Revue des maladies respiratoires最新文献

{"title":"In vivo and in vitro evolution of small cell lung cancer molecular subtypes under cytotoxic treatment","authors":"C. Pierre ,&nbsp;L. Callac ,&nbsp;M. Davilma ,&nbsp;U. Jarry ,&nbsp;Y. Le Guen ,&nbsp;H. Lena ,&nbsp;R. Pedeux ,&nbsp;C. Ricordel","doi":"10.1016/j.rmr.2025.02.013","DOIUrl":"10.1016/j.rmr.2025.02.013","url":null,"abstract":"<div><h3>Introduction</h3><div>Small cell lung cancer (SCLC) is an aggressive form of lung cancer with a high mortality rate. There is currently a “one-size fit all” strategy relying on chemotherapy plus immunotherapy. The emergence of a classification of SCLC into 4 subtypes, based on the expression of transcription factors (ASCL1, NEUROD₁and POU2F3 or triple negative) <span><span>[1]</span></span>, opens the way to personalised therapeutic strategies according to subtype-specific vulnerabilities <span><span>[2]</span></span>. Consequently, we sought to evaluate <em>in vitro</em> and <em>in vivo</em> the evolution of subtypes under chemotherapy.</div></div><div><h3>Methods</h3><div>Two complementary models have been developed to test our hypothesis:</div><div>1) <em>in vitro</em>: exposing SCLC lines (H₄₄₆ NEUROD₁ <!-->+<!--> <!--> H₆₉ ASCL1+ and H₅₂₆ POU2F3<!--> <!-->+<!--> <!-->) to carboplatin. The evolution of subtypes has been evaluated both at protein level using western blots and RNA level using qPCR.</div><div>2) <em>in vivo</em>: analysing CDXs (CTC-Derived Xenografts) tumours before and after exposure to chemotherapy. Cytotoxic drugs tested were carboplatin alone (n<!--> <!-->=<!--> <!-->4), combination of carboplatin and etoposide (n<!--> <!-->=<!--> <!-->4) and lurbinectedin (n<!--> <!-->=<!--> <!-->6). The expression of the different subtypes was characterised on tumours by immunohistochemical (IHC) staining using H-score.</div></div><div><h3>Results</h3><div>We observe a decrease of NEUROD₁ protein expression after exposure of H₄₄₆ cells to carboplatin. This phenotype was detectable only after 3 days of chemotherapy exposure and was independent of NEUROD₁ mRNA level. Similarly, we observe a decrease of ASCL1 and POU2F3 protein expression after carboplatin treatment in H₆₉ and H₅₂₆ cells, respectively. In CDXs models, we observed a global decrease of ASCL1 expression both after lurbinectedin and carboplatin/etoposide combination in the 54.01 CDX tumors, and a strong decrease of NEUROD₁expression after carboplatin in the 51.01 CDX tumors. Noticeably, POU2F3 positive cells emerge in hostpots within tumour samples after lurbinectedin treatment.</div></div><div><h3>Conclusion</h3><div>We demonstrate using both <em>in vitro</em> and <em>in vivo</em> models a decrease of neuro-endocrine transcription factors ASCL1 and NEUROD₁ under cytotoxic-pressure. The mechanisms responsible for those changes are still to be explored. This concept of cellular plasticity modulated by chemotherapy paves the way for therapeutic sequence guided by tumour's phenotype.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Page 188"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bénéfice de la réalité virtuelle immersive sur la dyspnée au cours d’une épreuve de sevrage en réanimation","authors":"D. Jimenez,&nbsp;M. Decavèle,&nbsp;M. Dres,&nbsp;T. Similowski,&nbsp;C. Morélot-Panzini","doi":"10.1016/j.rmr.2025.02.087","DOIUrl":"10.1016/j.rmr.2025.02.087","url":null,"abstract":"<div><h3>Introduction</h3><div>Une épreuve de sevrage en réanimation est un test permettant d’évaluer les capacités du patient à respirer sans l’aide du ventilateur et ainsi prédire les échecs d’extubation, afin de limiter les complications associées à l’intubation. Ce test est cependant à haut risque de générer une dyspnée. La dyspnée est définie comme un symptôme exprimant une expérience angoissante ou dérangeante de sa respiration. Elle est caractérisée par son aspect multidimensionnel et résulte d’un déséquilibre entre la réponse ventilatoire souhaitée et celle réellement obtenue. Plusieurs structures corticales sont impliquées dans son traitement, notamment l’amygdale, le cortex cingulaire