Advanced Emphysema Research Articles

Advanced Emphysema Leads to High False Positivity Rate for Pneumothorax in Point of Care Ultrasound

Advanced Emphysema Leads to High False Positivity Rate for Pneumothorax in Point of Care Ultrasound

Clinical Improvements after Endoscopic Lung Volume Reduction with Valves in Patients with advanced Emphysema and a 6-Minute-Walk-Test ≤140 m at Baseline

BackgroundData regarding the effectiveness and safety of endoscopic lung volume reduction with valves (ELVR) in emphysema patients with very low 6-Minute Walk Test (6-MWT) is limited. Patients with severe emphysema and very low exercise capacity, as indicated by a 6-MWT ≤140 m, are often excluded from clinical studies on ELVR, assuming limited therapeutics benefits and increased complication risk.Study Designs and MethodsThis study utilized data from the Lungenemphysemregister e.V., a large German national multi-center prospective open label clinical trial, and aimed to assess the outcomes of ELVR in patients with a baseline 6-MWT ≤140 m and dyspnea primarily attributed to hyperinflation.ResultsFifty-four patients with a baseline 6-MWT ≤140 m and 365 patients with a baseline 6-MWT between 140 m and 450 m were included in the study. Baseline characteristics were representative for patients with advanced lung emphysema. Patients with a 6-MWT ≤140 m at baseline had a lower FEV1, DLCO and higher symptom burden. In the 3-month-follow-up, patients of both groups showed statistically significant improvements in lung function parameters, exercise capacity and quality of life parameters compared to baseline. Patients with a 6-MWT ≤140 m at baseline showed significantly more 6-MWT improvement compared to patients with baseline 6-MWT between 140 m–450 m. Moreover, complication rates were similar in both groups.InterpretationIn summary, the data indicates that ELVR may be an effective and safe treatment for emphysema patients with a very low 6-MWT ≤140 m, if very limited exercise capacity is predominately caused by lung emphysema. Therefore future studies should include emphysema patients with a very low 6-MWT.

Assessment of Emphysema on X-ray Equivalent Dose Photon-Counting Detector CT

Objectives The aim of this study was to evaluate the feasibility and efficacy of visual scoring, low-attenuation volume (LAV), and deep learning methods for estimating emphysema extent in x-ray dose photon-counting detector computed tomography (PCD-CT), aiming to explore future dose reduction potentials. Methods One hundred one prospectively enrolled patients underwent noncontrast low- and chest x-ray dose CT scans in the same study using PCD-CT. Overall image quality, sharpness, and noise, as well as visual emphysema pattern (no, trace, mild, moderate, confluent, and advanced destructive emphysema; as defined by the Fleischner Society), were independently assessed by 2 experienced radiologists for low- and x-ray dose images, followed by an expert consensus read. In the second step, automated emphysema quantification was performed using an established LAV algorithm with a threshold of −950 HU and a commercially available deep learning model for automated emphysema quantification. Automated estimations of emphysema extent were converted and compared with visual scoring ratings. Results X-ray dose scans exhibited a significantly lower computed tomography dose index than low-dose scans (low-dose: 0.66 ± 0.16 mGy, x-ray dose: 0.11 ± 0.03 mGy, P < 0.001). Interreader agreement between low- and x-ray dose for visual emphysema scoring was excellent (κ = 0.83). Visual emphysema scoring consensus showed good agreement between low-dose and x-ray dose scans (κ = 0.70), with significant and strong correlation (Spearman ρ = 0.79). Although trace emphysema was underestimated in x-ray dose scans, there was no significant difference in the detection of higher-grade (mild to advanced destructive) emphysema (P = 0.125) between the 2 scan doses. Although predicted emphysema volumes on x-ray dose scans for the LAV method showed strong and the deep learning model excellent significant correlations with predictions on low-dose scans, both methods significantly overestimated emphysema volumes on lower quality scans (P < 0.001), with the deep learning model being more robust. Further, deep learning emphysema severity estimations showed higher agreement (κ = 0.65) and correlation (Spearman ρ = 0.64) with visual scoring for low-dose scans than LAV predictions (κ = 0.48, Spearman ρ = 0.45). Conclusions The severity of emphysema can be reliably estimated using visual scoring on CT scans performed with x-ray equivalent doses on a PCD-CT. A deep learning algorithm demonstrated good agreement and strong correlation with the visual scoring method on low-dose scans. However, both the deep learning and LAV algorithms overestimated emphysema extent on x-ray dose scans. Nonetheless, x-ray equivalent radiation dose scans may revolutionize the detection and monitoring of disease in chronic obstructive pulmonary disease patients.

