Transplantation pulmonaire (devenir à 6 mois des receveurs de greffons refusés au CHU de Nantes en raison d'un greffon jugé de mauvaise qualité et acceptés dans un autre centre de transplantation)

Introduction : La pénurie des greffons pulmonaires se grève d'une mortalité non nulle pour les patients sur liste d'attente. A Nantes on observe un taux élevé de refus de greffons. L'objectif de cette étude était l'analyse du devenir à 6 mois des receveurs de greffons pulmonaires refusés à Nantes en raison d'un greffon jugé de mauvaise qualité (greffon marginal) et acceptés dans un autre centre. Matériel et méthodes : Etude rétrospective sur l'année 2012. Les données étaient recueillies auprès de l'Agence de la Biomédecine et sur le logiciel COLT (COhort Lung Transplantation). Résultats : Il n'existait pas de différence significative en termes de survie et de VEMS à 6 mois pour ces patients par rapport aux receveurs de greffons classiques transplantés au CHU de Nantes. L'association d'anomalies à l'imagerie et de stigmates d'infection respiratoire semblait par contre délétère. Conclusion : Les greffons marginaux peuvent donc être acceptés sans altération de la survie ou de la fonction respiratoire à 6 mois.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

Étude descriptive des besoins des patients atteints de mucoviscidose candidats à la transplantation: proposition d’une liste de compétences

International audienceIntroduction: the objectives of this study are to appreciate the evolution of cystis fibrosis patient's perceptions about lung transplantation, one-two years after transplantation in order to identify their educational needs, and to collect their proposals to improve the preparation for transplantation.Method: Qualitative Study led by interviews with nine patients on the base of their concept map realized before the transplantation.Results: The patients confirm most of their initial perceptions. Some evolve positively (less pain, management of medicine easier than planned), others in a more negative sense (resuscitation, difficulty to have professional activity). The suggestions to improve preparation for transplantation are: stress management, psychological and physical preparation, quality of information during preparation and about period of resuscitation, meeting with transplanted patients, relations with caregivers.Conclusion: A list of competencies for patient therapeutic education before lung transplantation for cystic fibrosis is proposed. This list is useful for elaborating educational sessions to increase patient learning and to structure a therapeutic educational program around transplantation.Introduction : L'étude vise à apprécier l'évolution des représentations sur la greffe des patients atteints de mucoviscidose une à deux années après transplantation pulmonaire afin d'identifier leurs besoins éducatifs, et re-cueillir leurs propositions pour améliorer leur préparation.Méthode : Étude qualitative menée par entretiens auprès de neuf patients après transplantation à partir de leur carte conceptuelle réalisée avant la transplantation.Résultats : Les patients confirment la majorité de leurs représentations initiales. Certaines évoluent positivement (moins de douleur, gestion des médicaments plus facile que prévu), d'autres dans un sens plus négatif (réanimation, reprise d'une activité professionnelle difficile). La description des besoins qui en découle concerne : la gestion du stress pendant cette période, la préparation psychologique et physique, la qualité des informations au cours du bilan pré-greffe et relatives à la période de réanimation, la rencontre avec des patients greffés, les relations avec les soignants.Conclusion : L'analyse des résultats a permis de déterminer une liste de compétences et d'objectifs pour l'éducation thérapeutique des patients avant une transplantation pulmonaire pour mucoviscidose. Cette liste pourrait servir de base à l'élaboration de séances éducatives favorisant l'apprentissage des patients et structurant progressivement un programme d'éducation thérapeutique autour de la transplantation

A quality improvement program to reduce the time on the lung transplant waiting list at the Nantes University Hospital

Abstract Background In 2010, the time on the lung transplant waiting list in Nantes University Hospital (NUH) was 9.2 months, compared to a French national median of about 4 months. The NUH transplant unit performs both heart and lung transplantations, which can be seen as competing activities. To fix the problem, the adult Cystic Fibrosis (CF) team decided to engage in the French CF Quality Improvement Program (QIP PHARE-M) in 2012. The objectives were: i) To reduce the time on the lung transplant waiting list at the Nantes Transplant Unit by increasing the number of lung transplants per year twhile maintaining a 5-year survival rate above the French national average. ii) To improve the organization of the lung transplant access process and the quality of the waiting time for patients. Methods A quality controller was involved as the QIP referent to coach the CF quality team, analyze the pre-transplant process, and set up meaningful measures. Benchmarking was performed with other transplant units, and staff discussions were held with the Transplant Team (TT) to assess the outcomes of rejected donor lungs. Negotiations were made with the hospital administration. Plan, Do, Study and Act cycles were used to redesign the pre-transplant assessment in connection with the CF centers (CFC) referring patients to the NUH transplant unit. Results i) The flow of patients has been reorganized, decreasing the time spent in surgical intensive care by increasing the number of beds in the intensive care unit, and a chest physician has been recruited ii) The number of organs rejected has been reduced iii) Lung transplant activity has increased to 20–25 transplants per year, and the median waiting time was reduced to 3.5 months for patients transplanted in 2014 and to 1.85 months for patients transplanted in 2015 iv) Added-value activities including education, information, and psychosocial support are now offered to patients during the waiting time. Conclusion The QIP PHARE-M, including coaching by a quality-engineer, has helped our adult CF center address its specific lung transplant issues and redesign the lung transplant process for both local patients and patients referred by other CFC

