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Endobronchial Valves for Advanced Emphysema: An Endobronchial Follow-up

Salcedo, Pablo S. MD*; Seijo, Luis M. MD; Zulueta, Javier J. MD*

Journal of Bronchology & Interventional Pulmonology: January 2014 - Volume 21 - Issue 1 - p 47–50
doi: 10.1097/LBR.0000000000000035
Bronchoscopic Images

Lung volume reduction surgery is a therapeutic option for selected patients with advanced emphysema. However, it is an invasive procedure benefitting only a selected group of patients with heterogenous upper lobe predominant disease and limited exercise capacity. The most widely studied alternatives are endobronchial valves. Hundreds of patients worldwide have undergone endobronchial valve placement. Although short-term outcomes have been described, little is known about the long-term side effects following this treatment, and endoscopic follow-up is virtually nonexistent. The images, biopsies, and microbiologic evidence accrued from this patient are witnesses to the natural evolution of endobronchial valves in the airways and should offer a word of caution with regard to valve placement in patients with life expectancies exceeding those typical of severe chronic obstructive lung disease.

*Pulmonary Department, Clínica Universidad de Navarra, Pamplona

Pulmonary Department, IIS—Fundación Jimenez Díaz—CIBERES, Madrid, Spain

Disclosure: There is no conflict of interest or other disclosures.

Reprints: Luis M. Seijo, MD, Médico Adjunto, Servicio de Neumología, IIS—Fundación Jiménez Díaz—CIBERES, Avda de los Reyes Catolicos 2, Madrid 28040, Spain (e-mail:

Received May 24, 2013

Accepted November 13, 2014

Lung volume reduction surgery (LVRS) is a therapeutic option for selected patients with advanced emphysema. However, it is an invasive procedure benefitting only a selected group of patients with heterogenous upper lobe predominant disease and limited exercise capacity.1–7 Minimally invasive endoscopic alternatives to LVRS have been developed to match surgical results, while avoiding its morbidity and mortality. The most widely studied alternatives are endobronchial valves (EV).8–11

Experience with EV in the treatment of advanced emphysema, although limited, continues to grow. Several prospective randomized trials have been completed to date. Data regarding safety, efficacy, quality of life, and exercise tolerance is now available.1–7,12 However, long-term consequences and outcomes with valve placement are poorly understood because follow-up in most studies is limited to 12 months. We hereby describe the clinical and endoscopic follow-up of a patient 3 years after the valve placement. Most of the valves in this patient were eventually removed and replaced by a bioactive polymer in a sequential lung volume reduction endoscopic treatment.

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A 70-year -old man with upper lobe predominant severe emphysema and chronic obstructive lung disease (COPD) was initially assessed in 2008 for participation in a randomized trial of EV. The patient was included in the study after signing an informed consent approved by the institutional review board and the regional ethics committee. Ten EVs (Spiration Inc., Redmond, WA) were deployed in his upper lobes. Lobar occlusion was initially avoided to minimize the risk of pneumothorax. The patient improved dramatically following the treatment, relinquishing home oxygen therapy. However, despite a significant improvement in his quality of life scores, no change was observed in the 6-minute walk distance, lung volumes, or other objective parameters of lung function. The patient worsened after 2 years, experiencing progressive dyspnea (MMRC dyspnea sore of 3 in April 2011). He reported an average of 2 acute COPD exacerbations per year, with sputum isolates including Moraxella catarrhalis and Stenotrophomonas maltophilia in 2008 and 2009, respectively. Follow-up bronchoscopy was performed in May 2011. EV migration, fracture, or failure was ruled out. Most EVs were surrounded by granulation tissue (Fig. 1A). The presence of white, verrucous, exophytic lesions was observed affecting the surrounding mucosa as well as the EVs (Figs. 1B–D). Endobronchial biopsies were obtained from the abnormal mucosa revealing normal bronchial epithelium and mucus (Fig. 2A) and a moderate lymphoplasmacytic inflammatory infiltrate with mild fibrosis (Fig. 2B). No metaplasia or atypia was observed. Citrobacter freundii and S. maltophilia were isolated on culture of the bronchial aspirates and were treated appropriately. An additional EV was placed in the untreated right upper lobe (RUL) subsegment to attempt lobar occlusion without any subjective improvement. RUL valve removal was carried out in September of 2011 because of persistent cough and dyspnea despite repeated antibiotic therapy. This lobe was the most affected lobe based on lung perfusion scanning. Neisseria and Achromobacter species were isolated from the bronchial aspirate culture. Following a 3-month recovery period, his RUL segments were treated with a bioactive polymer (Aeriseal; Aeris Therapeutics, Woburn, MA), which led to a brief, yet, clinically significant improvement. He subsequently continued to experience recurrent COPD exacerbations, which were attributed to the remaining valves in his left upper lobe. The valve removal was undertaken during February of 2013. All valves on the left side could be removed except one. Multiple bacterial isolates were obtained both from the valves as well as the bronchial aspirates including Klebsiella pneumoniae, Morganella morganii, Corynebacterium amycolatum, and S. maltophilia. The patient received appropriate antibiotic treatment and has since improved clinically and physiologically with his FEV1 rising to 910 mL. His current chest x-ray exhibits both, the effect of Aeriseal treatment in the RUL as well as the remaining valve in the left upper lobe (Fig. 3).







