Author: "Gaëtan Deslée" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Gaëtan Deslée"' showing total 253 results

Start Over Author "Gaëtan Deslée"

253 results on '"Gaëtan Deslée"'

1. Glypican-3 is a key tuner of the Hedgehog pathway in COPD

Author: Laure M.G. Petit, Lynda Saber Cherif, Maëva A. Devilliers, Sarah Hatoum, Julien Ancel, Gonzague Delepine, Anne Durlach, Xavier Dubernard, Jean-Claude Mérol, Christophe Ruaux, Myriam Polette, Gaëtan Deslée, Jeanne-Marie Perotin, and Valérian Dormoy
Subjects: COPD, Airway epithelial cells, Hedgehog, GPC3, Science (General), Q1-390, Social sciences (General), H1-99
Abstract: Hedgehog (HH) pathway is involved in pulmonary development and lung homeostasis. It orchestrates airway epithelial cell (AEC) differentiation and contributes to respiratory pathogenesis. The core elements Gli2, Smo, and Shh were found altered in the bronchial epithelium of patients with chronic obstructive pulmonary disease (COPD). Here, we investigated the co-receptors to fully decipher the complex machinery of airway HH pathway activation in health and COPD. The core elements and co-receptors of HH signalling were investigated in lung cell populations using single-cell RNAseq analysis. The transcript levels of the principal co-receptor GPC3 were investigated on public RNAseq datasets and by RT-qPCR. The localisation of GPC3 was evaluated through immunofluorescent stainings on isolated bronchial AEC and tissues from non-COPD and COPD patients. GPC3 pharmacological modulation was achieved with Codrituzumab during AEC differentiation. We demonstrated that the core elements were not abundant in pulmonary cell populations. Focusing on co-receptors, GPC3 was the most expressed transcript in tracheobronchial epithelial cells. The decrease in GPC3 transcript levels correlated with the severity of airway obstrution in COPD patients. Finally, interfering with GPC3 signalling during AEC differentiation induced downregulation of the HH pathway attested by a decrease of Gli2 leading to reduced ciliogenesis and altered mucin production. GPC3 appears as a crucial co-receptor for the HH pathway in the respiratory context. The modulation of GPC3 may represent a novel experimental strategy to tune HH signalling in therapeutic perspectives.
Published: 2025
Full Text: View/download PDF

2. LRP1 involvement in FHIT-regulated HER2 signaling in non-small cell lung cancer

Author: Théophile Ponchel, Emma Loeffler, Julien Ancel, Audrey Brisebarre, Nathalie Lalun, Véronique Dalstein, Anne Durlach, Gaëtan Deslée, Stéphane Dedieu, Myriam Polette, and Béatrice Nawrocki-Raby
Subjects: NSCLC, FHIT, HER2, LRP1, EMT, Cytology, QH573-671
Abstract: The tumor suppressor fragile histidine triad (FHIT) is frequently lost in non-small cell lung cancer (NSCLC). We previously showed that a down-regulation of FHIT causes an up-regulation of the activity of HER2 associated to an epithelial-mesenchymal transition (EMT) and that lung tumor cells harboring a FHITlow/pHER2high phenotype are sensitive to anti-HER2 drugs. Here, we sought to decipher the FHIT-regulated HER2 signaling pathway in NSCLC. Transcriptomic analysis of tumor cells isolated from NSCLC revealed the endocytic receptor low density lipoprotein receptor-related protein 1 (LRP1), a central regulator of membrane trafficking and cell signaling, as a potential player of this signaling. In a cohort of 80 NSCLC assessed by immunohistochemistry, we found a significant association between a low FHIT expression and a high pHER2 and LRP1 expression by tumor cells. Experiments of FHIT silencing showed that FHIT regulated LRP1 expression both at the mRNA and protein levels in lung cell lines. Analyzing the relationship between LRP1 and HER2, we observed that an anti-HER2 targeted therapy reversed LRP1 overexpression induced by FHIT silencing whereas LRP1 silencing did not affect HER2 activity. Studying the functional role of LRP1, we showed that cell proliferation and invasion induced by FHIT silencing were LRP1-dependent. In addition, we found that the induction of vimentin upon FHIT inactivation was counteracted by LRP1 silencing. These results suggest that LRP1 acts downstream of HER2 to induce EMT and tumor progression following FHIT loss. Dual targeting of HER2 and LRP1 might represent a therapeutic strategy to more efficiently inhibit HER2 signaling in FHIT-negative NSCLC.
Published: 2025
Full Text: View/download PDF

3. Patient education needs in severe asthma, a pilot study

Author: Rodolphe Laurence, Julien Ancel, Maëva A. Devilliers, Sophie Carre, Sandra Dury, Valérian Dormoy, Gaëtan Deslée, and Jeanne-Marie Perotin
Subjects: Severe asthma, Phenotype, Patient education, Eosinophils, Age, Diseases of the respiratory system, RC705-779
Abstract: Abstract Background Severe asthma is characterized by frequent exacerbations, altered lung function, and impaired quality of life. Tailored patient education allows for the improvement of both asthma management and quality of life. Our study aimed to assess the needs of severe asthma patient in therapeutic education, according to previous therapeutic patient education background and asthma phenotype. Methods Consecutive patients monitored for severe asthma in a tertiary referral center were considered for inclusion and answered a questionnaire detailing their patient education needs and the topics they would like to discuss. Asthma history, clinical and biological data, and lung function results were recorded. Results Fifty-three patients were included and 47 (88.7%) expressed at least one need. The most frequently selected topics were “life with asthma” (83%), “treatment use” (68%), and “exacerbation management” (60%), independent of previous participation in a patient education program dedicated to asthma. Patients of older age at inclusion, uncontrolled asthma, and T2-high phenotypes were associated with different profiles of patient education needs. Conclusion Our study identified frequent and various patient educational needs among severe asthmatics, highlighting the importance of an in-depth assessment of severe asthmatics expectations and the crucial need for the development of dedicated educational tools.
Published: 2024
Full Text: View/download PDF

4. Current cough and sputum assessed by the cough and sputum assessment-questionnaire (CASA-Q) is associated with quality of life impairment in cystic fibrosis

Author: Lucie Charon, Claire Launois, Jeanne-Marie Perotin, Bruno Ravoninjatovo, Pauline Mulette, Julien Ancel, Thomas Guillard, Anaëlle Muggeo, Valérian Dormoy, Muriel Griffon, Sophie Carré, François Lebargy, Gaëtan Deslée, and Sandra Dury
Subjects: Cystic fibrosis, Quality of life, CASA-Q, CFQ-R, Cough, Sputum, Diseases of the respiratory system, RC705-779
Abstract: Abstract Background Cough and sputum are major symptoms in cystic fibrosis (CF) that contribute to the impairment of quality of life. Methods This prospective single centre cross-sectional pilot study aimed to evaluate the results of a self-administered questionnaire assessing cough and sputum symptoms (2 domains), and their impact (2 domains) on daily activities in the previous week, named the Cough and Sputum Assessment Questionnaire (CASA-Q) in CF adult patients at stable state, and to analyse associations with clinical, functional, microbiological, radiological data, and two quality of life scales: the Cystic Fibrosis Questionnaire Revised (CFQ-R) and the Saint George Respiratory Questionnaire (SGRQ). Results Forty-eight patients were included in this analysis (69% men; median age of 27.8 ± 8.1 years; median body mass index of 21.8 + 3.3 kg/m²; mean FEV1 of 64 ± 30% of the predicted value). The mean values of the CASA-Q domains were 58 ± 23 for cough symptoms, 77 ± 24 for cough impact, 62 ± 25 for sputum symptoms and 84 ± 21 for sputum impact. Impairment in CASA-Q cough and sputum domains was associated with dyspnea mMRC scale (p
Published: 2023
Full Text: View/download PDF

5. Airway ciliated cells in adult lung homeostasis and COPD

Author: Laure M.G. Petit, Randa Belgacemi, Julien Ancel, Lynda Saber Cherif, Myriam Polette, Jeanne-Marie Perotin, Nathalie Spassky, Charles Pilette, Denise Al Alam, Gaëtan Deslée, and Valérian Dormoy
Subjects: Diseases of the respiratory system, RC705-779
Abstract: Cilia are organelles emanating from the cell surface, consisting of an axoneme of microtubules that extends from a basal body derived from the centrioles. They are either isolated and nonmotile (primary cilia), or grouped and motile (motile cilia). Cilia are at the centre of fundamental sensory processes and are involved in a wide range of human disorders. Pulmonary cilia include motile cilia lining the epithelial cells of the conductive airways to orchestrate mucociliary clearance, and primary cilia found on nondifferentiated epithelial and mesenchymal cells acting as sensors and cell cycle keepers. Whereas cilia are essential along the airways, their regulatory molecular mechanisms remain poorly understood, resulting in a lack of therapeutic strategies targeting their structure or functions. This review summarises the current knowledge on cilia in the context of lung homeostasis and COPD to provide a comprehensive overview of the (patho)biology of cilia in respiratory medicine with a particular emphasis on COPD.
Published: 2023
Full Text: View/download PDF

6. Soluble biomarkers to predict clinical outcomes in non-small cell lung cancer treated by immune checkpoints inhibitors

Author: Julien Ancel, Valérian Dormoy, Béatrice Nawrocki Raby, Véronique Dalstein, Anne Durlach, Maxime Dewolf, Christine Gilles, Myriam Polette, and Gaëtan Deslée
Subjects: liquid biopsy, soluble biomarkers, immunotherapy, non-small cell lung cancer (NSCLC), neutrophil lymphocyte ratio (NLR), circulating tumor (ctDNA), Immunologic diseases. Allergy, RC581-607
Abstract: Lung cancer remains the first cause of cancer-related death despite many therapeutic innovations, including immune checkpoint inhibitors (ICI). ICI are now well used in daily practice at late metastatic stages and locally advanced stages after a chemo-radiation. ICI are also emerging in the peri-operative context. However, all patients do not benefit from ICI and even suffer from additional immune side effects. A current challenge remains to identify patients eligible for ICI and benefiting from these drugs. Currently, the prediction of ICI response is only supported by Programmed death-ligand 1 (PD-L1) tumor expression with perfectible results and limitations inherent to tumor-biopsy specimen analysis. Here, we reviewed alternative markers based on liquid biopsy and focused on the most promising biomarkers to modify clinical practice, including non-tumoral blood cell count such as absolute neutrophil counts, platelet to lymphocyte ratio, neutrophil to lymphocyte ratio, and derived neutrophil to lymphocyte ratio. We also discussed soluble-derived immune checkpoint-related products such as sPD-L1, circulating tumor cells (detection, count, and marker expression), and circulating tumor DNA-related products. Finally, we explored perspectives for liquid biopsies in the immune landscape and discussed how they could be implemented into lung cancer management with a potential biological–driven decision.
Published: 2023
Full Text: View/download PDF

7. HER2 Alterations in Non-Small Cell Lung Cancer: Biologico-Clinical Consequences and Interest in Therapeutic Strategies

Author: Emma Loeffler, Julien Ancel, Véronique Dalstein, Gaëtan Deslée, Myriam Polette, and Béatrice Nawrocki-Raby
Subjects: non-small cell lung cancer, oncogenic drivers, HER2 alterations, anti-HER2 targeted therapy, Science
Abstract: Lung cancer stands as the first cause of death by cancer in the world. Despite the improvement in patients’ outcomes in the past decades through the development of personalized medicine approaches, a substantial portion of patients remains ineligible for targeted therapies due to the lack of a “druggable” molecular target. HER2, a receptor tyrosine kinase member of the EGFR/ErbB family, is known to show oncogenic properties. In this review, we focus on the different HER2 dysregulation mechanisms that have been observed in non-small cell lung cancer (NSCLC): gene mutation, gene amplification, protein overexpression and protein hyper-phosphorylation, the latter suggesting that HER2 dysregulation can occur independently of any molecular aberration. These HER2 alterations inevitably have consequences on tumor biology. Here, we discuss how they are not only involved in abnormal proliferation and survival of cancer cells but also potentially in increased angiogenic properties, mesenchymal features and tumor immune escape. Finally, we review the impact of these HER2 alterations in various therapeutic approaches. While standard chemotherapy and groundbreaking immunotherapy seem rather ineffective for HER2-altered NSCLCs, the development of HER2-targeted therapies such as tyrosine kinase inhibitors, anti-HER2 antibodies and especially antibody–drug conjugates could provide new hopes for patients.
Published: 2023
Full Text: View/download PDF

8. Transcriptomic FHITlow/pHER2high signature as a predictive factor of outcome and immunotherapy response in non-small cell lung cancer

Author: Audrey Brisebarre, Julien Ancel, Théophile Ponchel, Emma Loeffler, Adeline Germain, Véronique Dalstein, Valérian Dormoy, Anne Durlach, Gonzague Delepine, Gaëtan Deslée, Myriam Polette, and Béatrice Nawrocki-Raby
Subjects: NSCLC, FHIT, HER2, transcriptomic signature, prognosis, immunotherapy response, Immunologic diseases. Allergy, RC581-607
Abstract: IntroductionIn recent decades, the development of immunotherapy and targeted therapies has considerably improved the outcome of non-small cell lung cancer (NSCLC) patients. Despite these impressive clinical benefits, new biomarkers are needed for an accurate stratification of NSCLC patients and a more personalized management. We recently showed that the tumor suppressor fragile histidine triad (FHIT), frequently lost in NSCLC, controls HER2 receptor activity in lung tumor cells and that tumor cells from NSCLC patients harboring a FHITlow/pHER2high phenotype are sensitive to anti-HER2 drugs. Here, we sought to identify the transcriptomic signature of this phenotype and evaluate its clinical significance.Materials and methodsWe performed RNA sequencing analysis on tumor cells isolated from NSCLC (n=12) according to FHIT/pHER2 status and a functional analysis of differentially regulated genes. We also investigated the FHITlow/pHER2high signature in The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LUAD) (n=489) and lung squamous cell carcinoma (LUSC) (n=493) cohorts and used the tumor immune dysfunction and exclusion (TIDE) model to test the ability of this signature to predict response to immune checkpoint inhibitors (ICI).ResultsWe showed that up-regulated genes in FHITlow/pHER2high tumors were associated with cell proliferation, metabolism and metastasis, whereas down-regulated genes were related to immune response. The FHITlow/pHER2high signature was associated with the higher size of tumors, lymph node involvement, and late TNM stages in LUAD and LUSC cohorts. It was identified as an independent predictor of overall survival (OS) in LUAD cohort. FHITlow/pHER2high tumors were also predictive of poor response to ICI in both LUAD and LUSC cohorts.ConclusionThese data suggest that ICI might not be a relevant option for NSCLC patients with FHITlow/pHER2high tumors and that anti-HER2 targeted therapy could be a good therapeutic alternative for this molecular subclass with poorer prognosis.
Published: 2022
Full Text: View/download PDF

9. IL-20 Cytokines Are Involved in the Repair of Airway Epithelial Barrier: Implication in Exposure to Cigarette Smoke and in COPD Pathology

Author: Olivia Barada, Sophie Salomé-Desnoulez, Fahima Madouri, Gaëtan Deslée, Christelle Coraux, Philippe Gosset, and Muriel Pichavant
Subjects: airway epithelial cells, IL-20 cytokine family, COPD and epithelial repair, Cytology, QH573-671
Abstract: Background: Dysregulated inflammation as seen in chronic obstructive pulmonary disease (COPD) is associated with impaired wound healing. IL-20 cytokines are known to be involved in wound healing processes. The purpose of this study was to use ex vivo and in vitro approaches mimicking COPD to evaluate the potential modulatory role of interleukin-20 (IL-20) on the inflammatory and healing responses to epithelial wounding. Methods: The expression of IL-20 cytokines and their receptors was investigated in lung-derived samples collected from non-COPD and COPD patients, from mice chronically exposed to cigarette smoke and from airway epithelial cells from humans and mice exposed in vitro to cigarette smoke. To investigate the role of IL-20 cytokines in wound healing, experiments were performed using a blocking anti-IL-20Rb antibody. Results: Of interest, IL-20 cytokines and their receptors were expressed in bronchial mucosa, especially on airway epithelial cells. Their expression correlated with the disease severity. Blocking these cytokines in a COPD context improved the repair processes after a lesion induced by scratching the epithelial layer. Conclusions: Collectively, this study highlights the implication of IL-20 cytokines in the repair of the airway epithelium and in the pathology of COPD. IL-20 subfamily cytokines might provide therapeutic benefit for patients with COPD to improve epithelial healing.
Published: 2023
Full Text: View/download PDF

