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Summary Background The use of cyclophosphamide in patients with acute exacerbation of idiopathic pulmonary fibrosis (IPF) is unknown. Our study was designed to evaluate the efficacy and safety of four cyclophosphamide pulses in addition to high-dose methylprednisolone in this population. Methods In this double-blind, placebo-controlled trial done in 35 departments across 31 hospitals in France, adult patients (≥18 years) with acute exacerbation of IPF and those with suspected acute exacerbation of IPF were randomly assigned in a 1:1 ratio using a web-based system to receive either intravenous pulses of cyclophosphamide (600 mg/m2) plus uromitexan as haemorrhagic cystitis prophylaxis (200 mg/m2) at the time of cyclophosphamide administration and then again, 4 h later, or placebo at days 0, 15, 30, and 60. Random assignment was stratified according to the severity of IPF and was block-balanced with variable block sizes of four or six patients. Patients receiving mechanical ventilation, with active infection, with active cancer, or who were registered on the lung transplant waiting list were excluded. All patients received standardised high-dose glucocorticoids. The investigators, patients, and the sponsor were masked to the treatment assignments. The primary endpoint was 3-month all-cause mortality, analysed by a χ2 test adhering to an intention-to-treat principle. The trial is now complete and registered with ClinicalTrials.gov , NCT02460588 . Findings Between Jan 22, 2016, and July 19, 2018, 183 patients were assessed for eligibility, of whom 120 patients were randomly assigned and 119 patients (62 [52%] with severe IPF) received at least one dose of cyclophosphamide (n=60) or placebo (n=59), all of whom were included in the intention-to-treat analysis. The 3-month all-cause mortality was 45% (27/60) in patients given cyclophosphamide compared with 31% (18/59) in the placebo group (difference 14·5% [95% CI −3·1 to 31·6]; p=0·10). Similar results were found after adjustment by IPF severity (odds ratio [OR] 1·89 [95% CI 0·89–4·04]). The risk of death at 3 months, independent of the treatment received, was higher with severe than non-severe IPF (OR 2·62 [1·12–6·12]) and was lower with the use of antifibrotic therapy (OR 0·33 [0·13–0·82]). Adverse events were similar between groups by 6 months (25 [42%] in the cyclophosphamide group vs 30 [51%] in the placebo group) and their proportion, including infections, did not differ. Overall infection was the main adverse event and occurred in 20 (33%) of 60 patients in the cyclophosphamide group versus 21 (36%) of 59 patients in the placebo group. Interpretation In patients with acute exacerbation of IPF, adding intravenous cyclophosphamide pulses to glucocorticoids increased 3-month mortality. These findings provide evidence against the use of intravenous cyclophosphamide in such patients. Funding Programme Hospitalier de Recherche Clinique of the French Ministry of Health (PHRC 2014–502), Roche Pharmaceuticals.

International audience; Lung transplantation (LTx) is a steadily expanding field. The considerable developments have been driven over the years by indefatigable work conducted at LTx centers to improve donor and recipient selection, combined with multifaceted efforts to overcome challenges raised by the surgical procedure, perioperative care, and long-term medical complications. One consequence has been a pruning away of contraindications over time, which has, in some ways, complicated the patient selection process. The Francophone Pulmonology Society (Société de Pneumology de Langue Française, SPLF) set up a task force to produce up-to-date working guidelines designed to assist pulmonologists in managing end-stage respiratory insufficiency, determining which patients may be eligible for LTx, and appropriately timing LTx-center referral. The task force examined the most recent literature and evaluated the risk factors that limit patient survival after LTx. Ideally, the objectives of LTx are to prolong life while also improving quality of life. The guidelines developed by the task force apply to a limited resource and are consistent with the ethical principles described below.

