From plugging air leaks to reducing lung volume: a review of the many uses of endobronchial valves.

INTRODUCTION: One-way endobronchial valve treatment improves lung function, exercise capacity, and quality of live in patients with severe emphysema and hyperinflation. Other areas of therapeutic application include treatment of persistent air leak (PAL), giant emphysematous bullae, native lung hyperinflation, hemoptysis, and tuberculosis. AREAS COVERED: In this review, we will assess the clinical evidence and safety of the different applications of one-way endobronchial valves (EBV). EXPERT OPINION: There is solid clinical evidence for the use of one-way EBV for lung volume reduction in emphysema. Treatment with one-way EBV can be considered for the treatment of PAL. The application of one-way EBV for giant bullae, post lung transplant native lung hyperinflation, hemoptysis, and tuberculosis is under investigation and more research is required to investigate the efficacy and safety of these applications.

Survival in COPD patients treated with bronchoscopic lung volume reduction.

BACKGROUND AND OBJECTIVE: Severe COPD patients can significantly benefit from bronchoscopic lung volume reduction (BLVR) treatments with coils or endobronchial valves. However, the potential impact of BLVR on survival is less understood. Therefore, our aim was to investigate the survival rate in patients who are evaluated for BLVR treatment and whether there is a difference in survival rate between patients who undergo BLVR treatment and patients who do not. METHODS: We included patients with COPD who visited our hospital for a consultation evaluating their eligibility for BLVR treatment and who performed pulmonary function tests during this visit. Furthermore, vital status was verified. RESULTS: In total 1471 patients were included (63% female, mean age 61 years). A total of 531 patients (35%) died during follow-up and the median survival time of the total population was 2694 days (95% confidence interval(CI) 2462-2926) which is approximately 7.4 years. The median survival time of patients who were treated with BLVR was significantly longer compared to patients who were not treated with BLVR (3133 days versus 2503 days, p < 0.001), and BLVR was found to be an independent predictor of survival when adjusting for other survival-influencing factors such as age, gender or severity of disease. CONCLUSIONS: Our results suggest that bronchoscopically reducing lung volume in patients with severe hyperinflation may lead to a survival benefit for a population with a severely reduced life expectancy.

HRCT characteristics of severe emphysema patients: Interobserver variability among expert readers and comparison with quantitative software.

PURPOSE: For a successful bronchoscopic lung volume reduction coil treatment it is important to place the coils in the most emphysematous lobes. Therefore assessment of the lobe with greatest destruction is essential. Our aims were to investigate the level of agreement among expert reviewers of HRCT-scans in emphysema patients and the comparison with QCT (quantitative computed tomography) software. METHOD: Five experienced CT-assessors, conducted a visual assessment of the baseline HRCT-scans of emphysema patients who participated in the RENEW bronchoscopic lung volume reduction coil study. On the same HRCT-scans, a QCT analysis was performed. RESULTS: In total 134 HRCT-scans were rated by all 5 experts. All 5 CT-assessors agreed on which was the most destructed lobe in 61 % of the left lungs (ƙ:0.459) and 60 % of the right lungs (ƙ:0.370). The consensus of the 5 assessors matched the QCT in the left lung for 77 % of the patients (ƙ:0.425) and in the right lung for 82 % (ƙ:0.524). CONCLUSIONS: Our results show that the interobserver agreement between five expert CT-assessors was only fair to moderate when evaluating the most destructed lobe. CT-assessor consensus improved matching with QCT determination of lobar destruction compared to individual assessor determinations. Because some CT-features are associated with treatment outcomes and important for optimal patient selection of bronchoscopic lung volume reduction treatment, we recommend including more than one CT-reviewer and supported by QCT measurements.

Temporary Right Middle Lobe Occlusion with a Blocking Device to Enable Collateral Ventilation Measurement of the Right Major Fissure.

