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Pieta C Wijsman,1,* Annika WM Goorsenberg,1,* Abilash Ravi,1,2,* Julia NS d’Hooghe,1 Barbara S Dierdorp,2 Tamara Dekker,2 Charlotte CLM van Schaik,1 Nick HT ten Hacken,3 Pallav L Shah,4– 6 Els JM Weersink,1 Elisabeth H Bel,1 Jouke T Annema,1 René Lutter,1,2 Peter I Bonta1 1Department of Pulmonary Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; 2Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; 3Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 4Department of Pulmonology, Royal Brompton Hospital, London, UK; 5National Heart & Lung Institute, Imperial College, London, UK; 6Department of Pulmonology, Chelsea & Westminster Hospital, London, UK*These authors contributed equally to this workCorrespondence: Peter I Bonta, Email p.i.bonta@amsterdamumc.nlBackground: Bronchial thermoplasty (BT) is a bronchoscopic treatment for severe asthma, of which the working mechanism and responder profile are partly unknown. The aim of this study is to analyse whether BT alters airway inflammation by epithelial gene expression, inflammatory cell counts and cytokines, and whether this relates to treatment response.Methods: In this clinical trial, 28 severe asthma patients underwent bronchoscopy before and after treatment to obtain bronchial brushes and bronchoalveolar lavage fluid (BALF) from treated and untreated airways. RNA was extracted from bronchial brushes for transcriptome analysis, and BALF cells and cytokines were analysed. Asthma quality of life questionnaires were used to distinguish responders from non-responders. We compared results before and after treatment, between treated and untreated airways, and between responders and non-responders.Results: Gene expression of airway epithelium related to airway inflammation gene set was significantly downregulated in treated airways compared to untreated airways, although this did not differ for patients before and after treatment. No differences were observed in cell counts and cytokines, neither from the untreated compared to treated airways, nor before and after treatment. At baseline, compared to non-responders, the expression of genes related to glycolysis in bronchial epithelium was downregulated and both BALF and blood eosinophil counts were higher in responders.Conclusion: Local differences in gene sets pertaining to epithelial inflammatory status were identified between treated and untreated airways after treatment, not resulting in changes in differential cell counts and cytokine analyses in BALF. Secondly, baseline epithelial glycolysis genes and eosinophil counts in BALF and blood were different between responders and non-responders. The observations from this study demonstrate the potential impact of BT on epithelial gene expression related to airway inflammation while also identifying a possible responder profile.Keywords: airway inflammation, bronchial thermoplasty, bronchoalveolar lavage fluid cells, cytokines, epithelial transcriptome

Olivier Taton,1 Vincent Heinen,2 Benjamin Bondue,1 Dirk-Jan Slebos,3,4 Pallav L Shah,5– 7 Kris Carron,8 Olivia Moens,9 Dimitri Leduc1 1Department of Pneumology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; 2Department of Pneumology, Centre Hospitalier Universitaire de Liège, Liège, Belgium; 3Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 4The Netherlands and GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; 5Royal Brompton Hospital, London, UK; 6National Heart & Lung Institute, Imperial College, London, UK; 7Chelsea and Westminster Hospital NHS Foundation Trust, London, UK; 8Department of Pneumology, AZ Delta, Menen, Belgium; 9Department of Radiology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, BelgiumCorrespondence: Olivier Taton, Department of Pneumology, Hôpital Erasme, Université Libre de Bruxelles, Route de Lennik, 808, Brussels, 1070, Belgium, Tel +3225553943, Email Olivier.taton@erasme.ulb.ac.beAbstract: Endoscopic lung volume reduction using unidirectional endobronchial valves is a new technique in the treatment of patients with severe emphysema. However, the movements of the thoracic structures after endobronchial valves insertion are still unpredictable We report the unusual outcome of six patients after valves insertion in the left upper lobe. They all developed a complete atelectasis of the target lobe, a pneumothorax and sequential genuine bullae in the treated left lung of unknown etiology. The chest CT scan prior to the valves insertion was unremarkable. Three patients developed an air–liquid level in the bullae the day before a bacterial infection of their left lower lobe. The three other patients had an uneventful spontaneous resolution of their bullae at long-term follow-up. Therefore, a conservative attitude should be followed in this particular setting.Keywords: endoscopic lung volume reduction, pneumothorax, chest CT scanner, chest tube drainage

