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Objectives This study aimed to estimate the prevalence of ANCA-associated vasculitis (AAV). That is, granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), in Southern France in 2018, and evaluate differences among Europeans and non-Europeans. Methods This population-based, cross-sectional study used four sources (hospitals, community-based physicians, laboratories, National Health Insurance) to identify adults ≥15 years diagnosed with GPA, MPA or EGPA, living in Hérault and Gard in 2018. Cases were defined using the ACR/EULAR classification criteria, and if necessary, the European Medicines Agency algorithm. Prevalence estimates were standardised to the world population and capture-recapture analysis was used to assess the comprehensiveness of the estimation. The influence of geographical origin was evaluated. Results A total of 202 patients were selected, with 86 cases of GPA (42.6%), 85 cases of MPA (42.1%) and 31 cases of EGPA (15.3%). The standardised prevalence estimates per million inhabitants for 2018 were: 103 (95%CI 84–125) for AAV, 48 (95%CI 35–64) for GPA, 39 (95%CI 28–53) for MPA and 16 (95%CI 9–26) for EGPA, 36 (95%CI 25–50) for anti-PR3 positive AAV, 46 (95%CI 34–61) for anti-MPO positive AAV, and 16 (95%CI 9–26) for ANCA-negative AAV. The global estimation of comprehensiveness by capture-recapture analysis was 80.5%. The number of AAV cases was higher for non-European residents (P  = 0.001), particularly for MPA (P   <  0.0001). Conclusion We provide a new estimate of AAV prevalence in France and show a higher prevalence of MPA in non-European patients. [ABSTRACT FROM AUTHOR]

Objective Pulmonary arterial hypertension (PAH) is a leading cause of death in MCTD. We aimed to describe PAH in well-characterized MCTD patients. Methods MCTD patients enrolled in the French Pulmonary Hypertension Registry with a PAH diagnosis confirmed by right heart catheterization were included in the study and compared with matched controls: MCTD patients without PAH, SLE patients with PAH and SSc patients with PAH. Survival rates were estimated by the Kaplan–Meier method and risk factors for PAH in MCTD patients and risk factors for mortality in MCTD-PAH were sought using multivariate analyses. Results Thirty-six patients with MCTD-PAH were included in the study. Comparison with MCTD patients without PAH and multivariate analysis revealed that pericarditis, polyarthritis, thrombocytopenia, interstitial lung disease (ILD) and anti-Sm antibodies were independent predictive factors of PAH/PH in MCTD. Estimated survival rates at 1, 5 and 10 years following PAH diagnosis were 83%, 67% and 56%, respectively. MCTD-PAH presentation and survival did not differ from SLE-PAH and SSc-PAH. Multivariate analysis revealed that tobacco exposure was an independent factor predictive of mortality in MCTD-PAH. Conclusion PAH is a rare and severe complication of MCTD associated with a 56% 10-year survival. We identified ILD, pericarditis, thrombocytopenia and anti-Sm antibodies as risk factors for PAH in MCTD and tobacco exposure as a predictor of mortality in MCTD-PAH. [ABSTRACT FROM AUTHOR]

Introduction: Discriminating asthma from chronic obstructive pulmonary disease (COPD) using medico-administrative databases is challenging but necessary for medico-economic analyses focusing on respiratory diseases. Artificial intelligence (AI) may improve dedicated algorithms.Objectives: To assess performance of different AI-based approaches to distinguish asthmatics from COPD patients in medico-administrative databases where the clinical diagnosis is absent. An "Asthma COPD Overlap" category was defined to further test whether AI can detect complexity.Methods: This study included 178,962 patients treated by two "R03" treatment prescriptions at least from January 2016 to December 2018 and managed by either a general practitioner and/or a pulmonologist participating in a permanent longitudinal observatory of prescription in ambulatory medicine (LPD). Clinical diagnoses are available in this database and were used as gold standards to develop diagnostic rules. Three types of AI approaches were explored using data restricted to demographics and treatment dispensations: multinomial regression, gradient boosting and recurrent neural networks (RNN). The best performing model (based on metric properties) was then applied to estimate the size of asthma and COPD populations based on a database (LRx) of treatment dispensations between July, 2018 and June, 2019.Results: The best models were obtained with the boosting approach and RNN, with an overall accuracy of 68%. Performance metrics were better for asthma than COPD. Based on LRx data, the extrapolated numbers of patients treated for asthma and COPD in France were 3.7 and 1.2 million, respectively. Asthma patients were younger than COPD patients (mean, 49.9 vs. 72.1 years); COPD occurred mostly in men (68%) compared to asthma (33%).Conclusion: AI can provide models with acceptable accuracy to distinguish between asthma, ACO and COPD in medico-administrative databases where the clinical diagnosis is absent. Deep learning and machine learning (RNN) had similar performances in this regard. [ABSTRACT FROM AUTHOR]

