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

Rationale: Trotz klinisch nachgewiesener Vorteile von Immun-Checkpoint-Inhibitoren (ICI) bei fortgeschrittenem Lungenkrebs wurden seltene, aber lebensbedrohliche immunbedingte unerwünschte Ereignisse (ibUE) berichtet. Pankreatitis ist ein seltenes ibUE, das bei jedem ICI auftreten kann. Überblick zum Patienten: Ein 53-jähriger Mann mit einem lokal fortgeschrittenen nicht-kleinzelligen Lungenkarzinom wurde mit einer Radiochemotherapie und anschließend mit Durvalumab behandelt. Zwölf Wochen nach Beginn der Therapie mit dem ICI berichtete der Patient über Bauchschmerzen und Anorexie. Blutuntersuchungen zeigten einen hohen Lipasegehalt. Eine abdominale Computertomographie zeigte eine geschwollene Bauchspeicheldrüse. Diese Befunde wurden durch eine Magnetresonanz-Cholangiopankreatikographie und eine biliopankreatische endoskopische Ultraschalluntersuchung bestätigt. Diagnosen: Immunbedingte Pankreatitis Grad IV. Behandlungen: Der Patient wurde mit einer Kortikosteroidtherapie behandelt, die zu einer klinischen, radiologischen und biologischen Verbesserung führte. Ergebnisse: Während des ersten Monats konnte die Kortikosteroidtherapie nicht unter 1mg/kg/d gesenkt werden, da die Symptome wieder auftraten und die Lipasämie wieder zunahm. Vier Monate nach dieser Episode starb der Patient an einer akuten Ischämie der unteren Gliedmaßen bei Einnahme von Erkenntnisse: Soweit wir wissen, wurde über immunbedingte Pankreatitis nur im Zusammenhang mit Therapien gegen den programmierten Zelltod 1 oder gegen das zytotoxische T-Lymphozyten-Antigen 4 berichtet, aber nie mit einer Therapie gegen den programmierten Zelltod-Liganden 1. Es ist wichtig, solche seltenen Fälle zu melden, um die Diagnose und das Management von ibUE zu verbessern

Summary Background Patients with COVID-19 pneumonia can have increased inflammation and elevated cytokines, including interleukin (IL)-6, which might be deleterious. Thus, sarilumab, a high-affinity anti-IL-6 receptor antibody, might improve the outcome of patients with moderate-to-severe COVID-19 pneumonia. Methods We did a multicentric, open-label, Bayesian randomised, adaptive, phase 2/3 clinical trial, nested within the CORIMUNO-19 cohort, to test a superiority hypothesis. Patients 18 years or older hospitalised with COVID-19 in six French centres, requiring at least 3L/min of oxygen but without ventilation assistance and a WHO Clinical Progression Scale [CPS] score of 5 were enrolled. Patients were randomly assigned (1:1) via a web-based system, according to a randomisation list stratified on centre and with blocks randomly selected among 2 and 4, to receive usual care plus 400 mg of sarilumab intravenously on day 1 and on day 3 if clinically indicated (sarilumab group) or usual care alone (usual care group). Primary outcomes were the proportion of patients with WHO-CPS scores greater than 5 on the 10-point scale on day 4 and survival without invasive or non-invasive ventilation at day 14. This completed trial is closed to new participants and is registered with ClinicalTrials.gov , NCT04324073 . Findings 165 patients were recruited from March 27 to April 6, 2020, and 148 patients were randomised (68 patients to the sarilumab group and 80 to the usual care group) and followed up for 90 days. Median age was 61·7 years [IQR 53·0–71·1] in the sarilumab group and 62·8 years [56·0–71·7] in the usual care group. In the sarilumab group 49 (72%) of 68 were men and in the usual care group 59 (78%) of 76 were men. Four patients in the usual care group withdrew consent and were not analysed. 18 (26%) of 68 patients in the sarilumab group had a WHO-CPS score greater than 5 at day 4 versus 20 (26%) of 76 in the usual care group (median posterior absolute risk difference 0·2%; 90% credible interval [CrI] −11·7 to 12·2), with a posterior probability of absolute risk difference greater than 0 of 48·9%. At day 14, 25 (37%) patients in the sarilumab and 26 (34%) patients in the usual care group needed ventilation or died, (median posterior hazard ratio [HR] 1·10; 90% CrI 0·69–1·74) with a posterior probability HR greater than 1 of 37·4%. Serious adverse events occurred in 27 (40%) patients in the sarilumab group and 28 (37%) patients in the usual care group (p=0·73). Interpretation Sarilumab treatment did not improve early outcomes in patients with moderate-to-severe COVID-19 pneumonia. Further studies are warranted to evaluate the effect of sarilumab on long-term survival. Funding Assistance publique—Hopitaux de Paris