BackgroundStandard of care for interstitial lung disease (ILD) with a nonspecific interstitial pneumonia (NSIP) pattern proposes mycophenolate mofetil (MMF) as one of the first step therapies while rituximab is used as rescue therapy.MethodsIn a randomised, double blind, two-parallel group, placebo-controlled trial (NCT02990286), patients with connective tissue disease-associated ILD or idiopathic interstitial pneumonia (with or without autoimmune feature) and a NSIP pattern (defined on NSIP pathological pattern or on integration of clinico-biological data and a NSIP-like HRCT pattern) were randomly assigned in a 1:1 ratio to receive rituximab (1000 mg) or placebo on day 1 and day 15 in addition to MMF (2 g daily) for six months. The primary endpoint was the change in percent of predicted forced vital capacity (FVC) from baseline to 6 months analysed by a linear mixed model for repeated measures analysis. Secondary endpoints included progression-free survival (PFS) up to 6 months and safety.FindingsBetween January 2017 and January 2019, 122 randomised patients received at least one dose of rituximab (n=63) or placebo (n=59). The least-squares mean change from baseline to 6 months in FVC (% predicted) was +1.60 (se1.13) in the rituximab+MMF group and −2.01 (se1.17) in the placebo+MMF group (between-group difference, 3.60 [95% CI 0.41 to 6.80]; p=0.0273). PFS was better in the rituximab+MMF group (crude HR 0.47 [95%CI 0.23 to 0.96]; p=0.03). Serious adverse events occurred in 26 patients of the rituximab+MMF group (41%) and in 23 of the placebo+MMF group (39%). Nine infections were reported in the rituximab+MMF group (five bacterial infections, 3 viral infections, 1 other) and four bacterial infections in the placebo+MMF group.InterpretationCombination of rituximab and MMF was superior to MMF alone in patients with ILD and a NSIP pattern. The use of this combination must consider the risk of viral infection.

Resume Objectif Decrire la presentation clinique, la distribution des lesions, le traitement et les resultats de la sarcoidose osseuse. Methodes Il s’agit d’une etude retrospective francaise multicentrique de patients atteints de sarcoidose confirmee par une biopsie a analyse des patients presentant un granulome confirme par une biopsie sans necrose caseeuse et, soit des manifestations cliniques d’atteintes osseuses, soit des anomalies osseuses a l’imagerie. Les patients presentant une sarcoidose avec atteinte osseuse (cas) ont ete compares a 264 patients atteints de sarcoidose sans manifestations osseuses apparies selon l’âge et le sexe (temoins). Resultats Dans le groupe sarcoidose osseuse (n = 88), 42 patients (48 %) presentaient des symptomes osseux touchant le squelette axial (69 %) et/ou appendiculaire (58 %). Les os les plus frequemment touches sur l’imagerie etaient le rachis (52 %), le pelvis (42 %), les mains (22 %) et le femur (19 %). Par rapport aux temoins, les cas avaient des taux plus eleves d’atteinte mediastinale (93 % contre 47 %), des ganglions lymphatiques extra-thoraciques (66 % contre 21 %), pulmonaire (90 % contre 65 %) et cutanee (44 % contre 23 %) (toutes les valeurs p Conclusion Le rachis et le pelvis etaient les os les plus frequemment touches chez les patients presentant une sarcoidose osseuse. Par rapport aux temoins, les patients atteints de sarcoidose osseuse avaient des taux plus eleves d’atteinte des ganglions lymphatiques thoraciques et extra-thoraciques, pulmonaire et cutanee et d’hypercalcemie. La reponse aux glucocorticoides combines avec le methotrexate ou l’hydroxychloroquine etait bonne chez la majorite des patients.

Objective Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic small-vessel vasculitis characterized by asthma, hypereosinophilia and ANCA positivity in 40% of patients. Renal involvement is rare and poorly described, leading to this renal biopsy-proven based study in a large EGPA cohort. Methods We conducted a retrospective multicentre study including patients fulfilling the 1990 ACR criteria and/or the 2012 revised Chapel Hill Consensus Conference criteria for EGPA and/or the modified criteria of the MIRRA trial, with biopsy-proven nephropathy. Results Sixty-three patients [27 women, median age 60 years (18–83)] were included. Renal disease was present at vasculitis diagnosis in 54 patients (86%). ANCA were positive in 53 cases (84%) with anti-MPO specificity in 44 (83%). All patients had late-onset asthma. Peripheral neuropathy was present in 29 cases (46%), alveolar haemorrhage in 10 (16%). The most common renal presentation was acute renal failure (75%). Renal biopsy revealed pauci-immune necrotizing GN in 49 cases (78%). Membranous nephropathy (10%) and membranoproliferative GN (3%) were mostly observed in ANCA-negative patients. Pure acute interstitial nephritis was found in six cases (10%); important interstitial inflammation was observed in 28 (44%). All patients received steroids with adjunctive immunosuppression in 54 cases (86%). After a median follow-up of 51 months (1–296), 58 patients (92%) were alive, nine (14%) were on chronic dialysis and two (3%) had undergone kidney transplantation. Conclusion Necrotizing pauci-immune GN is the most common renal presentation in ANCA-positive EGPA. ANCA-negative patients had frequent atypical renal presentation with other glomerulopathies such as membranous nephropathy. An important eosinophilic interstitial infiltration was observed in almost 50% of cases.

