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The serum level of the soluble Receptor for Advanced Glycation End-products (sRAGE) is a promising blood biomarker for the development, severity, and progression of chronic obstructive pulmonary disease (COPD). However, cigarette smoking causes a nearly instant drop in circulating sRAGE levels, strongly impacting on the variability in sRAGE levels. In the current study, we investigated the possible mechanism behind the sudden drop in sRAGE upon smoking. We showed that the number of activated neutrophils in blood significantly increases within two hours upon smoking three cigarettes within one hour. Furthermore, an increased expression of the leukocyte activation marker CD11b, which is a known ligand for RAGE, was observed upon smoking. Additionally, the in vitro activation of neutrophils increased their capacity to bind sRAGE. Together, these data indicate that smoking activates neutrophils in the circulation with concomitant upregulation of the RAGE ligand CD11b, leading to reduced levels of sRAGE in serum., Author(s): Valerie R. Wiersma [sup.1], Susan J. M. Hoonhorst [sup.2] [sup.3], Nick H. T. ten Hacken [sup.2], Maarten van den Berge [sup.2] [sup.3], Dirk-Jan Slebos [sup.2] [sup.3], Simon D. Pouwels [...]

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., Author(s): Marlies van Dijk [sup.1], Jorine E. Hartman [sup.1], Sonja W. S. Augustijn [sup.1], Nick H. T. ten Hacken [sup.1], Karin Klooster [sup.1], Dirk-Jan Slebos [sup.1] Author Affiliations: (1) grid.4494.d, [...]

Introduction: Persistent air leak (PAL) is associated with prolonged hospitalization, high morbidity and increased treatment costs. Conservative treatment consists of observation, chest tube drainage, and pleurodesis. Guidelines recommend surgical evaluation if air leak does not respond after 3–5 days. One-way endobronchial valves (EBV) have been proposed as a treatment option for patients with PAL in which surgical treatment is not feasible, high risk or has failed. We aimed to provide a comprehensive overview of reported EBV use for PAL and issue best practice recommendations based on multicenter experience. Methods: We conducted a retrospective observational case-series study at four different European academic hospitals and provided best practice recommendations based on our experience. A systematic literature review was performed to summarize the current knowledge on EBV in PAL. Results: We enrolled 66 patients, male (66.7%), median age 59.5 years. The most common underlying lung disease was chronic obstructive pulmonary disease (39.4%) and lung cancer (33.3%). The median time between pneumothorax and valve placement was 24.5 days (interquartile range: 14.0–54.3). Air leak resolved in 40/66 patients (60.6%) within 30 days after EBV treatment. Concerning safety outcome, no procedure-related mortality was reported and complication rate was low (6.1%). Five patients (7.6%) died in the first 30 days after intervention. Conclusion: EBV placement is a treatment option in patients with PAL. In this multicenter case-series of high-risk patients not eligible for lung surgery, we show that EBV placement resulted in air leak resolution in 6 out of 10 patients with a low complication rate. Considering the minimally invasive nature of EBV to treat PAL as opposed to surgery, further research should investigate if EBV treatment should be expanded in low to intermediate risk PAL patients. [ABSTRACT FROM AUTHOR]

Background and Objective: Both bronchoscopic lung volume reduction with endobronchial valves (BLVR‐EBV) and pulmonary rehabilitation (PR) are effective treatments for improving exercise capacity and patient‐reported outcomes in patients with severe Chronic Obstructive Pulmonary Disease (COPD). According to current recommendations, all BLVR‐EBV patients should have undergone PR first. Our aim was to study the effects of PR both before and after BLVR‐EBV compared to BLVR‐EBV alone. Methods: We included patients with severe COPD who were eligible for BLVR‐EBV and PR. Participants were randomized into three groups: PR before BLVR‐EBV, PR after BLVR‐EBV or BLVR‐EBV without PR. The primary outcome was change in constant work rate cycle test (CWRT) endurance time at 6‐month follow‐up of the PR groups compared to BLVR‐EBV alone. Secondary endpoints included changes in 6‐minute walking test, daily step count, dyspnoea and health‐related quality of life. Results: Ninety‐seven participants were included. At 6‐month follow‐up, there was no difference in change in CWRT endurance time between the PR before BLVR‐EBV and BLVR‐EBV alone groups (median: 421 [IQR: 44; 1304] vs. 787 [123; 1024] seconds, p = 0.82) or in any of the secondary endpoints, but the PR after BLVR‐EBV group exhibited a smaller improvement in CWRT endurance time (median: 107 [IQR: 2; 573], p = 0.04) and health‐related quality of life compared to BLVR‐EBV alone. Conclusion: The addition of PR to BLVR‐EBV did not result in increased exercise capacity, daily step count or improved patient‐reported outcomes compared to BLVR‐EBV alone, neither when PR was administered before BLVR‐EBV nor when PR was administered after BLVR‐EBV. Our findings suggest that a combination of pulmonary rehabilitation and bronchoscopic lung volume reduction with endobronchial valves (BLVR‐EBV) may not provide additional benefits compared to BLVR‐EBV alone at a group‐level. Future challenges lie in selecting patients for whom a combined rehabilitation trajectory would be beneficial. See relatededitorial [ABSTRACT FROM AUTHOR]

