Assessment of hyperinflation: comparison of Global Lung Function Initiative and European Community for Steel and Coal lung volume reference equations.

Background: Assessment of static hyperinflation severity is crucial to identify COPD patients eligible for lung volume reduction. The current recommendation of residual volume ≥175% predicted may need to be reconsidered owing to potential differences between the Global Lung Function Initiative (GLI) and the European Community for Steel and Coal (ECSC) reference equations for residual volume and concerns about using percentage of predicted. Methods: We compared the residual volume reference values derived from the GLI and ECSC equations using mathematically simulated data and used a receiver operating characteristic curve to establish a new GLI-derived z-score cut-off for residual volume using body plethysmography data from patients with severe COPD. Results: The GLI reference equation for residual volume consistently yields a lower predicted residual volume for individuals with an average or below-average height (females ≤163 cm and males ≤177 cm). Our clinical cohort consisted of 1011 patients with COPD (graded using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria as 38% GOLD 3 and 59% GOLD 4). In this cohort, a GLI-derived residual volume z-score of ≥2.9 could accurately replace the ECSC-derived 175% predicted cut-off and a z-score of ≥3.5 was established for the 200% predicted cut-off. Conclusion: There are substantial differences in predicted residual volume values between the GLI and ECSC equations, with the GLI generally yielding a lower predicted residual volume in the majority of individuals. A GLI-derived residual volume z-score of ≥2.9 could be used to replace the currently used cut-off of ≥175% predicted to identify potential lung volume reduction candidates.

Lung tensioning device coil treatment in patients with severe emphysema: a prospective safety and feasibility trial (EFFORT).

INTRODUCTION: Currently, there is a lack of bronchoscopic lung volume reduction options that do not depend on fissure integrity. Endobronchial coils have been extensively studied to address this need, but exhibited variable patient response and have been discontinued. Lung Tension Device (LTD) coils represent the next-generation coil treatment. This study aimed to evaluate safety, feasibility, and efficacy of LTD-coil treatment. METHODS: Patients with advanced emphysema and hyperinflation were enrolled at two European sites. LTD-coils (FreeFlow Medical, CA, USA) were implanted in the two most destructed lobes, as determined by quantitative CT analysis, in two separate procedures. The primary endpoint was 3-month follow-up after the last treatment. RESULTS: Fourteen patients (50% male, median age 64 years, FEV1 23%predicted, RV 249%predicted) received LTD-coil treatment: 12 received bilateral and 2 unilateral treatment. Six serious respiratory adverse events occurred within the initial 3 months post-treatment, including one device-associated death. Treatment significantly reduced in- and expiratory volume of the treated lobes (-410[-710,-340], p=.004 and -650[-730,-190] mL, p <.001, respectively) and improved quality of life (SGRQ total score -4.6[-21.0,-2.6], p<.001). However, at a group level, no significant improvements in pulmonary function or 6-minute walk distance were observed. Responder rates ranged from 18% to 54% for the different endpoints. CONCLUSION: This first-in-human study shows that the new LTD-coil procedure is feasible with a safety profile comparable to the previous coil treatment. While the treatment effectively reduced lobar volume and modestly improved quality of life up to 3 months follow-up, at a group level it did not significantly enhance pulmonary function or exercise capacity.

Lung volume reduction surgery is safe and feasible after initial endobronchial valve treatment for emphysema patients.

OBJECTIVES: Bronchoscopic lung volume reduction with endobronchial valves is a guideline treatment leading to improved pulmonary function, exercise tolerance and quality of life, in patients with advanced emphysema, severe hyperinflation and no collateral ventilation. After valve treatment, loss of the initial lung volume reduction effect can occur, as well as local valve-induced complications such as persistent haemoptysis. In these cases, a surgical lobectomy can be considered to achieve similar efficacy outcomes. We evaluated the safety and feasibility of a video-assisted thoracoscopic surgery lobectomy after valve treatment. METHODS: This single-centre retrospective study included patients who underwent an elective lobectomy after previous valve treatment. Data were evaluated for safety and efficacy for the additional surgical procedure. RESULTS: Twenty-one patients [73% female, median age 67 (7) years, forced expiratory volume in 1 s 29 (7) %pred, and residual volume 223 (58) %pred] were included. There was no 90-day mortality and there were no postoperative intensive care admissions. Pulmonary infections (14%) and prolonged air leak (14%) were the most common complications. In patients who underwent surgery due to loss or lack of effect of valve treatment, a lobectomy led to a significant improvement in pulmonary function; median forced expiratory volume in 1 s +75 (193) ml (P < 0.013), forced vital capacity +450 (572) ml (P = 0.001), residual volume -665 (715) ml (P = 0.005). In patients who underwent a lobectomy because of complications of valve treatment, all complications were resolved after surgery. CONCLUSIONS: We demonstrate that an elective lobectomy after an initial valve treatment is safe and feasible and restores the lung volume reduction effect.