Arschang Valipour,1 Pallav L Shah,2 Felix J Herth,3 Christophe Pison,4 Christian Schumann,5 Ralf-Harto Hübner,6 Peter I Bonta,7 Romain Kessler,8 Wolfgang Gesierich,9 Kaid Darwiche,10 Bernd Lamprecht,11 Thierry Perez,12 Dirk Skowasch,13 Gaetan Deslee,14 Armelle Marceau,15 Frank C Sciurba,16 Reinoud Gosens,17 Jorine E Hartman,18 Francesca Conway,2 Marina Duller,1 Martin Mayse,19 Holly S Norman,19 Dirk-Jan Slebos18 On behalf of the AIRFLOW-2 Trial Study Group1Department of Respiratory and Critical Care Medicine, Karl-Landsteiner-Institute for Lung Research and Pulmonary Oncology, Krankenhaus Nord-Klinik Floridsdorf, Vienna, Austria; 2Royal Brompton & Harefield NHS Trust, Chelsea & Westminster Hospital and Imperial College, London, UK; 3Thoraxklinik, Department of Pneumology and Critical Care Medicine and Translational Lung Research Center Heidelberg (TLRCH), University of Heidelberg, Heidelberg, Germany; 4CHU Grenoble Alpes, Service Hospitalier Universitaire Pneumologie Physiologie; Université Grenoble Alpes, Grenoble, France; 5Clinic of Pneumology, Thoracic Oncology, Sleep- and Respiratory Critical Care, Klinikverbund Allgaeu, Kempten and Immenstadt, Germany; 6Charité Universitätsmedizin Berlin, Medizinische Klinik m. Schw. Infektiologie und Pneumologie, Campus Virchow, Berlin, Germany; 7Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 8Service de Pneumologie, Nouvel Hôpital Civil, Université de Strasbourg, Strasbourg, France; 9Asklepios-Fachkliniken Munich-Gauting, Comprehensive Pneumology Center Munich, Gauting, Germany; 10Department of Pulmonary Medicine, Section of Interventional Pneumology, Ruhrlandklinik - University Hospital Essen, University of Duisburg-Essen, Essen, Germany; 11Department of Pulmonary Medicine, Kepler Universitatsklinikum GmbH, Linz, Austria; 12CHU de Lille – Hôpital Calmette, Lille, France; 13Department of Internal Medicine II - Cardiology/Pneumology, University of Bonn, Bonn, Germany; 14CHU de Reims, Hôpital Maison Blanche, Service de Pneumologie, Reims, France; 15Service de Pneumologie, Hôpital Universitaire Bichat, Paris, France; 16University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 17Department of Molecular Pharmacology, University of Groningen, Groningen, the Netherlands; 18Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; 19Nuvaira, Inc., Minneapolis, MN, USACorrespondence: Dirk-Jan SlebosDepartment of Pulmonary Diseases/Interventional Bronchoscopy AA11, University Medical Center Groningen, PO Box 30001, Groningen, the NetherlandsTel +31 503612357Fax +31503619320Email d.j.slebos@umcg.nlPurpose: COPD exacerbations are associated with worsening clinical outcomes and increased healthcare costs, despite use of optimal medical therapy. A novel bronchoscopic therapy, targeted lung denervation (TLD), which disrupts parasympathetic pulmonary innervation of the lung, has been developed to reduce clinical consequences of cholinergic hyperactivity and its impact on COPD exacerbations. The AIRFLOW-2 study assessed the durability of safety and efficacy of TLD additive to optimal drug therapy compared to sham bronchoscopy and optimal drug therapy alone in subjects with moderate-to-severe, symptomatic COPD two years post randomization.Patients and Methods: TLD was performed in COPD patients (FEV1 30– 60% predicted, CAT≥ 10 or mMRC≥ 2) in a 1:1 randomized, sham-controlled, double-blinded multicenter study (AIRFLOW-2) using a novel lung denervation system (Nuvaira, Inc., USA). Subjects remained blinded until their 12.5-month follow-up visit when control subjects were offered the opportunity to undergo TLD. A time-to-first-event analysis on moderate and severe and severe exacerbations of COPD was performed.Results: Eighty-two subjects (FEV1 41.6± 7.4% predicted, 50.0% male, age 63.7± 6.8 yrs, 24% with prior year respiratory hospitalization) were randomized. Time-to-first severe COPD exacerbation was significantly lengthened in the TLD arm (p=0.04, HR=0.38) at 2 years post-TLD therapy and trended towards similar attenuation for moderate and severe COPD exacerbations (p=0.18, HR=0.71). No significant changes in lung function or SGRQ-C were found 2 years post randomization between groups.Conclusion: In a randomized trial, TLD demonstrated a durable effect of significantly lower risk of severe AECOPD over 2 years. Further, lung function and quality of life remained stable following TLD.Clinical Trial Registration: NCT02058459.Keywords: COPD exacerbation, targeted lung denervation, bronchoscopy, COPD

Background: Evidence suggests that oxidative stress is a unifying feature underlying the toxic actions of particulate matter (PM). We have investigated whether individual plasma antioxidant concentrations (uric acid and vitamins C, A, and E) and 10 antioxidant genes modify the response to PM with respect to hospital admissions for chronic obstructive pulmonary disease (COPD) or asthma.Methods: Using a bidirectional, hospital-based, case-crossover study, 209 patients admitted for asthma or COPD to the Chelsea and Westminster Hospital (London), with 234 admissions, were recruited between May 2008 and July 2010. PM10 levels in the area of Kensington and Chelsea at the time of admission were compared with the levels 14 days before and 14 days after the event. Conditional logistic regression was used to estimate the effect of PM10 at several temporal lags, while controlling for confounders.Results: An increase in asthma/COPD admission rate was related to a 10 μg/m increase in PM10, with the highest effect noted 0-3 days before the exacerbation (for lag 0-3, odds ratio = 1.35 [95% confidence interval = 1.04-1.76]). Serum vitamin C modified the effect of PM10 on asthma/COPD exacerbations. A similar (although weaker) influence was observed for low levels of uric acid and vitamin E, whereas vitamin A showed no effect modification. GSTP1 (rs1695), SOD2 (rs4880), and Nrf2 (rs1806649) were associated with a trend toward an increased risk of hospital admissions during periods of high PM10 levels.Conclusions: Our study suggests that the concentration of antioxidants in patients' serum modifies the short-term effects of PM10 on asthma and COPD exacerbations. [ABSTRACT FROM AUTHOR]

