41 results on '"Bourdin, Arnaud"'
Search Results
2. The HHIP gene: from a candidate to an established participant in COPD susceptibility.
- Author
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Lahmar Z, Bergougnoux A, and Bourdin A
- Subjects
- Humans, Lung metabolism, Carrier Proteins, Membrane Glycoproteins metabolism, Pulmonary Disease, Chronic Obstructive genetics
- Abstract
Competing Interests: Declaration of interests Bourdin A: GSK—non-financial support during the conduct of the study; Acceleron Pharma, Actelion, Galapagos, Merck Sharp & Dohme, Nuvaira, Pulmonx, United Therapeutics, Vertex Pharmaceuticals—other; Boehringer Ingelheim—grants, personal fees; AstraZeneca, Chiesi, GSK, Regeneron Pharmaceuticals Inc., Sanofi—personal fees. Bergougnoux A: no conflict of interest. Lahmar Z: no conflict of interest.
- Published
- 2024
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3. Elevated Blood Pressure Occurs without Endothelial Dysfunction in a Rat Model of Pulmonary Emphysema.
- Author
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Desplanche E, Grillet PE, Wynands Q, Bideaux P, Alburquerque L, Charrabi A, Bourdin A, Cazorla O, Gouzi F, and Virsolvy A
- Subjects
- Male, Rats, Animals, Bisoprolol, Blood Pressure, Rats, Wistar, Stroke Volume, Pulmonary Emphysema, Heart Failure, Hypertension, Pulmonary Disease, Chronic Obstructive, Emphysema
- Abstract
Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease involving airway closure and parenchyma destruction (emphysema). Cardiovascular diseases are the main causes of morbi-mortality in COPD and, in particular, hypertension and heart failure with preserved ejection fraction (HFpEF). However, no mechanistic link has currently been established between the onset of COPD, elevated blood pressure (BP) and systemic vascular impairment (endothelial dysfunction). Thus, we aimed to characterize BP and vascular function and remodeling in a rat model of exacerbated emphysema focusing on the role of sympathetic hyperactivity. Emphysema was induced in male Wistar rats by four weekly pulmonary instillations of elastase (4UI) and exacerbation by a single dose of lipopolysaccharides (LPS). Five weeks following the last instillation, in vivo and ex vivo cardiac and vascular functions were investigated. Exacerbated emphysema induced cardiac dysfunction (HFpEF) and a BP increase in this COPD model. We observed vasomotor changes and hypotrophic remodeling of the aorta without endothelial dysfunction. Indeed, changes in contractile and vasorelaxant properties, though endothelium-dependent, were pro-relaxant and NO-independent. A β1-receptor antagonist (bisoprolol) prevented HFpEF and vascular adaptations, while the effect on BP increase was partial. Endothelial dysfunction would not trigger hypertension and HFpEF in COPD. Vascular changes appeared as an adaptation to the increased BP. The preventing effect of bisoprolol revealed a pivotal role of sympathetic hyperactivation in BP elevation. The mechanistic link between HFpEF, cardiac sympathetic activation and BP deserves further studies in this exacerbated-emphysema model, as well as in COPD patients.
- Published
- 2023
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4. Diastolic Cardiomyopathy Secondary to Experimentally Induced Exacerbated Emphysema.
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Grillet PE, Desplanche E, Wynands Q, Gouzi F, Bideaux P, Fort A, Scheuermann V, Lacampagne A, Virsolvy A, Thireau J, de Tombe P, Bourdin A, and Cazorla O
- Subjects
- Male, Rats, Animals, Lipopolysaccharides, Stroke Volume physiology, Rats, Wistar, Heart Failure complications, Pulmonary Emphysema pathology, Pulmonary Disease, Chronic Obstructive pathology, Emphysema, Cardiomyopathies complications
- Abstract
Chronic obstructive pulmonary disease (COPD) is a clinical entity of increasing significance. COPD involves abnormalities of the airways and, in emphysema, parenchymal pulmonary destruction. Cardiovascular disease has emerged as a significant comorbidity to COPD. Heart failure with preserved ejection fraction (HFpEF) appears to be particularly associated with COPD-emphysema. Traditional treatments have shown limited efficacy in improving COPD-associated HFpEF. This lack of therapeutic efficacy highlights the need to identify potential mechanisms that link COPD-emphysema to HFpEF. Therefore, we aimed to study the delayed cardiac physiological impacts in a rat model with acute exacerbated emphysema. Emphysema was induced by four weekly 4 units elastase (ELA) intratracheal pulmonary instillations and exacerbation by one final additional lipolysaccharide (LPS) instillation in male Wistar rats. At 5 weeks after the ELA and LPS exposure, in vivo and ex vivo pulmonary and cardiac measurements were performed. Experimental exacerbated emphysema resulted in decreased pulmonary function and exercise intolerance. Histological analysis revealed parenchymal pulmonary destruction without signs of inflammation or cardiac fibrosis. In vivo cardiac functional analysis revealed diastolic dysfunction and tachycardia. Ex vivo analysis revealed a cellular cardiomyopathy with decreased myofilament Ca
2+ sensitivity, cross-bridge cycling kinetics, and increased adrenergic PKA (protein kinase A)-dependent phosphorylation of troponin-I. Experimental exacerbated emphysema was associated with exercise intolerance that appeared to be secondary to increased β-adrenergic tone and subsequent cardiac myofilament dysfunction. A β1 -receptor antagonist treatment (bisoprolol) started 24 hours after ELA-LPS instillation prevented in vivo and ex vivo diastolic dysfunction. These results suggest that novel treatment strategies targeted to the cardiac myofilament may be beneficial to combat exacerbated emphysema-associated HFpEF.- Published
- 2023
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5. Airway epithelial type-2 alarmin profiles: Blood eosinophil counts remain in memory.
- Author
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Vernisse C, Tuaillon E, Suehs C, Gras D, Bedin AS, Charriot J, Knabe L, Vachier I, Chanez P, Petit A, and Bourdin A
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- Humans, Alarmins, Interleukin-33, Eosinophils, Interleukin-8, Cytokines metabolism, Thymic Stromal Lymphopoietin, Asthma genetics, Pulmonary Disease, Chronic Obstructive
- Abstract
Epithelial cytokines are involved in the orchestration of T1/T2 inflammatory patterns. We question the persistence of this trait in air-liquid interface (ALI) epithelial cultures and whether this local orientation can be related to systemic patterns (e.g., blood eosinophil counts [BECs]). We investigated alarmin release related to high versus low T2 phenotypes associated with chronic airway diseases. ALIs were reconstituted from 32 control, 40 chronic obstructive pulmonary disease, and 20 asthmatic patients. Interleukin-8 (IL-8; a T1-cytokine), IL-25, IL-33, and thymic stromal lymphopoietin (T2-alarmins) concentrations were assessed in subnatants at steady state and used to explain blood neutrophil and eosinophil counts. IL-25 and IL-8 levels were highest in asthma ALI-subnatants, whereas IL-33 was sparsely detected. Thymic stromal lymphopoietin levels were similar among groups. All asthma cell cultures were T1-high/T2-high, while chronic obstructive pulmonary disease and controls tended to be mixed. BECs were independently explained by both disease and in-culture T2-alarmin levels, irrespective of the T2-alarmin considered. The epithelial ALI-T2 signature was more frequently high in patients with a BEC > 300/mm
3 . Despite removal from an in vivo environment for ≥2 months, ALIs release disease-specific cytokine "cocktails" into their subnatants, suggesting continued persistence of alarmin orientation in differentiated cell line environments., (© 2023 Wiley-VCH GmbH.)- Published
- 2023
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6. Proteomic profiling of serum identifies a molecular signature that correlates with clinical outcomes in COPD.
- Author
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Dagher R, Fogel P, Wang J, Soussan D, Chiang CC, Kearley J, Muthas D, Taillé C, Berger P, Bourdin A, Chenivesse C, Leroy S, Anderson G, Humbles AA, Aubier M, Kolbeck R, and Pretolani M
- Subjects
- Humans, Proteomics, Pulmonary Disease, Chronic Obstructive
- Abstract
Objective: Novel biomarkers related to main clinical hallmarks of Chronic obstructive pulmonary disease (COPD), a heterogeneous disorder with pulmonary and extra-pulmonary manifestations, were investigated by profiling the serum levels of 1305 proteins using Slow Off-rate Modified Aptamers (SOMA)scan technology., Methods: Serum samples were collected from 241 COPD subjects in the multicenter French Cohort of Bronchial obstruction and Asthma to measure the expression of 1305 proteins using SOMAscan proteomic platform. Clustering of the proteomics was applied to identify disease subtypes and their functional annotation and association with key clinical parameters were examined. Cluster findings were revalidated during a follow-up visit, and compared to those obtained in a group of 47 COPD patients included in the Melbourne Longitudinal COPD Cohort., Results: Unsupervised clustering identified two clusters within COPD subjects at inclusion. Cluster 1 showed elevated levels of factors contributing to tissue injury, whereas Cluster 2 had higher expression of proteins associated with enhanced immunity and host defense, cell fate, remodeling and repair and altered metabolism/mitochondrial functions. Patients in Cluster 2 had a lower incidence of exacerbations, unscheduled medical visits and prevalence of emphysema and diabetes. These protein expression patterns were conserved during a follow-up second visit, and substanciated, by a large part, in a limited series of COPD patients. Further analyses identified a signature of 15 proteins that accurately differentiated the two COPD clusters at the 2 visits., Conclusions: This study provides insights into COPD heterogeneity and suggests that overexpression of factors involved in lung immunity/host defense, cell fate/repair/ remodelling and mitochondrial/metabolic activities contribute to better clinical outcomes. Hence, high throughput proteomic assay offers a powerful tool for identifying COPD endotypes and facilitating targeted therapies., Competing Interests: Marina Pretolani’s institution has received funding from AstraZeneca. Camille Taillé reports grants or personal fees from Sanofi, GlaxoSmithKline, AstraZeneca and Novartis, outside the submitted work. Patrick Berger reports grants or personal fees from AstraZeneca, Novartis Boehringer Ingelheim, Sanofi, Circassia, Menarini and AstraZeneca outside the submitted work. Arnaud Bourdin reports grants or personal fees from GlaxoSmithKline, Nuvaira, Pulmonx, Actelion, MSD, United Therapeutic, Vertex, Acceleron, Galapagos, AstraZeneca, Boehringer Ingelheim, Chiesi and Sanofi-Regeneron outside the submitted work. Rania Dagher, Chia-Chien Chiang, Jennifer Kearley and Daniel Muthas are employees and shareholders of AstraZeneca. Jingya Wang, Roland Kolbeck and Alison A. Humbles were previous employees of AstraZeneca. An European patent under the reference EP 22 305 676.3 was submitted on May 6, 2022. There are no additional patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2022 Dagher et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2022
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7. Rheology predicts sputum eosinophilia in patients with muco-obstructive lung diseases.
- Author
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Volpato M, Vialaret J, Hirtz C, Petit A, Suehs C, Patarin J, Matzner-Lober E, Vachier I, Molinari N, Bourdin A, and Charriot J
- Subjects
- Cross-Sectional Studies, Humans, Prospective Studies, Rheology, Sputum metabolism, Asthma metabolism, Eosinophilia metabolism, Pulmonary Disease, Chronic Obstructive metabolism
- Abstract
Background: Mucus is known to play a pathogenic role in muco-obstructive lung diseases, but little is known about the determinants of mucus rheology. The purpose of this study is to determine which sputum components influence sputum rheology in patients with muco-obstructive lung diseases., Methods: We performed a cross sectional prospective cohort study. Spontaneous sputum was collected from consecutive patients with muco-obstructive lung diseases. Sputum rheology was assessed using the Rheomuco® rheometer (Rheonova, Grenoble); the elastic modulus G', viscous modulus G″, and the critical stress threshold σc were recorded. Key quantitative and qualitative biological sputum components were determined by cytology, nucleic acid amplification tests and mass spectrometry., Results: 48 patients were included from January to August 2019. Among them, 10 had asthma, 14 COPD and 24 non-CF bronchiectasis (NCFB). The critical stress threshold σc predicted a sputum eosinophilia superior to 1.25% with 89.19% accuracy (AUC = 0.8762). G' and G″ are positively correlated with MUC5AC protein concentration ((rho = 0.361; P = .013) and (rho = 0.335; P = .021), respectively). σc was positively correlated with sputum eosinophilia (rho = 0.394; P = .012), MUC5B (rho = 0.552; P < .001) and total protein (rho = 0.490; P < .001) concentrations. G' and G″ were significantly higher in asthma patients (G' = 14.49[7.18-25.26]Pa, G'' = 3.0[2.16-5.38]Pa) compared to COPD (G' = 5.01[2.94-6.48]Pa, P = .010; G'' = 1.45[1.16-1.94]Pa, P = .006) and to NCFB (G' = 4.99[1.49-10.49]Pa, P = .003; G'' = 1.46[0.71-2.47]Pa, P = .002)., Conclusion: In muco-obstructive lung diseases, rheology predicts sputum eosinophilia and is correlated with mucin concentrations, regardless of the underlying disease., Clinical Trial Registration: (registrar, website, and registration number), where applicable NCT04081740., Competing Interests: Declaration of competing interest Dr. Suehs reports grants from Astra Zeneca, outside the submitted work. Dr Patarin is a full-time employee of Rheonova. Rheonova designed and built the rheometer used in this study. Pr. Molinari reports personal fees from Astra Zeneca, grants from GSK, outside the submitted work. Pr. Bourdin reports grants, personal fees, non-financial support and other from Astra Zeneca, grants, personal fees and other from GSK, grants, personal fees, non-financial support and other from Boeringher Ingelheim, personal fees, non-financial support and other from Novartis, personal fees and other from Teva, personal fees and other from Regeneron, personal fees, non-financial support and other from Chiesi Farmaceuticals, personal fees, non-financial support and other from Actelion, other from Gilead, personal fees and non-financial support from Roche, outside the submitted work. The remaining authors (MV, JV, CH, AP, EML, IV, JC) have no conflicts of interest to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2022
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8. Artificial intelligence to differentiate asthma from COPD in medico-administrative databases.