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.

[COPD: working with treatable traits]. / COPD: denken in behandelbare kenmerken.

COPD is the third most common chronic disease in the Netherlands and the number of patients is still rising. This article reviews causes of COPD, assesses the role of spirometry in diagnosing COPD, and considers ways to differentiate between COPD and heart failure, which can be difficult due to overlapping symptoms. To avoid a 'one size fits all' treatment, we elaborate on treatable traits - patient characteristics leading to specific treatment options- in order to optimize treatment for each individual patient. This applies both during stable disease and during exacerbations.

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.

[Advance care planning in COPD]. / Proactieve zorgplanning bij COPD.

COPD (Chronic Obstructive Pulmonary Disease) affects an estimated 600,000 Dutch citizens. This chronic disease often has an unpredictable and sometimes a very invalidating course, despite various treatment options. It is important to timely initiate advance care planning in this patient population, to address any disease-related worries, needs and wishes the patient has. In this way patients (and their caregivers) can stay in the lead regarding their chronic condition, by making decisions for (future) medical, psychological, spiritual, and social needs based upon good information, their values, beliefs and experiences.

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.

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.

Opioids in patients with COPD and refractory dyspnea: literature review and design of a multicenter double blind study of low dosed morphine and fentanyl (MoreFoRCOPD).

BACKGROUND: Refractory dyspnea or breathlessness is a common symptom in patients with advanced chronic obstructive pulmonary disease (COPD), with a high negative impact on quality of life (QoL). Low dosed opioids have been investigated for refractory dyspnea in COPD and other life-limiting conditions, and some positive effects were demonstrated. However, upon first assessment of the literature, the quality of evidence in COPD seemed low or inconclusive, and focused mainly on morphine which may have more side effects than other opioids such as fentanyl. For the current publication we performed a systematic literature search. We searched for placebo-controlled randomized clinical trials investigating opioids for refractory dyspnea caused by COPD. We included trials reporting on dyspnea, health status and/or QoL. Three of fifteen trials demonstrated a significant positive effect of opioids on dyspnea. Only one of four trials reporting on QoL or health status, demonstrated a significant positive effect. Two-thirds of included trials investigated morphine. We found no placebo-controlled RCT on transdermal fentanyl. Subsequently, we hypothesized that both fentanyl and morphine provide a greater reduction of dyspnea than placebo, and that fentanyl has less side effects than morphine. METHODS: We describe the design of a robust, multi-center, double blind, double-dummy, cross-over, randomized, placebo-controlled clinical trial with three study arms investigating transdermal fentanyl 12 mcg/h and morphine sustained-release 10 mg b.i.d. The primary endpoint is change in daily mean dyspnea sensation measured on a numeric rating scale. Secondary endpoints are change in daily worst dyspnea, QoL, anxiety, sleep quality, hypercapnia, side effects, patient preference, and continued opioid use. Sixty patients with severe stable COPD and refractory dyspnea (FEV1 < 50%, mMRC ≥ 3, on optimal standard therapy) will be included. DISCUSSION: Evidence for opioids for refractory dyspnea in COPD is not as robust as usually appreciated. We designed a study comparing both the more commonly used opioid morphine, and transdermal fentanyl to placebo. The cross-over design will help to get a better impression of patient preferences. We believe our study design to investigate both sustained-release morphine and transdermal fentanyl for refractory dyspnea will provide valuable information for better treatment of refractory dyspnea in COPD. Trial registration NCT03834363 (ClinicalTrials.gov), registred at 7 Feb 2019, https://clinicaltrials.gov/ct2/show/NCT03834363 .

[COPD: working with treatable traits]. / COPD: denken in behandelbare kenmerken.