Background: Whether the COVID-19 pandemic impacts Positive Airway Pressure (PAP) adherence over the long-term is unknown and only preliminary short-term data have been reported. Methods: With the aim of describing the impact of the first and second waves of COVID-19 on PAP adherence during 2020 in France, we designed a cross-sectional study of Sleep-Apnea (SA)-patients under PAP telemonitoring. To examine PAP adherence in adult SA patients, we assessed de-identified data from a non-profit healthcare provider database during the period January 1, 2019 to December 31, 2020. Included patients met the following criteria: (i) PAP-treated for at least 4 months before January 1, 2019 and with continuous PAP during both 2019 and 2020; (ii) ≥ 360 daily PAP telemonitored data per year. For PAP adherence, data were collected using the PAP-software. Results: 8477/10482 patients were finally included in the analysis [72.4% male, median age 70 years (IQ25–75: 61–77], 25.6% < 62 years old, initial Apnea–Hypopnea Index (AHI) of 41 (31–59)/h. Median PAP adherence was 7.21 (6.12–8.10) h/day in 2020 versus 7.12 (6.05–8.02) h/day in 2019, p < 0.001. The median difference in PAP adherence between the first 2020 lockdown and the corresponding 2019 weeks was 9.75 (CI95% 8.75–10.75) min/day, p < 0.001. The median difference in PAP adherence between the second 2020 lockdown and the corresponding 2019 weeks was 5.00 (CI95% 4.00–6.00) min/day, p < 0.001. If we consider the minimal clinically important difference of 30 min for PAP adherence, 30.4% and 26% of the patients increased their PAP adherence by at least 30 min during the first and second lockdowns respectively; 17.6% and 19.3% of the patients lowered their PAP adherence by at least 30 min in the first and second lockdowns, respectively. Conclusion: During the first and second lockdowns, the COVID-19 pandemic had a clinically irrelevant effect on PAP adherence for the study population. Future studies are needed to describe COVID-19 pandemic impact on PAP adherence not only for long-term PAP-treated SA patients but also for incident cases. Trial registration The COVADENE study was registered on March 1st, 2021 on ClinicalTrials.gov (Identifier: NCT04775966) [ABSTRACT FROM AUTHOR]

The use of cyclophosphamide in patients with acute exacerbation of idiopathic pulmonary fibrosis (IPF) is unknown. Our study was designed to evaluate the efficacy and safety of four cyclophosphamide pulses in addition to high-dose methylprednisolone in this population. In this double-blind, placebo-controlled trial done in 35 departments across 31 hospitals in France, adult patients (≥18 years) with acute exacerbation of IPF and those with suspected acute exacerbation of IPF were randomly assigned in a 1:1 ratio using a web-based system to receive either intravenous pulses of cyclophosphamide (600 mg/m2) plus uromitexan as haemorrhagic cystitis prophylaxis (200 mg/m2) at the time of cyclophosphamide administration and then again, 4 h later, or placebo at days 0, 15, 30, and 60. Random assignment was stratified according to the severity of IPF and was block-balanced with variable block sizes of four or six patients. Patients receiving mechanical ventilation, with active infection, with active cancer, or who were registered on the lung transplant waiting list were excluded. All patients received standardised high-dose glucocorticoids. The investigators, patients, and the sponsor were masked to the treatment assignments. The primary endpoint was 3-month all-cause mortality, analysed by a χ2 test adhering to an intention-to-treat principle. The trial is now complete and registered with ClinicalTrials.gov , NCT02460588. Between Jan 22, 2016, and July 19, 2018, 183 patients were assessed for eligibility, of whom 120 patients were randomly assigned and 119 patients (62 [52%] with severe IPF) received at least one dose of cyclophosphamide (n=60) or placebo (n=59), all of whom were included in the intention-to-treat analysis. The 3-month all-cause mortality was 45% (27/60) in patients given cyclophosphamide compared with 31% (18/59) in the placebo group (difference 14·5% [95% CI −3·1 to 31·6]; p=0·10). Similar results were found after adjustment by IPF severity (odds ratio [OR] 1·89 [95% CI 0·89–4·04]). The risk of death at 3 months, independent of the treatment received, was higher with severe than non-severe IPF (OR 2·62 [1·12–6·12]) and was lower with the use of antifibrotic therapy (OR 0·33 [0·13–0·82]). Adverse events were similar between groups by 6 months (25 [42%] in the cyclophosphamide group vs 30 [51%] in the placebo group) and their proportion, including infections, did not differ. Overall infection was the main adverse event and occurred in 20 (33%) of 60 patients in the cyclophosphamide group versus 21 (36%) of 59 patients in the placebo group. In patients with acute exacerbation of IPF, adding intravenous cyclophosphamide pulses to glucocorticoids increased 3-month mortality. These findings provide evidence against the use of intravenous cyclophosphamide in such patients. Programme Hospitalier de Recherche Clinique of the French Ministry of Health (PHRC 2014–502), Roche Pharmaceuticals. [ABSTRACT FROM AUTHOR]