- Author
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Joumaa H, Sigogne R, Maravic M, Perray L, Bourdin A, and Roche N
- Subjects
- Algorithms, Artificial Intelligence, Databases, Factual, Humans, Male, Asthma drug therapy, Pulmonary Disease, Chronic Obstructive
- Abstract
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., (© 2022. The Author(s).)
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- 2022
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9. Differentiation of Human Induced Pluripotent Stem Cells from Patients with Severe COPD into Functional Airway Epithelium.
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Ahmed E, Fieldes M, Bourguignon C, Mianné J, Petit A, Jory M, Cazevieille C, Boukhaddaoui H, Garnett JP, Hirtz C, Massiera G, Vachier I, Assou S, Bourdin A, and De Vos J
- Subjects
- Epithelium metabolism, Humans, Leukocytes, Mononuclear pathology, Respiratory Mucosa pathology, Induced Pluripotent Stem Cells, Pulmonary Disease, Chronic Obstructive metabolism
- Abstract
Background: Chronic Obstructive Pulmonary Disease (COPD), a major cause of mortality and disability, is a complex disease with heterogeneous and ill-understood biological mechanisms. Human induced pluripotent stem cells (hiPSCs) are a promising tool to model human disease, including the impact of genetic susceptibility. Methods: We developed a simple and reliable method for reprogramming peripheral blood mononuclear cells into hiPSCs and to differentiate them into air−liquid interface bronchial epithelium within 45 days. Importantly, this method does not involve any cell sorting step. We reprogrammed blood cells from one healthy control and three patients with very severe COPD. Results: The mean cell purity at the definitive endoderm and ventral anterior foregut endoderm (vAFE) stages was >80%, assessed by quantifying C-X-C Motif Chemokine Receptor 4/SRY-Box Transcription Factor 17 (CXCR4/SOX17) and NK2 Homeobox 1 (NKX2.1) expression, respectively. vAFE cells from all four hiPSC lines differentiated into bronchial epithelium in air−liquid interface conditions, with large zones covered by beating ciliated, basal, goblets, club cells and neuroendocrine cells, as found in vivo. The hiPSC-derived airway epithelium (iALI) from patients with very severe COPD and from the healthy control were undistinguishable. Conclusions: iALI bronchial epithelium is ready for better understanding lung disease pathogenesis and accelerating drug discovery.
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- 2022
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10. Position paper of the French Society of Respiratory Diseases regarding pharmacological treatment optimization for stable COPD in 2021.
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Zysman M, Baptista BR, Soumagne T, da Silva VM, Martin C, de Menonville CT, Boyer L, Degano B, Burgel PR, Perez T, Bourdin A, Raherison C, Pégliasco H, Piperno D, Zanetti C, Morel H, Delclaux B, Delafosse C, Lorenzo A, Housset B, Morélot-Panzini C, Chabot F, Devillier P, Deslée G, and Roche N
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- Humans, Pulmonary Disease, Chronic Obstructive drug therapy, Respiration Disorders
- Abstract
Competing Interests: Conflicts of Interest None.
- Published
- 2022
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11. Methods of Sputum and Mucus Assessment for Muco-Obstructive Lung Diseases in 2022: Time to "Unplug" from Our Daily Routine!
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Charriot J, Volpato M, Petit A, Vachier I, and Bourdin A
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- Humans, Lung, Mucus, Sputum, Cystic Fibrosis therapy, Pulmonary Disease, Chronic Obstructive diagnosis
- Abstract
Obstructive lung diseases, such as chronic obstructive pulmonary disease, asthma, or non-cystic fibrosis bronchiectasis, share some major pathophysiological features: small airway involvement, dysregulation of adaptive and innate pulmonary immune homeostasis, mucus hyperproduction, and/or hyperconcentration. Mucus regulation is particularly valuable from a therapeutic perspective given it contributes to airflow obstruction, symptom intensity, disease severity, and to some extent, disease prognosis in these diseases. It is therefore crucial to understand the mucus constitution of our patients, its behavior in a stable state and during exacerbation, and its regulatory mechanisms. These are all elements representing potential therapeutic targets, especially in the era of biologics. Here, we first briefly discuss the composition and characteristics of sputum. We focus on mucus and mucins, and then elaborate on the different sample collection procedures and how their quality is ensured. We then give an overview of the different direct analytical techniques available in both clinical routine and more experimental settings, giving their advantages and limitations. We also report on indirect mucus assessment procedures (questionnaires, high-resolution computed tomography scanning of the chest, lung function tests). Finally, we consider ways of integrating these techniques with current and future therapeutic options. Cystic fibrosis will not be discussed given its monogenic nature.
- Published
- 2022
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12. Roles of Mesenchymal Cells in the Lung: From Lung Development to Chronic Obstructive Pulmonary Disease.
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Nasri A, Foisset F, Ahmed E, Lahmar Z, Vachier I, Jorgensen C, Assou S, Bourdin A, and De Vos J
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- Airway Remodeling genetics, Cell Differentiation genetics, Epithelial-Mesenchymal Transition genetics, Epithelium growth & development, Epithelium metabolism, Epithelium pathology, Humans, Lung metabolism, Lung pathology, Mesenchymal Stem Cells cytology, Pulmonary Disease, Chronic Obstructive pathology, Respiratory Mucosa growth & development, Respiratory Mucosa metabolism, Lung growth & development, Mesenchymal Stem Cells metabolism, Organogenesis genetics, Pulmonary Disease, Chronic Obstructive genetics
- Abstract
Mesenchymal cells are an essential cell type because of their role in tissue support, their multilineage differentiation capacities and their potential clinical applications. They play a crucial role during lung development by interacting with airway epithelium, and also during lung regeneration and remodeling after injury. However, much less is known about their function in lung disease. In this review, we discuss the origins of mesenchymal cells during lung development, their crosstalk with the epithelium, and their role in lung diseases, particularly in chronic obstructive pulmonary disease.
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- 2021
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13. 3TR: a pan-European cross-disease research consortium aimed at improving personalised biological treatment of asthma and COPD.
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Porsbjerg C, Maitland-van der Zee AH, Brusselle G, Canonica GW, Agusti A, Faner R, Vogelmeier CF, Nawijn M, van den Berge M, Rusconi F, Pilette C, Ramiconi V, Coleman C, Chaudhuri R, Chung KF, Wedzicha J, Saglani S, Van der Schee MP, Heaney L, Bourdin A, Roberts G, Djukanovic R, Kuna P, Kupczyk M, Axmann J, Staudinger H, Clarke GW, Dahlen SE, and Brightling C
- Subjects
- Cross-Sectional Studies, Humans, Asthma drug therapy, Pulmonary Disease, Chronic Obstructive drug therapy
- Abstract
Competing Interests: Conflict of interest: C. Porsbjerg declares grants or contracts, consulting fees and payment or honoraria from AstraZeneca, GlaxoSmithKline, Novartis, TEVA, Sanofi, Chiesi and ALK in the 36 months prior to manuscript submission. Conflict of interest: A.H. Maitland-van der Zee declares unrestricted research grants from Vertex and Boehringer Ingelheim, and is the principal investigator of a Precision Medicine for more Oxygen (P4O2) public private partnership sponsored by Health Holland involving cash or in kind contributions from Boehringer Ingelheim, Breathomix, Fluidda, Ortec Logiqcare, Philips, Quantib-U, Smartfish, SODAQ, Thirona, TopMD and Novartis; consulting fees paid to their institution by AstraZeneca and Boehringer Ingelheim; and payment or honoraria paid to their institution by GlaxoSmithKline, all in the 36 months prior to manuscript submission. They declare that they are an unpaid member of the Data Safety Monitoring Board of the SOS BPD Study; that they are unpaid president of the Federation of Innovative Drug Research in the Netherlands (FIGON); and that they are president of the European Association of Systems Medicine. Conflict of interest: G. Brusselle declares payment or honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Sanofi and Teva in the 36 months prior to manuscript submission. Conflict of interest: G.W. Canonica declares no competing interests. Conflict of interest: A. Agusti declares no competing interests. Conflict of interest: R. Faner declares research grant payments from GlaxoSmithKline, Menarini, AstraZeneca, ISC-III and the Spanish National Health Service; consulting fees from GlaxoSmithKline; and payments or honoraria from Chiesi, all in the 36 months prior to manuscript submission. Conflict of interest: C.F. Vogelmeier declares grant payments to their institution from the German Ministry of Education and Science (BMBF), AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Grifols and Novartis; consulting fees from AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GlaxoSmithKline, Menarini, Novartis and Nuvaira; payments or honoraria from Aerogen, AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GlaxoSmithKline, Menarini and Novartis, all in the 36 months prior to manuscript submission. Conflict of interest: M. Nawijn declares unrestricted research grant payments to their institution from Chan Zuckerberg Initiative and GlaxoSmithKline in the 36 months prior to manuscript submission; and that they are coordinator of the Human Cell Atlas Lung Biological Network. Conflict of interest: M. van den Berge declares research grant payments to their institution from GlaxoSmithKline, AstraZeneca, Novartis, Genentech and Roche in the 36 months prior to manuscript submission. Conflict of interest: F. Rusconi declares no competing interests. Conflict of interest: C. Pilette declares no competing interests. Conflict of interest: V. Ramiconi declares unrestricted educational grant payments to her organisation from Novartis, Pfizer, AstraZeneca, Chiesi, GlaxoSmithKline, AbbVie, LeoPharma, Boehringer Ingelheim, Sanofi, Regeneron, OM Pharma, Merck Sharp & Dohme, Roche and DBV Technologies, in the 36 months prior to manuscript submission. Conflict of interest: C. Coleman is an employee of the European Lung Foundation. Conflict of interest: R. Chaudhuri declares funding from 3TR European Union Innovative Medicines Initiative 2 to their institution for the present manuscript. They also declare grant funding from AstraZeneca within a Medical Research Council project; lecture fees from GlaxoSmithKline, AstraZeneca, Teva, Chiesi, Sanofi and Novartis; support for attending conferences from Chiesi, Napp, Sanofi, Boehringer Ingelheim, GlaxoSmithKline and AstraZeneca; and participation on advisory boards for GlaxoSmithKline, AstraZeneca, Teva, Chiesi and Novartis, all in the 36 months prior to manuscript submission. Conflict of interest: K.F. Chung declares grant payments to their institution from the Medical Research Council (precision medicine for severe asthma), the Engineering and Physical Sciences Research Council (air pollution and asthma) and GlaxoSmithKline (eosinophils); consulting fees from the scientific committee of the Clean Breathing Institute (funded by the GlaxoSmithKline consumer division); speaking fees for engagements from Novartis and AstraZeneca; an educational grant paid to their institution for the 11th London International Cough Symposium from AstraZeneca, Merck, Shionogi, Nocion, Bellus and Bayer; participation on a data safety management board for Nocion (antitussive); and participation on advisory boards for Nocion, Shionogi and Merck (antitussives) and GlaxoSmithKline, Roche and Novartis (asthma and COPD), all in the 36 months prior to manuscript submission. Conflict of interest: J. Wedzicha declares grant payments to their institution from GlaxoSmithKline, AstraZeneca, Novartis, Genentech, Boehringer Ingelheim and Chiesi; paid participation on a Data Safety Monitoring Board for Virtus; and editorship of the American Journal of Respiratory and Critical Care Medicine, for which an honorarium is paid jointly to them and their institution. Conflict of interest: S. Saglani declares no competing interests. Conflict of interest: M.P. Van der Schee declares consulting fees from Owlstone Medical in the 36 months prior to manuscript submission; and that they hold stock or stock options in Owlstone Medical and Sanome. Conflict of interest: L. Heaney declares grant payments to their institution from Novartis UK, GlaxoSmithKline, Amgen, Genentech/Hoffmann la Roche, AstraZeneca, Medimmune, Aerocrine and Vitalograph; payments or honoraria from Novartis, Genentech/Hoffmann la Roche, Sanofi, Evelo Biosciences, GlaxoSmithKline, AstraZeneca, Teva, Theravance and Circassia; support for attending meetings from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Napp; and participation on advisory boards for Novartis, Genentech/Hoffmann la Roche, Sanofi, Evelo Biosciences, GlaxoSmithKline, AstraZeneca, Teva, Theravance and Circassia, all in the 36 months prior to manuscript submission. Conflict of interest: A. Bourdin declares unrestricted grant payments from AstraZeneca and Boehringer Ingelheim; advisory board fees from AstraZeneca, GlaxoSmithKline, Regeneron, Sanofi, Novartis, Chiesi, Amgen; lecture payments from AstraZeneca, GlaxoSmithKline, Regeneron, Sanofi, Novartis, Chiesi and Amgen; and support for attending meetings from AstraZeneca, GlaxoSmithKline, Regeneron, Sanofi and Novartis, all in the 36 months prior to manuscript submission. Conflict of interest: G. Roberts declares funding from 3TR European Union Innovative Medicines Initiative 2 to their institution for the present manuscript. Conflict of interest: R. Djukanovic declares consulting fees from Synairgen plc in the 36 months prior to manuscript submission; that they are chair of the European Respiratory Society Clinical Research Collaboration on severe asthma (SHARP); and that they hold shares in Synairgen plc. Conflict of interest: P. Kuna declares lecture fees from Adamed, AstraZeneca, Boehringer Ingelheim, Berlin Chimie, Menarini, Chiesi, HAL Allergy, Lekam, Mylan, Novartis, Polpharma and Teva in the 36 months prior to manuscript submission. Conflict of interest: M. Kupczyk declares funding from 3TR European Union Innovative Medicines Initiative 2 for the present manuscript. They also declare payment or honoraria from AstraZeneca, Chiesi, GlaxoSmithKline, Novartis, Lekam, Alvogen, Emma, Nexter and Berlin Chemie in the 36 months prior to manuscript submission. Conflict of interest: J. Axmann declares no competing interests. Conflict of interest: H. Staudinger declares that they are an employee of Sanofi Genzyme; and that they hold stock or stock options in Sanofi and Merck. Conflict of interest: G.W. Clarke declares that they are an employee of AstraZeneca; and that they hold stock or stock options in AstraZeneca. Conflict of interest: S.E. Dahlen declares consulting fees from AstraZeneca, Caiman Chemicals, GlaxoSmithKline, Merck, Novartis, Regeneron, Sanofi and Teva, outside the present manuscript. Conflict of interest: C. Brightling declares support from 3TR European Union Innovative Medicines Initiative 2 for the present manuscript. They also declare grant payments to their institution from GlaxoSmithKline, AstraZeneca, Novartis, Chiesi, Sanofi, Genentech, Merck, Mologic, 4DPharma and Gossamer; consulting fees paid to their institution from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi, Sanofi, Genentech, Merck, Mologic, 4DPharma, Gossamer, TEVA, Regeneron, Roche and CSL Behring, all in the 36 months prior to manuscript submission.
- Published
- 2021
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14. Generation of four severe early-onset chronic obstructive pulmonary disease (COPD) patient-derived induced pluripotent stem cell lines from peripheral blood mononuclear cells.
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Ahmed E, Fieldes M, Mianné J, Bourguignon C, Nasri A, Vachier I, Assou S, Bourdin A, and De Vos J
- Subjects
- Cell Differentiation, Cellular Reprogramming, Humans, Leukocytes, Mononuclear, Sendai virus, Induced Pluripotent Stem Cells, Pulmonary Disease, Chronic Obstructive
- Abstract
Evidence highlights the concept of multiple trajectories leading to COPD. Early-life events (i.e., in utero lung development) may influence the maximally attained lung function and increase the risk to develop COPD. Human pluripotent stem cells (hiPSC) represent a unique opportunity to model lung development. We generated hiPSC lines from four highly characterized COPD patients with early onset and severe phenotype. Peripheral blood mononuclear cells (PBMCs) were reprogrammed using integration-free Sendai Virus. The cell lines had normal karyotype, expressed pluripotency hallmarks, and differentiated into the three primary germ layers. These lines offer a tool to study early-life origins of COPD., (Copyright © 2021 CHU de Montpellier. Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
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15. Efficacy and Safety of Budesonide/Glycopyrronium/Formoterol Fumarate versus Other Triple Combinations in COPD: A Systematic Literature Review and Network Meta-analysis.
- Author
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Bourdin A, Molinari N, Ferguson GT, Singh B, Siddiqui MK, Holmgren U, Ouwens M, Jenkins M, and De Nigris E
- Subjects
- Administration, Inhalation, Adrenergic beta-2 Receptor Agonists therapeutic use, Bayes Theorem, Bronchodilator Agents adverse effects, Budesonide adverse effects, Drug Combinations, Formoterol Fumarate therapeutic use, Fumarates therapeutic use, Humans, Muscarinic Antagonists therapeutic use, Network Meta-Analysis, Quality of Life, Glycopyrrolate adverse effects, Pulmonary Disease, Chronic Obstructive drug therapy
- Abstract
In patients with chronic obstructive pulmonary disease (COPD) who experience further exacerbations or symptoms, despite being prescribed dual long-acting muscarinic antagonist (LAMA)/long-acting β
2 -agonist (LABA) or inhaled corticosteroid (ICS)/LABA therapies, triple ICS/LAMA/LABA therapy is recommended. A previous network meta-analysis showed comparable efficacy of the ICS/LAMA/LABA, budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR) 320/18/9.6 µg, to other fixed-dose and open combination triple therapies at 24 weeks in COPD. Subsequently, the ETHOS study was published, including data for 8509 patients, assessing the efficacy and safety of BUD/GLY/FOR over 52 weeks. This network meta-analysis (NMA) was conducted to compare the relative efficacy, safety, and tolerability of BUD/GLY/FOR 320/18/9.6 µg with other fixed-dose and open combination triple therapies in COPD over 52 weeks, including data from ETHOS. A systematic literature review was conducted to identify ≥ 10-week randomized controlled trials, including ≥ 1 fixed-dose or open combination triple-therapy arm, in patients with moderate-to-very severe COPD. The methodologic quality and risk of bias of included studies were assessed. Study results were combined using a three-level hierarchical Bayesian NMA model to assess efficacy and safety outcomes at or over 24 and 52 weeks. Meta-regression and sensitivity analyses were used to assess heterogeneity across studies. Nineteen studies (n = 37,741 patients) met the inclusion criteria of the review; 15 contributed to the base case network. LAMA/LABA dual combinations were combined as a single treatment group to create a connected network. Across all outcomes for exacerbations, lung function, symptoms, health-related quality of life, safety, and tolerability, the efficacy and safety of BUD/GLY/FOR were comparable to those of other triple ICS/LAMA/LABA fixed-dose (fluticasone furoate/umeclidinium/vilanterol and beclomethasone dipropionate/glycopyrronium bromide/formoterol fumarate) and open combinations at or over 24 and 52 weeks. Sensitivity analyses and meta-regression results for exacerbation outcomes were broadly in line with the base case NMA. In this NMA, BUD/GLY/FOR 320/18/9.6 μg showed comparable efficacy versus other ICS/LAMA/LABA fixed-dose or open combination therapies in terms of reducing exacerbation rates and improving lung function, symptoms and health-related quality of life in patients with moderate-to-very-severe COPD, in line with previously published meta-analysis results of triple combinations in COPD. The safety and tolerability profile of BUD/GLY/FOR was also found to be comparable to other triple combination therapies.- Published
- 2021
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16. Natural history and mechanisms of COPD.
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Lange P, Ahmed E, Lahmar ZM, Martinez FJ, and Bourdin A
- Subjects
- Adult, Humans, Longitudinal Studies, Lung, Smoking adverse effects, Asthma, Pulmonary Disease, Chronic Obstructive
- Abstract
The natural history of COPD is complex, and the disease is best understood as a syndrome resulting from numerous interacting factors throughout the life cycle with smoking being the strongest inciting feature. Unfortunately, diagnosis is often delayed with several longitudinal cohort studies shedding light on the long 'preclinical' period of COPD. It is now accepted that individuals presenting with different COPD phenotypes may experience varying natural history of their disease. This includes its inception, early stages and progression to established disease. Several scenarios regarding lung function course are possible, but it may conceptually be helpful to distinguish between individuals with normal maximally attained lung function in their early adulthood who thereafter experience faster than normal FEV
1 decline, and those who may achieve a lower than normal maximally attained lung function. This may be the main mechanism behind COPD in the latter group, as the decline in FEV1 during their adult life may be normal or only slightly faster than normal. Regardless of the FEV1 trajectory, continuous smoking is strongly associated with disease progression, development of structural lung disease and poor prognosis. In developing countries, factors such as exposure to biomass and sequelae after tuberculosis may lead to a more airway-centred COPD phenotype than seen in smokers. Mechanistically, COPD is characterized by a combination of structural and inflammatory changes. It is unlikely that all patients share the same individual or combined mechanisms given the heterogeneity of resultant phenotypes. Lung explants, bronchial biopsies and other tissue studies have revealed important features. At the small airway level, progression of COPD is clinically imperceptible, and the pathological course of the disease is poorly described. Asthmatic features can further add confusion. However, the small airway epithelium is likely to represent a key focus of the disease, combining impaired subepithelial crosstalk and structural/inflammatory changes. Insufficient resolution of inflammatory processes may facilitate these changes. Pathologically, epithelial metaplasia, inversion of the goblet to ciliated cell ratio, enlargement of the submucosal glands and neutrophil and CD8-T-cell infiltration can be detected. Evidence of type 2 inflammation is gaining interest in the light of new therapeutic agents. Alarmin biology is a promising area that may permit control of inflammation and partial reversal of structural changes in COPD. Here, we review the latest work describing the development and progression of COPD with a focus on lung function trajectories, exacerbations and survival. We also review mechanisms focusing on epithelial changes associated with COPD and lack of resolution characterizing the underlying inflammatory processes., (© 2021 Asian Pacific Society of Respirology.)- Published
- 2021
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17. Glycopyrrolate and formoterol fumarate for the treatment of COPD.
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Grillet PE, Le Souder C, Rohou J, Cazorla O, Charriot J, and Bourdin A
- Subjects
- Administration, Inhalation, Bronchodilator Agents therapeutic use, Humans, Formoterol Fumarate therapeutic use, Glycopyrrolate therapeutic use, Pulmonary Disease, Chronic Obstructive drug therapy
- Abstract
Introduction: Long acting bronchodilators are nowadays the central treatment for management of stable COPD. Several combinations exist within the market with different formulation devices. This article reviews a recent dual combination of glycopyrronium and formoterol fumarate in an innovative pMDI-fixed dual combination, Bevespi® Aerosphere., Areas Covered: This article explored the literature to understand the place of this novel combination and unique delivery drug device in today's therapeutic arsenal. Clinical efficacy and safety have been evaluated through the different clinical trials published in public databases., Expert Opinion: Within the fixed-dose combinations, Glycopyrrolate and formoterol fumarate offer a credible unique pMDI option to be given twice a day. LABA-LAMA offers an ICS-free alternative in COPD pharmacology which represents an important treatment option given the current debate over whether or not, maintenance triple therapy combined with ICS are benefic in the long term.
- Published
- 2021
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18. LAM is another small airway disease: lessons from microCT.