antérieur, l’insula et le cortex préfrontal. Elle est vécue comme l’un des pires souvenirs du séjour en réanimation et expose à un risque de stress post-traumatique important. La réalité virtuelle immersive (RVI) permet de simuler un environnement réalistique permettant d’immerger totalement le patient avec un accompagnement par un script hypnotique. Elle s’avère bénéfique sur la douleur, l’anxiété et semble soulager la dyspnée post-Covid. L’hypnose médicale soulage la dyspnée expérimentale chez le sujet sain et réduit l’anxiété de patients atteint de BPCO probablement par des modifications de l’activité corticale, et notamment du cortex pré-frontal et du cortex cingulaire antérieur. Nous formulons l’hypothèse est que la réalité virtuelle associée à un accompagnement hypnotique peut soulager la dyspnée et l’anxiété au cours d’une épreuve de sevrage, via des mécanismes de distraction, de réorientation de l’attention et en agissant sur des zones corticales d’intégration de la dyspnée.</div></div><div><h3>Méthodes</h3><div>Les patients majeurs intubés, communicants et éligibles à la réalisation d’une épreuve de sevrage seront randomisés dans un groupe RVI ou un groupe s’il rapportent une dyspnée cotée avec une EVA<!--> <!-->&gt;<!--> <!-->4/10 après 15<!--> <!-->minutes d’épreuve. La réponse au traitement sera évaluée par une EVA dyspnée, le score MV-RDOS, ainsi qu’avec des marqueurs de la commande respiratoire centrale (EMG des muscles extra-diaphragmatiques parasternaux et scalènes, P 0,1), ainsi que l’évolution de mesures physiologiques (fréquence respiratoire et fréquence cardiaque). Une évaluation de la tolérance sera réalisée par le sickness simulator questionnaire.</div><div>L’accord du CPP est en cours.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Pages 225-226"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effet de l’arrêt d’une exposition à l’hypoxie intermittente chronique sur l’évolution de la fibrose pulmonaire induite par la bléomycine","authors":"Z. Maakoul ,&nbsp;C. Planès ,&nbsp;N. Voituron ,&nbsp;E. Boncoeur","doi":"10.1016/j.rmr.2025.02.078","DOIUrl":"10.1016/j.rmr.2025.02.078","url":null,"abstract":"<div><div>La Fibrose Pulmonaire Idiopathique (FPI) est une pneumopathie interstitielle diffuse touchant le poumon profond, caractérisée par un épaississement de l’épithélium alvéolaire et un dépôt excessif de collagène. Plus de 60 % des patients atteints de FPI présentent, au moment du diagnostic, un Syndrome d’Apnée Hypopnée Obstructif du Sommeil (SAHOS) modéré à sévère. Notre laboratoire a montré que la gravité de la fibrose pulmonaire induite par la bléomycine (BLM) chez la souris était plus sévère et associée à des infiltrats inflammatoires lorsque les souris étaient exposées à l’hypoxie intermittente chronique (HIC), élément délétère du SAHOS <span><span>[1]</span></span>, <span><span>[2]</span></span>. Cet effet est exacerbé lorsque l’exposition à l’HIC précède l’induction de la fibrose. L’objet de cette étude et de documenter l’effet de l’arrêt de l’HIC au moment de l’induction de la fibrose pulmonaire sur la sévérité de celle-ci. Des souris C57BL/6 mâles adultes âgées de 8 semaines ont été exposées à l’HIC pendant 21<!--> <!-->jours (Nadir 7 % O₂, 8<!--> <!-->h/jour, 30 cycles/heure). Au terme de cette période, les animaux ont été instillés à la BLM (3,5<!--> <!-->UI/g) pour induire une fibrose pulmonaire, puis soit maintenus en HIC (groupe HIC/BLM -HIC) soit remis en air ambiant (groupe HIC/BLM-Air) pendant 21<!--> <!-->jours supplémentaires. Les poumons ont été prélevés à la fin de l’expérience afin d’étudier l’architecture pulmonaire et quantifier le collagène (colorations histologiques) et quantifier les cellules inflammatoires présentes (immunohistochimie). Lorsque l’exposition à l’HIC est arrêtée, la perte de masse consécutive à l’instillation de BLM semble moins importante. Nous observons également une atteinte moins sévère dans le groupe avec arrêt de l’HIC en comparaison avec le groupe maintenu en HIC, caractérisée par une occupation moins importante des zones de lésions (20 % vs 30 % en moyenne) avec une sévérité moindre de la fibrose pulmonaire et de manière générale, un espace alvéolaire plus important par rapport aux animaux maintenus en HIC. De plus, on observe également un pourcentage de collagène moins important. Par ailleurs, nous retrouvons de nombreuses cellules inflammatoires, majoritairement des macrophages. Leur proportion est trois fois plus importante pour les animaux HIC/BLM- HIC que pour les animaux HIC/BLM-Air.