Search

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.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.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).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.LifeArc and CW+.

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

This post-hoc analysis of the AIRFLOW-2 trial investigated the changes in airway CT-parameters after targeted lung denervation (TLD) and whether these changes are associated with treatment response. In the treatment group (n = 32), an improvement in air trapping was significantly associated with an improvement in residual volume (RV). Furthermore, improvements in Pi10 and airway lumen were significantly associated with an improvement in both RV and FEV1. Our results could suggest that when improving airway characteristics like decreasing airway wall thickness and increasing the airway lumen, this leads to less air trapping and an improvement in clinical outcomes.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has brought renewed attention to respiratory aerosol and droplet generation. While many studies have robustly quantified aerosol (20 µm diameter) generated by a cohort of 76 adults and children using a water-sensitive paper droplet deposition approach. Unvoiced and voiced activities spanning different levels of loudness, different lengths of sustained phonation, and a specific manner of articulation in isolation were investigated. We find that oral articulation drives >20 µm droplet generation, with breathing generating virtually no droplets and speaking and singing generating on the order of 250 droplets min−1. Lip trilling, which requires extensive oral articulation, generated the most droplets, whereas shouting “Hey,” which requires minimal oral articulation, generated relatively few droplets. Droplet size distributions were all broadly consistent, and no significant differences between the children and adult cohorts were identified. By comparing the aerosol and droplet emissions for the same participants, the full size distribution of respiratory aerosol (0.5–1000 µm) is reported. Although 20 µm droplets dominate the mass concentration. Accurate quantification of aerosol concentrations in the 10–70 μm size range remains very challenging; more robust aerosol analysis approaches are needed to characterize this size range.

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: Asthma is a heterogeneous disease with differences in onset, severity, and inflammation. Bronchial epithelial cells (BECs) contribute to asthma pathophysiology.Objective: We determined whether transcriptomes of BECs reflect heterogeneity in inflammation and severity in asthma, and whether this was affected in BECs from patients with severe asthma after their regeneration by bronchial thermoplasty.Methods: RNA sequencing was performed on BECs obtained by bronchoscopy from healthy controls (n = 16), patients with mild asthma (n = 17), patients with moderate asthma (n = 5), and patients with severe asthma (n = 17), as well as on BECs from treated and untreated airways of the latter (also 6 months after bronchial thermoplasty) (n = 23). Lipidome and metabolome analyses were performed on cultured BECs from healthy controls (n = 7); patients with severe asthma (n = 9); and, for comparison, patients with chronic obstructive pulmonary disease (n = 7).Results: Transcriptome analysis of BECs from patients showed a reduced expression of oxidative phosphorylation (OXPHOS) genes, most profoundly in patients with severe asthma but less profoundly and more heterogeneously in patients with mild asthma. Genes related to fatty acid metabolism were significantly upregulated in asthma. Lipidomics revealed enhanced levels of lipid species (phosphatidylcholines, lysophosphatidylcholines. and bis(monoacylglycerol)phosphate), whereas levels of OXPHOS metabolites were reduced in BECs from patients with severe asthma. BECs from patients with mild asthma characterized by hyperresponsive production of mediators implicated in neutrophilic inflammation had decreased expression of OXPHOS genes compared with that in BECs from patients with mild asthma with normoresponsive production. BECs obtained after thermoplasty had significantly increased expression of OXPHOS genes and decreased expression of fatty acid metabolism genes compared with BECs obtained from untreated airways.Conclusion: BECs in patients with asthma are metabolically different from those in healthy individuals. These differences are linked with inflammation and asthma severity, and they can be reversed by bronchial thermoplasty.

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

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.