Oral corticosteroids (OCS) are frequently used as relievers for acute asthma and controllers for severe asthma. However, the relief offered by OCS is counterbalanced by adverse effects. We aimed to describe how patients perceive OCS treatment benefits and risks, and how this could affect their adherence to the treatment. Patients aged ≥18 years with asthma registered with Carenity, an online patient community, were invited to respond to a questionnaire containing 35 closed and 3 open questions to assess their asthma and perceptions of OCS. 268/300 respondents were receiving or had received OCS for asthma (58 for long-term use and 107 for short-term use). The mean age at diagnosis was 21.3 years. 66% had uncontrolled asthma (GINA control score 3 or 4). Although 42% perceived OCS to be efficacious, 46% mentioned adverse effects. Respondents were mostly satisfied with OCS (median = 7.0/10), particularly for efficacy (median = 8.0/10). Respondents reported having strategies to avoid OCS, mainly because of adverse effects. 26% of respondents had previously reduced or stopped OCS; this proportion was 22% for short-term OCS users and 36% for long-term users. 15% of the respondents not receiving long-term OCS would take the treatment without doing anything else if long-term OCS were prescribed; 42% would seek an alternative treatment. OCS for asthma is perceived efficient but associated with adverse effects. Patients seek alternative treatment. [ABSTRACT FROM AUTHOR]

Background: The course of chronic obstructive pulmonary disease (COPD) is punctuated by exacerbations, most often of infectious origin, responsible for many intensive care unit (ICU) and intermediate care unit (IMCU) admissions. Our objective was to study in-hospital mortality during severe COPD exacerbations in ICU and IMCU based on the performance of bronchoscopy. Methods: A retrospective analysis was carried out on stays in ICUs for COPD exacerbation from the French Programme for the Medicalisation of Information Systems databases for the years 2014 and 2015. Propensity score matching of stays made it possible to constitute two comparable groups on the factors of excess mortality described in the literature (age, sex, SAPS 2, type of admission and bronchial tumour). Results: We identified 14,491 stays for COPD exacerbation in ICUs, 2586 of which received a bronchoscopy. Mortality was significantly higher in the fibroscopy group (31.32% versus 19.8%). After propensity score matching, we found an excess of mortality in the intervention group (OR = 1.749 [1.516–2.017]) associated with a significantly longer length of stay. The main diagnoses associated with an increased risk of death were pulmonary embolism (OR = 3.251 [1.126–9.384]), bacterial pneumonia (OR = 1.906 [1.173–3.098]) and acute respiratory failure (OR = 1.840 [1.486–2.278]). Conclusions: Performing bronchoscopy during ICU hospitalisations for severe COPD exacerbations was associated with increased mortality. This increased mortality appears to be related to a bias in patient selection with a procedure reserved for patients with the adverse course. [ABSTRACT FROM AUTHOR]

