) selfexpanding, tubular mesh that is covered with a 38

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silicone membrane to form a seal between the valve and the bronchial wall (Fig. 1) [16]. One-way exit of distal air and mucus is facilitated by the central duckbill [17,18]. The valve is preloaded in a delivery catheter inserted through the working channel of a standard flexible bronchoscope, and expands against the bronchial wall when deployed. Generally, a number of valves are placed in each patient and the procedure is well tolerated under conscious sedation. Clinical experience with the valve was achieved in the ’Endobronchial Valve for Emphysema Palliation Trial’ [19]. In this prospective trial, 321 patients with severe emphysema were randomly assigned to receive an endobronchial valve or standard medical care. The improvement in lung function was unimpressive. In a 6-month follow-up, lung function testing revealed an improvement in the endobronchial valve group with a mean difference of 6.8% in FEV1, and a difference of 5.8% in improvement in the 6-minute-walk distance. The most common adverse event was accumulation of secretions.

Intrabronchial valve (Spiration) Intrabronchial valve (IBV) has a self-expanding umbrella-shaped nitinol framework with distal anchors to secure the valve in place (Fig. 2). The valve can be deployed through the working channel of a flexible bronchoscope under direct vision [20]. The currently available data on IBV valves are limited to a multicenter study in patients who had bilateral therapy. No significant changes were detected on spirometry, although more than 50% of the patients registered a 4-point reduction on St. George’s Respiratory Questionnaire (SGRQ). A multicenter study with a large number of patients is currently in progress [21]. The IBV valve is approved by the US FDA for the treatment of a continuous air leak. Lung volume reduction coils Nitinol spring-like coils in a straightened configuration are passed through the working channel of a flexible bronchoscope into subsegmental airways (Fig. 3) (LVRC, PneumRx, Inc., Mountain View, California, USA). When deployed, they coil up and tether the lung. They have been designed for the use in patients with either homogeneous or heterogeneous emphysema. In a pilot study using coils in heterogeneous and in homogeneous emphysema, there were substantial improvements in pulmonary function, lung volumes, 6-min walk test and quality of life [22]. Another pilot study investigated the efficacy of lung volume reduction coil treatment in 16 patients with only severe heterogeneous emphysema [23]. A Volume 27  Number 1  February 2014

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Zephyr: Second – Generation endobronchial valve (a)

(b)

(c)

FIGURE 1. Endobronchial valves (Zephyr Pulmonx, Inc.). (a): Zephyr Valve. (b): the valve is deployed in the airway through the working channel of a fiberoptic bronchoscope. (c): endoscopic images of the Zephyr valve in situ. Reproduced with permission from [16]. Copyright ß 2010 BioMed Central Ltd.

median number of 10 coils per lobe were placed, with a total of 260 coils. Two to 4 weeks following implantation, all patients showed significant improvements in pulmonary function, exercise capacity and quality of life, with no severe adverse events. This technique remains very much in its

(a)

infancy of development, and more clinical trials will be needed [24]. Polymeric lung volume reduction The procedure consists of administration of a rapidly polymerizing foam sealant called BioLVR,

(b)

(c)

FIGURE 2. IBV valve (Spiration Inc., Olympus). IBV valve. Schematic illustration of the valve mechanism. Endoscopic image of the IBV valve in situ. (2a) and (2b) are reproduced with permission from Spiration Inc., Olympus. (2c) is original. 0952-7907 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

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(a)

(b)

FIGURE 3. Lung volume reduction coils: (3a) Chest radiography following the implantation of lung volume reduction coils in the right upper lobe. (Reproduced with permission of romPrGae¨tanDesle´e, University Hospital of Reims, France). (3b) LVRC, PneumRxInc.

developed by adding chondroitin sulfate to the fibrin mixture (Fig. 4) [25 ] (PLVR, Aeris therapeutics, Inc. Woburn, Massachusetts, USA). The procedure is performed under conscious sedation. A flexible bronchoscope is introduced into hyperinflated alveoli, and the sealant is injected into those alveoli. The sealant causes inflammatory reactions that lead to fibrosis with remodeling. Unlike endobronchial valves, this therapy is not reversible, and therefore long-term follow-up is mandatory [26]. Functional lung volume reduction can take 6–8 weeks to show positive effect [27]. One important characteristic of the technique is that because the hydrogel sealant blocks the interalveolar pores and channels, it has the advantage of eliminating collateral ventilation. The presence of collateral ventilation is one of the causes for failure of the endobronchial and intrabronchial valves to promote atelectasis [28]. The technique has been used in a sheep model of papain-induced emphysema. After BioLVR, a 16% reduction in total lung capacity and a 55% reduction in residual volume were noted. At autopsy, no evidence was found of abscess formation, infection or granulomas. Scar formation was seen in 91% of treated segments [29]. In a preliminary human study of biologic lung volume reduction, 22 patients with upper lobe predominant emphysema were treated with 20 ml of hydrogel/subsegment and 28 with 10 ml of hydrogel/subsegment [30]. The 6-month follow-up revealed a greater improvement in forced vital capacity, FEV1 and residual volume in the higher dose group. Chest CT at 6 months revealed scarring &&