Rationale: Bronchial thermoplasty (BT) is a bronchoscopic procedure in which controlled thermal energy is applied to the airway wall to decrease smooth muscle.Objectives: To evaluate the effectiveness and safety of BT versus a sham procedure in subjects with severe asthma who remain symptomatic despite treatment with high-dose inhaled corticosteroids and long-acting beta(2)-agonists.Methods: A total of 288 adult subjects (Intent-to-Treat [ITT]) randomized to BT or sham control underwent three bronchoscopy procedures. Primary outcome was the difference in Asthma Quality of Life Questionnaire (AQLQ) scores from baseline to average of 6, 9, and 12 months (integrated AQLQ). Adverse events and health care use were collected to assess safety. Statistical design and analysis of the primary endpoint was Bayesian. Target posterior probability of superiority (PPS) of BT over sham was 95%, except for the primary endpoint (96.4%).Measurements and Main Results: The improvement from baseline in the integrated AQLQ score was superior in the BT group compared with sham (BT, 1.35 +/- 1.10; sham, 1.16 +/- 1.23 [PPS, 96.0% ITT and 97.9% per protocol]). Seventy-nine percent of BT and 64% of sham subjects achieved changes in AQLQ of 0.5 or greater (PPS, 99.6%). Six percent more BT subjects were hospitalized in the treatment period (up to 6 wk after BT). In the posttreatment period (6-52 wk after BT), the BT group experienced fewer severe exacerbations, emergency department (ED) visits, and days missed from work/school compared with the sham group (PPS, 95.5, 99.9, and 99.3%, respectively).Conclusions: BT in subjects with severe asthma improves asthma-specific quality of life with a reduction in severe exacerbations and healthcare use in the posttreatment period. Clinical trial registered with www.clinialtrials.gov (NCT00231114). [ABSTRACT FROM AUTHOR]

Respiratory particles produced during vocalized and nonvocalized activities such as breathing, speaking, and singing serve as a major route for respiratory pathogen transmission. This work reports concomitant measurements of exhaled carbon dioxide volume (VCO 2 ) and minute ventilation (VE), along with exhaled respiratory particles during breathing, exercising, speaking, and singing. Exhaled CO 2 and VE measured across healthy adult participants follow a similar trend to particle number concentration during the nonvocalized exercise activities (breathing at rest, vigorous exercise, and very vigorous exercise). Exhaled CO 2 is strongly correlated with mean particle number ( r = 0.81) and mass ( r = 0.84) emission rates for the nonvocalized exercise activities. However, exhaled CO 2 is poorly correlated with mean particle number ( r = 0.34) and mass ( r = 0.12) emission rates during activities requiring vocalization. These results demonstrate that in most real-world environments vocalization loudness is the main factor controlling respiratory particle emission and exhaled CO 2 is a poor surrogate measure for estimating particle emission during vocalization. Although measurements of indoor CO 2 concentrations provide valuable information about room ventilation, such measurements are poor indicators of respiratory particle concentrations and may significantly underestimate respiratory particle concentrations and disease transmission risk.

Background and Objective: Bronchoscopic transbronchial lung cryobiopsy (TBLC) is a guideline-endorsed alternative to surgical lung biopsy for tissue diagnosis in unclassifiable interstitial lung disease (ILD). The reported incidence of post-procedural bleeding has varied widely. We aimed to characterize the incidence, severity and risk factors for clinically significant bleeding following TBLC using an expert-consensus airway bleeding scale, in addition to other complications and diagnostic yield., Methods: A retrospective cohort study of consecutive adult outpatients with unclassifiable ILD who underwent TBLC following multidisciplinary discussion at a single centre in the UK between July 2016 and December 2021. TBLC was performed under general anaesthesia with fluoroscopic guidance and a prophylactic endobronchial balloon., Results: One hundred twenty-six patients underwent TBLC (68.3% male; mean age 62.7 years; FVC 86.2%; DLCO 54.5%). Significant bleeding requiring balloon blocker reinflation for >20 min, admission to ICU, packed red blood cell transfusion, bronchial artery embolization, resuscitation or procedural abandonment, occurred in 10 cases (7.9%). Significant bleeding was associated with traction bronchiectasis on HRCT (OR 7.1, CI 1.1-59.1, p = 0.042), a TBLC histological pattern of UIP (OR 4.0, CI 1.1-14, p = 0.046) and the presence of medium-large vessels on histology (OR 37.3, CI 6.5-212, p < 0.001). BMI ≥30 (p = 0.017) and traction bronchiectasis on HRCT (p = 0.025) were significant multivariate predictors of longer total bleeding time (p = 0.017). Pneumothorax occurred in nine cases (7.1%) and the 30-day mortality was 0%. Diagnostic yield was 80.6%., Conclusion: TBLC has an acceptable safety profile in experienced hands. Radiological traction bronchiectasis and obesity increase the risk of significant bleeding following TBLC., (© 2024 Asian Pacific Society of Respirology.)