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Bourdin A, Gamez AS, Vachier I, and Crestani B
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- Humans, Lipopolysaccharides, X-Ray Microtomography, Airway Obstruction, Lymphangioleiomyomatosis, Pulmonary Disease, Chronic Obstructive
- Abstract
Competing Interests: Conflict of interest: A. Bourdin reports grants, personal fees and non-financial support from, and has been PI in clinical trials for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Actelion, personal fees and non-financial support from, and has been PI in clinical trials for Novartis, Regeneron and Chiesi Farmaceuticals, personal fees and non-financial support from Teva, personal fees from Gilead, non-financial support from, and has been PI in clinical trials for Roche, and has been PI in clinical trials for Nuvaira, outside the submitted work. Conflict of interest: A.S. Gamez has nothing to disclose. Conflict of interest: I. Vachier has nothing to disclose. Conflict of interest: B. Crestani has nothing to disclose.
- Published
- 2020
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19. Reply to: Altered Calcium in Ciliary Dysfunction: Potential Role of ER Stress and Ciliophagy.
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Petit A, Knabe L, Khelloufi K, Jory M, Gras D, Cabon Y, Begg M, Richard S, Massiera G, Chanez P, Vachier I, and Bourdin A
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- Calcium Channels, Endoplasmic Reticulum, Humans, Signal Transduction, Smokers, Calcium, Pulmonary Disease, Chronic Obstructive
- Published
- 2019
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20. Bronchial Epithelial Calcium Metabolism Impairment in Smokers and Chronic Obstructive Pulmonary Disease. Decreased ORAI3 Signaling.
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Petit A, Knabe L, Khelloufi K, Jory M, Gras D, Cabon Y, Begg M, Richard S, Massiera G, Chanez P, Vachier I, and Bourdin A
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- Adult, Aged, Benzamides pharmacology, Bronchi metabolism, Calcium Channels biosynthesis, Calcium Channels genetics, Calcium Signaling, Cells, Cultured, Cilia drug effects, Cilia physiology, Cytokines metabolism, Endoplasmic Reticulum metabolism, Epithelial Cells drug effects, Epithelial Cells metabolism, Female, Gene Expression Regulation, Humans, Interleukin-8 biosynthesis, Male, Middle Aged, Mucin 5AC biosynthesis, Mucus metabolism, Pyrazoles pharmacology, Respiratory Mucosa pathology, Signal Transduction physiology, Smoke, Smokers, Bronchi cytology, Calcium metabolism, Calcium Channels physiology, Pulmonary Disease, Chronic Obstructive metabolism, Respiratory Mucosa metabolism, Smoking metabolism
- Abstract
The airway epithelium represents a fragile environmental interface potentially disturbed by cigarette smoke (CS), the major risk factor for developing chronic obstructive pulmonary disease (COPD). CS leads to bronchial epithelial damage on ciliated, goblet, and club cells, which could involve calcium (Ca
2+ ) signaling. Ca2+ is a key messenger involved in virtually all fundamental physiological functions, including mucus and cytokine secretion, cilia beating, and epithelial repair. In this study, we analyzed Ca2+ signaling in air-liquid interface-reconstituted bronchial epithelium from control subjects and smokers (with and without COPD). We further aimed to determine how smoking impaired Ca2+ signaling. First, we showed that the endoplasmic reticulum (ER) depletion of Ca2+ stores was decreased in patients with COPD and that the Ca2+ influx was decreased in epithelial cells from smokers (regardless of COPD status). In addition, acute CS exposure led to a decrease in ER Ca2+ release, significant in smoker subjects, and to a decrease in Ca2+ influx only in control subjects. Furthermore, the differential expression of 55 genes involved in Ca2+ signaling highlighted that only ORAI3 expression was significantly altered in smokers (regardless of COPD status). Finally, we incubated epithelial cells with an ORAI antagonist (GSK-7975A). GSK-7975A altered Ca2+ influx and ciliary beating, but not mucus and cytokine secretion or epithelial repair, in control subjects. Our data suggest that Ca2+ signaling is impaired in smoker epithelia (regardless of COPD status) and involves ORAI3. Moreover, ORAI3 is additionally involved in ciliary beating.- Published
- 2019
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21. A Randomized, Double-Blind, Double-Dummy Study of Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Relative to Umeclidinium/Vilanterol Dry Powder Inhaler in COPD.
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Maltais F, Ferguson GT, Feldman GJ, Deslee G, Bourdin A, Fjällbrant H, Siwek-Posłuszna A, Jenkins MA, and Martin UJ
- Subjects
- Administration, Inhalation, Aged, Bronchodilator Agents therapeutic use, Double-Blind Method, Female, Forced Expiratory Volume drug effects, Humans, Male, Middle Aged, Muscarinic Antagonists therapeutic use, Respiratory Function Tests, Treatment Outcome, Benzyl Alcohols administration & dosage, Chlorobenzenes administration & dosage, Dry Powder Inhalers methods, Formoterol Fumarate administration & dosage, Glycopyrrolate administration & dosage, Metered Dose Inhalers statistics & numerical data, Pulmonary Disease, Chronic Obstructive drug therapy
- Abstract
Introduction: Glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI), formulated using co-suspension delivery technology, is the only approved fixed-dose combination long-acting muscarinic antagonist/long-acting β
2 -agonist (LAMA/LABA) delivered via MDI. Direct comparisons of GFF MDI versus other LAMA/LABAs have not previously been performed. We assessed the efficacy and safety of GFF MDI relative to umeclidinium/vilanterol dry powder inhaler (UV DPI) in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD)., Methods: In this phase IIIb randomized, double-blind, double-dummy, multicenter, 24-week study, patients received GFF MDI 18/9.6 μg (equivalent to glycopyrronium/formoterol fumarate dihydrate 14.4/10 μg; two inhalations per dose, twice-daily; n = 559) or UV DPI 62.5/25 μg (one inhalation, once-daily; n = 560). Primary endpoints were change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1 ) and peak change from baseline in FEV1 within 2 h post-dose, both over 24 weeks. Additional lung function, symptom and safety endpoints were also assessed., Results: For the primary endpoints, GFF MDI was non-inferior to UV DPI (using a margin of - 50 mL) for peak FEV1 (least squares mean [LSM] difference - 3.4 mL, 97.5% confidence interval [CI] - 32.8, 25.9) but not for trough FEV1 (LSM difference - 87.2 mL; - 117.0, - 57.4). GFF MDI was nominally superior to UV DPI for onset of action (p < 0.0001) and was nominally non-inferior to UV DPI for all symptom endpoints (Transition Dyspnea Index focal score, Early Morning/Night-Time Symptoms COPD instrument scores, and COPD Assessment Test score). Exacerbation and safety findings were similar between groups., Conclusions: Over 24 weeks of treatment, GFF MDI was non-inferior to UV DPI for peak FEV1 , but not for morning pre-dose trough FEV1 . GFF MDI had a faster onset of action versus UV DPI. There were no clinically meaningful differences between treatments in symptom endpoints. Both treatments were well tolerated with similar safety profiles., Trial Registration: NCT03162055 (Clinicaltrials.gov) FUNDING: AstraZeneca.- Published
- 2019
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22. CCSP counterbalances airway epithelial-driven neutrophilic chemotaxis.
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Knabe L, Petit A, Vernisse C, Charriot J, Pugnière M, Henriquet C, Sasorith S, Molinari N, Chanez P, Berthet JP, Suehs C, Vachier I, Ahmed E, and Bourdin A
- Subjects
- Humans, Interleukin-8 metabolism, Interleukin-8 pharmacology, Neutrophils drug effects, Pulmonary Disease, Chronic Obstructive metabolism, Recombinant Proteins pharmacology, Smoking, Sputum cytology, Bronchioles pathology, Chemotaxis, Leukocyte, Neutrophils cytology, Pulmonary Disease, Chronic Obstructive pathology, Uteroglobin pharmacology
- Abstract
Club cell secretory protein (CCSP) knockout mice exhibit increased airway neutrophilia, as found in chronic obstructive pulmonary disease (COPD). We therefore investigated whether treating COPD airway epithelia with recombinant human CCSP (rhCCSP) could dampen exaggerated airway neutrophilia.Control, smoker and COPD air-liquid interface (ALI) cultures exposed to cigarette smoke extract (CSE) were treated with and without rhCCSP. The chemotactic properties of the supernatants were assessed using Dunn chambers. Neutrophil chemotaxis along recombinant human interleukin 8 (rhIL8) gradients (with and without rhCCSP) was also determined. rhCCSP-rhIL8 interactions were tested through co-immunoprecipitation, Biacore surface plasmon resonance (SPR) and in silico modelling. The relationship between CCSP/IL8 concentration ratios in the supernatant of induced sputum from COPD patients versus neutrophilic airway infiltration assessed in lung biopsies was assessed.Increased neutrophilic chemotactic activity of CSE-treated ALI cultures followed IL8 concentrations and returned to normal when supplemented with rhCCSP. rhIL8-induced chemotaxis of neutrophils was reduced by rhCCSP. rhCCSP and rhIL8 co-immunoprecipitated. SPR confirmed this in vitro interaction (equilibrium dissociation constant=8 µM). In silico modelling indicated that this interaction was highly likely. CCSP/IL8 ratios in induced sputum correlated well with the level of small airway neutrophilic infiltration (r
2 =0.746, p<0.001).CCSP is a biologically relevant counter-balancer of neutrophil chemotactic activity. These different approaches used in this study suggest that, among the possible mechanisms involved, CCSP may directly neutralise IL8., Competing Interests: Conflict of interest: L. Knabe has nothing to disclose. Conflict of interest: A. Petit has nothing to disclose. Conflict of interest: C. Vernisse has nothing to disclose. Conflict of interest: J. Charriot has nothing to disclose. Conflict of interest: M. Pugnière has nothing to disclose. Conflict of interest: C. Henriquet has nothing to disclose. Conflict of interest: S. Sasorith has nothing to disclose. Conflict of interest: N. Molinari has nothing to disclose. Conflict of interest: P. Chanez has nothing to disclose. Conflict of interest: J-P. Berthet has nothing to disclose. Conflict of interest: C. Suehs has nothing to disclose. Conflict of interest: I. Vachier has nothing to disclose. Conflict of interest: E. Ahmed has nothing to disclose. Conflict of interest: A. Bourdin has nothing to disclose., (Copyright ©ERS 2019.)- Published
- 2019
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23. COPD beyond proximal bronchial obstruction: phenotyping and related tools at the bedside.
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Capron T, Bourdin A, Perez T, and Chanez P
- Subjects
- Airway Remodeling, Animals, Disability Evaluation, Hemodynamics, Humans, Lung blood supply, Lung physiopathology, Phenotype, Predictive Value of Tests, Prognosis, Pulmonary Disease, Chronic Obstructive physiopathology, Pulmonary Disease, Chronic Obstructive therapy, Respiration, Severity of Illness Index, Vascular Remodeling, Lung diagnostic imaging, Point-of-Care Testing, Pulmonary Disease, Chronic Obstructive diagnosis, Respiratory Function Tests, X-Ray Microtomography
- Abstract
Chronic obstructive pulmonary disease (COPD) is characterised by nonreversible proximal bronchial obstruction leading to major respiratory disability. However, patient phenotypes better capture the heterogeneously reported complaints and symptoms of COPD. Recent studies provided evidence that classical bronchial obstruction does not properly reflect respiratory disability, and symptoms now form the new paradigm for assessment of disease severity and guidance of therapeutic strategies. The aim of this review was to explore pathways addressing COPD pathogenesis beyond proximal bronchial obstruction and to highlight innovative and promising tools for phenotyping and bedside assessment. Distal small airways imaging allows quantitative characterisation of emphysema and functional air trapping. Micro-computed tomography and parametric response mapping suggest small airways disease precedes emphysema destruction. Small airways can be assessed functionally using nitrogen washout, probing ventilation at conductive or acinar levels, and forced oscillation technique. These tests may better correlate with respiratory symptoms and may well capture bronchodilation effects beyond proximal obstruction.Knowledge of inflammation-based processes has not provided well-identified targets so far, and eosinophils probably play a minor role. Adaptative immunity or specific small airways secretory protein may provide new therapeutic targets. Pulmonary vasculature is involved in emphysema through capillary loss, microvascular lesions or hypoxia-induced remodelling, thereby impacting respiratory disability., Competing Interests: Conflict of interest: T. Capron has nothing to disclose. Conflict of interest: A. Bourdin reports personal fees from Novartis, Sanofi, Genentech and Chiesi Farma, and grants and personal fees from GSK, AstraZeneca and Boeringher Ingelheim, outside the submitted work. Conflict of interest: T. Perez reports personal fees from Novartis, Chiesi and Boehringer Ingelheim, and grants from Astra Zeneca, outside the submitted work. Conflict of interest: P. Chanez reports grants and personal fees from ALK, Almirall, Boehringer Ingelheim, GSK, AstraZeneca, Novartis, TEVA and Chiesi, and grants from AMU, outside the submitted work., (Copyright ©ERS 2019.)
- Published
- 2019
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24. Asthma, COPD, and overlap in a national cohort: ACO on a gradient.
- Author
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Bourdin A, Suehs CM, Marin G, Vachier I, Matzner-Lober E, Chanez P, and Molinari N
- Subjects
- Adrenal Cortex Hormones therapeutic use, Adult, Asthma drug therapy, Humans, Pulmonary Disease, Chronic Obstructive drug therapy, Asthma diagnosis, Pulmonary Disease, Chronic Obstructive diagnosis
- Published
- 2018
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25. Epithelial ciliated beating cells essential for ex vivo ALI culture growth.
- Author
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Gras D, Petit A, Charriot J, Knabe L, Alagha K, Gamez AS, Garulli C, Bourdin A, Chanez P, Molinari N, and Vachier I
- Subjects
- Adult, Aged, Bronchoscopy, Case-Control Studies, Cell Culture Techniques methods, Culture Media, Epithelial Cells cytology, Female, France, Humans, Logistic Models, Male, Middle Aged, Multivariate Analysis, Proportional Hazards Models, Prospective Studies, Severity of Illness Index, Asthma pathology, Epithelial Cells physiology, Pulmonary Disease, Chronic Obstructive pathology, Respiratory Mucosa pathology, Smoking pathology
- Abstract
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.
- Published
- 2017
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26. Rising total costs and mortality rates associated with admissions due to COPD exacerbations.
- Author
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Molinari N, Chanez P, Roche N, Ahmed E, Vachier I, and Bourdin A
- Subjects
- Aged, Aged, 80 and over, Critical Care economics, Databases, Factual, Disease Progression, Female, France epidemiology, Humans, Incidence, Length of Stay economics, Longitudinal Studies, Male, Middle Aged, Process Assessment, Health Care trends, Pulmonary Disease, Chronic Obstructive diagnosis, Pulmonary Disease, Chronic Obstructive therapy, Registries, Respiration, Artificial economics, Risk Factors, Severity of Illness Index, Time Factors, Treatment Outcome, Hospital Costs trends, Hospital Mortality trends, Patient Admission economics, Process Assessment, Health Care economics, Pulmonary Disease, Chronic Obstructive economics, Pulmonary Disease, Chronic Obstructive mortality
- Abstract
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.
- Published
- 2016
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27. CCSP G38A polymorphism environment interactions regulate CCSP levels differentially in COPD.
- Author
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Knabe L, Varilh J, Bergougnoux A, Gamez AS, Bonini J, Pommier A, Petit A, Molinari N, Vachier I, Taulan-Cadars M, and Bourdin A
- Subjects
- Aged, Base Sequence, Cell Line, Conserved Sequence, Female, Gene-Environment Interaction, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Lipopolysaccharides pharmacology, Male, Middle Aged, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Prospective Studies, Pulmonary Disease, Chronic Obstructive blood, Smoking adverse effects, Smoking genetics, Transcriptional Activation, Uteroglobin blood, Pulmonary Disease, Chronic Obstructive genetics, Uteroglobin genetics
- Abstract
Impaired airway homeostasis in chronic obstructive pulmonary disease (COPD) could be partly related to club cell secretory protein (CCSP) deficiency. We hypothesize that CCSP G38A polymorphism is involved and aim to examine the influence of the CCSP G38A polymorphism on CCSP transcription levels and its regulatory mechanisms. CCSP genotype and CCSP levels in serum and sputum were assessed in 66 subjects with stable COPD included in a 1-yr observational study. Forty-nine of them had an exacerbation. In an in vitro study, the impact on the CCSP promoter of 38G wild-type or 38A variant was assessed. BEAS-2B cells were transfected by either the 38G or 38A construct, in the presence/absence of cigarette smoke extract (CSE) or lipopolysaccharides (LPS). Cotransfections with modulating transcription factors, p53 and Nkx2.1, identified by in silico analysis by using ConSite and TFSEARCH were conducted. A allele carrier COPD patients had lower serum and sputum CCSP levels, especially among active smokers, and a decreased body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) score. In vitro, baseline CCSP transcription levels were similar between the wild and variant constructs. CSE decreased more profoundly the CCSP transcription level of 38A transfected cells. The opposite effect was observed with p53 cotransfection. LPS stimulation induced CCSP repression in 38A promoter transfected cells. Cotransfection with Nkx2.1 significantly activated the CCSP promoters irrespective of the polymorphism. Circulating CCSP levels are associated with smoking and the CCSP G38A polymorphism. CSE, LPS, and the Nkx2.1 and p53 transcription factors modulated the CCSP promoter efficiency. The 38A polymorphism exaggerated the CCSP repression in response to p53 and CSE., (Copyright © 2016 the American Physiological Society.)
- Published
- 2016
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28. Supplementing defect in club cell secretory protein attenuates airway inflammation in COPD.
- Author
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Gamez AS, Gras D, Petit A, Knabe L, Molinari N, Vachier I, Chanez P, and Bourdin A
- Subjects
- Adult, Aged, Case-Control Studies, Cells, Cultured, Epithelial Cells drug effects, Epithelial Cells metabolism, Epithelial Cells pathology, Female, Humans, In Vitro Techniques, Interleukin-8 metabolism, Male, Middle Aged, Nicotine pharmacology, Pneumonia pathology, Pulmonary Disease, Chronic Obstructive metabolism, Pulmonary Disease, Chronic Obstructive pathology, Recombinant Proteins pharmacology, Smoking adverse effects, Pneumonia etiology, Pneumonia prevention & control, Pulmonary Disease, Chronic Obstructive complications, Uteroglobin pharmacology
- Abstract
Background: Club cell secretory protein (CCSP) is a protective biomarker associated with annual decline in lung function. COPD progression results from an imbalance between injury and repair initially triggered by cigarette smoking., Objective: We investigated the effect of CCSP as a therapeutic strategy to restore the balance between injury and repair in COPD simultaneously, validating an ex vivo air-liquid interface (ALI) culture of human bronchial epithelial cells., Methods: Endobronchial biopsy specimens (EBBs) were obtained from 13 patients with COPD, eight smokers, and eight control subjects. Morphometric analysis of the initial EBBs was performed. ALI cultures derived from the same EBBs were exposed to cigarette smoke extract (CSE) with or without exogenous recombinant human CCSP (rhCCSP) supplementation. CCSP and IL-8 concentrations were assessed at steady state and after CSE exposure., Results: Morphometric analysis of the initial EBBs showed increased cell density but decreased immunostaining of CCSP+ cells in EBBs of patients with COPD (P = .03 vs control subjects). At steady state, lower CCSP (P = .04) and higher IL-8 levels (P < .0001) were found in COPD ALI epithelium. Exogenous rhCCSP supplementation dampened CSE-induced IL-8-release in patients with COPD and returned to levels similar to those of smokers and control subjects (P = .0001). A negative correlation was found between IL-8-release in ALI and CCSP+ cell density in initial biopsy specimens (P = .0073)., Conclusions: In vitro, rhCCSP exogenous supplementation can reverse CSE-induced IL-8 release in biopsy specimens from patients with COPD, indicating a potential use of this strategy in vivo.
- Published
- 2015
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29. Club cells and CC16: another "smoking gun"? (With potential bullets against COPD).
- Author
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Knabe L, Fort A, Chanez P, and Bourdin A
- Subjects
- Animals, Humans, Lung metabolism, NF-kappa B metabolism, Pulmonary Disease, Chronic Obstructive metabolism, Smoke, Smoking metabolism, Nicotiana, Uteroglobin genetics, Uteroglobin metabolism
- Published
- 2015
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30. Is generalization of exhaled CO assessment in primary care helpful for early diagnosis of COPD?
- Author
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Molinari N, Abou-Badra M, Marin G, Ky CL, Amador N, Gamez AS, Vachier I, and Bourdin A
- Subjects
- Adult, Aged, Area Under Curve, Breath Tests, Early Diagnosis, Female, Humans, Male, Mass Screening, Middle Aged, ROC Curve, Carbon Monoxide analysis, Patient Acceptance of Health Care, Primary Health Care, Pulmonary Disease, Chronic Obstructive diagnosis, Smoking
- Abstract
Background: COPD is largely under-diagnosed and once diagnosed usually at a late stage. Early diagnosis is thoroughly recommended but most attempts failed as the disease is marginally known and screening marginally accepted. It is a rare cause of concern in primary care and spirometry is not very common. Exhaled carbon monoxide (eCO) is a 5-seconds easy-to-use device dedicated to monitor cigarette smoke consumption. We aimed to assess whether systematic eCO measurement in primary care is a useful tool to improve acceptance for early COPD diagnosis., Methods: This was a two-center randomized controlled trial enrolling 410 patients between March and May, 2013. Whatever was the reason of attendance to the clinic, all adults were proposed to measure eCO during randomly chosen days and outcomes were compared between the two different groups of patients (performing and not performing eCO). Primary outcome was the rates of acceptance for COPD screening., Results: Rate of acceptance for COPD screening was 28% in the eCO group and 26% in the other (P = 0.575). These rates increased to 48 and 51% in smokers (current and former). eCO significantly increased the rate of clinics during which a debate on smoking was initiated (42 vs. 24%, P = 0.001). eCO at 2.5 ppm was the discriminative concentration for identifying active smokers (ROC curve AUC: 0.935). Smoking was the only independent risk factor associated with acceptance for early COPD screening (OR = 364.6 (82.5-901.5) and OR = 78.5 (18.7-330.0) in current and former smokers, respectively) while eCO measurement was not., Conclusions: Early COPD diagnosis is a minor cause of concern in primary care. Systematic eCO assessment failed to improve acceptance for early COPD screening.
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- 2015
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31. Hospitalizations for COPD Exacerbations: Trends and Determinants of Death.
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Molinari N, Briand C, Vachier I, Malafaye N, Aubas P, Georgescu V, Roche N, Chanez P, and Bourdin A
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- Age Factors, Aged, Aged, 80 and over, Critical Care, Female, France, Humans, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive therapy, Respiration, Artificial, Respiratory Insufficiency epidemiology, Retrospective Studies, Risk Factors, Hospitalization statistics & numerical data, Pulmonary Disease, Chronic Obstructive complications, Pulmonary Disease, Chronic Obstructive mortality
- Abstract
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.
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- 2015
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32. Nonlinear weight and chronic obstructive pulmonary disease effect modeling to improve data fitting.
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Marin G, Molinari N, Gamez AS, Vachier I, and Bourdin A
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- Female, Humans, Male, Forced Expiratory Volume, Health Status, Obesity complications, Pulmonary Disease, Chronic Obstructive etiology, Smoking adverse effects, Weight Gain physiology
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- 2014
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33. Relationship between CT air trapping criteria and lung function in small airway impairment quantification.
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Bommart S, Marin G, Bourdin A, Molinari N, Klein F, Hayot M, Vachier I, Chanez P, Mercier J, and Vernhet-Kovacsik H
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- Aged, Aged, 80 and over, Breath Tests, Cross-Sectional Studies, Exhalation, Humans, Middle Aged, Prospective Studies, Reproducibility of Results, Respiratory Function Tests methods, Software, Asthma diagnosis, Asthma physiopathology, Pulmonary Disease, Chronic Obstructive diagnosis, Pulmonary Disease, Chronic Obstructive physiopathology, Tomography, X-Ray Computed methods
- Abstract
Background: Small airways are regarded as the elective anatomic site of obstruction in most chronic airway diseases. Expiratory computed tomography (CT) is increasingly used to assess obstruction at this level but there is no consensus regarding the best quantification method. We aimed to evaluate software-assisted CT quantification of air trapping for assessing small airway obstruction and determine which CT criteria better predict small airway obstruction on single breath nitrogen test (SBNT)., Methods: Eighty-nine healthy volunteers age from 60 to 90 years old, underwent spirometrically-gated inspiratory (I) and expiratory (E) CT and pulmonary function tests (PFTs) using SBNT, performed on the same day. Air trapping was estimated using dedicated software measuring on inspiratory and expiratory CT low attenuation area (LAA) lung proportion and mean lung density (MLD). CT indexes were compared to SBNT results using the Spearman correlation coefficient and hierarchical dendrogram analysis. In addition, receiver operating characteristic (ROC) curve analysis was performed to determine the optimal CT air-trapping criterion., Results: 43 of 89 subjects (48,3%) had dN2 value above the threshold defining small airway obstruction (i.e. 2.5% N2/l). Expiratory to inspiratory MLD ratio (r = 0.40) and LAA for the range -850 -1024 HU (r = 0.29) and for the range -850 -910 HU (r = 0.37) were positively correlated with SBNT results. E/I MLD was the most suitable criterion for its expression. Expiratory to inspiratory MLD ratio (E/I MLD) showed the highest AUC value (0.733) for small airway obstruction assessment., Conclusion: Among all CT criteria, all correlating with small airway obstruction on SBNT, E/I MLD was the most suitable criterion for its expression in asymptomatic subjects with mild small airway obstruction, Trial Registration: Registered at Clinicaltrials.gov, identifier: NCT01230879.