BACKGROUND: Absence of interlobar collateral ventilation is essential to achieve lobar volume reduction after endobronchial valve (EBV) treatment and can be assessed using the Chartis measurement. However, especially in lower lobe measurements, Chartis can be complicated by the "no-flow phenomenon", during which a sudden cessation of flow is observed, leading to an unreliable measurement. If this phenomenon occurs in the right lower lobe, when measuring collateral flow over the right major fissure, the entrance to the right middle lobe should be occluded, and the Chartis balloon should be placed in the right upper lobe. Both Watanabe spigots and balloon catheters can be used to achieve occlusion. OBJECTIVE: Our aim was to demonstrate that right middle lobe occlusion with a blocking device is helpful in obtaining a reliable Chartis outcome in case of the no-flow phenomenon in the right lower lobe. METHODS: We performed a retrospective analysis of patients scheduled for EBV treatment in an EBV registry between September 2016 and September 2019. RESULTS: We included 15 patients with severe emphysema (median age 63 years [range 47-73], 73% female, and FEV1 24% [range 19-36] of predicted), who required temporary middle lobe occlusion (12 Watanabe spigot, 3 balloon catheter). After occlusion, a reliable Chartis outcome was obtained in all patients. CONCLUSION: Temporary middle lobe occlusion using a blocking device is helpful in obtaining a reliable Chartis outcome in case of a right lower lobe no-flow phenomenon.

Patient Selection for Bronchoscopic Lung Volume Reduction.

Purpose: Bronchoscopic lung volume reduction (BLVR) is a valuable treatment option for carefully selected patients with severe COPD. There is limited knowledge about the characteristics and outcomes of patients referred to a specialized center for BLVR. The study objectives were to investigate the selection rate for BLVR treatment in patients referred for this treatment and to investigate the differences between patients that were selected for BLVR and patients that were not. Patients and Methods: We performed a retrospective analysis of patients with severe COPD who were referred to our hospital to assess eligibility for BLVR treatment. Our parameters included demographics, comorbidity, chest computed tomography characteristics, reasons for rejection from BLVR treatment and patient survival. Results: In total, 1500 patients were included (mean age 62 years, 50% female and forced expiratory volume in 1 s 33% of predicted). Out of this group, 282 (19%) patients were selected for BLVR treatment. The absence of a suitable target lobe for treatment, an unsuitable disease phenotype and insufficient lung hyperinflation were the most important factors for not being selected. Patients that were selected for any BLVR option lived significantly longer than the group of patients that were not selected for BLVR (median 3060 versus 2079 days, P<0.001). Conclusion: We found that only a small proportion of patients that are referred for BLVR treatment is eligible for a BLVR treatment, indicating a need for both better referral tools and for the development of new therapies for this group of patients. Furthermore, our data suggest that selection for BLVR is associated with a significant survival benefit.

A New Oxygen Uptake Measurement Supporting Target Selection for Endobronchial Valve Treatment.

BACKGROUND: Adequate target lobe selection for endobronchial valve (EBV) treatment in patients with severe emphysema is essential for treatment success and can be based on emphysema destruction, lobar perfusion, lobar volume, and collateral ventilation. As some patients have >1 target lobe for EBV treatment, we were interested whether we could identify the least functional lobe. OBJECTIVES: The objective of this study was to investigate the relationship between endoscopic lobar measurement of oxygen uptake, lobar destruction, and vascular volume, and whether this could help in identifying the least functional lobe and thus optimal target for EBV treatment. METHOD: We prospectively included patients who were scheduled for EBV treatment in our hospital. A customized gas analysis setup was used to measure lobar O2 uptake after lobar balloon occlusion. Quantitative CT analysis was performed to assess the degree of emphysematous destruction and lobar arterial and venous volumes. RESULTS: Twenty-one (5 male/16 female) patients with emphysema (median age 63 years, FEV1 25% of predicted, residual volume 234% of predicted) were included, and 49 endoscopic lobar measurements were performed. A lower O2 uptake significantly correlated with a higher degree of emphysematous lobar destruction (Spearman's ρ: 0.39, p < 0.01), and lower arterial and venous vascular volumes of the lobes (-0.46 and -0.47, respectively; both p < 0.001). CONCLUSIONS: Endoscopic measurement of lobar O2 uptake is feasible in patients with emphysema. Measurement of lobar O2 uptake helped to identify the least functional lobe and can be used as additional tool for EBV target lobe selection.

Significant Differences in Body Plethysmography Measurements Between Hospitals in Patients Referred for Bronchoscopic Lung Volume Reduction.