In recent decades, the development of immunotherapy and targeted therapies has considerably improved the outcome of non-small cell lung cancer (NSCLC) patients. Despite these impressive clinical benefits, new biomarkers are needed for an accurate stratification of NSCLC patients and a more personalized management. We recently showed that the tumor suppressor fragile histidine triad (FHIT), frequently lost in NSCLC, controls HER2 receptor activity in lung tumor cells and that tumor cells from NSCLC patients harboring a FHITWe performed RNA sequencing analysis on tumor cells isolated from NSCLC (n=12) according to FHIT/pHER2 status and a functional analysis of differentially regulated genes. We also investigated the FHITWe showed that up-regulated genes in FHITThese data suggest that ICI might not be a relevant option for NSCLC patients with FHIT

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.

The alteration of the mucociliary clearance is a major hallmark of respiratory diseases related to structural and functional cilia abnormalities such as chronic obstructive pulmonary diseases (COPD), asthma and cystic fibrosis. Primary cilia and motile cilia are the two principal organelles involved in the control of cell fate in the airways. We tested the effect of primary cilia removal in the establishment of a fully differentiated respiratory epithelium. Epithelial barrier integrity was not altered while multiciliated cells were decreased and mucous‐secreting cells were increased. Primary cilia homeostasis is therefore paramount for airway epithelial cell differentiation. Primary cilia‐associated pathophysiologic implications require further investigations in the context of respiratory diseases.

International audience; Rationale: Despite clinical-proven benefits of immune checkpoint inhibitors (ICIs) on advanced lung cancer, rare but life-threatening immune-related adverse events (irAEs) have been reported. Pancreatitis is a rare irAE that can occur with any ICI.Patient concerns: A 53-year-old man with locally advanced non–small cell lung carcinoma was treated with radiochemotherapy and then durvalumab (anti–programmed cell death ligand 1 therapy). Twelve weeks after the beginning of ICI, he reported abdominal pain and anorexia. Blood test showed high level of lipase. Abdominal computed tomography revealed a swollen pancreas. These findings were confirmed by magnetic resonance cholangiopancreatography and biliopancreatic endoscopic ultrasonography.Diagnoses: Grade IV immune-related pancreatitis.Interventions: The patient was treated with corticosteroid therapy, resulting in clinical, radiological, and biological improvement.Outcomes: During the first month, corticosteroid therapy could not be decreased under 1 mg/kg/d because of symptoms recurrence and lipasemia rerising. Four months after this episode, the patient died from acute ischemia of the lower limbs while he was on

Background While sleep disruption is a common complaint among children with cystic fibrosis (CF), only a few studies have investigated insomnia in adults. The aim of this study was to identify factors associated with insomnia in clinically stable adult CF patients. Methods Twenty-eight CF patients (18M/10F), with a median age of 27 (22–34) (median (interquartile range) years and a median of forced expiratory volume in one second of 72 (39–93) % predicted completed questionnaires on insomnia (Insomnia Severity Index, ISI), sleep quality (PSQI), daytime sleepiness (Epworth), restless legs syndrome (IRLS), pain (NRS), anxiety/depression (HAD) and quality of life (CFQ-R 14+). Respiratory assessment data, including symptoms, sputum analysis, arterial blood gases, 6-min walking test, pulmonary function tests and polysomnographic variables, were also analyzed. Results Forty-three percent of patients were insomniac (ISI > 7). Compared with non-insomniac patients (ISI ≤ 7), insomniac patients had more severely impaired quality of life and a higher HAD score: median anxiety score of 9 (8–11) vs 4 (3–6) (p p p 2 during sleep. Conclusions The strong association between insomnia, impaired quality of life and increased HAD score should prompt physicians to be particularly attentive to the management of anxiety and depression in adult CF patients with insomnia. Trial registration: On clinicaltrials.gov (NCT02924818, date of registration: October 5, 2016).