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 (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.

Efficacy and safety of simultaneous combined Zephyr and Spiration valve therapy in patients with advanced pulmonary emphysema

BackgroundEndoscopic lung volume reduction with valves is a minimally invasive treatment strategy for patients with severe pulmonary emphysema. Two valve systems are currently available: Zephyr and Spiration valves. As these can be implanted simultaneously in the same procedure, the question arose as to the effect on lung function, exercise capacity and subjective disease perception after combined valve treatment. MethodsWe conducted a retrospective analysis of 108 patients with combined, simultaneous treatment of Zephyr and Spiration valves. The decision on which and how many valves to implant was based on the individual patient anatomy. Effects on lung function, exercise capacity and atelectasis formation as well as complications were evaluated 90- and 180-days post-treatment (90d-FU and 180d-FU). ResultsAt 90d-FU (n = 90), the mean change was 86.7 ± 183.7 mL for FEV1 and -645.3 ± 1276.5 mL for RV, with responder rates of 39.8 % and 46.5 %, respectively. Complete atelectasis occurred in 16.7 % and partial atelectasis in 25.5 % of patients. Six-minute walking distance increased by 27.00 m [-1.50 – 68.50m]. The rates of pneumothorax (10.2 %) 6 months after treatment were not higher than in randomized controlled trials (RCTs). Likely due to the inclusion of high-risk patients, there was a higher incidence of severe COPD exacerbation (21.3 %) and pneumonia (12.0 %) compared to RCTs. ConclusionsThe combined implantation of Zephyr and Spiration valves resulted in significant clinical and functional improvements with an acceptable risk profile. Therefore, the ability to combine both valve types in severe emphysema could be a promising option in endoscopic lung volume reduction.

Twenty four-month follow-up after bullectomy, unilateral and bilateral lung volume reduction surgery: a single-center retrospective analysis of consecutive cases

PurposeWhile pharmacologic therapy remains the cornerstone of lung emphysema treatment, surgery is an additional therapeutic option in selected patient groups with advanced emphysema. The aim of lung volume reduction surgery (LVRS) is to improve lung function, exercise capacity, quality of life and survival. We sought to determine the therapeutic value of surgical resection in specific patients with lung emphysema.Patients and methodsA retrospective study was performed consisting of 58 patients with lung emphysema who underwent surgical intervention over a 10-year period and were followed for 2 years postoperatively. The clinical characteristics recorded were FEV1 (forced expiratory volume in 1 s), the 6-min walk test (6-MWT), the Modified Medical Research Council (mMRC), body mass index (BMI) and quality of life prior to and 6, 12 and 24 months after surgical intervention. Moreover, all peri- and post-operative complications were noted.ResultsOut of 58 emphysema patients (72% male, FEV1 (L) 2.21 ± 0.17, RV (L) 3.39 ± 0.55), 19 underwent surgical bullectomy, 31 unilateral LVRS and 8 sequential bilateral LVRS. Six months after surgery, there was a statistically significant improvement in FEV1, RV, TLC, 6-MWT and mMRC. Over a period of 12 to 24 months postoperatively, clinical benefit gradually declines most likely due to COPD progression but patients still experienced a significant improvement in FEV1. The most common postoperative complications were persistent air leakage (> 7 days), arrhythmia and subcutaneous emphysema in 60%, 51.6% and 22.4%, respectively. No deaths were observed after surgical intervention.ConclusionIn a selected patient population, surgery led to significant improvement of lung function parameters, exercise capacity and quality of life. Over a period of 12 to 24 months postoperatively, clinical benefit gradually decreased most likely due to COPD progression.