High prevalence of triazole resistance in Aspergillus fumigatus, especially mediated by TR/L98H, in a French cohort of patients with cystic fibrosis

Part of this work has been presented at the Fifth Congress on Trends in Medical Mycology, Valencia, Spain, 2011 (Abstract no. 308)International audienceOBJECTIVES:Triazole resistance in Aspergillus fumigatus due to a single azole resistance mechanism (TR/L98H) is increasingly reported in European countries. Data from patients with cystic fibrosis (CF) are limited. Our study aimed to investigate the prevalence and molecular mechanisms of azole resistance in A. fumigatus in a cohort of patients with CF.METHODS:Eighty-five A. fumigatus isolates from 50 CF patients, collected between January 2010 and April 2011, were retrospectively analysed for azole resistance using agar plates containing 4 mg/L itraconazole. MICs of itraconazole, voriconazole and posaconazole were determined according to EUCAST methodology for each isolate able to grow on this medium. Species identification was performed by sequencing of the β-tubulin gene. Sequencing analysis of the cyp51A gene and its promoter region was conducted.RESULTS:Nine isolates (four patients, 8% prevalence) were able to grow on itraconazole-containing agar plates. Itraconazole resistance was confirmed by EUCAST methodology (MICs >2 mg/L). All isolates had mutations in the cyp51A gene at residues previously involved in azole resistance: L98H (n = 5), M220T (n = 4) and G54R (n = 1). One patient had three genetically distinct azole-resistant isolates identified during the study. The isolates with L98H that were recovered from three patients (6% prevalence) also had the 34 bp tandem repeat in the promoter region of cyp51A (TR/L98H) and displayed multiazole resistance.CONCLUSIONS:We report an 8% prevalence of itraconazole resistance in CF patients in our centre, mostly driven by TR/L98H (6%). Our data confirm that TR/L98H occurs in France and can be highly prevalent in CF patients

Pregnancy after lung and heart–lung transplantation: a French multicentre retrospective study of 39 pregnancies

International audienc

Safety and pharmacokinetics of Roscovitine (Seliciclib) in cystic fibrosis patients chronically infected with Pseudomonas aeruginosa, a randomized, placebo-controlled study

International audienceBackground: The orally available kinase inhibitor R-roscovitine has undergone clinical trials against various cancers and is currently under clinical evaluation against Cushing disease and rheumatoid arthritis. Roscovitine displays biological properties suggesting potential benefits in CF: it partially corrects F508del-CFTR trafficking, stimulates the bactericidal properties of CF alveolar macrophages, and displays anti-inflammatory properties and analgesic effects.Methods: A phase 2 trial study (ROSCO-CF) was launched to evaluate the safety and effects of roscovitine in Pseudomonas aeruginosa infected adult CF patients carrying two CF causing mutations (at least one F508del-CFTR mutation) and harboring a FEV1 ≥40%. ROSCO-CF was a multicenter, double-blind, placebo-controlled, dose-ranging study (200, 400, 800 mg roscovitine, orally administered daily for 4 days/week/4 weeks).Results: Among the 34 volunteers enrolled, randomization assigned 11/8/8/7 to receive the 0 (placebo)/ 200/400/800 mg roscovitine doses, respectively. In these subjects with polypharmacy, roscovitine was relatively safe and well-tolerated, with no significant adverse effects (AEs) other than five serious AEs (SAEs) possibly related to roscovitine. Pharmacokinetics of roscovitine were rather variable among subjects. No significant efficacy, at the levels of inflammation, infection, spirometry, sweat chloride, pain and quality of life, was detected in roscovitine-treated groups compared to the placebo-treated group.Conclusion: Roscovitine was relatively safe and well-tolerated in CF patients especially at the 200 and 400 mg doses. However, there were 5 subject withdrawals due to SAEs in the roscovitine group and none in the placebo group. The lack of evidence for efficacy of roscovitine (despite encouraging cellular and animal results) may be due to high pharmacokinetics variability, short duration of treatment, and/or inappropriate dosing protocol