Bronchiolitis obliterans syndrome (BOS) is the main limitation to long-term survival following lung transplantation. Several studies generated promising results regarding the efficacy of extracorporeal photopheresis (ECP) in BOS management. We aimed to compare FEV1 evolution in ECP-treated versus non-ECP treated patients among BOS recipients.Overall, 25 BOS patients were included after receiving optimized treatment. Data were collected retrospectively. Twelve patients with moderate and refractory BOS received ECP treatment.Among non-ECP treated control patients (n = 13), six experienced persistent decline without undergoing ECP for various reasons. ECP stabilized pre-ECP lung function during the subsequent 6 to 24 months (repeated measures one-way Anova, p = 0.002), without any significant impact observed by either FEV1 decline speed prior to ECP or time between BOS diagnosis and ECP onset. ECP-treated patients displayed a similar risk of an additional permanent 20% or higher drop in FEV1 after BOS onset compared to controls, but a lower risk compared to control decliners (p = 0.05). ECP quickly stabilized FEV1 decline in refractory BOS patients compared to non-treated decliners.We confirmed that this therapeutic option against refractory BOS can be managed in a medium-size LTx center, with a satisfactory efficacy and an acceptable tolerance.

Poly(A)-specific ribonuclease (PARN) mutations have been associated with familial pulmonary fibrosis. This study aims to describe the phenotype of patients with interstitial lung disease (ILD) and heterozygous PARN mutations.We performed a retrospective, observational, non-interventional study of patients with an ILD diagnosis and a pathogenic heterozygous PARN mutation followed up in a centre of the OrphaLung network.We included 31 patients (29 from 16 kindreds and two sporadic patients). The median age at ILD diagnosis was 59 years (range 54 to 63). In total, 23 (74%) patients had a smoking history and/or fibrogenic exposure. The pulmonary phenotypes were heterogenous, but the most frequent diagnosis was idiopathic pulmonary fibrosis (n = 12, 39%). Haematological abnormalities were identified in three patients and liver disease in two. In total, 21 patients received a specific treatment for ILD: steroids (n = 13), antifibrotic agents (n = 11), immunosuppressants (n = 5) and N-acetyl cysteine (n = 2). The median forced vital capacity decline for the whole sample was 256 ml/year (range -363 to -148). After a median follow-up of 32 months (range 18 to 66), 10 patients had died and six had undergone lung transplantation. The median transplantation-free survival was 54 months (95% CI 29 to ∞). Extra-pulmonary features were less frequent with PARN mutation than telomerase reverse transcriptase (TERT) or telomerase RNA component (TERC) mutation.IPF is common among individuals with PARN mutation, but other ILD subtypes may be observed.

Survival after lung transplantation (LTx) still remains limited by chronic lung allograft dysfunction (CLAD), thought to represent a form of chronic rejection. We investigated whether the immune checkpoint HLA-G/ILT2 expressed by peripheral T-cell subpopulations could predict CLAD.We used data for 150 LTx recipients from COLT (Cohort-For-Lung-Transplantation) cohort with ≥1 available blood sample at 1-, 6-, or 12-months post-Tx. Analysis of T cells by flow cytometry focused on the ILT2 receptor of HLA-G and other markers (CD57, CD25, CD127). T-cell subset analyses compared stable patients and those with CLAD at 3 years post-LTx.With data for 78 stable and 72 CLAD patients, among 21 T-cell subsets expressing ILT2, only CD4+CD57+ILT2+ T cells were associated with outcome. At 1-month post-Tx, low proportion of CD4+CD57+ILT2+ T cells was associated with reduced 3-year incidence of CLAD (CD4+CD57+ILT2+ T cells ≤ first IQR [25%] vsfirst IQR, log-rank test, p = 0.028). Furthermore, the incidence of CLAD was higher with2.6- vs ≤2.6-fold increased proportion of CD4+CD57+ILT2+ T cells over the first year post-LTx (3-year freedom frequencies: 27% [95%CI: 8-50] vs 64% [95%CI: 48-77] (log-rank test, p = 0.014). On multivariable analysis, increased proportion of CD4+CD57+ILT2+ T cells over the first year predicted CLAD (hazard ratio 1.25; 95%CI: 1.09-1.44; p = 0.001). Focusing on CD4+CD57+ILT2+ T cells, we demonstrated ex vivo that they are cytotoxic CD4+ T cells, selectively inhibited by HLA-G.Our data suggest that an early increase of CD4+CD57+ILT2+ T cells after LTx may be associated with CLAD onset.