</div><div>En conclusion, lorsque l’on arrête l’exposition à l’HIC avant induction de la fibrose pulmonaire, Il semble que celle-ci soit moins sévère et moins inflammatoire, ce qui confirme le rôle majeur de l’HIC. Cette étude suggère par ailleurs l’importance du dépistage et de la prise en charge précoce de l’HI générée par le SAHOS. Les auteurs n’ont aucun conflit d’intérêts réel ou perçu, en relation avec ce résumé.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Page 220"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rôle du récepteur GPRX dans la dysplasie bronchopulmonaire","authors":"D. Benfarhone ,&nbsp;CM. Pilard ,&nbsp;I. Gauthereau ,&nbsp;C. Bouchet ,&nbsp;P. Esteves ,&nbsp;E. Dumas-de-la-Roque ,&nbsp;V. Freund-Michel ,&nbsp;C. Guibert ,&nbsp;G. Cardouat","doi":"10.1016/j.rmr.2025.02.022","DOIUrl":"10.1016/j.rmr.2025.02.022","url":null,"abstract":"<div><h3>Introduction</h3><div>La dysplasie bronchopulmonaire (DBP) est une pathologie des nouveau-nés prématurés, qui se caractérise par une altération du développement pulmonaire distal notamment une hypoalvéolisation et un défaut d’angiogenèse. Le récepteur couplé aux protéines G d’adhésion GPRX pourrait être impliqué dans les altérations du développement vasculaire pulmonaire caractéristiques de la DBP. En effet, différentes études suggèrent que ce récepteur régule l’intégrité de l’endothélium vasculaire et l’angiogenèse. En revanche, son rôle dans le développement de la DBP est inconnu.</div></div><div><h3>Méthodes</h3><div>Dans un premier temps, nous avons travaillé sur un modèle de ratons atteints de DBP, induite par une exposition à l’hyperoxie (14<!--> <!-->jours, 90 % d’O₂). La compliance pulmonaire a été évaluée par pléthysmographie invasive. L’alvéolisation, la densité vasculaire et l’expression de GPRX ont été évaluées par immunohistochimie et western-blotting. Dans un second temps, l’expression de GPRX a été évaluée par immunohistochimie et western-blotting sur des poumons fœtaux. Enfin, dans un dernier temps, nous avons travaillé sur des cellules endothéliales fœtales cultivées en conditions de normoxie ou d’hyperoxie (48<!--> <!-->h, 60 % d’O₂), un modèle mimant la DBP in vitro. L’expression de GPRX a été évaluée par western-blotting. La fonctionnalité du récepteur, son rôle dans l’activation des voies pro-angiogéniques et la migration cellulaire ont été évalués par imagerie calcique, western-blotting et inserts de culture Transwell en réponse à son peptide activateur : le peptide GAPX (500<!--> <!-->μM).</div></div><div><h3>Résultats</h3><div>In et ex vivo, les ratons atteints de DBP présentent une diminution de la compliance pulmonaire, une hypoalvéolisation et une diminution de la densité vasculaire. De plus, le récepteur GPRX est exprimé au niveau de l’endothélium vasculaire et son expression est diminuée en condition pathologique. Ex vivo, GPRX est exprimé dans l’endothélium vasculaire pulmonaire fœtal et son expression augmente au cours du développement pulmonaire. In vitro, l’expression et la fonctionnalité de GPRX sont diminuées en condition d’hyperoxie. Enfin, la stimulation de GRPX avec le peptide GAPX permet d’activer les voies de signalisation pro-angiogéniques situées en aval du récepteur, ainsi que la migration cellulaire.</div></div><div><h3>Conclusion</h3><div>Cette étude a permis de mieux caractériser la localisation, l’expression et la fonctionnalité du récepteur GPRX en conditions contrôle ou pathologique (DBP). L’expression et la fonctionnalité du récepteur semblent diminuées en condition pathologique, ce qui pourrait alors contribuer au défaut d’angiogenèse caractéristique de la DBP.