Background: Dupilumab is a monoclonal anti‐IL‐4Rα antibody developed for the treatment of severe asthma (SA). An early access programme for dupilumab was opened in France in SA patients experiencing unacceptable steroids side‐effects and/or life‐threatening exacerbations. Objective: To assess changes in asthma control between baseline and 12 months of treatment. Methods: Multi‐centre (n = 13) retrospective real‐life cohort study. This study is registered on ClinicalTrials.gov (NCT04022447). Results: Overall, 64 patients with SA (median age 51, interquartile range [44‐61]; 53% females) received dupilumab as add‐on therapy to maximal standard of care; and 76% were on oral daily steroids at baseline. After 12 months, median asthma control test score improved from 14 [7‐16] to 22 [17‐24] (P <.001); median forced expiratory volume in 1 seconds increased from 58% [47‐75] to 68% [58‐88] (P =.001); and daily prednisone dose was reduced from 20 [10‐30] to 5 [0‐7] mg/d (P <.001). Annual exacerbations decreased from 4 [2‐7] to 1 [0‐2] (P <.001). Hypereosinophilia ≥1500/mm3 was observed at least once during follow‐up in 16 patients (25%), persisting after 6 months in 8 (14%) of them. Increase in blood eosinophil count did not modify the clinical response during the study period. Injection‐site reaction was the most common side effect (14%). Three deaths were observed, none related to treatment by investigators. Conclusion & clinical relevance: In this first real‐life cohort study of predominantly steroid‐dependent SA, dupilumab significantly improved asthma control and lung function and reduced oral steroids use and exacerbations rate. Despite limitations due to the retrospective study, these results are consistent with controlled trials efficacy data. Further studies are required to assess the clinical significance and long‐term prognosis of sustained dupilumab‐induced hypereosinophilia. [ABSTRACT FROM AUTHOR]

Keywords: COVID-19; droplet; tuberculosis EN COVID-19 droplet tuberculosis 766 768 3 06/22/20 20200701 NES 200701 Whether Carl Flügge is a medical hero is no longer debated today (Fig. Imaging using high-resolution computed tomography (HRCT) scan, with typical features seen during the COVID pandemic may also be explored for TB in high-income countries, especially to discriminate between active and latent TB infection. In this period of epidemic decline, remaining COVID-19 clusters are unsurprisingly linked with already identified regional TB clusters such as squats and all places of precarious collective housing, where social distancing and barriers are impossible to access or apply. [Extracted from the article]

Background: Precapillary pulmonary hypertension (PH), and particularly pulmonary arterial hypertension (PAH), is a life-threatening complication of connective tissue diseases (systemic sclerosis, systemic lupus erythematosus, and mixed connective tissue disease). The relationship between PH and rheumatoid arthritis (RA) has not been clearly established. Objectives: The aim of the study was to evaluate the relationship between precapillary PH and RA. Methods: We identified patients with PH and suspected RA included in the French PH Registry between 1 May 2004 and 31 December 2012 and evaluated the prevalence of confirmed RA in this population. RA phenotypes, clinical, functional, and hemodynamic data, and patient outcomes were recorded. Results: RA was confirmed in 20 patients (70% female; mean age 52 years) with precapillary PH, including 10 patients with PAH, 6 with severe PH due to lung disease, and 4 with chronic thromboembolic PH. The prevalence of RA was 0.35% (95% CI: 0.23–0.54) in the French PH Registry and 0.58% (95% CI: 0.30–1.11) in idiopathic PAH, comparable to that in the general population. The RA phenotype was characterized by the presence of specific RA autoantibodies and joint erosions in 75% of the patients. The outcomes of PH in the RA patients were unremarkable compared to those in other patients from the registry, and RA therapies had no major impact on the cardiopulmonary parameters. Conclusion: When precapillary PH occurs in RA patients, all PH subsets may be identified. The RA prevalence in the French PH Registry is similar to that in the general population, which does not support a specific association or an indication for PH screening in RA patients. [ABSTRACT FROM AUTHOR]

Background: Bronchial epithelium plays a key role in orchestrating innate and adaptive immunity. The fate of ex vivo airway epithelial cultures growing at the air liquid interface (ALI) derived from human endobronchial biopsies or brushings is not easy to predict. Calibrating and differentiating these cells is a long and expensive process requiring rigorous expertise. Pinpointing factors associated with ALI culture success would help researchers gain further insight into epithelial progenitor behavior.Methods: A successful ALI culture was defined as one in which a pseudostratified epithelium has formed after 28 days in the presence of all differentiated epithelial cell types. A 4-year prospective bi-center study was conducted with adult subjects enrolled in different approved research protocols.Results: 463 consecutive endobronchial biopsies were obtained from normal healthy volunteers, healthy smokers, asthmatic patients and smokers with COPD. All demographic variables, the different fiber optic centers and culture operators, numbers of endo-bronchial biopsies and the presence of ciliated cells were carefully recorded. Univariate and multivariate models were developed. A stepwise procedure was used to select the final logistic regression model. ALI culture success was independently associated with the presence of living ciliated cells within the initial biopsy (OR = 2.18 [1.50-3.16], p < 0.001).Conclusion: This finding highlights the properties of the cells derived from the epithelium dedifferentiation process. The preferential selection of samples with ciliated beating cells would probably save time and money. It is still unknown whether successful ALI culture is related to indicators of general cell viability or a purported stem cell state specifically associated with ciliated beating cells. [ABSTRACT FROM AUTHOR]