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

Methods BT10+ was an international, multicentre, follow-up study of participants who were previously enrolled in the AIR, RISA, and AIR2 trials and who had 10 or more years of follow-up since bronchial thermoplasty treatment. Data on patient demographics, quality of life, lung function, CT scans (AIR2 participants only), severe exacerbations, and health-care use during the previous year were collected at the BT10+ 10-year outcomes study visit. The primary effectiveness endpoint was durability of the thermoplasty treatment effect, determined by comparing the proportion of participants who had severe exacerbations during the first and fifth years after bronchial thermoplasty treatment with the proportion of participants who had severe exacerbations during the 12-month period before the BT10+ visit. The primary safety endpoint was the absence of clinically significant post-treatment respiratory image changes after bronchial thermoplasty, defined as bronchiectasis or bronchial stenosis as confirmed by pulmonary volumetric highresolution CT scan at the BT10+ visit (AIR2 participants only). All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT03243292. The last patient was enrolled on Dec 11, 2018. The last patient completed follow-up on Jan 10, 2019.Findings The BT10+ study enrolled 192 (45%) of the 429 participants who were enrolled in the AIR, RISA, and AIR2 trials. The BT10+ participants comprised 136 who received bronchial thermoplasty (52% of the 260 participants who received bronchial thermoplasty in the original trials), and 56 sham or control participants (33% of 169 from the original trials). 18 (32%) sham or control participants received bronchial thermoplasty after the previous trials concluded. The participants included in BT10+ were followed for 10?8?15?6 years (median 12?1 years) post-treatment. Baseline characteristics were similar between participants enrolled in BT10+ and those not enrolled. Participants treated with bronchial thermoplasty had similar proportions of severe exacerbations at the BT10+ visit (34 [25%] of 136 participants) compared with 1 year (33 [24%] of 135 participants; difference 0?6%, 95% CI ?9?7 to 10?8) and 5 years (28 [22%] of 130 participants; difference 3?5%, ?6?7% to 13?6) after treatment. Quality of life measurements and spirometry were similar between year 1, year 5, and the BT10+ visit. At the BT10+ study visit, pulmonary high-resolution CT scans from AIR2 participants treated with bronchial thermoplasty showed that 13 (13%) of 97 participants had bronchiectasis. When compared with baseline high-resolution CT scans, six (7%) of 89 participants treated with bronchial thermoplasty who did not have bronchiectasis at baseline had developed bronchiectasis after treatment (5 classified as mild, 1 classified as moderate). Participants treated with bronchial thermoplasty after the original study and participants in the sham or control group also had reductions in severe exacerbations at the BT10+ visit compared with baseline.Summary Background Bronchial thermoplasty is an endoscopic treatment for uncontrolled asthma. Previous randomised clinical trials have shown that bronchial thermoplasty reduces severe exacerbations in people with asthma. However, the long-term efficacy and safety of bronchial thermoplasty beyond 5 years is unknown. The BT10+ study aimed to investigate the efficacy and safety of bronchial thermoplasty after 10 or more years of follow-up. Methods BT10+ was an international, multicentre, follow-up study of participants who were previously enrolled in the AIR, RISA, and AIR2 trials and who had 10 or more years of follow-up since bronchial thermoplasty treatment. Data on patient demographics, quality of life, lung function, CT scans (AIR2 participants only), severe exacerbations, and health-care use during the previous year were collected at the BT10+ 10-year outcomes study visit. The primary effectiveness endpoint was durability of the thermoplasty treatment effect, determined by comparing the proportion of participants who had severe exacerbations during the first and fifth years after bronchial thermoplasty treatment with the proportion of participants who had severe exacerbations during the 12-month period before the BT10+ visit. The primary safety endpoint was the absence of clinically significant post-treatment respiratory image changes after bronchial thermoplasty, defined as bronchiectasis or bronchial stenosis as confirmed by pulmonary volumetric high resolution CT scan at the BT10+ visit (AIR2 participants only). All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT03243292. The last patient was enrolled on Dec 11, 2018. The last patient completed follow-up on Jan 10, 2019. Findings The BT10+ study enrolled 192 (45%) of the 429 participants who were enrolled in the AIR, RISA, and AIR2 trials. The BT10+ participants comprised 136 who received bronchial thermoplasty (52% of the 260 participants who received bronchial thermoplasty in the original trials), and 56 sham or control participants (33% of 169 from the original trials). 18 (32%) sham or control participants received bronchial thermoplasty after the previous trials concluded. The participants included in BT10+ were followed for 10middot8-15middot6 years (median 12middot1 years) post-treatment. Baseline characteristics were similar between participants enrolled in BT10+ and those not enrolled. Participants treated with bronchial thermoplasty had similar proportions of severe exacerbations at the BT10+ visit (34 [25%] of 136 participants) compared with 1 year (33 [24%] of 135 participants; difference 0middot6%, 95% CI -9middot7 to 10middot8) and 5 years (28 [22%] of 130 participants; difference 3middot5%, -6middot7% to 13middot6) after treatment. Quality of life measurements and spirometry were similar between year 1, year 5, and the BT10+ visit. At the BT10+ study visit, pulmonary high-resolution CT scans from AIR2 participants treated with bronchial thermoplasty showed that 13 (13%) of 97 participants had bronchiectasis. When compared with baseline high-resolution CT scans, six (7%) of 89 participants treated with bronchial thermoplasty who did not have bronchiectasis at baseline had developed bronchiectasis after treatment (5 classified as mild, 1 classified as moderate). Participants treated with bronchial thermoplasty after the original study and participants in the sham or control group also had reductions in severe exacerbations at the BT10+ visit compared with baseline.Interpretation Our findings suggest that efficacy of bronchial thermoplasty is sustained for 10 years or more, with an acceptable safety profile. Therefore, bronchial thermoplasty is a long-acting therapeutic option for patients with asthma that remains uncontrolled despite optimised medical treatment. Funding Boston Scientific. Copyright (c) 2021 Elsevier Ltd. All rights reserved.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a worldwide pandemic. People with airways disease are at higher risk of respiratory infection, and viruses can trigger respiratory exacerbations. Patients with airways disease may therefore be more susceptible to SARS-CoV-2 infection, development of covid-19, or be at higher risk of adverse outcomes. Here we review susceptibility, based on current epidemiological studies, and explore biological mechanisms. Evidence from multiple large observational studies has shown chronic obstructive pulmonary disease (COPD) is a significant risk factor for covid-19 related mortality. Whether people with asthma are more susceptible to infection or severe outcomes has been much debated but appears to be related to their asthma phenotype and severity. To what extent these differences are biological or influenced by public health non-pharmacological interventions is difficult to quantify. Biological mechanisms that may influence susceptibility and adverse outcomes in airways disease include the increased expression of protein receptors enabling viral cell entry, dysfunctional epithelial airway immunity, type-2 inflammation and the use of inhaled corticosteroids. A better understanding of the susceptibility and mechanisms is essential for developing preventative and therapeutic strategies. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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 (e.g. 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.MethodsWe 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 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. ResultsAerosol 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 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 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.ConclusionsAll 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).