10. Identifying specific needs in adult cystic fibrosis patients: a pilot study using a custom questionnaire

Author: Sandra Dury, Jeanne-Marie Perotin, Bruno Ravoninjatovo, Catherine Llerena, Julien Ancel, Pauline Mulette, Muriel Griffon, Sophie Carré, Amélie Perrin, François Lebargy, Gaëtan Deslée, and Claire Launois
Subjects: Cystic fibrosis, Needs, Questionnaire, Quality of life, Fatigue, Diseases of the respiratory system, RC705-779
Abstract: Abstract Background Adult patients with cystic fibrosis (CF) experience daily physical symptoms and disabilities that can be challenging to address for health care teams. Methods We sought to identify the most frequent topics that CF adults need to discuss with health care teams using a custom questionnaire including 62 items. Results Fifty patients were included, 70% men, mean age 27.6 years, with a mean body mass index of 21.8 kg/m2. Mean FEV1% was 64% of predicted value. Forty-two percent of patients selected at least one topic. The most frequently selected topics were fatigue (20%), professional or scholar worries (18%), procreation (16%), physical activities (16%) and evolution of CF disease (16%). Women were more frequently concerned about fatigue, procreation and profession/school. Conclusions Using a custom questionnaire, we identified that CF adults express various unmet needs that extend beyond usual respiratory and nutritional concerns or treatment adherence. The interest of this questionnaire by health care team for improving therapeutic management of CF patients remains to be validated. Trial registration: The study was registered on ClinicalTrials.gov (NCT02924818) on 5th October 2016.
Published: 2021
Full Text: View/download PDF

11. CiliOPD: a ciliopathy-associated COPD endotype

Author: Jeanne-Marie Perotin, Myriam Polette, Gaëtan Deslée, and Valérian Dormoy
Subjects: COPD, Cilia, Transcriptomic, Diseases of the respiratory system, RC705-779
Abstract: Abstract The pathophysiology of chronic obstructive pulmonary disease (COPD) relies on airway remodelling and inflammation. Alterations of mucociliary clearance are a major hallmark of COPD caused by structural and functional cilia abnormalities. Using transcriptomic databases of whole lung tissues and isolated small airway epithelial cells (SAEC), we comparatively analysed cilia-associated and ciliopathy-associated gene signatures from a set of 495 genes in 7 datasets including 538 non-COPD and 508 COPD patients. This bio-informatics approach unveils yet undescribed cilia and ciliopathy genes associated with COPD including NEK6 and PROM2 that may contribute to the pathology, and suggests a COPD endotype exhibiting ciliopathy features (CiliOPD).
Published: 2021
Full Text: View/download PDF

12. The elastin peptide VGVAPG increases CD4+ T-cell IL-4 production in patients with chronic obstructive pulmonary disease

Author: Flora Lemaire, Sandra Audonnet, Jeanne-Marie Perotin, Pierre Gaudry, Sandra Dury, Julien Ancel, François Lebargy, Frank Antonicelli, Gaëtan Deslée, and Richard Le Naour
Subjects: COPD, T cells, Elastin peptides, Cytokines, IL-4, Flow cytometry, Diseases of the respiratory system, RC705-779
Abstract: Abstract Background In chronic obstructive pulmonary disease (COPD), lung-infiltrating inflammatory cells secrete proteases and participate in elastin breakdown and genesis of elastin-derived peptides (EP). In the present study, we hypothesized that the pattern of T lymphocytes cytokine expression may be modulated by EP in COPD patients. Methods CD4+ and CD8+ T-cells, sorted from peripheral blood mononuclear cells (PBMC) collected from COPD patients (n = 29) and controls (n = 13) were cultured with or without EP. Cytokine expression in T-cell phenotypes was analyzed by multicolor flow cytometry, whereas desmosine concentration, a specific marker of elastin degradation, was measured in sera. Results Compared with control, the percentage of IL-4 (Th2) producing CD4+ T-cells was decreased in COPD patients (35.3 ± 3.4% and 26.3 ± 2.4%, respectively, p
Published: 2021
Full Text: View/download PDF

13. Sonic hedgehog signalling as a potential endobronchial biomarker in COPD

Author: Julien Ancel, Randa Belgacemi, Jeanne-Marie Perotin, Zania Diabasana, Sandra Dury, Maxime Dewolf, Arnaud Bonnomet, Nathalie Lalun, Philippe Birembaut, Myriam Polette, Gaëtan Deslée, and Valérian Dormoy
Subjects: Chronic obstructive pulmonary disease, Hedgehog signalling pathway, Airway epithelial cells, Bronchoscopy, Diseases of the respiratory system, RC705-779
Abstract: Abstract Background The hedgehog (HH) pathway has been associated with chronic obstructive pulmonary disease (COPD) in genome-wide association studies and recent studies suggest that HH signalling could be altered in COPD. We therefore used minimally invasive endobronchial procedures to assess activation of the HH pathway including the main transcription factor, Gli2, and the ligand, Sonic HH (Shh). Methods Thirty non-COPD patients and 28 COPD patients were included. Bronchial brushings, bronchoalveolar lavage fluid (BALF) and bronchial biopsies were obtained from fiberoptic bronchoscopy. Characterization of cell populations and subcellular localization were evaluated by immunostaining. ELISA and RNAseq analysis were performed to identify Shh proteins in BAL and transcripts on lung tissues from non-COPD and COPD patients with validation in an external and independent cohort. Results Compared to non-COPD patients, COPD patients exhibited a larger proportion of basal cells in bronchial brushings (26 ± 11% vs 13 ± 6%; p
Published: 2020
Full Text: View/download PDF

14. Prevalence and Impact of Rheumatologic Pain in Cystic Fibrosis Adult Patients

Author: Axelle Schmoll, Claire Launois, Jeanne-Marie Perotin, Bruno Ravoninjatovo, Muriel Griffon, Sophie Carré, Pauline Mulette, Julien Ancel, Jean Hagenburg, François Lebargy, Gaëtan Deslée, Jean-Hugues Salmon, and Sandra Dury
Subjects: cystic fibrosis, pain, joint, spinal, rheumatologic, quality of life, Medicine (General), R5-920
Abstract: BackgroundWith the improvement of cystic fibrosis (CF) patient survival, the prevalence of long-term complications increased, among them rheumatologic disorders.MethodsThe aim of this prospective study was to evaluate the prevalence of spinal and joint pain, and their impact on disability, anxiety, depression, and quality of life in CF adult patients.ResultsForty-seven patients were analyzed, 72% of men, mean aged 28 years, with a mean body mass index of 22 kg/m2 and a mean FEV1% of 63%. Twenty-two patients (47%) described rheumatologic pain either spinal (n = 15, 32%) and/or joint pain (n = 14, 30%). Patients with spinal and/or joint pain were shorter (p = 0.023), more frequently colonized with Staphylococcus aureus (p < 0.008), had more frequent ΔF508 homozygous mutations (p = 0.014), and a trend for more impairment of the 6-min walking distance (p = 0.050). The presence of rheumatologic pain tended to be associated with disability according to the Health Assessment Questionnaire (HAQ) and anxiety. Compared with patients with no pain patients with both spinal and joint pain exhibited a more pronounced impact on the St George's Respiratory Questionnaire (SGRQ).ConclusionRheumatologic pain is frequent in CF adult patients, and may affect daily living, anxiety and quality of life. Systematic assessment of rheumatologic pain should be included in the management of CF patients.
Published: 2022
Full Text: View/download PDF

15. Assessment of the Association between Entropy in PET/CT and Response to Anti-PD-1/PD-L1 Monotherapy in Stage III or IV NSCLC

Author: Julie Malet, Julien Ancel, Abdenasser Moubtakir, Dimitri Papathanassiou, Gaëtan Deslée, and Maxime Dewolf
Subjects: entropy, immune checkpoint inhibitors, non-small cell lung cancer, positron-emission tomography, Science
Abstract: Anti-PD-1/PD-L1 therapy indications are broadened in non-small cell lung cancer (NSCLC) although immune checkpoint inhibitors (ICI) do not provide benefits for the entire population. Texture features based on positron emission tomography/computed tomography (PET/CT), especially entropy (based on a gray-level co-occurrence matrix (GLCM)), could be interesting as predictors in NSCLC. The aim of our retrospective study was to evaluate the association between GLCM-entropy and response to anti-PD-1/PD-L1 monotherapy at the first evaluation in stage III or IV NSCLC, comparing patients with progressive disease (PD) and non-progressive disease (non-PD). In total, 47 patients were included. Response Evaluation Criteria in Solid Tumors (RECIST 1.1) were used to evaluate the response to ICI treatment (nivolumab, pembrolizumab, or atezolizumab). At the first evaluation, 25 patients were PD and 22 were non-PD. GLCM-entropy was not predictive of response at the first evaluation. Furthermore, GLCM-entropy was not associated with progression-free survival (PFS) (p = 0.393) or overall survival (OS) (p = 0.220). Finally, GLCM-entropy measured in PET/CT performed before ICI initiation in stage III or IV NSCLC was not predictive of response at the first evaluation. However, this study demonstrates the feasibility of using texture parameters in routine clinical practice. The interest of measuring PET/CT texture parameters in NSCLC remains to be evaluated in larger prospective studies.
Published: 2023
Full Text: View/download PDF

16. Extended Bacteria Culture-Based Clustering Identifies a Phenotype Associating Increased Cough and Enterobacterales in Stable Chronic Obstructive Pulmonary Disease

Author: Anaëlle Muggeo, Jeanne-Marie Perotin, Audrey Brisebarre, Sandra Dury, Valérian Dormoy, Claire Launois, Julien Ancel, Pauline Mulette, Christophe de Champs, Gaëtan Deslée, and Thomas Guillard
Subjects: COPD—chronic obstructive pulmonary disease, Enterobacterales, microbiota, extended culture, stable state, Microbiology, QR1-502
Abstract: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by airflow limitation. This chronic respiratory disease represents the third leading cause of death worldwide. Alteration of the airway microbiota has been reported to be associated with exacerbation frequency in COPD, but its role on the symptoms in patients at stable state is still incompletely described. This study aimed to determine whether bacteria isolated in sputum can be associated with the clinical features of COPD patients within stable state. Our study highlights, for the first time, that altered microbiota with Enterobacterales is associated with pejorative clinical symptoms in stable COPD patients. The airway microbiota of 38 patients was analyzed using an extended culture approach and mass spectrometry identification. Cluster analysis by principal coordinate analysis of the bacterial communities showed that the patients could be classified into three distinct clusters in our cohort. The clusters showed no differences in proportions of the phylum, but one of them was associated with a high prevalence of Enterobacterales (71.4% in cluster 1 vs. 0% in cluster 3), loss of microbiota diversity, and higher bacterial load (107 vs. 105 CFU/ml, respectively) and characterized by predominant cough and impact on mental health. These novel findings, supported by further studies, could lead to modifying the processing of COPD sputum in the everyday practice of clinical microbiology laboratories.
Published: 2021
Full Text: View/download PDF

17. The Nicotinic Receptor Polymorphism rs16969968 Is Associated with Airway Remodeling and Inflammatory Dysregulation in COPD Patients

Author: Lynda Saber Cherif, Zania Diabasana, Jeanne-Marie Perotin, Julien Ancel, Laure M. G. Petit, Maëva A. Devilliers, Arnaud Bonnomet, Nathalie Lalun, Gonzague Delepine, Uwe Maskos, Philippe Gosset, Myriam Polette, Anaëlle Muggeo, Thomas Guillard, Gaëtan Deslée, and Valérian Dormoy
Subjects: COPD, airways, epithelial remodeling, nicotinic receptors, rs16969968, inflammation, Cytology, QH573-671
Abstract: Genome-wide association studies unveiled the associations between the single nucleotide polymorphism rs16969968 of CHRNA5, encoding the nicotinic acetylcholine receptor alpha5 subunit (α5SNP), and nicotine addiction, cancer, and COPD independently. Here, we investigated α5SNP-induced epithelial remodeling and inflammatory response in human COPD airways. We included 26 α5SNP COPD patients and 18 wild-type α5 COPD patients in a multi-modal study. A comparative histologic analysis was performed on formalin-fixed paraffin-embedded lung tissues. Isolated airway epithelial cells from bronchial brushings were cultivated in the air-liquid interface. Broncho-alveolar fluids were collected to detect inflammatory mediators. Ciliogenesis was altered in α5SNP COPD bronchial and bronchiolar epithelia. Goblet cell hyperplasia was exacerbated in α5SNP small airways. The broncho-alveolar fluids of α5SNP COPD patients exhibited an increase in inflammatory mediators. The involvement of the rs16969968 polymorphism in airway epithelial remodeling and related inflammatory response in COPD prompts the development of innovative personalized diagnostic and therapeutic strategies.
Published: 2022
Full Text: View/download PDF

18. Whole-Exome Sequencing of Bronchial Epithelial Cells Reveals a Genetic Print of Airway Remodelling in COPD

Author: Adeline Germain, Jeanne-Marie Perotin, Gonzague Delepine, Myriam Polette, Gaëtan Deslée, and Valérian Dormoy
Subjects: whole-exome sequencing, airway epithelial cells, COPD, Biology (General), QH301-705.5
Abstract: The remodelling of the airways is a hallmark of chronic obstructive pulmonary disease, but it is highly heterogeneous and erratically distributed in the airways. To assess the genetic print of remodelling in chronic obstructive pulmonary disease (COPD), we performed a comparative whole-exome sequencing analysis on microdissected bronchial epithelia. Lung resections from four non-COPD and three COPD subjects (ex-smokers and current smokers) were formalin-fixed paraffin-embedded (FFPE). Non-remodelled and remodelled bronchial epithelia were isolated by laser microdissection. Genomic DNA was captured and sequenced. The comparative quantitative analysis identified a list of 109 genes as having variants in remodelled epithelia and 160 genes as having copy number alterations in remodelled epithelia, mainly in COPD patients. The functional analysis highlighted cilia-associated processes. Therefore, bronchial-remodelled epithelia appeared genetically more altered than non-remodelled epithelia. Characterizing the unique molecular print of airway remodelling in respiratory diseases may help uncover additional factors contributing to epithelial dysfunctions, ultimately providing additional targetable proteins to correct epithelial remodelling and improve lung function.
Published: 2022
Full Text: View/download PDF

19. Impaired Ciliary Beat Frequency and Ciliogenesis Alteration during Airway Epithelial Cell Differentiation in COPD

Author: Julien Ancel, Randa Belgacemi, Zania Diabasana, Jeanne-Marie Perotin, Arnaud Bonnomet, Maxime Dewolf, Claire Launois, Pauline Mulette, Gaëtan Deslée, Myriam Polette, and Valérian Dormoy
Subjects: chronic obstructive pulmonary disease, cilia, airway epithelial cells, CBF, CiliOPD, Medicine (General), R5-920
Abstract: Chronic obstructive pulmonary disease (COPD) is a frequent respiratory disease. However, its pathophysiology remains partially elucidated. Epithelial remodeling including alteration of the cilium is a major hallmark of COPD, but specific assessments of the cilium have been rarely investigated as a diagnostic tool in COPD. Here we explore the dysregulation of the ciliary function (ciliary beat frequency (CBF)) and differentiation (multiciliated cells formation in air-liquid interface cultures) of bronchial epithelial cells from COPD (n = 17) and non-COPD patients (n = 15). CBF was decreased by 30% in COPD (11.15 +/− 3.37 Hz vs. 7.89 +/− 3.39 Hz, p = 0.037). Ciliary differentiation was altered during airway epithelial cell differentiation from COPD patients. While the number of multiciliated cells decreased (p < 0.005), the number of primary ciliated cells increased (p < 0.05) and primary cilia were shorter (p < 0.05). Altogether, we demonstrate that COPD can be considered as a ciliopathy through both primary non-motile cilia modifications (related to airway epithelial cell repair and remodeling) and motile cilia function impairment (associated with decrease sputum clearance and clinical respiratory symptoms). These observations encourage considering cilia-associated features in the complex COPD physiopathology and highlight the potential of cilia-derived biomarkers for diagnosis.
Published: 2021
Full Text: View/download PDF