During the evaluation of potential bronchoscopic lung volume reduction (BLVR) candidates in our hospital, we frequently observe patients with a lower residual volume (RV) value compared to the value measured in their referring hospital, although both measured by body plethysmography. We explored to what degree RV and other pulmonary function measurements match between referring hospitals and our hospital. We retrospectively analyzed a total of 300 patients with severe emphysema [38% male, median age 62 years (range 38-81), median forced expiratory volume in 1 s 29% (range 14-65) of predicted, and a median of 40 packyears (range 2-125)]. We measured a median RV of 4.47 l (range 1.70-7.57), which was a median 310 ml lower than in the referring hospitals (range - 3.04 to + 1.94), P < 0.001). In conclusion, this retrospective analysis demonstrated differences in RV measurements between different hospitals in patients with severe emphysema. Overestimation of RV can lead to unnecessary referrals for BLVR and potential treatment failures. To avoid disappointment and unnecessary hospital visits, it is important that body plethysmography measurements are accurately performed by applying preferably the unlinked method in these patients.

Collateral Ventilation Measurement Using Chartis: Procedural Sedation vs General Anesthesia.

BACKGROUND: Absence of interlobar collateral ventilation is key to successful endobronchial valve treatment in patients with severe emphysema and can be functionally assessed by using the Chartis measurement. This system has been validated during spontaneous breathing, undergoing procedural sedation (PS), but can also be performed under general anesthesia. Performing the Chartis measurement under PS is often challenging because of coughing, mucus secretion, and difficulties in maintaining an adequate level of sedation. The objective of this study was to investigate whether there is a difference in Chartis measurement outcomes between PS and general anesthesia. METHODS: In this prospective study, patients underwent Chartis measurements under both PS and general anesthesia. Study outcomes were Chartis measurement duration, number of measurements, feasibility, and success rate. RESULTS: The study included 30 patients with severe emphysema (mean age, 62 years; median FEV1, 29% of predicted). Chartis measurement duration was significantly longer under PS than under general anesthesia (mean, 20.3 ± 4.2 min vs 15.1 ± 4.4 min; P < .001). There was no difference in the number (median [range]) of measurements performed (2 [1-3] for PS vs 1 [1-3] for general anesthesia; P = 1.00). Chartis measurement was more feasible during general anesthesia (median sum of all feasibility scores, 12 [range, 6-26] for PS vs 7 [5-13] for general anesthesia; P < .001). There was no statistical difference in success rate: 77% of PS cases vs 97% of general anesthesia cases (P = .07). CONCLUSIONS: This study found that Chartis measurement under general anesthesia is faster and more feasible to perform compared with performance with PS, without affecting measurement outcomes. TRIAL REGISTRATION: Clinicaltrials.gov; No. NCT03205826; URL: www.clinicaltrials.gov.

Lung volume reduction with endobronchial coils for patients with emphysema.

The lung volume reduction coil treatment is a minimally invasive bronchoscopic treatment option for emphysema patients who suffer from severe hyperinflation. The treatment is aimed at a large group of patients where lung volume reduction surgery and bronchoscopic lung volume reduction using endobronchial valves are no option, or alternatively, can be offered as a bridge to lung transplantation. The nitinol coil exhibits a shape memory effect and is biologically inert. The lung volume reduction coil procedure is performed in two separate treatment sessions, targeting one lobe per session, with the contralateral lobe being treated 4 to 8 weeks after the first session. In one treatment session, around 10 to 14 coils, thereby treating an entire lobe, are being placed. Selecting optimally treated, symptomatic chronic obstructive pulmonary disease (COPD) patients with emphysema and severe hyperinflation, while avoiding significant airway disease such as asthma, chronic bronchitis and bronchiectasis, is key to achieve treatment success. Three randomized clinical trials investigating lung volume reduction coil treatment have been published until now, reporting the results of 452 treated patients up to 12 months after coil treatment. Lung volume reduction coil treatment results in significant improvement of pulmonary function outcomes and quality of life in patients with severe hyperinflation. The most common complications of lung volume reduction coil treatment are: COPD exacerbations, pneumonia, Coil Associated Opacity and an increased risk of pneumothorax. The purpose of this article is to describe the coil technique and review the available literature regarding effect, safety and future perspectives of lung volume reduction with coils for emphysema patients.

Chartis Measurement of Collateral Ventilation: Conscious Sedation versus General Anesthesia - A Retrospective Comparison.

