European Respiratory Society International Congress 2021: Highlights from best-abstract awardees

This article provides an overview of some of the highlights of the @EuroRespSoc Congress 2021 from the perspective of the best-abstract awardees of the ERS Assembliesinfo:eu-repo/semantics/publishedVersio

European respiratory society international congress 2021: Highlights from best-abstract awardees

This article provides an overview of some of the highlights of the @EuroRespSoc Congress 2021 from the perspective of the best-abstract awardees of the ERS Assemblies @EarlyCareerERS @OrphaLung https://bit.ly/3JCjHYS Every year, the European Respiratory Society (ERS) offers grants to recognise the best overall abstracts of the 14 ERS Assemblies submitted for the ERS International Congress, covering all respiratory areas. The authors of the best abstract (i.e. the highest average score of abstract reviewers and only those who have not applied or were not eligible for a sponsored award) were invited to write a short summary about their virtual Congress experience and view on the evolving field of research in light of their respective Assembly. This article provides an overview of some of the Congress highlights and gives the stage to the promising best-abstract awardees as they are the future of the ERS

European Respiratory Society International Congress 2021: highlights from best-abstract awardees

Support statement: J. De Brandt is funded by the Flemish government. The Research of FWO (Research Foundation - Flanders) Aspirant J. De Brandt is sponsored by FWO-grant #11B4718N.Every year, the European Respiratory Society (ERS) offers grants to recognise the best overall abstracts of the 14 ERS Assemblies submitted for the ERS International Congress, covering all respiratory areas. The authors of the best abstract (i.e. the highest average score of abstract reviewers and only those who have not applied or were not eligible for a sponsored award) were invited to write a short summary about their virtual Congress experience and view on the evolving field of research in light of their respective Assembly. This article provides an overview of some of the Congress highlights and gives the stage to the promising best-abstract awardees as they are the future of the ERS.info:eu-repo/semantics/publishedVersio

Nutritional impact of CFTR modulators in children with cystic fibrosis

BackgroundNutritional status is a major prognostic factor for breathing and the survival of patients with cystic fibrosis (CF). Since 2012, the development of CFTR modulators has considerably transformed the outcome of this disease. Indeed, both lung function and body mass index are improved by CFTR modulators, such as Lumacaftor/Ivacaftor. However, few data exist regarding the outcome of nutritional intakes under Lumacaftor/Ivacaftor.MethodsWe conducted a prospective single-center study in children with CF treated with Lumacaftor/Ivacaftor to evaluate their nutritional intake before and after treatmentResultsThirty-four children were included in this study, with a median age of 12.4 years [11.9; 14.7]. There was no significant improvement in weight, height or BMI. Patients' total energy intake was not significantly changed with Lumacaftor/Ivacaftor, while carbohydrate intakes decreased significantly. We found that blood levels of vitamin E and Selenium were significantly increased under Lumacaftor/Ivacaftor, without a significant increase in supplementation. In patients with a BMI Z-score < 0 at treatment initiation, there was a significant improvement in weight and BMI Z-score, while TEI and carbohydrate intakes were significantly lower.ConclusionWe showed that treatment with Lumacaftor/Ivacaftor improved the nutritional status of patients without necessarily being associated with an increase in nutritional intake. Although these data need to be confirmed in larger cohorts, they support the hypothesis that weight gain under modulators is multifactorial, and may be related to a decrease in energy expenditure or an improvement in absorption

J Clin Med

In cystic fibrosis (CF), cystic fibrosis transmembrane regulator (CFTR) dysfunction leads to digestive disorders that promote intestinal inflammation and dysbiosis enhancing gastrointestinal symptoms. In pancreatic insufficiency CF patients, both intestinal inflammation and dysbiosis, are associated with an increase in the fecal calprotectin (FC) level. However, associations between the FC level, gastrointestinal symptoms, and quality of life (QoL) remain poorly studied. We aimed to assess such associations in pancreatic insufficiency CF children. The FC level was measured in pancreatic insufficiency CF children's stool samples. Children and their parents completed two questionnaires: The Gastrointestinal Symptoms Scales 3.0-PedsQL(TM) and the Quality of Life Pediatric Inventory 4.0-PedsQL(TM). Lower scores indicated worse symptomatology or QoL. Thirty-seven CF children were included. A FC level above 250 µg/g was associated with worse gastrointestinal symptoms and QoL scores. The FC level was inversely correlated with several gastrointestinal scores assessed by children (i.e., Total, "Heart Burn Reflux", "Nausea and Vomiting", and "Gas and Bloating"). Several QoL scores were correlated with gastrointestinal scores. The FC level was weakly associated with clinical parameters. Some gastrointestinal and QoL scores were related to disease severity associated parameters. In CF, the FC level, biomarker previously related to intestinal inflammation and dysbiosis, was associated with worse digestive symptoms and QoL scores