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

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. 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. 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. We demonstrate that an elective lobectomy after an initial valve treatment is safe and feasible and restores the lung volume reduction effect.

First in vivo Experiment with PulmValve Endobronchial Valve: Feasibility, Efficiency, and Safety

Plain Language SummaryEndoscopic lung volume reduction with endobronchial valves has been widely recognized as a treatment for advanced emphysema and chronic obstructive pulmonary disease. The main challenges include the technical complexity of implanting valves in the upper lobes and the number of valves required. These issues may be addressed by using larger diameter endobronchial valves in the lobar bronchi. The newly developed PulmValve System offers five variants of valves designed to accommodate airways with diameters ranging from 7.0 to 15.0 mm. The system is specifically designed for lobar bronchial implantation, with valve diameters within the range of 10.5–16.5 mm. Our study reports the successful implantation and subsequent removal post-placement of the PulmValve (PV-13) within a short operative time in healthy porcine models. During an 84-day follow-up period, significant atelectasis was induced in the distal lung without evidence of device migration, malfunction, or severe complications.

Implementation of an enhanced recovery protocol for lung volume reduction surgery: an observational cohort study.

Lung volume reduction surgery (LVRS) is an established therapeutic option for advanced emphysema. To improve patients' safety and reduce complications, an enhanced recovery protocol (ERP) was implemented. This study aims to describe and evaluate the short-term outcome of this ERP. This retrospective single-centre study included all consecutive LVRS patients (1 January 2017 until 15 September 2020). An ERP for LVRS was implemented and stepwise optimised from 1 August 2019, it consisted of changes in pre-, peri- and postoperative care pathways. Patients were compared before and after implementation of ERP. Primary outcome was incidence of postoperative complications (Clavien-Dindo), and secondary outcomes included chest tube duration, incidence of prolonged air leak (PAL), length of stay (LOS) and 90-day mortality. Lung function and exercise capacity were evaluated at 3 and 6 months post-LVRS. Seventy-six LVRS patients were included (pre-ERP: n=41, ERP: n=35). The ERP cohort presented with lower incidence of postoperative complications (42% vs 83%, P=0.0002), shorter chest tube duration (4 vs 12 days, P<0.0001) with a lower incidence of PAL (21% vs 61%, P=0.0005) and shorter LOS (6 vs 14 days, P<0.0001). No in-hospital mortality occurred in the ERP cohort versus 4 pre-ERP. Postoperative forced expiratory volume in 1 s was higher in the ERP cohort compared to pre-ERP at 3 months (1.35 vs 1.02 l) and at 6 months (1.31 vs 1.01 l). Implementation of ERP as part of a comprehensive reconceptualisation towards LVRS, demonstrated fewer postoperative complications, including PAL, resulting in reduced LOS. Improved short-term functional outcomes were observed at 3 and 6 months.

Treatable traits in advanced emphysema patients eligible for bronchoscopic lung volume reduction with endobronchial valves