Following publication of the original article [1], we were notified that the first and last author names have been swapped. The original article has been corrected., SCOPUS: er.j, info:eu-repo/semantics/published

Rationale: Bronchial thermoplasty (BT) is a bronchoscopic treatment for severe asthma targeting airway smooth muscle (ASM). Observational studies have shown ASM mass reduction after BT, but appropriate control groups are lacking. Furthermore, as treatment response is variable, identifying optimal candidates for BT treatment is important. Objectives: First, to assess the effect of BT on ASM mass, and second, to identify patient characteristics that correlate with BT response. Methods: Patients with severe asthma (n = 40) were randomized to immediate (n = 20) or delayed (n = 20) BT treatment. Before randomization, clinical, functional, blood, and airway biopsy data were collected. In the delayed control group, reassessment, including biopsies, was performed after 6 months of standard clinical care, followed by BT. In both groups, post-BT data including biopsies were obtained after 6 months. ASM mass (% positive desmin or a-smooth muscle actin area in the total biopsy) was calculated with automated digital analysis software. Associations between baseline characteristics and Asthma Control Questionnaire and Asthma Quality of Life Questionnaire (AQLQ) improvement were explored. Measurements and Main Results: Median ASM mass decreased by .50% in the immediate BT group (n = 17) versus no change in the delayed control group (n = 19) (P = 0.0004). In the immediate group, Asthma Control Questionnaire scores improved with 20.79 (interquartile range [IQR], 21.61 to 0.02) compared with 0.09 (IQR, 20.25 to 1.17) in the delayed group (P = 0.006). AQLQ scores improved with 0.83 (IQR, 20.15 to 1.69) versus 20.02 (IQR, 20.77 to 0.75) (P = 0.04). Treatment response in the total group (n = 35) was positively associated with serum IgE and eosinophils but not with baseline ASM mass. Conclusions: ASM mass significantly decreases after BT when compared with a randomized non–BT-treated control group. Treatment response was associated with serum IgE and eosinophil levels but not with ASM mass.

