Les pneumopathies interstitielles diffuses de l'enfant (à propos de 19 cas au CHU d'Amiens)

Les pneumopathies interstitielles diffuses sont rares chez l'enfant, elles sont souvent méconnues et sous estimées. Il s'agit d'un groupe hétérogène d'affections correspondant à une réponse tissulaire excessive au niveau de l'interstitium inter alvéolaire allant de l'alvéolite aigue à la fibrose interstitielle irréversible. Elles se caractérisent par une clinique frustre et non spécifique, un infiltrat pulmonaire diffus, une atteinte restrictive et des échanges gazeux anormaux. Notre travail avait pour but de faire le point sur cette pathologie au CHU d'Amiens par une étude rétrospective sur 20 ans. Nous avons donc travaillé sur 19 dossiers. Le diagnostic est évoqué le plus souvent à la suite d'une symptomatologie respiratoire ayant amené à réaliser un cliché thoracique, mais dans un certain nombre de cas, en particulier dans l'histiocytose langerhansienne, l'atteinte pulmonaire est de découverte fortuite lors d'un bilan pulmonaire systématique. La démarche diagnostique doit être rigoureuse et complète afin de permettre un diagnostic précis. Les explorations paracliniques sont une grande aide au diagnostic mais l'étude histologique est souvent indispensable. Dans notre travail la réalisation d'une biopsie pulmonaire n'a été réalisée que dans 16% des cas mais une étude anatomopathologique a été réalisée chez 63% des enfants. Les traitements ont fait le plus souvent appel à la corticothérapie orale (68% des cas). Le pronostic pulmonaire fut mauvais pour 4 enfants et nous avons eu deux décès. Notre travail nous a permis de constater la faible prévalence des pneumopathies interstitielles au CHU d'Amiens. Les pneumopathies interstitielles diffuses de l'enfant continue d'être un challenge pour le pédiatre car son diagnostic reste difficile et la prise en charge thérapeutique est loin d'être optimale et elle évolue peu. Ces difficultés font que les pneumopathies interstitielles gardent souvent un pronostic réservéAMIENS-BU Santé (800212102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Change in phase 3 slope of exhaled CO2 in response to beta 2 agonist inhalation is associated with asthma control in children

European-Respiratory-Society (ERS) International Congress, Milan, ITALY, SEP 09-13, 2017International audienc

Development of the nasal cavity during infancy: A restrospective CT imaging study

Body: Rationale: Upper airway and nasal airflow resistance are significant in infancy, due to the fact that infants are nasal breathers in early life, and that obstructive nasal diseases are frequent at this age. Nasal flow resistance is closely determined by anatomy, which rapidly changes with growth. The goal of this study was to assess standardized measurements of the nasal cavity dimensions in the first 2 years of life. Methods: 34 head CT scans of infants aged 4.13±4.08 months (range: 0.07 to 19.4, 17 male, 17 female) available in the Amiens University Hospital Dept. of Radiology database were retrospectively analyzed. Infants with craniofacial deformities were excluded. Images were 3D reconstructed, axially oriented and the nasal cavity was segmented by density thresholding from nares to vocal cords. Surface areas of the piriform and choanal apertures were automatically computed in the coronal plane, in standardized positions based on bony reference points. Results:Piriform surface area measured (mean±SD): 54.3±13.8 mm2 (range: 29.1 - 83.9), and was significantly correlated to age (R=0.59, p<0.001), and height (R=0.57, p<0.001). Choanal aperture surface area: 81.3±28.1 mm2 (range: 38.0 – 164.7), and was significantly correlated to age (R=0.74, p<10-6), and height (R=0.71, p<10-5). Conclusions: These data suggest that the nasal cavity anterior and posterior apertures grow rapidly during the first 2 years of life, and that their dimensions are closely correlated to age and height. Further investigation will focus on how the anatomic growth of the nasal cavity in early life affects airflow resistance