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and atelectasis in the previously hyperinflated area in the high-dose, but not in the low-dose group (Fig. 4). Biological lung volume reduction appears to be safe, and the response is dose-dependent. It is estimated that to achieve a result comparable to the removal of 20–30% of lung volume, as many as 12 subsegments may need to be sealed [31]. Airway bypass stents Airway bypass stenting or bronchial fenestration is a technique used to decompress areas of emphysema by placing a drug-eluting stent through a bronchial wall into an area with severe emphysematous disease (Fig. 5) [32] (EASE, Bronchus Technologies, Inc. Mountain View, California, USA). In these emphysematous areas, progressively distended distal emphysematous airways impose a high resistance to the outflow of trapped air. They act as a valve mechanism allowing the air to enter the low-resistance emphysematous space but prevent air outflow, therefore, the natural course of these emphysematous airways is to increase in size. In endoscopic airway bypass, newly created low-resistance bronchial fenestrations allow trapped air to escape by bypassing high-resistance obstructed airways and decrease their size [32,33]. Airway bypass procedures that are performed under general anesthesia are best indicated for patients with homogenous emphysema. A flexible bronchoscope, using a mini Doppler to identify a vessel-free area is introduced. Bronchial fenestration is followed by the placement of a paclitaxel-eluting stent to prevent granulation tissue from obstructing the stent. Volume 27  Number 1  February 2014

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Polymeric lung volume reduction (a)

(b)

6 months following the treatment

Baseline

FIGURE 4. Polymeric lung volume reduction (PLVR, Aeris therapeutics, Inc.): (a): CT scan of the patient prior to treatment. (b): CT scan 6 months following treatment with biological sealant. Note the shift of the interlobar fissure (arrows), which shows the target lobe volume reduction. CT, computed tomography. (Adapted with permission from [25 ]. Adaptations are themselves works protected by copyright. So in order to publish this adaptation, authorization must be obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation. &&

Airway bypass was studied in 35 patients. The results showed significant improvements in spirometry, 6-minute walk and St. George’s Respiratory Questionnaire after 1 month but were not sustained after 6 months. The multicenter ‘Exhale Airway Stents for Emphysema’ study of 208 patients confirmed that after 6 months the respiratory parameters were not significantly improved compared with a control group [34,35].

Bronchoscopic thermal vapor ablation Bronchoscopic thermal vapor ablation [(BTVA), Uptake Medical, Seattle, Washington, USA)] is another experimental technique developed to induce lung volume reduction. This technique consists of delivering heated water vapor for a few seconds through a special Inter Vapor catheter inserted through the working channel of a bronchoscope. Controlled doses of steam at 125 degrees C

TIME

(a)

A valve mechanism (c)

(b)

FIGURE 5. Airway bypass stents. (a): Schematic representation of the progressively increasing volume of emphysematous airway with time (original). (b): The reduction in size of the emphysematous airway following the insertion of the airway stents. (original). (c): Airway bypass stents: endoscopic image of the airway stent in situ (EASE, Broncos Technologies, Inc.). (5C Reproduced with permission from [32]. 0952-7907 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

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Bronchoscopy thermal vapor ablation (BTVA, Uptake Medical, Seattle, Wash., USA) (a)

(b)

(c)

Baseline

Six months following vapor ablation

FIGURE 6. Bronchoscopic thermal vapor ablation (BTVA, Uptake Medical). (a): Schematic illustration of the bronchoscopic thermal vapor Ablation technique. Prior to the application of the vapor, the catheter balloon is inflated to seal the targeted emphysematous airway. (b): CT scan of the patients prior to treatment. (c): CT scan of the patient 6 months following vapor ablation treatment. Note the scarring and the reduction in the size of the right upper lobe. CT computed tomography. (Adapted with permission from [25 ]. Adaptations are themselves works protected by copyright. So in order to publish this adaptation, authorization must be obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation. &&

induce an inflammatory reaction with subsequent fibrosis and scarring leading to lung volume reduction [36] (Fig. 6) [25 ]. In one study, 11 patients with heterogeneous emphysema treated by unilateral BTVA confirmed the feasibility and an acceptable safety profile. Furthermore, an improvement in health-related quality of life was observed [37]. A recently published multinational single arm study evaluated the efficacy of the bronchoscopic thermal vapor ablation in 44 patients with upper lobe predominant emphysema. A total of 24 patients received BTVA doses of 10 cal/g. Six months following the treatment, they experienced significant improvement in lung function, exercise capacity and health-related quality of life [38]. &&