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- 2014
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34. An update on the efficacy and safety of aclidinium bromide in patients with COPD.
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Alagha K, Bourdin A, Tummino C, and Chanez P
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- Clinical Trials as Topic, Humans, Receptors, Muscarinic classification, Receptors, Muscarinic drug effects, Tropanes adverse effects, Tropanes pharmacokinetics, Muscarinic Antagonists therapeutic use, Pulmonary Disease, Chronic Obstructive drug therapy, Tropanes therapeutic use
- Abstract
Aclidinium is a potent and selective muscarinic antagonist, which interacts rapidly with muscarinic receptors and shows subnanomolar affinity for the five human muscarinic receptors (M(1)-M(5)); its association rate for the M(3) receptor is similar to that of ipratropium and 2.6 times faster than that of tiotropium. Aclidinium dissociates slightly faster from M(2) and M(3) receptors than tiotropium but much more slowly than ipratropium. A potent bronchodilatory activity has been observed after inhaled administration of aclidinium. Aclidinium undergoes rapid hydrolysis in the plasma into two major compounds, the alcohol (LAS34823) and the carboxylic acid (LAS34850) metabolites, resulting in low and transient systemic exposure to the active drug. The two major metabolites show no significant affinity for human muscarinic receptors. A potent bronchodilatory activity has been observed after inhaled administration of aclidinium. Clinical trials have provided evidence of sustained bronchodilation similar to that observed with tiotropium. Trial results have confirmed the positive safety profile of aclidinium, particularly in terms of a very low propensity to cause anticholinergic adverse events. Aclidinium is now moving to phase III clinical development for chronic obstructive pulmonary disease (COPD).
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- 2011
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35. Non-invasive assessment of small airway remodelling in smokers.
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Bourdin A, Kotsimbos T, Nguyen K, Vachier I, Mainprice B, Farce M, Paganin F, Marty-Ané C, Vernhet H, Godard P, and Chanez P
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- Aged, Cohort Studies, Female, Humans, Lung pathology, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive diagnosis, Pulmonary Disease, Chronic Obstructive metabolism, Respiratory Function Tests, Airway Remodeling, Interleukin-8 metabolism, Pulmonary Disease, Chronic Obstructive physiopathology, Smoking physiopathology, Sputum metabolism, Uteroglobin metabolism
- Abstract
Smoking associated COPD progression is likely to be directly linked to differential injury and repair dynamics in small airways (SA). Although IL8 is a well-accepted marker for injured airway epithelium, Clara cells [the predominant proliferating cells in SA] and SCGB1A1 protein [their major secretory product] have only recently emerged as potential SA repair markers. We therefore postulate that the SCGB1A1/IL8 ratio in the airways of smokers would be inversely associated with physiological, radiological and clinical measures of COPD. A cross-sectional cohort of 28 smokers undergoing surgery for peripheral nodule was recruited (24M/4F, age 61 +/- 11 y, FEV1s 76 +/- 20%, smoking 40 +/- 12 p.y). SCGB1A1 and IL8 were measured by ELISA in the induced sputum (IS) 3 to 5 days prior to surgery as well as by immunohistochemistry from lung tissue (also assessed morphometrically) obtained distant to the cancer surgery site. COPD was assessed using standard clinical, functional and radiological parameters. Log-transformed IS-SCGB1A1 was linearly correlated with SCGB1A1-positive epithelial cells detected via immunohistochemistry (r = .533, p = .001), while IS-IL8 was positively related to SA infiltrating neutrophils (Elastase-positive cells). There was a striking negative correlation between IS-SCGB1A1/IL8 levels and whole airway thickness [SA < 2 mm] at morphometry (r = -0.83, p < 0.0001). IS-SCGB1A1/IL8 levels were also inversely associated with nitrogen slope [r = -0.52, p < 0.001] and HRCT SA score [r = -0.51, p < 0.001]. In a multivariate analysis the IS-SCGB1A1/IL8 ratio was a stronger predictor than both the physiological and radiological measures of SA disease assessed. The SCGB1A1/IL8 ratio measured in sputum is a potentially valuable biomarker for non-invasive assessment of SA remodelling in smokers.
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- 2010
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36. Effects of inhaled corticosteroids on pathology in asthma and chronic obstructive pulmonary disease.
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Chanez P, Bourdin A, Vachier I, Godard P, Bousquet J, and Vignola AM
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- Administration, Inhalation, Airway Resistance drug effects, Biopsy, Needle, Bronchoscopy, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Immunohistochemistry, Male, Prognosis, Risk Assessment, Severity of Illness Index, Treatment Outcome, Adrenal Cortex Hormones administration & dosage, Asthma drug therapy, Asthma pathology, Pulmonary Disease, Chronic Obstructive drug therapy, Pulmonary Disease, Chronic Obstructive pathology
- Abstract
The effects of inhaled corticosteroids (ICSs) have been investigated in asthma and chronic obstructive pulmonary disease (COPD) using endobronchial biopsies. In asthma, most studies have shown reductions in infiltrating eosinophils, mast cells, and T lymphocytes. Cell-associated mediators, such as cytokines derived from type 2 T-helper lymphocytes, are decreased as assessed by immunostaining and molecular biology techniques. More recently, attention has been devoted to the effect of ICSs on structural changes. In asthma, ICSs have been shown in some studies to affect collagen deposition (size of the reticular basement membrane), the number of vessels, or epithelial integrity. The correlations between those findings and various clinical and functional outcomes are far from clear. A long-term study has shown a decrease in the basement membrane size in a group of patients with asthma treated according to their level of airway hyperreactivity. In COPD, ICSs generally do not decrease neutrophils, macrophages, and CD8(+) T lymphocytes. The effects of these drugs on structural changes in COPD have not been investigated extensively. Long-term prospective studies are needed to demonstrate the potential for ICSs to affect the natural history of chronic bronchial diseases.
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- 2004
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37. Artificial intelligence to differentiate asthma from COPD in medico-administrative databases
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Joumaa, Hassan, Sigogne, Raphael, Maravic, Milka, Perray, Lucas, Bourdin, Arnaud, Roche, Nicolas, MORNET, Dominique, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IQVIA, Hôpital Lariboisière-Fernand-Widal [APHP], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Mucoviscidose et bronchopathies chroniques : biopathologie et phénotypes cliniques (EA 2511), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)
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[SDV.IB] Life Sciences [q-bio]/Bioengineering ,[INFO.INFO-AI] Computer Science [cs]/Artificial Intelligence [cs.AI] ,Pulmonary and Respiratory Medicine ,Male ,Databases, Factual ,Epidemiology ,Healthcare administrative databases ,Chronic obstructive pulmonary disease ,[INFO.INFO-IA]Computer Science [cs]/Computer Aided Engineering ,[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,[INFO.INFO-IA] Computer Science [cs]/Computer Aided Engineering ,Asthma ,Prevalence ,COPD ,Algorithms ,ICD code ,[INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI] ,Pulmonary Disease, Chronic Obstructive ,Artificial Intelligence ,[SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,Humans ,[SDV.IB]Life Sciences [q-bio]/Bioengineering ,[SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology ,[SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology - Abstract
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.
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- 2021
38. Rising total costs and mortality rates associated with admissions due to COPD exacerbations
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Molinari , Nicolas, Chanez , Pascal, Roche , Nicolas, Ahmed , Engi, Vachier , Arnaud, Bourdin , Arnaud, Vachier , Isabelle, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pneumologie et Soins Intensifs Respiratoires, Université Paris Descartes - Paris 5 (UPD5)-Hôpitaux Universitaires Paris Centre, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] ( PhyMedExp ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Montpellier ( UM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Centre recherche en CardioVasculaire et Nutrition ( C2VN ), Institut National de la Recherche Agronomique ( INRA ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ) -Hôpitaux Universitaires Paris Centre, CHU Saint-Eloi-Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve, MORNET, Dominique, and Centre recherche en CardioVasculaire et Nutrition (C2VN)
- Subjects
Male ,Time Factors ,Databases, Factual ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Severity of Illness Index ,Pulmonary Disease, Chronic Obstructive ,0302 clinical medicine ,Patient Admission ,Risk Factors ,030212 general & internal medicine ,Hospital Mortality ,Longitudinal Studies ,Registries ,Hospital Costs ,health care economics and organizations ,ComputingMilieux_MISCELLANEOUS ,Aged, 80 and over ,COPD ,Mortality rate ,Incidence (epidemiology) ,Incidence ,Process Assessment, Health Care ,Middle Aged ,3. Good health ,[SDV] Life Sciences [q-bio] ,Treatment Outcome ,Disease Progression ,Female ,France ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Critical Care ,education ,macromolecular substances ,Bronchoscopies ,03 medical and health sciences ,COPD exacerbation ,Severity of illness ,medicine ,Humans ,Intensive care medicine ,Admissions ,Aged ,Mechanical ventilation ,Hospitalizations ,[ SDV ] Life Sciences [q-bio] ,business.industry ,Research ,COPD management ,Length of Stay ,medicine.disease ,Respiration, Artificial ,respiratory tract diseases ,Pneumonia ,030228 respiratory system ,Copd exacerbation ,Deaths ,Emergency medicine ,business - Abstract
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
- Published
- 2016
39. AIRWAYS-ICPs (European Innovation Partnership on Active and Healthy Ageing) from concept to implementation