Front Pediatr

BACKGROUND: Nutritional status is a major prognostic factor for breathing and the survival of patients with cystic fibrosis (CF). Since 2012, the development of CFTR modulators has considerably transformed the outcome of this disease. Indeed, both lung function and body mass index are improved by CFTR modulators, such as Lumacaftor/Ivacaftor. However, few data exist regarding the outcome of nutritional intakes under Lumacaftor/Ivacaftor. METHODS: We conducted a prospective single-center study in children with CF treated with Lumacaftor/Ivacaftor to evaluate their nutritional intake before and after treatment. RESULTS: Thirty-four children were included in this study, with a median age of 12.4 years [11.9; 14.7]. There was no significant improvement in weight, height or BMI. Patients' total energy intake was not significantly changed with Lumacaftor/Ivacaftor, while carbohydrate intakes decreased significantly. We found that blood levels of vitamin E and Selenium were significantly increased under Lumacaftor/Ivacaftor, without a significant increase in supplementation. In patients with a BMI Z-score < 0 at treatment initiation, there was a significant improvement in weight and BMI Z-score, while TEI and carbohydrate intakes were significantly lower. CONCLUSION: We showed that treatment with Lumacaftor/Ivacaftor improved the nutritional status of patients without necessarily being associated with an increase in nutritional intake. Although these data need to be confirmed in larger cohorts, they support the hypothesis that weight gain under modulators is multifactorial, and may be related to a decrease in energy expenditure or an improvement in absorption

SARS-CoV-2 transmission via apical syncytia release from primary bronchial epithelia and infectivity restriction in children epithelia

The beta-coronavirus SARS-CoV-2 is at the origin of a persistent worldwide pandemic. SARS-CoV-2 infections initiate in the bronchi of the upper respiratory tract and are able to disseminate to the lower respiratory tract eventually causing acute severe respiratory syndrome with a high degree of mortality in the elderly. Here we use reconstituted primary bronchial epithelia from adult and children donors to follow the infection dynamic following infection with SARS-CoV-2. We show that in bronchial epithelia derived from adult donors, infections initiate in multi-ciliated cells. Then, infection rapidly spread within 24-48h throughout the whole epithelia. Within 3-4 days, large apical syncytia form between multi-ciliated cells and basal cells, which dissipate into the apical lumen. We show that these syncytia are a significant source of the released infectious dose. In stark contrast to these findings, bronchial epithelia reconstituted from children donors are intrinsically more resistant to virus infection and show active restriction of virus spread. This restriction is paired with accelerated release of IFN compared to adult donors. Taken together our findings reveal apical syncytia formation as an underappreciated source of infectious virus for either local dissemination or release into the environment. Furthermore, we provide direct evidence that children bronchial epithelia are more resistant to infection with SARS-CoV-2 providing experimental support for epidemiological observations that SARS-CoV-2 cases’ fatality is linked to age. Significance Statement Bronchial epithelia are the primary target for SARS-CoV-2 infections. Our work uses reconstituted bronchial epithelia from adults and children. We show that infection of adult epithelia with SARS-CoV-2 is rapid and results in the synchronized release of large clusters of infected cells and syncytia into the apical lumen contributing to the released infectious virus dose. Infection of children derived bronchial epithelia revealed an intrinsic resistance to infection and virus spread, probably as a result of a faster onset of interferon secretion. Thus, our data provide direct evidence for the epidemiological observation that children are less susceptible to SARS-CoV-2

Pathophysiology of preschool severe asthma : impact of bronchial remodeling and mechanisms involved in bronchial smooth muscle remodelling