Disseminated Scedosporium/Pseudallescheria Infection after Double-Lung Transplantation in Patients with Cystic Fibrosis▿

We report a case of disseminated Scedosporium/Pseudallescheria infection due to Pseudallescheria boydii sensu stricto after lung transplantation in a patient with cystic fibrosis. Dissemination occurred under voriconazole. Despite surgery and combination therapy with voriconazole, caspofungin, and terbinafine, the patient died 8 months after transplantation. Previously reported cases are reviewed

Incidence and risk factors of anastomotic complications after lung transplantation

Background: Anastomotic complications are common after lung transplantation (1.4–33% of cases) and still associated with a high morbi-mortality. Methods: The current study is a monocenter retrospective analysis of symptomatic anastomotic complications (SAC) occurring after lung transplantation between 2010 and 2016, using the macroscopic, diameter, and suture (M-D-S) classification from consensus of French experts in bronchoscopy. The objectives were to determine incidence from surgery, risk factors, and impact of survival of SAC. We defined SAC as M-D-S abnormalities (stenosis ⩾ 50% or dehiscence) requiring bronchoscopic or surgical interventions. Results: A total of 121 patients were included. SAC occurred in 26.5% of patients ( n  = 32), divided in symptomatic stenosis for 23.7% ( n  = 29), and symptomatic dehiscence in 2.5% ( n  = 3). In multivariate analysis, donor bacterial lung infection [HR 2.08 (1.04–4.17), p  = 0.04] and age above 50 years [HR 3.26 (1.04–10.26), p  = 0.04] were associated with SAC occurrence. Cystic fibrosis etiology was associated with better survival on Kaplan–Meier curve ( p  < 0.001). SAC [HR 2.15 (1.07–4.32), p  = 0.03] was independently associated with worst survival. The 29 symptomatic patients because of stenosis required endoscopic procedure, of whom 16 patients needed bronchial stent placement. Four patients underwent surgery: three patients because of dehiscence and one because of severe bilateral stenosis (re-transplantation). Discussion: SAC occurred in 26.5% of patients. Donor lung infection was the only alterable identified factors. The increase rate of SAC in older patients above 50 years of age encourages in regular endoscopic monitoring

Systematic Analysis of Blood Cell Transcriptome in End-Stage Chronic Respiratory Diseases

International audienceBackgroundEnd-stage chronic respiratory diseases (CRD) have systemic consequences, such as weight loss and susceptibility to infection. However the mechanisms of such dysfunctions are as yet poorly explained. We hypothesized that the genes putatively involved in these mechanisms would emerge from a systematic analysis of blood mRNA profiles from pre-transplant patients with cystic fibrosis (CF), pulmonary hypertension (PAH), and chronic obstructive pulmonary disease (COPD).MethodsWhole blood was first collected from 13 patients with PAH, 23 patients with CF, and 28 Healthy Controls (HC). Microarray results were validated by quantitative PCR on a second and independent group (7PAH, 9CF, and 11HC). Twelve pre-transplant COPD patients were added to validate the common signature shared by patients with CRD for all causes. To further clarify a role for hypoxia in the candidate gene dysregulation, peripheral blood mononuclear cells from HC were analysed for their mRNA profile under hypoxia.ResultsUnsupervised hierarchical clustering allowed the identification of 3 gene signatures related to CRD. One was common to CF and PAH, another specific to CF, and the final one was specific to PAH. With the common signature, we validated T-Cell Factor 7 (TCF-7) and Interleukin 7 Receptor (IL-7R), two genes related to T lymphocyte activation, as being under-expressed. We showed a strong impact of the hypoxia on modulation of TCF-7 and IL-7R expression in PBMCs from HC under hypoxia or PBMCs from CRD. In addition, we identified and validated genes upregulated in PAH or CF, including Lectin Galactoside-binding Soluble 3 and Toll Like Receptor 4, respectively.ConclusionsSystematic analysis of blood cell transcriptome in CRD patients identified common and specific signatures relevant to the systemic pathologies. TCF-7 and IL-7R were downregulated whatever the cause of CRD and this could play a role in the higher susceptibility to infection of these patients