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

Background In chronic obstructive pulmonary disease (COPD), lung-infiltrating inflammatory cells secrete proteases and participate in elastin breakdown and genesis of elastin-derived peptides (EP). In the present study, we hypothesized that the pattern of T lymphocytes cytokine expression may be modulated by EP in COPD patients. Methods CD4+ and CD8+ T-cells, sorted from peripheral blood mononuclear cells (PBMC) collected from COPD patients (n = 29) and controls (n = 13) were cultured with or without EP. Cytokine expression in T-cell phenotypes was analyzed by multicolor flow cytometry, whereas desmosine concentration, a specific marker of elastin degradation, was measured in sera. Results Compared with control, the percentage of IL-4 (Th2) producing CD4+ T-cells was decreased in COPD patients (35.3 ± 3.4% and 26.3 ± 2.4%, respectively, p + T-cells, of which only one expressed high IL-4 levels in association with high levels of desmosine and strong smoking exposure (n = 7). Upon stimulation with VGVAPG, a bioactive EP motif, the percentage of CD4+ T cells expressing IL-4 significantly increased in COPD patients (p Conclusions The present study demonstrates that the VGVAPG elastin peptide modulates CD4+ T-cells IL-4 production in COPD. Monitoring IL-4 in circulating CD4+ T-cells may help to better characterize COPD phenotypes and could open a new pharmacologic opportunity through CD4+ T-cells stimulation via the VGVAPG/S-gal receptor in order to favor an anti-inflammatory response in those COPD patients.

International audience; No abstract available

Despite its efficacy in solid tumours, in particular HER2+ breast cancer, HER2-targeted therapy has given rise to disappointing results in non-small cell lung cancer (NSCLC). With the aim of refining the target population for anti-HER2 therapies in NSCLC, we investigated the relationships between HER2 and the tumour suppressor fragile histidine triad (FHIT) in lung tumour cells. First, we observed a negative correlation between FHIT expression and the activated form of HER2 (pHER2) in NSCLC samples and in lung tumour cell lines. Moreover, the silencing or overexpression of FHIT in lung cell lines led to an increase or decrease of HER2 activity, respectively. We also demonstrated that two anti-HER2 drugs, irbinitinib and trastuzumab, restore a more epithelial phenotype and counteract cell invasiveness and growth of FHIT-silenced tumour cell lines. Finally, we showed that the FHITlow /pHER2high phenotype predicts sensitivity to an anti-HER2 therapy in primary tumour cells from NSCLC patients. Our results show that FHIT regulates the activity of HER2 in lung tumour cells and that FHIT-inactivated tumour cells are sensitive to HER2 inhibitors. A new subclass of patients with NSCLC may be eligible for an anti-HER2 therapy. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Background Obesity is a risk factor for dyspnea. However, investigations of daily living obesity-related dyspnea are limited and its mechanisms remain unclear. We aimed to analyze the relationships between dyspnea in daily living, lung function, and body composition in patients with obesity.Methods One-hundred and thirty patients (103 women/27 men), candidate for bariatric surgery, with a mean ± SD Body Mass Index (BMI) of 44.8 ± 6.8 kg/m² were included. Dyspnea was assessed by the modified Medical Research Council (mMRC) scale. Comorbidities, laboratory parameters, pulmonary function tests, arterial blood gases, six-minute walk test (6MWT), handgrip strength, and DXA body composition were analyzed.Results Thirty-one percent of patients exhibited disabling dyspnea in daily living (mMRC ≥ 2). Compared with patients without disabling dyspnea (mMRC < 2), significant dyspnea (mMRC ≥ 2) was associated with a lower 6MWT distance (395 ± 103 m vs 457 ± 73 m, pvs 54 ± 27%, p=0.024), Vital Capacity (95 ± 14 vs 106 ± 15%, pvs 105 ± 15%, p=0.002), a higher BMI (48.2 ± 7.7 vs 43.2 ± 5.7 kg/m², p=0.001) and a higher percentage of fat mass in the trunk (46 ± 5 vs 44 ± 5 p=0.012) and android region (52 ± 4 vs 51 ± 4%, p=0.024). There was no difference regarding comorbidities (except hypertension), laboratory parameters, and sarcopenia markers between patients with (mMRC ≥ 2) and without (mMRC < 2) disabling dyspnea. Conclusion Dyspnea in patients with obesity is associated with a reduction in lung volumes and a higher percentage of fat mass in central body regions. How dyspnea and body composition may change with interventions like physical activity or bariatric surgery remains to be investigated. Trial Registration Reims University Hospital Institutional Review Board (IRB-17-10-2012).

