|Subject:||Endobronchial Valve Devices|
|Policy #:||SURG.00119||Current Effective Date:||04/05/2016|
|Status:||Reviewed||Last Review Date:||02/04/2016|
This document addresses the use of endobronchial valve devices (EBVs). This type of device is intended to provide one-way airflow blockage in segmental or subsegmental bronchi for individuals with pulmonary conditions complicated by air leaks or hyperinflation. Endobronchial valve devices are usually placed transorally into the lungs using flexible bronchoscopic tools.
Note: Please see the following documents for related information:
Investigational and Not Medically Necessary:
The use of endobronchial valve devices is considered investigational and not medically necessary for the treatment of any condition including, but not limited to, emphysema and pulmonary air leaks.
The use of endobronchial valves (EBVs) has been investigated for the treatment of various pulmonary conditions complicated by air leaks or hyperinflation. The available literature addresses several different devices, the Emphasys EBV® and the Zephyr® endobronchial valve (both manufactured by Pulmonx; Redwood City, CA), the IBV® Valve (Spiration, Inc., Redmond, WA), and the Endobronchial Watanabe Spigots (EWS®, Novatech, France). At this time, only the IBV device has U.S. Food and Drug Administration (FDA) approval for use in the U.S.
EBV for Emphysema
The vast majority of the available literature regarding the use of EBVs addresses the treatment of severe emphysema (Coxson, 2008; de Oliveira, 2006; Snell, 2003; Sterman, 2010; Toma, 2003; Venuta, 2005; Wan, 2006; Wood, 2007; Yim, 2004). There are additional studies that describe the use of EBVs as a bridge to transplantation (Venuta, 2010), for the treatment of chronic obstructive pulmonary disease (COPD) (Hopkinson, 2005), and as treatment for pulmonary air leaks due to a variety of etiologies (Travaline, 2009). Without exception, these reports are all case series studies involving small study populations. The largest study included 98 subjects (Wan, 2006), but the majority involved fewer than 40 subjects. Most of these studies, including the larger ones, have reported significant loss to follow-up and are of short duration, with most reporting data from between 3 and 6 months follow-up. Only three reports have followed subjects 12 months or longer, but these studies suffered significant (42% to 80%) loss to follow-up.
The initial data from these limited studies demonstrates mixed results, with some studies reporting significant improvements in pulmonary function (Oliveira, 2006; Toma, 2003; Venuta, 2005; Wan, 2006; Yim, 2004) and others reporting none (Coxson, 2008; Snell, 2003; Sterman, 2010; Wood, 2007). Additionally, there is a wide reporting gap with regard to complications. While some studies report no serious complications, most studies report serious device- or procedure-related complications such as pneumothorax, pneumonia, exacerbation of COPD, brochospasm, and in one case, death. Due to the limited utility of these studies, because of the aforementioned methodological flaws and conflicting results, the reported results from these studies are not particularly useful in assessing the long-term safety and efficacy of EBVs.
One large-scale randomized clinical trial (RCT) addressed the use of Zephyr endobronchial valves. The VENT Study was an international trial conducted at 31 sites in the U.S and 32 in Europe. In 2010, Sciurba and others published the findings from the U.S. study for individuals with advanced heterogenous emphysema (n=321). Study participants were randomized in a 2:1 fashion to receive EBV placement procedure or standard medical care. Study subjects were followed for 12 months post intervention. The authors reported modest improvements in lung function, exercise tolerance, and symptoms. The 6-minute walk test increased 9.3 m in the EBV group as compared to 10.7 m in the control group (p=0.02). The clinical significance of this small change is not clear. Similarly, while the St. George's Respiratory Questionnaire score decreased 2.8 points for the EBV group as compared to a 0.6 point decrease in the control group (p=0.04), the clinical significance of this change is also unclear. No significant difference was reported between groups in relation to composite complication scores. However, when individual complications were addressed separately, subjects in the EBV group experienced significantly more episodes of COPD exacerbations requiring hospitalization, massive hemoptysis, pneumothorax and air leaks. The authors reported that at the 12 month follow-up, 8 participants were removed from the study due to implant migration. No data was