BACKGROUND AND OBJECTIVE:Endobronchial valve (EBV) therapy is an established intervention for patients with advanced emphysema with lung hyperinflation, improving pulmonary function, exercise capacity, and quality of life. Although comorbidities are highly prevalent in this patient population, their effect on EBV treatment outcomes remains unclear. This study aimed to investigate the impact of comorbidities on clinical EBV treatment response in routine clinical practice. METHODS:Baseline and 12-month follow-up data were extracted from a prospective registry of EBV procedures conducted between 2016 and 2023. Comorbidities were self-reported via a questionnaire and validated with medical records. Patients were stratified by comorbidity burden: <3 and ≥ 3 comorbidities. Between-group comparisons included relative changes in forced expiratory volume in 1 s (FEV1), residual volume (RV), 6-min walk distance (6MWD), St. George's Respiratory Questionnaire (SGRQ), safety outcomes, and patient-reported satisfaction. RESULTS:In total, 202 patients were included of whom 103 (51%) had ≥3 (range 3-7) comorbidities. Both comorbidity groups demonstrated significant improvements in FEV1, RV, 6MWD, and SGRQ at 12 months following EBV treatment, with no significant differences between groups. Notably, patients with a higher comorbidity burden did not show a higher rate of adverse events. Additionally, both groups reported similarly high levels of satisfaction with treatment outcomes, with more than three quarter of patients expressing satisfaction. CONCLUSIONS:Our results show that EBV treatment provided similar favourable clinical improvements with comparable safety profiles, regardless of patients their comorbidity burden. These findings underscore the importance of considering patients with comorbidities for EBV evaluation and referral.

OBJECTIVES:Endobronchial valve (EBV) treatment can significantly improve pulmonary function, exercise capacity, and quality of life in patients with advanced emphysema and lung hyperinflation. However, the impact of age on treatment response to EBV remains unclear, despite its increasing relevance in an aging population. This study aimed to assess the effect of age on clinical outcomes following EBV treatment in a real-world population. METHODS:Baseline, 6-month, and 12-month follow-up data were obtained from our registry of EBV procedures performed between 2016 and 2024. Patients were stratified according to age: <70 years and ≥70 years. Age-related differences in relative changes in forced expiratory volume in 1 second (FEV1), residual volume (RV), 6-minute walk distance (6MWD), and St George's Respiratory Questionnaire (SGRQ) scores were assessed, together with safety outcomes, achievement of patient-specific goals, and patient satisfaction. RESULTS:A total of 476 patients were included, of whom 79 (17%) were aged ≥70 years (range, 70-80 years). Both age groups demonstrated significant improvements in FEV1, RV, 6MWD, and SGRQ scores at both follow-up visits, with no significant differences between groups. Importantly, adverse events did not occur more frequently among older patients. Additionally, achievement of patient-specific goals was comparable between groups, although patients aged ≥70 years reported slightly greater satisfaction with treatment outcomes than those aged <70 years. CONCLUSIONS:Our findings indicate that EBV treatment resulted in comparable clinical improvements and similar safety profiles regardless of patient age. These findings highlight the importance of referral and screening of older patients with emphysema to assess their eligibility for EBV treatment.

BACKGROUND:One of the most prevalent and impactful symptoms in COPD is persistent dyspnoea, occurring in the majority of patients with advanced COPD. Opioids, mostly morphine, have been investigated and suggested as treatment in palliative care guidelines. However, in recent years multiple trials on morphine for persistent dyspnoea have shown no clinical benefit, and there are concerns regarding adverse events. Transdermal fentanyl has not yet been investigated for this indication. METHODS:We performed a multicentre, crossover, double-dummy randomised controlled trial, investigating transdermal fentanyl (12 μg·h-1), morphine (10 mg per os twice daily) and placebo, during three treatment periods of 2 weeks (including a 3-day washout period). Patients with persistent dyspnoea despite optimal therapy and modified Medical Research Council dyspnoea scale score ≥3 caused by COPD, forced expiratory volume in 1 s (FEV1) <50% predicted and stable disease were included. The primary end-point was change in mean daily dyspnoea score on a Numeric Rating Scale (NRS). Secondary outcomes were change in worst daily dyspnoea (NRS), health status (Clinical COPD Questionnaire), anxiety (Hospital Anxiety and Depression Scale-Anxiety), hypercapnia (capillary blood gas), mastery (Chronic Respiratory Questionnaire-Mastery) and sleep quality (NRS). RESULTS:Between April 2019 and November 2024, 59 randomisations were performed in 58 participants (mean±sd 69±7 years; 54% female; FEV1 33±10% predicted); 37 participants completed the study. The main reasons for study discontinuation were exacerbations (n=13) and side-effects (n=7). There were no significant differences between both fentanyl and morphine compared to placebo for mean and worst dyspnoea, sleep, health status, mastery, anxiety, hypercapnia or side-effects (except for a possible difference in vomiting). CONCLUSION:This study demonstrated no positive effect of transdermal fentanyl nor oral morphine compared to placebo in the treatment of persistent dyspnoea in COPD.

