Endobronchial Lung Volume Reduction: A Continued Search for Physiology-Based Therapies

As COPD continues to cause significant morbidity and mortality worldwide, the search for safe and effective therapies continues. To date, the only therapies for COPD that have shown to improve survival are smoking cessation,¹ oxygen therapy,^2,3 and lung volume reduction surgery (LVRS) in a subgroup of patients.⁴ However, a significant number of patients with advanced COPD that we encounter in the outpatient clinic have already exhausted two of these therapies and may not be appropriate candidates for LVRS. The most common patient is the former smoker receiving oxygen therapy who has homogeneous or diffuse destruction of lung tissue. This patient is frequently a poor surgical candidate by virtue of his or her low exercise capacity, low FEV₁, low Dlco, or significant comorbidities. In these patients, endobronchial strategies that minimize the serious morbidity associated with LVRS,⁵ such as persistent air leak, respiratory failure, pneumonia, cardiac arrhythmias, and peridiaphragmatic scarring,⁶ appear very attractive.

The two endobronchial volume reduction technologies currently available are based on different physiologic principles.^7,8 The first one is based on the collapse of anatomic airway passages into destroyed segments of the lung, thus reducing the lung volume. This technique includes the use of one-way valves, fibrin, trypsin, glue, etc. The second one is based on changing the flow dynamics by opening extraanatomical airway passages and directing the flow of air from hyperinflated areas to larger airways bypassing the flow-limited segments of the emphysematous airways.^9,10

It appears, at least by physiologic principle, that the blockade of air entry during inspiration, while allowing gas exit during exhalation and mucus drainage, has resulted in lung volume reduction and reduction of hyperinflation in varying degrees when used in patients with heterogeneous upper lobe emphysema. These results are encouraging but have produced primarily subjective improvement in dyspnea scores and composite (health-related quality of life [QOL]) outcomes without clinically significant changes in objective physiologic outcome measures. Furthermore, these strategies appear to be short-lived when compared with LVRS and have mainly addressed patients with heterogeneous upper-lobe disease.

On the other hand, the creation of airway bypass channels experience is limited but rapidly growing. To date, experience has been reported with the Broncus Bypass Tract System (Broncus Technologies; Mountain View, CA) for 19 patients, and there is a recently finalized, larger clinical trial awaiting review of data. The 19 patients showed an immediate improvement in dyspnea score and lung function tests (FEV₁, FVC, and residual volume). Particularly interesting were the health-related QOL markers, reduction in residual volume, and improvement of dyspnea and vital capacity in a subset of patients with homogeneous disease with significant hyperinflation (total lung capacity >133% predicted).¹⁰

Regarding safety, the Broncus Technologies device was used in a safety trial in patients undergoing lobectomy for lung cancer or lung transplant due to emphysema.¹¹ There were no major complications and two minor cases of bleeding. The initial technique involved the use of endobronchial ultrasound to decrease the risk of vascular puncture and create bronchial fenestrations using a radiofrequency probe.

Further simplification of the technique involves the use of a 22-gauge transbronchial needle, followed by an angioplasty catheter with an expandable balloon and placement of a metallic stent. In order to prevent early closure of the newly formed channels, the use of mitomycin-C and paclitaxel has shown promise at 20 and 12 weeks, respectively, in canine models.¹²

Most recently, the Exhale Airway Stents for Emphysema (EASE) trial, an international multicenter, randomized, sham-controlled study, investigated the safety and effectiveness of airway bypass in patients with severe homogeneous emphysema. The EASE trial recently finalized enrollment, and the researchers presented an abstract at the 2009 American Thoracic Society meeting in San Diego, CA, describing their experience at one of the centers.¹³ Their results were encouraging, although preliminary, as the endpoints for clinical effectiveness will be measured at 6 months and followed up for 5 years (Figs 1-5).

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This is an exciting time in the world of emphysema and interventional pulmonary medicine. With new technologies becoming available, there is a renewed responsibility for the pulmonologist to identify therapies that may benefit his or her patients and act accordingly with timely referral.

 

References

1. Anthonisen NR, Skeans MA, Wise RA, et al. The effects of a smoking cessation intervention on 14.5-year mortality: a randomized clinical trial. Ann Intern Med 2005; 142:233-239
2. Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease. Ann Intern Med 1980; 93:391-398
3. Report of the Medical Research Council Working Party. Long-term domiciliary oxygen therapy in chronic bronchitis and emphysema. Lancet 1981; 1:681-685
4. 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
5. Naunheim KS, Wood DE, Krasna MJ, et al. Predictors of operative mortality and cardiopulmonary morbidity in the NETT. J Thorac Cardiovas Surg 2006; 131:43-53
6. Gelb AF, McKenna RJ, Brenner M, et al. Lung function after bilateral lower lobe lung volume reduction surgery in α₁-antitrypsin emphysema. Eur Respir J 1999; 14:928-933
7. Ingenito EP, Wood DE, Utz JP. Bronchoscopic lung volume reduction in severe emphysema. Proc Am Thorac Soc 2008; 5:454-460
8. Sahi H, Karnak D, Meli Y, et al. Bronchoscopic approach to COPD. COPD 2008; 5:125-131
9. Lausberg HF, Chino K, Patterson GA, et al. Bronchial fenestration improves expiratory flow in emphysematous human lungs. Ann Thorac Surg 2003; 75:393-397
10. Macklem PT, Cardosa P, Snell G, et al. Airway bypass: a new treatment for emphysema [abstract]. Proc Am Thorac Soc 2006; 167:A726
11. Choong CK, Haddad FJ, Gee EY, et al. Feasibility and safety of airway bypass stent patency. J Thorac Cardiovasc Surg 2005; 129:632-638
12. 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; 131:60-64
13. Voelker KG, Horiuchi TK, Ferreira GJ, et al. Airway bypass for severe homogeneous emphysema: initial experience in one US center [abstract]. Am J Respir Crit Care Med 2009; 179:A4390

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Submitted by: Erik Folch, MD, MSc, and Michael Machuzak, MD

Acknowledgement: The authors would like to extend their appreciation to Terese Bogucki at Broncus Technologies for providing photographs and diagrams for this manuscript. Dr. Machuzak was a one-time consultant with Bronchus Technologies in January 2008.