Rationale: The relationship between the initial treatment strategy and survival in pulmonary arterial hypertension (PAH) remains uncertain. Objectives: To evaluate the long-term survival of patients with PAH categorized according to the initial treatment strategy. Methods: A retrospective analysis of incident patients with idiopathic, heritable, or anorexigen-induced PAH enrolled in the French Pulmonary Hypertension Registry (January 2006 to December 2018) was conducted. Survival was assessed according to the initial strategy: monotherapy, dual therapy, or triple-combination therapy (two oral medications and a parenteral prostacyclin). Measurements and Main Results: Among 1,611 enrolled patients, 984 were initiated on monotherapy, 551 were initiated on dual therapy, and 76 were initiated on triple therapy. The triple-combination group was younger and had fewer comorbidities but had a higher mortality risk. The survival rate was higher with the use of triple therapy (91% at 5 yr) as compared with dual therapy or monotherapy (both 61% at 5 yr) ( P  < 0.001). Propensity score matching of age, sex, and pulmonary vascular resistance also showed significant differences between triple therapy and dual therapy (10-yr survival, 85% vs. 65%). In high-risk patients ( n  = 243), the survival rate was higher with triple therapy than with monotherapy or dual therapy, whereas there was no difference between monotherapy and double therapy. In intermediate-risk patients ( n  = 1,134), survival improved with an increasing number of therapies. In multivariable Cox regression, triple therapy was independently associated with a lower risk of death (hazard ratio, 0.29; 95% confidence interval, 0.11-0.80; P  = 0.017). Among the 148 patients initiated on a parenteral prostacyclin, those on triple therapy had a higher survival rate than those on monotherapy or dual therapy. Conclusions: Initial triple-combination therapy that includes parenteral prostacyclin seems to be associated with a higher survival rate in PAH, particularly in the youngest high-risk patients.