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Bousquet, Jean, Barbara, Cristina, Bateman, E. D., Bel, E. H., Bewick, M., Chavannes, Niels H., Cruz, A. A., Haahtela, T., Hellings, P. W., Khaltaev, N., Carlsen, K. Lodrup, Muraro, A., Cordeiro, C. R., Rosado-Pinto, J., Samolinski, B., Strandberg, T., Valiulis, A., Yorgancioglu, A., Zuberbier, T., Adcock, I. M., Addis, A., Agache, I., Agusti, A., Alonso, A., Annesi-Maesano, I., Anto, Josep M., Bachert, C., Baena-Cagnani, C. E., Bai, C., Baigenzhin, A. K., Barnes, P. J., Beck, L., Bedbrook, Anna, Benezet, O., Bennoor, K. S., Benson, M., Bernabeu-Wittel, M., Bindslev-Jensen, C., Blain, Hubert, Blasi, F., Bonini, M., Bonini, S., Boulet, L. P., Bourdin, Arnaud, Bourret, Rodolphe, Brightling, C. E., Briggs, A. H., Brozek, J. L., Buhl, R., Bush, A., Caimmi, D. P., Calderon, M. A., Calverley, P. M., Camargos, P. A. M., Camuzat, Thierry, Canonica, G. W., Carlsen, K. H., Casale, T. B., Cazzola, M., A.M, Cepeda Sarabia, Cesario, A., Chen, Y. Z., Chkhartishvili, E., Chiron, R., Chuchalin, Alexander G., Chung, K. F., Cox, L., Crooks, George, Custovic, Adnan, Dahl, R., Dahlen, S. E., Blay, F. De, Dedeu, Antoni, Deleanu, D., Demoly, Pascal, Devillier, P., Didier, A., Dinh-Xuan, A. T., Djukanovic, R., Dokic, D., Douagui, H. B., Dubakiene, R., Eglin, S., Elliot, F., Emuzyte, R., Fabbri, Leonardo M., Fink-Wagner, A., Fletcher, M., Fokkens, W. J., Fonseca, J. A., Franco, A., Frith, P., Furber, A., Gaga, M., Gamkrelidze, A., Garcia-Aymerich, Judith, Gonzalez-Diaz, S. N., Gouzi, Fares, Garces, J., Guzmán, M. A., Harrison, D., Hayot, M., Heaney, L. G., Heinrich, J., Hooper, J., Humbert, M., Hyland, M. E., Iaccarino, G., Jakovenko, D., Jardim, J. R., Jeandel, Claude, Jenkins, C., Johnston, S. L., Jonquet, Olivier, Joos, G., Jung, K. S., Kalayci, O., Karunanithi, S., Keil, T., Kolek, V., Kowalski, M. L., Kull, I., Kuna, P., Kvedariene, V., Le, Tuyen D., Louis, R., MacNee, W., Mair, A., Manning, P. J., Keenoy, M. E. Manuel, Majer, I., Masjedi, M. R., Melén, E., Gomes, Elisabete Melo, Menzies-Gow, A., Mercier, G., Mercier, Jacques, Michel, J. P., Miculinic, N., Mihaltan, F., Milenkovic, B., Molimard, M., Momas, I., Montilla-Santana, A., Almeida, M. Morais, Morgan, M., N'Diaye, M., Nafti, S., Nekam, K., Neou, A., Nicod, L., O'Hehir, R. E., Ohta, K., Paggiaro, P. L., Palkonen, S., Palmer, S., Papadopoulos, N. G., Papi, A., Passalacqua, G., Pavord, I., Pedersen, S., Pigearias, B., Plavec, D., Postma, D. S., Price, D., Rabe, K. F., Radier-Pontal, F., Redon, Josep, Rennard, S., Roberts, J., Robine, J. M., Roca, J., Roche, N., Rodenas, F., Roggeri, A., Rolland, C., Ryan, D., Sanchez-Borges, M., Schunemann, H. J., Sheikh, A., Shields, K. M., Siafakas, N., Sibille, Y., Similowski, T., Small, I., Sola-Morales, O., Sooronbaev, T., Stelmach, R., Sterk, P. J., Stiris, T., Sud, P., Tellier, V., To, T., Todo-Bom, A., Triggiani, M., Valenta, R., Valero, A. L., Valovirta, E., Vandenplas, O., Ganse, E. Van, Vasankari, T., Vestbo, J., Vezzani, G., Viegi, Giovanni, Visier, L., Vogelmeier, C., Vontetsianos, T., Wagstaff, R., Wallaert, B., Wahn, U., Whalley, B., Wickman, M., Williams, D. M., Wilson, N., Yawn, B. P., Yiallouros, Panayiotis K., Yusuf, O. M., Zar, H. J., Zhong, N., Zidarn, M., Yiallouros, Panayiotis K. [0000-0002-8339-9285], Custovic, Adnan [0000-0001-5218-7071], Bousquet, Jean, Barbara, Cristina, Bateman, Eric, Bel, Elisabeth, Bewick, Mike, Chavannes, Niels H., Cruz, Alvaro A., Haahtela, Tari, Hellings, Peter W., Khaltaev, Nikolai, Carlsen, Karin Lodrup, Muraro, Antonella, Cordeiro, Carlos Robalo, Rosado Pinto, Jose, Samolinski, Boleslaw, Strandberg, Timo, Valiulis, Aruna, Yorgancioglu, Arzu, Zuberbier, Torsten, Adcock, I., Addis, A., Agache, I., Agusti, A., Alonso, A., Annesi Maesano, I., Anto, J. M., Bachert, C., Baena Cagnani, C., Bai, C., Baigenzhin, A., Barnes, P. J., Beck, L., Bedbrook, A., Benezet, O., Bennoor, K. S., Benson, M., Bernabeu Wittel, M., Bindslev Jensen, C., Blain, H., Blasi, F., Bonini, M., Bonini, Sergio, Boulet, L. P., Bourdin, A., Bourret, R., Bousquet, P. J., Brightling, C. E., Briggs, A., Brozek, J., Buhl, R., Bush, A., Caimmi, D., Calderon, M., Calverley, P., Camargos, P., Camuzat, T., Canonica, G. W., Carlsen, K. H., Casale, T. B., Cazzola, M., Cepeda Sarabia, A. M., Cesario, A., Chen, Y. Z., Chkhartishvili, E., Chiron, R., Chuchalin, A., Chung, K. F., Cox, L., Crooks, G., Crooks, M. G., Custovic, A., Dahl, R., Dahlen, S. E., De Blay, F., Dedeu, T., Deleanu, D., Demoly, P., Devillier, P., Didier, A., Dinh Xuan, A. T., Djukanovic, R., Dokic, D., Douagui, H., Dubakiene, R., Eglin, S., Elliot, F., Emuzyte, R., Fabbri, L., Fink Wagner, A., Fletcher, M., Fokkens, W. J., Fonseca, J., Franco, A., Frith, P., Furber, A., Gaga, M., Gamkrelidze, A., Garcia Aymerich, J., González Díaz, S., Gouzi, F., Garcés, J., Guzmán, M. A., Harrison, D., Hayot, M., Heaney, L., Heinrich, J., Hooper, J., Humbert, M., Hyland, M., Iaccarino, G., Jakovenko, D., Jardim, J., Jeandel, C., Jenkins, C., Johnston, S. L., Jonquet, O., Joos, G., Jung, K. S., Kalayci, O., Karunanithi, S., Keil, T., Kolek, V., Kowalski, M., Kull, I., Kuna, P., Kvedariene, V., Le, L. T., Louis, R., Macnee, W., Mair, A., Manning, P., Manuel Keenoy, M. E., Majer, I., Masjedi, M. R., Melén, E., Melo Gomes, E., Menzies Gow, A., Mercier, G., Mercier, J., Michel, J. P., Miculinic, N., Mihaltan, F., Milenkovic, B., Molimard, M., Momas, I., Montilla Santana, A., Morais Almeida, M., Morgan, M., N'Diaye, M., Nafti, S., Nekam, Null, Neou, A., Nicod, L., O'Hehir, R., Ohta, K., Paggiaro, P., Palkonen, S., Palmer, S., Papadopoulos, N. G., Papi, A., Passalacqua, G., Pavord, I., Pedersen, S., Pigearias, B., Plavec, D., Postma, D. S., Price, D., Rabe, K. F., Radier Pontal, F., Redon, J., Rennard, S., Roberts, J., Robine, J. M., Roca, J., Roche, N., Rodenas, F., Roggeri, A., Rolland, C., Ryan, D., Sanchez Borges, M., Schünemann, H. J., Sheikh, A., Shields, M., Siafakas, N., Sibille, Y., Similowski, T., Small, I., Sola Morales, O., Sooronbaev, T., Stelmach, R., Sterk, P. J., Stiris, T., Sud, P., Tellier, V., To, T., Todo Bom, A., Triggiani, M., Valenta, R., Valero, A. L., Valovirta, E., Vandenplas, O., Van Ganse, E., Vasankari, T., Vestbo, J., Vezzani, G., Viegi, G., Visier, L., Vogelmeier, C., Vontetsianos, T., Wagstaff, R., Wallaert, B., Wahn, U., Whalley, B., Wickman, M., Williams, D., Wilson, N., Yawn, B. P., Yiallouros, P., Yusuf, O., Zar, H. J., Zhong, N., Zidarn, M., Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pulmonology, Ear, Nose and Throat, Groningen Research Institute for Asthma and COPD (GRIAC), Bousquet, J., Barbara, C., Bateman, E., Bel, E., Bewick, M., Chavannes, N. H., Cruz, A. A., Haahtela, T., Hellings, P. W., Khaltaev, N., Carlsen, K. L., Muraro, A., Cordeiro, C. R., Rosado-Pinto, J., Samolinski, B., Strandberg, T., Valiulis, A., Yorgancioglu, A., Zuberbier, T., Baena-Cagnani, C., Bernabeu-Wittel, M., Bonini, S., Fink-Wagner, A., Gonzalez-Diaz, S., Garces, J., Guzman, M. A., Melen, E., Menzies-Gow, A., Montilla-Santana, A., Nekam, Sanchez-Borges, M., Schunemann, H. J., and Sola-Morales, O.
- Subjects
Pediatrics ,Aging ,IMPACT ,Respiratory System ,GUIDELINES ,[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,Pulmonary Disease, Chronic Obstructive ,0302 clinical medicine ,Risk Factors ,Surveys and Questionnaires ,PROGRAM ,Surveys and Questionnaire ,030212 general & internal medicine ,Respiratory system ,ComputingMilieux_MISCELLANEOUS ,health care economics and organizations ,Respiratory Function Test ,media_common ,GINA STRATEGY ,integumentary system ,musculoskeletal, neural, and ocular physiology ,respiratory system ,Middle Aged ,humanities ,Adult ,Aged ,Asthma ,Chronic Disease ,Europe ,Humans ,Respiration Disorders ,Respiratory Function Tests ,Pulmonary and Respiratory Medicine ,3. Good health ,ALLERGIC RHINITIS ,CHRONIC RESPIRATORY-DISEASES ,Editorial ,General partnership ,GA(2)LEN ,Human ,Chronic Obstructive ,medicine.medical_specialty ,UNION ,Pulmonary disease ,Socio-culturale ,Pulmonary Disease ,03 medical and health sciences ,medicine ,media_common.cataloged_instance ,European union ,Intensive care medicine ,business.industry ,Risk Factor ,Respiration Disorder ,medicine.disease ,nervous system diseases ,Chronic disease ,DEFINITION ,030228 respiratory system ,Healthy ageing ,business ,SEVERE ASTHMA - Abstract
Chronic respiratory diseases (CRDs) are major non-communicable diseases (NCDs) [1, 2] that induce a significant burden. Asthma often occurs along the life cycle from early childhood, affecting 30 million children and adults under 45 years of age in Europe [3]. Chronic obstructive pulmonary disease (COPD) has an estimated annual death rate of over 3 million people globally [1, 2]. The annual direct and indirect costs in the 28 European Union (EU) countries due to COPD or asthma are estimated at 48 billion euros and 34 billion euros respectively [3]. Rhinitis occurs in over 100 million people in Europe, and indirect costs are enormous [4]. Asthma is a common risk factor for COPD [5, 6]. CRDs impact ageing and should be prevented, recognised and managed across the life cycle to promote active and healthy ageing (AHA). There is an urgent need to act globally. European Innovation Partnerships (EIPs) aim to enhance EU competitiveness and tackle societal challenges through research and innovation. To tackle the potential of ageing in the EU, the European Commission, within its Innovation Union policy, launched the EIP on AHA (between the Directorate General for Health and Food Safety (DG Santé) and Directorate General for Communications Networks, Content and Technology (DG CONNECT)) [7]. The B3 Action Plan promotes integrated care models for chronic diseases, including the use of remote monitoring. The initiative AIRWAYS-ICPs (integrated care pathways for airway diseases) [8] has been approved by the EIP on AHA as the model of chronic diseases of the B3 Action Plan. It is a Research Demonstration Project of the World Health Organization's Global Alliance against Chronic Respiratory Diseases (GARD) [1]. AIRWAYS-ICPs was initiated in 2013 by the WHO Collaborating Centre of Montpellier and the EIP on AHA Reference Site MACVIA-LR (Contre les MAladies Chroniques Pour un VIeillissement Actif en Languedoc-Roussillon, France) led by the Région Languedoc-Roussillon (France) [9]. 47 4 1028 1033
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- 2015
40. Hospitalizations for COPD Exacerbations: Trends and Determinants of Death
- Author
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Molinari, Nicolas, Briand, Camille, Vachier, Arnaud, Malafaye, Nicolas, Aubas, Pierre, Georgescu, Vera, Roche, Nicolas, Chanez, Pascal, Bourdin, Arnaud, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Biostatistique et Processus Spatiaux (BioSP), Institut National de la Recherche Agronomique (INRA), Aix Marseille Université (AMU), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] ( PhyMedExp ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Montpellier ( UM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve, Biostatistique et Processus Spatiaux ( BIOSP ), Institut National de la Recherche Agronomique ( INRA ), Aix Marseille Université ( AMU ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Biostatistique et Processus Spatiaux (BIOSP)
- Subjects
Aged, 80 and over ,Male ,Critical Care ,[ SDV ] Life Sciences [q-bio] ,[SDV]Life Sciences [q-bio] ,education ,Age Factors ,macromolecular substances ,Middle Aged ,Respiration, Artificial ,admissions ,Hospitalization ,Pulmonary Disease, Chronic Obstructive ,deaths ,COPD exacerbation ,Risk Factors ,Humans ,Female ,France ,Respiratory Insufficiency ,COPD epidemiology ,hospitalizations ,ComputingMilieux_MISCELLANEOUS ,Aged ,Retrospective Studies - Abstract
to understand epidemiological trends in severe COPD exacerbations through analyzes of hospitalizations and deaths during three consecutive years in a French administrative region area.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).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.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.