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Spiration’s EV were designed to remain in the airway indefinitely in patients with advanced emphysema, although they can be removed in case complications arise or placement is suboptimal. In fact, one of the chief advantages of the EBV system compared with other methods of lung volume reduction, both surgical and endoscopic, is its potential reversibility.8–13 Valve removal may be necessary for a variety of reasons including misplacement, migration, worsening dyspnea, local complications, infection, or failure to meet clinical expectations. Removal is simple in most cases, especially soon after deployment but can be quite complicated if the valves have been in place for a prolonged period of time. In some cases, granulation tissue, inflammation, fibrosis, and infection can set in and make valve removal challenging or impossible. Valve removal was necessary in <10% of all 71 patients treated as part of the European EBV randomized trial in which this particular patient was enrolled. Progressive worsening of dyspnea despite an excellent initial result, failure of lobar exclusion probably due to the presence of collateral ventilation following a second intervention, and recurrent COPD exacerbations attributed to foreign body–related colonization of the airway by various pathogens were the reasons for valve removal in our patient.

Medical device-related colonization and infection of the treated airway is a well known phenomenon. For example, self-expandable metallic stents may erode adjacent structures, fracture, and become colonized by bacteria following placement for airway stenosis. Granulation tissue and epithelialization of the stents make their removal in many cases quite challenging even shortly after the placement. Stent-related complications are common and particularly challenging in patients with benign airway disease with long-term potential. Such complications led the Food and Drug Administration to recommend their use in patients with benign stenosis only as a last resort and limiting their use to malignant airway diseases, which is frequently associated with limited life expectancies.14,15

Endoscopic alternatives to EV have also been plagued by complications related to foreign body reactions as was the case with the Exhale system (Broncus Technologies Inc., Mountain View, CA). This endoscopic alternative was designed to act as a fenestration in the airway facilitating a bypass tract to reduce hyperinflation and air trapping. The technique is more complicated than valve placement, irreversible, and may have potentially catastrophic complications.16 In the Ease trial, 31% of the devices became occluded by granulation tissue and secretions making the benefits of treatment short-lived at best.8,11,17,18 The bioactive polymer appears safe; yet, treatment is also irreversible. Long-term data with this strategy are also lacking.19

Most studies of EV provide detailed information regarding functional outcomes and the patients’ physiologic response.1–7 Systematic endoscopic follow-up is not recommended or deemed necessary and was not routinely performed in most of the studies published to date. However, given what we know of stent-related complications, it is not surprising that some, if not all patients, might experience foreign body–related complications at some point during the follow-up. Although data from a single patient cannot be generalized, our patient’s clinical evolution is illustrative of what might happen to some patients treated with EV after years of follow-up, the complications that might arise and the challenges that may be encountered trying to remove valves which have been in place longer than a few months.

The verrucous lesions we encountered in our patient have not been described in the literature of valve placement but are commonly seen in patients with longstanding or inadvertent foreign body aspiration.2 Long-term follow-up in patients following valve placement was heretofore limited to 5 patients and 2 years of follow-up.2 At present, most valve placement protocols do not include routine endoscopic follow-up, as most patients with advanced emphysema might not tolerate sequential bronchoscopy and follow-up is usually limited in the context of a well-designed clinical trial to 1 year. However, some endoscopic volume reduction experts are currently performing routine bronchoscopic follow-up of these patients in order to identify those at risk and to remove valves which have become infected or may be the cause of recurrent COPD exacerbations (Dr Rosell, personal oral communication).

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Hundreds of patients worldwide have undergone endobronchial valve placement as a minimally invasive alternative to LVRS. Although short-term outcomes have been described, little is known about the long-term side effects following this treatment, and endoscopic follow-up is limited. The images, biopsies, and microbiologic evidence accrued from this patient are witnesses to the natural evolution of EV in the airways and should offer a word of caution with regard to valve placement in patients with life expectancies exceeding those typical of severe COPD.

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emphysema; bronchoscopy; endobronchial valves; lung volume reduction

© 2014 by Lippincott Williams & Wilkins.