20. Nuclear protein in testis carcinoma of the mediastinum: a case report

Author: Gonçalo Boleto, Jeanne-Marie Perotin, Claire Launois, Emmanuelle Uro-Coste, Philippe Birembaut, Sandra Dury, Hervé Vallerand, François Lebargy, Gaëtan Deslée, and Juliette Vella-Boucaud
Subjects: NUT carcinoma, Superior vena cava syndrome, Mediastinal neoplasms, Medicine
Abstract: Abstract Background Nuclear protein in testis carcinoma is a rare and very aggressive undifferentiated cancer which characteristically arises in the midline of the head, neck, and mediastinum. Case presentation We describe the case of a 46-year-old white woman admitted for superior vena cava syndrome revealing a mediastinal tumor. Pathological examination of specimens obtained by mediastinoscopy revealed an undifferentiated tumor with solid growth and positive immunoreactivity for p40 and negative immunoreactivity for cytokeratin markers. Immunohistochemical staining was positive for nuclear protein in testis, allowing the diagnosis of nuclear protein in testis midline carcinoma of the mediastinum. Conclusions We present a rare case of mediastinal nuclear protein in testis carcinoma with diagnosis based on nuclear protein in testis protein positivity and atypical immunohistochemical features including p40 positivity and anti-cytokeratin negativity. Physicians must remain aware of the possibility of nuclear protein in testis carcinoma especially in young patients with thoracic symptoms and suspicion of neoplasm.
Published: 2017
Full Text: View/download PDF

21. Airway epithelial cell differentiation relies on deficient Hedgehog signalling in COPD

Author: Randa Belgacemi, Emilie Luczka, Julien Ancel, Zania Diabasana, Jeanne-Marie Perotin, Adeline Germain, Nathalie Lalun, Philippe Birembaut, Xavier Dubernard, Jean-Claude Mérol, Gonzague Delepine, Myriam Polette, Gaëtan Deslée, and Valérian Dormoy
Subjects: Medicine, Medicine (General), R5-920
Abstract: Background: Hedgehog (HH) pathway is constantly under scrutiny in the context of organ development. Lung morphogenesis requires HH signalling which participates thereafter to the pulmonary homeostasis by regulating epithelial cell quiescence and repair. Since epithelial remodelling is a hallmark of Chronic Obstructive Pulmonary Disease (COPD), we investigated whether the main molecular actors of HH pathway participate to airway epithelial cell differentiation and we analysed their alterations in COPD patients. Methods: Sonic HH (Shh) secretion was assessed by ELISA in airway epithelial cell (AEC) air-liquid interface culture supernatants. HH pathway activation was evaluated by RT-qPCR, western blot and immunostaining. Inhibition of HH signalling was achieved upon Shh chelation during epithelial cell differentiation. HH pathway core components localization was investigated in lung tissues from non-COPD and COPD patients. Findings: We demonstrate that progenitors of AEC produced Shh responsible for the activation of HH signalling during the process of differentiation. Preventing the ligand-induced HH activation led to the establishment of a remodelled epithelium with increased number of basal cells and reduced ciliogenesis. Gli2 activating transcription factor was demonstrated as a key-element in the regulation of AEC differentiation. More importantly, Gli2 and Smo were lost in AEC from COPD patients. Interpretation: Our data suggest that HH pathway is crucial for airway epithelial cell differentiation and highlight its role in COPD-associated epithelial remodelling. Keywords: Chronic obstructive pulmonary disease, Airway epithelial cells, Differentiation, Cilia, Hedgehog
Published: 2020
Full Text: View/download PDF

22. Improvement of dyspnea after bariatric surgery is associated with increased Expiratory Reserve Volume: A prospective follow-up study of 45 patients.

Author: Louis Boissière, Jeanne-Marie Perotin-Collard, Eric Bertin, Isabelle Gaubil, Ana Diaz Cives, Coralie Barbe, Sandra Dury, Julie Nardi, François Lebargy, Gaëtan Deslée, and Claire Launois
Subjects: Medicine, Science
Abstract: To assess the effects of bariatric surgery in patients with obesity on dyspnea and to analyze the relationships between improvement of dyspnea after bariatric surgery and changes in pulmonary function, especially Expiratory Reserve Volume (ERV) which is the lung volume abnormality most frequently associated with obesity.Forty-five patients (5 males/40 females, mean Body Mass Index = 46.2 ± 6.8 kg/m2) were evaluated before and 6 to 12 months after bariatric surgery. Dyspnea was assessed by the modified Medical Research Council (mMRC) scale. Pulmonary function tests, arterial blood gases and six-minute walk test were performed. Laboratory parameters including C-Reactive Protein (CRP) were analyzed.Ninety percent of patients were dyspneic before surgery (mMRC scale ≥ 1) versus 59% after surgery (p
Published: 2017
Full Text: View/download PDF

23. Increased iron sequestration in alveolar macrophages in chronic obstructive pulmonary disease.

Author: Quentin Philippot, Gaëtan Deslée, Tracy L Adair-Kirk, Jason C Woods, Derek Byers, Susan Conradi, Sandra Dury, Jeanne Marie Perotin, François Lebargy, Christelle Cassan, Richard Le Naour, Michael J Holtzman, and Richard A Pierce
Subjects: Medicine, Science
Abstract: Free iron in lung can cause the generation of reactive oxygen species, an important factor in chronic obstructive pulmonary disease (COPD) pathogenesis. Iron accumulation has been implicated in oxidative stress in other diseases, such as Alzheimer's and Parkinson's diseases, but little is known about iron accumulation in COPD. We sought to determine if iron content and the expression of iron transport and/or storage genes in lung differ between controls and COPD subjects, and whether changes in these correlate with airway obstruction. Explanted lung tissue was obtained from transplant donors, GOLD 2-3 COPD subjects, and GOLD 4 lung transplant recipients, and bronchoalveolar lavage (BAL) cells were obtained from non-smokers, healthy smokers, and GOLD 1-3 COPD subjects. Iron-positive cells were quantified histologically, and the expression of iron uptake (transferrin and transferrin receptor), storage (ferritin) and export (ferroportin) genes was examined by real-time RT-PCR assay. Percentage of iron-positive cells and expression levels of iron metabolism genes were examined for correlations with airflow limitation indices (forced expiratory volume in the first second (FEV1) and the ratio between FEV1 and forced vital capacity (FEV1/FVC)). The alveolar macrophage was identified as the predominant iron-positive cell type in lung tissues. Furthermore, the quantity of iron deposit and the percentage of iron positive macrophages were increased with COPD and emphysema severity. The mRNA expression of iron uptake and storage genes transferrin and ferritin were significantly increased in GOLD 4 COPD lungs compared to donors (6.9 and 3.22 fold increase, respectively). In BAL cells, the mRNA expression of transferrin, transferrin receptor and ferritin correlated with airway obstruction. These results support activation of an iron sequestration mechanism by alveolar macrophages in COPD, which we postulate is a protective mechanism against iron induced oxidative stress.
Published: 2014
Full Text: View/download PDF

24. Bronchoscopic Lung Volume Reduction Coil Treatment for Severe Emphysema: A Systematic Review and Meta-Analysis of Individual Participant Data

Author: Sharyn A. Roodenburg, Jorine E. Hartman, Gaëtan Deslée, Felix J.F. Herth, Karin Klooster, Frank C. Sciurba, Pallav L. Shah, Arschang Valipour, Zaid Zoumot, and Dirk-Jan Slebos
Subjects: Emphysema, Pulmonary and Respiratory Medicine, Meta-analysis, Bronchoscopic lung volume reduction, Chronic obstructive pulmonary disease, Bronchoscopy
Abstract: Background: Lung volume reduction coil (LVR-coil) treatment provides a minimally invasive treatment option for severe emphysema patients which has been studied in multiple clinical trials. Objectives: The aim of the study was to assess the effect of LVR-coil treatment on pulmonary function, quality of life, and exercise capacity using individual participant data. Method: PubMed, Web of Science, and EMBASE were searched until May 17, 2021. Prospective single-arm and randomized controlled trials that evaluated the effect of LVR-coil treatment on forced expiratory volume in 1 s (FEV1), residual volume (RV), St. George Respiratory Questionnaire (SGRQ) total score, and/or 6-min walk distance (6MWD) and were registered in an official clinical trial database were eligible for inclusion. Individual patient data were requested, and a linear mixed effects model was used to calculate overall treatment effects. Results: Eight trials were included in the final analysis, representing 680 individual patients. LVR-coil treatment resulted in a significant improvement in FEV1 at 3- (0.09 L [95% confidence interval (95% CI): 0.06–0.12]) and 6-month follow-up (0.07 L [95% CI: 0.03–0.10]), a significant reduction in RV at 3- (−0.45L [95% CI: −0.62 to −0.28]), 6- (−0.33L [95% CI: −0.52 to −0.14]), and 12-month follow-up (−0.36L [95% CI: −0.64 to −0.08]), a significant reduction in SGRQ total score at 3- (−12.3 points [95% CI: −15.8 to −8.8]), 6- (−10.1 points [95% CI: −12.8 to −7.3]), and 12-month follow-up (−9.8 points [95% CI: −15.0 to −4.7]) and a significant increase in 6MWD at 3-month follow-up (38 m [95% CI: 18–58]). Conclusions: LVR-coil treatment in emphysema patients results in sustained improvements in pulmonary function and quality of life and shorter lived improvements in exercise capacity. Since the owner of this LVR-coil has decided to stop the production and newer generations LVR-coils are currently being developed, these results can act as a reference for future studies and clinical guidance.
Published: 2022
Full Text: View/download PDF

25. Immunbedingte Pankreatitis aufgrund einer Anti-PD-L1-Therapie bei einem Patienten mit nicht-kleinzelligem Lungenkrebs: Ein Fallbericht

Author: Julie Malet, Boutheina Melki, Stéphane Chouabe, and Gaëtan Deslée
Abstract: Rationale: Trotz klinisch nachgewiesener Vorteile von Immun-Checkpoint-Inhibitoren (ICI) bei fortgeschrittenem Lungenkrebs wurden seltene, aber lebensbedrohliche immunbedingte unerwünschte Ereignisse (ibUE) berichtet. Pankreatitis ist ein seltenes ibUE, das bei jedem ICI auftreten kann. Überblick zum Patienten: Ein 53-jähriger Mann mit einem lokal fortgeschrittenen nicht-kleinzelligen Lungenkarzinom wurde mit einer Radiochemotherapie und anschließend mit Durvalumab behandelt. Zwölf Wochen nach Beginn der Therapie mit dem ICI berichtete der Patient über Bauchschmerzen und Anorexie. Blutuntersuchungen zeigten einen hohen Lipasegehalt. Eine abdominale Computertomographie zeigte eine geschwollene Bauchspeicheldrüse. Diese Befunde wurden durch eine Magnetresonanz-Cholangiopankreatikographie und eine biliopankreatische endoskopische Ultraschalluntersuchung bestätigt. Diagnosen: Immunbedingte Pankreatitis Grad IV. Behandlungen: Der Patient wurde mit einer Kortikosteroidtherapie behandelt, die zu einer klinischen, radiologischen und biologischen Verbesserung führte. Ergebnisse: Während des ersten Monats konnte die Kortikosteroidtherapie nicht unter 1mg/kg/d gesenkt werden, da die Symptome wieder auftraten und die Lipasämie wieder zunahm. Vier Monate nach dieser Episode starb der Patient an einer akuten Ischämie der unteren Gliedmaßen bei Einnahme von Erkenntnisse: Soweit wir wissen, wurde über immunbedingte Pankreatitis nur im Zusammenhang mit Therapien gegen den programmierten Zelltod 1 oder gegen das zytotoxische T-Lymphozyten-Antigen 4 berichtet, aber nie mit einer Therapie gegen den programmierten Zelltod-Liganden 1. Es ist wichtig, solche seltenen Fälle zu melden, um die Diagnose und das Management von ibUE zu verbessern
Published: 2022
Full Text: View/download PDF

26. Sarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1): An open-label randomised controlled trial

Author: Anatole Harrois, Florence Patin, Anaïs Razurel, Laure Allanic, Grégoire Martin de Frémont, Vincent Jachiet, Gonçalo Boleto, Eric D'Ortenzio, Xavier Mariette, Philippe Dieudé, Etienne Canouï, Z Julia, Nathalie Dournon, Jean-Sébastien Hulot, David Lebeaux, Eric Mariotte, Dorothee Vallois, Laurence Berard, Nicolas Gambier, Christiane Verny, Mathilde Le Marchand, Mitja Jevnikar, Jean-Jacques Mourad, Marjolaine Morgand, Bertrand Guidet, Alexandre Moores, Prissile Bakouboula, Frédéric Pène, Pascal Richette, Martine Meunier, Juliette Camuset, Stéphane Jauréguiberry, Lynda Chalal, Mamadou Salif Cisse, Marie-Hélène Legros, Yann Nguyen, Damien Roux, Robin Deleris, Maxence Decavele, Patrice Cacoub, Isabelle Dusanter, Patricia Senet, Nassim Mahtal, Raphael Borie, Philippe Benoit, Blandine Denis, Luca Semerano, Sebastien Abad, Marie Dubert, Marie Lachatre, Marine Livrozet, Nathan Ebstein, Lakhdar Mameri, Adrien Michon, Olivier Sanchez, Aurélien Guffroy, Pierre Dupland, Jérôme Pacanowski, Yasmina Ferfar, Tassadit Hadjam, Anne-Marie Roques, Celine Comparon, Solaya Chalal, A Soria, Isabelle Lehir, Anne Gysembergh-Houal, Stéphanie Alary, Valérie Dejean, Elena Kiouris, Estelle Henry, Sophie Diemunsch, Jonathan London, Fanny Charbonnier, Alexandre Demoule, Louise Bondeelle, Samira Saleh-Mghir, Lise Bernard, Brigitte Sabatier, Anne Jacolot, Aurelie Sautereau, Pierre Faye, Benjamin Fournier, Noémie Abisror, Awa Ndiaye, Ruben Benainous, Damien Sène, Emmanuelle Sacco, Isabelle Debrix, Gabriel Nisand, Régis Peffault de Latour, Anne Sophie Korganow, Kévin Cardet, Perrine Guillaume-Jugnot, Soumeya Hammal, B. Duchemann, Elena Fois, Jean-Benoit Arlet, Christine Broissand, Yaël Amara, Matheus Vieira, Sophie Caillat-Zucman, Madona Sakkal, Juliette Djadi-Prat, Jean-Louis Teboul, Hélène François, Stéphane Renaud, Sylviane Ravato, Alaki Thiemele, Gabrielle Archer, Alain Fourreau, David Boutboul, Arsène Mekinian, Antoine Gros, Morgane Faure, Anne Pattyn, Camille Petit-Hoang, Jessica Krause le Garrec, Antony Canellas, Jean-Michel Molina, Zakaria Ait Hamou, Eric Oksenhendler, Ilias Koumis, Marie-Aude Penet, Catherine Boussard, Vincent Fallet, Guillaume Geri, Loic Kassegne, Bernard Cholley, Lucie Biard, Elodie Perrodeau, Tomas Urbina, David Schmitz, johann Cailhol, Elise Morawiec, Audrey Phibel, Sophie Renet, Emmanuel Weiss, Faouzi Saliba, Kristina Beziriganyan, Abdellatif Tazi, Isabelle Peigney, Bertrand Dunogue, Rémy Gauzit, Damien Bergerot, Bob Heger, Ines Ben-Mabrouk, Jade Ghosn, Benjamin Planquette, Alexis Régent, François Weill, Yasmina Mekid, Rosa Da Silva, Victor Lancon, Marc Michel, Nadia Anguel, Anne Claire Desbois, François Danion, Brigitte Ranque, Mohamed Belloul, Nadège Lemarié, Amélie Cransac, Marine Nadal, Lalia Djaghout, Anne Tréhan, Samy Figueiredo, Hakim Meddah, Aurélie Clan Hew Wai, Julie Delemazure, Soraya Fellahi, Jacques-Eric Gottenberg, Matthieu Uzzan, Jean-Charles Duclos-Vallée, Tabassome Simon, Vanessa Rathouin, Yves Hansmann, Hélène Gros, Syllia Belazouz, Nathalie Marin, Camille Rolland-Debord, Edouard Lefèvre, Sophie-Rym Hamada, Tristan Martin, Annabelle Stoclin, Frédéric Duée, Helene Chambrin-Lauvray, Ramdane Meftali, Miguel Alejandro Vasquez-Ibarra, Isabelle Madeleine, Simon Valayer, Anne Adda, Marie-Thérèse Tremorin, Nicolas Meyer, Vixra Keo, Lara Zafrani, Caroline Semaille, Maxime Dougados, Olivier Olivier, Emeline Colomba, Florence Morin, Claire Rouzaud, Paul Michel Mertes, Claire Montlahuc, Anne Blanchard, Valérie Pourchet-Martinez, Constance Delaugerre, Nicolas Carlier, Jacques Cadranel, Nicolas Noel, Kahina Cheref, Bao Phung, Moez Jallouli, Ulrich Clarac, Marthe Rigal, Mireille Adda, Lionel Galicier, Fanny Domont, Lee S. Nguyen, Férial Berbour, Fanny Pommeret, Celine Dupré, Gaël Leprun, Jean-Luc Diehl, Laetitia Languille, Philippe Blanche, Abolfazl Mohebbi, Mathilde Noaillon, Olivier Collange, Paul Jaubert, Anne Daguenel-Nguyen, Sandrine Briois, Anne-Lise Pouliquen, Coralie Bloch Queyrat, Clément Jourdaine, Cédric Pierron, Geoffrey Rossi, Chloe McAvoy, Claire Courtin, Mathias Cornic, C Rioux, Christine Lemagner, Martin Dres, Emmanuelle Guillot, Marc Garnier, Safaa Nemlaghi, Guillaume Grailles, Yazdan Yazdanpanah, Veronique Joly, Thiziri Sadaoui, Marion Bouhris, Vincent Castelain, Muriel Fartoukh, Sébastien Cavelot, Sophie Ohlmann-Caillard, Valentina Isernia, Bruno Crestani, Thinhinane Bariz, Benjamin Chaigne, Emmanuel Andrès, Frédéric Blanc, Alain Wynckel, Louise-Laure Mariani, Yasmine Messaoudi, Naima Sguiouar, Amina Kebir, Asmaa Mamoune, Caroline Gaudefroy, Victoire De Lastours, Pierre Diemunsch, Etienne Lengliné, Claire Tantet, Julien Mayaux, Benjamin G. Chousterman, Arthur Pavot, Anne Rachline, Gwenaël Lorillon, Hassan Joumaa, Nicolas Lefebvre, Elodie Baudry, Nicolas Bonnet, Fanny Defrancq, Véronique Vigna, Yves Cohen, Amira Benattia, Martin Siguier, Sophie Georgin-Lavialle, Emmanuelle Bugnet, Lamiae Grimaldi, Olivia Daconceicao, Olivier Hermine, Mathieu Vautier, Florence Tubach, Marion Licois, Anaïs Codorniu, Fanny Alby-Laurent, Jérémie Zerbit, Aude Jacob, Benedicte Giroux-Leprieur, Carine Karachi, Laurent Cylly, Edouard Flamarion, Gladys Aratus, Charléne Jouve, Robin Dhote, Claire Davoine, Valentin Greigert, Gaelle Leroux, Cécile Kedzia, Guillaume Lefèvre, Catherine Metzger, Olivier Benveniste, Clairelyne Dupin, Marie-Alexandra Alyanakian, Mathieu Oberlin, Julien Poissy, Linda Gimeno, Adrien Contejean, Segolene Toquet, Jeanne CHAUFFiER, Mathieu Jozwiak, Laurent Savale, Virginie Zarrouk, Cécile Yelnik, Mandy Nizard, Mourad Djadel, F-Xavier Lescure, Agnes Maurer, Geoffroy Liégeon, Arthur Neuschwander, Hélène Lafoeste, Gaëtan Deslée, Frédéric De Blay, Claire Pernin, Cloé Comarmond, Anne Hutt, Ridha Belilita, Laurence Lecomte, Sophie-Caroline Sacleux, Nathalie Rozensztajn, Jean-Jacques Tudesq, Benjamin Terrier, Solène Fabre, Lelia Escaut, Eva Chatron, Emmanuelle Blin, Pauline Jouany, Sara Sambin, Chistophe Willekens, Nabil Raked, Jean-Simon Rech, Serge Bureau, Boris Bienvenu, Elisabeth Coupez, Tali-Anne Szwebel, Lydia Suarez, Chaouki Bouras, Kamyl Baghli, Emilia Stan, Valérie Camara-Clayette, Fanette Denies, Nathalie Menage, Paul Legendre, Axelle Fuentes, Oriane Puéchal, Charlotte Kaeuffer, Guillaume Becker, Clara Campos-Vega, Armand Mekontso-Dessaps, Pernelle Vauboin, Yurdagul Uzunhan, F Louni, Marie hélène Pari, Myriam Virlouvet, Nicolas Belaube, Hugues Cordel, Nathalie Chavarot, Olivier Sitbon, Jean-Daniel Lelievre, Matthieu Mahévas, Julie Smati, Olivier Clovet, Marc Bardou, Ada Clarke, Gilles Garcia, Anouk Walter-Petrich, Hala Semri, Vasco Honsel, Giovanna Melica, Pierre Mora, Olivier Fain, A Gervais, Marc Humbert, Yves Allenbach, Céline Verstuyft Verstuyft, Blandine Lehmann, Pascal Martel, Aida Zahrate-Ghoul, Karine Martin, Alexandre Bourgoin, Baptiste Duceau, Philippe Ravaud, Celine Wilpotte, Sylvie Le Gac, Michaël Darmont, Aurélie Durel Maurisse, Younes Keroumi, Aude Rigolet, Julie Chas, Pierre-Louis Tharaux, Caroline Morbieu, Valérie Paquet, Eric Vicaut, Pascaline Choinier, Samir Hamiria, Elsa Feredj, Frédéric Schlemmer, Gilles Pialoux, Zeina Louis, Marion Parisey, David Montani, Jean-Pierre Riveline, Jean-Marie Michot, Pascal Lim, Eliane Bertrand, Gaelle Clavere, Julie Jambon, Stéphane Brin, Saskia Flamand, Jeanne Meunier, Geoffroy Volle, Martin De Sarcus, Marie Vayssettes, Thomas Papo, Caroline Hauw-Berlemont, Gabriel Baron, Jeremy Arzoine, Loren Soyez-Herkert, Maria Pereira, Antoine Parrot, Johanna Oziel, Carole Burger, Eric Noll, Paul Vermes, Jeanne Goupil de Bouille, Xavier Monnet, Paul Crespin, Sarah Dalibey, Thierno Dieye, Renaud Felten, Jean-Philippe Bastard, Younes El Amine, Timothee Bironne, Damien Vanhoye, Amine Ghembaza, Laure Berton, Yvon Ruch, Thomas Volpe, Thomas Gorget, Jaouad Benhida, Julien Saussereau, Elodie Issorat, Virginie Elisee, Adrien Mirouse, Cecile Larcheveque, Laurène Deconinck, A. Dossier, Félix Ackermann, Greggory Ducrocq, Anne Bergeron, Laurence Annonay, Camille Knosp, Laurence Drouard, Adrien Joseph, Hilario Nunes, Hanane Fodil, Sabrine Ouamri, Belkacem Asselate, Julie Fillon, Dominique Dautel, Isabelle Brindele, Robin Charreteur, S Lariven, Elie Azoulay, Sami Kolta, Cédric Sublon, Florence Bellenfant, Melissa Clément, Lola-Jade Palmieri, Bruno Mourvillier, Ewa Kozaliewicz, Vincent Provitolo, Marie Lecronier, Julien Chabert, Matthieu Resche-Rigon, Stéphan Pavy, Naura Gamany, Dorothée Chopin, Aïcha Bah, Moustafa Benafla, Corinne Guerin, Pierre Tissieres, Nathalie Costedoat-Chalumeau, Nessima Yelles, Emmanuel Chatelus, Jean-Christophe Corvol, Luc Mouthon, Marie Gilbert, Matthieu Lemoine, Lucie Aunay, Candice Estellat, Laure Choupeaux, Dhiaa Meriem Hai, Bernard Goichot, Céline Louapre, Roza Rahli, Nathalie De Castro, Christian Richard, Malikhone Chansombat, Kamil Chitour, Joseph Emmerich, Elodie Drouet, Julien Pottecher, Eric Demonsant, Alexandra Beurton, Raphaël Porcher, Lauren Demerville, Amélie Servettaz, Annabelle Pourbaix, Philippe Manivet, Pierre-Grégoire Guinot, Nicolas Champtiaux, Caroline Pradon, Annick Tibi, Julien Le Marec, Nawal Derridj, Mohamad Zaidan, Eric Marquis, Mickael Henriques, Bruno Mégarbane, Aline Frazier, Ramon Junquera, Diane Le Pluart, Coralie Gernez, Yacine Boudali, Dimitri Fremont, Pierrick Le Borgne, Corinne Pernot, Mélanie Dehais, Claire Madelaine, Dominique Roulot, Georgina Maalouf, Constance Guillaud, Corine Nyanou, Karine Celli Lebras, Sophie Granville, Sabrina Brahmi, Catherine Le Bourlout, Hassan Tarhini, Asmaa Mabrouki, Hakim Tayebi, Sophie Ismael, Jonathan Marey, Sophie Bayer, Gabriel Steg, Antoine Fayol, Catherine Fauvaux, Delphine Feyeux, Côme Bureau, Alexandre Morel, Agathe Bounhiol, Alexandre Buffet, Souad Benarab, Luc Haudebourg, Pierre Le Guen, Damien Vimpere, Xavier Jaïs, Clotilde Le Tiec Le Tiec, Sophie Bulifon, Pélagie Thibaut, Alison Klasen, Claire Pacheco, Anne Godier, Marie Antignac, Domitille Molinari, Philippe Durand, Olivier Lambotte, Paul Henri Grisot, Anne Lise Jegu, Vincent Poindron, Ruxandra Burlacu, Denis Jesuthasan, Sarah Benghanem, Solen Kernéis, Antoine Bachelard, Jacques Duranteau, Karine Lacombe, Olivia Lenoir, Mathilde Vallet, Sara Virolle, Léa Resmini, Liem Binh Luong Nguyen, Marie Matignon, Céline Leplay, and Claire Aguilar
Subjects: medicine.medical_specialty, business.industry, Immunology, Hazard ratio, Absolute risk reduction, Articles, medicine.disease, law.invention, Clinical trial, Pneumonia, Sarilumab, Rheumatology, Randomized controlled trial, law, Internal medicine, Cohort, medicine, Immunology and Allergy, Adverse effect, business
Abstract: Summary Background Patients with COVID-19 pneumonia can have increased inflammation and elevated cytokines, including interleukin (IL)-6, which might be deleterious. Thus, sarilumab, a high-affinity anti-IL-6 receptor antibody, might improve the outcome of patients with moderate-to-severe COVID-19 pneumonia. Methods We did a multicentric, open-label, Bayesian randomised, adaptive, phase 2/3 clinical trial, nested within the CORIMUNO-19 cohort, to test a superiority hypothesis. Patients 18 years or older hospitalised with COVID-19 in six French centres, requiring at least 3L/min of oxygen but without ventilation assistance and a WHO Clinical Progression Scale [CPS] score of 5 were enrolled. Patients were randomly assigned (1:1) via a web-based system, according to a randomisation list stratified on centre and with blocks randomly selected among 2 and 4, to receive usual care plus 400 mg of sarilumab intravenously on day 1 and on day 3 if clinically indicated (sarilumab group) or usual care alone (usual care group). Primary outcomes were the proportion of patients with WHO-CPS scores greater than 5 on the 10-point scale on day 4 and survival without invasive or non-invasive ventilation at day 14. This completed trial is closed to new participants and is registered with ClinicalTrials.gov , NCT04324073 . Findings 165 patients were recruited from March 27 to April 6, 2020, and 148 patients were randomised (68 patients to the sarilumab group and 80 to the usual care group) and followed up for 90 days. Median age was 61·7 years [IQR 53·0–71·1] in the sarilumab group and 62·8 years [56·0–71·7] in the usual care group. In the sarilumab group 49 (72%) of 68 were men and in the usual care group 59 (78%) of 76 were men. Four patients in the usual care group withdrew consent and were not analysed. 18 (26%) of 68 patients in the sarilumab group had a WHO-CPS score greater than 5 at day 4 versus 20 (26%) of 76 in the usual care group (median posterior absolute risk difference 0·2%; 90% credible interval [CrI] −11·7 to 12·2), with a posterior probability of absolute risk difference greater than 0 of 48·9%. At day 14, 25 (37%) patients in the sarilumab and 26 (34%) patients in the usual care group needed ventilation or died, (median posterior hazard ratio [HR] 1·10; 90% CrI 0·69–1·74) with a posterior probability HR greater than 1 of 37·4%. Serious adverse events occurred in 27 (40%) patients in the sarilumab group and 28 (37%) patients in the usual care group (p=0·73). Interpretation Sarilumab treatment did not improve early outcomes in patients with moderate-to-severe COVID-19 pneumonia. Further studies are warranted to evaluate the effect of sarilumab on long-term survival. Funding Assistance publique—Hopitaux de Paris
Published: 2022
Full Text: View/download PDF

27. Endobronchial Coil System versus Standard-of-Care Medical Management in the Treatment of Subjects with Severe Emphysema

Author: Felix J.F. Herth, Dirk-Jan Slebos, Ralf-Harto Huebner, Armelle Marceau, Dirk Skowasch, Romain Kessler, Karin Klooster, Hervé Dutau, Francesca Conway, Hervé Mal, Arschang Valipour, Kaid Darwiche, Martin Hetzel, Gaëtan Deslée, Arnaud Bourdin, Michaela Bezzi, P Hammerl, Christian Schumann, Christian Grah, Charles-Hugo Marquette, Jacques Boutros, Franz Stanzel, Christophe Pison, Pallav L. Shah, University Medical Center Groningen [Groningen] (UMCG), Klinik Floridsdorf [Wien], FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Université Côte d'Azur (UCA), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Royal Brompton Hospital, Centre Hospitalier Universitaire de Reims (CHU Reims), Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire [Grenoble] (CHU), Klinik für Anthroposophische Medizin, Krankenhaus vom Roten Kreuz Bad Cannstatt, Klinikverbund Kempten-Oberallgäu gGmbH, Nouvel Hôpital Civil de Strasbourg, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Universitätsklinikum Bonn (UKB), Ruhrlandklinik University Hospital, Lungenfachklinik Immenhausen, Lungenklinik Hemer, Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia [Brescia], Service de Pneumologie et Allergie - Hôpital Nord [Marseille], Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University Medical Center Heidelberg, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Groningen Research Institute for Asthma and COPD (GRIAC)
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Bronchoscopic lung volume reduction, Endobronchial coil treatment, [SDV]Life Sciences [q-bio], Medizin, Hyperinflation, Severity of Illness Index, Quality of life, Internal medicine, Bronchoscopy, MINIMAL IMPORTANT DIFFERENCE, Interventional Pulmonology, Humans, Medicine, Lung volumes, Prospective Studies, Respiratory system, Pneumonectomy, Adverse effect, Aged, Aged, 80 and over, Emphysema, business.industry, Prostheses and Implants, Middle Aged, respiratory system, 3. Good health, respiratory tract diseases, Clinical trial, LUNG-VOLUME REDUCTION, Electromagnetic coil, Early Termination of Clinical Trials, Cohort, Cardiology, Female, business
Abstract: Background: Bronchoscopic lung volume reduction using endobronchial coils is a new treatment for patients with severe emphysema. To date, the benefits have been modest and have been suggested to be much larger in patients with severe hyperinflation and nonmulti-comorbidity. Objective: We aimed to evaluate the efficacy and safety of endobronchial coil treatment in a randomized multicenter clinical trial using optimized patient selection. Method: Patients with severe emphysema on HRCT scan with severe hyperinflation (residual volume [RV] ≥200% predicted and RV/total lung capacity [TLC] >55%) were randomized to coil treatment or control. Primary outcome measures were differences in the forced expiratory volume in 1 s (FEV1) and St George’s Respiratory Questionnaire (SGRQ) total score at 6 months. Results: Due to premature study termination, a total of 120 patients (age 63 ± 7 years, FEV1 29 ± 7% predicted, RV 251 ± 41% predicted, RV/TLC 67 ± 6%, and SGRQ 58 ± 13 points), instead of 210 patients, were randomized. At study termination, 91 patients (57 coil and 34 control) had 6-month results available. Analyses showed significantly greater improvements in favor of the coil group. The increase in FEV1 was greater in the coil group than that in the control group by + 10.3 [+4.7 to +16.0] % and in SGRQ by −10.6 [−15.9 to −5.4] points. At study termination, there were 5 (6.8%) deaths in the coil cohort reported. Conclusion: Despite early study termination, coil treatment compared to control results in a significant improvement in the lung function and quality of life benefits for up to 6 months in patients with emphysema and severe hyperinflation. These improvements were of clinical importance but were associated with a higher likelihood of serious adverse events.
Published: 2021
Full Text: View/download PDF