Background: Pulmonary venoocclusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) predominantly characterized by pulmonary vein and capillary involvement. An association between chemotherapy, in particular mitomycin C (MMC), and PVOD has been reported., Research Question: What are the characteristics of MMC-induced PVOD, and what is the prognosis for patients with MMC-induced PVOD?, Study Design and Methods: We report the clinical, functional, radiologic, and hemodynamic characteristics at diagnosis and outcomes of patients with PVOD from the French PH Registry after exposure to MMC. The results are expressed as the median (minimum-maximum)., Results: From June 2011 to December 2018, 17 incident cases of MMC-induced PVOD were identified. At diagnosis, these patients had severe clinical and functional impairment, with 12 patients having a New York Heart Association (NYHA) functional class of III or IV and a 6-min walk distance of 220 (0-465) m. Right heart catheterization confirmed severe precapillary PH with a mean pulmonary artery pressure of 38 (30-52) mm Hg, a cardiac index of 2.2 (1.5-4) L/(min × m 2 ), and pulmonary vascular resistance of 8.3 (5.1-14.5) Wood units. The diffusing capacity of the lungs for carbon monoxide was markedly decreased at 31% (20%-51%) of the theoretical values associated with severe hypoxemia. MMC was withdrawn for all patients, and 14 patients received specific pulmonary arterial hypertension (PAH) therapies. Among these patients, mild but statistically insignificant improvements were observed in NYHA functional class (P = .10), 6-min walk distance (P = .09), and pulmonary vascular resistance (-4.7 Wood units; P = .052) at reassessment (median delay of 4.8 months). Three patients experienced pulmonary edema requiring the cessation or reduction of PAH treatment. The median overall survival was 20 months, and the 6-, 12-, and 24-month survival rates were 76%, 58%, and 18%, respectively., Interpretation: PVOD after MMC treatment is a rare but life-threatening complication associated with a poor prognosis despite MMC withdrawal and PAH-specific therapy., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Mepolizumab was available in France as part of an early access programme for patients with severe eosinophilic asthma (nominative autorisation temporaire d'utilisation [temporary use authorisation] (nATU)) before its commercialisation. This study aimed to characterise patients who received mepolizumab in the nATU., Methods: This retrospective, observational study analysed data from the hospital medical records of patients up to 24 months after treatment initiation. Study objectives were to describe patient baseline characteristics, the evolution of disease severity and treatment modifications during follow-up; safety was also investigated., Findings: Overall, 146 patients who received ≥1 dose of mepolizumab were included. At inclusion, patients had a mean age of 58.2 years with a mean severe asthma duration of 13.4 years, and 37.0% had respiratory allergies. Patients experienced, on average, 5.8 exacerbations per patient per year at baseline, 0.6 and 0.5 of which required hospitalisation and emergency department visits, respectively. These values improved to 0.6, 0.1 and 0.1 exacerbations per patient per year, respectively, at 24 months of follow-up. Most patients (92.8%) were using oral corticosteroids at baseline, compared with 34.7% by 24 months of follow-up. Moreover, mean blood eosinophil counts improved from 722 cells·µL -1 at baseline to 92 cells·µL -1 at 24 months of follow-up; lung function and asthma control followed a similar trend., Interpretation: Results confirm findings from clinical trials, demonstrating that mepolizumab is associated with important improvements in several clinically meaningful outcomes and has a favourable safety profile in a population with severe eosinophilic asthma, outside of the controlled environment of a clinical trial., Competing Interests: Conflict of interest: C. Taillé reports that the study and manuscript preparation support was funded by GlaxoSmithKline; grants and personal fees for consultancy and lectures from GlaxoSmithKline, AstraZeneca, Novartis, Roche, Sanofi, Chiesi and TEVA, outside the submitted work. Conflict of interest: P. Chanez reports that the study and manuscript preparation support was funded by GlaxoSmithKline; personal fees for advisory board work from Almirall, grants and personal fees for lectures from Alk-Abello, Boston Scientific and Centocor, grants and personal fees for consultancy, advisory board work and lectures from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis and Teva, personal fees for consultancy and advisory board work from Johnson & Johnson and Sanofi, personal fees for consultancy from Merck Sharp & Dohme, grants from Roche, outside the submitted work. Conflict of interest: G. Devouassoux reports that the study and manuscript preparation support was funded by GlaxoSmithKline; grants and personal fees for consultancy and meeting participation from Novartis Pharma, AstraZeneca, GlaxoSmithKline, ALK, TEVA, personal fees for consultancy and meeting participation from MundiPharma, grants and personal fees for consultancy from Boehringer Ingelheim, personal fees for consultancy from Vivisol, grants from Sanofi, Vitalair, AB Science, Amgen, Lilly and Roche, grants and personal fees for meeting participation from Chiesi and MSD, personal fees for meeting participation from AGIR a dom, Orkyn, Stallergene and Takeda, outside the submitted work. Conflict of interest: A. Didier reports that the study and manuscript preparation support was funded by GlaxoSmithKline; personal fees for consultancy and meeting participation from Novartis Pharma, AstraZeneca and GlaxoSmithKline, personal fees for consultancy from Chiesi, Boehringer Ingelheim, Mundi Pharma, TEVA, ALK and Menarini, outside the submitted work. Conflict of interest: C. Pison reports that the study and manuscript preparation support was funded by GlaxoSmithKline; grants, personal fees for lectures and non-financial support for meeting attendance from Novartis, AstraZeneca, GlaxoSmithKline, Chiesi, Boehringer Ingelheim and Sanofi, grants and personal fees for consultancy and lectures from Mundi Pharma and MSD, outside the submitted work. Conflict of interest: G. Garcia reports that the study and manuscript preparation support was funded by GlaxoSmithKline; personal fees for advisory board work from Novartis and Sanofi, personal fees for advisory board work and consultancy from AstraZeneca, personal fees for consultancy from GlaxoSmithKline, non-financial support for travel from Oxyvie, outside the submitted work. Conflict of interest: J. Charriot reports that the study and manuscript preparation support was funded by GlaxoSmithKline. Conflict of interest: S. Bouée reports that the study and manuscript preparation support was funded by GlaxoSmithKline; is an employee of CEMKA, and reports grants from GlaxoSmithKline, outside the submitted work. Conflict of interest: A. Gruber reports that the study and manuscript preparation support was funded by GlaxoSmithKline; and is an employee and shareholder of GlaxoSmithKline, outside the submitted work. Conflict of interest: C. Pribil reports that the study and manuscript preparation support was funded by GlaxoSmithKline; and is an employee and shareholder of GlaxoSmithKline, outside the submitted work. Conflict of interest: A. Bourdin reports that the study and manuscript preparation support was funded by GlaxoSmithKline; personal fees for clinical trial work from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Chiesi, Novartis and Sanofi, outside the submitted work. Conflict of interest: M. Humbert reports that the study and manuscript preparation support was funded by GlaxoSmithKline; personal fees for consultancy, speaking at conferences, and participation in clinical research projects from AstraZeneca, GlaxoSmithKline, Novartis, Roche, Sanofi and TEVA, outside the submitted work., (Copyright ©ERS 2020.)