To describe the clinical presentation, distribution of lesions, treatment, and outcomes of osseous sarcoidosis.A French retrospective multicenter study of patients with biopsy-proven sarcoidosis analyzed patients with 1) a biopsy-proven granuloma without caseous necrosis, and either 2) osseous clinical manifestations, or 3) abnormal osseous imaging. Sarcoidosis patients with osseous involvement (cases) were compared with 264 age- and sex-matched sarcoidosis patients with no osseous manifestations (controls).In the osseous sarcoidosis group (n=88), forty-two (48%) patients had osseous-related symptoms involving the axial (69%) and/or appendicular (58%) skeleton. On imaging, the most commonly affected bones were in the spine (52%), pelvis (42%), hands (22%) and femur (19%). Compared with controls, cases had higher rates of mediastinal (93% vs. 47%) and extra-thoracic lymph node involvement (66% vs. 21%), pulmonary (90% vs. 65%) and cutaneous involvement (44% vs. 23%) (all P0.0001), and hypercalcemia (8.5% vs. 2%, P=0.014). Spleen/liver and gastrointestinal involvement were less frequent in the osseous sarcoidosis group (29% vs. 45%, and 1% vs. 17%, respectively, P0.0001). Response rates to with glucocorticoids alone, glucocorticoids plus methotrexate or glucocorticoids plus hydroxychloroquine were 23/44 (52%), 9/13 (69%) and 4/6 (67%), respectively.In patients with osseous sarcoidosis the spine and pelvis were the most commonly affected bones. Compared with controls, cases with osseous sarcoidosis have higher rates of thoracic and extra-thoracic lymph node involvement, pulmonary and cutaneous involvement, and hypercalcemia. Most patients with osseous sarcoidosis had a good response to glucocorticoids in combination with methotrexate or hydroxychloroquine.

Poly(A)-specific ribonuclease (PARN) mutations have been associated with familial pulmonary fibrosis. However, the phenotype of patients with interstitial lung disease (ILD) and PARN mutations is poorly described. We performed a retrospective, observational, non-interventional study. All the patients with an ILD diagnosis and a pathogenic heterozygous PARN mutation, followed in one of the OrphaLung center, were included. We included 30 patients (24 patients from 11 kindreds and 6 sporadic patients with early onset of ILD or extra-pulmonary phenotype). The median age at diagnosis of ILD was 59 years (range 54 - 64). Twenty-three patients (77 %) had a smoking history and/or a fibrogenic exposure. The pulmonary phenotypes were heterogenous but the most frequent diagnosis was idiopathic pulmonary fibrosis (IPF; n=15, 50%). Hematological abnormalities were identified in 3 patients and liver disease in 2 patients. Twenty-one patients received a specific treatment for ILD: steroids (n=13), antifibrotic (n= 11), immunosuppressants (n=5) and N-acetyl cysteine (n=2). The median decline of FVC for the whole population was 292 ml/year (range 146 - 657). After a median follow-up of 2.8 years 8 patients had died and 6 had undergone lung transplantation. The median transplantation-free survival was 4.5 years. PARN mutation carriers were older, and extra-pulmonary manifestations were less frequent as compared to TERT or TERC mutation carriers. PARN mutations are most frequently associated with IPF, but other ILD may be observed. Such phenotypic heterogeneity requires a thorough evaluation of PARN-associated ILD patients in order to define tailored therapeutic strategies.

