In patients whose chronic advanced emphysema limits daily activity, bronchoscopic lung volume reduction (BLVR) therapy with valve replacement may offer a nonsurgical option.1,2 Valve replacement improves exercise tolerance, lung function, and quality of life (QoL).1,2  Emerging evidence shows that valve replacement may offer greater survival benefits: 5-year survival rate of 44% to 63% with valve therapy vs 14% with surgical lung volume reduction.1,3

There are 2 types of valves that have been shown to restrict inspiratory airflow to hyperinflated lung regions.1 By reducing the size of the hyperexpanded portions of the lung, the valves improve overall respiratory mechanics.1

The outer cylindrical frame of the endobronchial valve (EBV), which was approved by the US Food and Drug Administration (FDA) in June 2018, has a wire mesh and lumen that has a 1-way valve.1,4 The investigational intrabronchial valve (IBV) has a nickel titanium alloy wire frame that prevents air from flowing inward yet allows expiratory flow to escape around the valve’s pliable covering.1,4-5 Both types of valves come in different sizes and are inserted via catheter.1

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Valve Therapy Compared With Other Modalities

Another minimally invasive modality, endobronchial coils, are also investigational.5 In a meta-analysis of 3 randomized controlled trials (RCTs) of endobronchial coils, 6 RCTs of endobronchial valves (EBV), and 2 RCTs of intrabronchial valves (IBV), both EBV and coils demonstrated clinically significant improvement in forced expiratory volume in 1 second (FEV1), 6-minute walk test (6MWT), and St George’s Respiratory Questionnaire (SGRQ) score from baseline, but IBV was not superior to conventional treatment.6

BLVR therapy, however, is not for every patient with advanced emphysema.1 Patient selection is critical in valve replacement therapy.1 Although patients are usually symptomatic with emphysematous chronic obstructive pulmonary disease (COPD), they cannot have had 3 or more exacerbations within a year; moderate or severe heart failure; or unstable cardiovascular disease, including stroke or myocardial infarction, within 6 months.1 To avoid pleural adhesions, valve replacements should not be attempted in patients who have had procedures in the target lung.1

How EBV Benefits Patients With Emphysema

A meta-analysis by Low and colleagues of 5 RCTs (N=703) demonstrated short-term improvement in patients with advanced emphysema by reducing hyperinflation and inducing atelectasis with minimally invasive EBV.7

The weighted mean difference (WMD) for FEV1 in the EBV group compared with the control group was 11.43 (95% CI, 6.05-16.80; P <.0001) and −5.69 for the SGRQ score (95% CI, −8.67 to −2.70; P =.0002).7 However, there was no significant difference between the groups in the 6MWT (14.12; 95% CI, −4.71 to 32.95; P =.14). Overall, complications between the groups were not significant, except for pneumothorax (relative risk [RR], 8.16; 95% CI, 2.21-30.11; P =.002), hemoptysis (RR, 5.01; 95% CI, 1.12-22.49; P =.04), and valve migration (RR, 8.64; 95% CI, 2.01-37.13; P =.004).7

“With the recent FDA approval of using endobronchial valves for severe emphysema, clinicians should strongly consider placing the valves in patients who have respiratory symptoms attributed to COPD such as dyspnea, limitation in activities, or poor quality of life due to breathlessness,” said pulmonology and critical care medicine fellow See-Wei Low, MD, from the University of Arizona in Tucson, in an interview with Pulmonology Advisor.

Predicting Complications in Valve Replacement Procedures

To better characterize the factors leading to EBV posttreatment pneumothorax, van Geffen and colleagues scanned 64 patients (mean age, 59 years; 67% women) with high-resolution computed tomography (HRCT) before the valve replacement. The number and location of pretreatment adhesions as detected by HRCT were associated with a higher risk for pneumothorax.8 Patients who developed pneumothorax had 2.7 (interquartile range [IQR], 1.9-4) adhesions compared with 1.7 (IQR, 1-2.7) in patients who did not develop pneumothorax (P <.01). Of the patients who developed pneumothorax, 25% were treated for upper lobe hyperinflation and 18% received lower lobe treatment.8

“One could advise pulmonologists to assess the CT scan prior to the intervention for pleural adhesions; if multiple adhesions are found and the patient is deemed to have an increased pneumothorax risk, several options can be considered to reduce risks,” said pulmonologist Wouter H. van Geffen, MD, PhD, from Medical Center Leeuwarden, and the University of Groningen in The Netherlands. “The most promising options are additional bed rest for 48 hours, cough suppression, and prolonged in-hospital observation.”