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Page 192"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of perinatal exposure to nanoparticles on lung function","authors":"T. Bellil ,&nbsp;L. Plantade ,&nbsp;B. Costes ,&nbsp;R. Souktani ,&nbsp;J. Rose ,&nbsp;S. Bellusci ,&nbsp;A. Aissat ,&nbsp;S. Lanone ,&nbsp;Y. Watanabe","doi":"10.1016/j.rmr.2025.02.046","DOIUrl":"10.1016/j.rmr.2025.02.046","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Nanoparticles (NP) are organic, inorganic, or composite materials with 3 dimensions between 1 and 100&lt;!--&gt; &lt;!--&gt;nm. Due to their physico-chemical characteristics, which give them interesting properties, they can be found in many daily products. In particular, Titanium dioxide (TiO&lt;sub&gt;2&lt;/sub&gt;) NP are widely used in industry in many applications (food additives, cosmetics, pigments, drugs etc.) due to their large range of properties (ultraviolet absorption, antimicrobial effect, food brightening and whitening agent etc.). This raises questions about their potential effect on health, particularly in the perinatal period, when the developing organism is more vulnerable to environmental stressors. Indeed, in mice models, TiO&lt;sub&gt;2&lt;/sub&gt;NP administered to pregnant or lactating mice can reach the fetus, crossing the placental barrier via the bloodstream, or the offspring after translocation in the breastmilk. However, the long-term consequences of such exposure are still poorly studied. Our goal is to better understand the perinatal toxicity of TiO&lt;sub&gt;2&lt;/sub&gt;NP on lung development and function, by studying two distinct TiO&lt;sub&gt;2&lt;/sub&gt;NP with different sizes and crystalline phases.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Pregnant and/or lactating C57BL/6&lt;!--&gt; &lt;!--&gt;J mice were exposed to 10&lt;!--&gt; &lt;!--&gt;nm anatase (Ti10) and 21&lt;!--&gt; &lt;!--&gt;nm anatase/rutile (P25) NP by non-surgical intra-tracheal instillation (100&lt;!--&gt; &lt;!--&gt;μg of NP) once a week, during the 3 weeks of gestation and/or lactation. The pulmonary phenotype of the offspring was analyzed on juvenile mice (D&lt;sub&gt;23&lt;/sub&gt;, 23 days after birth) and on adult mice (D&lt;sub&gt;60&lt;/sub&gt;, 60 days after birth) with n&lt;!--&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;8-12 per group. Mice were weighed every week from D&lt;sub&gt;9&lt;/sub&gt;to D&lt;sub&gt;60&lt;/sub&gt;. The pulmonary function was measured by two different techniques: whole-body plethysmography (VivoFlow®), a non-invasive technique on awake mice that measures respiratory times and the FlexiVent® system, an invasive technique on anesthetized mice that evaluates lung mechanical properties.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Perinatal exposure to P25 induced a decrease in body weight for both males and females from D&lt;sub&gt;16&lt;/sub&gt;until D&lt;sub&gt;60&lt;/sub&gt;. Ti10 exposure induced a decrease in body weight for males from D&lt;sub&gt;32&lt;/sub&gt;and a transient increase in females body weight from D&lt;sub&gt;16&lt;/sub&gt;to D&lt;sub&gt;37&lt;/sub&gt;. In juvenile mice, perinatal exposure to P25 and Ti10 NP induced abnormalities in respiratory parameters with no change in mechanical properties of the lung. Indeed, P25 gestational exposure induced a decrease of tidal volume (0.1873&lt;!--&gt; &lt;!--&gt;±&lt;!--&gt; &lt;!--&gt;0.0178&lt;!--&gt; &lt;!--&gt;ml n&lt;!--&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;11 &lt;em&gt;vs.&lt;/em&gt; 0.2120&lt;!--&gt; &lt;!--&gt;±&lt;!--&gt; &lt;!--&gt;0.0332 n&lt;!--&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;8) wheareas Ti10 gestational&lt;!--&gt; &lt;!--&gt;+&lt;!--&gt; &lt;!--&gt;postnatal exposure induced an increase of tidal volume (0.1472&lt;!--&gt; &lt;!--&gt;±&lt;!--&gt; &lt;!--&gt;0.0169&lt;!--&gt; &lt;!--&gt;ml n&lt;!--&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;11 &lt;em&gt;vs.