Revue des maladies respiratoires最新文献

{"title":"Développement et caractérisation d’un modèle d’alvéolosphère 3D modulable, dérivé de cellules épithéliales alvéolaires humaines de type II pour l’étude de la physiopathologie de l’emphysème","authors":"M. Gueçamburu ,&nbsp;A. Pavot ,&nbsp;E. Sammaniego ,&nbsp;C. Jeannière ,&nbsp;Y. Belaroussi ,&nbsp;M. Thumerel ,&nbsp;H. Begueret ,&nbsp;E. Maurat ,&nbsp;K. Raasch ,&nbsp;G. Maucort ,&nbsp;F. Decoeur ,&nbsp;V. Studer ,&nbsp;P. Berger ,&nbsp;P. Henrot ,&nbsp;I. Dupin ,&nbsp;M. Zysman","doi":"10.1016/j.rmr.2025.02.074","DOIUrl":"10.1016/j.rmr.2025.02.074","url":null,"abstract":"<div><h3>Contexte</h3><div>Les modèles de culture tridimensionnels (3D) de l’emphysème offrent un outil unique pour améliorer la compréhension des mécanismes sous-jacents. Le principal défi reste de réduire l’hétérogénéité de taille et de forme des alvéolosphères, généralement cultivées dans du Matrigel. L’objectif principal est d’étudier les mécanismes de l’emphysème à l’aide d’un modèle 3D-alvéolosphère ajustable, durable et reproductible à partir de cellules épithéliales alvéolaires de type II humaines (AEC2).</div></div><div><h3>Méthodes</h3><div>Des cellules AEC2 isolées par tri immunomagnétique (HTII-280+) à partir de 46 échantillons pulmonaires de fumeurs et non-fumeurs ont été cultivées dans des micro-puits d’hydrogel 3D de forme et de taille ajustables, par photopolymérisation. Des analyses morphologiques (taille, lumière) et phénotypiques [immunomarquage, qPCR, microscopie électronique à transmission (MET)] ont été effectuées aux jours (J) 1, 7, 14 et 21. Ensuite, nous avons modélisé l’emphysème par exposition chronique à 5 % d’extrait de fumée de cigarette (CSE) pendant 5<!--> <!-->jours consécutifs et effectué les mêmes analyses.</div></div><div><h3>Résultats</h3><div>Les alvéolosphères 3D ont été maintenues en culture pendant 21<!--> <!-->jours. La formation progressive d’une lumière centrale, observée in vivo, a été observée dès J7 et maintenue jusqu’à J21. Les jonctions serrées suggèrent la formation d’une barrière épithéliale (MET et immunomarquage ZO-1). Les marqueurs des cellules AEC1 (expression de p2xr4, pdpn) sont apparus progressivement de J1 à J21 tandis que les marqueurs des cellules AEC2 (expression de abca3, sftpa, sftpc) ont persisté au fil du temps. Les images MET ont confirmé la synthèse de surfactant (corps lamellaires, corps lipidiques). L’exposition au CSE pendant 5<!--> <!-->jours a entraîné une diminution de la viabilité cellulaire (calcein, FACS), une désorganisation architecturale, une augmentation des marqueurs de stress oxydatif (expression de hmox, nqo1) et une libération de cytokines (MIF, IL8) dans le surnageant.</div></div><div><h3>Interprétation</h3><div>Nous avons pu obtenir un modèle 3D-alvéolosphère standardisé, ajustable et reproductible à partir de cellules AEC2 humaines, reproduisant les principales caractéristiques du poumon natif. L’exposition au CSE offre une opportunité d’étudier les voies physiopathologiques impliquées dans l’emphysème.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Pages 218-219"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791533","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":"Development of cutting-edge preclinical models to study the response of small-cell lung cancer to current therapies","authors":"L. Martinetti ,&nbsp;M. Harel ,&nbsp;A. Faili ,&nbsp;S. Kayal ,&nbsp;H. Phuong Pham ,&nbsp;M. Touati ,&nbsp;M. Davilma ,&nbsp;C. Ricordel ,&nbsp;V. Quiniou ,&nbsp;U. Jarry ,&nbsp;R. Pedeux","doi":"10.1016/j.rmr.2025.02.012","DOIUrl":"10.1016/j.rmr.2025.02.012","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Small cell lung cancer (SCLC) is the most aggressive subtype of lung cancer. Although the combination of chemotherapy and immune checkpoint inhibitors has recently shown slight improvement in outcome, the prognosis remains very poor. The development of relevant preclinical models is a crucial step towards new therapies. Here, we present the models we are currently using and developing in the laboratory: xenografts derived from Circulating Tumor Cells from SCLC patients (CDXs), CDXs on humanized mice (Hu-CD&lt;sub&gt;34+&lt;/sub&gt;-NXG), and CDXs on a cutting-edge combination of Hu-CD&lt;sub&gt;34+&lt;/sub&gt;-NXG with controlled gut microbiota (‘MESHCAP’ model, meaning Exogenous Microbiota and Humanized Mice for Lung Cancer).