Clinical problems in rare interstitial lung diseases

International audienceIntroduction: Interstitial lung disease ( LD) in children (chlLD) is rare and Often severe. This study aims at analyzing the ep demiology of chlLD in France from 2000 to 2022.Methods: This study was retrospective and multicentric, A questionnaire was sent to all the RespiRare centers to collect the clinical, radiological, biological, histological and genetic data of the patients.Results: 617 patients (0-18 years) were included in 42 centers. 84 patients were excluded. The median age at diagnosis was 0.3 years with 17% of familial forms, The main investigations performed were: chest CT scan (92%), bronchoalveolar avage (52%), genetic ana ysis (78%), lung biopsy (23%). The main treatments were: corticosteroids (93%), oxygen therapy (52.2%), enteral nutrition (29%), hydroxychloroqu•ne (16%), azThromycin (26%), immunosuppressive drugs (210/0). The follovFup time was from O to 18,9 years (median duration 3,5years). The survival rate at 5 years was 68%. The overall incidence and preva ence were estimated at 38/million and 35/million children respectively.Conclusion: This arge chlLD epidemiological study confirms the Span •sh data with a higher incidence and prevalence than previous y described. The arge amount Of phenotypic data collected will allow better understanding ch LD and harmonizing their management

Clinical problems in rare interstitial lung diseases

International audienceIntroduction: Interstitial lung disease ( LD) in children (chlLD) is rare and Often severe. This study aims at analyzing the ep demiology of chlLD in France from 2000 to 2022.Methods: This study was retrospective and multicentric, A questionnaire was sent to all the RespiRare centers to collect the clinical, radiological, biological, histological and genetic data of the patients.Results: 617 patients (0-18 years) were included in 42 centers. 84 patients were excluded. The median age at diagnosis was 0.3 years with 17% of familial forms, The main investigations performed were: chest CT scan (92%), bronchoalveolar avage (52%), genetic ana ysis (78%), lung biopsy (23%). The main treatments were: corticosteroids (93%), oxygen therapy (52.2%), enteral nutrition (29%), hydroxychloroqu•ne (16%), azThromycin (26%), immunosuppressive drugs (210/0). The follovFup time was from O to 18,9 years (median duration 3,5years). The survival rate at 5 years was 68%. The overall incidence and preva ence were estimated at 38/million and 35/million children respectively.Conclusion: This arge chlLD epidemiological study confirms the Span •sh data with a higher incidence and prevalence than previous y described. The arge amount Of phenotypic data collected will allow better understanding ch LD and harmonizing their management

Clinical problems in rare interstitial lung diseases

International audienceIntroduction: Interstitial lung disease ( LD) in children (chlLD) is rare and Often severe. This study aims at analyzing the ep demiology of chlLD in France from 2000 to 2022.Methods: This study was retrospective and multicentric, A questionnaire was sent to all the RespiRare centers to collect the clinical, radiological, biological, histological and genetic data of the patients.Results: 617 patients (0-18 years) were included in 42 centers. 84 patients were excluded. The median age at diagnosis was 0.3 years with 17% of familial forms, The main investigations performed were: chest CT scan (92%), bronchoalveolar avage (52%), genetic ana ysis (78%), lung biopsy (23%). The main treatments were: corticosteroids (93%), oxygen therapy (52.2%), enteral nutrition (29%), hydroxychloroqu•ne (16%), azThromycin (26%), immunosuppressive drugs (210/0). The follovFup time was from O to 18,9 years (median duration 3,5years). The survival rate at 5 years was 68%. The overall incidence and preva ence were estimated at 38/million and 35/million children respectively.Conclusion: This arge chlLD epidemiological study confirms the Span •sh data with a higher incidence and prevalence than previous y described. The arge amount Of phenotypic data collected will allow better understanding ch LD and harmonizing their management

The expanded French compassionate programme for elexacaftor–tezacaftor–ivacaftor use in people with cystic fibrosis without a F508del CFTR variant: a real-world study

