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.

Highlights from the 11th Bronchitis International Symposium: "Heterogeneity of Lung Disease in a Changing Environment," Groningen, The Netherlands, 2024.

This meeting report provides an overview of the highlights of the Bronchitis XI international symposium, held in June 2024 in Groningen, The Netherlands. The theme of this year's symposium was "heterogeneity of lung disease in a changing environment," and the symposium contained five different sessions focused on (i) heterogeneity of chronic lung disease, (ii) environmental changes with impact on lung disease, (iii) the aging lung, (iv) bronchitis, and (v) innovative therapy. The highlights from each of these sessions will be discussed separately, providing an overview of latest studies, new data, and enthralling discussions.

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.

Optimizing clinical outcomes for bronchoscopic lung volume reduction with Zephyr® valves.

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

Perspectives of Patients and Professionals on Implementing a Computer Adaptive Vision-Related Quality of Life Outcome (CAT-EyeQ) in Clinical Practice.

Purpose: The CAT-EyeQ is a computer adaptive test (CAT) which measures vision-related quality of life in patients having exudative retinal diseases. The aim of this study is to investigate the usability of the CAT-EyeQ in clinical practice and identify potential barriers and facilitators for implementation (problem analysis). Methods: Patients and health care professionals participated in the study regarding the usability of the CAT-EyeQ, and clinic managers and health care professionals were included in the problem analysis for implementation. In total, we conducted 18 semi-structured interviews. The Consolidated Framework for Implementation Research (CFIR) was used to develop the interview guides and to structure results. Results: Six themes were derived from the usability study and problem analysis: (1) quality of the CAT-EyeQ and the applicability to patients' needs and preferences, (2) embedding the CAT-EyeQ in current practice, (3) implementation climate of the eye hospitals, (4) attitude of professionals, (5) engaging and encouraging professionals, and (6) integration of the CAT-EyeQ in health care - needs after piloting. Conclusions: Patients and professionals mentioned that the CAT-EyeQ improved insight into the impact of eye diseases on a patient's daily life, it allowed for more attention on the patient perspective and the structured measurement of vision-related quality of life. The main perceived barriers mentioned by professionals for using the CAT-EyeQ were lack of time and the integration of the patient-reported outcome measure (PROM) results within the electronic patient record (EPR). Translational Relevance: The CAT-EyeQ, accompanied by an overview of stakeholder perspectives resulting from this implementation study, can now be used in clinical practice.

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.

From plugging air leaks to reducing lung volume: a review of the many uses of endobronchial valves.

INTRODUCTION: One-way endobronchial valve treatment improves lung function, exercise capacity, and quality of live in patients with severe emphysema and hyperinflation. Other areas of therapeutic application include treatment of persistent air leak (PAL), giant emphysematous bullae, native lung hyperinflation, hemoptysis, and tuberculosis. AREAS COVERED: In this review, we will assess the clinical evidence and safety of the different applications of one-way endobronchial valves (EBV). EXPERT OPINION: There is solid clinical evidence for the use of one-way EBV for lung volume reduction in emphysema. Treatment with one-way EBV can be considered for the treatment of PAL. The application of one-way EBV for giant bullae, post lung transplant native lung hyperinflation, hemoptysis, and tuberculosis is under investigation and more research is required to investigate the efficacy and safety of these applications.

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.

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.

The additional diagnostic value of virtual bronchoscopy navigation in patients with pulmonary nodules - The NAVIGATOR study.

BACKGROUND: The number of solitary pulmonary nodules to be evaluated is expected to increase and therefore we need to improve diagnostic and therapeutic tools to approach these nodules. To prevent patients from futile invasive procedures and receiving treatment without histological confirmation of cancer, we evaluated the value of virtual bronchoscopy navigation to obtain a diagnosis of the solitary pulmonary nodule in a real-world clinical setting. METHODS: In the NAVIGATOR single center, prospective, observational cohort study patients underwent a virtual bronchoscopy navigation procedure with or without guide sheet tunnelling to assess a solitary pulmonary nodule. Nodules were considered not accessible if a diagnosis could not be obtained by either by CT-guided transthoracic biopsy or conventional bronchoscopy. RESULTS: Between February 2021 and January 2022 35 patients underwent the virtual bronchoscopy navigation procedure. The overall diagnostic yield was 77% and was dependent on size of the nodule and chosen path, with highest yield in lesions with an airway path. Adverse events were few and manageable. CONCLUSION: Virtual bronchoscopy navigation with or without sheet tunnelling is a new technique with a good diagnostic yield, also in patients in whom previously performed procedures failed to establish a diagnosis and/or alternative procedures are considered not feasible based on expected yield and/or safety. Preventing futile or more invasive procedures like surgery or transthoracic punctures with a higher complication rate is beneficial for patients, and allowed treatment adaptation in two-third of the analyzed patient population.

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.

Optimizing Computer Adaptive Test Performance: A Hybrid Simulation Study to Customize the Administration Rules of the CAT-EyeQ in Macular Edema Patients.