IntroductionPatients with advanced emphysema eligible for bronchoscopic lung volume reduction (BLVR) using endobronchial valves (EBV) are characterized by severe static lung hyperinflation, which can be considered a treatable trait. Other treatable traits (TTs), which are assumed to be present in this highly selected patient group, have not been studied in detail nor how they may affect health-related quality of life (HRQL). AimsWe aimed to evaluate a spectrum of TTs in COPD patients eligible for EBV treatment and their association with HRQL. MethodsThe SoLVE study (NCT03474471) was a prospective multicenter randomized controlled trial to examine the impact of pulmonary rehabilitation in COPD patients receiving EBV. The presence/absence of 16 TTs was based on pre-defined thresholds. HRQL was assessed with the St. George's Respiratory Questionnaire (SGRQ). Subjects were stratified into two groups, using the median split method, into higher or lower SGRQ total score. Logistic regression assessed the odds ratio (OR) of having a higher SGRQ total score per TT. ResultsNinety-seven subjects were included, the mean number of TTs per patient was 8.1 ± 2.5. Low physical activity (95%), poor exercise capacity (94%) and severe fatigue (75%) were the most prevalent TTs. The sum of TTs present in a subject was associated with the SGRQ total score (r = 0.53; p < 0.001). Severe fatigue, depression, and anxiety were predictors of having a higher SGRQ total score. ConclusionsA high prevalence and co-occurrence of multiple TTs were identified in emphysema patients eligible for EBV. Patients with a higher number of TTs were more likely to have worse HRQL.

Bronchoscopic lung volume reduction by instillation of fibrinogen and thrombin in COPD patients with homogenous emphysema

BackgroundThe new endobronchial therapy called biological lung volume reduction (BioLVR) involves using a rapid polymerizing sealant to block off the most emphysematous portions of the lungs. The primary mechanism of action is resorption atelectasis, which is then followed by inflammation and remodeling of the airspace. The remodeling process will result in the formation of scars, leading to the contraction of the lung tissue. As a result, a decrease in functional lung volume is anticipated for a period of 6–8 weeks.ObjectiveAssessing the safety and effectiveness of bronchoscopic installation of (fibrinogen and thrombin) in COPD patients with homogeneous emphysema in terms of radiological, physiological, and quality of life outcomes.MethodsBetween December 2017 and December 2019, 40 COPD patients with homogeneous emphysema were studied using a fiber optic bronchoscope while they were awake but sedated. Tanta University Hospitals’ chest medicine department collaborated with the diagnostic radiology department of the Faculty of Medicine.ResultsAll the following parameters were reduced from their initial values: HRCT volumetry, RV/TLC, mMRC dyspnea scale, CAT score, 6MWT, FEV1, and the FEV1/FVC ratio at the first, third, and sixth months from the beginning (p = 0.001). One individual (0.025%) had pneumonia, whereas three individuals had COPD (0.075%). Using fibrin glue produced locally, biological lung volume reduction (Bio LVR) may be an effective treatment for advanced homogenous emphysema.ConclusionBy using locally prepared fibrin glue the biologic lung volume reduction (Bio LVR) may be a convenient method to treat advanced homogenous emphysema.

Lung volume reduction surgery is safe and leads to functional improvement in patients who fail or cannot undergo bronchoscopic lung volume reduction

BackgroundBronchoscopic lung volume reduction (BLVR) has supplanted surgery in the treatment of patients with advanced emphysema, but not all patients qualify for it. Our study aimed to investigate the outcomes of lung volume reduction surgery (LVRS) among patients who either failed BLVR or were not candidates for it. MethodsWe conducted a retrospective analysis of patients who underwent LVRS for upper lobe–predominant emphysema at a single tertiary center between March 2018 and December 2022. The main outcomes measures were preoperative and postoperative respiratory parameters, perioperative morbidity, and mortality. ResultsA total of 67 LVRS recipients were evaluated, including 10 who had failed prior valve placement. The median patient age was 69 years, and 35 (52%) were male. All procedures were performed thoracoscopically, with 36 patients (53.7%) undergoing bilateral LVRS. The median hospital length of stay was 7 days (interquartile range, 6-11 days). Prolonged air leak (>7 days) occurred in 20 patients. There was one 90-day mortality from a nosocomial pneumonia (non–COVID-related) and no further deaths at 12 months. There were mean improvements of 10.07% in forced expiratory volume in 1 second and 4.74% in diffusing capacity of the lung for carbon monoxide, along with a mean decrease 49.2% in residual volume (P < .001 for all). The modified Medical Research Council dyspnea scale was improved by 1.84 points (P < .001). ConclusionsLVRS can be performed safely in patients who are not candidates for BLVR and those who fail BLVR and leads to significant functional improvement. Long-term follow-up is necessary to ensure the sustainability of LVRS benefits in this patient population.