&lt;/em&gt;","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Pages 204-205"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applying single cell profiling to assess drug anti fibrotic properties in the human precision cut lung slice model of fibrosis","authors":"A. Justet ,&nbsp;N. Mitash ,&nbsp;R.H. Pineda ,&nbsp;T. Adams ,&nbsp;A. Balayev ,&nbsp;N. Abu Hussein ,&nbsp;M. Ishizuka ,&nbsp;H. Kim ,&nbsp;J. Khoury ,&nbsp;J. David Cala-García ,&nbsp;F. Ahangari ,&nbsp;X. Yan ,&nbsp;N. Kaminski ,&nbsp;M. Königshoff","doi":"10.1016/j.rmr.2025.02.083","DOIUrl":"10.1016/j.rmr.2025.02.083","url":null,"abstract":"<div><div>Much of our understanding of pulmonary fibrosis has been derived from mechanistic observations from animal models and many of the drugs currently studied were developed with very limited preclinical evidence for relevance to the human disease. Here, as part of the Pulmonary Fibrosis Connectome Project we used human precision lung cut slices (PCLS) and single nuclear RNA sequencing (snRNAseq) to determine the effect of several compounds targeting key fibrotic pathways and validating drugs predicted as anti-fibrotic.</div></div><div><h3>Methods</h3><div>Four PCLS slices per control donor (<em>n</em> <!-->=<!--> <!-->2) at day 5 after DMSO, FC, FC<!--> <!-->+<!--> <!-->treatment were washed in cold 1X PBS and snap frozen. Fibrotic Cocktail (FC) contained TGFb, TNFa, PDGF and LPA, for 5 days, as previously described 1. Treatment included IPF FDA-approved drugs (Nintedanib), as well as drugs currently in clinical trials. Single nuclei suspensions were barcoded using the 10x Chromium Single Cell platform, cDNA libraries generated and sequenced on Illumina platform and integrated together using RCPA. To build the heatmap we calculated the average mean expression of gene of interest within each cell type and across the different conditions.</div></div><div><h3>Results</h3><div>250,000 single nuclei transcriptomes obtained from 2 donors (2 PCLS per condition, 9 conditions) were analyzed. Fibrotic cocktail stimulation induced the emergence of aberrant basaloid cells (Panel A). No treatment stimulation influenced cell type proportions (Panel B). However, several treatments significantly affected the gene signature of fibroblast and aberrant basaloid cells signature, including Verteporfin, and FDA approved drug targeting YAP-TEAD signaling. Verteporfin led to a significant decrease of ECM or profibrotic genes such as MMP1, TNC, FN1, COL6A6, SERPINE1 and CDH₂ (Panel C). In addition to the gene expression changes, preliminary and ongoing ligand receptor analysis suggests treatment condition significantly modified cellular connectivity of the aberrant basal cells in particular with the alveolar epithelial cells, as compared to the fibrotic condition (Panel D) (<span><span>Fig. 1</span></span>).</div></div><div><h3>Conclusion</h3><div>Applying SnRNA seq to PCLS treated with drugs is an innovative and promising model to assess and potentially predict drug efficacy in human tissues, at a cellular resolution on both abnormal cell populations and cell specific fibrotic gene expression patterns and connectivity.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Page 223"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using dual energy CT Scans to analyse blood perfusion compensation following resection of cancerous lobes","authors":"M. Puig ,&nbsp;A. Gille ,&nbsp;S. Bommart ,&nbsp;A. Bourdin ,&nbsp;N. Molinari ,&nbsp;K. Hireche ,&nbsp;M. Morand","doi":"10.1016/j.rmr.2025.02.023","DOIUrl":"10.1016/j.rmr.2025.02.023","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Comparison of pulmonary perfusion before and after lung resection may provide a better understanding of compensation phenomena and, more importantly, additional clinical information for the inclusion of patients in these surgeries. To evaluate the pulmonary perfusion mechanisms in patients with lung diseases (COPD, nodule…), we used a novel approach using Dual energy CT scan (DECT). The aim is to produce a perfusion profile in surviving lobes, before and after surgery, allowing to quantize and localize potential changes in blood perfusion.