Abstract Background Targeted lung denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung reducing clinical consequences of cholinergic hyperactivity. The AIRFLOW-1 study assessed safety and TLD dose in patients with moderate-to-severe, symptomatic COPD. This analysis evaluated the long-term impact of TLD on COPD exacerbations, pulmonary function, and quality of life over 3 years of follow up. Methods TLD was performed in a prospective, energy-level randomized (29 W vs 32 W power), multicenter study (NCT02058459). Additional patients were enrolled in an open label confirmation phase to confirm improved gastrointestinal safety after procedural modifications. Durability of TLD was evaluated at 1, 2, and 3 years post-treatment and assessed through analysis of COPD exacerbations, pulmonary lung function, and quality of life. Results Three-year follow-up data were available for 73.9% of patients (n = 34). The annualized rate of moderate to severe COPD exacerbations remained stable over the duration of the study. Lung function (FEV1, FVC, RV, and TLC) and quality of life (SGRQ-C and CAT) remained stable over 3 years of follow-up. No new gastrointestinal adverse events and no unexpected serious adverse events were observed. Conclusion TLD in COPD patients demonstrated a positive safety profile out to 3 years, with no late-onset serious adverse events related to denervation therapy. Clinical stability in lung function, quality of life, and exacerbations were observed in TLD treated patients over 3 years of follow up.

Background and Purpose In patients with severe emphysema, dynamic hyperinflation is superimposed on top of already existing static hyperinflation. Static hyperinflation reduces significantly after bronchoscopic lung volume reduction (BLVR). In this study, we investigated the effect of BLVR compared to standard of care (SoC) on dynamic hyperinflation. Methods Dynamic hyperinflation was induced by a manually paced tachypnea test (MPT) and was defined by change in inspiratory capacity (IC) measured before and after MPT. Static and dynamic hyperinflation measurements were performed both at baseline and 6 months after BLVR with endobronchial valves or coils (treatment group) or SoC (control group). Results Eighteen patients underwent BLVR (78% female, 57 (43-67) years, FEV.sub.1 25(18-37) %predicted, residual volume 231 (182-376) %predicted). Thirteen patients received SoC (100% female, 59 (44-74) years, FEV.sub.1 25 (19-37) %predicted, residual volume 225 (152-279) %predicted. The 6 months median change in dynamic hyperinflation in the treatment group was: + 225 ml (range - 113 to + 803) (p < 0.01) vs 0 ml (- 1067 to + 500) in the control group (p = 0.422). An increase in dynamic hyperinflation was significantly associated with a decrease in residual volume (r = - 0.439, p < 0.01). Conclusion Bronchoscopic lung volume reduction increases the ability for dynamic hyperinflation in patients with severe emphysema. We propose this is a consequence of improved static hyperinflation., Author(s): Marlies van Dijk [sup.1] [sup.2], Karin Klooster [sup.1], Jorine E. Hartman [sup.1], Nick H. T. ten Hacken [sup.1], Dirk-Jan Slebos [sup.1] Author Affiliations: (1) Department of Pulmonary Diseases, University [...]

Background Bronchoscopic lung volume reduction techniques are minor invasive treatment modalities for severely hyperinflated emphysema patients. The severity of static lung hyperinflation determines eligibility and success rate for these treatments. However, it is not exactly known what parameter should be used to optimally reflect hyperinflation. Commonly used parameters are residual volume (RV) and the RV/Total lung capacity (TLC) ratio. Other parameters reflecting hyperinflation are Inspiratory Capacity/TLC and forced vital capacity. Objectives To define which of these function parameters is the most optimal reflection of hyperinflationin in relation to patient-related outcomes. Methods In a retrospective cohort study, data from measurements during baseline visits of eight studies were pooled. Primary outcomes were RV/TLC ratio and RV as percentage of predicted (RV%pred), both measured by bodyplethysmography, compared to the patient-related outcome variables: 6-min walk distance (6MWD), the St. George's Respiratory Questionnaire (SGRQ), and the modified Medical Research Council (mMRC). Results Two hundred seventy-four COPD patients (mean age 59 years; 66% female), FEV.sub.1 0.74 ± 0.28 L, RV 4.94 ± 1.06 L, 6MWD of 339 ± 95 m, were included in the analysis. Significant correlations (all p < 0.01) were found between RV%pred and 6MWD (r = - 0.358), SGRQ (r = 0.184), and mMRC (r = 0.228). Also, there was a significant correlation between RV/TLC ratio and 6MWD (r = - 0.563), SGRQ (r = 0.289) and mMRC (r = 0.354). Linear regression analyses showed that RV/TLC ratio was a better predictor of patient outcomes than RV%pred. Conclusion This study demonstrates that both RV/TLC ratio and RV%pred are relevant indicators of hyperinflation in patients with severe emphysema in relation to patient-related outcomes. RV/TLC ratio is more strongly related to the patient-related outcomes than RV%pred., Author(s): Wouter W. de Weger [sup.1], Karin Klooster [sup.1], Nick H. ten Hacken [sup.1], Marlies van Dijk [sup.1], Jorine E. Hartman [sup.1], Dirk-Jan Slebos [sup.1] Author Affiliations: (1) grid.4494.d, 0000 [...]

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., Author(s): Jorrit B. A. Welling [sup.1] [sup.2] [sup.3] , Jorine E. Hartman [sup.1] [sup.2] , Nick H. T. Ten Hacken [sup.1] [sup.2] , Sonja W. S. Augustijn [sup.1] [sup.2] , [...]

The article examines the impact of endobronchial valve (EBV) sizing on granulation tissue formation and treatment outcomes in patients with advanced emphysema. It finds that many implanted EBVs were oversized based on computed tomography-derived airway lumen diameters, but this sizing issue was not directly linked to granulation tissue formation.