Baseline characteristics from a 3-year longitudinal study to phenotype subjects with COPD: the FOOTPRINTS study

BackgroundFOOTPRINTS® is a prospective, longitudinal, 3-year study assessing the association between biomarkers of inflammation/lung tissue destruction and chronic obstructive pulmonary disease (COPD) severity and progression in ex-smokers with mild-to-severe COPD. Here, we present baseline characteristics and select biomarkers of study subjects.MethodsThe methodology of FOOTPRINTS® has been published previously. The study population included ex-smokers with a range of COPD severities (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages 1–3), ex-smokers with COPD and alpha-1-antitrypsin deficiency (A1ATD) and a control group of ex-smokers without airflow limitation (EwAL). At study entry, data were collected for: demographics, disease characteristics, history of comorbidities and COPD exacerbations, symptoms, lung function and volume, exercise capacity, soluble biomarkers, and quantitative and qualitative computed tomography. Baseline data are presented with descriptive statistical comparisons for soluble biomarkers in the individual GOLD and A1ATD groups versus EwAL.ResultsIn total, 463 subjects were enrolled. The per-protocol set comprised 456 subjects, mostly male (64.5%). The mean (standard deviation) age was 60.7 (6.9) years. At baseline, increasing pulmonary symptoms, worse lung function, increased residual volume, reduced diffusing capacity of the lung for carbon monoxide (DLco) and greater prevalence of centrilobular emphysema were observed with increasing disease severity amongst GOLD 1–3 subjects. Subjects with A1ATD (n = 19) had similar lung function parameters to GOLD 2–3 subjects, a high residual volume comparable to GOLD 3 subjects, and similar air trapping to GOLD 2 subjects. Compared with EwAL (n = 61), subjects with A1ATD had worse lung function, increased residual volume, reduced DLco, and a greater prevalence of confluent or advanced destructive emphysema. The soluble inflammatory biomarkers white blood cell count, fibrinogen, high-sensitivity C-reactive protein and plasma surfactant protein were higher in GOLD 1–3 groups than in the EwAL group. Interleukin-6 was expressed less often in EwAL subjects compared with subjects in the GOLD and A1ATD groups. Soluble receptor for advanced glycation end product was lowest in GOLD 3 subjects, indicative of more severe emphysema.ConclusionsThese findings provide context for upcoming results from FOOTPRINTS®, which aims to establish correlations between biomarkers and disease progression in a representative COPD population.Trial registration number: NCT02719184, study start date 13/04/2016.

Clinical, physiological, and radiological different phenotypes of COPD patients

BackgroundCOPD is a heterogeneous lung disorder with multiple phenotypes and endotypes. This study aimed to identify the diverse clinical, physiological, and radiological phenotypes of COPD. Moreover, to provide whether there was a possible relation between FEV1%, FVC%, and FEV1/FVC ratio, [both before and after broncho-dilation with the diameters of the airway at three diverse levels throughout both inspiratory and expiratory phases of respiration].ResultsThis study included 50 cases, that were classified according to the radiological phenotypes into 5 groups [29 cases (58%) were mild [centrilobular emphysema) CLE)], 8 cases (16%) were moderate CLE, 5 cases (10%) were [confluent emphysema (CON)], 5 cases (10%) were [advanced destructive emphysema (ADE)] and 3 cases (6%) were [para septal emphysema (PSE)]. There was no considerable variance in the frequency of COPD clinical phenotypes among the diverse radiological phenotypes. There was a moderate positive correlation between the predicted FEV1% and the corresponding inter-luminal diameter at the selected levels (RB1, and LB3) in the inspiratory phase of respiration (P < 0.001 and p = 0.001 respectively) (r = 0.58, 0.46 respectively). and there was a moderate positive correlation in the expiratory phase of respiration between the predicted FEV1% and the equivalent inter-luminal diameter at the selected levels (RB1, and LB3) (P < 0.001 respectively) (r = 0.62, 0.51 respectively).ConclusionsWe confirmed that COPD is a highly heterogeneous illness, with multiple diverse clinical, physiological, and radiological phenotypes. Furthermore, HRCT can well be allied with pulmonary function tests (PFT).

