Optimizing Clinical Outcomes for Bronchoscopic Lung Volume Reduction with Zephyr® Valves.

Bronchoscopic lung volume reduction treatment with Zephyr one-way valves is an effective guideline-based treatment option for patients with severe emphysema and hyperinflation. However, in some cases the treatment response is less than anticipated or there might be a loss of initial treatment effect. Reasons for the lack of response can include incorrect assessment of collateral ventilation, improper valve placement, or patient related factors. Loss of initial benefit can be due to granulation tissue formation and subsequent valve dysfunction, or there may be side effects such as excessive coughing or infectious problems. Careful follow-up after treatment with valves is important and evaluation with a CT scan and/or bronchoscopy is helpful if there is no improvement after treatment or loss of initial benefit. This paper aims to describe the most important causes and provide a strategy of how to approach and manage these patients.

Impact of Endobronchial Valve Treatment on Lung Function Decline.

INTRODUCTION: Endobronchial valve (EBV) treatment has been shown to be beneficial for patients with severe emphysema. The forced expiratory volume in 1 s (FEV1) was found to be significantly higher compared to baseline for up to 3 years after treatment although the magnitude of improvement gradually decreases over time. So far, it has not been investigated whether this treatment decelerates the decline in lung function. Therefore, our aim was to investigate the lung function decline before and after EBV treatment. METHODS: We included patients who were treated with EBVs in our hospital, of whom pre-treatment spirometry results were available (at least 4 measurements within at least 2 years before treatment) and who had an annual FEV1 measurement up to 3 years after treatment. RESULTS: In total, 45 patients were included (73% female, FEV1: 28 ± 7% of predicted, residual volume: 232 ± 32% of predicted) who had a mean pre-treatment FEV1 decline of -64 mL/year. Mean FEV1 "decline" after treatment was +13 mL/year, since FEV1 was still above the baseline level at 3-year follow-up. However, the FEV1 decline between 1 and 3 years of follow-up was not significantly different compared to the pre-treatment decline (-73 mL/year, p = 0.179). CONCLUSIONS: Our results show that the EBV treatment does not influence the progression of disease in terms of lung function decline. However, the treatment does improve the FEV1 up to a level that is still comparable 3 years after treatment with the baseline level.

Response to endobronchial valve treatment: it's all about the target lobe.

Background: Bronchoscopic lung volume reduction using endobronchial valves (EBV) has been shown to be beneficial for severe emphysema patients. The most important predictor of treatment response is absence of collateral ventilation between the treatment target and ipsilateral lobe. However, there are still a substantial number of nonresponders and it would be useful to improve the pre-treatment identification of responders. Presumably, predictors of response will be multifactorial, and therefore our aim was to explore whether we can identify response groups using a cluster analysis. Methods: At baseline and 1 year follow-up, pulmonary function, exercise capacity and quality of life were measured. A quantitative chest computed tomography scan analysis was performed at baseline and 2-6 months follow-up. The cluster analysis was performed using a hierarchical agglomerative method. Results: In total, 428 patients (69% female, mean±sd age 61±8 years, forced expiratory volume in 1 s 27±8% predicted, residual volume 254±50% pred) were included in our analysis. Three clusters were generated: one nonresponder cluster and two responder clusters. Despite solid technical procedures, the nonresponder cluster had significantly less clinical response after treatment compared to the other clusters. The nonresponder cluster was characterised by significantly less emphysematous destruction, less air trapping and a higher perfusion of the target lobe, and a more homogeneous distribution of emphysema and perfusion between the target and ipsilateral lobe. Conclusions: We found that target lobe characteristics are the discriminators between responders and nonresponders, which underlines the importance of visual and quantitative assessment of the potential treatment target lobe when selecting patients for EBV treatment.

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.

Improved exercise capacity results in a survival benefit after endobronchial valve treatment.