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The CLIPPCAIR prospective study enrolls patients undergoing pulmonary resection due to non-small cell lung cancer, with the majority having pulmonary comorbidities such as COPD. 30 patients from this study were examinated. CLIPPCAIR focuses on patients scheduled for resection, excluding those with COPD stages 3 or 4. Patients performed a FEV1 (Forced Expiratory Volume in 1 second), and a FVC (Forced Vital Capacity) to assess their respiratory performances. The recording of these measurements provides elements to determine the COPD GOLD. For each patient, a DECT with an iodine injection (350&lt;!--&gt; &lt;!--&gt;mg/mL, Iomeron, Bracco Imaging) is achieved and reconstructed by GE Revolution (KvP switch between 80 and 140.200&lt;!--&gt; &lt;!--&gt;mA). Iodine concentration and lung parenchyma density maps were then generated. Iodine concentration is used as a biomarker for blood concentration. Lung blood vessels are segmented using Machine Learning. Then, the blood concentration is measured in voxels located in alveolar and small vessel areas, &lt;em&gt;i.e.&lt;/em&gt; non large vessels areas. The “large” vessels are those segmented by the ML algorithm, meaning a diameter larger than the voxel resolution, giving a cross-sectional area of 2.6 mm&lt;sup&gt;2&lt;/sup&gt;. This perfusion metric is plotted against the distance to the nearest blood vessel of cross-sectional area greater than 5 mm&lt;sup&gt;2&lt;/sup&gt; (BV5) (figure 1). This is done before and after surgery in all remaining lobes. It is then possible to compare the perfusion profile of the lobes before and after the resection.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Patients from the CLIPPCAIR cohort lost on average 21 % (standard deviation: 5.2) of their volume, while only showing a slight decrease of their DLCO and FEV1 performances, respectively 7.2 (6.7)% and 5.9 (5.5)%. While these metrics are not a complete picture of respiratory performances, their moderate decrease highlights the existence of compensation mechanisms in the remaining lobes. Indeed, we observe a statistically significant increase of 5.1 (1.6)% in iodine concentration -a proxy for blood perfusion- in the remaining lobes post surgery (p-value&lt;!--&gt; &lt;!--&gt;&lt;&lt;!--&gt; &lt;!--&gt;0.05).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Patients undergoing lung resection show much better DLCO and FEV1 than expected. We show that there is an increase in blood perfusion in the remaining lung parenchym","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Page 193"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A postbiotic supplementation in early life impacted Respiratory Syncytial Virus infection in mice","authors":"C. Chottin ,&nbsp;S. Holowacz ,&nbsp;C. Ferret ,&nbsp;S. Riffault ,&nbsp;E. Jacouton ,&nbsp;D. Descamps","doi":"10.1016/j.rmr.2025.02.062","DOIUrl":"10.1016/j.rmr.2025.02.062","url":null,"abstract":"<div><h3>Introduction</h3><div>The Respiratory Syncytial Virus (RSV) causes severe bronchiolitis in children with 30% of them affected each year. Infection in neonates is characterised by a Th2 immune response and a low Th1 increasing the risk to develop asthma later. Oral probiotics supplementation reduced RSV infection by modulating the lung immune response <span><span>[1]</span></span>. However, no study describes nor the effect of postbiotics or inanimate bacteria in very early life.</div></div><div><h3>Methods</h3><div>Five-days-old BALBC mice were randomly divided into two groups, one receiving tyndallized Bifidobacterium breve LA708 (equivalent to 5<!--> <!-->×<!--> <!-->108<!--> <!-->CFU before tyndallization) or the other PBS as negative control every day during 2 weeks. Luciferase recombinant RSV (205<!--> <!-->×<!--> <!-->103<!--> <!-->pfu per animal) was intranasally inoculated at day 21 to half the mice in both groups. Infection was recorded in vivo by bioluminescence in lung and snout at 1.4 and 10 days post infection (dpi). Animals were necropsied and tissues and bronchoalveolar fluid (BALF) were collected for analysis of viral replication (bioluminescence activity) and lung inflammation (luminex assay and cytometry).