L'asthme est la maladie chronique la plus fréquente chez l’enfant. Les enfants d'âge préscolaire (6 ans). Dans l'asthme de l'adulte, l'augmentation de masse du MLB est liée à une prolifération ex vivo et in vitro accrue des cellules musculaires lisses bronchiques (CMLB) liée à une homéostasie calcique altérée, qui, à son tour, augmente la biogenèse et la masse mitochondriales. Les mécanismes responsables du remodelage du MLB restent cependant totalement inconnu chez l’enfant asthmatique préscolaire.Nos objectifs étaient i) de déterminer de nouvelles classes d’asthmatiques sévères d’âge préscolaire en fonction des paramètres de remodelage bronchique et ii) d’identifier les mécanismes impliqués dans le remodelage du MLB chez ces enfants avec une attention particulière sur le rôle des mitochondries. De biopsies bronchiques ont été réalisées chez des enfants asthmatiques sévères d’âge préscolaire et des témoins (étude P'tit ASTHME, NCT02806466). Les paramètres du remodelage bronchique ont été évalués par immunohistochimie et inclus dans des analyses en classes latentes. La prolifération des CMLB a été évaluée ex vivo. Des cultures primaires de CMLB ont été établies. Nous avons évalué, in vitro, leur prolifération, leur contenu en ATP, leur respiration mitochondriale, masse mitochondriale et biogenèse mitochondriale et la signalisation calcique. Nous avons également étudié la dynamique mitochondriale de fission et de fusion ainsi que la mitophagie. En utilisant des analyses en classes latentes basées sur le remodelage bronchique, nous avons identifié parmi les asthmatiques sévères, 2 classes latentes distinctes. Les patients de la classe 1 présentaient un épaississement accru de la RBM, une augmentation de la néoangiogenèse et de la masse du MLB ainsi qu’un risque accru d'exacerbation comparés à ceux de la classe 2. Les asthmatiques sévères présentaient une augmentation de la masse du MLB, et leur CMLB présentaient une augmentation de la prolifération, de la respiration, de la réponse calcique, de la biogenèse et de la masse mitochondriale par rapport aux témoins (n=12). De plus, la masse du MLB était corrélée au nombre d'exacerbations et prédictive de la persistance de l'asthme à l'âge scolaire. De plus, les asthmatiques ayant la masse de MLB la plus élevée avaient une prolifération cellulaire et une masse mitochondriale de BSM plus importantes. Cette dernière n'était pas liée à une biogenèse mitochondriale accrue mais à une diminution de la fission mitochondriale médiée par DRP1 conduisant à une diminution de la mitophagie dépendante de PINK1. La mitophagie et la fission mitochondriale pourraient donc représenter de nouvelles cibles pour le remodelage du BSM, qui caractérise les asthmatiques sévères sujets aux exacerbations.Asthma is the most frequent chronic disease in children. Preschool children (6 years old). In adult asthma, the increased BSM mass has been linked in vitro and ex vivo to an increased BSM cell proliferation. This increased proliferation was related to an altered calcium homeostasis, which, in turn, enhanced both mitochondrial biogenesis and mass. However, the mechanisms responsible for BSM remodeling and the role of mitochondria, in the specific situation of preschool wheezing children, remain totally unknown.We aimed i) to determine new classes of severe preschool wheezers based on bronchial remodeling parameters and ii) to identify the mechanisms involved in BSM remodeling in severe preschool wheezers with a special attention on the role of mitochondria.Bronchial remodeling parameters have been assessed by immunochemistry on bronchial biopsies performed in severe preschool wheezers and controls (P’tit ASTHME study, NCT02806466). All these parameters were implemented in latent class analyses to define new groups of patients based on bronchial remodeling. BSM cell proliferation was also assessed ex vivo by immunochemistery and PCNA and Ki67 stainings. In addition, we also established primary BSM cell cultures and assessed in vitro, BSM cell proliferation, ATP content, mitochondrial respiration, mitochondrial mass, mitochondrial biogenesis and calcium signaling. We also investigated mitochondrial dynamic processes of fission and fusion as well as mitophagy.Using bronchial remodeling-based latent class analyses, we identified among severe preschool wheezers, 2 distinct latent classes. Preschool wheezers from Class 1 had an increased RBM thickening, neoangiogenesis and BSM mass and were at high risk of exacerbation compared to those from Class 2. In addition, we identified that severe wheezers had an increased BSM mass, BSM cell proliferation, mitochondrial respiration, biogenesis, and mass enhanced by alteration in calcium homeostasis compared to controls. Moreover, BSM mass was correlated with the number of exacerbations and predictive of exacerbation-prone asthma (> 2 asthma exacerbations per year) and to asthma persistence at school age. We also demonstrated that a subgroup of wheezers with high BSM mass had an increased BSM cell proliferation and mitochondrial mass in vitro compared to those with low BSM mass. This latter was not related to an increased mitochondrial biogenesis but to a decreased DRP1-mediated mitochondrial fission leading to a decreased PINK1-dependent mitophagy. Mitophagy and mitochondrial fission may therefore represent new targets for the BSM remodeling, which characterizes exacerbation-prone preschool wheezers

Pathophysiology of preschool severe asthma : impact of bronchial remodeling and mechanisms involved in bronchial smooth muscle remodelling