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.

Treatment options for severe asthma are limited, particularly in those patients who do not meet criteria for biologicals. Targeted lung denervation (TLD) is the bronchoscopic ablation of the peribronchial vagal nerve trunks to reduce cholinergic stimulation of airway smooth muscle and submucosal glands. This report describes the experience of the first 2 asthma patients treated with TLD worldwide. The participants were 54 and 51 years of age, and both had severe asthma (GINA 5) (FEV1: 53% and 113% of predicted; AQLQ scores: 5.3 and 4.4). Both participants were treated with TLD in a single day-case procedure under general anaesthesia. Lung function, health status, and adverse event data were collected at baseline and 12 months after TLD. No treatment-related serious adverse events were reported up to 12 months. Cough symptoms improved in both participants, and 1 participant reported a marked reduction in rescue medication use at 6 months. There were no significant changes in spirometry, lung volumes, or health status. In conclusion, TLD was performed safely in both participants, but more evidence is needed to clarify safety and efficacy of TLD in severe asthma. Therefore, further investigation of the treatment in severe asthma patients would be useful.

Some patients hospitalized with acute COVID-19 suffer respiratory symptoms that persist for many months. We delineated the immune-proteomic landscape in the airway and peripheral blood of healthy controls and post-COVID-19 patients 3 to 6 months after hospital discharge. Post-COVID-19 patients showed abnormal airway (but not plasma) proteomes, with elevated concentration of proteins associated with apoptosis, tissue repair and epithelial injury versus healthy individuals. Increased numbers of cytotoxic lymphocytes were observed in individuals with greater airway dysfunction, while increased B cell numbers and altered monocyte subsets were associated with more widespread lung abnormalities. 1 year follow-up of some post-COVID-19 patients indicated that these abnormalities resolved over time. In summary, COVID-19 causes a prolonged change to the airway immune landscape in those with persistent lung disease, with evidence of cell death and tissue repair linked to ongoing activation of cytotoxic T cells., Graphical Abstract, Many individuals recovering from acute SARS-CoV-2 infection suffer prolonged respiratory dysfunction for months to years after viral clearance. Vijayakumar, Boustani, Ogger, Papadaki et al. show that individuals with persistent symptoms 3-6 months after infection have an altered airway immune cell landscape and evidence of ongoing lung damage. Importantly, different immune cell types correlate with the severity of distinct aspects of ongoing respiratory disease.

Introduction Our goal was to evaluate if traffic-light driven personalized care for COVID-19 was associated with improved survival in acute hospital settings. Methods Discharge outcomes were evaluated before and after prospective implementation of a real-time dashboard with feedback to ward-based clinicians. Thromboembolism categories were “medium-risk” (D-dimer >1000 ng/mL or CRP >200 mg/L); “high-risk” (D-dimer >3000 ng/mL or CRP >250 mg/L) or “suspected” (D-dimer >5000 ng/mL). Cytokine storm risk was categorized by ferritin. Results 939/1039 COVID-19 positive patients (median age 67 years, 563/939 (60%) male) completed hospital encounters to death or discharge by 21st May 2020. Thromboembolism flag criteria were reached by 568/939 (60.5%), including 238/275 (86.6%) of the patients who died, and 330/664 (49.7%) of the patients who survived to discharge, p < 0.0001. Cytokine storm flag criteria were reached by 212 (22.6%) of admissions, including 80/275 (29.1%) of the patients who died, and 132/664 (19.9%) of the patients who survived, p < 0.0001. The maximum thromboembolism flag discriminated completed encounter mortality (no flag: 37/371 [9.97%] died; medium-risk: 68/239 [28.5%]; high-risk: 105/205 [51.2%]; and suspected thromboembolism: 65/124 [52.4%], p < 0.0001). Flag criteria were reached by 535 consecutive COVID-19 positive patients whose hospital encounter completed before traffic-light introduction: 173/535 (32.3% [95% confidence intervals 28.0, 36.0]) died. For the 200 consecutive admissions after implementation of real-time traffic light flags, 46/200 (23.0% [95% confidence intervals 17.1, 28.9]) died, p = 0.013. Adjusted for age and sex, the probability of death was 0.33 (95% confidence intervals 0.30, 0.37) before traffic light implementation, 0.22 (0.17, 0.27) after implementation, p < 0.001. In subgroup analyses, older patients, males, and patients with hypertension (p ≤ 0.01), and/or diabetes (p = 0.05) derived the greatest benefit from admission under the traffic light system. Conclusion Personalized early interventions were associated with a 33% reduction in early mortality. We suggest benefit predominantly resulted from early triggers to review/enhance anticoagulation management, without exposing lower-risk patients to potential risks of full anticoagulation therapy.

