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Background: Lung volume reduction coil (LVR-coil) treatment provides a minimally invasive treatment option for severe emphysema patients which has been studied in multiple clinical trials. Objectives: The aim of the study was to assess the effect of LVR-coil treatment on pulmonary function, quality of life, and exercise capacity using individual participant data. Method: PubMed, Web of Science, and EMBASE were searched until May 17, 2021. Prospective single-arm and randomized controlled trials that evaluated the effect of LVR-coil treatment on forced expiratory volume in 1 s (FEV1), residual volume (RV), St. George Respiratory Questionnaire (SGRQ) total score, and/or 6-min walk distance (6MWD) and were registered in an official clinical trial database were eligible for inclusion. Individual patient data were requested, and a linear mixed effects model was used to calculate overall treatment effects. Results: Eight trials were included in the final analysis, representing 680 individual patients. LVR-coil treatment resulted in a significant improvement in FEV1 at 3- (0.09 L [95% confidence interval (95% CI): 0.06–0.12]) and 6-month follow-up (0.07 L [95% CI: 0.03–0.10]), a significant reduction in RV at 3- (−0.45L [95% CI: −0.62 to −0.28]), 6- (−0.33L [95% CI: −0.52 to −0.14]), and 12-month follow-up (−0.36L [95% CI: −0.64 to −0.08]), a significant reduction in SGRQ total score at 3- (−12.3 points [95% CI: −15.8 to −8.8]), 6- (−10.1 points [95% CI: −12.8 to −7.3]), and 12-month follow-up (−9.8 points [95% CI: −15.0 to −4.7]) and a significant increase in 6MWD at 3-month follow-up (38 m [95% CI: 18–58]). Conclusions: LVR-coil treatment in emphysema patients results in sustained improvements in pulmonary function and quality of life and shorter lived improvements in exercise capacity. Since the owner of this LVR-coil has decided to stop the production and newer generations LVR-coils are currently being developed, these results can act as a reference for future studies and clinical guidance.

Background: Bronchoscopic lung volume reduction using endobronchial coils is a new treatment for patients with severe emphysema. To date, the benefits have been modest and have been suggested to be much larger in patients with severe hyperinflation and nonmulti-comorbidity. Objective: We aimed to evaluate the efficacy and safety of endobronchial coil treatment in a randomized multicenter clinical trial using optimized patient selection. Method: Patients with severe emphysema on HRCT scan with severe hyperinflation (residual volume [RV] ≥200% predicted and RV/total lung capacity [TLC] >55%) were randomized to coil treatment or control. Primary outcome measures were differences in the forced expiratory volume in 1 s (FEV1) and St George’s Respiratory Questionnaire (SGRQ) total score at 6 months. Results: Due to premature study termination, a total of 120 patients (age 63 ± 7 years, FEV1 29 ± 7% predicted, RV 251 ± 41% predicted, RV/TLC 67 ± 6%, and SGRQ 58 ± 13 points), instead of 210 patients, were randomized. At study termination, 91 patients (57 coil and 34 control) had 6-month results available. Analyses showed significantly greater improvements in favor of the coil group. The increase in FEV1 was greater in the coil group than that in the control group by + 10.3 [+4.7 to +16.0] % and in SGRQ by −10.6 [−15.9 to −5.4] points. At study termination, there were 5 (6.8%) deaths in the coil cohort reported. Conclusion: Despite early study termination, coil treatment compared to control results in a significant improvement in the lung function and quality of life benefits for up to 6 months in patients with emphysema and severe hyperinflation. These improvements were of clinical importance but were associated with a higher likelihood of serious adverse events.

Background: So far, 3 randomized controlled trials have shown that the endobronchial treatment using coils is safe and effective. However, the more exact underlying mechanism of the treatment and best predictors of response are unknown. Objectives: The aim of the study was to gain more knowledge about the underlying physiological mechanism of the lung volume reduction coil treatment and to identify potential predictors of response to this treatment. Methods: This was a prospective nonrandomized single-center study which included patients who were bilaterally treated with coils. Patients underwent an extensive number of physical tests at baseline and 3 months after treatment. Results: Twenty-four patients (29% male, mean age 62 years, forced expiratory volume in 1 s [FEV1] 26% pred, residual volume (RV) 231% pred) were included. Three months after treatment, significant improvements were found in spirometry, static hyperinflation, air trapping, airway resistance, treated lobe RV and treated lobes air trapping measured on CT scan, exercise capacity, and quality of life. The change in RV and airway resistance was significantly associated with a change in FEV1, forced vital capacity, air trapping, maximal expiratory pressure, dynamic compliance, and dynamic hyperinflation. Predictors of treatment response at baseline were a higher RV, larger air trapping, higher emphysema score in the treated lobes, and a lower physical activity level. Conclusions: Our results confirm that emphysema patients benefit from endobronchial coil treatment. The primary mechanism of action is decreasing static hyperinflation with improvement of airway resistance which consequently changes dynamic lung mechanics. However, the right patient population needs to be selected for the treatment to be beneficial which should include patients with severe lung hyperinflation, severe air trapping, and significant emphysema in target lobes.