Contexte Le Royaume-Uni (UK) presente des taux de mortalite et d’hospitalisation pour Broncho Pneumopathie Chronique Obstructive (BPCO) plus eleves que ceux de la France. Ces differences pourraient etre dues a des differences de prise en charge : le but de cette etude etait de decrire la consommation de soins des patients BPCO et les couts associes dans les 2 pays. Methode Il s’agissait d’une etude transversale repetee chaque annee entre 2008 et 2017, realisee pour la France sur l’Echantillon Generaliste de Beneficiaires (EGB), et pour le UK sur la base du Clinical Practice Research Datalink (CPRD). Les patients, âges de 40 ans ou plus, ont ete inclus chaque annee, identifies par une hospitalisation pour BPCO ou par la prise de bronchodilatateurs (LABA, LAMA, association fixe [AF] LABA/ICS, AF LABA/LAMA) sur 3 trimestres consecutifs. Nous avons decrit, pour chaque annee d’etude : – les caracteristiques socio-demographiques, le nombre d’exacerbations severes (hospitalisations) et les comorbidites ; – a consommation de soins et les couts associes en termes de visites medicales, hospitalisations, et types de medicaments dispenses. Resultats L’âge moyen des patients BPCO etait stable dans le temps et legerement plus eleve au UK (71 ans) qu’en France (67 ans) ; il en etait de meme pour la proportion d’hommes dans la population (UK : 51 %, France : 53 %). Le taux de mortalite des patients etait stable au cours du temps, et legerement plus eleve au UK (3 %) qu’en France (2 %). Dans les 2 pays, le diabete etait la comorbidite la plus frequente et sa prevalence augmentait au cours du temps en France (14 % en 2008, 17 % en 2017) alors qu’elle restait stable au UK (∼12 %). Le taux d’exacerbations severes etait plus eleve au UK qu’en France et il augmentait au cours du temps (de 4 % a 6 % en France, et de 12 % a 28 % en Angleterre de 2008 a 2017). En 2008, le taux d’hospitalisations toutes causes etait plus eleve au UK (39 %) qu’en France (30 %) et il augmentait entre 2008 et 2017 au UK (59 % en 2017), alors qu’il restait stable en France. Le taux de passages aux urgences etait aussi plus eleve au UK, et il augmentait plus fortement au cours du temps qu’en France (de 27 % a 45 % au UK, de 11 % a 16 % en France de 2009 a 2017). Alors que le taux de visite chez le medecin generaliste etait similaire entre les 2 pays en 2008 (∼96 %), il a fortement chute entre 2008 et 2017 au UK (78 %), alors qu’il est reste stable en France durant la meme periode. Les dispensations d’ICS/LABA en AF ont fortement augmente au UK entre 2008 et 2017, mais restaient toujours plus elevees en France (70 % vs 58 % en 2017). Les dispensations de corticoides oraux etaient plus frequentes en France (45 %), mais elles ont beaucoup augmente au UK (de 25 % a 39 %) alors qu’elles sont restees stable en France entre 2008 et 2017. Les couts associes a la prise en charge de la BPCO augmentaient dans les 2 pays entre 2008 et 2017. Les couts les plus importants en France etaient ceux des traitements, alors qu’au UK, les couts des visites etaient les plus eleves. Conclusion Nous avons mis en evidence des differences de profils et de pratiques dans la prise en charge de la BPCO en France et au UK, qui pourraient en partie expliquer les differences observees entre les 2 pays en termes de mortalite et d’hospitalisation, malgre la difficulte a identifier des populations de severite comparable. Ces resultats seront statistiquement compares ulterieurement, afin de pouvoir tirer des conclusions plus robustes.