L'asthme est la maladie chronique la plus fréquente chez l’enfant. Les enfants d'âge préscolaire (6 ans). Dans l'asthme de l'adulte, l'augmentation de masse du MLB est liée à une prolifération ex vivo et in vitro accrue des cellules musculaires lisses bronchiques (CMLB) liée à une homéostasie calcique altérée, qui, à son tour, augmente la biogenèse et la masse mitochondriales. Les mécanismes responsables du remodelage du MLB restent cependant totalement inconnu chez l’enfant asthmatique préscolaire.Nos objectifs étaient i) de déterminer de nouvelles classes d’asthmatiques sévères d’âge préscolaire en fonction des paramètres de remodelage bronchique et ii) d’identifier les mécanismes impliqués dans le remodelage du MLB chez ces enfants avec une attention particulière sur le rôle des mitochondries. De biopsies bronchiques ont été réalisées chez des enfants asthmatiques sévères d’âge préscolaire et des témoins (étude P'tit ASTHME, NCT02806466). Les paramètres du remodelage bronchique ont été évalués par immunohistochimie et inclus dans des analyses en classes latentes. La prolifération des CMLB a été évaluée ex vivo. Des cultures primaires de CMLB ont été établies. Nous avons évalué, in vitro, leur prolifération, leur contenu en ATP, leur respiration mitochondriale, masse mitochondriale et biogenèse mitochondriale et la signalisation calcique. Nous avons également étudié la dynamique mitochondriale de fission et de fusion ainsi que la mitophagie. En utilisant des analyses en classes latentes basées sur le remodelage bronchique, nous avons identifié parmi les asthmatiques sévères, 2 classes latentes distinctes. Les patients de la classe 1 présentaient un épaississement accru de la RBM, une augmentation de la néoangiogenèse et de la masse du MLB ainsi qu’un risque accru d'exacerbation comparés à ceux de la classe 2. Les asthmatiques sévères présentaient une augmentation de la masse du MLB, et leur CMLB présentaient une augmentation de la prolifération, de la respiration, de la réponse calcique, de la biogenèse et de la masse mitochondriale par rapport aux témoins (n=12). De plus, la masse du MLB était corrélée au nombre d'exacerbations et prédictive de la persistance de l'asthme à l'âge scolaire. De plus, les asthmatiques ayant la masse de MLB la plus élevée avaient une prolifération cellulaire et une masse mitochondriale de BSM plus importantes. Cette dernière n'était pas liée à une biogenèse mitochondriale accrue mais à une diminution de la fission mitochondriale médiée par DRP1 conduisant à une diminution de la mitophagie dépendante de PINK1. La mitophagie et la fission mitochondriale pourraient donc représenter de nouvelles cibles pour le remodelage du BSM, qui caractérise les asthmatiques sévères sujets aux exacerbations.Asthma is the most frequent chronic disease in children. Preschool children (6 years old). In adult asthma, the increased BSM mass has been linked in vitro and ex vivo to an increased BSM cell proliferation. This increased proliferation was related to an altered calcium homeostasis, which, in turn, enhanced both mitochondrial biogenesis and mass. However, the mechanisms responsible for BSM remodeling and the role of mitochondria, in the specific situation of preschool wheezing children, remain totally unknown.We aimed i) to determine new classes of severe preschool wheezers based on bronchial remodeling parameters and ii) to identify the mechanisms involved in BSM remodeling in severe preschool wheezers with a special attention on the role of mitochondria.Bronchial remodeling parameters have been assessed by immunochemistry on bronchial biopsies performed in severe preschool wheezers and controls (P’tit ASTHME study, NCT02806466). All these parameters were implemented in latent class analyses to define new groups of patients based on bronchial remodeling. BSM cell proliferation was also assessed ex vivo by immunochemistery and PCNA and Ki67 stainings. In addition, we also established primary BSM cell cultures and assessed in vitro, BSM cell proliferation, ATP content, mitochondrial respiration, mitochondrial mass, mitochondrial biogenesis and calcium signaling. We also investigated mitochondrial dynamic processes of fission and fusion as well as mitophagy.Using bronchial remodeling-based latent class analyses, we identified among severe preschool wheezers, 2 distinct latent classes. Preschool wheezers from Class 1 had an increased RBM thickening, neoangiogenesis and BSM mass and were at high risk of exacerbation compared to those from Class 2. In addition, we identified that severe wheezers had an increased BSM mass, BSM cell proliferation, mitochondrial respiration, biogenesis, and mass enhanced by alteration in calcium homeostasis compared to controls. Moreover, BSM mass was correlated with the number of exacerbations and predictive of exacerbation-prone asthma (> 2 asthma exacerbations per year) and to asthma persistence at school age. We also demonstrated that a subgroup of wheezers with high BSM mass had an increased BSM cell proliferation and mitochondrial mass in vitro compared to those with low BSM mass. This latter was not related to an increased mitochondrial biogenesis but to a decreased DRP1-mediated mitochondrial fission leading to a decreased PINK1-dependent mitophagy. Mitophagy and mitochondrial fission may therefore represent new targets for the BSM remodeling, which characterizes exacerbation-prone preschool wheezers