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., Competing Interests: Declaration of competing interest PS declares consulting fees and educational fees. AV declares educational fees. GJC declares grants/contract, consulting fees, educational fees and participation on a DSMB. FJFH declares educational and consulting fees. DKH declares consulting fees and educational fees. AM declares consulting fees and educational fees. AC declares consulting fees and educational fees. MD declares consulting fees and support for attending meetings by GSK. JK declares consulting fees and educational fees. NS is a full-time employee of Pulmonx Corporation and declares stock options. DJS declares grants/contracts, consulting fees, educational fees and support for attending meetings. MP declares grants, consulting fees, educational fees, support for attending meetings and leadership or fiduciary roles. Regarding the consensus opinion meeting: PS, FJFH, RS, DH, RM, AM, RA, LK, AC, JK, DJS, and MP received travel and accommodation support and honoraria from Pulmonx. AV received an honorarium from Pulmonx. DEW, MD, GJC and TDK have no conflict., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Excessive dynamic airway collapse (EDAC) is a recognized cause of exertional dyspnea arising due to invagination of the trachea and/or main bronchi. EDAC is typically assessed by evaluating large airway movement with forced expiratory maneuvers. This differs from the respiratory response to exercise hyperpnea. We aimed to evaluate large airway movement during physical activity, with continuous bronchoscopy during exercise (CBE), in healthy subjects and compare findings with resting bronchoscopic maneuvers and imaging techniques. Twenty-eight individuals were recruited to complete two visits including treadmill-based CBE, to voluntary exhaustion, and cine magnetic resonance imaging (MRI) with forced expiratory maneuvers at rest. Twenty-five subjects [aged 29 (26-33) yr, 52% female] completed the study ( n = 2 withdrew before bronchoscopy, and one was unable to tolerate insertion of bronchoscope). The majority (76%) achieved a peak heart rate of >90% predicted during CBE. The procedure was prematurely terminated in five subjects ( n = 3; elevated blood pressure and n = 2; minor oxygen desaturation). The CBE assessment enabled adequate tracheal visualization in all cases. Excessive dynamic airway collapse (tracheal collapse ≥50%) was identified in 16 subjects (64%) on MRI, and in six (24%) individuals during resting bronchoscopy, but in no cases with CBE. No serious adverse events were reported, but minor adverse events were evident. The CBE procedure permits visualization of large airway movement during physical activity. In healthy subjects, there was no evidence of EDAC during strenuous exercise, despite evidence during forced maneuvers on imaging, thus challenging conventional approaches to diagnosis. NEW & NOTEWORTHY This study demonstrates that large airway movement can be visualized with bronchoscopy undertaken during vigorous exercise. This approach does not require sedation and permits characterization of the behavior of the large airways and the tendency toward collapse during upright, ambulatory exercise. In healthy individuals, the response pattern of the large airways during exercise appears to differ markedly from the pattern of airway closure witnessed during forced expiratory maneuvers, assessed via imaging.

Introduction: Lung volume reduction surgery (LVRS) and endobronchial valve (EBV) placement can produce substantial benefits in appropriately selected people with emphysema. The UK Lung Volume Reduction (UKLVR) registry is a national multicentre observational study set up to support quality standards and assess outcomes from LVR procedures at specialist centres across the UK., Methods: Data were analysed for all patients undergoing an LVR procedure (LVRS/EBV) who were recruited into the study at participating centres between January 2017 and June 2022, including; disease severity and risk assessment, compliance with guidelines for selection, procedural complications and survival to February 2023., Results: Data on 541 patients from 14 participating centres were analysed. Baseline disease severity was similar in patients who had surgery n=244 (44.9%), or EBV placement n=219 (40.9%), for example, forced expiratory volume in 1 s (FEV 1) 32.1 (12.1)% vs 31.2 (11.6)%. 89% of cases had discussion at a multidisciplinary meeting recorded. Median (IQR) length of stay postprocedure for LVRS and EBVs was 12 (13) vs 4 (4) days(p=0.01). Increasing age, male gender and lower FEV 1 %predicted were associated with mortality risk, but survival did not differ between the two procedures, with 50 (10.8%) deaths during follow-up in the LVRS group vs 45 (9.7%) following EBVs (adjusted HR 1.10 (95% CI 0.72 to 1.67) p=0.661) CONCLUSION: Based on data entered in the UKLVR registry, LVRS and EBV procedures for emphysema are being performed in people with similar disease severity and long-term survival is similar in both groups., Competing Interests: Competing interests: SCB reports educational fees from PulmonX. CEB reports research grants from NIHR and Astra Zeneca and is a member on an advisory board for Roche. JWD declares he has received honoraria for participating in advisory boards and given lectures at meetings supported by GSK, Boerhinger Ingelheim, Chiesi, AstraZeneca, Fisher & Paykel, Aerogen; he has received sponsorship for attending international scientific meetings from Chiesi. TH reports speaker fees from Astra Zeneca. SVK reports consultancy work for PulmonX and is on the advisory board for Intuitive Surgical. PLS reports lecture fees from PulmonX., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Airway remodeling is a prominent feature of asthma, which involves increased airway smooth muscle mass and altered extracellular matrix composition. Bronchial thermoplasty (BT), a bronchoscopic treatment for severe asthma, targets airway remodeling., Objective: We sought to investigate the effect of BT on extracellular matrix composition and its association with clinical outcomes., Methods: This is a substudy of the TASMA trial. Thirty patients with severe asthma were BT-treated, of whom 13 patients were treated for 6 months with standard therapy (control group) before BT. Demographic data, clinical data including pulmonary function, and bronchial biopsies were collected. Biopsies at BT-treated and nontreated locations were analyzed by histological and immunohistochemical staining. Associations between histology and clinical outcomes were explored., Results: Six months after treatment, it was found that the reticular basement membrane thickness was reduced from 7.28 μm to 5.74 μm (21% relative reduction) and the percentage area of tissue positive for collagen increased from 26.3% to 29.8% (13% relative increase). Collagen structure analysis revealed a reduction in the curvature frequency of fibers. The percentage area positive for fibulin-1 and fibronectin increased by 2.5% and 5.9%, respectively (relative increase of 124% and 15%). No changes were found for elastin. The changes in collagen and fibulin-1 negatively associated with changes in FEV 1 reversibility., Conclusions: Besides reduction of airway smooth muscle mass, BT has an impact on reticular basement membrane thickness and the extracellular matrix arrangement characterized by an increase in tissue area occupied by collagen with a less dense fiber organization. Both collagen and fibulin-1 are negatively associated with the change in FEV 1 reversibility., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: JKQ has been supported by institutional research grants from the Industrial Strategy Challenge Fund, the Medical Research Council, Health Data Research, GSK, Boehringer Ingelheim, Asthma + Lung UK, and AstraZeneca, and has received personal fees for advisory board participation, consultancy, or speaking fees from GlaxoSmithKline, Evidera, Chiesi, AstraZeneca, and Insmed, unrelated to the topic of this Comment. PLS declares no competing interests.