presented regarding tissue erosion. The authors stated that their findings indicate that the use of EBVs may be more beneficial for individuals with severe heterogenous emphysema and intact interlobar fissures. In 2012, Herth and colleagues reported on the results of the VENT study in the European study population. The report includes 111 subjects randomized to receive treatment with the Zephyr device and 60 to receive standard medical management. A total of 157 subjects (92%) completed the study. At 6 months, the EBV subjects demonstrated a significant improvement compared with the controls for mean change in cycle ergometry (2 ± 14 W vs. -3 ± 10 W; p=0.04) and St George's Respiratory Questionnaire (SGRQ) (-5 ± 14 points vs. 0.3 ± 13 points; p=0.047). No significant change was noted with regard to FEV1 (7 ± 20% vs. 0.5 ± 19%; p=0.067). At 12 months, subjects in the EBV group had significantly improved FEV1 (6 ± 26% vs. -2 ± 20%; p=0.0499) and cycle ergometry workload (1 ± 13 W vs. -5 ± 12 W; p=0.03) scores compared with controls. Complete fissure as measured by CT scan was noted in 63 subjects (37.1%, 44 EBV group vs. 19 control, no p-value provided). In these individuals, EBV therapy was associated with significant (p≤0.05) or borderline significant (p≤0.10) improvement for FEV1, cycle ergometry workload and St George's Respiratory Questionnaire (SGRQ) score. Target lung volume reduction (TLVR) was achieved in a significantly greater number of EVB subjects vs. controls, when complete fissure was noted on CT. Lobular occlusion was noted in 48% (53 of 111) of EBV subjects. Among these subjects, those with complete fissure (n=20) had significantly higher lung volume reduction. Furthermore, in those EBV subjects with lobular occlusion, both 6 and 12 month clinical outcomes were better than in those without lobular occlusion or controls. Rates for serious complications did not differ significantly at either endpoint. Over the 12 month follow-up, the rates for valve expectoration, aspiration or migration was 12.6% (14 of 111) over 386 days. While these reports provide some data regarding the short-term safety of the Zephyr device, further data is needed to evaluate the efficacy and long-term safety of these devices, as well as optimal candidate selection criteria.
Retrospective data from the VENT study, which was analyzed by Argula and colleagues (2013), investigated the impact of perfusion on the 6 month improvement in 6-minute walk test distance (6MWTD). They reported that subjects with a low target lobe regional perfusion had a significant improvement in 6MWTD when compared with those with a high baseline target lobe regional perfusion (30.24 m vs. 3.72 m, p=0.03). Shifts in perfusion after EBV therapy occurred only in subjects with high baseline perfusion and did not correlate with improved 6MWTD. They also reported an interesting interaction between gender and baseline perfusion of the target lobe, where women had a better improvement in 6MWTD compared with men, as long as lobar exclusion was achieved. This effect was independent of baseline perfusion. These results may help identify subpopulations of individuals with emphysema who could benefit from EBV treatment, but additional data from prospective trials is warranted to fully understand which populations stand to benefit from EBVs.
Another retrospective analysis of VENT data was published by Valipour in 2013, who reported on the impact of EBV treatment on BODE Index scores. The BODE is a multidimensional grading system, which has been shown to be useful in predicting the risk of future COPD exacerbations, hospitalizations and/or death in individuals with COPD. The authors reported clinically significant improvement in BODE scores in 44% of EBV subjects and in 24.7% of controls (p=0.001). Worsening BODE scores were noted in 25% of EBV subjects and 39% of controls (p=0.001). The degree of target lobar volume reduction (TLVR) was reported to have a significant impact on BODE scores, with improvements in the BODE index of at least 1 point observed in 67%, 37%, and 41% of subjects with TLVR > 50%, TLVR between 20% and 50%, and TLVR < 20%, respectively (p=0.011 for intergroup differences). Baseline BODE score was reported as the only independent predictor of changes in BODE scores at 6 months. A safety analysis found significant differences in the rate of pulmonary/thoracic adverse events, with a higher rate occurring in EBV subjects compared with controls. This difference was mainly driven by the following subcategories of adverse events: hemoptysis (42% in EBV subjects vs. 2% in control subjects, p<0.0001), and noncardiac chest pain (16% compared with 3% respectively, p=0.0018).