Endoscopic lung volume reduction (ELVR) therapies are gaining prominence as a treatment option with guideline recommendations by COPD GOLD and NICE and the recent FDA approval for endobronchial valves. The transition from an experiment-based therapy only to clinical care comes with new challenges. A significant volume of evidence-based data has been published; all data demonstrate consistent improvements in several aspects of patient outcomes. Patients suffering from severe air trapping and thoracic hyperinflation seem to benefit the most from ELVR. In addition to lung function, baseline assessment should ideally include cardiopulmonary exercise testing, high-resolution computer tomography scan, perfusion scintigraphy, and echocardiography. This expert ELVR statement updates best practice recommendations from 2017 regarding patient selection and utilization of these various techniques for treating patients with advanced emphysema.

Bronchoscopic thermal vapor ablation (BTVA) represents one of the endoscopic lung volume reduction (ELVR) techniques that aims at hyperinflation reduction in patients with advanced emphysema to improve respiratory mechanics. By targeted segmental vapor ablation, an inflammatory response leads to tissue and volume reduction of the most diseased emphysematous segments. So far, BTVA has been demonstrated in several single-arm trials and 1 multinational randomized controlled trial to improve lung function, exercise capacity, and quality of life in patients with upper lobe-predominant emphysema irrespective of the collateral ventilation. In this review, we emphasize the practical aspects of this ELVR method. Patients with upper lobe-predominant emphysema, forced expiratory volume in 1 second (FEV1) between 20 and 45% of predicted, residual volume (RV) > 175% of predicted, and carbon monoxide diffusing capacity (DLCO) ≥20% of predicted can be considered for BTVA treatment. Prior to the procedure, a special software assists in identifying the target segments with the highest emphysema index, volume and the highest heterogeneity index to the untreated ipsilateral lung lobes. The procedure may be performed under deep sedation or preferably under general anesthesia. After positioning of the BTVA catheter and occlusion of the target segment by the occlusion balloon, heated water vapor is delivered in a predetermined specified time according to the vapor dose. After the procedure, patients should be strictly monitored to proactively detect symptoms of localized inflammatory reaction that may temporarily worsen the clinical status of the patient and to detect complications. As the data are still very limited, BTVA should be performed within clinical trials or comprehensive registries where the product is commercially available.

Interest in endoscopic lung volume reduction (ELVR) technologies for emphysema is consistently growing. In the last couple of months, several endoscopic options (e.g., endo- or intrabronchial valves, coil implants, and thermal vapor ablation) that have been evaluated in randomized controlled trials have been reported with the ultimate goal of improving respiratory mechanics and alleviating chronic dyspnea. Patients presenting with severe air trapping and thoracic hyperinflation have the greatest potential to derive benefit from ELVR procedures. Baseline assessment should ideally include cardiological evaluation, high-resolution computed tomography scan and perfusion scintigraphy, full pulmonary function tests, and cardiopulmonary exercise testing. This expert statement updates best practice recommendations regarding patient selection and utilization of these various techniques for the treatment of patients with advanced emphysema.

Background: Lung cancer is one of the commonest malignancies with a worldwide incidence of 1.6 million cases each year. Although the main aetiological factor has been identified (cigarette smoking), the progression of lung cancer from early changes such as dysplasia through to cancer is still not fully understood. Furthermore, current research techniques are reliant on obtaining tissue biopsies, a process that alters the natural history of the very process under investigation. Hence, there is a need for developing optical biopsy techniques. Objectives: To prospectively evaluate the feasibility of endocytoscopy and confocal endomicroscopy in the detection of malignant and pre-malignant changes in the airways. Methods: Findings with endocytoscopy and endomicroscopy were compared with conventional biopsies obtained from the same areas in 25 patients undergoing bronchoscopy for evaluation of endobronchial abnormalities and in 5 healthy control subjects. Results: Endocytoscopy was technically more difficult, and interpretable images were only obtained in 21 of the patients evaluated, and hence, complete information including histopathological information was available in 21 patients. Endocytoscopy appeared to correlate with the histopathological findings on tissue biopsy, and was able to distinguish normal epithelium from dysplasia and carcinoma. Confocal endomicroscopy was a more reliable technique with adequate visual information obtained in all patients examined but was unable to distinguish between dysplasia and carcinoma. Conclusion: This feasibility study suggests that endocytoscopy may have the potential to fulfil the role of optical biopsy in the evaluation of the pathogenesis of lung cancer.