BACKGROUND: Absence of interlobar collateral ventilation using the Chartis measurement is the key predictor for successful endobronchial valve treatment in severe emphysema. Chartis was originally validated in spontaneous breathing patients under conscious sedation (CS); however, this can be challenging due to cough, mucus secretion, mucosal swelling, and bronchoconstriction. Performing Chartis under general anesthesia (GA) avoids these problems and may result in an easier procedure with a higher success rate. However, using Chartis under GA with positive pressure ventilation has not been validated. OBJECTIVES: In this study we investigated the impact of anesthesia technique, CS versus GA, on the feasibility and outcomes of Chartis measurement. METHODS: We retrospectively analyzed all Chartis measurements performed at our hospital from October 2010 until December 2017. RESULTS: We analyzed 250 emphysema patients (median forced expiratory volume in 1 s 26%, range 12-52% predicted). In 121 patients (48%) the measurement was performed using CS, in 124 (50%) using GA, and in 5 (2%) both anesthesia techniques were used. In total, 746 Chartis readings were analyzed (432 CS, 277 GA, and 37 combination). Testing under CS took significantly longer than GA (median 19 min [range 5-65] vs. 11 min [3-35], p < 0.001) and required more measurements (3 [1-13] vs. 2 [1-6], p < 0.001). There was no significant difference in target lobe volume reduction after treatment (-1,123 mL [-3,604 to 332] in CS vs. -1,251 mL [-3,333 to -1] in GA, p = 0.35). CONCLUSIONS: In conclusion, Chartis measurement under CS took significantly longer and required more measurements than under GA, without a difference in treatment outcome. We recommend a prospective trial comparing both techniques within the same patients to validate this approach.

Minimal important difference of target lobar volume reduction after endobronchial valve treatment for emphysema.

BACKGROUND AND OBJECTIVE: Target lobar volume reduction (TLVR) is an important efficacy outcome measure for bronchoscopic lung volume reduction (BLVR) treatment using one-way endobronchial valves (EBV) in patients with severe emphysema. The commonly used cut-off value for TLVR that expresses a perceivable clinical benefit is -350 mL. However, a scientifically determined minimal important difference (MID) for TLVR never has been published. The objective of the present study was to determine the MID for TLVR on HRCT in patients who were treated with EBV. METHODS: A total of 318 patients with severe emphysema from two BLVR trials were analysed. Anchor-based methods were used to define the TLVR MID at 6 months follow-up. Forced expiratory volume in 1 s (FEV1 ), residual volume (RV) and St. George's Respiratory Questionnaire (SGRQ) were used as anchors. RESULTS: The calculated TLVR MID with each anchor was: FEV1 -587 mL, RV -534 mL and SGRQ -560 mL. The combined MID (average of the three anchor-based MIDs) was -563 mL. CONCLUSION: Using the anchor-based method, we established a TLVR MID of -563 mL in patients with severe emphysema at 6 months follow-up after EBV treatment. This value can be useful for both interpreting the results from trials and clinical practice, as well as for designing future studies on lung volume reduction.

The minimal important difference for the St George's Respiratory Questionnaire in patients with severe COPD.

The St George's Respiratory Questionnaire (SGRQ) is a validated, commonly used questionnaire for measuring quality of life in patients with chronic obstructive pulmonary disease (COPD). The current established minimal important difference (MID) for SGRQ scores in an average COPD population is -4 units. However, for patients with severe COPD, the MID has not been thoroughly validated. We re-determined the SGRQ MID for this patient group.115 severe COPD patients (forced expiratory volume in 1 s (FEV1) 26±9% of predicted, SGRQ score 62±11 units; mean±sd,) who participated in seven different bronchoscopic lung volume reduction clinical trials were included in the analysis. Anchor- and distribution-based methods were used to define the MID for SGRQ scores. FEV1, 6-min walk distance and residual volume were used as anchors.Combining both anchor- and distribution-based methods, we identified a SGRQ MID of -8.3 units at 1 month and -7.1 units at 6 months.This study proposes an alternative SGRQ MID for patients with severe COPD of -8.3 units at 1 month and -7.1 units at 6 months follow-up after intervention. Our new MID estimates could be applied for both interpreting SGRQ outcomes as well as sample size determination in future clinical trials investigating interventions in severe COPD patients.