Patients with severe emphysema have limited treatment options and only derive a small benefit from optimal medical treatment. The only other therapy to have significant clinical beneficial effect in emphysema is LVRS but the perceived risk and invasiveness of surgery has fuelled bronchoscopic approaches to induce lung volume reduction. There are multiple bronchoscopic methods for achieving volume reduction in severe emphysema: EBV, airway bypass procedure, endobronchial coils, thermal (vapour) sclerosis and chemical sclerosis (sealants). Optimal patient selection is key to successful patient outcomes. This review discusses bronchoscopic approaches for emphysema treatment which has progressed through clinical trials to clinical practice.

For over 150 years, bronchoscopy, especially flexible bronchoscopy, has been a mainstay for airway inspection, the diagnosis of airway lesions, therapeutic aspiration of airway secretions, and transbronchial biopsy to diagnose parenchymal lung disorders. Its utility for the diagnosis of peripheral pulmonary nodules and therapeutic treatments besides aspiration of airway secretions, however, has been limited. Challenges to the wider use of flexible bronchoscopy have included difficulty in navigating to the lung periphery, the avoidance of vasculature structures when performing diagnostic biopsies, and the ability to biopsy a lesion under direct visualization. The last 10-15 years have seen major advances in thoracic imaging, navigational platforms to direct the bronchoscopist to lung lesions, and the ability to visualize lesions during biopsy. Moreover, multiple new techniques have either become recently available or are currently being investigated to treat a broad range of airway and lung parenchymal diseases, such as asthma, emphysema, and chronic bronchitis, or to alleviate recurrent exacerbations. New bronchoscopic therapies are also being investigated to not only diagnose, but possibly treat, malignant peripheral lung nodules. As a result, flexible bronchoscopy is now able to provide a new and expanding armamentarium of diagnostic and therapeutic tools to treat patients with a variety of lung diseases. This State-of-the-Art review succinctly reviews these techniques and provides clinicians an organized approach to their role in the diagnosis and treatment of a range of lung diseases.

The largest randomised controlled trial evaluating results of lung volume reduction surgery (LVRS) was conducted by the National Emphysema Treatment Trial (NETT) that published a series of reports for outcomes up to 24 months. However, patient outcomes were difficult to interpret due to limitations in and the presentation of conventional statistical analyses applied to longitudinal data. We reevaluated the NETT results using longitudinal data methodology to report longer-term outcomes to facilitate interpretation by clinicians and patients who are considering LVRS for emphysema management.Trial data were released by the United States National Institutes of Health and the National Heart, Lung, and Blood Institute and analyzed using a mixed-effects model. Data on the difference in lung function variables between patients receiving LVRS vs medical care out to 5 years were estimated and are presented.The 5-year differences in patients randomised to LVRS were a small but sustained improvement in lung function indicators of forced expiratory volume in 1 second, forced vital capacity, and residual volume of +1.4% (P.001), +3.44% (P.001) and -19.49% (P.001) of the predicted values, respectively. With regards to physiological function, the 5-year difference in patients randomised to LVRS was an overall 0.89 W improvement in maximum workload (P = .069), -4.12 improvement in shortness of breath score (P.001), and 0.088 improvement in quality of well-being score (P = .102).Our results suggest that LVRS continues to have an important role in the treatment of patients with severe emphysema, with long-term benefits to lung function variables and a sustained improvement to the relief of dyspnea.