Background Few studies analyzed gender-related outcomes and characteristics differences of patients with idiopathic pulmonary fibrosis (IPF). The aim of the study was to explore gender differences in a French IPF cohort. Methods 236 patients with incident IPF were included in the multicentric longitudinal prospective cohort COhorte FIbrose (COFI), and followed for 5 years. Men and women were compared for characteristics atinclusion (t-test, Chi2 or ANOVA) and survival (Log rank, Cox model). Results The population consisted of 51 (22%) women and 185(78%) men. At inclusion women significantly differed from men for an older age (> 65 years, 78 vs. 61%, P = 0.028), a lower proportion of smokers (P Conclusions At diagnosis women appear to have a distinct imaging pattern and a better FVC, which may be due to less exposure history compared to men. However, outcomes remain comparable in both sexes. Less access to lung transplantation in women may be due to age and comorbidities.

Background Low income is a known prognostic indicator of various chronic respiratory diseases but has not been studied in idiopathic pulmonary fibrosis (IPF). We hypothesize that a low income has an adverse prognostic impact on IPF. Methods Patients were selected from the French national prospective cohort COFI. Patient's income was assessed through the median city-level income provided by the French National Institute of Statistics and Economic Studies according to his/her residential address. Patients were classified in two groups as “low income” vs. “higher income” depending on whether their annual city-level income was estimated to be Results 200 patients were included. The average follow-up was 33.8 ± 22.7 months. Patients in the low income group were more likely to be of non-European origin (42 vs. 17%, P Conclusions Low income appears to be a prognostic factor of progression free survival in IPF. And patients with low incomes may also be exposed more frequently to occupational exposures and to higher cumulative exposure to fine particles.

Study questionIn patients with sarcoidosis, past and ongoing immunosuppressive regimens, recurrent disease in the transplant and extrapulmonary involvement may affect outcomes of lung transplantation. We asked whether sarcoidosis lung phenotypes can be differentiated and, if so, how they relate to outcomes in patients with pulmonary sarcoidosis treated by lung transplantation.Patients and methodsWe retrospectively reviewed data from 112 patients who met international diagnostic criteria for sarcoidosis and underwent lung or heart–lung transplantation between 2006 and 2019 at 16 European centres.ResultsPatient survival was the main outcome measure. At transplantation, median (interaquartile range (IQR)) age was 52 (46–59) years; 71 (64%) were male. Lung phenotypes were individualised as follows: 1) extended fibrosis only; 2) airflow obstruction; 3) severe pulmonary hypertension (sPH) and airflow obstruction; 4) sPH, airflow obstruction and fibrosis; 5) sPH and fibrosis; 6) airflow obstruction and fibrosis; 7) sPH; and 8) none of these criteria, in 17%, 16%, 17%, 14%, 11%, 9%, 5% and 11% of patients, respectively. Post-transplant survival rates after 1, 3, and 5 years were 86%, 76% and 69%, respectively. During follow-up (median (IQR) 46 (16–89) months), 31% of patients developed chronic lung allograft dysfunction. Age and extended lung fibrosis were associated with increased mortality. Pulmonary fibrosis predominating peripherally was associated with short-term complications.Answer to the study questionPost-transplant survival in patients with pulmonary sarcoidosis was similar to that in patients with other indications for lung transplantation. The main factors associated with worse survival were older age and extensive pre-operative lung fibrosis.

Resume Introduction Plusieurs parametres clinico-biologiques permettent d’estimer la quantite d’oxygene disponible pour l’organisme. La saturation en oxygene mesuree a l’oxymetre de pouls (SpO2), la saturation arterielle en oxygene (SaO2) et la pression partielle arterielle en oxygene (PaO2) mesurees par gazometrie sont les plus utilisees. Observation Nous rapportons le cas d’une patiente hospitalisee pour bilan d’insuffisance respiratoire decouverte dans un contexte de dyspnee d’effort chronique. La SpO2 etait diminuee tout comme la SaO2 mesuree par gazometrie malgre une PaO2 dans les normes. La dissociation entre les valeurs de PaO2 et de SaO2 nous a permis d’aboutir au diagnostic d’hemoglobinopathie (hemoglobine Bassett). Conclusion Le diagnostic d’hemoglobinopathie est a evoquer devant une desaturation en oxygene avec bilan respiratoire et cardiologique sans anomalie. Il ne semble pas y avoir d’argument pour proposer a ces patients une oxygenotherapie en condition stable.