BACKGROUND: Bronchoscopic lung volume reduction using endobronchial valves (EBV) is a treatment option for selected patients with advanced emphysema. The treatment significantly improves pulmonary function, exercise capacity, quality of life, and potentially improves survival. Our main aim was to assess whether treatment response significantly influences survival time after EBV treatment. METHODS: We evaluated treatment response at 6-week and 1-year follow-up of all patients treated with EBVs between 2008 and 2020. Survival status was retrieved on December 1, 2021. Patients were defined as responders or non-responders based on known minimal important differences for FEV1, residual volume (RV), RV/Total Lung Capacity (TLC) ratio, 6-min walk distance (6MWD), St. George's Respiratory Questionnaire (SGRQ), target lobe volume reduction (TLVR), and complete lobar atelectasis. Uni- and multivariate cox regression models were used to evaluate the effect of response on survival time. RESULTS: A total of 428 patients were included. EBV treatment resulted in significant improvements in pulmonary function, exercise capacity and quality of life. Median survival was 8.2 years after treatment. SGRQ and 6MWD response were independent predictors for improved survival time (Hazard Ratio (HR) 0.50 [0.28-0.89], p = .02 and HR 0.54 [0.30-0.94], p = .03, respectively). The presence of a complete lobar atelectasis did not significantly affect survival, neither did pulmonary function improvements. CONCLUSIONS: Our results suggest that improvement in exercise capacity and quality of life after EBV treatment are associated with a survival benefit, independent of improvements in pulmonary function, reduction in target lobe volume or the presence of complete lobar atelectasis.

Prevalence and Impact of COVID-19 among Severe COPD Patients post Bronchoscopic Lung Volume Reduction Treatment with Endobronchial Valves.

BACKGROUND: The COVID-19 pandemic has a great impact on numberless aspects of our society. In our bronchoscopic lung volume reduction interventional program, we work with severe COPD patients on a daily basis. OBJECTIVES: We were interested in the prevalence and outcome of COVID-19, impact of the pandemic on daily life, and the vaccination coverage in our severe COPD patients who have been treated with one-way endobronchial valves. METHOD: A questionnaire, which consisted of questions related to the infection rate, treatment, and outcome of COVID-19 infections; feelings of anxiety related to the pandemic; adherence to preventive measures; and willingness to be vaccinated; was sent to our patients in June 2021. RESULTS: The questionnaire was sent to 215 patients, and the response rate was 100%. The vaccination rate was 97% in our surveyed population. The majority of patients (63%) indicated that they were quite or very anxious to get infected with COVID-19. Twenty-five (11.5%) patients were diagnosed with COVID-19, with none of these patients having been vaccinated at the time of infection. The infection rate reported in this study is comparable to that of the general Dutch population. However, the hospital admission rate and mortality rates are higher. CONCLUSIONS: Our results show that the SARS-CoV-2 infection rate in severe COPD patients treated with endobronchial valves was comparable with the general population; however, the hospital admission and mortality rates were worse.

Bronchoscopic Lung Volume Reduction in Patients with Emphysema due to Alpha-1 Antitrypsin Deficiency.

BACKGROUND: Bronchoscopic lung volume reduction using one-way endobronchial valves (EBVs) is a valid therapy for severe emphysema patients. However, alpha-1 antitrypsin (AAT)-deficient patients were excluded from the majority of clinical trials investigating this intervention. OBJECTIVES: The aim of this study was to investigate the feasibility, efficacy, and safety of EBV treatment in patients with AAT deficiency (AATD) or a reduced AAT level. METHOD: A retrospective analysis was performed of all patients treated with EBV with confirmed AATD or with a reduced AAT serum level at the University Medical Center Groningen between 2013 and 2021. Baseline and 6-month follow-up assessment included chest CT, pulmonary function measurement, 6-min walking distance (6MWD), and St. George's Respiratory Questionnaire (SGRQ). RESULTS: In total, 53 patients were included, 30 patients in the AATD group (AAT <0.6 g/L or confirmed ZZ phenotype) and 23 patients in the reduced AAT group (AAT 0.6-1 g/L). In both groups, all response variables improved significantly after treatment. There was a median increase in forced expiratory volume in 1 s of 105 mL (12% relative) and 280 mL (31% relative) in the AATD and reduced AAT groups, respectively. 6MWD increased by 62 min and 52 min, and SGRQ decreased by 12.5 patients and 18.7 patients, respectively. A pneumothorax occurred in 10% and 13% of patients, and no patients died. CONCLUSIONS: EBV treatment in patients with emphysema and AATD or a reduced AAT level is feasible and results in significant improvements in pulmonary function, exercise capacity, and quality of life and has an acceptable safety profile.