Background: Severe asthma (SA) is defined by treatment intensity. The availability of national databases allows accurate estimation of the prevalence, long-term outcomes, and costs of SA., Objective: To provide accurate information on SA, focusing on comorbidities, mortality, health care resource consumption, and associated costs., Methods: A cohort of patients with SA identified in 2012 was extracted from a French representative claims database and followed for 3 years. Their characteristics, comorbidities, mortality, and direct costs were compared with a matched control group without asthma., Results: A total of 690 patients with SA were matched to 2070 patients without asthma (mean age, 61 years; 65.7% women). The prevalence of SA was estimated to be 0.18% to 0.51% of the French adult population. Comorbidities were more frequent in patients with SA (73.9% suffered from cardiovascular disease vs 54.3% in controls; P < .001). A total of 58.7% of patients with SA used oral corticosteroids (OCS) in 2012 with a mean intake of 3.3 boxes/year/patient and 9% received ≥6 dispensings of OCS. A total of 6.7% were treated by omalizumab. Patients with SA were more frequently hospitalized (33.2% vs 19.7%; P < .001), more frequently consulted a general practitioner (97.8% vs 83.9%; P < .001) (9.8 ± 6.8 vs 6.2 ± 5.3 consultations/year; P < .001), and 31% have consulted a private respiratory physician. Compared with controls, 3-year cumulative mortality was higher in SA (7.1% vs 4.5%; P = .007). Direct medical cost was $9227 versus $3950 (P < .001) mostly driven by medication costs., Conclusions: The prevalence of SA in the French adult population is at least 18 of 10,000. Burden of disease is high with respect to comorbidities, mortality, and asthma-related health care resource use., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Endobronchial coil treatment (ECT) is a minimally invasive procedure developed for palliative care of patients with severe emphysema. ECT has demonstrated a decrease in hyperinflation, an improvement in quality of life, and an acceptable safety profile in randomized controlled trials (RCTs). Because alpha-1 antitrypsin deficiency (AATD) is a classical exclusion criterion in RCTs, there is no available data for ECT in AATD. In this post hoc analysis of the REVOLENS study (Réduction volumique endobronchique par spirales; ClinicalTrials.gov Identifier: NCT01822795), a multicenter 1:1 RCT which compared bilateral ECT with usual care in severe emphysema, we analyzed the efficacy and safety results at 1 year in six patients with AATD (five males, one female; mean age: 52±9 years) who underwent ECT. A significant decrease in hyperinflation (0.35 L decrease in residual volume [RV]) was observed in four out of six patients at 6 months and three out of six patients at 12 months, and an improvement in quality of life (improvement of 4 points in the St George's Respiratory Questionnaire [SGRQ]) was observed in four out of six patients at both 6 and 12 months. Efficacy results at 6 and 12 months from the six AATD patients were compared with 84 non-AATD patients who underwent ECT, and no statistically significant differences were found for FEV 1 , RV, 6MWT score and SGRQ score. Respiratory-related serious adverse event was limited to pneumonia in one AATD patient at 1 year post-ECT. This post hoc study suggests that AATD patients may have similar efficacy and safety outcomes at 1 year as non-AATD patients. Because of the paucity of available data, appropriately powered studies are needed to determine the effects of ECT in AATD., Competing Interests: Disclosure Gaëtan Deslee has been involved as an investigator in previous studies sponsored by BTG/PneumRx, and received travel reimbursements and speaker fees for educational sessions and consulting from BTG/PneumRx. Hervé Mal received honorarium from Boehringer, Bayer, Roche, Astellas, Chiesi, Actellion, Pfizer, Novartis, and GlaxoSmithKline outside the submitted work. Hervé Dutau received travel reimbursements and speaker fees for educational sessions and consulting from BTG/PneumRx. Arnaud Bourdin received honorarium from Astra Zeneca, GlaxoSmithKline, Boehringer, Novartis, Teva, Chiesi, Actellion, Gilead, and Roche outside the submitted work. Jean Michel Vergnon received travel reimbursements and speaker fees for educational sessions from BTG/PneumRx. Christophe Pison received honorarium from BTG/PneumRx and his hospital received funds to conduct trials from Holaira, PulmonX, and BTG/PneumRx. Charles Hugo Marquette has been involved as an investigator in previous studies sponsored by BTG/PneumRx, and received travel reimbursements and speaker fees for educational sessions and consulting from BTG/PneumRx. The authors report no other conflicts of interest in this work.

