Emerging therapies for COPD: Bronchoscopic treatment of emphysema
- Michael S Machuzak, MD
Michael S Machuzak, MD
- Department of Pulmonary, Allergy and Critical Care Medicine
- Cleveland Clinic
- Thomas R Gildea, MD, MS
Thomas R Gildea, MD, MS
- Department of Pulmonary, Allergy and Critical Care Medicine and Transplant Center
- Cleveland Clinic
Emphysema is a form of chronic obstructive pulmonary disease (COPD) that is defined by abnormal and permanent enlargement of the airspaces distal to the terminal bronchioles and is associated with destruction of the alveolar walls. The destruction of alveolar walls causes loss of elastic recoil, early airway closure during exhalation, and air trapping in the distal air spaces. Alveolar wall destruction with formation of emphysematous blebs and bullae leads to loss of gas exchanging surface (also known as increased physiologic dead space). In addition, air trapping and hyperinflation press the diaphragm into a flat configuration, rather than its normal domed shape, and place all the muscles of respiration at a mechanical overstretch disadvantage. In combination, these processes lead to refractory dyspnea.
Lung volume reduction surgery (LVRS, also called reduction pneumoplasty or bilateral pneumectomy) is a surgical treatment for patients with advanced emphysema whose dyspnea is poorly controlled with the usual therapies (eg, short and long acting bronchodilators, inhaled glucocorticoids, supplemental oxygen, and pulmonary rehabilitation) . LVRS entails reducing the lung volume by wedge excisions of emphysematous tissue. However, surgical morbidity is high and non-pulmonary comorbidities may preclude surgery.
Bronchoscopic lung volume reduction (bLVR) refers to techniques developed to treat hyperinflation due to emphysema via a flexible bronchoscope.
The devices and techniques for bLVR will be reviewed here. The general management of COPD, an overview of flexible bronchoscopy, and the roles of lung volume reduction surgery, bullectomy, and lung transplantation in the management of advanced COPD are discussed separately. (See "Management of stable chronic obstructive pulmonary disease" and "Flexible bronchoscopy in adults: Overview" and "Lung volume reduction surgery in COPD" and "Lung transplantation: General guidelines for recipient selection".)
RATIONALE FOR LUNG VOLUME REDUCTION
The mechanisms by which lung volume reduction might provide benefit in patients with emphysema are not known with certainty. However, it is believed that the removal of diseased, hyperinflated areas of lung would have the following benefits:
- Fishman A, Martinez F, Naunheim K, et al. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med 2003; 348:2059.
- West, JB. Pulmonary Pathophysiology; the essentials, 5th, Lippincott, Williams & Williams, Baltimore 1998. p.49.
- Ingenito EP, Wood DE, Utz JP. Bronchoscopic lung volume reduction in severe emphysema. Proc Am Thorac Soc 2008; 5:454.
- Herth FJ, Gompelmann D, Ernst A, Eberhardt R. Endoscopic lung volume reduction. Respiration 2010; 79:5.
- Snell GI, Holsworth L, Borrill ZL, et al. The potential for bronchoscopic lung volume reduction using bronchial prostheses: a pilot study. Chest 2003; 124:1073.
- Toma TP, Hopkinson NS, Hillier J, et al. Bronchoscopic volume reduction with valve implants in patients with severe emphysema. Lancet 2003; 361:931.
- Yim AP, Hwong TM, Lee TW, et al. Early results of endoscopic lung volume reduction for emphysema. J Thorac Cardiovasc Surg 2004; 127:1564.
- 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.
- Hillerdal G, Mindus S. One- to four-year follow-up of endobronchial lung volume reduction in alpha-1-antitrypsin deficiency patients: a case series. Respiration 2014; 88:320.
- Strange C, Herth FJ, Kovitz KL, et al. Design of the Endobronchial Valve for Emphysema Palliation Trial (VENT): a non-surgical method of lung volume reduction. BMC Pulm Med 2007; 7:10.
- Sciurba FC, Ernst A, Herth FJ, et al. A randomized study of endobronchial valves for advanced emphysema. N Engl J Med 2010; 363:1233.
- Herth FJ, Noppen M, Valipour A, et al. Efficacy predictors of lung volume reduction with Zephyr valves in a European cohort. Eur Respir J 2012; 39:1334.
- Coxson HO, Nasute Fauerbach PV, Storness-Bliss C, et al. Computed tomography assessment of lung volume changes after bronchial valve treatment. Eur Respir J 2008; 32:1443.
- Terry PB, Traystman RJ, Newball HH, et al. Collateral ventilation in man. N Engl J Med 1978; 298:10.
- Macklem PT. Collateral ventilation. N Engl J Med 1978; 298:49.
- Fessler HE. Collateral ventilation, the bane of bronchoscopic volume reduction. Am J Respir Crit Care Med 2005; 171:423.
- Aljuri N, Freitag L. Validation and pilot clinical study of a new bronchoscopic method to measure collateral ventilation before endobronchial lung volume reduction. J Appl Physiol (1985) 2009; 106:774.