RATIONALE Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition. COPD exacerbations cause a significant socio-economic and symptom burden and are associated with high mortality. Add-on biological treatments for selected COPD patients with type 2 airway inflammation and frequent exacerbations are emerging. Currently, the prevalence of uncontrolled COPD with type 2 airway inflammation in a real-world setting is uncertain and warranted to facilitate policymakers, pharmaceutical companies and healthcare professionals. Therefore, the aim of this study was to assess the prevalence of uncontrolled COPD with type 2 airway inflammation in patients treated in a secondary care setting in the Netherlands. METHODS This retrospective study analyzed a cohort of COPD patients treated by pulmonologists at Franciscus Hospital Rotterdam, the Netherlands, between April 2022 and April 2024. The prevalence of uncontrolled COPD was assessed in the cohort and extrapolated to the secondary care Dutch COPD population. Uncontrolled disease was defined as ≥2 moderate exacerbations or ≥1 exacerbation with hospitalization in the previous 12 months, despite optimal inhalation therapy (either triple therapy or dual bronchodilator therapy with blood eosinophil count <0.100[asterisk]10^9/L). Type 2 inflammation was defined as blood eosinophil count ≥0.300[asterisk]10^9/L and/or fractional exhaled nitric oxide (FeNO) ≥25ppb, which was assessed in a subset of patients in whom both biomarkers were available. Ninety-five percent confidence intervals (95%CI) were calculated for population proportions. Nationwide data on COPD and patients treated in secondary care were used to extrapolate to a national prevalence. It was assumed that the prevalence in this cohort was representative of the secondary care COPD population. RESULTS Among 2278 identified COPD patients 34% (95%CI 33.7-34.5) met the exacerbation criterium; 618 patients, 27% (95%CI 26.8-27.5) had a combination of exacerbations and optimal inhalation therapy and were classified as being uncontrolled. In 172 of these patients, FeNO was assessed. Type 2 inflammation (elevated FeNO and/or eosinophils) was found in 87 patients, 51% (95%CI 49.1-52.1), based on different biomarker profiles (Figure). Our cohort reflects 2.9% of the entire Dutch secondary care COPD population (n=78,263), extrapolating to a prevalence of 21,232 (27%) of COPD patients suffering from uncontrolled disease, with an estimation of 10,739 (14%) patients with type 2 inflammation. CONCLUSIONS Over 25% of COPD patients optimally treated by pulmonologists continue to have exacerbations. Our findings suggest that 51% of these uncontrolled patients have biomarker profiles that could be a potential target for different type 2 inflammation biological treatments.

Rationale: Despite advancements in emphysema treatment, high morbidity and mortality rates highlight the need for innovative therapies. A novel self-expanding nitinol airway scaffold was designed to alleviate lung hyperinflation by connecting emphysematous parenchyma with central bronchi, releasing trapped air. Objectives: To assess the feasibility, safety, and initial outcomes of airway scaffolds in treating emphysema-related hyperinflation. Methods: We conducted a pooled analysis of two first-in-human studies (NCT05949645, NCT05854550) involving patients with heterogeneous or homogeneous emphysema treated bronchoscopically with up to three permanent airway scaffolds per lung. Measurements and Main Results: The primary outcome was safety, measured by procedure- and/or device-related serious adverse events over 6 months. Secondary outcomes were technical feasibility, pulmonary function, quality of life, symptoms, exercise capacity at 3 and 6 months, and airway patency assessment by high-resolution computed tomography. Sixty severe emphysema patients (33 female, 27 male; mean age, 66 ± 8 yr; mean residual volume percent predicted, 255 ± 47%) were included. Ninety-eight procedures were performed, and 328 airway scaffolds were successfully placed. A proportion of 21.7% of patients experienced at least one related serious adverse event within 6 months, including pneumonia (10.0%) and chronic obstructive pulmonary disease exacerbation (5.0%), but no pneumothoraxes occurred. Residual volume improved (decreased) from baseline by a mean [95% confidence interval] of 866 [626, 1,106] ml at 3 months and 753 [512, 994] ml at 6 months. Clinically meaningful improvements were further observed in spirometry, quality of life, symptoms, and exercise capacity. Conclusions: This study provides the first clinical evidence of the feasibility, safety, and initial outcomes after treatment with airway scaffolds in patients with emphysema-related hyperinflation.

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 (Free Flow Medical, Fremont, 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 posttreatment, including one device-associated death. Treatment significantly reduced in- and expiratory volume of the treated lobes (-410 [-710, -340], p = 0.004 and -650 [-730, -190] mL, p < 0.001, respectively) and improved quality of life (SGRQ total score -4.6 [-21.0, -2.6], p < 0.001). However, at a group level, no significant improvements in pulmonary function or 6-min 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.

Background Assessment of static hyperinflation severity is crucial to identify COPD patients eligible for lung volume reduction. The current recommendation of residual volume >= 75% 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 GLIderived 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.

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.

BackgroundAssessment of static hyperinflation severity is crucial to identify COPD patients eligible for lung volume reduction. The current recommendation of residual volume (RV)≥175% predicted may need reconsideration due to potential differences between the Global Lung Function Initiative (GLI) and the European Community for Steel and Coal (ECSC) reference equations for RV and concerns about using %predicted.MethodsWe compared the RV reference values derived from the GLI and ECSC using mathematical simulated data and used a receiver operating characteristic curve to establish a new GLI-derived z-score cut-off for RV using body plethysmography data of severe COPD patients.ResultsThe GLI reference equation for RV consistently yields a lower predicted RV 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 (38% GOLD stage III and 59% stage IV). In this cohort, a GLI-derived RV z-score of ≥2.9 could accurately replace the ECSC-derived 175% predicted cut-off and for 200% predicted, a z-score of ≥3.5 was established.ConclusionThere are substantial differences in predicted RV values between the GLI and ECSC, with the GLI generally yielding a lower predicted RV in the majority of individuals. A GLI-derived RV 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.

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.

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.

"HRCT-Approximated Perfusion is Comparable to Nuclear Perfusion Imaging in Severe COPD." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.

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.

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.