Bronchoscopic Lung Volume Reduction: Highlighting the Patient Selection Process

Patients with advanced emphysema frequently experience severe dyspnea that is inadequately treated with medical therapy alone. Over the past 4 years, we have seen increased usage of bronchoscopic lung volume reduction (BLVR) with endobronchial valves. Success of the procedure is dependent on patient selection because it is not necessarily appropriate for all patients with severe emphysema. (Table 1) The purpose of this review is to highlight the selection process at a single institution. We also discuss the influence of this process on outcomes. Between March 1, 2019, and October 12, 2021, 2402 patients were referred to a dedicated chronic obstructive pulmonary disease clinic at Mayo Clinic – Rochester, whereas 161 patients were subsequently referred for multidisciplinary BLVR review. Of those patients, 53 (32.9%) were selected to receive valves and 35 (21.7%) ultimately underwent the procedure. The main reasons for exclusion included an incompatible quantitative computed tomography analysis (n=37, 34.3%), presence of pulmonary nodule or active malignancy (n=14, 13.0%), or need for completion of pulmonary rehabilitation (n=9, 8.3%). Full or partial (>70%) target lobe collapse was observed in 58.6% of patients who received valves. Those with collapse experienced statistically significant improvements in spirometric measures. Twelve patients experienced a pneumothorax (34.3%), with 10 patients requiring thoracostomy tube placement and prolonged hospitalization (median, 11 days; range, 4-39 days). Nineteen patients required a secondary procedure within the first year. The study highlights how a multidisciplinary approach to the BLVR selection process enables individualization of a complex procedure and enhances the exclusion of inappropriate candidates.

Surgical or bronchoscopic lung volume reduction for emphysema therapy

More than 20 years ago, surgical lung volume reduction (LVRS) was already established in patients with advanced emphysema as a palliative therapy option that reduces respiratory distress and improves lung function and quality of life. In addition, bronchoscopic procedures (BLVR) aimed at volume reduction have existed for just over 10 years. The advantages and disadvantages of LVRS and BLVR are discussed in this article.

The impact of emphysema heterogeneity on treatment response after endobronchial valve treatment.

Lung volume reduction with endobronchial valves can significantly improve functional outcomes in patients with advanced emphysema. The extent and spatial distribution pattern of emphysema shows considerable heterogeneity, which might affect response to endobronchial valve treatment. Our aim was to study the effect of emphysema heterogeneity on change in clinical outcomes after endobronchial valve treatment. Data were collected from our national registry of patients who received endobronchial valve treatment between 2016 and 2020. We assessed the association between the heterogeneity index, absolute difference in destruction between the target and ipsilateral lobe, and relative change in forced expiratory volume in 1 s (FEV1), residual volume (RV), St George's Respiratory Questionnaire (SGRQ) and 6-min walk distance (6MWD) at 6-week, 6-month and 12-month follow-up. In total, 236 patients were included. Heterogeneity index was significantly associated with improvements in FEV1, RV and 6MWD at all follow-up visits, and in SGRQ at the 6- and 12-month follow-up visits. The majority of patients, independent of heterogeneity index, showed clinically meaningful improvements based on minimal important difference thresholds. Heterogeneity index influences the degree of clinical improvement after endobronchial valve treatment where in general a more heterogeneous distribution translates to larger improvements. However, patients with a more homogeneous distribution also showed clinically meaningful improvements. Therefore, we believe emphysema heterogeneity alone should not be used as a decisive patient selection criterion, but should be weighed in the context of all other relevant patient and target lobe characteristics when deciding on a patient's treatment eligibility.