Purposes Following a hospitalization for COPD, dual and triple therapies were compared in terms of persistence and relations with outcomes (exacerbations, health care resource use and costs). Methods This was a historical observational database study. All patients aged ≥45 hospitalized for COPD between 2007 and 2015 were identified in a 1/97th random sample of French claims data. Patients receiving dual therapy within 60 days after hospitalization were compared to patients receiving triple therapy, after propensity score matching on disease severity. Results Of the 3,089 patients hospitalized for COPD, 1,538 (49.8%) received either dual or triple therapy in the 2 months following inclusion, and 1,500 (48.6%) had at least 30 days of follow-up available; 846 (27.4%) received dual therapy, and 654 (21.2%) received triple therapy. After matching, the number of exacerbations was 2.4 per year in the dual vs 2.3 in the triple group (p=0.45). Among newly treated patients (n=206), persistence at 12 months was similar in the dual and triple groups (48% vs 41%, respectively, p=0.37). As compared to patients on dual therapy, more patients on triple therapy received oral corticosteroids (49.1 vs 40.4%, p=0.003) or were hospitalized for any reason (67% vs 55.8%, p=0.0001) or for COPD (35.3 vs 25.1%, p=0.0002) during follow-up. Cost of care was higher for patients on triple than for those on dual therapy (€11,877.1 vs €9,825.1, p=0.01). Conclusion Following hospitalizations for COPD, patients on dual and triple therapy experienced recurrent exacerbations, limited adherence to therapies and high cost of care. Patients on triple therapy appeared more severe than those on dual therapy, as reflected by exacerbations and health care resource use.

Background: The 6-min walk test (6MWT) allows exercise tolerance to be assessed, and it has a significant prognostic value in COPD. The goal of this study was to analyse the determinants (obtained in routine practice) of a low 6-min walking distance (6MWD) and exercise-induced desaturation (EID) in COPD, including comorbidities. Methods: Patients were recruited from the real-life French COPD cohort "Initiatives BPCO". A low 6MWD was defined as 30 kg/m2), low BMI (BMI

Background: Bronchoscopic lung volume reduction (BLVR) using valves and coils has been approved for use since 2003 and 2010, respectively. Objective(s): To study adoption patterns of BLVR in an early-adopting country, and to estimate potential treatment volumes in other European countries. Methods: Therapy- and age-specific volumes for endobronchial valve and coil procedures were obtained from German federal statistics for 2007–2016. Therapy-specific and total BLVR procedure volumes and growth were computed, and patterns in treatment age and device utilization analyzed. Patient volumes for other European countries were predicted using mean German patient volumes of the last 3 data years and age-specific population and emphysema incidences. Results: Over the study period, annual BLVR procedure volumes grew from 91 to 2,053 (+2,256%), reaching a peak of 2,556 procedures in 2013. Coil procedures constituted 36% of the total volume in 2016. Treatment age was stable over time, with highest procedure counts in age group 60–64 years for valves and 65–69 years for coils. A limited increase in device use per procedure was observed. For ­Germany, 1,655 newly treated BLVR patients were estimated per year, approximating about 5% of the annual newly diagnosed severe emphysema cases. Predicted volume estimates for other European countries ranged from 1 for Liechtenstein to 1,226 for France. Conclusions: Analysis of ­German procedure data show pronounced BLVR therapy uptake in the early years of adoption, with the more recently introduced coil therapy used in about one-third of patients. Estimated patient volumes to date constitute only a small fraction of the severe emphysema population.

International audience; Le reflux gastro‐oesophagien (RGO) est une des pathologies les plus fréquemment associées à l’asthme, avec un impact sur le contrôle et la qualité de vie des patients. Le traitement du RGO repose sur des mesures hygiéno‐diététiques, un traitement médicamenteux anti‐acide et, dans certains cas, une prise en charge chirurgicale par fundoplicature. Si l’impact de mesures hygiéno‐diététiques seules sur l’asthme n’a pas été étudié, l’efficacité d’un traitement par inhibiteurs de la pompe à protons sur le contrôle de l’asthme, le débit expiratoire de pointe ou la qualité de vie a été analysée dans plusieurs essais randomisés contrôlés, détaillés dans cette revue. Les données d’efficacité de la prise en charge chirurgicale reposent principalement sur des études observationnelles rétrospectives ou prospectives, également détaillées. Devant l’impact limité du traitement du RGO dans l’asthme, les recommandations actuelles sont de limiter un traitement médical du RGO aux asthmes associés à un RGO symptomatique. Il n’existe pas actuellement de données suffisantes pour recommander un traitement chirurgical du RGO pour l’indication spécifique de l’asthme.