</div></div><div><h3>Results</h3><div>All infected animals showed a mean radiance of around 1<!--> <!-->×<!--> <!-->104 in lungs and 1<!--> <!-->×<!--> <!-->105 in snouts at 1 and 4 dpi confirming the infection. B. breve LA708 showed no effect on infection at 1dpi in either the snouts or lungs. However, animals supplemented with B. breve LA708 exhibited lower infection in snouts at 4 dpi compared with animals supplemented with PBS. Similarly, although all mice were free of infection at 10 dpi in the LA708 group, a few mice still exhibited lung infection in the PBS one. An analysis of the immune response was then performed to decipher the effect of the strain. At 1 dpi, infected animals supplemented with B. breve LA708 showed a higher but non-significant number of polynuclear neutrophils and lymphocytes in BALF compared with infected control mice (<em>P</em> <!-->=<!--> <!-->0.13) without affecting the total number of cells. Similarly, it seemed that IFN-b, TNF-a and IL-6 were increased in the lungs of animals supplemented with B. breve LA708 compared with infected control mice at 4<!--> <!-->dpi. At 4 and 10<!--> <!-->dpi, lungs of infected neonates supplemented with B. breve LA708 expressed an increased level of CD₄₅ <!-->+<!--> <!-->leucocytes compared to those supplemented with PBS with an enhance on the proportion of CD₈ <!-->+<!--> <!-->lymphocytes, NK cells and type 1 innate lymphoid cells (ILC1) among lymphocytes.</div></div><div><h3>Conclusion</h3><div>These data indicated that early supplementations with the postbiotic B. breve LA708 reduced infection in neonates, probably through a faster recruitment of innate immune cells and an activation of Th1 response in the lungs.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Pages 212-213"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altération de l’implication des septines dans l’infection des cellules épithéliales bronchiques par P. aeruginosa en contexte de mucoviscidose","authors":"S. Brax ,&nbsp;C. Gaudin ,&nbsp;M. Ruffin ,&nbsp;C. Calmel ,&nbsp;H. Corvol ,&nbsp;L. Guillot","doi":"10.1016/j.rmr.2025.02.068","DOIUrl":"10.1016/j.rmr.2025.02.068","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;L’atteinte respiratoire est la principale cause de mortalité chez les personnes atteintes de mucoviscidose. Tout au long de l’évolution de cette maladie, les infections pulmonaires répétées et l’inflammation chronique qui en résulte endommagent progressivement le tissu bronchique, entraînant un déclin de la fonction pulmonaire. Pseudomonas aeruginosa (&lt;em&gt;P.&lt;/em&gt; &lt;em&gt;aeruginosa&lt;/em&gt;), une bactérie à Gram négatif retrouvée chez près de 50 % des patients adultes, est particulièrement préoccupante en raison de sa résistance élevée aux antibiotiques, rendant nécessaire le développement de nouveaux traitements (Cystic Fibrosis Transmembrane conductance Regulator) et une meilleure compréhension des mécanismes d’infection cellulaire. Dans notre étude, nous nous sommes focalisés sur le cytosquelette de septines (SEPT), connu pour jouer un rôle clé dans les processus d’interaction hôte-pathogène ainsi que dans le maintien de la fonction de barrière cellulaire. Cependant, le rôle anti-infectieux des SEPT dans le contexte de la mucoviscidose reste à ce jour insuffisamment élucidé.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Méthodes&lt;/h3&gt;&lt;div&gt;Nous avons utilisé des cellules épithéliales bronchiques primaires de patients atteints de mucoviscidose (CF) et de doneur sains (non CF), deux lignées cellulaires épithéliales bronchiques, 16HBE (type sauvage et F508del/F508del) et BEAS-2B. La souche PAK-GFP (Green Fluorescent Protein) de &lt;em&gt;P.&lt;/em&gt; &lt;em&gt;aeruginosa&lt;/em&gt; a été utilisée. Des ARN interférents (siARN) ciblant les SEPT2, 7 ou 9 ont été utilisés pour inhiber leur expression. L’expression des SEPT a été étudiée par qPCR et western blot. Des expériences d’internalisation bactérienne ont été réalisées avec de la tobramycine. L’elexacaftor (3&lt;!--&gt; &lt;!--&gt;μM)/tezacaftor (3&lt;!--&gt; &lt;!