Chronic obstructive pulmonary disease (COPD) is a progressive condition comprising a constellation of disorders from chronic bronchitis, airflow obstruction through to emphysema. The global burden of COPD is estimated at more than 6% of the population. The standard of care is based on a combination of smoking cessation, immunization, pharmacological treatments and pulmonary rehabilitation. However, the more advanced stages of COPD are challenging to manage. In this situation, our current standards of care do not adequately control patient symptoms nor halt the progressive decline. For the emphysema phenotype, lung volume reduction surgery has shown a beneficial effect in selected patients but is counterbalanced by the morbidity experienced by some patients. Bronchoscopic volume reduction technologies have been developed to improve the clinical situation of emphysema patients. This expert statement provides broad guidance regarding patient selection and the current position of the available techniques for patients with advanced emphysema. (C) 2016 S. Karger AG, Basel

Endobronchial ultrasound has been one of the success stories of the last decade, and the utility of the procedure continues to expand. Originally, it was developed for the staging and diagnosis of lung cancer, but its use rapidly expanded to other malignancies and even benign disease. We present the case of a patient originally referred with suspected endocarditis who was found to have a mass involving the right ventricle and the pulmonary outflow tract. Endobronchial ultrasound-guided biopsy was used to obtain a tissue diagnosis from the cardiac mass.

Chronic obstructive pulmonary disease remains one of the most common causes of morbidity and mortality globally. The disease is generally managed with pharmacotherapy, as well as guidance about smoking cessation and pulmonary rehabilitation. Endoscopic lung volume reduction (ELVR) has been proposed for the treatment of advanced emphysema, with the aim of obtaining the same clinical and functional advantages of surgical lung volume reduction whilst potentially reducing risks and costs. There is a growing body of evidence that certain well-defined sub-groups of patients with advanced emphysema may benefit from ELVR, provided the selection criteria are met and a systematic approach is followed. ELVR devices, particularly unidirectional valves and coils, are currently being rolled out to many countries outside of the USA and Europe, although very few centres currently have the capacity to correctly evaluate and provide ELVR to prospective candidates. The high cost of these interventions underpins the need for careful patient selection to best identify those who may or may not benefit from ELVR-related procedures. The aim of this review is to provide the practicing pulmonologist with an overview of the practical aspects and current evidence for the use of the various techniques available, and to suggest an evidence-based approach for the appropriate use of these devices, particularly in emerging markets, where there should be a drive to develop and equip key specialised ELVR units. (C) 2015 S. Karger AG, Basel

Emphysema is characterised by airflow obstruction, hyperinflation, and resultant dyspnoea. It is worth investigating whether decompression improves lung mechanics and enhances quality of life (QoL).The purpose of this study was to describe the feasibility and safety of creating a transthoracic pneumostoma to enable lung reduction.A transthoracic 10-mm diameter Portaero Access Tube (Portaero™, Cupertino, CA, USA) was implanted via a third intercostal space incision in 15 severe emphysema patients [mean age 63 years, forced expiratory volume in 1 s 54% predicted, diffusing capacity for carbon monoxide 31% predicted, residual volume 246% predicted, Six-Minute Walk Test 296 m]. Four weeks later, an 8-mm Portaero Disposable Tube (3-8 cm in length) was substituted and changed daily thereafter. The targeted primary endpoints were a ≥12% increase in forced expiratory volume in 1 s and a decrease of ≥4 points in Saint George's Respiratory Questionnaire score at 6 months.Sixteen procedures were performed on 15 patients, complicated by 1 intercostal haemorrhage, 1 pneumothorax, and universal mild surgical emphysema. Early patency issues were common, but often responded to external endoscopic debridement or argon plasma laser. Three-month patency was achieved in 9 of 15 patients, and 6 of these had long-term patency (mean of 4 years). Patency was associated with potentially useful long-term improvements or stability in spirometry, residual volume, and QoL. However, the primary endpoints were not met at 6 months.The creation and maintenance of a transthoracic pneumostoma appears feasible and safe in patients with severe emphysema. Further studies refining patient selection (perhaps via chest computed tomography collateral ventilation and fissure assessments), techniques, and tube materials are suggested.