Long-term follow-up after bronchoscopic lung volume reduction valve treatment for emphysema.

Background: Multiple studies have shown that patients with severe emphysema can significantly benefit from bronchoscopic lung volume reduction endobronchial valve (EBV) treatment up to 1 year after treatment. However, hardly any data exist on longer term follow-up, especially on quality of life. Our aim was to investigate long-term follow-up after EBV treatment up to 3 years including quality of life in a real-life routine clinical setting. Methods: We retrospectively included patients who underwent EBV treatment in our hospital in the Netherlands at least 3 years prior. Patients were invited for annual visits to our hospital, and spirometry, body plethysmography, 6-min walk distance (6MWD) test and St George's Respiratory Questionnaire (SGRQ) were performed during these visits. Results: At 1-, 2- and 3-year follow-up, data were available from 189, 146 and 112 patients, respectively. Forced expiratory volume in 1 s, residual volume and SGRQ total score significantly improved up to 3 years after treatment compared with baseline, and 6MWD up to 2 years after treatment. In general, the magnitude of improvements gradually decreased over time. Conclusions: Our results show that patients can benefit at least up to 3 years after EBV treatment. For the first time we found that patients can also benefit in terms of quality of life in the long term, which is an important outcome for this group of patients with end-stage COPD.

A multicenter, prospective, single-arm clinical investigation of a modified staged treatment algorithm using the AeriSeal system - The STAGE trial.

INTRODUCTION: Treatment with AeriSeal is an alternate treatment option to achieve lung volume reduction in patients with severe COPD and emphysema who are not eligible for valve treatment. This study aimed to assess the safety and mode of action of a modified staged treatment algorithm with a staged treatment with lower dose of AeriSeal. METHODS: We performed a prospective, multicenter feasibility study. AeriSeal was administered during two sequential bronchoscopies: 2 subsegments of a lobe treated with two 5 mL doses, followed by two 10 mL doses in a contralateral lobe after 6 weeks. RESULTS: A total of 14 patients (36% male, mean FEV1 28.4% ± 6.7% of predicted) were enrolled. Ten patients completed both treatments, four were treated unilaterally. AeriSeal treatment resulted in significant TLVR (median 220.5 mL) at 3 months follow up. There were no significant changes from baseline at 12 months in lung function, exercise capacity and quality of life. During the 3-month post-treatment period, respiratory SAEs included 5 COPD exacerbations in 4 (28.6%) subjects, post-treatment acute inflammatory response (PAIR) in 2 (14.3%) subjects, and 1 respiratory failure event in 1 (7.1%) subject. CONCLUSION: The staged and lower dosed administration of AeriSeal does not impact the overall safety profile in terms of reducing the type and frequency of respiratory SAEs previously reported for a single-stage treatment. A larger volume of AeriSeal than used in this study may be necessary to provide meaningful clinical benefits.

Biodegradable Stent Placement for Airway Kinking After Bronchoscopic Lung Volume Reduction Treatment.

Symptomatic airway kinking after bronchoscopic lung volume reduction with endobronchial valves is rare. Owing to the development of the desired lobar atelectasis, the position of the airways of the nontreated lobe changes, and that might lead to invalidating symptoms. We present a case of a patient with symptomatic airway kinking after treatment with endobronchial valves, who was successfully treated with a single placement of a biodegradable stent. Placement of a biodegradable stent can be considered for symptomatic patients with airway kinking.

An adjusted and time-saving method to measure collateral ventilation with Chartis.