28. Transcriptomic FHIT

Author: Audrey, Brisebarre, Julien, Ancel, Théophile, Ponchel, Emma, Loeffler, Adeline, Germain, Véronique, Dalstein, Valérian, Dormoy, Anne, Durlach, Gonzague, Delepine, Gaëtan, Deslée, Myriam, Polette, and Béatrice, Nawrocki-Raby
Abstract: In recent decades, the development of immunotherapy and targeted therapies has considerably improved the outcome of non-small cell lung cancer (NSCLC) patients. Despite these impressive clinical benefits, new biomarkers are needed for an accurate stratification of NSCLC patients and a more personalized management. We recently showed that the tumor suppressor fragile histidine triad (FHIT), frequently lost in NSCLC, controls HER2 receptor activity in lung tumor cells and that tumor cells from NSCLC patients harboring a FHITWe performed RNA sequencing analysis on tumor cells isolated from NSCLC (n=12) according to FHIT/pHER2 status and a functional analysis of differentially regulated genes. We also investigated the FHITWe showed that up-regulated genes in FHITThese data suggest that ICI might not be a relevant option for NSCLC patients with FHIT
Published: 2022

29. Primary ciliogenesis is a crucial step for multiciliated cell determinism in the respiratory epithelium

Author: Xavier Dubernard, Randa Belgacemi, Gaëtan Deslée, Jean-Claude Mérol, Christophe Ruaux, Valérian Dormoy, Zania Diabasana, Jeanne-Marie Perotin, Antony Hoarau, Myriam Polette, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Reims (CHU Reims), Clinique mutualiste La Sagesse, Hôpital Maison Blanche, and dormoy, valerian
Subjects: 0301 basic medicine, Mucociliary clearance, [SDV]Life Sciences [q-bio], Short Communication, Context (language use), Respiratory Mucosa, Biology, 03 medical and health sciences, 0302 clinical medicine, Ciliogenesis, Homeostasis, Humans, Respiratory system, ComputingMilieux_MISCELLANEOUS, Cells, Cultured, Epithelial cell differentiation, Cilium, cilia, airway epithelium, Cell Biology, respiratory system, 3. Good health, Cell biology, [SDV] Life Sciences [q-bio], cell differentiation, 030104 developmental biology, 030220 oncology & carcinogenesis, Motile cilium, Molecular Medicine, Respiratory epithelium
Abstract: The alteration of the mucociliary clearance is a major hallmark of respiratory diseases related to structural and functional cilia abnormalities such as chronic obstructive pulmonary diseases (COPD), asthma and cystic fibrosis. Primary cilia and motile cilia are the two principal organelles involved in the control of cell fate in the airways. We tested the effect of primary cilia removal in the establishment of a fully differentiated respiratory epithelium. Epithelial barrier integrity was not altered while multiciliated cells were decreased and mucous‐secreting cells were increased. Primary cilia homeostasis is therefore paramount for airway epithelial cell differentiation. Primary cilia‐associated pathophysiologic implications require further investigations in the context of respiratory diseases.
Published: 2021
Full Text: View/download PDF

30. Insomnia in adults with cystic fibrosis: strong association with anxiety/depression and impaired quality of life

Author: Bruno Ravoninjatovo, Jeanne-Marie Perotin, Camille Guguen, Sandra Dury, Julien Ancel, C. Launois, Pauline Mulette, Coralie Barbe, Gaëtan Deslée, Dominique Perdu, Thomas Guillard, François Lebargy, Antoine Dumazet, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Universitaire de Reims (CHU Reims)
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, Quality of life, medicine.medical_specialty, Insomnia, [SDV]Life Sciences [q-bio], Pain, Anxiety, Severity of Illness Index, Cystic fibrosis, Pulmonary function testing, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Sleep Initiation and Maintenance Disorders, Surveys and Questionnaires, Internal medicine, medicine, Humans, 030212 general & internal medicine, Restless legs syndrome, Depression (differential diagnoses), Psychiatric Status Rating Scales, lcsh:RC705-779, Depression, business.industry, lcsh:Diseases of the respiratory system, medicine.disease, Respiratory Function Tests, 3. Good health, 030228 respiratory system, Sputum, Female, Anxiety-depression, France, medicine.symptom, business, Sleep, Research Article
Abstract: Background While sleep disruption is a common complaint among children with cystic fibrosis (CF), only a few studies have investigated insomnia in adults. The aim of this study was to identify factors associated with insomnia in clinically stable adult CF patients. Methods Twenty-eight CF patients (18M/10F), with a median age of 27 (22–34) (median (interquartile range) years and a median of forced expiratory volume in one second of 72 (39–93) % predicted completed questionnaires on insomnia (Insomnia Severity Index, ISI), sleep quality (PSQI), daytime sleepiness (Epworth), restless legs syndrome (IRLS), pain (NRS), anxiety/depression (HAD) and quality of life (CFQ-R 14+). Respiratory assessment data, including symptoms, sputum analysis, arterial blood gases, 6-min walking test, pulmonary function tests and polysomnographic variables, were also analyzed. Results Forty-three percent of patients were insomniac (ISI > 7). Compared with non-insomniac patients (ISI ≤ 7), insomniac patients had more severely impaired quality of life and a higher HAD score: median anxiety score of 9 (8–11) vs 4 (3–6) (p p p 2 during sleep. Conclusions The strong association between insomnia, impaired quality of life and increased HAD score should prompt physicians to be particularly attentive to the management of anxiety and depression in adult CF patients with insomnia. Trial registration: On clinicaltrials.gov (NCT02924818, date of registration: October 5, 2016).
Published: 2021
Full Text: View/download PDF

31. Safety of denervation following targeted lung denervation therapy for COPD: AIRFLOW-1 3-year outcomes

Author: Anna Mayr, Justin L. Garner, Pallav L. Shah, Vincent Ninane, Christophe Pison, Thierry Perez, Bruno Degano, Gaëtan Deslée, Dirk-Jan Slebos, Alexander D. Peterson, Wim Janssens, Jorine E. Hartman, Romain Kessler, Arschang Valipour, Martin Mayse, Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Royal Brompton and Harefield NHS Foundation Trust, Chelsea and Westminster Hospital, Imperial College London, University Medical Center Groningen [Groningen] (UMCG), Université libre de Bruxelles (ULB), University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université de Strasbourg (UNISTRA), Nouvel Hôpital Civil de Strasbourg, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Klinik Floridsdorf [Wien], Nuvaira, Inc., Minneapolis, MN, USA, The AIRFLOW-1 clinical trial was funded by Nuvaira, Inc., Minneapolis, MN, USA., Groningen Research Institute for Asthma and COPD (GRIAC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), and dormoy, valerian
Subjects: Male, medicine.medical_specialty, Time Factors, medicine.drug_class, Forced Expiratory Volume/physiology, Anticholinergic, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Lung/diagnostic imaging, Pulmonary function testing, Pulmonary Disease, 03 medical and health sciences, FEV1/FVC ratio, 0302 clinical medicine, Quality of life, Double-Blind Method, Chronic Obstructive/diagnosis, Internal medicine, Bronchoscopy, medicine, Humans, COPD, 030212 general & internal medicine, Prospective Studies, Adverse effect, Denervation, lcsh:RC705-779, Lung, business.industry, Nerves, Research, Généralités, lcsh:Diseases of the respiratory system, medicine.disease, Acetylcholine, 3. Good health, respiratory tract diseases, medicine.anatomical_structure, 030228 respiratory system, Denervation/methods, Pulmonary Disease, Chronic Obstructive/diagnosis, Quality of Life, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Female, business, Targeted lung denervation, Follow-Up Studies
Abstract: Following publication of the original article [1], we were notified that the first and last author names have been swapped. The original article has been corrected., SCOPUS: er.j, info:eu-repo/semantics/published
Published: 2021
Full Text: View/download PDF

32. Immune-related pancreatitis due to anti-PD-L1 therapy in a patient with non-small cell lung cancer: A case report

Author: Julie Malet, Boutheina Melki, Stéphane Chouabe, Gaëtan Deslée, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier de Charleville-Mezières, Service des maladies respiratoires et allergiques [CHU Reims], Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and dormoy, valerian
Subjects: Male, Lung Neoplasms, durvalumab, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, General Medicine, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Middle Aged, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, B7-H1 Antigen, lung cancer, Antineoplastic Agents, Immunological, [SDV.CAN] Life Sciences [q-bio]/Cancer, Pancreatitis, Carcinoma, Non-Small-Cell Lung, immune-related pancreatitis, case report, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Humans, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy
Abstract: International audience; Rationale: Despite clinical-proven benefits of immune checkpoint inhibitors (ICIs) on advanced lung cancer, rare but life-threatening immune-related adverse events (irAEs) have been reported. Pancreatitis is a rare irAE that can occur with any ICI.Patient concerns: A 53-year-old man with locally advanced non–small cell lung carcinoma was treated with radiochemotherapy and then durvalumab (anti–programmed cell death ligand 1 therapy). Twelve weeks after the beginning of ICI, he reported abdominal pain and anorexia. Blood test showed high level of lipase. Abdominal computed tomography revealed a swollen pancreas. These findings were confirmed by magnetic resonance cholangiopancreatography and biliopancreatic endoscopic ultrasonography.Diagnoses: Grade IV immune-related pancreatitis.Interventions: The patient was treated with corticosteroid therapy, resulting in clinical, radiological, and biological improvement.Outcomes: During the first month, corticosteroid therapy could not be decreased under 1 mg/kg/d because of symptoms recurrence and lipasemia rerising. Four months after this episode, the patient died from acute ischemia of the lower limbs while he was on
Published: 2022
Full Text: View/download PDF

33. Position paper of the French Society of Respiratory Diseases regarding pharmacological treatment optimization for stable COPD in 2021

Author: Maeva Zysman, Bruno Ribeiro Baptista, Thibaud Soumagne, Vanessa Marques da Silva, Clémence Martin, Charlotte Thibault de Menonville, Laurent Boyer, Bruno Degano, Pierre-Régis Burgel, Thierry Perez, Arnaud Bourdin, Chantal Raherison, Hervé Pégliasco, Daniel Piperno, Christophe Zanetti, Hughes Morel, Bertrand Delclaux, Christian Delafosse, Alain Lorenzo, Bruno Housset, Capucine Morélot-Panzini, François Chabot, Philippe Devillier, Gaëtan Deslée, Nicolas Roche, Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Pneumologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Henri Mondor, Centre Hospitalier Universitaire [Grenoble] (CHU), Université Grenoble Alpes (UGA), CHU Lille, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer environnement (EPICENE ), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen [Fondation Ambroise Paré - Marseille], CM PAROT, Lyon, Centre Hospitalier Régional d'Orléans (CHRO), Centre hospitalier Troyes (CH Troyes), Centre Hospitalier Simone Veil (CH Simone Veil), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Centre Hospitalier Intercommunal de Créteil (CHIC), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UPRES EA 220, Pôle des maladies respiratoires, Hôpital Foch, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Universitaire de Reims (CHU Reims)
Subjects: Pulmonary and Respiratory Medicine, [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience; No abstract available
Published: 2022
Full Text: View/download PDF

34. The elastin peptide VGVAPG increases CD4+ T-cell IL-4 production in patients with chronic obstructive pulmonary disease

Author: Julien Ancel, Jeanne-Marie Perotin, Pierre Gaudry, Gaëtan Deslée, Richard Le Naour, Flora Lemaire, Frank Antonicelli, Sandra Dury, Sandra Audonnet, François Lebargy, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Universitaire de Reims (CHU Reims)
Subjects: Adult, CD4-Positive T-Lymphocytes, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], T cells, Peripheral blood mononuclear cell, Flow cytometry, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Humans, COPD, Receptor, Cells, Cultured, Interleukin 4, Aged, 030304 developmental biology, lcsh:RC705-779, 0303 health sciences, biology, medicine.diagnostic_test, business.industry, Research, IL-4, lcsh:Diseases of the respiratory system, Middle Aged, medicine.disease, Desmosine, Endocrinology, 030228 respiratory system, chemistry, Leukocytes, Mononuclear, biology.protein, Cytokines, Female, Interleukin-4, Elastin peptides, business, Oligopeptides, Elastin, CD8
Abstract: Background In chronic obstructive pulmonary disease (COPD), lung-infiltrating inflammatory cells secrete proteases and participate in elastin breakdown and genesis of elastin-derived peptides (EP). In the present study, we hypothesized that the pattern of T lymphocytes cytokine expression may be modulated by EP in COPD patients. Methods CD4+ and CD8+ T-cells, sorted from peripheral blood mononuclear cells (PBMC) collected from COPD patients (n = 29) and controls (n = 13) were cultured with or without EP. Cytokine expression in T-cell phenotypes was analyzed by multicolor flow cytometry, whereas desmosine concentration, a specific marker of elastin degradation, was measured in sera. Results Compared with control, the percentage of IL-4 (Th2) producing CD4+ T-cells was decreased in COPD patients (35.3 ± 3.4% and 26.3 ± 2.4%, respectively, p + T-cells, of which only one expressed high IL-4 levels in association with high levels of desmosine and strong smoking exposure (n = 7). Upon stimulation with VGVAPG, a bioactive EP motif, the percentage of CD4+ T cells expressing IL-4 significantly increased in COPD patients (p Conclusions The present study demonstrates that the VGVAPG elastin peptide modulates CD4+ T-cells IL-4 production in COPD. Monitoring IL-4 in circulating CD4+ T-cells may help to better characterize COPD phenotypes and could open a new pharmacologic opportunity through CD4+ T-cells stimulation via the VGVAPG/S-gal receptor in order to favor an anti-inflammatory response in those COPD patients.
Published: 2021
Full Text: View/download PDF

35. <scp> FHIT low </scp> / <scp> pHER2 high </scp> signature in non‐small cell lung cancer is predictive of <scp>anti‐HER2</scp> molecule efficacy

Author: Julien Ancel, Julie Routhier, Antoine Jonquet, Gaëtan Deslée, Philippe Birembaut, Jérôme Cutrona, Gonzague Delepine, Maxime Dewolf, Véronique Dalstein, Amina Jouida, Jordan Da silva, Myriam Polette, and B. Nawrocki-Raby
Subjects: 0301 basic medicine, medicine.medical_treatment, Cell, Pathology and Forensic Medicine, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Trastuzumab, FHIT, medicine, Gene silencing, skin and connective tissue diseases, Lung cancer, neoplasms, business.industry, medicine.disease, respiratory tract diseases, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Cell culture, 030220 oncology & carcinogenesis, Cancer research, business, medicine.drug
Abstract: Despite its efficacy in solid tumours, in particular HER2+ breast cancer, HER2-targeted therapy has given rise to disappointing results in non-small cell lung cancer (NSCLC). With the aim of refining the target population for anti-HER2 therapies in NSCLC, we investigated the relationships between HER2 and the tumour suppressor fragile histidine triad (FHIT) in lung tumour cells. First, we observed a negative correlation between FHIT expression and the activated form of HER2 (pHER2) in NSCLC samples and in lung tumour cell lines. Moreover, the silencing or overexpression of FHIT in lung cell lines led to an increase or decrease of HER2 activity, respectively. We also demonstrated that two anti-HER2 drugs, irbinitinib and trastuzumab, restore a more epithelial phenotype and counteract cell invasiveness and growth of FHIT-silenced tumour cell lines. Finally, we showed that the FHITlow /pHER2high phenotype predicts sensitivity to an anti-HER2 therapy in primary tumour cells from NSCLC patients. Our results show that FHIT regulates the activity of HER2 in lung tumour cells and that FHIT-inactivated tumour cells are sensitive to HER2 inhibitors. A new subclass of patients with NSCLC may be eligible for an anti-HER2 therapy. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Published: 2020
Full Text: View/download PDF

36. Association Between Obesity-Related Dyspnea in Daily Living, Lung Function and Body Composition Analyzed by DXA: A Prospective Study of 130 Patients