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;CTCs are collected from patients blood at the time of SCLC diagnosis. Isolation is performed by immunomagnetic negative selection, followed by a flow cytometry sorting of CD&lt;sub&gt;56+&lt;/sub&gt;/CD&lt;sub&gt;45−&lt;/sub&gt; cells labeled with fluorescent antibodies.&lt;/div&gt;&lt;div&gt;For CDXs generation, CTCs are injected subcutaneously into immunodeficient NSG mice.&lt;/div&gt;&lt;div&gt;For humanized CDXs, CDXs are subcutaneously grafted into humanized CD&lt;sub&gt;34+&lt;/sub&gt; NXG mice. To control gut microbiota composition (MESHCAP model), the original microbiota from mice is depleted by a specific cocktail of antibiotics. NXG mice are then inoculated with a specific bacterial consortium prior to CD&lt;sub&gt;34+&lt;/sub&gt; humanization.&lt;/div&gt;&lt;div&gt;In all three models, subcutaneous tumor growth is monitored manually. When tumor size reaches 1000&lt;!--&gt; &lt;!--&gt;mm&lt;sup&gt;3&lt;/sup&gt;, the animals are sacrificed and the tumor removed. Tissues are fixed and used for immunochemistry, or snap-frozen for subsequent genetic or transcriptomic analysis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;We have developed a unique method for isolating live CTCs from the blood of SCLC patients. This EpCAM-independent method is based on the CD&lt;sub&gt;56+&lt;/sub&gt; marker frequently expressed on the membrane surface of SCLC cells.&lt;/div&gt;&lt;div&gt;To date, we have successfully generated 5 CDXs from CTCs of SCLC patients. These models show rapid tumor growth, supporting the tumorigenic properties of CD&lt;sub&gt;56+&lt;/sub&gt;-CTCs. Initial trials of CDXs grafted onto humanized mice show a partial response to immunotherapy.&lt;/div&gt;&lt;div&gt;Development of our MESHCAP mouse model is underway, and preliminary results on depletion of gut microbiota and humanization of the immune system are encouraging. Our bacterial consortium, supposedly beneficial for immunotherapy, has been cultured and will be inoculated in mice.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;We have developed CDX-based mouse models that are relevant and effective for studying response to SCLC treatment. While conventional CDXs models allow us to study response to chemotherapy, inhibitors etc., transplantation of humanized mice broaden research possibilities by enabling us to test immunotherapeutic strategies. We also expect to analyze the impact","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Page 187"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791539","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":"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":"Une tumeur médiastinale postérieure rare, le cas d’un myélolipome extrasurrénalien thoracique","authors":"D. Marquette ,&nbsp;A. Causeret ,&nbsp;F. Llamas Gutierrez ,&nbsp;M. Mauduit ,&nbsp;B. Richard De Latour","doi":"10.1016/j.rmr.2025.02.010","DOIUrl":"10.1016/j.rmr.2025.02.010","url":null,"abstract":"<div><h3>Introduction</h3><div>Le myélolipome est une tumeur bénigne, rare, habituellement de la surrénale. Dans de rares cas, elle peut avoir une localisation extra-surrénalienne, dont thoracique.</div></div><div><h3>Observation</h3><div>Nous rapportons le cas ici de la découverte fortuite d’une masse médiastinale postérieure avec composante graisseuse, non fixante au TEP scanner. Devant l’aspect atypique à l’imagerie et l’absence de certitude diagnostique, le patient a bénéficié d’une prise en charge chirurgicale qui a permis de poser le diagnostic de myélolipome extrasurrénalien et d’en faire l’exérèse.</div></div><div><h3>Conclusion</h3><div>Le myélolipome extrasurrénalien est une tumeur rare, de bon pronostic et le plus souvent de découverte fortuite. Sa prise en charge est principalement chirurgicale. Une surveillance est possible selon la taille de la lésion et sa localisation.</div></div><div><h3>Introduction</h3><div>Myelolipoma is a rare, benign, usually adrenal. tumor, In rare cases, it may be extra-adrenal, for example thoracic.