- Gompelmann D, Eberhardt R, Michaud G, et al. Predicting atelectasis by assessment of collateral ventilation prior to endobronchial lung volume reduction: a feasibility study. Respiration 2010; 80:419.
- Herth FJ, Eberhardt R, Gompelmann D, et al. Radiological and clinical outcomes of using Chartis™ to plan endobronchial valve treatment. Eur Respir J 2013; 41:302.
- Klooster K, ten Hacken NH, Hartman JE, et al. Endobronchial Valves for Emphysema without Interlobar Collateral Ventilation. N Engl J Med 2015; 373:2325.
- Ninane V, Geltner C, Bezzi M, et al. Multicentre European study for the treatment of advanced emphysema with bronchial valves. Eur Respir J 2012; 39:1319.
- Wood DE, McKenna RJ Jr, Yusen RD, et al. A multicenter trial of an intrabronchial valve for treatment of severe emphysema. J Thorac Cardiovasc Surg 2007; 133:65.
- Jones PW. Interpreting thresholds for a clinically significant change in health status in asthma and COPD. Eur Respir J 2002; 19:398.
- Sciurba FC, Criner GJ, Strange C, et al. Effect of Endobronchial Coils vs Usual Care on Exercise Tolerance in Patients With Severe Emphysema: The RENEW Randomized Clinical Trial. JAMA 2016; 315:2178.
- Deslée G, Mal H, Dutau H, et al. Lung Volume Reduction Coil Treatment vs Usual Care in Patients With Severe Emphysema: The REVOLENS Randomized Clinical Trial. JAMA 2016; 315:175.
- Deslee G, Klooster K, Hetzel M, et al. Lung volume reduction coil treatment for patients with severe emphysema: a European multicentre trial. Thorax 2014; 69:980.
- Slebos DJ, Klooster K, Ernst A, et al. Bronchoscopic lung volume reduction coil treatment of patients with severe heterogeneous emphysema. Chest 2012; 142:574.
- Herth FJ, Eberhard R, Gompelmann D, et al. Bronchoscopic lung volume reduction with a dedicated coil: a clinical pilot study. Ther Adv Respir Dis 2010; 4:225.
- Hillerdal G, Gustafsson G, Wegenius G, et al. Large emphysematous bullae. Successful treatment with thoracoscopic technique using fibrin glue in poor-risk patients. Chest 1995; 107:1450.
- Reilly J, Washko G, Pinto-Plata V, et al. Biological lung volume reduction: a new bronchoscopic therapy for advanced emphysema. Chest 2007; 131:1108.
- Ernst A, Anantham D. Endoscopic management of emphysema. Clin Chest Med 2010; 31:117.
- Berger RL, Decamp MM, Criner GJ, Celli BR. Lung volume reduction therapies for advanced emphysema: an update. Chest 2010; 138:407.
- Ingenito EP, Reilly JJ, Mentzer SJ, et al. Bronchoscopic volume reduction: a safe and effective alternative to surgical therapy for emphysema. Am J Respir Crit Care Med 2001; 164:295.
- Ingenito EP, Berger RL, Henderson AC, et al. Bronchoscopic lung volume reduction using tissue engineering principles. Am J Respir Crit Care Med 2003; 167:771.
- 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.
- Refaely Y, Dransfield M, Kramer MR, et al. Biologic lung volume reduction therapy for advanced homogeneous emphysema. Eur Respir J 2010; 36:20.
- Strange, C, Criner, G, Leeds, W, et al. Improved Efficacy of Biological Lung Volume Reduction (BLVR) Therapy with Lobar Targeting. Am J Respir Crit Care Med 2009; 179:A4391.
- Herth FJ, Gompelmann D, Stanzel F, et al. Treatment of advanced emphysema with emphysematous lung sealant (AeriSeal®). Respiration 2011; 82:36.
- Come CE, Kramer MR, Dransfield MT, et al. A randomised trial of lung sealant versus medical therapy for advanced emphysema. Eur Respir J 2015; 46:651.
- Snell GI, Hopkins P, Westall G, et al. A feasibility and safety study of bronchoscopic thermal vapor ablation: a novel emphysema therapy. Ann Thorac Surg 2009; 88:1993.
- 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.
- Higuchi T, Reed A, Oto T, et al. Relation of interlobar collaterals to radiological heterogeneity in severe emphysema. Thorax 2006; 61:409.
- Lausberg HF, Chino K, Patterson GA, et al. Bronchial fenestration improves expiratory flow in emphysematous human lungs. Ann Thorac Surg 2003; 75:393.
- Choong CK, Phan L, Massetti P, et al. Prolongation of patency of airway bypass stents with use of drug-eluting stents. J Thorac Cardiovasc Surg 2006; 131:60.
- Choong CK, Haddad FJ, Gee EY, Cooper JD. Feasibility and safety of airway bypass stent placement and influence of topical mitomycin C on stent patency. J Thorac Cardiovasc Surg 2005; 129:632.
- 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.
- Shah PL, Slebos DJ, Cardoso PF, et al. Bronchoscopic lung-volume reduction with Exhale airway stents for emphysema (EASE trial): randomised, sham-controlled, multicentre trial. Lancet 2011; 378:997.