The use and availability of diverse advanced X-ray based imaging and guidance systems in the field of interventional pulmonology are rapidly growing. This popularity links inextricably to an increase in ionizing radiation use. Knowing ionizing radiation is hazardous, knowledge and competent use of X-ray imaging and guidance systems are important. The globally implemented As Low As Reasonably Achievable (ALARA) principle demands careful attention to minimize radiation exposure while achieving the precise goals of the intervention and imaging therein. To allow careful and targeted weighing of risk against reward while using X-ray based equipment, proper background knowledge of physics as well as imaging system aspects are needed. This white paper summarizes the principles of ionizing radiation which are crucial to enhance awareness and interpretation of dosimetric quantities. Consecutively, a consensus on standards for reporting radiation exposure in interventional pulmonology procedures is indicated to facilitate comparisons between different systems, approaches and results. Last but not least, it provides a list of practical measures, considerations and tips to optimize procedural imaging as well as reduce radiation dose to patients and staff., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

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., (© 2024 S. Karger AG, Basel.)

Purpose of Review: Chronic bronchitis is a phenotype of chronic obstructive pulmonary disease (COPD), characterized by chronic cough and sputum production, associated with an increased rate of COPD exacerbations and hospital admissions, a more rapid decline in lung function and reduced life expectancy. Despite optimal medical therapy, chronic bronchitis remains difficult to treat. Interventional bronchoscopic procedures offer novel therapeutic approaches to this highly symptomatic condition., Recent Findings: A characteristic feature of chronic bronchitis is the presence of an abnormal epithelium with excessive mucus producing cells, parasympathetic overactivity, and airway inflammation. Metered cryospray and bronchial rheoplasty are designed to target this abnormal epithelium to reduce mucus production and inflammation. Targeted lung denervation aims to reduce parasympathetic overactivity, which may drive mucus hypersecretion. Here, we review the available evidence to determine the safety and efficacy across the bronchoscopic interventions., Summary: Interventional bronchoscopy is a rapidly expanding field and its application in the treatment of chronic bronchitis has been recognized by the Global initiative for chronic Obstructive Lung Disease (GOLD). The outcomes from the latest clinical trials will guide future treatment approaches in patients with difficult to treat chronic bronchitis., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Clinical trials show different effects of remdesivir on clinical outcomes relative to COVID-19 severity at hospital admission; in Europe, there are few real-world data., Methods: A multicentre, multinational retrospective cohort study in adult patients hospitalised with PCR-confirmed COVID-19 was conducted to understand remdesivir clinical use in different countries and to describe outcomes for patients receiving remdesivir stratified by oxygen use. Primary endpoints were all-cause mortality at day 28 and hospitalisation duration. Patients were categorised by baseline disease severity: no supplemental oxygen (NSO); low flow oxygen ≤ 6 litres (l)/minute (LFO); high flow oxygen > 6 l/minute (HFO)., Results: Four hundred and forty-eight (448) patients (72 [16.1%] HFO; 295 [65.8%] LFO; 81 (18.1%] NSO) were included; median age was 65 years and 64% were male. Mortality was higher in patients on HFO (rate 23.6%) compared to LFO (10.2%; p = 0.001) or NSO (6.2%; p = 0.002). Duration of hospitalisation was longer in patients on HFO (13 days) compared to LFO (9 days; p = 0.003) and NSO (9 days; p = 0.021). Patients who initiated remdesivir ≥ 2 days compared to within a day of hospitalisation had a 4.2 times higher risk of death, irrespective of age, sex, comorbidities, and oxygen support at baseline. Requirement for mechanical ventilation/ECMO and readmission within 28 days of discharge was similar across groups. Remdesivir use and outcomes differed by country., Conclusions: A higher mortality rate and duration of hospitalisation was seen in remdesivir-treated COVID-19 patients on HFO compared to LFO and NSO. Initiation of remdesivir upon admission as opposed to delayed initiation has a mortality benefit., Clinical Trials Registration: NCT04847622., Competing Interests: Declaration of Competing Interest EM, RH, and PH are employees of Gilead Sciences Inc and own stock/stock options. CR received grants from ViiV, Gilead Sciences, Aidsfonds, Dutch Federation Medical Specialist, Erasmus MC, ZonMW, Health∼Holland. AC has received grants/research support, and honoraria or consultation fees from Gilead Sciences, Janssen, MSD, and ViiV. LM has received consultation fees from Gilead Sciences, Angelini and MSD. AS has received honoraria for lectures and advisory boards from Pfizer, MSD, Menarini, Shionogi, Angelini, Roche, and Gilead Sciences. AS has also received a grant from Pfizer and Gilead Sciences., (Copyright © 2023. Published by Elsevier Masson SAS.)