Purpose: In previous research the EyeQ item bank, which measures vision-related quality of life (Vr-QoL), was calibrated for future use as a computer adaptive test (CAT). The aim of the current study was to define optimal administration rules. Methods: CAT simulations were performed using real responses. Patients (N = 704; mean age, 76.2 years), having macular edema completed the EyeQ. Four CAT simulations were performed, which were set with different administration rules regarding length, accuracy level and the association with best health, which means the test was aborted after the first 4 responses of having no complaints. Results: The CATDefault showed a mean test length of 6.9 and 15.1% unreliable estimations. Extending the test length to 15 items (CATAlt1) resulted in a mean test length of 7.3 and slightly decreased the percentage unreliable estimations (11.5%). Under CATAlt2, the percentage unreliable estimations was 15.1% and the mean test length was 9.7. Percentages of floor/ceiling effects for CATDefault, CATAlt1, and CATAlt2 were 3.1, 3.0, and 3.1, respectively. CATBestHealth reduced the mean test length to 5.9 and showed 18.2% unreliably estimated patients, of which 14.2% had floor/ceiling scores. Conclusions: This study shows that the CATBestHealth provided reliably estimated ability scores, with a negligible increase in the number of unreliably estimated patients and ensures that patients having little or no vision-related quality of life problems are minimally burdened with completing items. Translational Relevance: The computer adaptive test EyeQ, set with optimal administration rules, can now be used for the computer adaptive assessment of vision-related quality of life in patients suffering from exudative retinal diseases in ophthalmic clinical practice.

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

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

MR lymphangiography of lymphatic abnormalities in children and adults with Noonan syndrome.

Noonan syndrome is associated with complex lymphatic abnormalities. We report dynamic-contrast enhanced MR lymphangiography (DCMRL) findings in children and adults with Noonan syndrome to further elucidate this complex disease spectrum. A retrospective evaluation of patients with confirmed Noonan syndrome and clinical signs of lymphatic dysfunction undergoing DCMRL between 01/2019 and 04/2021 was performed. MRL included T2-weighted imaging (T2w) and DCMRL. Clinical history/presentation and genetic variants were recorded. T2w-imaging was evaluated for central lymphatic abnormalities and edema distribution. DCMRL was evaluated regarding the presence of cisterna chyli/thoracic duct, lymphatic leakages, pathological lymphatic reflux and abnormal lymphatic perfusion. The time from start of contrast-injection to initial enhancement of the thoracic duct venous junction was measured to calculate the speed of contrast propagation. Eleven patients with Noonan syndrome with lymphatic abnormalities (5 female, 6 male; 7 infants, 4 adults; mean age 10.8 ± 16.4 years) were identified (PTPN11 n = 5/11 [45.5%], RIT1 n = 5/11 [45.5%], KRAS n = 1/11 [9%]). Patients had a chylothorax (n = 10/11 [91%]) and/or pulmonary lymphangiectasia [dilated pulmonary lymph vessels] (n = 9/11 [82%]). Mediastinal/pulmonary edema was depicted in 9/11 (82%) patients. The thoracic duct (TD) was (partially) absent in 10/11 (91%) cases. DCMRL showed lymphatic reflux into intercostal (n = 11/11 [100%]), mediastinal (n = 9/11 [82%]), peribronchial (n = 8/11 [73%]), peripheral (n = 5/11 [45.5%]) and genital lymphatics (n = 4/11 [36%]). Abnormal pulmonary/pleural lymphatic perfusion was seen in 8/11 patients (73%). At infancy peripheral/genital edema was more prevalent in patients with RIT1 than PTPN11 (n = 3/5 vs. n = 0/5). Compared to patients with PTPN11 who had fast lymphatic enhancement in 4/5 patients, enhancement took markedly longer in 4/5 patients with RIT1-mutations. Thoracic duct dysplasia, intercostal reflux and pulmonary/pleural lymphatic perfusion are characteristic findings in patients with Noonan syndrome presenting with chylothorax and/or pulmonary lymphangiectasia. Central lymphatic flow abnormalities show possible phenotypical differences between PTPN11 and RIT1-mutations.

A peculiar case of syphilis infection: The great imitator is on the rise.

The incidence of syphilis is on the rise worldwide and can pose many diagnostic and therapeutic difficulties for doctors. Given the wide variety of presenting symptoms, syphilis is also known as the great imitator, which in turn frequently leads to a pronounced diagnostic- and therapeutic delay for patients. Here we present a case report of syphilitic uveitis and papillitis accompanied by acute vision loss, a rare presentation of a tertiary syphilis infection that clinically mimicked a giant cell arteritis (GCA) or arteritic anterior ischemic optic neuropathy (AAION). The patient was treated with high-dose intravenous benzyl penicillin after which full vision was restored. By presenting this case, we hope to raise awareness for the increasing incidence of syphilis infections and stress the importance of syphilis testing in patients with otherwise unexplained uveitis.