CONCLUSION The benefit from surgical treatment of emphysema, at best, is limited to a small, specific subgroup of patients. In an attempt to improve the quality of life of the majority of the patients who are not candidates for surgical treatment, noninvasive 42

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endoscopic lung volume reduction methods have been explored. BLVR therapy appears to be safer than surgery and presents an attractive alternative for COPD patients who are physiologically fragile. Unfortunately, the recent data are not conclusive; these therapies remain experimental and any benefits unproven. However, the data that are emerging are encouraging. These techniques continue to evolve, and clinical experience is being accumulated [25 ,12]. In the USA, BLVR remains in the experimental stage. Some procedures are already approved for clinical use in Europe. It is not the case of ‘one therapy fits all’. The treatment modalities should be individualized to each patient. Endobronchial valves are designed to exclude the most affected emphysematous regions from ventilation and if segmental or lobar absorption atelectasis can be induced, a physiological effect similar to surgical lung volume reduction may be achieved. Airway bypass stents target homogenous emphysema, whereas valves and thermal vapor ablation target heterogeneous emphysema. Biological sealants and &&

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endoscopic coil implants have been used in both homogenous and heterogeneous emphysema [39 ]. In a recent editorial, it was stated: ‘We cannot be pleased with the current results, but we have learned a lot and we are aimed in the right direction. Certainly BLVR is a cutting-edge treatment that can potentially be applied in a very wide range of patients’ [39 ]. &

&

Acknowledgements None. Conflicts of interest Dr. Cohen developed the Cohen Flexitip Endobronchial Blocker with COOK Medical, Critical Care (Bloomington, Indiana, USA).

REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Summary Health Statistics for U.S, Adults: National Health Interview Survey 2008. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics; 2008; 112. 2. Lopez AD, Shibuya K, Rao C, et al. Chronic obstructive pulmonary disease: current burden and future projections. Eur Respi J 2006; 27:397–412. 3. Lopez AD, Mathers CD, Ezzati M, et al. Global burden of disease and risk factors. Washington (DC): World Bank; 2006. 4. Brantigan OC, Mueller E, Kress MB. A surgical approach to pulmonary emphysema. Am Rev Respir Dis 1959; 80:194. 5. Cooper JD, Trulock EP, Triantafillou AN, et al. Bilateral pneumonectomy (volume reduction) for chronic obstructive pulmonary disease. J Thorac Cardiovasc Surg 1995; 109:106–119. 6. Fessler HE, Reilly JR, Sugarbaker DJ. Lung volume reduction surgery for emphysema. N Engl J M 2004; 351:2562–2563. 7. Geddes D, Davies M, Koyama H, et al. Effect of lung-volume-reduction surgery in patients with severe emphysema. N Engl J Med 2000; 343:239. 8. Fishman A, Martinez F, Naunheim K, et al. National Emphysema Treatment & Trial Research Group: a randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med 2003; 348:2059–2073. This is the NETT study that compared the surgical versus the medical treatment of the patients with end stage COPD. The negative outcome of the surgical group played a major role in the declining popularity of LVRS. 9. Naunheim KS. Lung volume reduction surgery: a vanishing operation? J Thorac Cardiovasc Surg 2007; 133:1412–1413. 10. Herth FJF, Gompelmann D, Ernst A, Eberhardt R. Endoscopic lung volume & reduction. Respiration 2010; 79:5–13. This article reviews the various methods of BLVR and incorporates the clinical experience of the leaders in this field. 11. Sabanathan S, Richardson J, Pieri-Davies S. Bronchoscopic lung volume reduction. J Cardiovasc Surg (Torino) 2003; 44:101–108. 12. Ernst A, Anantham D. Bronchoscopic lung volume reduction. Semin Thoracic Surg 2010; 22:330–337. 13. Gaissert HA, Trulock EP, Cooper JD, et al. Comparison of early functional results after volume reduction or lung transplantation for chronic obstructive pulmonary disease. J Thorac Cardiovasc Surg 1996; 111:296. 14. Higuchi T, Reed A, Oto T, et al. Relation of interlobar collaterals to radiological heterogeneity in severe emphysema. Thorax 2006; 61:409–413. 15. Berger RL, DeCamp MM, Criner GJ, et al. Lung volume reduction therapies for advanced emphysema: an update. Chest 2010; 138:407–417.