The BeLieVeR-HIFi study was a randomized controlled double-blind study involving 50 subjects with heterogeneous emphysema and intact interlobar fissures who were assigned to treatment with either the Zephyr endobronchial valve (n=25) or a sham procedure (n=25) (Davey, 2015). All subjects were followed for 3 months post-operatively. Significant improvements in the EBV group vs. controls were noted with regard to increased FEV1 (median 8.77% vs. 2.88%; Mann-Whitney p=0.0326), 6-minutes walking time (25 meters vs. 3 meters; p=0.0119), and change in endurance time (25 seconds vs -10.8 seconds, p=0.0256). In the EBV group, 8 subjects were scored as having complete lung collapse in the isolated portion of the lung, 5 with a band of atelectasis, 2 with some volume reduction, and 8 with no change. There were 2 deaths in the EBV group and 1 control subject was unable to attend the follow-up assessment because of a prolonged pneumothorax. Additionally, 2 EBV subjects had pneumothorax responding to standard therapy, and 4 EBV subjects expectorated the valves before 3 months. These were replaced in 3 of the 4 subjects. The authors concluded that unilateral lobar occlusion with EBVs produced significant improvements in lung function, but there was a risk of significant complications. They noted that further trials are needed that compare valve placement with lung volume reduction surgery.
In 2015, Klooster published the results of a blinded RCT involving 34 subjects with severe emphysema assigned to treatment with the Zephyr endobronchial valve compared to 34 subjects assigned to standard medical care. Subjects were followed for 6 months following EVB placement. The EBV group had 9 subjects lost to follow-up vs. 1 subject in the control group. In the intent-to-treat analysis, the authors report that there was significant improvement noted in the EBV group vs. the control group in FEV1, forced vital capacity (FVC), and 6-minute walk distance (p<0.01 for all). Similar findings were reported in the per-protocol analysis (p=0.001 for all). Additional improvements in the EBV group vs. controls in the per-protocol analysis included St. Georges Respiratory Questionnaire (SGRQ; p<0.001) and the Clinical COPD Questionnaire (CCQ; p=0.002). The authors reported that EBV-related "unacceptable adverse events" had occurred in 7 of 34 (21%) of EBV group subjects. Overall 23 serious adverse events were noted in the EBV group vs. 5 in the control group (p<0.001), including pneumothorax (p=0.02) and additional events requiring valve removal or replacement procedures. Pneumothorax was reported in 6 of 34 EBV subjects (18%). The high rate of complications in this study with carefully selected subjects warrants additional investigation.
Kotecha and colleagues published the results of a small retrospective case series of individuals with emphysema treated with the Emphasys endobronchial device (2009). Only 16 of the original 23 subjects completed the study with greater than 15 months follow-up. The authors report that small but statistically significant improvements in FEV1 were found in 6 of 16 subjects (30.8% pre-treatment vs. 34.1% post-treatment). Small but statistically significant improvements in DLco were also noted in 11 of 16 subjects (34.7% pre-treatment vs. 39.5% post-treatment). However, these improvements were not correlated with functional changes in the study population, so it is difficult to assess their clinical relevance. Three subjects who failed to have any significant improvement post valve placement subsequently underwent lung transplantation. All three explanted lungs were examined macroscopically. In all three cases extensive mature granulation tissue had formed around the valves, possibly obstructing the valve opening and interfering with valve patency.
Further investigation into the safety and efficacy of EBV therapy in subjects with emphysema is warranted.
EBV for Pulmonary Air Leaks
EBVs have also been proposed for the treatment of pulmonary air leaks. The vast majority of the available literature addressing this approach has been in the form of case reports (Anile, 2006; Dalar, 2013; De Giacomo, 2006; Feller-Kopman, 2006; Ferguson, 2006; Mitchell, 2006; Schweigert, 2010; Snell, 2005). However, there is a growing body of literature, in the form of small case series studies. The largest available case series study published to date was conducted by Travaline and others (2009), and reported on the outcomes of 40 subjects with prolonged pulmonary air leaks treated with the Zephyr device. At the end of a mean 66 days of follow-up (range 7-166 days), 47.5% of subjects had complete resolution, 45.0% had a significant reduction, and 5.0% had no change in condition. No correlation was found between the location of the valve placement or air leak etiology and outcomes. Six of the 40 subjects had adverse reactions due to valve placement including valve expectoration, oxygen desaturation, valve malpositioning requiring replacement, and pneumonia. Eight of the subjects had the valves removed at the end of the study period. While these findings are promising, further studies with larger populations and longer follow-up time are warranted to provide additional data regarding the safety and efficacy of this treatment method.