Background International guidelines recommend that annual influenza vaccination be performed in patients with idiopathic pulmonary fibrosis (IPF). Viral infections are recognized to be triggers of acute exacerbation (AE). The purpose of this study was to investigate the role of annual influenza vaccination on AE occurrence. Methods 236 patients with incident IPF were included in the multicentric longitudinal prospective cohort COhorte FIbrose (COFI), and followed for 5 years. Influenza vaccination status was requested annually. We have defined aone-year vaccination coverage from September the first to August the 30th of the following year. 638 annual observations were available with an informed vaccination status. To evaluate the association between annual influenza vaccination and AE occurrence, two mixed-effect Cox regression was used. For the second model we divided patients in 3 groups: – patients vaccinated every year; – patients vaccinated at least half of the years of follow-up; – patients vaccinated less than half the years of follow-up. Only the first AE was considered. The definition of AE was that of Akira et al. Results Mean follow-up was 33.2 ± 23.6 months. 36 AEs occurred in 33 patients. Of the 33 patients, only 27 had an informed vaccination status in the year of their AE. Nine (33%) patients who experienced an AE weren’t vaccinated. For 141 (22%) annual observations, the patient didn’t receive the vaccine. In this model, influenza vaccination was associated with a decreased occurrence of AE but this did not reach the level of significance in this small population (HR:0.58 CI95%0.23-1.46, P = 0.25). In the first group patients were vaccinated every year and consisted of hundred and thirty-three individuals. The second group was composed of patients vaccinated at least half of the years of follow-up, with 35 patients. And 36 patients were vaccinated less than half the years of follow-up in the last group. In the second model, patients vaccinated less than half the years of follow-up were significantly more at risk to present AE compared to patients who were vaccinated every year (HR:2.77 CI95%1.11-6.93, P = 0.03). Conclusions In our IPF cohort, only about half of the patients had influenza vaccination coverage throughout the follow-up period. Annual influenza vaccination seems to reduce the risk of AE but due to a lack of power this association was not significant. However patients vaccinated less than half the years of follow-up were significantly more at risk to present AE compared to patients who were vaccinated every year. A study with a larger number of patients is highly desirable to confirm this association.

Purpose Lung transplantation (TxP) is now a validated treatment of end-stage pulmonary diseases, but long-term survival are still hampered by the development of chronic allograft dysfunction (CLAD) affecting> 50% of patients. Bronchiolitis obliterans syndrome/obliterative bronchiolitis (BOS/OB) is the most common manifestation of CLAD. Survival after onset of BOS is poor ( Methods A phase III clinical randomized trial to assess the efficacy of Nintedanib in LTx recipients with BOS.Inclusion criteria: n=80 LTx recipients with BOS 0p-1-2, with a decline of FEV1> 200ml within the previous year.Primary Objective: to assess Nintedanib efficacy in the reduction of the rate of decline of FEV1 (forced expiratory volume in 1 sec) at a dose of 150 mg twice daily (bid) compared to placebo over 6 months. Secondary Objectives: to assess Nintedanib efficacy and tolerance in the treatment of BOS 0p-1-2, based on the change over 6 months of : 6WT, QOL, BOS grade/graft failure, O2 saturation, KL-6, SPD, VEGF, PDGF parameters, and tolerance. Results The trial was started in December 2019 among 8 french LTx centers (Hopital Foch, Bichat, HEGP/Cochin, Marie-Lannelongue, Marseille, Bordeaux, Strasbourg, and Grenoble), for a total duration of inclusion anticipated at 36 months. On October 15th 2020, 14 patients were already included. Conclusion Infinitix-BOS is the first therapeutic randomized trial testing the efficacy of nintedanib in LTx recipients with BOS. In case of demonstrated effectiveness of Nintedanib, the benefit for LTx patients with BOS seems high in terms of stabilization of lung function and enhancement of survival.