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- 2015
41. Integrated care pathways for airway diseases (AIRWAYS-ICPs)
- Author
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Bousquet, Jean, Addis, A., Adcock, I. M., Agache, I., Agusti, A., Alonso, A., Annesi-Maesano, I., Anto, Josep M., Bachert, C., Baena-Cagnani, C. E., Bai, C., Baigenzhin, A. K., Barbara, Cristina, Barnes, P. J., Bateman, E. D., Beck, L., Bedbrook, Anna, Bel, E. H., Benezet, O., Bennoor, K. S., Benson, M., Bernabeu-Wittel, M., Bewick, M., Bindslev-Jensen, C., Blain, Hubert, Blasi, F., Bonini, M., Bonini, S., Boulet, L. P., Bourdin, Arnaud, Bourret, Rodolphe, Brightling, C. E., Briggs, A. H., Brozek, J. L., Buhl, R., Bush, A., Caimmi, D. P., Calderon, M. A., Calverley, P. M., Camargos, P. A. M., Camuzat, Thierry, Canonica, G. W., Carlsen, K. H., Casale, T. B., Cazzola, M., A.M, Cepeda Sarabia, Cesario, A., Chen, Y. Z., Chkhartishvili, E., Chavannes, Niels H., Chiron, R., Chuchalin, Alexander G., Chung, K. F., Cox, L., Crooks, George, Cruz, A. A., Custovic, Adnan, Dahl, R., Dahlen, S. E., Blay, F. De, Dedeu, Antoni, Deleanu, D., Demoly, Pascal, Devillier, P., Didier, A., Dinh-Xuan, A. T., Djukanovic, R., Dokic, D., Douagui, H. B., Dubakiene, R., Eglin, S., Elliot, F., Emuzyte, R., Fabbri, Leonardo M., Fink-Wagner, A., Fletcher, M., Fokkens, W. J., Fonseca, J. A., Franco, A., Frith, P., Furber, A., Gaga, M., Garces, J., Garcia-Aymerich, Judith, Gamkrelidze, A., Diaz, S. González, Gouzi, Fares, Guzmán, M. A., Haahtela, T., Harrison, D., Hayot, M., Heaney, L. G., Heinrich, J., Hellings, P. W., Hooper, J., Humbert, M., Hyland, M. E., Iaccarino, G., Jakovenko, D., Jardim, J. R., Jeandel, Claude, Jenkins, C., Johnston, S. L., Jonquet, Olivier, Joos, G., Jung, K. S., Kalayci, O., Karunanithi, S., Keil, T., Khaltaev, N., Kolek, V., Kowalski, M. L., Kull, I., Kuna, P., Kvedariene, V., Le, Tuyen D., Carlsen, K. C. Lodrup, Louis, R., MacNee, W., Mair, A., Majer, I., Manning, P. J., Keenoy, E. De Manuel, Masjedi, M. R., Melén, E., Gomes, Elisabete Melo, Menzies-Gow, A., Mercier, G., Mercier, Jacques, Michel, J. P., Miculinic, N., Mihaltan, F., Milenkovic, B., Molimard, M., Momas, I., Montilla-Santana, A., Almeida, M. Morais, Morgan, M., N'Diaye, M., Nafti, S., Nekam, K., Neou, A., Nicod, L., O'Hehir, R. E., Ohta, K., Paggiaro, P. L., Palkonen, S., Palmer, S., Papadopoulos, N. G., Papi, A., Passalacqua, G., Pavord, I., Pigearias, B., Plavec, D., Postma, D. S., Price, D., Rabe, K. F., Radier-Pontal, F., Redon, Josep, Rennard, S., Roberts, J., Robine, J. M., Roca, J., Roche, N., Rodenas, F., Roggeri, A., Rolland, C., Rosado-Pinto, J., Ryan, D., Samolinski, B., Sanchez-Borges, M., Schunemann, H. J., Sheikh, A., Shields, K. M., Siafakas, N., Sibille, Y., Similowski, T., Small, I., Sola-Morales, O., Sooronbaev, T., Stelmach, R., Sterk, P. J., Stiris, T., Sud, P., Tellier, V., To, T., Todo-Bom, A., Triggiani, M., Valenta, R., Valero, A. L., Valiulis, A., Valovirta, E., Ganse, E. Van, Vandenplas, O., Vasankari, T., Vestbo, J., Vezzani, G., Viegi, Giovanni, Visier, L., Vogelmeier, C., Vontetsianos, T., Wagstaff, R., Wahn, U., Wallaert, B., Whalley, B., Wickman, M., Williams, D. M., Wilson, N., Yawn, B. P., Yiallouros, Panayiotis K., Yorgancioglu, A., Yusuf, O. M., Zar, H. J., Zhong, N., Zidarn, M., Zuberbier, T., Bousquet, J., Addis, A., Adcock, I., Agache, I., Agusti, A., Alonso, A., Annesi-Maesano, I., Anto, J. M., Bachert, C., Baena-Cagnani, C. E., Bai, C., Baigenzhin, A., Barbara, C., Barnes, P. J., Bateman, E. D., Beck, L., Bedbrook, A., Bel, E. H., Benezet, O., Bennoor, K. S., Benson, M., Bernabeu-Wittel, M., Bewick, M., Bindslev-Jensen, C., Blain, H., Blasi, F., Bonini, M., Bonini, S., Boulet, L. P., Bourdin, A., Bourret, R., Bousquet, P. J., Brightling, C. E., Briggs, A., Brozek, J., Buhl, R., Bush, A., Caimmi, D., Calderon, M., Calverley, P., Camargos, P. A., Camuzat, T., Canonica, G. W., Carlsen, K. H., Casale, T. B., Cazzola, M., Cepeda Sarabia, A. M., Cesario, A., Chen, Y. Z., Chkhartishvili, E., Chavannes, N. H., Chiron, R., Chuchalin, A., Chung, K. F., Cox, L., Crooks, G., Crooks, M. G., Cruz, A. A., Custovic, A., Dahl, R., Dahlen, S. E., De Blay, F., Dedeu, T., Deleanu, D., Demoly, P., Devillier, P., Didier, A., Dinh-Xuan, A. T., Djukanovic, R., Dokic, D., Douagui, H., Dubakiene, R., Eglin, S., Elliot, F., Emuzyte, R., Fabbri, L., Fink Wagner, A., Fletcher, M., Fokkens, W. J., Fonseca, J., Franco, A., Frith, P., Furber, A., Gaga, M., Garces, J., Garcia-Aymerich, J., Gamkrelidze, A., Gonzales-Diaz, S., Gouzi, F., Guzman, M. A., Haahtela, T., Harrison, D., Hayot, M., Heaney, L. G., Heinrich, J., Hellings, P. W., Hooper, J., Humbert, M., Hyland, M., Iaccarino, G., Jakovenko, D., Jardim, J. R., Jeandel, C., Jenkins, C., Johnston, S. L., Jonquet, O., Joos, G., Jung, K. S., Kalayci, O., Karunanithi, S., Keil, T., Khaltaev, N., Kolek, V., Kowalski, M. L., Kull, I., Kuna, P., Kvedariene, V., Le, L. T., Lodrup Carlsen, K. C., Louis, R., Macnee, W., Mair, A., Majer, I., Manning, P., De Manuel Keenoy, E., Masjedi, M. R., Melen, E., Melo-Gomes, E., Menzies-Gow, A., Mercier, G., Mercier, J., Michel, J. P., Miculinic, N., Mihaltan, F., Milenkovic, B., Molimard, M., Momas, I., Montilla-Santana, A., Morais-Almeida, M., Morgan, M., N'Diaye, M., Nafti, S., Nekam, K., Neou, A., Nicod, L., O'Hehir, R., Ohta, K., Paggiaro, P., Palkonen, S., Palmer, S., Papadopoulos, N. G., Papi, A., Passalacqua, G., Pavord, I., Pigearias, B., Plavec, D., Postma, D. S., Price, D., Rabe, K. F., Radier Ponta, F., Redon, J., Rennard, S., Roberts, J., Robine, J. M., Roca, J., Roche, N., Rodenas, F., Roggeri, A., Rolland, C., Rosado-Pinto, J., Ryan, D., Samolinski, B., Sanchez-Borges, M., Schunemann, H. J., Sheikh, A., Shields, M., Siafakas, N., Sibille, Y., Similowski, T., Small, I., Sola-Morales, O., Sooronbaev, T., Stelmach, R., Sterk, P. J., Stiris, T., Sud, P., Tellier, V., To, T., Todo-Bom, A., Triggiani, M., Valenta, R., Valero, A. L., Valiulis, A., Valovirta, E., Van Ganse, E., Vandenplas, O., Vasankari, T., Vestbo, J., Vezzani, G., Viegi, G., Visier, L., Vogelmeier, C., Vontetsianos, T., Wagstaff, R., Wahn, U., Wallaert, B., Whalley, B., Wickman, M., Williams, D. M., Wilson, N., Yawn, B. P., Yiallouros, P. K., Yorgancioglu, A., Yusuf, O. M., Zar, H. J., Zhong, N., Zidarn, M., Zuberbier, T., Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Department of Allergy and Clinical Immunology, Faculty of Medicine-Transylvania University, Applied Tumor Virology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Ghent University Hospital, Laboratoire d'ingénierie osteo-articulaire et dentaire (LIOAD), Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), iQ4U consultants Ltd, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Department of Pathophysiology and Transplantation, Università degli Studi di Milano = University of Milan (UNIMI), Istituto di Geoscienze e Georisorse, Pavia, Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy and Department of Medicine-University of Naples Federico II = Università degli studi di Napoli Federico II, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Department of Infection, Immunity and Inflammation, Royal Brompton Hospital, Région Languedoc-Roussillon-Midi-Pyrénées, Service de physiologie et explorations fonctionelles [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University Hospital Southampton, Vilnius University [Vilnius], IMIM-Hospital del Mar, Generalitat de Catalunya, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, University Hospitals Leuven [Leuven], University of Edinburgh, Pneumology Department, Marius Nasta Institute of Pneumology, Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw - Poland-Faculté de Pharmacie de Paris, Monash University [Melbourne], Allergy and Respiratory Diseases, Università degli studi di Genova = University of Genoa (UniGe), Mécanismes moléculaires dans les démences neurodégénératives (MMDN), Université Montpellier 2 - Sciences et Techniques (UM2)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurophysiologie Respiratoire Expérimentale et Clinique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), AcademicMedical Center, Oslo University Hospital [Oslo], University of Coimbra [Portugal] (UC), Division of Clinical Immunology and Allergy, University of Naples Federico II = Università degli studi di Napoli Federico II, University of Turku, Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Consiglio nazionale delle ricerche, Instituto di fisiologia clinica, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Service de Pneumologie et Immuno-Allergologie [CHU LIlle], Pole Cardio-vasculaire et pulmonaire [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University Hospital of Cologne [Cologne], Çocuk Sağlığı ve Hastalıkları, AII - Amsterdam institute for Infection and Immunity, Pulmonology, Ear, Nose and Throat, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of Milan, CNR, Rome, Italy and Department of Medicine-University of Naples Federico II, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), University of Helsinki, University of Genoa (UNIGE), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Università degli studi di Napoli Federico II, Groningen Research Institute for Asthma and COPD (GRIAC), Yiallouros, Panayiotis K. [0000-0002-8339-9285], Custovic, Adnan [0000-0001-5218-7071], and Γιάλλουρος, Παναγιώτης
- Subjects
Aging ,Settore MED/10 - Malattie dell'Apparato Respiratorio ,International Cooperation ,Respiratory System ,Medically Underserved Area ,Comorbidity ,Disease ,Early intervention ,Medical and Health Sciences ,[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,Pulmonary Disease, Chronic Obstructive ,0302 clinical medicine ,Disease control ,Risk Factors ,Chronic obstructive lung disease ,Health care ,030212 general & internal medicine ,Rhiniti ,media_common ,Rhinitis ,Environmental exposure ,Child health care ,3. Good health ,ALLERGIC RHINITIS ,Europe ,CHRONIC RESPIRATORY-DISEASES ,PERFORMANCE PROGRAM ,Action plan ,SIMULATION ,Asthma ,Decision Making ,European Union ,Guidelines as Topic ,Humans ,Pulmonary Disease ,Chronic Obstructive ,Quality of Life ,Respiration Disorders ,World Health Organization ,SMOKING ,Human ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Chronic respiratory tract disease ,DIAGNOSIS ,OBSTRUCTIVE PULMONARY-DISEASE ,03 medical and health sciences ,Quality of life (healthcare) ,EUROPEAN-UNION ,medicine ,MANAGEMENT ,media_common.cataloged_instance ,European union ,Intensive care medicine ,business.industry ,Public health ,Risk Factor ,ta3121 ,Respiration Disorder ,Integrated care ,030228 respiratory system ,Physical therapy ,Clinical Medicine ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,SEVERE ASTHMA - Abstract
International audience; The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYS-ICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).
- Published
- 2014
Catalog
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