Author: François Lebargy, Lois Bolko, Gaëtan Deslée, Jean Hagenburg, Eric Bertin, Sandra Dury, Aurore Thierry, Jean-Hugues Salmon, C. Launois, Valérian Dormoy, and Jeanne-Marie Perotin
Subjects: medicine.medical_specialty, business.industry, Internal medicine, medicine, Daily living, Prospective cohort study, business, medicine.disease, Obesity, Lung function
Abstract: Background Obesity is a risk factor for dyspnea. However, investigations of daily living obesity-related dyspnea are limited and its mechanisms remain unclear. We aimed to analyze the relationships between dyspnea in daily living, lung function, and body composition in patients with obesity.Methods One-hundred and thirty patients (103 women/27 men), candidate for bariatric surgery, with a mean ± SD Body Mass Index (BMI) of 44.8 ± 6.8 kg/m² were included. Dyspnea was assessed by the modified Medical Research Council (mMRC) scale. Comorbidities, laboratory parameters, pulmonary function tests, arterial blood gases, six-minute walk test (6MWT), handgrip strength, and DXA body composition were analyzed.Results Thirty-one percent of patients exhibited disabling dyspnea in daily living (mMRC ≥ 2). Compared with patients without disabling dyspnea (mMRC < 2), significant dyspnea (mMRC ≥ 2) was associated with a lower 6MWT distance (395 ± 103 m vs 457 ± 73 m, pvs 54 ± 27%, p=0.024), Vital Capacity (95 ± 14 vs 106 ± 15%, pvs 105 ± 15%, p=0.002), a higher BMI (48.2 ± 7.7 vs 43.2 ± 5.7 kg/m², p=0.001) and a higher percentage of fat mass in the trunk (46 ± 5 vs 44 ± 5 p=0.012) and android region (52 ± 4 vs 51 ± 4%, p=0.024). There was no difference regarding comorbidities (except hypertension), laboratory parameters, and sarcopenia markers between patients with (mMRC ≥ 2) and without (mMRC < 2) disabling dyspnea. Conclusion Dyspnea in patients with obesity is associated with a reduction in lung volumes and a higher percentage of fat mass in central body regions. How dyspnea and body composition may change with interventions like physical activity or bariatric surgery remains to be investigated. Trial Registration Reims University Hospital Institutional Review Board (IRB-17-10-2012).
Published: 2021
Full Text: View/download PDF

37. Dual versus triple therapy in patients hospitalized for COPD in France: a claims data study

Author: Hervé Pegliasco, Bruno Housset, Philippe Devillier, F. Dalon, Eric Van Ganse, Maeva Nolin, Gaëtan Deslée, Nicolas Roche, and Manon Belhassen
Subjects: COPD, medicine.medical_specialty, business.industry, General Medicine, medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Disease severity, Internal medicine, Claims data, Propensity score matching, Health care, medicine, Resource use, In patient, 030212 general & internal medicine, business, Cost of care
Abstract: Purposes Following a hospitalization for COPD, dual and triple therapies were compared in terms of persistence and relations with outcomes (exacerbations, health care resource use and costs). Methods This was a historical observational database study. All patients aged ≥45 hospitalized for COPD between 2007 and 2015 were identified in a 1/97th random sample of French claims data. Patients receiving dual therapy within 60 days after hospitalization were compared to patients receiving triple therapy, after propensity score matching on disease severity. Results Of the 3,089 patients hospitalized for COPD, 1,538 (49.8%) received either dual or triple therapy in the 2 months following inclusion, and 1,500 (48.6%) had at least 30 days of follow-up available; 846 (27.4%) received dual therapy, and 654 (21.2%) received triple therapy. After matching, the number of exacerbations was 2.4 per year in the dual vs 2.3 in the triple group (p=0.45). Among newly treated patients (n=206), persistence at 12 months was similar in the dual and triple groups (48% vs 41%, respectively, p=0.37). As compared to patients on dual therapy, more patients on triple therapy received oral corticosteroids (49.1 vs 40.4%, p=0.003) or were hospitalized for any reason (67% vs 55.8%, p=0.0001) or for COPD (35.3 vs 25.1%, p=0.0002) during follow-up. Cost of care was higher for patients on triple than for those on dual therapy (€11,877.1 vs €9,825.1, p=0.01). Conclusion Following hospitalizations for COPD, patients on dual and triple therapy experienced recurrent exacerbations, limited adherence to therapies and high cost of care. Patients on triple therapy appeared more severe than those on dual therapy, as reflected by exacerbations and health care resource use.
Published: 2019
Full Text: View/download PDF

38. Predictors in routine practice of 6-min walking distance and oxygen desaturation in patients with COPD: impact of comorbidities

Author: Thierry Perez, Pascale Nesme-Meyer, Olivier Le Rouzic, Isabelle Court-Fortune, Pierre-Régis Burgel, Denis Caillaud, Gaëtan Deslée, Nicolas Roche, Graziella Brinchault-Rabin, Maeva Zysman, Roger Escamilla, Pascal Chanez, Gilles Jebrak, and Jean-Louis Paillasseur
Subjects: medicine.medical_specialty, COPD, Multivariate analysis, business.industry, Hyperinflation, General Medicine, medicine.disease, Comorbidity, Obesity, respiratory tract diseases, 3. Good health, 03 medical and health sciences, FEV1/FVC ratio, Walking distance, 0302 clinical medicine, 030228 respiratory system, Internal medicine, Cohort, Medicine, 030212 general & internal medicine, business
Abstract: Background: The 6-min walk test (6MWT) allows exercise tolerance to be assessed, and it has a significant prognostic value in COPD. The goal of this study was to analyse the determinants (obtained in routine practice) of a low 6-min walking distance (6MWD) and exercise-induced desaturation (EID) in COPD, including comorbidities. Methods: Patients were recruited from the real-life French COPD cohort "Initiatives BPCO". A low 6MWD was defined as 30 kg/m2), low BMI (BMI
Published: 2019
Full Text: View/download PDF

39. Chr15q25 Genetic Variant rs16969968 Alters Cell Differentiation in Respiratory Epithelia

Author: Zania, Diabasana, Jeanne-Marie, Perotin, Randa, Belgacemi, Julien, Ancel, Pauline, Mulette, Claire, Launois, Gonzague, Delepine, Xavier, Dubernard, Jean-Claude, Mérol, Christophe, Ruaux, Philippe, Gosset, Uwe, Maskos, Myriam, Polette, Gaëtan, Deslée, Valérian, Dormoy, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Reims (CHU Reims), Clinique mutualiste La Sagesse, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Neurobiologie intégrative des Systèmes cholinergiques / Integrative Neurobiology of Cholinergic Systems (NISC), Institut Pasteur [Paris] (IP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), This work was supported by Funding from University of Reims Champagne-Ardenne (Université de Reims Champagne-Ardenne, URCA), the French National Institute of Health and Medical Research (Institut National de la Santé et de la Recherche Médicale, Inserm) and a grant from the Research Institute in Public Health (IReSP) in association with the National Institute of Cancer (INCa). It was carried out in the framework of the Federative Research Structure CAP-Santé and benefited from the Project Research and Innovation in Inflammatory Respiratory Diseases (RINNOPARI)., Sorbonne Université (SU)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and dormoy, valerian
Subjects: Lung Diseases, rs16969968, QH301-705.5, Nerve Tissue Proteins, Respiratory Mucosa, Receptors, Nicotinic, Polymorphism, Single Nucleotide, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], mental disorders, Humans, Genetic Predisposition to Disease, remodelling, Biology (General), QD1-999, Cells, Cultured, Chromosomes, Human, Pair 15, Gene Expression Profiling, Communication, Cell Differentiation, Tobacco Use Disorder, differentiation, Chemistry, Gene Expression Regulation, inflammation, Multigene Family, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, airway epithelial cells
Abstract: International audience; The gene cluster region, CHRNA3/CHRNA5/CHRNB4, encoding for nicotinic acetylcholine receptor (nAChR) subunits, contains several genetic variants linked to nicotine addiction and brain disorders. The CHRNA5 single-nucleotide polymorphism (SNP) rs16969968 is strongly associated with nicotine dependence and lung diseases. Using immunostaining studies on tissue sections and air-liquid interface airway epithelial cell cultures, in situ hybridisation, transcriptomic and cytokines detection, we analysed rs16969968 contribution to respiratory airway epithelial remodelling and modulation of inflammation. We provide cellular and molecular analyses which support the genetic association of this polymorphism with impaired ciliogenesis and the altered production of inflammatory mediators. This suggests its role in lung disease development.
Published: 2021
Full Text: View/download PDF

40. Consommation de soins des patients BPCO en France et au Royaume-Uni entre 2008 et 2017, et coûts associés

Author: Eric Van Ganse, Dermot Ryan, Hannah R Whittaker, Gaëtan Deslée, Claire Marant Micallef, Maeva Nolin, F. Dalon, Christophe Pison, Jennifer K Quint, Manon Belhassen, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), and Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Epidemiology, [SDV]Life Sciences [q-bio], Public Health, Environmental and Occupational Health, ComputingMilieux_MISCELLANEOUS, 3. Good health
Abstract: Contexte Le Royaume-Uni (UK) presente des taux de mortalite et d’hospitalisation pour Broncho Pneumopathie Chronique Obstructive (BPCO) plus eleves que ceux de la France. Ces differences pourraient etre dues a des differences de prise en charge : le but de cette etude etait de decrire la consommation de soins des patients BPCO et les couts associes dans les 2 pays. Methode Il s’agissait d’une etude transversale repetee chaque annee entre 2008 et 2017, realisee pour la France sur l’Echantillon Generaliste de Beneficiaires (EGB), et pour le UK sur la base du Clinical Practice Research Datalink (CPRD). Les patients, âges de 40 ans ou plus, ont ete inclus chaque annee, identifies par une hospitalisation pour BPCO ou par la prise de bronchodilatateurs (LABA, LAMA, association fixe [AF] LABA/ICS, AF LABA/LAMA) sur 3 trimestres consecutifs. Nous avons decrit, pour chaque annee d’etude : – les caracteristiques socio-demographiques, le nombre d’exacerbations severes (hospitalisations) et les comorbidites ; – a consommation de soins et les couts associes en termes de visites medicales, hospitalisations, et types de medicaments dispenses. Resultats L’âge moyen des patients BPCO etait stable dans le temps et legerement plus eleve au UK (71 ans) qu’en France (67 ans) ; il en etait de meme pour la proportion d’hommes dans la population (UK : 51 %, France : 53 %). Le taux de mortalite des patients etait stable au cours du temps, et legerement plus eleve au UK (3 %) qu’en France (2 %). Dans les 2 pays, le diabete etait la comorbidite la plus frequente et sa prevalence augmentait au cours du temps en France (14 % en 2008, 17 % en 2017) alors qu’elle restait stable au UK (∼12 %). Le taux d’exacerbations severes etait plus eleve au UK qu’en France et il augmentait au cours du temps (de 4 % a 6 % en France, et de 12 % a 28 % en Angleterre de 2008 a 2017). En 2008, le taux d’hospitalisations toutes causes etait plus eleve au UK (39 %) qu’en France (30 %) et il augmentait entre 2008 et 2017 au UK (59 % en 2017), alors qu’il restait stable en France. Le taux de passages aux urgences etait aussi plus eleve au UK, et il augmentait plus fortement au cours du temps qu’en France (de 27 % a 45 % au UK, de 11 % a 16 % en France de 2009 a 2017). Alors que le taux de visite chez le medecin generaliste etait similaire entre les 2 pays en 2008 (∼96 %), il a fortement chute entre 2008 et 2017 au UK (78 %), alors qu’il est reste stable en France durant la meme periode. Les dispensations d’ICS/LABA en AF ont fortement augmente au UK entre 2008 et 2017, mais restaient toujours plus elevees en France (70 % vs 58 % en 2017). Les dispensations de corticoides oraux etaient plus frequentes en France (45 %), mais elles ont beaucoup augmente au UK (de 25 % a 39 %) alors qu’elles sont restees stable en France entre 2008 et 2017. Les couts associes a la prise en charge de la BPCO augmentaient dans les 2 pays entre 2008 et 2017. Les couts les plus importants en France etaient ceux des traitements, alors qu’au UK, les couts des visites etaient les plus eleves. Conclusion Nous avons mis en evidence des differences de profils et de pratiques dans la prise en charge de la BPCO en France et au UK, qui pourraient en partie expliquer les differences observees entre les 2 pays en termes de mortalite et d’hospitalisation, malgre la difficulte a identifier des populations de severite comparable. Ces resultats seront statistiquement compares ulterieurement, afin de pouvoir tirer des conclusions plus robustes.
Published: 2021
Full Text: View/download PDF

41. Traitement du reflux gastro-œsophagien (RGO) dans l’asthme

Author: C. Launois, Pauline Mulette, Jeanne-Marie Perotin, Sandra Dury, Valérian Dormoy, Gaëtan Deslée, Julien Ancel, J. Hagenburg, François Lebargy, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Universitaire de Reims (CHU Reims)
Subjects: Pulmonary and Respiratory Medicine, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, [SDV]Life Sciences [q-bio], Fundoplicature, 030212 general & internal medicine, Asthme, Reflux gastro-oesophagien, Inhibiteur de la pompe à protons
Abstract: International audience; Le reflux gastro‐oesophagien (RGO) est une des pathologies les plus fréquemment associées à l’asthme, avec un impact sur le contrôle et la qualité de vie des patients. Le traitement du RGO repose sur des mesures hygiéno‐diététiques, un traitement médicamenteux anti‐acide et, dans certains cas, une prise en charge chirurgicale par fundoplicature. Si l’impact de mesures hygiéno‐diététiques seules sur l’asthme n’a pas été étudié, l’efficacité d’un traitement par inhibiteurs de la pompe à protons sur le contrôle de l’asthme, le débit expiratoire de pointe ou la qualité de vie a été analysée dans plusieurs essais randomisés contrôlés, détaillés dans cette revue. Les données d’efficacité de la prise en charge chirurgicale reposent principalement sur des études observationnelles rétrospectives ou prospectives, également détaillées. Devant l’impact limité du traitement du RGO dans l’asthme, les recommandations actuelles sont de limiter un traitement médical du RGO aux asthmes associés à un RGO symptomatique. Il n’existe pas actuellement de données suffisantes pour recommander un traitement chirurgical du RGO pour l’indication spécifique de l’asthme.
Published: 2021
Full Text: View/download PDF

42. Optimisation du traitement médicamenteux des patients atteints de BPCO en état stable. Position de la Société de pneumologie de langue française. Actualisation 2021

Author: François Chabot, B. Ribeiro Baptista, Laurent Boyer, Thibaud Soumagne, Nicolas Roche, Bruno Degano, Clémence Martin, V Marques da Silva, A. Lorenzo, Chantal Raherison, P. Devillier, Arnaud Bourdin, Hervé Pegliasco, M Zysman, C. Thibault De Menonville, C Delafosse, Thierry Perez, Pierre-Régis Burgel, D. Piperno, C. Morelot Panzini, Bruno Housset, Gaëtan Deslée, C Zanetti, H. Morel, B. Delclaux, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), and Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Pulmonary and Respiratory Medicine, COPD, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], MEDLINE, French, medicine.disease, language.human_language, 3. Good health, Pharmacological treatment, 03 medical and health sciences, Position (obstetrics), 0302 clinical medicine, 030228 respiratory system, language, Medicine, In patient, 030212 general & internal medicine, business, Intensive care medicine, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021
Full Text: View/download PDF

43. Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial

Author: Mathieu Vautier, Florence Tubach, Marion Licois, Estelle Henry, Marie-Alexandra Alyanakian, Julien Poissy, Solaya Chalal, Anne Gysembergh-Houal, Stéphanie Alary, Sophie Diemunsch, Jonathan London, Camille Petit-Hoang, Ruben Benainous, Catherine Metzger, Olivier Benveniste, Hala Semri, Charléne Jouve, Robin Dhote, johann Cailhol, Elise Morawiec, Kristina Beziriganyan, Mathieu Oberlin, Paul Legendre, Hélène François, Claire Davoine, F Louni, Myriam Virlouvet, Stéphane Renaud, Christiane Verny, Bertrand Guidet, Bob Heger, Lara Zafrani, Pierre-Louis Tharaux, Mandy Nizard, Adrien Contejean, Segolene Toquet, Ulrich Clarac, Sylviane Ravato, Gaëtan Deslée, Frédéric De Blay, Christian Richard, Raphaël Porcher, Malikhone Chansombat, Marie Lachatre, Ines Ben-Mabrouk, Matthieu Uzzan, Lauren Demerville, Amélie Servettaz, Annabelle Pourbaix, Philippe Manivet, Fanny Charbonnier, Pierre-Grégoire Guinot, Alexandre Demoule, Nicolas Champtiaux, Nicolas Belaube, Jean-Pierre Riveline, Kamil Chitour, Joseph Emmerich, Arthur Neuschwander, Mickael Henriques, Anne Hutt, Arthur Pavot, Anne Rachline, Elena Fois, Audrey Phibel, Xavier Monnet, Jean-Charles Duclos-Vallée, Félix Ackermann, Maria Pereira, Anne Sophie Korganow, Elodie Drouet, Tabassome Simon, Morgane Faure, Anne Pattyn, Aida Zahrate-Ghoul, Karine Martin, Jean-Jacques Tudesq, Gladys Aratus, Kévin Cardet, Julien Pottecher, Eric Demonsant, Arsène Mekinian, Rémy Gauzit, Julie Smati, Robin Deleris, Jean-Simon Rech, Boris Bienvenu, Nicolas Lefebvre, Elodie Baudry, Nicolas Bonnet, Alexis Régent, François Weill, Lalia Djaghout, Anne Tréhan, Isabelle Lehir, Elena Kiouris, Sophie Renet, Yasmina Mekid, Vanessa Rathouin, David Montani, Annick Tibi, Anne Blanchard, Fanette Denies, Nathalie Menage, Guillaume Becker, Valérie Camara-Clayette, Loic Kassegne, Nathalie Chavarot, Aurélie Clan Hew Wai, Jeremy Arzoine, Louise Bondeelle, Mohamad Zaidan, S Lariven, Laurent Cylly, Edouard Flamarion, Chaouki Bouras, Florence Bellenfant, Melissa Clément, Lola-Jade Palmieri, Marie hélène Pari, Lionel Galicier, Valérie Dejean, Delphine Feyeux, Naima Sguiouar, Anne Bergeron, Laurence Annonay, Anouk Walter-Petrich, Camille Knosp, Laurence Drouard, Thiziri Sadaoui, Julie Delemazure, Antoine Parrot, Carole Burger, Laurence Berard, Nicolas Gambier, Eric Marquis, Isabelle Madeleine, Gwenaël Lorillon, Matthieu Resche-Rigon, Yves Hansmann, Claire Rouzaud, Hélène Gros, Sophie Caillat-Zucman, Bernard Cholley, Celine Wilpotte, Chistophe Willekens, Lydia Suarez, Syllia Belazouz, Valérie Pourchet-Martinez, Dhiaa Meriem Hai, Olivier Collange, Paul Jaubert, Marie-Thérèse Tremorin, Nathalie Marin, Diane Le Pluart, Madona Sakkal, Juliette Djadi-Prat, Alexandre Morel, Agathe Bounhiol, Xavier Jaïs, Nicolas Meyer, Vixra Keo, Michaël Darmont, Benedicte Giroux-Leprieur, Anatole Harrois, Anne Adda, Yaël Amara, Fanny Pommeret, Antony Canellas, Matheus Vieira, Clotilde Le Tiec Le Tiec, Corinne Pernot, Bernard Goichot, Céline Louapre, Roza Rahli, Anne Jacolot, Anne Daguenel-Nguyen, Marie Dubert, Anaïs Razurel, Aurelie Sautereau, Mitja Jevnikar, Pierre Faye, Jeanne CHAUFFiER, Mathieu Jozwiak, Laurent Savale, Florence Patin, Kahina Cheref, Mélanie Dehais, Paul Michel Mertes, Caroline Morbieu, Valérie Paquet, Dominique Roulot, Giovanna Melica, Pauline Jouany, Frédéric Schlemmer, Blandine Lehmann, Pascal Martel, Tomas Urbina, Yazdan Yazdanpanah, Veronique Joly, Damien Bergerot, Claire Courtin, Benjamin Fournier, Guillaume Grailles, Asmaa Mamoune, Caroline Gaudefroy, Charlotte Kaeuffer, Bruno Crestani, Thinhinane Bariz, C Rioux, Karine Celli Lebras, Sophie Granville, Marion Bouhris, Hugues Cordel, Jean-Marie Michot, Mohamed Belloul, Nadège Lemarié, Philippe Dieudé, Sylvie Le Gac, Matthieu Mahévas, Pascal Richette, Anaïs Codorniu, Camille Rolland-Debord, Edouard Lefèvre, Sophie-Rym Hamada, Tristan Martin, Vincent Castelain, Aude Rigolet, Valentin Greigert, Gaelle Leroux, Simon Valayer, Eliane Bertrand, Eric Vicaut, Stéphane Brin, Jacques-Eric Gottenberg, Olivier Clovet, Marc Bardou, Muriel Fartoukh, Valentina Isernia, Ada Clarke, Bao Phung, Grégoire Martin de Frémont, Jeanne Meunier, Gonçalo Boleto, David Lebeaux, Hassan Tarhini, Asmaa Mabrouki, Pascaline Choinier, Etienne Canouï, Eric D'Ortenzio, Constance Guillaud, Corine Nyanou, Alexandre Moores, Linda Gimeno, Victoire De Lastours, F-Xavier Lescure, Claire Montlahuc, Sophie Georgin-Lavialle, A Soria, Xavier Mariette, Sophie Ismael, Prissile Bakouboula, Olivier Lambotte, Jérémie Zerbit, Aude Jacob, Z Julia, Nathalie Dournon, Marthe Rigal, Mireille Adda, Nathan Ebstein, Frédéric Duée, Helene Chambrin-Lauvray, Ramdane Meftali, Hélène Lafoeste, Coralie Bloch Queyrat, Sabrina Brahmi, Catherine Le Bourlout, Nicolas Noel, Emmanuelle Guillot, Hakim Tayebi, Sandrine Briois, Anne-Lise Pouliquen, Lakhdar Mameri, Sophie-Caroline Sacleux, Nathalie Rozensztajn, Lelia Escaut, Clément Jourdaine, Cédric Pierron, Marc Garnier, Yves Cohen, Abdellatif Tazi, Maxence Decavele, Paul Henri Grisot, Patrice Cacoub, Laure Allanic, Amira Benattia, Martin Siguier, Luca Semerano, Jean-Sébastien Hulot, Jean-Jacques Mourad, Sara Sambin, Miguel Alejandro Vasquez-Ibarra, Nabil Raked, Christine Lemagner, Martin Dres, Clara Campos-Vega, Tali-Anne Szwebel, Benjamin Chaigne, Emmanuel Andrès, Gabriel Steg, Frédéric Blanc, Isabelle Peigney, Catherine Fauvaux, Côme Bureau, Samira Saleh-Mghir, Julie Jambon, Pierre Dupland, Anne Lise Jegu, Mamadou Salif Cisse, Damien Roux, Moez Jallouli, Philippe Blanche, Sébastien Cavelot, Sophie Ohlmann-Caillard, Louise-Laure Mariani, Adrien Michon, Alain Wynckel, Saskia Flamand, Safaa Nemlaghi, Benjamin G. Chousterman, Geoffroy Volle, Cécile Kedzia, Fanny Domont, Lee S. Nguyen, Férial Berbour, Pierre Diemunsch, Celine Dupré, Etienne Lengliné, Claire Tantet, Gaël Leprun, Sara Virolle, Perrine Guillaume-Jugnot, Soumeya Hammal, B. Duchemann, Mathilde Le Marchand, Vincent Poindron, Victor Lancon, Ruxandra Burlacu, Guillaume Lefèvre, Kamyl Baghli, Emilia Stan, Yann Nguyen, Olivier Sanchez, Olivier Sitbon, Loren Soyez-Herkert, Fanny Defrancq, Véronique Vigna, Aurélien Guffroy, Martine Meunier, Pierre Mora, Léa Resmini, Liem Binh Luong Nguyen, Jean-Luc Diehl, Johanna Oziel, Emmanuelle Bugnet, Lamiae Grimaldi, Olivia Daconceicao, Marie Matignon, Mourad Djadel, Yasmine Messaoudi, Hassan Joumaa, Isabelle Dusanter, Sarah Benghanem, Julien Mayaux, Marc Michel, Claire Pernin, Antoine Gros, Nassim Mahtal, Philippe Benoit, Cloé Comarmond, Laurence Lecomte, Patricia Senet, Sebastien Abad, Jérôme Pacanowski, Céline Leplay, Claire Aguilar, Cédric Sublon, Jesuthasan Denis, Régis Peffault de Latour, Gabrielle Archer, Alain Fourreau, Emmanuelle Blin, Lise Bernard, Alexandra Beurton, Alexandre Buffet, Pierre Le Guen, Clairelyne Dupin, Olivier Fain, A Gervais, Marc Humbert, Yves Allenbach, Alexandre Bourgoin, Agnes Maurer, Eric Noll, Virginie Elisee, Adrien Mirouse, Cecile Larcheveque, Carine Karachi, Samy Figueiredo, Hakim Meddah, Greggory Ducrocq, Jeanne Goupil de Bouille, Awa Ndiaye, Jessica Krause le Garrec, Maxime Dougados, Yasmina Ferfar, Damien Vimpere, Olivier Olivier, Annabelle Stoclin, Jean-Louis Teboul, Ridha Belilita, Serge Bureau, Naura Gamany, Emeline Colomba, Baptiste Duceau, Philippe Ravaud, Corinne Guerin, Florence Morin, Pélagie Thibaut, Younes Keroumi, Julie Chas, Elisabeth Coupez, Laetitia Languille, Mathias Cornic, Jean-Michel Molina, Caroline Pradon, Alison Klasen, Zakaria Ait Hamou, Armand Mekontso-Dessaps, Yurdagul Uzunhan, Samir Hamiria, Anne Godier, Elsa Feredj, Nessima Yelles, Jean-Benoit Arlet, Christine Broissand, Belkacem Asselate, Jaouad Benhida, Julien Le Marec, Nawal Derridj, Laurène Deconinck, A. Dossier, Eric Oksenhendler, Eva Chatron, Lucie Aunay, Candice Estellat, Julie Fillon, Marie Antignac, Jade Ghosn, Ilias Koumis, David Schmitz, Domitille Molinari, Soraya Fellahi, Bruno Mégarbane, Aline Frazier, Ramon Junquera, Vincent Provitolo, Marie Lecronier, Dimitri Fremont, Pierrick Le Borgne, Emmanuel Weiss, Faouzi Saliba, Stéphan Pavy, Geoffrey Rossi, Chloe McAvoy, Eric Mariotte, Dorothee Vallois, Sabrine Ouamri, Pierre Tissieres, Luc Mouthon, Blandine Denis, Celine Comparon, Emmanuelle Sacco, Frédéric Pène, Marjolaine Morgand, Vasco Honsel, Laure Choupeaux, Bruno Mourvillier, Ewa Kozaliewicz, Marie-Hélène Legros, Isabelle Debrix, Gabriel Nisand, Julien Chabert, Juliette Camuset, Stéphane Jauréguiberry, Lynda Chalal, Marine Livrozet, Lucie Biard, Elodie Perrodeau, Brigitte Sabatier, Raphael Borie, Rosa Da Silva, Nathalie Costedoat-Chalumeau, Emmanuel Chatelus, Jean-Christophe Corvol, Nathalie De Castro, David Boutboul, Benjamin Planquette, Anne Claire Desbois, François Danion, Brigitte Ranque, Amélie Cransac, Marine Nadal, Coralie Gernez, Yacine Boudali, Claire Madelaine, Georgina Maalouf, Jonathan Marey, Sophie Bayer, Antoine Fayol, Souad Benarab, Luc Haudebourg, Sophie Bulifon, Claire Pacheco, Philippe Durand, Olivier Hermine, Fanny Alby-Laurent, Geoffroy Liégeon, Axelle Fuentes, Jean-Daniel Lelievre, Gilles Garcia, Céline Verstuyft Verstuyft, Marie-Aude Penet, Constance Delaugerre, Nicolas Carlier, Aurélie Durel Maurisse, Gilles Pialoux, Zeina Louis, Marion Parisey, Pascal Lim, Gaelle Clavere, Martin De Sarcus, Marie Vayssettes, Thomas Papo, Adrien Joseph, Hilario Nunes, Hanane Fodil, Solen Kernéis, Antoine Bachelard, Jacques Duranteau, Karine Lacombe, Olivia Lenoir, Mathilde Vallet, Isabelle Brindele, Robin Charreteur, Elie Azoulay, Dorothée Chopin, Aïcha Bah, Moustafa Benafla, Marie Gilbert, Matthieu Lemoine, Abolfazl Mohebbi, Mathilde Noaillon, Amina Kebir, Virginie Zarrouk, Cécile Yelnik, Benjamin Terrier, Solène Fabre, Paul Crespin, Sarah Dalibey, Thierno Dieye, Renaud Felten, Oriane Puéchal, Pernelle Vauboin, Caroline Hauw-Berlemont, Gabriel Baron, Paul Vermes, Yvon Ruch, Dominique Dautel, Tassadit Hadjam, Anne-Marie Roques, Jean-Philippe Bastard, Younes El Amine, Damien Sène, Alaki Thiemele, Catherine Boussard, Vincent Fallet, Timothee Bironne, Damien Vanhoye, Guillaume Geri, Amine Ghembaza, Bertrand Dunogue, Nadia Anguel, Laure Berton, Caroline Semaille, Thomas Volpe, Jacques Cadranel, Thomas Gorget, Julien Saussereau, Elodie Issorat, Sami Kolta, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Porcher, Raphaël
Subjects: Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, 0302 clinical medicine, Randomized controlled trial, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, education.field_of_study, Hazard ratio, Articles, Middle Aged, Intensive care unit, Hospitals, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Hospitalization, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Treatment Outcome, [SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, France, medicine.drug, Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Critical Care, Population, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, education, Critical Care Outcomes, Aged, Mechanical ventilation, Anakinra, SARS-CoV-2, business.industry, Comment, COVID-19, Bayes Theorem, Pneumonia, medicine.disease, Respiration, Artificial, COVID-19 Drug Treatment, Clinical trial, Interleukin 1 Receptor Antagonist Protein, 030228 respiratory system, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business, Interleukin-1
Abstract: International audience; Background: Patients with COVID-19 pneumonia have an excess of inflammation and increased concentrations of cytokines including interleukin-1 (IL-1). We aimed to determine whether anakinra, a recombinant human IL-1 receptor antagonist, could improve outcomes in patients in hospital with mild-to-moderate COVID-19 pneumonia.Methods: In this multicentre, open-label, Bayesian randomised clinical trial (CORIMUNO-ANA-1), nested within the CORIMUNO-19 cohort, we recruited patients from 16 University hospitals in France with mild-to-moderate COVID-19 pneumonia, severe acute respiratory syndrome coronavirus 2 infection confirmed by real-time RT-PCR, requiring at least 3 L/min of oxygen by mask or nasal cannula but without ventilation assistance, a score of 5 on the WHO Clinical Progression Scale (WHO-CPS), and a C-reactive protein serum concentration of more than 25 mg/L not requiring admission to the intensive care unit at admission to hospital. Eligible patients were randomly assigned (1:1) using a web-based secure centralised system, stratified by centre and blocked with varying block sizes (randomly of size two or four), to either usual care plus anakinra (200 mg twice a day on days 1-3, 100 mg twice on day 4, 100 mg once on day 5) or usual care alone. Usual care was provided at the discretion of the site clinicians. The two coprimary outcomes were the proportion of patients who had died or needed non-invasive or mechanical ventilation by day 4 (ie, a score of >5 on the WHO-CPS) and survival without need for mechanical or non-invasive ventilation (including high-flow oxygen) at day 14. All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT04341584, and is now closed to accrual.Findings: Between April 8 and April 26, 2020, we screened 153 patients. The study was stopped early following the recommendation of the data and safety monitoring board, after the recruitment of 116 patients: 59 were assigned to the anakinra group, and 57 were assigned to the usual care group. Two patients in the usual care group withdrew consent and were not analysed. In the analysable population, the median age was 66 years (IQR 59 to 76) and 80 (70%) participants were men. In the anakinra group, 21 (36%) of 59 patients had a WHO-CPS score of more than 5 at day 4 versus 21 (38%) of 55 in the usual care group (median posterior absolute risk difference [ARD] -2·5%, 90% credible interval [CrI] -17·1 to 12·0), with a posterior probability of ARD of less than 0 (ie, anakinra better than usual care) of 61·2%. At day 14, 28 (47%; 95% CI 33 to 59) patients in the anakinra group and 28 (51%; 95% CI 36 to 62) in the usual care group needed ventilation or died, with a posterior probability of any efficacy of anakinra (hazard ratio [HR] being less than 1) of 54·5% (median posterior HR 0·97; 90% CrI 0·62 to 1·52). At day 90, 16 (27%) patients in the anakinra group and 15 (27%) in the usual care group had died. Serious adverse events occurred in 27 (46%) patients in the anakinra group and 21 (38%) in the usual care group (p=0·45).Interpretation: Anakinra did not improve outcomes in patients with mild-to-moderate COVID-19 pneumonia. Further studies are needed to assess the efficacy of anakinra in other selected groups of patients with more severe COVID-19.Funding: The Ministry of Health, Programme Hospitalier de Recherche Clinique, Foundation for Medical Research, and AP-HP Foundation.
Published: 2021
Full Text: View/download PDF