Endobronchial Valve Replacements in Patients with Advanced Emphysema After Endoscopic Lung Volume Reduction.

Up to 41% of patients with endobronchial valve implantation need revision bronchoscopies and valve replacements most likely due to valve dysfunction or lack of benefit. So far, no data is available whether valve replacements lead to the desired lobar volume reduction and therapy benefit. We conducted a single-center retrospective analysis of patients with endobronchial valve implantation and at least one valve replacement. Indications and number of revision bronchoscopies and valve replacements were evaluated. Therapy benefit regarding lung function and exercise capacity as well as development of complete lobar atelectasis was investigated and possible predictors identified. We identified 73 patients with 1-12 revision bronchoscopies and 1-5 valve replacements. The main indication for revision bronchoscopy in this group was lack of therapy benefit (44.2%). Lung function and exercise capacity showed improvements in about one-third of patients even years after the initial implantation. A total of 26% of all patients showed a complete lobar atelectasis at the end of the observation period, 56.2% had developed lung volume reduction. The logistic regression revealed the development of a previous complete lobar atelectasis as predictor for a complete lobar atelectasis at final follow-up. Oral cortisone long-term therapy was also shown as predictive factor. The probability for a final complete lobar atelectasis was 69.2% if a lobar atelectasis had developed before. Valve replacements are more likely to be beneficial in patients who develop a re-aeration of a previous lobar atelectasis following valve implantation. Every decision for revision bronchoscopy must be taken carefully.

Validation of RAH VQ SPECT/CT lobar quantification program using a modified version of GE Q lung.

The value of ventilation-perfusion (VQ) single photon emission tomography/computed tomography (SPECT/CT) lobar quantification for pre-operative assessment of lobectomy and lung volume reduction is known. Our in-house developed software, RAH ventilation perfusion SPECT/CT quantification (RAHVQSQ) has been shown to be able to identify the target lobe for collapse in bronchoscopic lung volume reduction (BLVR) for advanced emphysema. We have proven inter and intra observer reproducibility but are yet to validate the accuracy of our program. This study aims to validate the accuracy of our quantitative program through comparison with a modified version of GE Q lung which is a commercial program certified for clinical use. Ventilation-perfusion SPECT/CT data of 19 subjects from our previous study using RAHVQSQ for BLVR assessment were re-analysed using Q lung by 2 technologists independently and in a blinded fashion to determine lobar differential ventilation, perfusion and volume percentages. The data were from GE Hawkeye 4 and external CT, thus a modified version of Q lung was used. To determine interobserver variation in the 3 parameters between the 3 assessors, intraclass correlation coefficient (ICC) and Bland-Altman limits of agreement (LoA) were generated. Paired comparisons between the 3 assessors had high ICC (range for ventilation: 0.69-0.97; perfusion: 0.69-0.97; volume: 0.63-0.97) and means of LoA differences close to zero (range for ventilation: -0.04 - 0.10; perfusion: 0.00-0.02; volume: -0.12 - 0.09) were noted indicative of good concordance for all parameters. Using VQ SPECT/CT data of participants with advanced airway disease, our study has found a close concordance of estimated differential lobar ventilation, perfusion and volume percentages using RAHVQSQ when compared with a duplicated blinded assessment using Q lung. The good concordance supports the validity of our quantitative methodology.

Bronchoscopic lung volume reduction

Bronchoscopic lung volume reduction is as a safe and effective therapy for patients with advanced emphysema, suffering from breathlessness despite optimal medical therapy. By reducing hyperinflation, it improves lung function, exercise capacity and quality of life. The technique includes one-way endobronchial valves, thermal vapor ablation and endobronchial coils. Patient selection is the key to a successful therapy; hence the indication should be evaluated in a multidisciplinary emphysema team meeting. The procedure can lead to a potentially life-threatening complication. Therefore, an adequate post-procedural patient management is crucial.