INTRODUCTION: Bronchoscopic lung volume reduction with endobronchial valves is an important treatment option in selected patients with severe emphysema and absence of collateral ventilation in the treatment target lobe. The Chartis system provides an important physiological assessment of the presence or absence of collateral ventilation. We aimed to evaluate a new feature and determine whether low flow during a Chartis measurement is predictive for the absence of collateral ventilation, and whether this allows for a procedure to be shortened by earlier terminating the Chartis measurement. This is measured with the "volume trend for the previous 20 s" (VT20). METHODS: We retrospectively evaluated 249 Chartis assessments of patients scheduled for bronchoscopic lung volume reduction procedures. The VT20 was calculated, and several thresholds were compared between patients with collateral ventilation (CV positive) and without collateral ventilation (CV negative). RESULTS: 100% of the CV negative patients reached a threshold of VT20 ≤6 mL, whereas all CV positive patients reached a VT20 ≥7 mL. The median "time saved" between VT20=6 mL and end of assessment was 60 s (range 5-354 s). CONCLUSION: The threshold of VT20 ≤6 mL is a reliable method to exclude the presence of collateral ventilation when air flow rates are low and can therefore reduce bronchoscopic lung volume procedure times.

Revision Bronchoscopy After Endobronchial Valve Treatment for Emphysema: Indications, Findings and Outcomes.

Background: Endobronchial valve (EBV) treatment is an effective treatment for patients with severe emphysema. Revision bronchoscopies after endobronchial valve treatment can be essential to prolong the effect of treatment or address long-term complications. Purpose: To evaluate the indications, endoscopic findings and outcomes of revision bronchoscopies and investigate if any predictors for granulation tissue formation, after EBV treatment, can be identified. Patients and Methods: Patients who underwent EBV treatment between 2016 and 2019 in our hospital, as routine care, were included. If a patient underwent a revision bronchoscopy, data regarding revision bronchoscopies, including indication, finding, intervention and pulmonary function testing (PFT) after revision bronchoscopy were analysed. Results: One hundred seventy-nine patients were included of which 41% required at least one revision bronchoscopy. In 43% of the revision bronchoscopy patients, the indication was loss of initial treatment effect. In 53% of the revision bronchoscopy patients, granulation tissue was found to be the underlying cause. Valve replacement(s) were performed in 51% of the revision bronchoscopy cases. Permanent valve removal was required in 13% of all patients. Overall, revision bronchoscopies led to improvements in PFT outcomes for patients experiencing no or a loss of initial treatment effect. No clinically relevant predictors for granulation tissue formation were identified. Conclusion: Performing a revision bronchoscopy after EBV treatment is a useful procedure leading to an improved treatment effect in most patients. Granulation tissue formation, causing valve dysfunction, is the most common cause of longer term problems.

Minimal important difference of change in patient-specific goals in severe emphysema patients.

Change in patient's personal treatment goals is an important patient-reported outcome and can be measured by the patient-specific complaints (PSC) questionnaire. This paper establishes the MID for this questionnaire as -5.9 points. https://bit.ly/3kwvWKM.

Treatment of severe stable COPD: the multidimensional approach of treatable traits.

Now that additional treatment options for severe chronic obstructive pulmonary disease (COPD) have emerged in recent years, patients with severe COPD should not be left in the rather hopeless situation of "there is nothing to improve" any more. Inertia or fatalism is a disservice to our patients. Ranging from advanced care planning to quite intense and demanding therapies such as multidisciplinary pulmonary rehabilitation, (endoscopic) lung volume reduction, chronic noninvasive ventilation and lung transplantation, caregivers should try to provide a personalised treatment for every severe COPD patient. In this review, we aim to describe the multidimensional approach to these patients at our centre along the lines of treatable traits leading to specific additional treatment modalities on top of standard care.

Endobronchial valve therapy for severe emphysema: an overview of valve-related complications and its management.

INTRODUCTION: Bronchoscopic lung volume reduction treatment with one-way valves is an effective guideline treatment option for patients with severe emphysema. However, important challenges and adverse reactions may occur after treatment. AREAS COVERED: This review summarizes the complications after endobronchial and intrabronchial valve treatment that have been described by the currently published randomized controlled trials and other relevant papers regarding the complications and its management. In case there was no relevant literature regarding these subjects, recommendations are based on expert opinion. Complications include pneumothorax, post-obstruction pneumonia and hemoptysis. Also, the treatment may not be effective due to the presence of collateral ventilation or misplaced valves. Furthermore, an initial beneficial effect may vanish due to granulation tissue formation, valve dysfunction or valve migration. Careful follow-up after treatment with valves is important. Evaluation with a CT-scan and/or bronchoscopy is needed if there is no improvement after treatment, loss of benefit, or occurrence of important adverse events during follow-up. EXPERT OPINION: Treating severe emphysema patients with one-way valves requires continuous dedication and expertise, especially to achieve an optimal outcome and elegantly deal with the various complications after treatment.