International audience

International audience; Background: Patients with COVID-19 pneumonia have an excess of inflammation and increased concentrations of cytokines including interleukin-1 (IL-1). We aimed to determine whether anakinra, a recombinant human IL-1 receptor antagonist, could improve outcomes in patients in hospital with mild-to-moderate COVID-19 pneumonia.Methods: In this multicentre, open-label, Bayesian randomised clinical trial (CORIMUNO-ANA-1), nested within the CORIMUNO-19 cohort, we recruited patients from 16 University hospitals in France with mild-to-moderate COVID-19 pneumonia, severe acute respiratory syndrome coronavirus 2 infection confirmed by real-time RT-PCR, requiring at least 3 L/min of oxygen by mask or nasal cannula but without ventilation assistance, a score of 5 on the WHO Clinical Progression Scale (WHO-CPS), and a C-reactive protein serum concentration of more than 25 mg/L not requiring admission to the intensive care unit at admission to hospital. Eligible patients were randomly assigned (1:1) using a web-based secure centralised system, stratified by centre and blocked with varying block sizes (randomly of size two or four), to either usual care plus anakinra (200 mg twice a day on days 1-3, 100 mg twice on day 4, 100 mg once on day 5) or usual care alone. Usual care was provided at the discretion of the site clinicians. The two coprimary outcomes were the proportion of patients who had died or needed non-invasive or mechanical ventilation by day 4 (ie, a score of >5 on the WHO-CPS) and survival without need for mechanical or non-invasive ventilation (including high-flow oxygen) at day 14. All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT04341584, and is now closed to accrual.Findings: Between April 8 and April 26, 2020, we screened 153 patients. The study was stopped early following the recommendation of the data and safety monitoring board, after the recruitment of 116 patients: 59 were assigned to the anakinra group, and 57 were assigned to the usual care group. Two patients in the usual care group withdrew consent and were not analysed. In the analysable population, the median age was 66 years (IQR 59 to 76) and 80 (70%) participants were men. In the anakinra group, 21 (36%) of 59 patients had a WHO-CPS score of more than 5 at day 4 versus 21 (38%) of 55 in the usual care group (median posterior absolute risk difference [ARD] -2·5%, 90% credible interval [CrI] -17·1 to 12·0), with a posterior probability of ARD of less than 0 (ie, anakinra better than usual care) of 61·2%. At day 14, 28 (47%; 95% CI 33 to 59) patients in the anakinra group and 28 (51%; 95% CI 36 to 62) in the usual care group needed ventilation or died, with a posterior probability of any efficacy of anakinra (hazard ratio [HR] being less than 1) of 54·5% (median posterior HR 0·97; 90% CrI 0·62 to 1·52). At day 90, 16 (27%) patients in the anakinra group and 15 (27%) in the usual care group had died. Serious adverse events occurred in 27 (46%) patients in the anakinra group and 21 (38%) in the usual care group (p=0·45).Interpretation: Anakinra did not improve outcomes in patients with mild-to-moderate COVID-19 pneumonia. Further studies are needed to assess the efficacy of anakinra in other selected groups of patients with more severe COVID-19.Funding: The Ministry of Health, Programme Hospitalier de Recherche Clinique, Foundation for Medical Research, and AP-HP Foundation.

In recent years, many bronchoscopic techniques have been developed in chronic obstructive airway inflammatory diseases, including asthma, COPD and emphysema. The main techniques with available data from randomised controlled trials are: 1) bronchial thermoplasty in asthma; 2) valves, coils and thermal vapor ablation in emphysema; and 3) targeted lung denervation in COPD. The objectives of this article are to describe the levels of evidence for efficacy and safety, long-term follow-up results beyond 1 year, and current recommendations for clinical practice from international guidelines for each technique.