Aerosol particles of respirable size are exhaled when individuals breathe, speak and sing and can transmit respiratory pathogens between infected and susceptible individuals. The COVID-19 pandemic has brought into focus the need to improve the quantification of the particle number and mass exhalation rates as one route to provide estimates of viral shedding and the potential risk of transmission of viruses. Most previous studies have reported the number and mass concentrations of aerosol particles in an exhaled plume. We provide a robust assessment of the absolute particle number and mass exhalation rates from measurements of minute ventilation using a non-invasive Vyntus Hans Rudolf mask kit with straps housing a rotating vane spirometer along with measurements of the exhaled particle number concentrations and size distributions. Specifically, we report comparisons of the number and mass exhalation rates for children (12–14 years old) and adults (19–72 years old) when breathing, speaking and singing, which indicate that child and adult cohorts generate similar amounts of aerosol when performing the same activity. Mass exhalation rates are typically 0.002–0.02 ng s−1from breathing, 0.07–0.2 ng s−1from speaking (at 70–80 dBA) and 0.1–0.7 ng s−1from singing (at 70–80 dBA). The aerosol exhalation rate increases with increasing sound volume for both children and adults when both speaking and singing.

For selected patients with advanced emphysema, bronchoscopic lung volume reduction with one-way valves can lead to clinically relevant improvements of airflow obstruction, hyperinflation, exercise capacity, and quality of life. The most common complication of this procedure is pneumothorax with a prevalence of up to ±34% of the treated patients. Patients who develop a pneumothorax also experience meaningful clinical benefits once the pneumothorax is resolved. Timely resolution of a post-valve treatment pneumothorax requires skilled and adequate pneumothorax management. This expert panel statement is an updated recommendation of the 2014 statement developed to help guide pneumothorax management after valve placement. Additionally, mechanisms for pneumothorax development, risk assessment, prevention of pneumothorax, and outcomes after pneumothorax are addressed. This recommendation is based on a combination of the current scientific literature and expert opinion, which was obtained through a modified Delphi method.

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

SummarySome patients hospitalized with acute COVID19 suffer respiratory symptoms that persist for many months. To characterize the local and systemic immune responses associated with this form of ‘Long COVID’, we delineated the immune and proteomic landscape in the airway and peripheral blood of normal volunteers and patients from 3 to 6 months after hospital discharge. The bronchoalveolar lavage (but not peripheral blood) proteome was abnormal in patients with post-COVID19 lung disease with significantly elevated concentration of proteins associated with apoptosis, tissue repair and epithelial injury. This correlated with an increase in cytotoxic lymphocytes (especially tissue resident CD8+T cells), lactate dehydrogenase and albumin (biomarkers of cell death and barrier integrity). Follow-up of a subset of these patients greater than 1-year post-COVID19 indicated these abnormalities resolved over time. Collectively, these data indicate that COVID-19 results in a prolonged change to the airway immune landscape in those with persistent lung disease, with evidence of cell death and tissue repair linked to ongoing activation of cytotoxic T cells.HighlightsThe post-COVID19 airway is characterized by increased cytotoxic lymphocytes.Distinct airway proteomes are associated with the airway immune cell landscape.The peripheral blood does not predict immune-proteome alterations in the airway post-COVID19.Persistent abnormalities in the airway immune-proteome post-COVID19 airways correlate with ongoing epithelial damage.

As many as 25% of all patients undergoing invasive pulmonary procedures are receiving at least one antiplatelet or anticoagulant agent. For those undergoing elective procedures, the decision-making process is uncomplicated and the procedure may be postponed until the antiplatelet or anticoagulant agent may be safely held. However, many invasive pulmonary procedures are semi-elective or emergent in nature in which case a risk-benefit calculation and discussion occur between the provider and patient or surrogate decision-maker. Therefore, it is critical for providers to have an awareness of the risk of bleeding complications with different pulmonary procedures on various antiplatelet and anticoagulant agents. This systematic review summarizes the bleeding complications associated with different pulmonary procedures in patients on various antiplatelet or anticoagulant agents in the literature and reveals a paucity of high-quality evidence across a wide spectrum of pulmonary procedures and antiplatelet or anticoagulant agents. The results of this review can help inform providers of the bleeding risk in these patients to aid in the shared decision-making process and risk vs benefit discussion.

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.