Background: To examine trends in mortality, costs and in-hospital management and outcomes of severe COPD exacerbations admitted in France., Methods: Patients hospitalized from 2007 to 2012 with COPD exacerbation as the primary diagnosis were identified from the exhaustive French medico-administrative hospitalizations database records. Four groups of severe COPD exacerbations were defined: hospitalisation in a general ward (GW) without acute respiratory failure (ARF), GW with ARF, ICU without invasive mechanical ventilation (MV), and ICU with MV., Results: A 15.48 % increase in admissions from 113 276 in 2007 to 133 497 in 2012 was recorded. Age (+9.9 months), gender (-2.5 % of male) and length of stay (-0.29 day) slightly changed while the number of ICU admissions increased markedly (+41.78 %). In-hospital mortality rates increased (+8.06 %, p < .001) and followed seasonal variations peaking in winter. Total hospitalizations costs increased from 602 to 678 millions euros (+12.6 %). Pneumonia-related mortality increased (+37.2 %). A progressive replacement of chest X-ray by CT scan was observed (-41.3 % vs +31.7 %) while fewer spirometries (-13.7 %) and bronchoscopies (-22.6 %) were performed., Conclusion: The incidence of severe COPD exacerbations and the proportion of ICU-managed patients are still increasing in France. Rising total costs and mortality rates especially related to pneumonia advocate for rethinking COPD management plans., Trial Registration: Not applicable.

Objectives: to understand epidemiological trends in severe COPD exacerbations through analyzes of hospitalizations and deaths during three consecutive years in a French administrative region area., Methods: Medico-administrative records of hospitalizations for COPD exacerbations were sorted from 2010 to 2012 using selected International Classification of Diseases (ICD10) codes. Four groups of hospitalization for COPD severe exacerbations were elicited leading to hospitalizations (general ward without respiratory failure, general ward with acute respiratory distress, ICU without mechanical ventilation, ICU with mechanical ventilation)., Results: Data extraction identified 5007, 4986 and 5359 admissions related to 4136, 4155 and 4460 patients in 2010, 2011 and 2012, respectively. Marked seasonal variations were observed. Duration of stay (median (IQR), 7 (7) vs 9 (8) vs 10 (9) vs 14 (16) days, P < .001), death rates (3.6% vs 14.2% vs 14.4% vs 21.2%, P < .01), number of co-morbid conditions (median (IQR), 2 (2) vs 2 (2) vs 4 (5) vs 4 (4.5), P < .01), type of institution (64.9% in public institution vs 79.9% vs 87.8% vs 76.6%, P < .01) were significantly associated with the hospitalization group and more than 8% of admissions led to death (3% to 24%). Age, type of institution and past hospitalizations were independent risk factors for deaths. Readmissions were infrequent but mainly related to the worsening of the co-morbid conditions., Conclusion: COPD severe exacerbations are frequent and lead to an important numbers of deaths related to the severity of acute respiratory failure and the number of co-morbid conditions.

Randomized studies show that the best results come from patient-focused educational programs based on self-management (written and individualized action plan, self-monitoring, and regular medical review). The simple provision of information about asthma does not improve health outcomes. Teenagers with asthma are the most fragile patients, because of the lack of specific management for them. Repeated sessions are recommended and educational programs, started in childhood, might make it possible to prevent or at least decrease the risks of non-adherence during adolescence. The absence of consensus on educational interventions impedes the legibility of their impact.