Introduction Le syndrome obesite-hypoventilation (SOH) est une cause frequente d’insuffisance respiratoire chronique dont la prevalence a augmente au cours des dernieres annees. Le diagnostic de SOH est encore souvent fait a l’occasion d’une hospitalisation pour decompensation respiratoire. Un depistage precoce permettrait de mettre en route des traitements appropries et d’eviter des complications graves. Nous presentons ici les caracteristiques a l’inclusion des patients de l’etude « COHYPOB ». Methodes Il s’agit d’une etude longitudinale, prospective, ouverte, multicentrique francaise (10 centres). Nous avons recrute 187 sujets obeses (IMC ≥ 30 kg/m 2), volontaires, ambulants, sans syndrome obesite hypoventilation connu (= normocapniques le jour). 26 sujets ont ete exclus en raison de la decouverte d’un syndrome d’apnees obstructives du sommeil (SAOS) severe, necessitant un traitement par PPC. Nous avons compare un groupe de patients sans hypoventilation nocturne (HN) avec un groupe de patients presentant des signes d’HN (> 10 episodes de desaturation nocturne ou SpO2 moyenne nocturne Resultats Nous avons inclus 161 sujets, 26 % d’hommes et 74 % de femmes. L’âge moyen etait de 47 ± 13 ans. L’indice de masse corporelle moyen etait de 37 ± 5 kg/m2. 87 (54 %) patients presentaient des signes d’HN isolee. En analyse univariee, les patients obeses avec HN etaient plus âges (53 ± 12 vs 41 ± 11; p = 0.001), plus obeses (IMC: 38,4 ± 5,4 vs 36,0 ± 3,7 kg/m2; p = 0,002), plus dyspneiques a l’effort (p = 0,003), plus somnolents (score d’Epworth: 7,4 ± 4,5 vs 6 ± 3,6; p = 0,034) et plus hypoxemiques le jour (PaO2: 86 ± 13 vs 92 ± 14 mmHg; p = 0,01). Il n’y avait pas de difference significative entre les 2 groupes pour la PaCO2 diurne ni pour les volumes et debits pulmonaires. Conclusion Dans une cohorte de sujets obeses, la moitie presente une hypoventilation nocturne. Le suivi longitudinal de cette cohorte devrait permettre de determiner si cette HN precede la survenue du syndrome obesite hypoventilation.

International audience; Lung cancer is one of the most common solid cancers and represents the leading cause of cancer death worldwide. Over the last decade, research on the epithelial-mesenchymal transition (EMT) in lung cancer has gained increasing attention. Here, we review clinical and histological features of non-small-cell lung cancer associated with EMT. We then aimed to establish potential clinical implications of EMT in current therapeutic options, including surgery, radiation, targeted therapy against oncogenic drivers, and immunotherapy.