A series involving 24 subjects with persistent pulmonary air leaks treated with the EWS device was published by Sasada and others (2011). Treatment was indicated for air leaks due to pneumothorax (n=15), empyema (n=8), or postsurgical complications (n=1). Twelve subjects (50%) had complete resolution of air leaks and 7 (29.2%) had a reduction in air leaks. Five (20.8%) showed no improvement. Twenty-three subjects required thoracic drainage tubes, which were successfully removed after EBV treatment in 15 subjects (65.2%). Of the 24 subjects, 4 experienced severe respiratory failure requiring mechanical ventilation but were successfully treated. Complications included EBV migration (n=4), atelectasis (n=3), pneumonia (n=2), fever (n=2), and lung abscess (n=1), but none resulted in death. Six subjects underwent removal of the EBV devices including 4 subjects with abscess and atelectasis. Two additional subjects underwent removal at their request.
Firlinger (2013) reported on 13 consecutive subjects with high comorbidity and evidence of continuous air leaks and chest tubes for at least 7 days. Each subject received treatment with the EWS device. Ten subjects were considered responders, and 3 were non-responders. After valve implantation, air leak flow decreased significantly from 871 ± 551 mL/min to 61 ± 72 mL/min immediately after the intervention (p<0.001). The mean duration of chest tube drainage was 18 ± 8 days before and 9 ± 6 days after the intervention (p<0.01). Long-term follow-up was available for 9 subjects. No adverse events related to the valve implantation were reported. Seven subjects underwent valve removal without any further complications.
Dooms and colleagues described the use of EBVs in 10 subjects who had undergone lung cancer resection surgery with subsequent persistent air leaks refractory to conservative therapy. The median air leak cessation was reported to be 2 days after treatment. Overall, a significant decrease in FEV1 was found at airway closure by valve implantation (p=0.0002). Chest tube removal occurred at a median of 4 days (range 1-14 days). Three subjects experienced a recurrence of limited air leaks (<50% of initial value) due to valve displacement without migration. Upon bronchoscopic evaluation, shallow depth of the bronchus was reported as the cause. No deaths, no cardiovascular complications, and no implant-related events were reported. One subject suffered from respiratory insufficiency requiring negative positive pressure ventilation for 2 weeks until the valves were removed.
Based on the limited evidence available, the use of EBVs for pulmonary air leaks is promising. However, the available studies are not rigorous in their methodology or in their sample sizes. Further study is warranted with well designed and conducted trials.
In individuals with severe emphysema, diseased tissues progressively lose their elasticity and fail to expand and contract properly, impeding air flow and gas exchange. In more advanced forms of the disease, the elasticity of lung tissue is completely lost, leading to permanently open air sacs that cannot contribute to ventilation. The diseased tissue fails to contract normally, which results in portions of the chest cavity being taken up by nonfunctional tissue. This constricts the existing healthy tissue, making it less efficient and results in poorer overall lung function. In emphysema, diseased tissue may occur throughout the lung or may be heterogeneous, occurring more severely in certain areas.
One method of treating heterogeneous emphysema is lung volume reduction surgery (LVRS). This procedure has been developed to remove the most diseased lung tissue, providing more space in the chest cavity for healthier lung tissue to expand, and resulting in improved ventilation and lung function. LVRS is a drastic and permanent surgical procedure and it has only been used in the most serious cases.
Some individuals may develop air leaks in lung tissue due to a wide variety of reasons, including trauma, disease or due to complications of surgery. An air leak in the pulmonary tract may be due to a hole between the lung and the pleural space, or a passageway that has been created between functional lung tissue and adjacent tissues. Air leaks significantly impair lung function and usually require surgical treatment if they do not spontaneously resolve.
Endobronchial valve devices have been developed as a method to isolate diseased or problematic portions of the lung without a major surgical procedure. These devices are designed to fit snugly into segmental or subsegmental bronchi and allow the flow of air and secretions out of the targeted portion of the lung but prevent return flow. The devices may be permanently implanted or can be removed at a later date, if needed. In cases of emphysema, these devices have been proposed as an alternative to LVRS. The placement of endobronchial valve devices has been used in experimental studies to isolate diseased portions of the lung without the need for a major surgical procedure. The valves allow the air trapped in severely diseased portions of the lung to be forced out with normal respiratory movement. Prevention of return air flow causes a reduction in the size of diseased portions of the lung, allows expansion of healthier tissue and improves function of healthier tissue. This procedure may be referred to transbronchoscopic lung volume reduction surgery.
In the case of air leaks, the use of endobronchial valves allows isolation of the area of the lung where the air leak is located, allowing normal function in the rest of the lung. This procedure isolates the problematic area of the lung, and may allow tissues to heal, resolving the air leak problem.