International audienceBackground Elexacaftor-tezacaftor-ivacaftor has been approved in Europe for people with cystic fibrosis with at least one F508del CFTR variant. Additionally, it is approved by the US Food and Drug Administration (FDA) for people with cystic fibrosis with at least one of 177 rare variants. The aims of this study were to describe the clinical response to elexacaftor-tezacaftor-ivacaftor for people with cystic fibrosis without a F508del CFTR variant in France and to determine CFTR variant responsiveness to elexacaftor-tezacaftor-ivacaftor based on the observed clinical response. Methods The French compassionate programme expanded access to elexacaftor-tezacaftor-ivacaftor to people with cystic fibrosis, aged 6 years and older, without a F508del variant, excluding those with two variants previously characterised as non-responsive. Participants at France's 47 cystic fibrosis centres were given a 4-6 week trial of elexacaftor-tezacaftor-ivacaftor and response was determined by a centralised committee based on evolution of clinical data, lung function, and sweat chloride concentration. Responsiveness of individual CFTR variants was derived from observed clinical responses. Findings The first compassionnate programme was launched on May 19, 2022; by March 8, 2024, 516 people with cystic fibrosis had been identified for inclusion in this real-word study: 37 were not included due to the presence of two variants previously characterised as non-responsive to elexacaftor-tezacaftor-ivacaftor, and 479 (229 females [48%] and 250 males [52%]) received elexacaftor-tezacaftor-ivacaftor for 4-6 weeks. Among 443 participants who received no CFTR modulator before elexacaftor-tezacaftor-ivacaftor, 83 had at least one FDAapproved variant, of whom 81 (98%) were responders and continued elexacaftor-tezacaftor-ivacaftor; in responders, mean absolute change in sweat chloride was -44•5 mmol/L (95% CI -39•1 to -49•8) and percentage of predicted FEV 1 (ppFEV 1 ) was 11•1 percentage points (95% CI 8•4 to 13•7; both comparisons p&lt;0•0001). Among 360 participants with no FDA-approved variant and no previous CFTR modulator, 177 (49%) were responders; in responders, mean absolute change in sweat chloride was -20•5 mmol/L (-17•2 to -23•8) and ppFEV 1 was 13•2 percentage points (11•4 to 15•0; both comparisons p&lt;0•0001). Among 36 participants who were receiving ivacaftor before elexacaftortezacaftor-ivacaftor, 32 (89%) continued elexacaftor-tezacaftor-ivacaftor. Of 251 individual CFTR variants, 64 (28 FDA-approved) were classified as responsive or possibly responsive to elexacaftor-tezacaftor-ivacaftor, and 123 (two FDA-approved) as non-responsive or possibly non-responsive to elexacaftor-tezacaftor-ivacaftor. Interpretation In France, over half of the population with cystic fibrosis without a F508del variant responded to elexacaftor-tezacaftor-ivacaftor, with most responders having no FDA-approved variant. The treatment period was relatively short and further research is warranted to describe the long-term safety and effectiveness of elexacaftortezacaftor-ivacaftor in this population.</div

Genotypic and phenotypic characterisation of respiratory syncytial virus after nirsevimab breakthrough infections: a large, multicentre, observational, real-world study

International audienceBackgroundNirsevimab, a long-acting monoclonal antibody, has been approved for the prevention of respiratory syncytial virus (RSV) infection in infants. In France, more than 210 000 single doses were administered in infants younger than 1 year during the 2023–24 season. In this context, the selection and spread of escape variants might be a concern. Here, we aimed to characterise RSV associated with breakthrough infection.MethodsWe did a multicentre, national, observational study in France during the 2023–24 RSV season in RSV-infected infants (aged &lt;1 year) who either received or did not receive a dose of nirsevimab before their first RSV season. We excluded infants with insufficient information about nirsevimab treatment or without parental consent. We used respiratory samples collected in each laboratory for full-length RSV RNA sequencing to analyse changes in the nirsevimab binding site Ø. We tested clinical RSV isolates for neutralisation by nirsevimab. We analysed F candidate substitutions by fusion-inhibition assay.FindingsOf the 695 RSV infected infants, we analysed 545 (78%) full-length RSV genome sequences: 260 (48%) from nirsevimab-treated breakthrough infections (236 [91%] RSV-A and 24 [9%] RSV-B) and 285 (52%) from untreated RSV-infected infants (236 [83%] RSV-A and 49 [17%] RSV-B). Analysis of RSV-A did not reveal any substitution in site Ø known to be associated with resistance to nirsevimab. Two (8%) of 24 RSV-B breakthrough infections had resistance-associated substitutions: F:N208D (dominant resistance-associated substitution) and a newly described F:I64M plus F:K65R combination (minority resistance-associated substitution), both of which induced high levels of resistance in the fusion-inhibition assay.InterpretationThis study is, to the best of our knowledge, the largest genotypic and phenotypic surveillance study of nirsevimab breakthrough infections to date. Nirsevimab breakthrough variants remain very rare despite the drug's widespread use. The detection of resistance-associated substitutions in the RSV-B F protein highlights the importance of active molecular surveillance