Maéva Zysman,1 Gaëtan Deslee,2 Thierry Perez,3 Pierre-Régis Burgel,4 Olivier Le Rouzic,3 Graziella Brinchault-Rabin,5 Pascale Nesme-Meyer,6 Isabelle Court-Fortune,7 Gilles Jebrak,8 Pascal Chanez,9 Denis Caillaud,10 Jean-Louis Paillasseur,11 Nicolas Roche4 1Pulmonary Department, Pôle Cardio-thoracique, CHU Haut-Lévèque, INSERM U1045, Bordeaux, France; 2Pulmonary Department, Maison Blanche University Hospital, INSERM U01250, Reims, France; 3University Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 – UMR 9017 – CIIL - Center for Infection and Immunity of Lille, Lille, France; 4Respiratory Medicine, Cochin Hospital, AP-HP and Université de Paris, Institut Cochin, INSERM U1016, Paris, France; 5Service de Pneumologie, Hôpital Pontchaillou, Rennes, France; 6Service de Pneumologie, Hôpital de la Croix-Rousse, Lyon, France; 7Service de Pneumologie, CHU Saint Etienne, Saint Etienne, France; 8Service de Pneumologie, Hôpital Bichat, AP-HP, Paris, France; 9Département des Maladies Respiratoires, AP-HM, Université de la Méditerranée, Marseille, France; 10Service de Pneumologie, Hôpital Gabriel Montpied, CHU, Clermont-Ferrand, France; 11EFFI-STAT, Paris, FranceCorrespondence: Maéva ZysmanAvenue de Magellan, Service des Maladies Respiratoires, CHU Haut Lévèque, Pessac, 33600, FranceTel +33 5 56 79 56 79Email maeva.zysman@chu-bordeaux.frBackground: Chronic respiratory failure may occur as a consequence of chronic obstructive pulmonary disease (COPD) and is associated with significant morbidity and mortality. Hypoxemia is determined by underlying disease characteristics and comorbidities. Severe hypoxemia is typically only found in subjects with severe airflow obstruction (FEV1< 50% predicted). However, how hypoxemia relates to disease characteristics is not fully understood.Methods: In the French Initiatives BPCO real-life cohort, arterial blood gases were routinely collected in most patients. Relationships between severe hypoxemia, defined by a Pa02< 60 mmHg (8 kPa) and clinical/lung function features, comorbidities and mortality were assessed. In subjects with severe hypoxemia, clinical characteristics and comorbidities were compared between those with non-severe versus severe airflow limitation. Classification and regression trees (CART) were used to define clinically relevant subgroups (phenotypes).Results: Arterial blood gases were available from 887 subjects, of which 146 (16%) exhibited severe hypoxemia. Compared to subjects with a PaO2≥ 60 mmHg, the severe hypoxemia group exhibited higher mMRC dyspnea score, lower FEV1, higher RV and RV/TLC, more impaired quality of life, lower 6-minute walking distance, less frequent history of asthma, more frequent diabetes and higher 3-year mortality rate (14% versus 8%, p=0.026). Compared to subjects with Pa02< 60 mmHg and FEV1< 50% (n=115, 13%), those with severe hypoxemia but FEV1≥ 50% predicted (n=31) were older, had higher BMI, less hyperinflation, better quality of life and a higher rate of diabetes (29% versus 13%, p=0.02). Severe hypoxemia was better related to CART-defined phenotypes than to GOLD ABCD classification.Conclusion: In this cohort of stable COPD subjects, severe hypoxemia was associated with worse prognosis and more severe symptoms, airflow limitation and hyperinflation. Compared to subjects with severe hypoxemia and severe airflow limitation, subjects with severe hypoxemia despite non-severe airflow limitation were older, had higher BMI and more diagnosed diabetes.Trial Registration: 04– 479.Keywords: chronic obstructive pulmonary disease, severe hypoxemia, airflow limitation

Introduction La BPCO est une maladie pulmonaire inflammatoire caracterisee par un remodelage de l’epithelium des voies aeriennes et de l’emphyseme. Le principal facteur de risque est l’inhalation de fumee de cigarette essentiellement constituee de nicotine. Cet agoniste est un ligand des recepteurs nicotiniques a l’acetylcholine (nAChRs) retrouves dans l’epithelium respiratoire. Etant donne que le polymorphisme nucleotidique simple (SNP) du gene CHRNA5 codant pour la sous-unite α5 des nAChRs (rs16969968) est associe a la diminution de la fonction respiratoire dans la BPCO, nous proposons d’etudier le role du SNPα5 dans les remaniements et les alterations de la fonctionnalite de l’epithelium des voies aeriennes. Methodes Le gene chrna5 a ete genotype sous forme sauvage, heterozygote et homozygote a partir d’ADN cellulaires issus de brossages bronchiques (n = 39) dans le but d’obtenir la repartition du SNPα5 dans l’epithelium des voies aeriennes humaines. En parallele, des coupes histologiques ont ete realisees a partir de tissus pulmonaires issus de patients BPCO (n = 10) et non-BPCO (n = 11) afin de comprendre le lien entre le polymorphisme et les caracteristiques morpho-histologiques de l’epithelium respiratoire par immunohistochimie. Resultats L’analyse des coupes histologiques a permis de mettre en evidence l’association significative du polymorphisme α5 avec une augmentation de l’hyperplasie des cellules basales (15,71 ± 6,86 %), ainsi qu’une diminution du nombre de cellules ciliees (28,25 ± 6,62 %) independamment de la pathologie. Par ailleurs, les etudes de genotypage ont montre que plus de la moitie de la population etudiee exprime le SNPα5, ce dernier etant associe a une diminution de la fonction respiratoire et a l’augmentation de l’emphyseme. Conclusions Ces resultats suggerent une influence du SNPα5 sur le remodelage de l’epithelium respiratoire et sur les alterations de la fonction respiratoire. Par la suite, il sera interessant d’etudier l’effet in vitro de la nicotine associee au SNP sur l’expression des cellules epitheliales (ciliees, basales, caliciformes) ainsi que sur l’expression de cytokines pro-inflammatoires au cours de la differenciation cellulaire.