Currently, only one bronchial valve device has been reviewed by the FDA. The IBV Valve System, (Spiration, Inc. Redmond, WA) was granted a humanitarian device exemption (HDE) for the indication of controlling prolonged air leaks of the lung, or significant air leaks that are likely to become prolonged air leaks, following lobectomy, segmentectomy, or lung volume reduction surgery (LVRS). The IBV device consists of an endobronchial valve and a deployment catheter. Using a flexible bronchoscope, the catheter is used to place the small umbrella-shaped valve into the lung. Other valves have been described in the medical research literature including: the Emphasys EBV and the Zephyr endobronchial valve (both manufactured by Pulmonx; Redwood City, CA), and Endobronchial Watanabe Spigots (EWS, Novatech, France).
The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.
When services are Investigational and Not Medically Necessary:
When the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.
|31647||Bronchoscopy, rigid or flexible, including fluoroscopic guidance, when performed; with balloon occlusion, when performed, assessment of air leak, airway sizing, and insertion of bronchial valve(s), initial lobe|
|31648||Bronchoscopy, rigid or flexible, including fluoroscopic guidance, when performed; with removal of bronchial valve(s), initial lobe|
|31649||Bronchoscopy, rigid or flexible, including fluoroscopic guidance, when performed; with removal of bronchial valve(s), each additional lobe|
|31651||Bronchoscopy, rigid or flexible, including fluoroscopic guidance, when performed; with balloon occlusion, when performed, assessment of air leak, airway sizing, and insertion of bronchial valve(s), each additional lobe|
|0BH30GZ-0BH38GZ||Insertion of endobronchial valve into right main bronchus [by approach; includes codes 0BH30GZ, 0BH33GZ, 0BH34GZ, 0BH37GZ, 0BH38GZ]|
|0BH40GZ-0BH48GZ||Insertion of endobronchial valve into right upper lobe bronchus [by approach; includes codes 0BH40GZ, 0BH43GZ, 0BH44GZ, 0BH47GZ, 0BH48GZ]|
|0BH50GZ-0BH58GZ||Insertion of endobronchial valve into right middle lobe bronchus [by approach; includes codes 0BH50GZ, 0BH53GZ, 0BH54GZ, 0BH57GZ, 0BH58GZ]|
|0BH60GZ-0BH68GZ||Insertion of endobronchial valve into right lower lobe bronchus [by approach; includes codes 0BH60GZ, 0BH63GZ, 0BH64GZ, 0BH67GZ, 0BH68GZ]|
|0BH70GZ-0BH78GZ||Insertion of endobronchial valve into left main bronchus [by approach; includes codes 0BH70GZ, 0BH73GZ, 0BH74GZ, 0BH77GZ, 0BH78GZ]|
|0BH80GZ-0BH88GZ||Insertion of endobronchial valve into left upper lobe bronchus [by approach; includes codes 0BH80GZ, 0BH83GZ, 0BH84GZ, 0BH87GZ, 0BH88GZ]|
|0BH90GZ-0BH98GZ||Insertion of endobronchial valve into lingula bronchus [by approach; includes codes 0BH90GZ, 0BH93GZ, 0BH94GZ, 0BH97GZ, 0BH98GZ]|
|0BHB0GZ-0BHB8GZ||Insertion of endobronchial valve into left lower lobe bronchus [by approach; includes codes 0BHB0GZ, 0BHB3GZ, 0BHB4GZ, 0BHB7GZ, 0BHB8GZ]|
Peer Reviewed Publications:
Bronchoscopic lung volume reduction surgery
IBV Valve System
Transbronchoscopic lung volume reduction surgery
Zephyr Endobronchial Valve System
The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.
|Reviewed||02/04/2016||Medical Policy & Technology Assessment Committee (MPTAC) review. Updated Rationale and Reference sections. Removed ICD-9 codes from Coding section.|
|Reviewed||02/13/2014||MPTAC review. Updated Rationale and Reference sections.|
|Reviewed||02/14/2013||MPTAC review. Updated rationale and reference sections.|
|01/01/2013||Updated Coding section with 01/01/2013 CPT changes; removed 0250T, 0251T, 0252T deleted 12/31/2012.|
|Reviewed||02/17/2011||MPTAC review. Updated Rationale and Reference sections.|
|New||11/18/2010||MPTAC review. Initial document development.|