Introduction: Phonation and speech are known sources of respirable aerosol in humans. Voice assessment and treatment manipulate all the subsystems of voice production, and previous work (Saccente-Kennedy et al., 2022) has demonstrated such activities can generate >10 times more aerosol than conversational speech and 30 times more aerosol than breathing. Aspects of voice therapy may therefore be considered aerosol generating procedures and pose a greater risk of potential airborne pathogen (eg, SARS-CoV-2) transmission than typical speech. Effective mitigation measures may be required to ensure safe service delivery for therapist and patient., Objective: To assess the effectiveness of mitigation measures in reducing detectable respirable aerosol produced by voice assessment/therapy., Methods: We recruited 15 healthy participants (8 cis-males, 7 cis-females), 9 of whom were voice-specialist speech-language pathologists. Optical Particle Sizers (OPS) (Model 3330, TSI) were used to measure the number concentration of respirable aerosol particles (0.3 µm-10 µm) generated during a selection of voice assessment/therapy tasks, both with and without mitigation measures in place. Measurements were performed in a laminar flow operating theatre, with near-zero background aerosol concentration, allowing us to quantify the number concentration of respiratory aerosol particles produced. Mitigation measures included the wearing of Type IIR fluid resistant surgical masks, wrapping the same masks around the end of straws, and the use of heat and moisture exchange microbiological filters (HMEFs) for a water resistance therapy (WRT) task., Results: All unmitigated therapy tasks produced more aerosol than unmasked breathing or speaking. Mitigation strategies reduced detectable aerosol from all tasks to a level significantly below, or no different to, that of unmasked breathing. Pooled filtration efficiencies determined that Type IIR surgical masks reduced detectable aerosol by 90%. Surgical masks wrapped around straws reduced detectable aerosol by 96%. HMEF filters were 100% effective in mitigating the aerosol from WRT, the exercise that generated more aerosol than any other task in the unmitigated condition., Conclusions: Voice therapy and assessment causes the release of significant quantities of respirable aerosol. However, simple mitigation strategies can reduce emitted aerosol concentrations to levels comparable to unmasked breathing., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: COVID-19 has overwhelmed health services globally. Oral antiviral therapies are licensed worldwide, but indications and efficacy rates vary. We aimed to evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19., Methods: We conducted a multicentre, open-label, randomised controlled trial of oral favipiravir in adult patients who were newly admitted to hospital with proven or suspected COVID-19 across five sites in the UK (n=2), Brazil (n=2) and Mexico (n=1). Using a permuted block design, eligible and consenting participants were randomly assigned (1:1) to receive oral favipiravir (1800 mg twice daily for 1 day; 800 mg twice daily for 9 days) plus standard care, or standard care alone. All caregivers and patients were aware of allocation and those analysing data were aware of the treatment groups. The prespecified primary outcome was the time from randomisation to recovery, censored at 28 days, which was assessed using an intention-to-treat approach. Post-hoc analyses were used to assess the efficacy of favipiravir in patients aged younger than 60 years, and in patients aged 60 years and older. The trial was registered with clinicaltrials.gov, NCT04373733., Findings: Between May 5, 2020 and May 26, 2021, we assessed 503 patients for eligibility, of whom 499 were randomly assigned to favipiravir and standard care (n=251) or standard care alone (n=248). There was no significant difference between those who received favipiravir and standard care, relative to those who received standard care alone in time to recovery in the overall study population (hazard ratio [HR] 1·06 [95% CI 0·89-1·27]; n=499; p=0·52). Post-hoc analyses showed a faster rate of recovery in patients younger than 60 years who received favipiravir and standard care versus those who had standard care alone (HR 1·35 [1·06-1·72]; n=247; p=0·01). 36 serious adverse events were observed in 27 (11%) of 251 patients administered favipiravir and standard care, and 33 events were observed in 27 (11%) of 248 patients receiving standard care alone, with infectious, respiratory, and cardiovascular events being the most numerous. There was no significant between-group difference in serious adverse events per patient (p=0·87)., Interpretation: Favipiravir does not improve clinical outcomes in all patients admitted to hospital with COVID-19, however, patients younger than 60 years might have a beneficial clinical response. The indiscriminate use of favipiravir globally should be cautioned, and further high-quality studies of antiviral agents, and their potential treatment combinations, are warranted in COVID-19., Funding: LifeArc and CW+., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (BLVR) with endobronchial valves can improve outcomes in appropriately selected patients with emphysema. However, no direct comparison data exist to inform clinical decision making in people who appear suitable for both procedures. Our aim was to investigate whether LVRS produces superior health outcomes when compared with BLVR at 12 months., Methods: This multicentre, single-blind, parallel-group trial randomised patients from five UK hospitals, who were suitable for a targeted lung volume reduction procedure, to either LVRS or BLVR and compared outcomes at 1 year using the i-BODE score. This composite disease severity measure includes body mass index, airflow obstruction, dyspnoea and exercise capacity (incremental shuttle walk test). The researchers responsible for collecting outcomes were masked to treatment allocation. All outcomes were assessed in the intention-to-treat population., Results: 88 participants (48% female, mean±sd age 64.6±7.7 years, forced expiratory volume in 1 s percent predicted 31.0±7.9%) were recruited at five specialist centres across the UK and randomised to either LVRS (n=41) or BLVR (n=47). At 12 months follow-up, the complete i-BODE was available in 49 participants (21 LVRS/28 BLVR). Neither improvement in the i-BODE score (LVRS -1.10±1.44 versus BLVR -0.82±1.61; p=0.54) nor in its individual components differed between groups. Both treatments produced similar improvements in gas trapping (residual volume percent predicted: LVRS -36.1% (95% CI -54.6- -10%) versus BLVR -30.1% (95% CI -53.7- -9%); p=0.81). There was one death in each treatment arm., Conclusion: Our findings do not support the hypothesis that LVRS is a substantially superior treatment to BLVR in individuals who are suitable for both treatments., Competing Interests: Conflict of interest: D. Waller reports lecture honoraria from PulmonX Ltd, outside the submitted work. N.J. Greening reports grants from GSK, consulting fees from Genentech, lecture honoraria from AstraZeneca and Chiesi, travel support from Chiesi, outside the submitted work. P.L. Shah reports lecture honoraria from PulmonX Ltd, outside the submitted work. R. Bilancia reports lecture honoraria and travel support from Intuitive, outside the submitted work. R. Lawson is a Member of British Thoracic Society COPD Specialist Advisory group, a Member of South Yorkshire Clinical Senate, and a Member of South Yorkshire and Bassetlaw Respiratory Clinical Network, outside the submitted work. All other authors have nothing to disclose., (Copyright ©The authors 2023.)