An Integrative Approach of the Fissure Completeness Score and Chartis Assessment in Endobronchial Valve Treatment for Emphysema.

Purpose: Lung volume reduction using one-way endobronchial valves is a bronchoscopic treatment for patients with severe emphysema without collateral ventilation between the treatment target lobe and the ipsilateral lobe(s). CT-scan fissure analysis is often used as a surrogate to predict the absence of collateral ventilation. We aimed to evaluate the predictive value of the fissure completeness score (FCS) compared to the functional Chartis measurement of collateral ventilation and to provide cut-off values of the FCS in patient selection. Patients and Methods: Multicenter study in patients eligible for treatment with one-way valves. The FCS was calculated by quantitative CT analysis (Thirona, the Netherlands) and compared to status of interlobar collateral ventilation measured with Chartis system (PulmonX, USA). Thresholds were calculated for the predictive values of the presence of collateral ventilation. Results: An FCS >95% of the left major fissure had a positive predictive value (PPV) of 91%, with 1 in 11 fissures demonstrating collateral ventilation with Chartis measurement, whereas an FCS of ≤80% had a negative predictive value (NPV) of 100% for the presence of collateral ventilation. For the right major fissure, the NPV was 100% for an FCS ≤90%, but 69.7% for the right upper lobe fissure. Conclusion: Quantitative CT analysis is recommended in all patients evaluated for endobronchial valves. Patients with incomplete fissures (left major fissure: FCS <80%; right major fissure: <90%) can be excluded from Chartis measurement and endobronchial valve treatment. In patients with more complete fissures, the FCS is not specific enough for endobronchial valve treatment decisions. In this case, additional Chartis measurements are always recommended in the right lung. For the left lung, Chartis assessments may be omitted if the FCS is >95%.

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.

First in Human Experience of the Performance of the New 5.5-LP Size Zephyr Endobronchial Valve.

BACKGROUND: Bronchoscopic lung volume reduction using the Zephyr® endobronchial valve (EBV) is a guideline treatment for patients with advanced emphysema. To achieve volume reduction, it is crucial that there is absence of collateral ventilation and a complete occlusion of the target lobe. While 3 EBV sizes (4.0; 4.0-LP; and 5.5) are currently available to accommodate all airway sizes, local anatomical variations sometimes warrant a valve with a wide diameter but shorter length. To address this, a new "low profile" 5.5-LP EBV has been introduced. OBJECTIVE: In this study, we evaluated the feasibility, safety, and efficacy of this new 5.5-LP EBV. METHODS: This was a single-center, prospective, open-label study. Patients were included if eligible for valve treatment with a local anatomy suitable to place at least one 5.5-LP EBV. Feasibility of placement of the 5.5-LP EBV was reported. Safety, CT parameters, pulmonary function tests, and St. George's Respiratory Questionnaire (SGRQ) were assessed at baseline and 6 weeks after treatment. RESULTS: We included 30 patients with severe chronic obstructive pulmonary disease (forced expiratory volume in 1 s [FEV1] 29 ± 10%; [RV] 242 ± 46%; and SGRQ 56 ± 11 points). Besides the regular EBV sizes, a median of 1 (1-3) of the new 5.5-LP EBV was placed. No valve adjustment was needed during the initial procedure. A single asymptomatic small pneumothorax was observed in 1 patient. In 4 patients, a revision bronchoscopy was performed due to absence of clinical benefit. In 1 patient, this was related to a dislocation of the 5.5-LP EBV. Clinically relevant improvements were seen in target lobar volume reduction (-1,554 mL), FEV1 +39%, RV -960 mL, and SGRQ -18 points. CONCLUSIONS: In this first in human study, the 5.5-LP EBV could be placed into wide segments with a shorter landing length without unexpected complications and with good efficacy outcomes.