Background Severe emphysema is a debilitating condition with few treatment options. Lung volume reduction procedures in the treatment of severe emphysema have shown excellent results in selected patients but their exact role remains unclear with studies reporting a wide variation in outcomes. We therefore aimed to evaluate the effects of volume reduction. Methods We did a systematic review and meta-analysis. We searched MEDLINE on Sept 29, 2016, for trials of lung volume reduction in patients with emphysema, and we did an updated search on Embase and PubMed on June 18, 2018. We only included randomised controlled studies published in English evaluating the intervention with either sham or standard of care. Inclusion was limited to trials of techniques in which there was sustainable volume reduction. Primary outcomes were residual volume, FEV 1, St George's Respiratory Questionnaire (SGRQ), and 6-min walk distance (6MWT). Secondary outcomes were severe adverse events (including mortality), short-term mortality, and overall mortality. We extracted summary level data from the trial publications and where necessary we obtained unpublished data. A random-effects model with the I (2) statistic was used to determine heterogeneity and trial weight in each analysis. The study is registered with the PROSPERO database, number CRD42016045705. Findings We identified 4747 references in the search, and included 20 randomised controlled trials of lung volume reduction involving 2794 participants with emphysema. Following lung volume reduction from any of the interventions in pooled analyses (ie, surgery, endobronchial valve, endobronchial coil, or sclerosing agents), the mean differences compared with the control were reduction in residual volume of 0.58 L (95% CI -0.80 to -0.37), increase in FEV1 of 15.87% (95% CI 12.27 to 19.47), improvement in 6MWT of 43.28 m (31.36 to 55.21), and reduction in the SGRQ of 9.39 points (-10.92 to -7.86). The odds ratio for a severe adverse event, which included mortality, was 6.21 (95% CI 4.02 to 9.58) following intervention. Regression analysis showed improvements relative to the degree of volume reduction: FEV 1 (r(2) = 0.86; p Interpretation Despite limitations of high risk of bias and heterogeneity for some analyses, our results provide support that lung volume reduction in patients with severe emphysema on maximal medical treatment has clinically meaningful benefits. These benefits should be considered alongside potential adverse events. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

Rationale: This is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of Zephyr Endobronchial Valve (EBV) in patients with little to no collateral ventilation out to 12 months.Objectives: To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation in the treated lobe.Methods: Subjects were enrolled with a 2:1 randomization (EBV/standard of care [SoC]) at 24 sites. Primary outcome at 12 months was the Delta EBV-SoC of subjects with a post-bronchodilator FEV1 improvement from baseline of greater than or equal to 15%. Secondary endpoints included absolute changes in post-bronchodilator FEV1, 6-minute-walk distance, and St. George's Respiratory Questionnaire scores.Measurements and Main Results: A total of 190 subjects (128 EBV and 62 SoC) were randomized. At 12 months, 47.7% EBV and 16.8% SoC subjects had a Delta FEV1 greater than or equal to 15% (P Conclusions: Zephyr EBV provides clinically meaningful benefits in lung function, exercise tolerance, dyspnea, and quality of life out to at least 12 months, with an acceptable safety profile in patients with little or no collateral ventilation in the target lobe.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in an unprecedented shutdown in social and economic activity, with the cultural sector particularly severely affected. Restrictions on musical performances have arisen from a perception that there is a significantly higher risk of aerosol production from singing than speaking, based upon high-profile examples of clusters of COVID-19 following choral rehearsals. However, comparing aerosol generation from different types of vocalization, including singing, across a range of volumes is a rapidly evolving area of research. Here, we measured aerosols from singing, speaking and breathing from a large cohort of 25 professional singers in a range of musical genres in a zero-background environment, allowing unequivocal attribution of aerosol production to specific vocalizations. We do not assess the relative volumes at which people speak and sing. However, both showed steep increases in mass concentration with increase in loudness (spanning a factor of 20–30 across the dynamic range measured, p < 0.001). At the quietest volume (50 to 60 dBA), neither singing (p = 0.19) nor speaking (p = 0.20) were significantly different to breathing. At the loudest volume (90 to 100 dBA), a statistically significant difference (p < 0.001) was observed between singing and speaking, but with singing only generating a factor of between 1.5 and 3.4 more aerosol mass. Guidelines for musical performances should be based on the loudness and duration of the vocalization, the number of participants and the environment in which the activity occurs, rather than the type of vocalization. Mitigations such as the use of amplification and increased attention to ventilation should be employed where practicable. Copyright © 2021 American Association for Aerosol Research