Rapid Improvement after Starting Elexacaftor–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and Advanced Pulmonary Disease

International audienceRationale: Elexacaftor-tezacaftor-ivacaftor is a CFTR (cystic fibrosis [CF] transmembrane conductance regulator) modulator combination, developed for patients with CF with at least one Phe508del mutation. Objectives: To evaluate the effects of elexacaftor-tezacaftor- ivacaftor in patients with CF and advanced respiratory disease. Methods: A prospective observational study, including all patients aged ⩾12 years and with a percent-predicted FEV1 (ppFEV1) <40 who initiated elexacaftor-tezacaftor-ivacaftor from December 2019 to August 2020 in France was conducted. Clinical characteristics were collected at initiation and at 1 and 3 months. Safety and effectiveness were evaluated by September 2020. National-level transplantation and mortality figures for 2020 were obtained from the French CF and transplant centers and registries. Measurements and Main Results: Elexacaftor-tezacaftor- ivacaftor was initiated in 245 patients with a median (interquartile range) ppFEV1 = 29 (24-34). The mean (95% confidence interval) absolute increase in the ppFEV1 was +15.1 (+13.8 to +16.4; P < 0.0001), and the mean (95% confidence interval) in weight was +4.2 kg (+3.9 to +4.6; P < 0.0001). The number of patients requiring long-term oxygen, noninvasive ventilation, and/or enteral tube feeding decreased by 50%, 30%, and 50%, respectively (P < 0.01). Although 16 patients were on the transplant waiting list and 37 were undergoing transplantation evaluation at treatment initiation, only 2 received a transplant, and 1 died. By September 2020, only five patients were still on the transplantation path. Compared with the previous 2 years, a twofold decrease in the number of lung transplantations in patients with CF was observed in 2020, whereas the number of deaths without transplantation remained stable. Conclusions: In patients with advanced disease, elexacaftor-tezacaftor-ivacaftor is associated with rapid clinical improvement, often leading to the indication for lung transplantation being suspended

Impact of COVID-19 infection on lung function and nutritional status amongst individuals with cystic fibrosis: A global cohort study

International audienceBackground: Factors associated with severe COVID-19 infection have been identified; however, the impact of infection on longer-term outcomes is unclear. The objective of this study was to examine the impact of COVID-19 infection on the trajectory of lung function and nutritional status in people with cystic fibrosis (pwCF).Methods: This is a retrospective global cohort study of pwCF who had confirmed COVID-19 infection diagnosed between January 1, 2020 and December 31, 2021. Forced expiratory volume in one second percent predicted (ppFEV 1 ) and body mass index (BMI) twelve months prior to and following a diagnosis of COVID-19 were recorded. Change in mean ppFEV 1 and BMI were compared using a t-test. A linear mixed-effects model was used to estimate change over time and to compare the rate of change before and after infection.Results: A total of 6,500 cases of COVID-19 in pwCF from 33 countries were included for analysis. The mean difference in ppFEV 1 pre-and post-infection was 1.4 %, (95 % CI 1.1, 1.7). In those not on modulators, the difference in rate of change pre-and post-infection was 1.34 %, (95 % CI -0.88, 3.56) per year (p = 0.24) and -0.74 % (-1.89, 0.41) per year (p = 0.21) for those on elexacaftor/tezacaftor/ivacaftor. No clinically significant change was noted in BMI or BMI percentile before and after COVID-19 infection.Conclusions: No clinically meaningful impact on lung function and BMI trajectory in the year following infection with COVID-19 was identified. This work highlights the ability of the global CF community to unify and address critical issues facing pwCF