Purpose: To assess if dual-energy computed tomographic pulmonary angiography (DECTPA) derived lobar iodine quantification can provide an accurate estimate of lobar perfusion in patients with severe emphysema, and offer an adjunct to single-photon emission CT perfusion scintigraphy (SPECT-PS) in assessing suitability for lung volume reduction (LVR)., Materials and Methods: Patients with severe emphysema (forced expiratory volume in 1 s <49% predicted) undergoing evaluation for LVR between May 2018 and April 2020 imaged with both SPECT-PS and DECTPA were included in this retrospective study. DECTPA perfused blood volume maps were automatically segmented and lobar iodine mass was estimated and compared with lobar technetium (Tc99m) distribution acquired with SPECT-PS. Pearson correlation and Bland-Altman analysis were used for intermodality comparison between DECTPA and SPECT-PS. Univariate and adjusted multivariate linear regression were modelled to ascertain the effect sizes of possible confounders of disease severity, sex, age, and body mass index on the relationship between lobar iodine and Tc99m values. Effective radiation dose and adverse reactions were recorded., Results: In all, 123 patients (64.5±8.8 y, 71 men; mean predicted forced expiratory volume in 1 s 32.1 ±12.7%,) were eligible for inclusion. There was a linear relationship between lobar perfusion values acquired using DECTPA and SPECT-PS with statistical significance ( P <0.001). Lobar relative perfusion values acquired using DECTPA and SPECT-PS had a consistent relationship both by linear regression and Bland-Altman analysis (mean bias, -0.01, mean r2 0.64; P <0.0001). Individual lobar comparisons demonstrated moderate correlation ( r =0.79, 0.78, 0.84, 0.78, 0.8 for the right upper, middle, lower, left upper, and lower lobes, respectively, P <0.0001). The relationship between lobar iodine and Tc99m values was not significantly altered after controlling for confounders including symptom and disease severity, age, sex, and body mass index., Conclusions: DECTPA provides an accurate estimation of lobar perfusion, showing good agreement with SPECT-PS and could potentially streamline preoperative assessment for LVR., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Voice assessment and treatment involve the manipulation of all the subsystems of voice production, and may lead to production of respirable aerosol particles that pose a greater risk of potential viral transmission via inhalation of respirable pathogens (eg, SARS-CoV-2) than quiet breathing or conversational speech., Objective: To characterise the production of respirable aerosol particles during a selection of voice assessment therapy tasks., Methods: We recruited 23 healthy adult participants (12 males, 11 females), 11 of whom were speech-language pathologists specialising in voice disorders. We used an aerodynamic and an optical particle sizer to measure the number concentration and particle size distributions of respirable aerosols generated during a variety of voice assessment and therapy tasks. The measurements were carried out in a laminar flow operating theatre, with a near-zero background aerosol concentration, allowing us to quantify the number concentration and size distributions of respirable aerosol particles produced from assessment/therapy tasks studied., Results: Aerosol number concentrations generated while performing assessment/therapy tasks were log-normally distributed among individuals with no significant differences between professionals (speech-language pathologists) and non-professionals or between males and females. Activities produced up to 32 times the aerosol number concentration of breathing and 24 times that of speech at 70-80 dBA. In terms of aerosol mass, activities produced up to 163 times the mass concentration of breathing and up to 36 times the mass concentration of speech. Voicing was a significant factor in aerosol production; aerosol number/mass concentrations generated during the voiced activities were 1.1-5 times higher than their unvoiced counterpart activities. Additionally, voiced activities produced bigger respirable aerosol particles than their unvoiced variants except the trills. Humming generated higher aerosol concentrations than sustained /a/, fricatives, speaking (70-80 dBA), and breathing. Oscillatory semi-occluded vocal tract exercises (SOVTEs) generated higher aerosol number/mass concentrations than the activities without oscillation. Water resistance therapy (WRT) generated the most aerosol of all activities, ∼10 times higher than speaking at 70-80 dBA and >30 times higher than breathing., Conclusions: All activities generated more aerosol than breathing, although a sizeable minority were no different to speaking. Larger number concentrations and larger particle sizes appear to be generated by activities with higher suspected airflows, with the greatest involving intraoral pressure oscillation and/or an oscillating oral articulation (WRT or trilling)., Competing Interests: Competing interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Chest drain displacement is a common clinical problem that occurs in 9-42% of cases and results in treatment failure or additional pleural procedures conferring unnecessary risk. A novel chest drain with an integrated intrapleural balloon may reduce the risk of displacement., Methods: A prospective randomised controlled trial comparing the balloon drain to standard care (12 F chest drain with no balloon) with the primary outcome of objectively defined unintentional or accidental chest drain displacement., Results: 267 patients were randomised (primary outcome data available in 257, 96.2%). Displacement occurred less frequently using the balloon drain (displacement 5 of 128, 3.9%; standard care