16. Strange C, Herth FJ, Kovitz KL, et al. Design of the Endobronchial Valve for Emphysema Palliation Trial (VENT): a nonsurgical method of lung volume reduction. BMC Pulm Med 2007; 7:10; Copyright ß 2010 BioMed Central Ltd. 17. Wan IY, Toma TP, Geddes DM, et al. Bronchoscopic lung volume reduction for end-stage emphysema: report on the first 98 patients. Chest 2006; 129:518–526. 18. Venuta F, de Giacomo T, Rendina EA, et al. Bronchoscopic lung-volume reduction with one-way valves in patients with heterogeneous emphysema. Ann Thorac Surg 2005; 79:411–416. 19. Sciurba FC, Ernst A, Herth FJ, et al. VENT Study Research Group: a randomized study of endobronchial valves for advanced emphysema. N Engl J Med 2010; 363:1233–1244. 20. Springmeyer SC, Bollinger CT, Waddell TK, et al. Treatment of heterogeneous emphysema using the Spiration IBV valves. Thorac Surg Clin 2009; 19:247–253. 21. Sterman DH, Mehta AC, Wood DE, et al. IBV Valve US Pilot Trial Research Team: a multicenter pilot study of a bronchial valve for the treatment of severe emphysema. Respiration 2010; 79:222–233. 22. Herth FJF, Eberhardt R, Ernst A. Pilot study of an improved lung volume reduction coil for the treatment of emphysema. Am J Respir Crit Care Med 2009; 179:A6160. 23. Slebos DJ, Klooster K, Ernst A, et al. Bronchoscopic lung volume reduction coil treatment of patients with severe heterogeneous. Chest 2012; 142:574– 582. 24. Herth FJ, Eberhard R, Gompelmann D, et al. Bronchoscopic lung volume reduction with a dedicated coil: a clinical pilot study. Ther Adv J Respir Dis 2010; 4:225–231. 25. Gompelmann D, Herth FJF. Endoscopic lung volume reduction. Emphysema. && In: Mahadeva R, editor. Tech, Rijeka. Croatia: Croatia; 2012. ; ISBN: 978953-51-0433-9, 16. This article has a comprehensive review of all the methods of currently available LVR. 26. Berger RL, Decamp MM, Criner GJ, Celli BR. Lung volume reduction therapies for advanced emphysema: an update. Chest 2010; 138:407. 27. Herth FJ, Eberhardt R, Ingenito EP, et al. Assessment of a novel lung sealant for performing endoscopic volume reduction therapy in patients with advanced Emphysema. Expert Rev Med Devices 2011; 8:307–312. 28. Reilly J, Washko G, Pinto-Plata V, et al. Biological lung volume reduction: a new bronchoscopic therapy for advanced emphysema. Chest 2007; 131:1108–1113. 29. Rafael Y, Grandfield M, Kramer MR, et al. Biological lung volume reduction therapy for advanced homogeneous emphysema. Eur Respir J 2010; 36:20– 27. 30. Herth FJ, Gompelmann D, Stanzel F, et al. Treatment of advanced emphysema with emphysematous lung sealant (AeriSeal). Respiration 2011; 82:36–45. 31. Criner GJ, Pinto-Plata V, Strange C, et al. Biologic lung volume reduction in advanced upper lobe emphysema: phase 2 results. Am J Respir Crit Care Med 2009; 179:791–798. 32. Cardoso PF, Snell GI, Hopkins P, et al. Clinical application of airway bypass with paclitaxel- eluting stents: early results. J Thorac Cardiovasc Surg 2007; 134:974–981. 33. Choong CK, Macklem PT, Pierce JA, et al. Airway bypass improves the mechanical properties of explanted emphysematous lungs. Am J Respir Crit Care Med 2008; 178:902–905. 34. Shah P, Slebos DJ, Cardoso PF, et al., EASE trial study group. Bronchoscopic lung volume reduction with Exhale airway stents for emphysema (EASE trial): randomized, sham-controlled, multicentre trial. Lancet 2011; 378:997– 1005. 35. Henning F, Lausberg MD, Kimiaki C, et al. Bronchial fenestration improves expiratory flow in emphysematous human lungs. Ann Thorac Surg 2003; 75:393–398. 36. Snell GI, Hopkins P, Wetsall G, et al. A feasibility and safety study of bronchoscopic thermal vapor ablation: a novel emphysema therapy. Ann Thorac Surg 2009; 88:1993–1998. 37. Emery MJ, Eveland RL, Eveland K, et al. Lung volume reduction by bronchoscopic administration of steam. Am J Respir Crit Care Med 2010; 182:1282– 1291. 38. Snell G, Herth FJ, Hopkins P, et al. Bronchoscopic thermal vapour ablation therapy in the management of heterogeneous emphysema. Eur Respir J 2012; 39:1326. 39. Flandes Aldeyturriaga J. Bronchoscopic lung volume reduction: 7 lessons & learned(editorial). Arch Bronconeumol 2012; 48:221–222. This article has an excellent summary and recommendations on the current status of BLVR.

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Bronchoscopic treatment of end-stage chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a progressive, debilitating disease that in its final stages cripples the patient. The disappointing r...
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