</div></div><div><h3>Observation</h3><div>We report the case of the fortuitous discovery of a posterior mediastinal mass with a fatty component, not immediately identifiable on the PET scan. Because of the atypical appearance on imaging and the lack of diagnostic certainty, the patient received surgical management, which has ultimately made it possible to accurately diagnose and curatively remove extra-adrenal myelolipoma.</div></div><div><h3>Conclusion</h3><div>Most often incidentally detected, extra-adrenal myelolipoma is a rare tumor with a good prognosis. Management is primarily surgical. Monitoring of the lesion depends on its size and location.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Pages 237-241"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573196","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":"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":"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":"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":"Une méthode simple pour dépister la distension dynamique pulmonaire : le test de tachypnée rythmée par un métronome","authors":"G. Simon,&nbsp;J. Moulinié,&nbsp;Q. Lorber,&nbsp;M. Hayot,&nbsp;F. Gouzi","doi":"10.1016/j.rmr.2024.12.005","DOIUrl":"10.1016/j.rmr.2024.12.005","url":null,"abstract":"<div><div>La distension pulmonaire dynamique est un déterminant de la dyspnée des malades respiratoires chroniques. Sa mise en évidence permet d’en expliquer la cause, d’orienter et évaluer l’efficacité des traitements. Cependant, la mesure de la capacité inspiratoire (CI) lors d’une épreuve d’effort maximale (EFx), est limitée par le difficile accès des patients à cet examen. Une méthode alternative, plus simple et accessible, est la mesure de la CI au cours d’un test de tachypnée rythmée par un métronome (TRM). Malgré certaines études ayant fait état d’une faible spécificité, cette méthode est apparue faisable, mais aussi reproductible, valide en particulier pour la dyspnée des activités de la vie journalière, et sensible aux traitements. La standardisation méthodologique est détaillée dans la présente revue, de même que le décalage observé entre les changements de CI au cours de l’EFx et au cours du TRM. En conclusion, la recherche d’une distension dynamique peut être réalisée pour tout patient en consultation de pneumologie via le test de TRM. Le seuil de 11 % de base de baisse de la CI par rapport à sa valeur de base au cours du test TRM peut être retenu pour le dépistage de la distension dynamique, même s’il faut rester prudent pour l’interprétation en cas de test positif. Le suivi des variations de CI sur le test TRM permet de surveiller l’évolution du patient et la réponse aux traitements.</div></div><div><div>Lung dynamic hyperinflation (DH) is one of the main determinants of dyspnea in chronic respiratory disease patients. Producing evidence of DH is critical during dyspnea assessment, the objectives being to explain the cause, to target treatments, and to monitor their efficacy. The gold standard method consists in repeated measurement of inspiratory capacity (IC) during cardiopulmonary exercise testing (CPET). Unfortunately, access to CPET is limited and assessment of IC during CPET can be challenging in some patients. An alternative method consists in assessment of IC during the testing known as metronome-paced tachypnea (MPT) challenge. This method is feasible, repeatable, valid (i.e. corelated with dyspnea patients’ activities of daily living), and responsive to treatments. However, while its diagnostic performance is acceptable, it is lacking in specificity. Methodological standardization is detailed in the present review, as are the differences between IC changes in CPET and in MPT. As a means of assessing DH, MPT challenge is not only applicable to patients outside a pulmonary function test laboratory, but also easily affordable to any chest physician equipped with a simple spirometry device. A diagnosis threshold of 11% for IC decrease during MPT challenge can be used, albeit while bearing in mind the possibility of a false positive result. Moreover, assessment of IC variations during MPT can help to monitor a patient's overall evolution and response to treatments.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Pages 228-236"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365853","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":"Effect of repetitive magnetic stimulation on respiratory function after cervical spinal cord injury","authors":"W. Chen ,&nbsp;L. Ngoma ,&nbsp;S. Vinit ,&nbsp;I. Vivodtzev","doi":"10.1016/j.rmr.2025.02.084","DOIUrl":"10.1016/j.rmr.2025.02.084","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Traumatic cervical spinal cord injuries (cSCI) damage respiratory pathways leading to life-threatening respiratory insufficiency. Inflammation is known to play a role in limiting neural regeneration after injury, thereby exacerbating respiratory dysfunction and refrain respiratory recovery. Repetitive Magnetic Stimulation (rMS) has emerged as a promising therapeutic intervention in SCI, demonstrating potential in reducing inflammation at the spinal level. In this project, we aim to explore the therapeutic potential of rMS in enhancing respiratory function by attenuating neuro-inflammation in a mouse cervical hemi-contusion (HC) model, which closely mimics the pathophysiology of human cSCI.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Eighteen adult Swiss male mice underwent hemi-contusion at the C3-C5 level (C3HC, &lt;em&gt;n&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;15) or laminectomy (&lt;em&gt;n&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;3) and received either high-frequency (10&lt;!--&gt; &lt;!--&gt;Hz) rMS or sham treatment for 10 days (9 trains of 100 biphasic pulses, separated by 30 s intervals between trains delivered at 80% MO (percentage of maximum output of the stimulator), 900 stimulations per protocol). Animals that showed a reduction of more than 20% from baseline were divided into two groups: (1) C3HC&lt;!--&gt; &lt;!--&gt;+&lt;!--&gt; &lt;!--&gt;sham rMS (&lt;em&gt;n&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;5); (2) C3HC&lt;!--&gt; &lt;!--&gt;+&lt;!--&gt; &lt;!--&gt;rMS (&lt;em&gt;n&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;6). Respiratory function was assessed using whole-body plethysmography before (Day 0) and after C3HC (Day 7) and after intervention (Day 21) and provide amplitude (tidal volume, V&lt;sub&gt;T&lt;/sub&gt;) and respiratory frequency (&lt;em&gt;f&lt;/em&gt;&lt;sub&gt;R&lt;/sub&gt;). Moreover, diaphragm activity was measured by in-situ electromyography (EMG). All spinal cord samples were collected for Immunofluorescence experiments.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;In the whole group of mice, SCI led to a mean decrease in V&lt;sub&gt;T&lt;/sub&gt; of 37% without differences between groups. Mice which received rMS, exhibited a recovery in V&lt;sub&gt;T&lt;/sub&gt; greater than spontaneous recovery as measured in the sham rMS group and there was a trend to significant difference between groups (rMS: D&lt;sub&gt;21&lt;/sub&gt;vs. D&lt;sub&gt;7&lt;/sub&gt;: 6.5&lt;!--&gt; &lt;!--&gt;±&lt;!--&gt; &lt;!--&gt;1.1&lt;!--&gt; &lt;!--&gt;μL/g vs. 4.1&lt;!--&gt; &lt;!--&gt;±&lt;!--&gt; &lt;!--&gt;1.2&lt;!--&gt; &lt;!--&gt;μL/g, sham rMS: D&lt;sub&gt;21&lt;/sub&gt;vs. D&lt;sub&gt;7&lt;/sub&gt;: 4.5&lt;!--&gt; &lt;!--&gt;±&lt;!--&gt; &lt;!--&gt;0.5&lt;!--&gt; &lt;!--&gt;μL/g vs. 3.3&lt;!--&gt; &lt;!--&gt;±&lt;!--&gt; &lt;!--&gt;1.3&lt;!--&gt; &lt;!--&gt;μL/g, 2 ways RM ANOVA, &lt;em&gt;p&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;0.05). There was no significant change observed for &lt;em&gt;f&lt;/em&gt;&lt;sub&gt;R&lt;/sub&gt;. As a result, similar changes were observed for V&lt;sub&gt;E&lt;/sub&gt; than V&lt;sub&gt;T&lt;/sub&gt; after rMS or Sham but differences between groups were not significant. In addition, at D&lt;sub&gt;21&lt;/sub&gt;, the activity of the ipsilateral (injured side) hemidiaphragm tended to be lower than control values (Laminectomy) but only in the sham group, for both ventral and medial hemidiaphragms (Ventral: sham rMS vs. lami: 5.0&lt;!--&gt; &lt;!--&gt;±&lt;!--&gt; &lt;!--&gt;1.4 vs. 7.3&lt;!--&gt; ","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Pages 223-224"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791407","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}