lence, the susceptibility factors of the affected patient groups, the predictive clinical features and the impact of vaccinations and available pharmaceutical and supportive treatments have provided lessons for preparedness for pandemics in the future [7] . Against this backdrop, we are reminded that, at an individual level, the diagnosis of viral pneumonia with particular reference to the demonstration of viral pathogenicity is difficult. More specifically, in patients with a critical illness and severe respiratory failure not primarily suspected to be due to a virus, the challenges of recognizing viral etiology, diagnostic sampling, testing and treatment of viral pneumonitis remain complex. The herpesvirus family is a group of viruses (Herpesviridae) characterized by their ability to remain latent within tissues following initial infection and a tendency to reactivate at mucocutaneous sites [8] . The most common forms involved in the respiratory tract are herpes simplex virus (HSV) 1, cytomegalovirus (CMV), Epstein-Barr virus (EBV) and human herpes virus (HHV) 6 and 8. The prevalence of oropharyngeal HSV1 in healthy adults is 2–3% [9, 10] . This is similar to the prevalence in hospitalized non-intensive care unit (ICU) patients [11] . A reactivation of herpesviruses may occur due to local Acute viral respiratory infections are the most common illnesses experienced by people worldwide. Most notable amongst these are rhinoviruses, influenza (Flu A and B), adenoviruses, picornaviruses, respiratory syncytial virus, parainfluenza viruses 1–3, human metapneumovirus, human coronaviruses and the herpesviruses. Their reported frequency ranges from 0 to 7 per annum, and this diminishes with increasing age [1] . At least one such virus is isolated in up to 53% of patients attending an emergency department with acute respiratory tract infections [2] . Respiratory viruses are usually self-resolving in the immunocompetent host. In those who are immunocompromised as well as in a proportion of otherwise well individuals, however, they can pose potentially lifethreatening consequences. This situation is perhaps best epitomized by the influenza pandemic of 1918 that had a fatality rate of millions [3] . In recent years, the world has experienced equally fearful but less catastrophic pandemics; accurate population data from these have provided insights into risk factors, outcomes and confounding factors. The epidemics of severe acute respiratory syndrome (SARS), swine flu (H1N1) and the so-called Middle East respiratory syndrome have challenged populations and global healthcare systems over the last decade [4–6] . Fortunately, the careful retrospective analysis of their viruPublished online: February 28, 2014

However, perceptions from the NETT study influenced the design of subsequent randomised controlled trials with endobronchial valves [7, 8] . The inclusion and exclusion criteria were similar and the focus was on patients with heterogeneous emphysema. Furthermore, the same CT scoring method was employed. This system is based on visually estimating severity of emphysema in three zones (upper, middle and lower) and scoring them as: 0 (no destruction), 1 (1–25%), 2 (26–50%), 3 (51–75%) and 4 (76–100%). Heterogeneous emphysema was defined as a difference in scores of at least 2 among the three zones in one lung whereas a difference of zero or 1 was classified as homogeneous emphysema. The flaw with this method is that obvious heterogenous emphysema with 75% destruction in the upper lobe and 26% destruction in the lower lobe is scored as 3 and 2, respectively, and is hence classified as homogenous disease. Conversely, 76% destruction in the upper lobe and 50% destruction in the lower lobe are scored as 4 and 2, respectively, and with the difference in scores being 2, this is classified as heterogenous disease. Consequently, some patients may have been included who did not have the optimal emphysema phenotype. Interpreting the phenotypical composition of patients in these studies is also impossible. The consequence is that, although these trials met their end points COPD is currently the third leading cause of death globally [1] and has a prevalence of >5% in both Europe [2] and the USA [3] . It is the cause of physical impairment, incapacity and a reduced quality of life as well as extensive utilisation of healthcare resources. Reducing the volume of hyperinflated lungs is a logical approach to treatment, especially if this can be achieved by removing or shrinking the most diseased portions of the lung, thereby contributing to the least gas exchange. Lung volume reduction surgery, where the worst affected areas of emphysematous lungs are resected, improves survival and quality of life, but is associated with significant morbidity and a 5.5% mortality [4] . The message from the NETT (National Emphysema Treatment Trial) and a Cochrane collaboration analysis was that patients with homogenous emphysema have the greatest risk for mortality and morbidity [4, 5] . Thus, a view developed that only a minority of patients with emphysema, those with heterogeneous upper-lobe disease and a low exercise capacity benefitted, and then at a high financial cost. There has therefore been a push in the last decade to develop simpler, safer and cheaper methods of emulating the volume loss achieved by surgical resection. Unidirectional endobronchial valves were the first to be used in human trials and appeared promising [6] . Published online: July 2, 2014

Tracheobronchial amyloidosis is one of many causes of endobronchial stenosis and nodularity, the concrete diagnosis of which currently requires the finding of apple-green birefringence from endobronchial biopsies. Bronchoscopic probe-based confocal endomicroscopy (pCLE) is a novel optical biopsy technique which provides real-time images of the lattice structure of the bronchial basement membrane – a finding lost in malignancy. This case study outlines the imperfect, essentially palliative management of this rare disease, and shows for the first time the unusual dappled in vivo pCLE images of amyloid-affected endobronchium.