COPD is the third most common chronic disease in the Netherlands and the number of patients is still rising. This article reviews causes of COPD, assesses the role of spirometry in diagnosing COPD, and considers ways to differentiate between COPD and heart failure, which can be difficult due to overlapping symptoms. To avoid a 'one size fits all' treatment, we elaborate on treatable traits - patient characteristics leading to specific treatment options- in order to optimize treatment for each individual patient. This applies both during stable disease and during exacerbations.

Expert Statement: Pneumothorax Associated with One-Way Valve Therapy for Emphysema: 2020 Update.

For selected patients with advanced emphysema, bronchoscopic lung volume reduction with one-way valves can lead to clinically relevant improvements of airflow obstruction, hyperinflation, exercise capacity, and quality of life. The most common complication of this procedure is pneumothorax with a prevalence of up to ±34% of the treated patients. Patients who develop a pneumothorax also experience meaningful clinical benefits once the pneumothorax is resolved. Timely resolution of a post-valve treatment pneumothorax requires skilled and adequate pneumothorax management. This expert panel statement is an updated recommendation of the 2014 statement developed to help guide pneumothorax management after valve placement. Additionally, mechanisms for pneumothorax development, risk assessment, prevention of pneumothorax, and outcomes after pneumothorax are addressed. This recommendation is based on a combination of the current scientific literature and expert opinion, which was obtained through a modified Delphi method.

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.

Comparison of Multiple Diagnostic Tests to Measure Dynamic Hyperinflation in Patients with Severe Emphysema Treated with Endobronchial Coils.

PURPOSE: For this study, we aimed to compare dynamic hyperinflation measured by cardiopulmonary exercise testing (CPET), a six-minute walking test (6-MWT), and a manually paced tachypnea test (MPT) in patients with severe emphysema who were treated with endobronchial coils. Additionally, we investigated whether dynamic hyperinflation changed after treatment with endobronchial coils. METHODS: Dynamic hyperinflation was measured with CPET, 6-MWT, and an MPT in 29 patients before and after coil treatment. RESULTS: There was no significant change in dynamic hyperinflation after treatment with coils. Comparison of CPET and MPT showed a strong association (rho 0.660, p < 0.001) and a moderate agreement (BA-plot, 202 ml difference in favor of MPT). There was only a moderate association of the 6-MWT with CPET (rho 0.361, p 0.024). CONCLUSION: MPT can be a suitable alternative to CPET to measure dynamic hyperinflation in severe emphysema but may overestimate dynamic hyperinflation possibly due to a higher breathing frequency.

Patient Satisfaction and Attainment of Patient-Specific Goals after Endobronchial Valve Treatment.

Rationale: Bronchoscopic lung volume reduction with endobronchial valves (EBVs) significantly improves clinical outcomes in patients with severe emphysema. However, patient-reported outcomes like patient satisfaction and patient-specific treatment goals were never investigated.Objectives: To investigate the patient-satisfaction level 1 year after treatment and patient-specific goals before and 1 year after EBV treatment. Furthermore, the study aimed to investigate whether the level of patient satisfaction or change in goals was associated with change in the clinical outcome.Methods: We prospectively included patients who underwent EBV treatment as part of regular care in our hospital and asked patients to report and score their personal treatment goals on the patient-specific complaint (PSC) questionnaire at baseline and after 1 year of follow-up and to complete a patient-satisfaction questionnaire at 1 year of follow-up.Results: Of the 134 patients who were treated with EBV, 109 filled out the patient-satisfaction questionnaire and 88 filled out the PSC questionnaire at baseline and 1 year after treatment. When adjusting for the patients who were lost to follow-up, 91% of the patients in total would recommend the EBV treatment to other patients. Seventy-five percent of the patients were (very) satisfied with the treatment and 11% were (very) unsatisfied. The three most frequently reported patient-specific goals to improve were walking (reported by 77% of the patients), taking a shower/washing/getting dressed (35%), and completing household chores (32%). Both the total PSC questionnaire sum score (mean change, -6.01 ± 6.0) and all individual reported goals significantly improved 1 year after treatment (P < 0.001). Furthermore, a higher patient-satisfaction level and larger improvement in goals was significantly associated with an improvement in forced expiratory volume in 1 second, residual volume, dyspnea severity, and quality of life.Conclusions: We found that the patient-satisfaction level is high and patient-specific goals significantly improve 1 year after EBV treatment. We believe that the individual patient's goals are important in the process of shared decision-making before treatment, as they can be used to identify unrealistic expectations beforehand and prevent disappointment afterward.Clinical trial registered at clinicaltrials.gov (NCT02815683).