--&gt;μM)/ivacaftor (1&lt;!--&gt; &lt;!--&gt;μM) (ETI) a été utilisé pour restaurer l’expression et la fonction du régulateur de la conductance transmembranaire de la mucoviscidose (CFTR).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Résultats&lt;/h3&gt;&lt;div&gt;L’étude des niveaux d’expression en ARNm des SEPT dans les cellules bronchiques montre des profils comparables entre des cellules CF et non-CF. De plus, nous avons observé que les SEPT2, 7 et 9 étaient celles qui avaient les plus importants niveaux d’expression. L’inhibition de l’expression des SEPT2, 7 et 9 par siARN a induit une augmentation du nombre de bactéries intracellulaire dans les cellules non-CF mais pas dans les CF (lignées cellulaires et cellules primaires). Suggérant que ces trois protéines limitent l’invasion bactérienne intracellulaire en condition physiologique mais pas dans le contexte CF. Par la suite nous avons observé que cette action limitante ne survenait pas dans les phases précoces de l’infection. Enfin, la restauration de la protéine CFTR via pré-traitement à l’ETI ne rétabli pas l’action des SEPT en contexte CF suggérant ainsi que l’altération de ce mécanisme n’est pas liée à la fonction de CFTR.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Les résulta","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Pages 215-216"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virus-induced cellular senescence causes pulmonary sequelae post-influenza infection","authors":"L. Lipskaia ,&nbsp;V. Sencio ,&nbsp;A. Houssaini ,&nbsp;F. Angulo ,&nbsp;E. Born ,&nbsp;V. Gros ,&nbsp;E. Marcos ,&nbsp;L. Deruyter ,&nbsp;S. Abid ,&nbsp;M. Goekyildirim ,&nbsp;S. Heumel ,&nbsp;V. Contreras ,&nbsp;J.M. Flaman ,&nbsp;R. Le Grand ,&nbsp;R. Le Goffic ,&nbsp;D. Bernard ,&nbsp;S. Adnot ,&nbsp;F.R. Trottein","doi":"10.1016/j.rmr.2025.02.058","DOIUrl":"10.1016/j.rmr.2025.02.058","url":null,"abstract":"<div><h3>Introduction</h3><div>The Influenza A virus (IAV) infection dramatically raises rates of morbidity and mortality throughout the world. Our hypothesis is that respiratory viral infections can cause cellular senescence, which can hinder lung healing and lead to long-term lung impairments like emphysema and fibrosis.</div></div><div><h3>Methods</h3><div>To investigate whether IAV-induced cell senescence results in long-term lung damage in a mouse model, we employed pharmacological, genetic, and immunolabelling techniques.</div></div><div><h3>Results</h3><div>Cellular senescence was observed in the bronchial epithelia of mice infected with a sublethal dose of IAV H₁N1p2009, beginning on day 4 post-infection (dpi) and progressing to the parenchyma on day 7. Even 28 days after infection, cellular senescence persisted; at 90 dpi, it started to decline. The lungs displayed senescence-related indicators, such as upregulated p16 and p21 and DNA damage expression triggered by gamma-H₂A. X. On day 28, the infection greatly altered the lungs’ structure and remodeling, resulting in fibrosis, abrasion of the airway epithelium, emphysema, and damage to the bronchi and alveoli, particularly in regions where senescent cell accumulation took place. Similar findings were found in nonhuman primates infected with IAV, where senescent cells within the bronchi survived due to insufficient repair of the airway epithelium. When rapalog AP20187 was used to deplete p16-expressing cells, lung fibrosis, emphysema, and inflammation were reduced in p16-ATTAC mice. Remarkably, the airway epithelium healed completely 28 days following the injury, demonstrating the rapidity with which the epithelial repair mechanism operates. Treatment with the senolytic drug ABT-263 also effectively increases epithelial repair, but emphysema and fibrosis did not change.</div></div><div><h3>Conclusion</h3><div>The virus-induced cellular senescence responsible for part of the influenza after effects in the lungs. Targeting senescent cells specifically could be advantageous in terms of therapy.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Pages 210-211"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}