A study of 449 patients with emphysema (mean age, 64 years; 53.7% men) who underwent endoscopic valve therapy showed marked improvement in lung function and survival.2 Approximately one-third of patients (29%) developed complete lobar atelectasis, 11% developed pneumothorax without lobar atelectasis, and 58% experienced target lobe volume reduction. Patients who had atelectasis had better FEV1 rates, residual volume, and total lung capacity yet showed no significant difference in the BODE (body mass index, airflow obstruction, dyspnea score, and exercise capacity) index score. Patients whose valve therapy resulted in lobar atelectasis showed a greater survival benefit compared with patients without atelectasis (5-year survival rate, 65.3% vs 43.9%, respectively; P =.009).2 Pneumothorax in 84 patients had no effect on their survival (P =.52).2

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Factors Associated With Long-Term Survival

Researchers continue to predict survival outcomes in patients who undergo valve replacement.9 In a post hoc analysis of the STELVIO (Endobronchial Valves for Emphysema Without Interlobar Collateral Ventilation; Nederlands Trial Register No. NTR2876) trial, Klooster and colleagues found that the BODE score, the inspiratory capacity to total lung capacity ratio (IC/TLC), and the 6MWT can predict long-term survival.9 For example, a BODE score of <5 points was linked to >67% increased survival at 4 years postprocedure. Likewise, an IC/TLC ratio of <25% was associated with a mortality rate of 71% at median 34-month follow-up.9 Half of the patients whose 6MWT was <350-meter mark died within a year of the procedure.9

“Only approximately 1 out of 10 patients with advanced emphysema are eligible for valve treatment, so in some patients, coil treatment could be a good alternative,” explained Karin Klooster, PhD, from the department of pulmonary diseases at the University of Groningen, in an interview with Pulmonology Advisor. “However, this treatment is not commercially available. So, the only efficacious treatment could be lung volume reduction surgery.”

Summary and Clinical Applicability

BLVR therapy with EBV replacement shows the most promise for improving lung function, exercise tolerance, and QoL in patients with advanced emphysema. Further studies are needed to determine long-term survival.

Limitations and Disclosures



  1. Valipour A. Valve therapy in patients with emphysematous type of chronic obstructive pulmonary disease (COPD): from randomized trials to patient selection in clinical practice. J Thorac Dis. 2018;10(suppl 23):S2780-S2796.
  2. Gompelmann D, Benjamin N, Bischoff E, et al. Survival after endoscopic valve therapy in patients with severe emphysema [published online September 18, 2018]. Respiration. doi:10.1159/000492274
  3. Naunheim KS, Wood DE, Mohsenifar Z, et al; for the National Emphysema Treatment Trial Research Group. Long-term follow-up of patients receiving lung-volume-reduction surgery versus medical therapy for severe emphysema by the National Emphysema Treatment Trial Research Group. Ann Thorac Surg. 2006;82(2):431-443.
  4. US Food and Drug Administration (FDA). Zephyr® Endobronchial Valve System – P180002. Accessed November 10, 2018.
  5. FDAnews Device Daily Bulletin. FDA rejects endobronchial coil system for treating severe emphysema. . Accessed November 10, 2018.
  6. Wang Y, Lai TW, Xu F, et al. Efficacy and safety of bronchoscopic lung volume reduction therapy in patients with severe emphysema: a meta-analysis of randomized controlled trials. Oncotarget. 2017;8(44):78031-78043.
  7. Low SW, Lee JZ, Desai H, Hsu CH, Sam AR, Knepler JL. Endobronchial valves therapy for advanced emphysema: a meta-analysis of randomized trials [published online June 12, 2018]. J Bronchology Interv Pulmonol.  doi:10.1097/LBR.0000000000000527
  8. van Geffen WH, Klooster K, Hartman JE, et al. Pleural adhesion assessment as a predictor for pneumothorax after endobronchial valve treatment. Respiration. 2017;94(2):224-231.
  9. Klooster K, Hartman JE, Ten Hacken NHT, Slebos DJ. Improved predictors of survival after endobronchial valve treatment in patients with severe emphysema. Am J Respir Crit Care Med. 2017;195(9):1272-1274.

This article originally appeared on Pulmonology Advisor