displacement 13 of 129, 10.1%) but this was not statistically significant (OR for drain displacement 0.36, 95% CI 0.13-1.0, Chi-squared 1 degree of freedom (df)=2.87, p=0.09). Adjusted analysis to account for minimisation factors and use of drain sutures demonstrated balloon drains were independently associated with reduced drain fall-out rate (adjusted OR 0.27, 95% CI 0.08-0.87, p=0.028). Adverse events were higher in the balloon arm than the standard care arm (balloon drain 59 of 131, 45.0%; standard care 18 of 132, 13.6%; Chi-squared 1 df=31.3, p<0.0001)., Conclusion: Balloon drains reduce displacement compared with standard drains independent of the use of sutures but are associated with increased adverse events specifically during drain removal. The potential benefits of the novel drain should be weighed against the risks, but may be considered in practices where sutures are not routinely used., Competing Interests: Conflict of interest: N.M. Rahman receives consultancy fees from Rocket Medical UK. None of the other authors report any conflict of interests relevant to the production of this article. Rocket Medical UK provided funding to conduct the study, and clinical materials to conduct the study, but had no role in design, conduct, analysis or publication of the manuscript. R.M. Mercer received funding from the Royal Brompton and Harefield Charitable Trust. All other authors disclose no potential conflicts of interest., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Chronic obstructive pulmonary disease (COPD) remains one of the most common causes of morbidity and mortality in South Africa. Endoscopic lung volume reduction (ELVR) was first proposed by the South African Thoracic Society (SATS) for the treatment of advanced emphysema in 2015. Since the original statement was published, there has been a growing body of evidence that a certain well-defined sub-group of patients with advanced emphysema may benefit from ELVR, to the point where the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines and the United Kingdom National Institute for Health and Care Excellence (NICE) advocate the use of endoscopic valves based on level A evidence. Patients aged 40 - 75 years with severe dyspnoea (COPD Assessment Test score ≥10) despite maximal medical therapy and pulmonary rehabilitation, with forced expiratory volume in one second (FEV 1 ) 20 - 50%, hyperinflation with residual volume (RV) >175% or RV/total lung capacity (TLC) >55% and a six-minute walking distance (6MWD) of 100 - 450 m (post-rehabilitation) should be referred for evaluation for ELVR, provided no contraindications (e.g. severe pulmonary hypertension) are present. Further evaluation should focus on the extent of parenchymal tissue destruction on high-resolution computed tomography (HRCT) of the lungs and interlobar collateral ventilation (CV) to identify a potential target lobe. Commercially available radiology software packages and/or an endobronchial catheter system can aid in this assessment. The aim of this statement is to provide the South African medical practitioner and healthcare funders with an overview of the practical aspects and current evidence for the judicious use of the valves and other ELVR modalities which may become available in the country., Competing Interests: Conflicts of interest: FJFH, D-JS and PLS have treated patients in clinical trials, sponsored by PneumRx/BTG (USA), Pulmonx (Switzerland) and Spiration (USA). The rest of the authors have nothing to declare.

Background Data on the long-term pulmonary sequelae in COVID-19 are lacking. Purpose To assess symptoms, functional impairment, and residual pulmonary abnormalities on serial chest CT scans in COVID-19 survivors discharged from hospital at up to 1-year follow-up. Materials and Methods Adult patients with COVID-19 discharged between March 2020 and June 2020 were prospectively evaluated at 3 months and 1 year through systematic assessment of symptoms, functional impairment, and thoracic CT scans as part of the PHENOTYPE study, an observational cohort study in COVID-19 survivors. Lung function testing was limited to participants with CT abnormalities and/or persistent breathlessness. Bonferroni correction was used. Results Eighty participants (mean age, 59 years ± 13 [SD]; 53 men) were assessed. At outpatient review, persistent breathlessness was reported in 37 of the 80 participants (46%) and cough was reported in 17 (21%). CT scans in 73 participants after discharge (median, 105 days; IQR, 95-141 days) revealed persistent abnormalities in 41 participants (56%), with ground-glass opacification (35 of 73 participants [48%]) and bands (27 of 73 participants [37%]) predominating. Unequivocal signs indicative of established fibrosis (ie, volume loss and/or traction bronchiectasis) were present in nine of 73 participants (12%). Higher admission serum C-reactive protein (in milligrams per liter), fibrinogen (in grams per deciliter), urea (millimoles per liter), and creatinine (micromoles per liter) levels; longer hospital stay (in days); older age (in years); and requirement for invasive ventilation were associated with CT abnormalities at 3-month follow-up. Thirty-two of 41 participants (78%) with abnormal findings at 3-month follow-up CT underwent repeat imaging at a median of 364 days (range, 360-366 days), with 26 (81%) showing further radiologic improvement (median, 18%; IQR, 10%-40%). Conclusion CT abnormalities were common at 3 months after COVID-19 but with signs of fibrosis in a minority. More severe acute disease was linked with CT abnormalities at 3 months. However, radiologic improvement was seen in the majority at 1-year follow-up. ClinicalTrials.gov identifier: NCT04459351. © RSNA, 2022 Online supplemental material is available for this article.