44. Health-Related Quality of Life in Adults with Cystic Fibrosis: Familial, Occupational, Social, and Mental Health Predictors

Author: Julien Ancel, Claire Launois, Jeanne-Marie Perotin, Bruno Ravoninjatovo, Pauline Mulette, Jean Hagenburg, Julie Malet, Muriel Griffon, Sophie Carré, François Lebargy, Gaëtan Deslée, Sandra Dury, Service des maladies respiratoires et allergiques [CHU Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), and dormoy, valerian
Subjects: [SDV] Life Sciences [q-bio], Health Information Management, Leadership and Management, [SDV]Life Sciences [q-bio], cystic fibrosis, quality of life, anxiety, depression, CFQ-R, Health Policy, Health Informatics
Abstract: International audience; Background: Cystic Fibrosis (CF) adult patients experience daily physical symptoms and disabilities that may impact their quality of life and mental health. Methods: This prospective study aimed to evaluate the relative contribution of the familial, occupational, and social environment, besides that of the main physical and mental health factors, to the quality of life of CF adult patients using the Cystic Fibrosis Questionnaire-Revised (CFQ-R) in a multivariate model. Results: Fifty patients were analyzed (70% of men; median age of 25 years; median body mass index of 21 kg/m²; median FEV1 of 57%). Anxiety and depression scores were negatively associated with 9 of the 12 CFQ-R domains. When controlling for anxiety and depression, FEV1% and BMI were significant positive predictors of several domains of the CFQ-R. All the familial, occupational, and social components analyzed but one (professional training) were predictors of at least one domain of the CFQ-R. Conclusion: Anxiety and depression explained a greater proportion of the variance than physical variables (age, sex, BMI, FEV1%, and exacerbation in the last year) in CF HRQoL. Many familial, occupational, and social components were also specifically and independently predictors of some HRQoL domains. Their screening might help identifying CF patients eligible for specific interventions, focusing on the impaired QoL dimensions.
Published: 2022
Full Text: View/download PDF

45. Bronchiectasis in renal transplant patients: a cross-sectional study

Author: Pauline Mulette, Jeanne-Marie Perotin, Anaëlle Muggeo, Thomas Guillard, Audrey Brisebarre, Hélène Meyer, Jean Hagenburg, Julien Ancel, Valérian Dormoy, Vincent Vuiblet, Claire Launois, François Lebargy, Gaëtan Deslee, and Sandra Dury
Subjects: Bronchiectasis, Extended culture, CT scan, Renal transplantation, Quality of life, Medicine
Abstract: Abstract Background Bronchiectasis is a chronic airway disease characterized by permanent and irreversible abnormal dilatation of bronchi. Several studies have reported the development of bronchiectasis after renal transplantation (RT), but no prospective study specifically assessed bronchiectasis in this population. This study aimed to compare features of patients with bronchiectasis associated with RT to those with idiopathic bronchiectasis. Methods Nineteen patients with bronchiectasis associated with RT (RT-B group) and 23 patients with idiopathic bronchiectasis (IB group) were prospectively included in this monocentric cross-sectional study. All patients underwent clinical, functional, laboratory, and CT scan assessments. Sputum was collected from 25 patients (n = 11 with RT-B and n = 14 with IB) and airway microbiota was analyzed using an extended microbiological culture. Results Dyspnea (≥ 2 on mMRC scale), number of exacerbations, pulmonary function tests, total bronchiectasis score, severity and prognosis scores (FACED and E-FACED), and quality of life scores (SGRQ and MOS SF-36) were similar in the RT-B and IB groups. By contrast, chronic cough was less frequent in the RT-B group than in the IB group (68% vs. 96%, p = 0.03). The prevalence and diversity of the airway microbiota in sputum were similar in the two groups. Conclusion Clinical, functional, thoracic CT scan, and microbiological characteristics of bronchiectasis are overall similar in patients with IB and RT-B. These results highlight that in RT patients, chronic respiratory symptoms and/or airway infections should lead to consider the diagnosis of bronchiectasis. Further studies are required to better characterize the pathophysiology of RT-B including airway microbiota, its incidence, and impact on therapeutic management.
Published: 2024
Full Text: View/download PDF

46. Bronchoscopic management of asthma, COPD and emphysema

Author: Gaëtan Deslée, Valérian Dormoy, C. Launois, Jeanne-Marie Perotin, Maxime Dewolf, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), and Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, 0302 clinical medicine, Bronchoscopy, medicine, Humans, 030212 general & internal medicine, Asthma copd, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, Asthma, Emphysema, lcsh:RC705-779, COPD, Lung, Bronchial thermoplasty, business.industry, Evidence-based medicine, lcsh:Diseases of the respiratory system, respiratory system, medicine.disease, 3. Good health, respiratory tract diseases, Clinical Practice, medicine.anatomical_structure, Pulmonary Emphysema, 030228 respiratory system, Airway, business
Abstract: In recent years, many bronchoscopic techniques have been developed in chronic obstructive airway inflammatory diseases, including asthma, COPD and emphysema. The main techniques with available data from randomised controlled trials are: 1) bronchial thermoplasty in asthma; 2) valves, coils and thermal vapor ablation in emphysema; and 3) targeted lung denervation in COPD. The objectives of this article are to describe the levels of evidence for efficacy and safety, long-term follow-up results beyond 1 year, and current recommendations for clinical practice from international guidelines for each technique.
Published: 2021
Full Text: View/download PDF

47. Hypoventilation nocturne dans la cohorte de patients obèses « COHYPOB »

Author: Gaëtan Deslée, C. Gut-Gobert, Ronald C. Kessler, Benjamin Renaud-Picard, Frédéric Gagnadoux, Alexandre Leclercq, E. Chatron, J.L. Pépin, Matthieu Canuet, and Université de Reims Champagne-Ardenne (URCA)
Subjects: Pulmonary and Respiratory Medicine, [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS, 3. Good health
Abstract: Introduction Le syndrome obesite-hypoventilation (SOH) est une cause frequente d’insuffisance respiratoire chronique dont la prevalence a augmente au cours des dernieres annees. Le diagnostic de SOH est encore souvent fait a l’occasion d’une hospitalisation pour decompensation respiratoire. Un depistage precoce permettrait de mettre en route des traitements appropries et d’eviter des complications graves. Nous presentons ici les caracteristiques a l’inclusion des patients de l’etude « COHYPOB ». Methodes Il s’agit d’une etude longitudinale, prospective, ouverte, multicentrique francaise (10 centres). Nous avons recrute 187 sujets obeses (IMC ≥ 30 kg/m 2), volontaires, ambulants, sans syndrome obesite hypoventilation connu (= normocapniques le jour). 26 sujets ont ete exclus en raison de la decouverte d’un syndrome d’apnees obstructives du sommeil (SAOS) severe, necessitant un traitement par PPC. Nous avons compare un groupe de patients sans hypoventilation nocturne (HN) avec un groupe de patients presentant des signes d’HN (> 10 episodes de desaturation nocturne ou SpO2 moyenne nocturne Resultats Nous avons inclus 161 sujets, 26 % d’hommes et 74 % de femmes. L’âge moyen etait de 47 ± 13 ans. L’indice de masse corporelle moyen etait de 37 ± 5 kg/m2. 87 (54 %) patients presentaient des signes d’HN isolee. En analyse univariee, les patients obeses avec HN etaient plus âges (53 ± 12 vs 41 ± 11; p = 0.001), plus obeses (IMC: 38,4 ± 5,4 vs 36,0 ± 3,7 kg/m2; p = 0,002), plus dyspneiques a l’effort (p = 0,003), plus somnolents (score d’Epworth: 7,4 ± 4,5 vs 6 ± 3,6; p = 0,034) et plus hypoxemiques le jour (PaO2: 86 ± 13 vs 92 ± 14 mmHg; p = 0,01). Il n’y avait pas de difference significative entre les 2 groupes pour la PaCO2 diurne ni pour les volumes et debits pulmonaires. Conclusion Dans une cohorte de sujets obeses, la moitie presente une hypoventilation nocturne. Le suivi longitudinal de cette cohorte devrait permettre de determiner si cette HN precede la survenue du syndrome obesite hypoventilation.
Published: 2021
Full Text: View/download PDF

48. Clinical Impact of the Epithelial-Mesenchymal Transition in Lung Cancer as a Biomarker Assisting in Therapeutic Decisions

Author: Christine Gilles, Gaëtan Deslée, Julien Ancel, Maxime Dewolf, Béatrice Nawrocky-Raby, Véronique Dalstein, Myriam Polette, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), and dormoy, valerian
Subjects: Oncology, medicine.medical_specialty, Histology, Lung Neoplasms, medicine.medical_treatment, 0206 medical engineering, epithelial-mesenchymal transition, [SDV.CAN]Life Sciences [q-bio]/Cancer, 02 engineering and technology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Targeted therapy, resistance, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], medicine, Humans, Epithelial–mesenchymal transition, Lung cancer, Cancer death, therapy, business.industry, Immunotherapy, 021001 nanoscience & nanotechnology, medicine.disease, 020601 biomedical engineering, 3. Good health, Biomarker, non-small-cell lung cancer, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Anatomy, 0210 nano-technology, business, Biomarkers
Abstract: International audience; Lung cancer is one of the most common solid cancers and represents the leading cause of cancer death worldwide. Over the last decade, research on the epithelial-mesenchymal transition (EMT) in lung cancer has gained increasing attention. Here, we review clinical and histological features of non-small-cell lung cancer associated with EMT. We then aimed to establish potential clinical implications of EMT in current therapeutic options, including surgery, radiation, targeted therapy against oncogenic drivers, and immunotherapy.
Published: 2021
Full Text: View/download PDF

49. Burden and Characteristics of Severe Chronic Hypoxemia in a Real-World Cohort of Subjects with COPD

Author: Olivier Le Rouzic, Denis Caillaud, Gaëtan Deslée, Jean-Louis Paillasseur, Nicolas Roche, Pascale Nesme-Meyer, Pascal Chanez, Thierry Perez, Maeva Zysman, Isabelle Court-Fortune, Pierre-Régis Burgel, Gilles Jebrak, Graziella Brinchault-Rabin, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], macromolecular substances, International Journal of Chronic Obstructive Pulmonary Disease, severe hypoxemia, Hypoxemia, chronic obstructive pulmonary disease, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Quality of life, Internal medicine, Diabetes mellitus, Forced Expiratory Volume, medicine, Humans, 030212 general & internal medicine, Hypoxia, Lung, ComputingMilieux_MISCELLANEOUS, Asthma, Original Research, COPD, business.industry, Mortality rate, General Medicine, medicine.disease, 3. Good health, respiratory tract diseases, Respiratory Function Tests, 030228 respiratory system, nervous system, Cohort, Cardiology, Quality of Life, Arterial blood, medicine.symptom, business, circulatory and respiratory physiology, airflow limitation
Abstract: Maéva Zysman,1 Gaëtan Deslee,2 Thierry Perez,3 Pierre-Régis Burgel,4 Olivier Le Rouzic,3 Graziella Brinchault-Rabin,5 Pascale Nesme-Meyer,6 Isabelle Court-Fortune,7 Gilles Jebrak,8 Pascal Chanez,9 Denis Caillaud,10 Jean-Louis Paillasseur,11 Nicolas Roche4 1Pulmonary Department, Pôle Cardio-thoracique, CHU Haut-Lévèque, INSERM U1045, Bordeaux, France; 2Pulmonary Department, Maison Blanche University Hospital, INSERM U01250, Reims, France; 3University Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 – UMR 9017 – CIIL - Center for Infection and Immunity of Lille, Lille, France; 4Respiratory Medicine, Cochin Hospital, AP-HP and Université de Paris, Institut Cochin, INSERM U1016, Paris, France; 5Service de Pneumologie, Hôpital Pontchaillou, Rennes, France; 6Service de Pneumologie, Hôpital de la Croix-Rousse, Lyon, France; 7Service de Pneumologie, CHU Saint Etienne, Saint Etienne, France; 8Service de Pneumologie, Hôpital Bichat, AP-HP, Paris, France; 9Département des Maladies Respiratoires, AP-HM, Université de la Méditerranée, Marseille, France; 10Service de Pneumologie, Hôpital Gabriel Montpied, CHU, Clermont-Ferrand, France; 11EFFI-STAT, Paris, FranceCorrespondence: Maéva ZysmanAvenue de Magellan, Service des Maladies Respiratoires, CHU Haut Lévèque, Pessac, 33600, FranceTel +33 5 56 79 56 79Email maeva.zysman@chu-bordeaux.frBackground: Chronic respiratory failure may occur as a consequence of chronic obstructive pulmonary disease (COPD) and is associated with significant morbidity and mortality. Hypoxemia is determined by underlying disease characteristics and comorbidities. Severe hypoxemia is typically only found in subjects with severe airflow obstruction (FEV1< 50% predicted). However, how hypoxemia relates to disease characteristics is not fully understood.Methods: In the French Initiatives BPCO real-life cohort, arterial blood gases were routinely collected in most patients. Relationships between severe hypoxemia, defined by a Pa02< 60 mmHg (8 kPa) and clinical/lung function features, comorbidities and mortality were assessed. In subjects with severe hypoxemia, clinical characteristics and comorbidities were compared between those with non-severe versus severe airflow limitation. Classification and regression trees (CART) were used to define clinically relevant subgroups (phenotypes).Results: Arterial blood gases were available from 887 subjects, of which 146 (16%) exhibited severe hypoxemia. Compared to subjects with a PaO2≥ 60 mmHg, the severe hypoxemia group exhibited higher mMRC dyspnea score, lower FEV1, higher RV and RV/TLC, more impaired quality of life, lower 6-minute walking distance, less frequent history of asthma, more frequent diabetes and higher 3-year mortality rate (14% versus 8%, p=0.026). Compared to subjects with Pa02< 60 mmHg and FEV1< 50% (n=115, 13%), those with severe hypoxemia but FEV1≥ 50% predicted (n=31) were older, had higher BMI, less hyperinflation, better quality of life and a higher rate of diabetes (29% versus 13%, p=0.02). Severe hypoxemia was better related to CART-defined phenotypes than to GOLD ABCD classification.Conclusion: In this cohort of stable COPD subjects, severe hypoxemia was associated with worse prognosis and more severe symptoms, airflow limitation and hyperinflation. Compared to subjects with severe hypoxemia and severe airflow limitation, subjects with severe hypoxemia despite non-severe airflow limitation were older, had higher BMI and more diagnosed diabetes.Trial Registration: 04– 479.Keywords: chronic obstructive pulmonary disease, severe hypoxemia, airflow limitation
Published: 2021
Full Text: View/download PDF

50. Chronic obstructive pulmonary disease and the COVID-19 pandemic: Reciprocal challenges

Author: Laurent Boyer, Nicolas Roche, Gaëtan Deslée, Jésus Gonzalez, Thierry Perez, Pierre-Régis Burgel, Maeva Zysman, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), and Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Pneumonia, Viral, Pulmonary disease, Comorbidity, Severity of Illness Index, Article, Betacoronavirus, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, 0302 clinical medicine, Adrenal Cortex Hormones, Internal medicine, Severity of illness, Pandemic, Diabetes Mellitus, Prevalence, medicine, Humans, 030212 general & internal medicine, Pandemics, ComputingMilieux_MISCELLANEOUS, COPD, biology, SARS-CoV-2, Viral Epidemiology, business.industry, Nebulizers and Vaporizers, COVID-19, medicine.disease, biology.organism_classification, 3. Good health, Oxygen, Cerebrovascular Disorders, Pneumonia, 030228 respiratory system, Cardiovascular Diseases, Hypertension, Coronavirus Infections, business
Abstract: International audience
Published: 2020
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

253 results on '"Gaëtan Deslée"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources