Pub Date : 2025-06-01DOI: 10.1016/j.rmr.2025.04.004
A. Dinh , F. Barbier , J.-P. Bedos , M. Blot , V. Cattoir , Y.-E. Claessens , X. Duval , P. Fillâtre , M. Gautier , Y. Guegan , S. Jarraud , A. Le Monnier , D. Lebeaux , P. Loubet , C. de Margerie , P. Serayet , Y. Tandjaoui-Lambotte , E. Varon , Y. Welker , D. Basille
{"title":"Corrigendum de « Actualisation des recommandations de prise en charge des pneumonies aiguës communautaires chez l’adulte par la Société de pathologie infectieuse de langue française (SPILF) et la Société de pneumologie de langue française (SPLF). Avec le soutien de la Société de réanimation de langue française, (SRLF), de la Société française de microbiologie (SFM), de la Société française de radiologie (SFR) et de la Société française de médecine d’urgence (SFMU) » [RMR 42 (3) (2025) 168–86]","authors":"A. Dinh , F. Barbier , J.-P. Bedos , M. Blot , V. Cattoir , Y.-E. Claessens , X. Duval , P. Fillâtre , M. Gautier , Y. Guegan , S. Jarraud , A. Le Monnier , D. Lebeaux , P. Loubet , C. de Margerie , P. Serayet , Y. Tandjaoui-Lambotte , E. Varon , Y. Welker , D. Basille","doi":"10.1016/j.rmr.2025.04.004","DOIUrl":"10.1016/j.rmr.2025.04.004","url":null,"abstract":"","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 6","pages":"Pages 328-329"},"PeriodicalIF":0.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011775","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}
Pub Date : 2025-06-01DOI: 10.1016/j.rmr.2025.04.005
C. Thibon , L. Vecellio , J.-C. Dubus , G. Reychler
La nébulisation est une thérapie couramment utilisée chez les patients atteints de pathologies respiratoires, y compris ceux porteurs de virus respiratoires tels que le SARS-CoV-2, le virus grippal et le VRS. Depuis l’épidémie de COVID-19, les émissions de particules dans l’environnement lors de la nébulisation suscitent des interrogations. En effet, bien que ce traitement soit connu pour exposer les soignants aux particules médicamenteuses, le risque de dispersion virale reste peu documenté dans la littérature. Cette revue narrative explore ce risque dans le but de susciter des réflexions et des recommandations pour réduire le risque de contamination aéroportée des soignants lors d’une prochaine épidémie, ainsi que dans le cadre de la gestion des virus saisonniers.
Nebulization is a commonly applied therapy for patients with respiratory conditions, encompassing those infected with respiratory viruses such as SARS-CoV-2, influenza and RSV. Since the COVID-19 pandemic occurred, concerns have arisen regarding the release into the environment of airborne particles during nebulization. While this treatment is known to expose healthcare workers to drug particles, the risk of viral dispersion remains poorly documented in the literature. The following narrative review explores this risk with the aim of fostering discussions and recommendations, the objectives being to minimize airborne contamination risk for healthcare workers during future epidemics, and in the management of seasonal viruses.
{"title":"La nébulisation présente-t-elle un risque de transmission virale ? Une revue narrative","authors":"C. Thibon , L. Vecellio , J.-C. Dubus , G. Reychler","doi":"10.1016/j.rmr.2025.04.005","DOIUrl":"10.1016/j.rmr.2025.04.005","url":null,"abstract":"<div><div>La nébulisation est une thérapie couramment utilisée chez les patients atteints de pathologies respiratoires, y compris ceux porteurs de virus respiratoires tels que le SARS-CoV-2, le virus grippal et le VRS. Depuis l’épidémie de COVID-19, les émissions de particules dans l’environnement lors de la nébulisation suscitent des interrogations. En effet, bien que ce traitement soit connu pour exposer les soignants aux particules médicamenteuses, le risque de dispersion virale reste peu documenté dans la littérature. Cette revue narrative explore ce risque dans le but de susciter des réflexions et des recommandations pour réduire le risque de contamination aéroportée des soignants lors d’une prochaine épidémie, ainsi que dans le cadre de la gestion des virus saisonniers.</div></div><div><div>Nebulization is a commonly applied therapy for patients with respiratory conditions, encompassing those infected with respiratory viruses such as SARS-CoV-2, influenza and RSV. Since the COVID-19 pandemic occurred, concerns have arisen regarding the release into the environment of airborne particles during nebulization. While this treatment is known to expose healthcare workers to drug particles, the risk of viral dispersion remains poorly documented in the literature. The following narrative review explores this risk with the aim of fostering discussions and recommendations, the objectives being to minimize airborne contamination risk for healthcare workers during future epidemics, and in the management of seasonal viruses.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 6","pages":"Pages 318-327"},"PeriodicalIF":0.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187858","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}
Pub Date : 2025-05-01DOI: 10.1016/j.rmr.2025.02.092
S. Neveu , J. Antonowicz , M. Colantonio , R. Deleris , C. Raherison-Semjen
Une granulomatose avec polyangéite (GPA) a été diagnostiquée chez une patiente Afro-Caribéenne de 65 ans présentant initialement une hypoacousie et de multiples lésions pulmonaires dont une masse de 6 cm. Une biopsie pulmonaire de la masse était en faveur d’une vascularite. Une progression rapide de la maladie était notée avec surdité presque complète et une aphasie, une insuffisance rénale aiguë, et des troubles de conscience à la suite d’une crise d’épilepsie sur syndrome d’encéphalopathie postérieure réversible (PRES). Le décès eut lieu un mois après l’admission, en lien avec une pneumonie acquise sous ventilation mécanique. Les symptômes ORL sont fréquemment les premiers signes de GPA et doivent alerter le clinicien quand ils sont accompagnés de nodules pulmonaires, même chez un patient Afro-Caribéen où la GPA est considérée exceptionnelle. La GPA est une maladie rare associée aux anticorps anti-cytoplasme des neutrophiles (ANCA) avec spécificité anti-protéinase 3 (PR3). Le diagnostic est basé sur un ensemble de critères à la fois cliniques, radiologiques, et biologiques. Une biopsie d’une lésion pulmonaire, même si inconstamment spécifique, peut aider à établir le diagnostic. Ce cas clinique permet d’illustrer les particularités de présentation clinique de la GPA et la potentielle sévérité de ses formes multi-organes.
Granulomatosis with polyangiitis (GPA) was diagnosed in a 65-year-old Afro-Caribbean patient presenting initially with hearing loss and a pseudo-tumoral 6 cm lung mass. Lung biopsy findings favored the diagnosis of vasculitis. Rapid disease progression was noted with near-complete deafness and lack of speech, severe renal failure necessitating dialysis, and persisting disturbance of consciousness following tonic-clonic seizures due to posterior reversible encephalopathy syndrome (PRES). The patient died one month after admission due to ARDS secondary to ventilator-associated pneumonia. Otological symptoms are frequently the first signs of GPA and should alert the clinician when concomitant with lung nodules, even among Afro-Caribbean patients, in whom GPA is unusual. GPA is a rare disease occurring nearly exclusively in Caucasian populations and is associated with anti-neutrophil cytoplasm antibodies (ANCA) with anti-proteinase 3 (PR3) specificity. Diagnosis is based on clinical, radiological, and biological findings. While pathology from lung localizations is inconsistently specific and rarely made, it can help to establish the diagnosis. This clinical case aptly illustrates the specific clinical presentation of GPA and the potential severity of its multi-organ manifestations.
{"title":"Une hypoacousie révélant une granulomatose avec polyangéite : un cas rare en population Afro-Caribéenne","authors":"S. Neveu , J. Antonowicz , M. Colantonio , R. Deleris , C. Raherison-Semjen","doi":"10.1016/j.rmr.2025.02.092","DOIUrl":"10.1016/j.rmr.2025.02.092","url":null,"abstract":"<div><div>Une granulomatose avec polyangéite (GPA) a été diagnostiquée chez une patiente Afro-Caribéenne de 65 ans présentant initialement une hypoacousie et de multiples lésions pulmonaires dont une masse de 6<!--> <!-->cm. Une biopsie pulmonaire de la masse était en faveur d’une vascularite. Une progression rapide de la maladie était notée avec surdité presque complète et une aphasie, une insuffisance rénale aiguë, et des troubles de conscience à la suite d’une crise d’épilepsie sur syndrome d’encéphalopathie postérieure réversible (PRES). Le décès eut lieu un mois après l’admission, en lien avec une pneumonie acquise sous ventilation mécanique. Les symptômes ORL sont fréquemment les premiers signes de GPA et doivent alerter le clinicien quand ils sont accompagnés de nodules pulmonaires, même chez un patient Afro-Caribéen où la GPA est considérée exceptionnelle. La GPA est une maladie rare associée aux anticorps anti-cytoplasme des neutrophiles (ANCA) avec spécificité anti-protéinase 3 (PR3). Le diagnostic est basé sur un ensemble de critères à la fois cliniques, radiologiques, et biologiques. Une biopsie d’une lésion pulmonaire, même si inconstamment spécifique, peut aider à établir le diagnostic. Ce cas clinique permet d’illustrer les particularités de présentation clinique de la GPA et la potentielle sévérité de ses formes multi-organes.</div></div><div><div>Granulomatosis with polyangiitis (GPA) was diagnosed in a 65-year-old Afro-Caribbean patient presenting initially with hearing loss and a pseudo-tumoral 6<!--> <!-->cm lung mass. Lung biopsy findings favored the diagnosis of vasculitis. Rapid disease progression was noted with near-complete deafness and lack of speech, severe renal failure necessitating dialysis, and persisting disturbance of consciousness following tonic-clonic seizures due to posterior reversible encephalopathy syndrome (PRES). The patient died one month after admission due to ARDS secondary to ventilator-associated pneumonia. Otological symptoms are frequently the first signs of GPA and should alert the clinician when concomitant with lung nodules, even among Afro-Caribbean patients, in whom GPA is unusual. GPA is a rare disease occurring nearly exclusively in Caucasian populations and is associated with anti-neutrophil cytoplasm antibodies (ANCA) with anti-proteinase 3 (PR3) specificity. Diagnosis is based on clinical, radiological, and biological findings. While pathology from lung localizations is inconsistently specific and rarely made, it can help to establish the diagnosis. This clinical case aptly illustrates the specific clinical presentation of GPA and the potential severity of its multi-organ manifestations.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 5","pages":"Pages 286-290"},"PeriodicalIF":0.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630891","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}
Pub Date : 2025-05-01DOI: 10.1016/j.rmr.2025.03.002
T. Grosz , G. Calcaianu , C. Palpacuer , M. Riou , L. Kassegne , C. Marcot , T. Degot , J. Leroux , L. Kalmuk , M. Fore , R. Kessler , B. Renaud-Picard
Introduction
La prise en charge par traitements inhalés de la bronchopneumopathie chronique obstructive (BPCO) en France suit les propositions de la société de pneumologie de langue française (SPLF). Nous avons mené au sein de deux centres hospitaliers Alsaciens, une étude rétrospective pour déterminer le taux de conformité des prescriptions de ces traitements.
Méthodes
Les données des patients suivis pour BPCO ont été collectées entre août 2022 et janvier 2023. Les phénotypes Asthma-COPD Overlap et Overlap syndrome ont été exclus de l’étude. Les données recueillies étaient issues de la dernière consultation de pneumologie réalisée par le patient dans l’un des deux centres.
Résultats
Parmi les 250 patients recrutés, 183 (73,2 %) présentaient une prescription conforme. Parmi les patients avec une prescription non-conforme, 38 avaient une sur-prescription (56,7 %), surtout secondaire à un usage non indiqué de corticostéroïdes inhalés (CSI), et 29 présentaient une sous-prescription (43,3 %), principalement due à une absence de traitement par bronchodilatateurs de longue durée d’action.
Conclusions
La prescription des traitements dans la BPCO reste non optimale avec une proportion élevée de non-conformités thérapeutiques, notamment une sur-prescription de CSI. Des études complémentaires seront à réaliser pour développer des stratégies visant à améliorer les pratiques de prescriptions.
Introduction
The use of inhaled treatments for chronic obstructive pulmonary disease (COPD) in France follows the management proposals issued by the Société de Pneumologie de Langue Française (SPLF). We conducted a retrospective study in two hospitals in Alsace, France to determine the rate of compliance with the recommended treatments.
Methods
Data were collected from patients with follow-up for COPD between August 2022 and January 2023. Asthma-COPD Overlap and Overlap syndrome phenotypes were excluded from the study. The data were extracted from the patient's most recent pulmonology consultation at one of the two centers.
Results
Out of the 250 patients recruited, 183 (73.2%) had compliant prescriptions. Among those with non-compliant prescriptions, 38 exhibited over-prescribing (56.7%), often secondary to inappropriate use of inhaled corticosteroids (ICS), while 29 cases showed under-prescribing (43.3%), due mainly to lack of treatment with long-acting bronchodilators.
Conclusions
Treatment prescription in COPD remains sub-optimal, with a high proportion of therapeutic non-conformities, especially the over-prescribing of ICS. Further studies are needed to develop strategies for improving prescribing practices.
{"title":"Évaluation du suivi des propositions de prescriptions pour la BPCO en Alsace","authors":"T. Grosz , G. Calcaianu , C. Palpacuer , M. Riou , L. Kassegne , C. Marcot , T. Degot , J. Leroux , L. Kalmuk , M. Fore , R. Kessler , B. Renaud-Picard","doi":"10.1016/j.rmr.2025.03.002","DOIUrl":"10.1016/j.rmr.2025.03.002","url":null,"abstract":"<div><h3>Introduction</h3><div>La prise en charge par traitements inhalés de la bronchopneumopathie chronique obstructive (BPCO) en France suit les propositions de la société de pneumologie de langue française (SPLF). Nous avons mené au sein de deux centres hospitaliers Alsaciens, une étude rétrospective pour déterminer le taux de conformité des prescriptions de ces traitements.</div></div><div><h3>Méthodes</h3><div>Les données des patients suivis pour BPCO ont été collectées entre août 2022 et janvier 2023. Les phénotypes <em>Asthma-COPD Overlap et Overlap syndrome</em> ont été exclus de l’étude. Les données recueillies étaient issues de la dernière consultation de pneumologie réalisée par le patient dans l’un des deux centres.</div></div><div><h3>Résultats</h3><div>Parmi les 250 patients recrutés, 183 (73,2 %) présentaient une prescription conforme. Parmi les patients avec une prescription non-conforme, 38 avaient une sur-prescription (56,7 %), surtout secondaire à un usage non indiqué de corticostéroïdes inhalés (CSI), et 29 présentaient une sous-prescription (43,3 %), principalement due à une absence de traitement par bronchodilatateurs de longue durée d’action.</div></div><div><h3>Conclusions</h3><div>La prescription des traitements dans la BPCO reste non optimale avec une proportion élevée de non-conformités thérapeutiques, notamment une sur-prescription de CSI. Des études complémentaires seront à réaliser pour développer des stratégies visant à améliorer les pratiques de prescriptions.</div></div><div><h3>Introduction</h3><div>The use of inhaled treatments for chronic obstructive pulmonary disease (COPD) in France follows the management proposals issued by the <em>Société de Pneumologie de Langue Française (SPLF)</em>. We conducted a retrospective study in two hospitals in Alsace, France to determine the rate of compliance with the recommended treatments.</div></div><div><h3>Methods</h3><div>Data were collected from patients with follow-up for COPD between August 2022 and January 2023. Asthma-COPD Overlap and Overlap syndrome phenotypes were excluded from the study. The data were extracted from the patient's most recent pulmonology consultation at one of the two centers.</div></div><div><h3>Results</h3><div>Out of the 250 patients recruited, 183 (73.2%) had compliant prescriptions. Among those with non-compliant prescriptions, 38 exhibited over-prescribing (56.7%), often secondary to inappropriate use of inhaled corticosteroids (ICS), while 29 cases showed under-prescribing (43.3%), due mainly to lack of treatment with long-acting bronchodilators.</div></div><div><h3>Conclusions</h3><div>Treatment prescription in COPD remains sub-optimal, with a high proportion of therapeutic non-conformities, especially the over-prescribing of ICS. Further studies are needed to develop strategies for improving prescribing practices.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 5","pages":"Pages 243-251"},"PeriodicalIF":0.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764987","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}
Pub Date : 2025-05-01DOI: 10.1016/j.rmr.2025.03.001
P. Le Guen , N. Poté , M.-P. Debray , V. Gounant , B. Crestani , C. Taillé
Introduction
L’hyperplasie neuroendocrine pulmonaire diffuse idiopathique, plus connue sous l’acronyme DIPNECH (« diffuse idiopathic pulmonary neuroendocrine cell hyperplasia »), est une pathologie chronique rare, touchant majoritairement les femmes de plus de 60 ans.
État des connaissances
La DIPNECH associe des signes cliniques non spécifiques (toux chronique, dyspnée), une obstruction bronchique et des signes évocateurs au scanner thoracique (signes de bronchiolite, nodules, micronodules multiples). Le diagnostic est le plus souvent histologique retrouvant une hyperplasie des cellules neuroendocrines, des tumorlets et, de manière inconstante, des tumeurs carcinoïdes et une bronchiolite constrictive.
Perspectives
Il n’existe actuellement aucune recommandation pour le traitement de la DIPNECH et la littérature se limite à des cas cliniques et des séries rétrospectives. Les inhibiteurs de mTOR et les analogues de la somatostatine sont des pistes thérapeutiques qui nécessitent d’être validées par des essais thérapeutiques. Un suivi fonctionnel et une surveillance par scanner sont nécessaires pour dépister les complications.
Conclusions
La DIPNECH est une pathologie rare, généralement insidieuse, mais pouvant parfois évoluer vers une insuffisance respiratoire chronique et la formation de tumeurs carcinoïdes. Le diagnostic doit être évoqu, en particulier chez les femmes d’âge mûr présentant une toux chronique.
Introduction
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare, chronic condition that predominantly affects women over the age of 60.
Current knowledge
DIPNECH combines non-specific clinical signs (chronic cough, dyspnea), bronchial obstruction on PFT and signs suggestive of bronchiolitis on chest CT associated with nodules and multiple micronodules. The diagnosis is most often histological, associating neuroendocrine cell hyperplasia, tumorlets and, inconsistently, carcinoid tumors and constrictive bronchiolitis.
Prospects
There are currently no recommendations for DIPNECH treatment and the literature is limited to case reports and retrospective series. Inhibitors of mTOR and somatostatin analogs are possible treatments requiring validation by clinical trials. Functional follow-up and CT scan monitoring are necessary in order to detect complications.
Conclusions
DIPNECH is a rare, usually insidious pathology, and may in some cases expose the patient to a risk of tumor and chronic respiratory failure. The diagnosis should be made in the event of a chronic cough in a middle-aged woman.
{"title":"L’hyperplasie neuroendocrine pulmonaire diffuse idiopathique (DIPNECH)","authors":"P. Le Guen , N. Poté , M.-P. Debray , V. Gounant , B. Crestani , C. Taillé","doi":"10.1016/j.rmr.2025.03.001","DOIUrl":"10.1016/j.rmr.2025.03.001","url":null,"abstract":"<div><h3>Introduction</h3><div>L’hyperplasie neuroendocrine pulmonaire diffuse idiopathique, plus connue sous l’acronyme DIPNECH (« <em>diffuse idiopathic pulmonary neuroendocrine cell hyperplasia</em> »), est une pathologie chronique rare, touchant majoritairement les femmes de plus de 60 ans.</div></div><div><h3>État des connaissances</h3><div>La DIPNECH associe des signes cliniques non spécifiques (toux chronique, dyspnée), une obstruction bronchique et des signes évocateurs au scanner thoracique (signes de bronchiolite, nodules, micronodules multiples). Le diagnostic est le plus souvent histologique retrouvant une hyperplasie des cellules neuroendocrines, des tumorlets et, de manière inconstante, des tumeurs carcinoïdes et une bronchiolite constrictive.</div></div><div><h3>Perspectives</h3><div>Il n’existe actuellement aucune recommandation pour le traitement de la DIPNECH et la littérature se limite à des cas cliniques et des séries rétrospectives. Les inhibiteurs de mTOR et les analogues de la somatostatine sont des pistes thérapeutiques qui nécessitent d’être validées par des essais thérapeutiques. Un suivi fonctionnel et une surveillance par scanner sont nécessaires pour dépister les complications.</div></div><div><h3>Conclusions</h3><div>La DIPNECH est une pathologie rare, généralement insidieuse, mais pouvant parfois évoluer vers une insuffisance respiratoire chronique et la formation de tumeurs carcinoïdes. Le diagnostic doit être évoqu, en particulier chez les femmes d’âge mûr présentant une toux chronique.</div></div><div><h3>Introduction</h3><div>Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare, chronic condition that predominantly affects women over the age of 60.</div></div><div><h3>Current knowledge</h3><div>DIPNECH combines non-specific clinical signs (chronic cough, dyspnea), bronchial obstruction on PFT and signs suggestive of bronchiolitis on chest CT associated with nodules and multiple micronodules. The diagnosis is most often histological, associating neuroendocrine cell hyperplasia, tumorlets and, inconsistently, carcinoid tumors and constrictive bronchiolitis.</div></div><div><h3>Prospects</h3><div>There are currently no recommendations for DIPNECH treatment and the literature is limited to case reports and retrospective series. Inhibitors of mTOR and somatostatin analogs are possible treatments requiring validation by clinical trials. Functional follow-up and CT scan monitoring are necessary in order to detect complications.</div></div><div><h3>Conclusions</h3><div>DIPNECH is a rare, usually insidious pathology, and may in some cases expose the patient to a risk of tumor and chronic respiratory failure. The diagnosis should be made in the event of a chronic cough in a middle-aged woman.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 5","pages":"Pages 262-273"},"PeriodicalIF":0.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743450","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}
Pub Date : 2025-05-01DOI: 10.1016/j.rmr.2025.03.003
L. Maurier , A.-L. Chéné , P. Hulo , J. Chen , C. Sagan , E. Pons-Tostivint
<div><h3>Introduction</h3><div>Les anticorps conjugués ou <em>antibody-drug conjugate (ADC)</em> représentent une nouvelle classe thérapeutique prometteuse chez les patients porteurs d’un cancer broncho-pulmonaire non à petites cellules (CBNPC). Les études évaluant les ADC ont mis en évidence un profil de toxicité pulmonaire sous forme de pneumopathie interstitielle diffuse (PID).</div></div><div><h3>État des connaissances</h3><div>Parmi les patients porteurs d’un CBNPC, dans les études évaluant le trastuzumab-deruxtecan (cible <em>Her-2</em>), les incidences de PID vont de 10,7 à 26,0 %, et de 3,6 à 25,0 % dans celles évaluant de la datopotamab-deruxtecan (cible <em>TROP-2</em>). Une incidence de 9,9 % de PID est retrouvée pour le telisotuzumab-vedotin (cible <em>c-MET</em>) et de 5 % pour le patritumab-deruxtecan (cible <em>Her-3</em>). Aucun cas de PID n’a été décrite dans les études évaluant le sacituzumab-govitecan (cible <em>TROP-2</em>) et le tusamitamab-ravtansine (cible <em>CEACAM5</em>).</div></div><div><h3>Perspectives</h3><div>Les comorbidités respiratoires, une insuffisance rénale ou la posologie et le type de l’ADC seraient des facteurs de risque de PID. Des études associent désormais les ADC à de l’immunothérapie, avec peu de données disponibles à ce jour sur la toxicité pulmonaire.</div></div><div><h3>Conclusion</h3><div>Plusieurs ADC sont associés à la survenue de PID, de grade et d’intensité variable. Cela nécessite une connaissance des risques, des modalités diagnostiques et thérapeutiques afin de pouvoir dépister et traiter rapidement leur survenue.</div></div><div><h3>Introduction</h3><div>Antibody-drug conjugates (ADCs) represent a promising new therapeutic class in non-small-cell lung cancer (NSCLC) patients. Studies assessing ADC have highlighted a pulmonary toxicity profile in the form of interstitial lung disease (ILD).</div></div><div><h3>State of the art</h3><div>Several ADCs for NSCLC are currently being developed. In studies evaluating Trastuzumab-Deruxtecan (<em>Her-2</em> target), incidence of drug-induced ILD ranged from 10.7 to 26.0%, and from 3.6 to 25.0% in those evaluating Datopotamab-Deruxtecan (<em>TROP-2</em> target). Incidence of 9.9 and 5% of ILD was observed with Telisotuzumab-Vedotin (<em>c-MET</em> target) and Patritumab-Deruxtecan (<em>Her-3</em> target), respectively. No cases of ILD have been reported with Sacituzumab-Govitecan (<em>TROP-2</em> target) or Tusamitamab-Ravtansine (<em>CEACAM5</em> target).</div></div><div><h3>Perspectives</h3><div>Several risk factors for ADC-induced ILD seem to emerge, including respiratory comorbidities, renal insufficiency, or type and dosage of ADC. Current studies are focusing on the combination of ADC and immunotherapy, although there are few data now available on pulmonary toxicity profiles.</div></div><div><h3>Conclusion</h3><div>Among the many ADCs being developed, several can cause ILD of varying grades and intensity. Knowledge of their risks, diagnostic and
{"title":"Pneumopathies interstitielles diffuses induites par les anticorps conjugués","authors":"L. Maurier , A.-L. Chéné , P. Hulo , J. Chen , C. Sagan , E. Pons-Tostivint","doi":"10.1016/j.rmr.2025.03.003","DOIUrl":"10.1016/j.rmr.2025.03.003","url":null,"abstract":"<div><h3>Introduction</h3><div>Les anticorps conjugués ou <em>antibody-drug conjugate (ADC)</em> représentent une nouvelle classe thérapeutique prometteuse chez les patients porteurs d’un cancer broncho-pulmonaire non à petites cellules (CBNPC). Les études évaluant les ADC ont mis en évidence un profil de toxicité pulmonaire sous forme de pneumopathie interstitielle diffuse (PID).</div></div><div><h3>État des connaissances</h3><div>Parmi les patients porteurs d’un CBNPC, dans les études évaluant le trastuzumab-deruxtecan (cible <em>Her-2</em>), les incidences de PID vont de 10,7 à 26,0 %, et de 3,6 à 25,0 % dans celles évaluant de la datopotamab-deruxtecan (cible <em>TROP-2</em>). Une incidence de 9,9 % de PID est retrouvée pour le telisotuzumab-vedotin (cible <em>c-MET</em>) et de 5 % pour le patritumab-deruxtecan (cible <em>Her-3</em>). Aucun cas de PID n’a été décrite dans les études évaluant le sacituzumab-govitecan (cible <em>TROP-2</em>) et le tusamitamab-ravtansine (cible <em>CEACAM5</em>).</div></div><div><h3>Perspectives</h3><div>Les comorbidités respiratoires, une insuffisance rénale ou la posologie et le type de l’ADC seraient des facteurs de risque de PID. Des études associent désormais les ADC à de l’immunothérapie, avec peu de données disponibles à ce jour sur la toxicité pulmonaire.</div></div><div><h3>Conclusion</h3><div>Plusieurs ADC sont associés à la survenue de PID, de grade et d’intensité variable. Cela nécessite une connaissance des risques, des modalités diagnostiques et thérapeutiques afin de pouvoir dépister et traiter rapidement leur survenue.</div></div><div><h3>Introduction</h3><div>Antibody-drug conjugates (ADCs) represent a promising new therapeutic class in non-small-cell lung cancer (NSCLC) patients. Studies assessing ADC have highlighted a pulmonary toxicity profile in the form of interstitial lung disease (ILD).</div></div><div><h3>State of the art</h3><div>Several ADCs for NSCLC are currently being developed. In studies evaluating Trastuzumab-Deruxtecan (<em>Her-2</em> target), incidence of drug-induced ILD ranged from 10.7 to 26.0%, and from 3.6 to 25.0% in those evaluating Datopotamab-Deruxtecan (<em>TROP-2</em> target). Incidence of 9.9 and 5% of ILD was observed with Telisotuzumab-Vedotin (<em>c-MET</em> target) and Patritumab-Deruxtecan (<em>Her-3</em> target), respectively. No cases of ILD have been reported with Sacituzumab-Govitecan (<em>TROP-2</em> target) or Tusamitamab-Ravtansine (<em>CEACAM5</em> target).</div></div><div><h3>Perspectives</h3><div>Several risk factors for ADC-induced ILD seem to emerge, including respiratory comorbidities, renal insufficiency, or type and dosage of ADC. Current studies are focusing on the combination of ADC and immunotherapy, although there are few data now available on pulmonary toxicity profiles.</div></div><div><h3>Conclusion</h3><div>Among the many ADCs being developed, several can cause ILD of varying grades and intensity. Knowledge of their risks, diagnostic and","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 5","pages":"Pages 274-285"},"PeriodicalIF":0.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916871","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}
Pub Date : 2025-05-01DOI: 10.1016/j.rmr.2025.04.001
S. Deslais , C. Pierre , T. Goter , C. Giordanengo , M.-A. Lester , Y. Le Guen , H. Lena , C. Ricordel
Introduction
Les inhibiteurs de points de contrôle immunitaires ont révolutionné la prise en charge des cancers bronchiques non à petites cellules avancés (CBNPC). La proportion de patients « long survivants » est estimée entre 8 et 16 %, mais cette population reste mal connue.
Matériel et méthodes
L’étude BREATH est une étude observationnelle rétrospective incluant des patients porteurs d’un CBNPC métastatique ou localement avancé non irradiable, traités par immunothérapie et présentant une maladie contrôlée pendant au moins 12 mois après la première injection. L’objectif principal est de décrire les caractéristiques de cette population.
Résultats
L’étude a inclus 49 patients. Après 51 mois de suivi médian, la médiane de survie sans progression (SSP) ou de survie globale (SG) n’est pas atteinte. À 36 mois, la SSP était de 64,7 % et la SG de 91,6 %. Les patients ayant reçu un schéma complet d’immunothérapie (2 ans) ont eu une meilleure SSP (HR = 0,046 ; IC à 95 % [0,14–0,98] ; p = 0,03) que ceux ayant reçu un schéma incomplet. Un taux d’albumine ≥ 35 g/L à l’initiation de l’immunothérapie était le seul facteur associé à une SSP prolongée en analyse multivariée.
Conclusion
Les patients porteurs d’un CBNPC avancé avec un contrôle prolongé sous immunothérapie présentent une survie est exceptionnellement longue indiquant un changement de paradigme dans nos pratiques.
Introduction
Immune checkpoint inhibitors have revolutionized the management of advanced non-small cell lung cancer (NSCLC). While the proportion of “long-term survivors” is estimated to be between 8% and 16%, this population remains poorly understood.
Methods
BREATH is a retrospective observational study including patients with metastatic or non-radically treatable locally advanced NSCLC, treated with immunotherapy and presenting with controlled disease for at least 12 months after the first immunotherapy injection. The main objective is to describe the characteristics of this population.
Results
Forty-nine patients were included in the study. After a median follow-up of 51 months, median progression-free survival (PFS) or overall survival (OS) was not reached. At 36 months, PFS was 64.7% and OS was 91.6%. Patients who received a complete immunotherapy regimen (two years) had a higher rate of PFS (HR 0.046; 95% CI [0.14–0.98]; P = 0.03) than those who received an incomplete regimen. An albumin level ≥ 35 g/L at the start of immunotherapy was the only factor associated in multivariate analysis with prolonged PFS.
Conclusion
Patients with advanced NSCLC and prolonged disease control under immunotherapy exhibit exceptionally long survival, pointin
{"title":"CBNPC avancés présentant un contrôle prolongé sous immunothérapie : Cohorte BREATH","authors":"S. Deslais , C. Pierre , T. Goter , C. Giordanengo , M.-A. Lester , Y. Le Guen , H. Lena , C. Ricordel","doi":"10.1016/j.rmr.2025.04.001","DOIUrl":"10.1016/j.rmr.2025.04.001","url":null,"abstract":"<div><h3>Introduction</h3><div>Les inhibiteurs de points de contrôle immunitaires ont révolutionné la prise en charge des cancers bronchiques non à petites cellules avancés (CBNPC). La proportion de patients « long survivants » est estimée entre 8 et 16 %, mais cette population reste mal connue.</div></div><div><h3>Matériel et méthodes</h3><div>L’étude BREATH est une étude observationnelle rétrospective incluant des patients porteurs d’un CBNPC métastatique ou localement avancé non irradiable, traités par immunothérapie et présentant une maladie contrôlée pendant au moins 12 mois après la première injection. L’objectif principal est de décrire les caractéristiques de cette population.</div></div><div><h3>Résultats</h3><div>L’étude a inclus 49 patients. Après 51 mois de suivi médian, la médiane de survie sans progression (SSP) ou de survie globale (SG) n’est pas atteinte. À 36 mois, la SSP était de 64,7 % et la SG de 91,6 %. Les patients ayant reçu un schéma complet d’immunothérapie (2 ans) ont eu une meilleure SSP (HR<!--> <!-->=<!--> <!-->0,046 ; IC à 95 % [0,14–0,98] ; <em>p</em> <!-->=<!--> <!-->0,03) que ceux ayant reçu un schéma incomplet. Un taux d’albumine<!--> <!-->≥<!--> <!-->35<!--> <!-->g/L à l’initiation de l’immunothérapie était le seul facteur associé à une SSP prolongée en analyse multivariée.</div></div><div><h3>Conclusion</h3><div>Les patients porteurs d’un CBNPC avancé avec un contrôle prolongé sous immunothérapie présentent une survie est exceptionnellement longue indiquant un changement de paradigme dans nos pratiques.</div></div><div><h3>Introduction</h3><div>Immune checkpoint inhibitors have revolutionized the management of advanced non-small cell lung cancer (NSCLC). While the proportion of “long-term survivors” is estimated to be between 8% and 16%, this population remains poorly understood.</div></div><div><h3>Methods</h3><div>BREATH is a retrospective observational study including patients with metastatic or non-radically treatable locally advanced NSCLC, treated with immunotherapy and presenting with controlled disease for at least 12 months after the first immunotherapy injection. The main objective is to describe the characteristics of this population.</div></div><div><h3>Results</h3><div>Forty-nine patients were included in the study. After a median follow-up of 51 months, median progression-free survival (PFS) or overall survival (OS) was not reached. At 36 months, PFS was 64.7% and OS was 91.6%. Patients who received a complete immunotherapy regimen (two years) had a higher rate of PFS (HR 0.046; 95% CI [0.14–0.98]; <em>P</em> <!-->=<!--> <!-->0.03) than those who received an incomplete regimen. An albumin level<!--> <!-->≥<!--> <!-->35<!--> <!-->g/L at the start of immunotherapy was the only factor associated in multivariate analysis with prolonged PFS.</div></div><div><h3>Conclusion</h3><div>Patients with advanced NSCLC and prolonged disease control under immunotherapy exhibit exceptionally long survival, pointin","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 5","pages":"Pages 252-261"},"PeriodicalIF":0.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916914","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}
Pub Date : 2025-04-01DOI: 10.1016/j.rmr.2025.02.047
T. Bellil , L. Plantade , B. Costes , R. Souktani , J. Rose , S. Bellusci , A. Aissat , S. Lanone , Y. Watanabe
<div><h3>Introduction</h3><div>Nanoparticles (NP) are materials with 3 dimensions between 1 and 100<!--> <!-->nm Due to their physico-chemical characteristics, they can be found in many daily products. In particular, Titanium dioxide (TiO<sub>2</sub>) NP are widely used in industry in many applications owing 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<sub>2</sub>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. Our goal is to better understand the perinatal toxicity of TiO<sub>2</sub>NP on lung development and function, by studying two distinct TiO<sub>2</sub>NP with different sizes and crystalline phases.</div></div><div><h3>Methods</h3><div>Pregnant and/or lactating C57BL/6<!--> <!-->J mice were exposed to 10<!--> <!-->nm anatase (Ti10) and 21<!--> <!-->nm anatase/rutile (P25) NP by intra-tracheal instillation (100<!--> <!-->μg of NP) once a week, during the gestation and/or the lactation. The pulmonary phenotype of the offspring was analyzed on juvenile and adult mice weighed every week from D<sub>9</sub>to D<sub>60</sub>. The pulmonary function was measured by two 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.</div></div><div><h3>Results</h3><div>Perinatal exposure to P25 induced a decrease in body weight for both males and females from D<sub>16</sub>until D<sub>60</sub>. Ti10 exposure induced a decrease in body weight for males from D<sub>32</sub>and a transient increase in females from D<sub>16</sub>to D<sub>37</sub>. In juvenile mice, perinatal exposure to P25 and Ti10 NP induced abnormalities in respiratory parameters with no change in lung mechanical properties. Indeed, P25 gestational exposure induced a decrease of tidal volume wheareas Ti10 exposure induced an increase of tidal volume. At the adult age, only P25 exposure provoked male specific modifications on the mechanical properties characterized by a decrease of inspiratory capacity and forced vital capacity.</div></div><div><h3>Conclusion</h3><div>TiO<sub>2</sub>NP maternal exposure had an impact on the offspring, while this impact is different for the 2 NP tested. Ti10 exposure induced transient changes on the body weight and on the respiratory parameters that do not last until the adult age. On the other hand, P25 exposure provoked a permanent decrease in body weight, induced transient abnormalities of the respiratory parameters in juvenile mice and lung mechanical defects at the adult age.
{"title":"Effects of perinatal exposure to nanoparticles on lung function","authors":"T. Bellil , L. Plantade , B. Costes , R. Souktani , J. Rose , S. Bellusci , A. Aissat , S. Lanone , Y. Watanabe","doi":"10.1016/j.rmr.2025.02.047","DOIUrl":"10.1016/j.rmr.2025.02.047","url":null,"abstract":"<div><h3>Introduction</h3><div>Nanoparticles (NP) are materials with 3 dimensions between 1 and 100<!--> <!-->nm Due to their physico-chemical characteristics, they can be found in many daily products. In particular, Titanium dioxide (TiO<sub>2</sub>) NP are widely used in industry in many applications owing 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<sub>2</sub>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. Our goal is to better understand the perinatal toxicity of TiO<sub>2</sub>NP on lung development and function, by studying two distinct TiO<sub>2</sub>NP with different sizes and crystalline phases.</div></div><div><h3>Methods</h3><div>Pregnant and/or lactating C57BL/6<!--> <!-->J mice were exposed to 10<!--> <!-->nm anatase (Ti10) and 21<!--> <!-->nm anatase/rutile (P25) NP by intra-tracheal instillation (100<!--> <!-->μg of NP) once a week, during the gestation and/or the lactation. The pulmonary phenotype of the offspring was analyzed on juvenile and adult mice weighed every week from D<sub>9</sub>to D<sub>60</sub>. The pulmonary function was measured by two 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.</div></div><div><h3>Results</h3><div>Perinatal exposure to P25 induced a decrease in body weight for both males and females from D<sub>16</sub>until D<sub>60</sub>. Ti10 exposure induced a decrease in body weight for males from D<sub>32</sub>and a transient increase in females from D<sub>16</sub>to D<sub>37</sub>. In juvenile mice, perinatal exposure to P25 and Ti10 NP induced abnormalities in respiratory parameters with no change in lung mechanical properties. Indeed, P25 gestational exposure induced a decrease of tidal volume wheareas Ti10 exposure induced an increase of tidal volume. At the adult age, only P25 exposure provoked male specific modifications on the mechanical properties characterized by a decrease of inspiratory capacity and forced vital capacity.</div></div><div><h3>Conclusion</h3><div>TiO<sub>2</sub>NP maternal exposure had an impact on the offspring, while this impact is different for the 2 NP tested. Ti10 exposure induced transient changes on the body weight and on the respiratory parameters that do not last until the adult age. On the other hand, P25 exposure provoked a permanent decrease in body weight, induced transient abnormalities of the respiratory parameters in juvenile mice and lung mechanical defects at the adult age.","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Page 205"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791794","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}
Pub Date : 2025-04-01DOI: 10.1016/j.rmr.2025.02.035
A. Gombault, S. Huot-Marchand, C. Véront, S. Carignon, VFJ. Quesniaux, B. Ryffel, P. Broz, N. Riteau, I. Couillin
Introduction
Environmental air pollutants including ozone cause severe lung injury and aggravate respiratory diseases such as asthma and COPD. Ozone is a major air pollutant causing pulmonary inflammation evolving into lung emphysema and/or fibrosis in mice exposed to ozone but the mechanisms are not well understood. Innate immune sensors such as nucleotide-oligomerization domain-like receptors (NLRs) are able to form cytosolic complexes named inflammasomes that mediate inflammatory cytokines production and immunological cell death. Among NLRs, NLRP3 was shown to be involved in establishment of lung inflammation to ozone. However, the role of NLRP6, another NLR in involved in inflammasome scaffold, like NLRP6 in ozone-induced lung pathologies is unknown.
Methods
Using a 6 weeks model of chronic ozone exposure in mice, we explored the role of the innate receptor NLRP6 in the context of immunological cell death, in ozone exposure-associated pulmonary inflammation.
Results
We found that Nlrp6 deficiency dampens airway and lung inflammation with reduced neutrophils, eosinophils influx and production of associated chemokines/cytokines including Th2 response, remodeling factor production, collagen deposition and fibrosis in response to chronic ozone exposure. Interestingly, we observed increased NLRP6 expression in bronchial epithelial cells, pneumocytes and infiltrating macrophages in lung tissue and airway macrophages upon chronic ozone exposure. Mechanistically, we report that chronic ozone promotes NLRP6-mediated caspase-1- and caspase11-dependent gasdermin D activation in alveolar type 1 pneumocytes suggesting NLRP6 inflammasome drives lung inflammation. Moreover, gasdermin D deficiency leads to reduced pulmonary inflammation after chronic ozone exposure. Mice deficient for NLRP6 in alveolar epithelial cells display reduced inflammation with impaired caspase-1/11 and gasdermin D activation in lungs, which confirms NLRP6-driven inflammation in these cells. Finally, we found that caspase-3Casp3/8 and gasdermin E activation depends on NLRPlrp6.
Conclusion
In conclusion we provide the first evidence that NLRP6 is a key player in chronic ozone pulmonary inflammation associated with the induction of both gasdermin-D and gasdermin E-dependent pyroptosisimmunogenic cell death.
{"title":"Chronic ozone induces lung inflammation through NLRP6-dependent activation of pyroptosis pathways in pneumocytes","authors":"A. Gombault, S. Huot-Marchand, C. Véront, S. Carignon, VFJ. Quesniaux, B. Ryffel, P. Broz, N. Riteau, I. Couillin","doi":"10.1016/j.rmr.2025.02.035","DOIUrl":"10.1016/j.rmr.2025.02.035","url":null,"abstract":"<div><h3>Introduction</h3><div>Environmental air pollutants including ozone cause severe lung injury and aggravate respiratory diseases such as asthma and COPD. Ozone is a major air pollutant causing pulmonary inflammation evolving into lung emphysema and/or fibrosis in mice exposed to ozone but the mechanisms are not well understood. Innate immune sensors such as nucleotide-oligomerization domain-like receptors (NLRs) are able to form cytosolic complexes named inflammasomes that mediate inflammatory cytokines production and immunological cell death. Among NLRs, NLRP3 was shown to be involved in establishment of lung inflammation to ozone. However, the role of NLRP6, another NLR in involved in inflammasome scaffold, like NLRP6 in ozone-induced lung pathologies is unknown.</div></div><div><h3>Methods</h3><div>Using a 6 weeks model of chronic ozone exposure in mice, we explored the role of the innate receptor NLRP6 in the context of immunological cell death, in ozone exposure-associated pulmonary inflammation.</div></div><div><h3>Results</h3><div>We found that Nlrp6 deficiency dampens airway and lung inflammation with reduced neutrophils, eosinophils influx and production of associated chemokines/cytokines including Th2 response, remodeling factor production, collagen deposition and fibrosis in response to chronic ozone exposure. Interestingly, we observed increased NLRP6 expression in bronchial epithelial cells, pneumocytes and infiltrating macrophages in lung tissue and airway macrophages upon chronic ozone exposure. Mechanistically, we report that chronic ozone promotes NLRP6-mediated caspase-1- and caspase11-dependent gasdermin D activation in alveolar type 1 pneumocytes suggesting NLRP6 inflammasome drives lung inflammation. Moreover, gasdermin D deficiency leads to reduced pulmonary inflammation after chronic ozone exposure. Mice deficient for NLRP6 in alveolar epithelial cells display reduced inflammation with impaired caspase-1/11 and gasdermin D activation in lungs, which confirms NLRP6-driven inflammation in these cells. Finally, we found that caspase-3Casp3/8 and gasdermin E activation depends on NLRPlrp6.</div></div><div><h3>Conclusion</h3><div>In conclusion we provide the first evidence that NLRP6 is a key player in chronic ozone pulmonary inflammation associated with the induction of both gasdermin-D and gasdermin E-dependent pyroptosisimmunogenic cell death.</div></div>","PeriodicalId":21548,"journal":{"name":"Revue des maladies respiratoires","volume":"42 4","pages":"Page 199"},"PeriodicalIF":0.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791871","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}
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