Purpose Patients with short telomeres and interstitial lung disease (ILD) appear to have increased mortality and bronchiolitis obliterans syndrome after lung transplant. Given the dysfunctional response of short telomere patients to cell damage and stress due to cell senescence, they may be more susceptible to impaired large airway healing. We hypothesized that post-transplant airway complications, including dehiscence and bronchial stenosis, would be more common in the short telomere ILD transplant population. Methods We studied 63 recipients transplanted at two centers between 2009 and 2019 with ILD and short telomeres, defined either by telomere length below the 1st percentile for age in any lineage or below the 10th percentile in the lymphocyte lineage by flow-FISH telomere length analysis of peripheral blood lymphocytes, with or without the presence of a known telomere-related mutation. The primary outcomes were the presence of dehiscence or of significant stenosis (i.e. requiring dilation or stenting) after transplant. The control population was 4,359 adult recipients with ILD transplanted over similar years, taken from the Scientific Registry of Transplant Recipients (SRTR). Results Among the short telomere cohort, 6 patients (9.5%) had dehiscence and 9 (14.3%) had stenosis compared to 1.4% and 3.4%, respectively, in the SRTR cohort. When adjusted for age, sex, and bilaterality, the presence of short telomeres was associated with a significantly higher odds of dehiscence (odds ratio (OR)=7.34, 95% confidence interval (CI)=3.01-17.92, p Conclusion We identified an association between the presence of short telomeres and post-transplant large airway complications, including dehiscence and significant stenosis. Airway complications may be a contributor to worse outcomes in patients with telomere-related ILD.

Introduction La survie apres transplantation pulmonaire (TxP) reste limitee par la survenue d’une dysfunction chronique pulmonaire (CLAD), qui touche > 50 % des greffes. La forme obstructive de CLAD, bronchiolite obliterante (BO)/syndrome de BO (SBO), est le phenotype le plus frequent de CLAD (80% des cas). Les lesions de BO semblent dues a des agressions repetees de l’epithelium bronchique avec developpement d’une cicatrice fibreuse. Il n’existe actuellement pas de traitement demontre pour stabiliser le SBO. Le role crucial de la dysfonction de reparation fibrotique est demontre dans la BO via le remodellage bronchique, l’augmentation de matrice extra-cellulaire, la transition epithelio-mesenchymateuse, l’augmentation des facteurs de croissance PDGF, VEGF, FGF, IGF- Le TKI Nintedanib, demontre efficace dans la fibrose pulmonaire idiopathique, et qui cible ces facteurs de croissance, est une molecule candidate. Un essai therapeutique testant le nintedanib dans la BOS post-TxP a debute en France fin 2019. Methodes Essai multicentrique, randomise double aveugle contre placebo, evaluant l’efficacite du Nintedanib dans le traitement du syndrome de bronchiolite obliterante grade 0-p et grade 1-2 chez les patients greffes pulmonaires. Criteres d’inclusion: BOS 0-p, 1, 2 et forme mixte de CLAD (criteres ISHLT). Objectif principal: evaluer l’efficacite du nintedanib sur la reduction du taux de declin du VEMS dans le SBO post-TxP (150 mg × 2/j versus placebo pendant 6 mois (± 100 mg × 2/j si effets secondaires). Objectifs secondaires: evaluer l’efficacite du nintedanib sur l’evolution de: 6WT, QOL (SGRQ); mesures repetees VEMS; grade BOS; Saturation O2; ainsi que frequence des effets secondaires, et evolution de parametres sanguins KL-6, SPD, VEGF, PDGF. Resultats L’essai a ete ouvert entre dec 2019 et mars 2020 parmi 8 centres de greffe en France (Hopital Foch, Bichat, HEGP/Cochin, Marie-Lannelongue, Marseille, Bordeaux, Strasbourg et Grenoble), pour une duree d’inclusion prevue de 36 mois. Au 31/08/2020, 7 patients greffes ont ete inclus dans 3 centres. Afin d’augmenter le nombre de patients eligibles, une modification du protocole du 2/07/2020, permet d’inclure desormais les patients avec BOS grade 0-p et les regreffes. Conclusion InfinitixBOS est le 1er essai therapeutique randomise controle evaluant l’efficacite du Nintedanib dans les formes obstructives/mixtes de CLAD. En cas de demonstration d’une efficacite sur la fonction pulmonaire, le benefice au patient est eleve au vu de la frequence du SBO.

Introduction La vaccination antigrippale est recommandee chaque annee chez les patients atteints de fibrose pulmonaire idiopathique (FPI). Les infections virales sont reconnues comme des triggers d’exacerbation aigue (EA). L’objectif de cette etude etait d’etudier l’influence de la vaccination annuelle contre la grippe sur le risque d’EA. Methodes La cohorte prospective longitudinale multicentrique COhorte FIbrose (COFI) comporte 236 FPI et suivi a dure 5 ans. Le statut de vaccinal contre la grippe a ete demande chaque annee. Nous avons defini la couverture vaccinale du 1er septembre au 30 aout de l’annee suivante. 638 visites annuelles etaient disponibles avec un statut vaccinal renseigne. L’etude entre la vaccination grippale et l’incidence des EA a ete realisee par un premier modele de Cox a effets aleatoire puis par un second modele de Cox en divisant les patients en trois groupes: (1) les patients vaccines chaque annee, (2) ceux vaccines pendant au moins la moitie des annees de suivi, (3) ceux vaccines moins de la moitie des annees de suivi. Resultats Le suivi moyen etait de 33,2 ± 23,6 mois. 36 EA sont survenues chez 33 patients. Sur les 33 patients, seuls 27 avaient un statut vaccinal precise l’annee de l’EA. Neuf (33%) des patients ayant presente une EA n’ont pas ete vaccines. Pour 141 (22%) visites annuelles, les patients n’ont pas ete vaccines. 133 patients ont ete vaccines chaque annee de suivi. 35 ont ete vaccines pendant au moins la moitie des annees de suivi, et 36 patients ont ete vaccines pendant moins de la moitie des annees de suivi. Dans le premier modele, la vaccination contre la grippe est associee a une diminution de la frequence des EA, mais l’association est non significative (HR: 0,58 CI95%0,23–1,46, p = 0,25). Dans le second modele, les patients vaccines pendant moins de la moitie des annees de suivi etaient significativement plus exposes au risque d’EA compares aux patients vaccines chaque annee (HR: 2,77 CI95%1.11–6.93, p = 0,03). Conclusion Dans COFI seulement environ la moitie des patients avaient une couverture vaccinale contre la grippe tout au long du suivi. La vaccination annuelle contre la grippe semble reduire le risque d’EA, mais par manque de puissance, cette association n’etait pas significative. Les patients vaccines pendant moins de la moitie des annees de suivi etaient plus exposes au risque d’EA que les patients vaccines chaque annee.

Background Atrial arrhythmias (AAs) are frequent after lung transplantation (LT) and late postoperatively. Several predictive factors of early postoperative AAs after LT have been identified but those of late AAs remain unknown. Whether AA after LT affects mortality is still being debated. This study assessed in a large cohort of LT patients the incidence of AAs early and late after surgery, their predictive factors and their effect on mortality.Methods and Results:We studied 271 consecutive LT patients over 9 years. Mean follow-up was 2.9±2.4 years. 33% patients developed postoperative AAs. Age (odds ratio (OR) 2.35; confidence interval (CI) [1.31-4.24]; P=0.004) and chronic obstructive pulmonary disease (OR 2.13; CI [1.12-4.03]; P=0.02) were independent predictive factors of early AAs. Late AAs occurred 2.2±2.7 years after transplant in 8.8% of the patients. Pretransplant systolic pulmonary arterial pressure (PTsPAP) was the only independent predictive factor of late AA (OR 1.028; CI [1.001-1.056]; P=0.04). Double LT was associated with long-term freedom from atrial fibrillation (AF) but not from atrial flutter (AFL). Early and late AAs after surgery had no effect on mortality. Double LT was associated with better survival. Conclusions Early AA following LT is common in contrast with the low occurrence of late, often organized, AA. Early and late AAs do not affect mortality. PTsPAP is an independent predictor of late AA. Double LT protects against late AF but not AFL.

Objective To guide nosology and classification of patients with eosinophilic granulomatosis with polyangiitis (EGPA) based on phenotype and presence or absence of ANCA. Methods Organ manifestations and ANCA status were retrospectively analyzed based on the presence or not of predefined definite vasculitis features or surrogates of vasculitis in patients asthma, eosinophilia, and at least one systemic organ manifestation attributable to systemic disease. Results The study population included 157 patients (mean age 49.4 ± 14.1), with a follow-up of 7.4 ± 6.4 years. Patients with ANCA (31%) more frequently had weight loss, myalgias, arthralgias, biopsy-proven vasculitis, glomerulonephritis on biopsy, hematuria, leukocytoclastic capillaritis and/or eosinophilic infiltration of arterial wall on biopsy, and other renal disease. A total of 41% of patients had definite vasculitis manifestations (37%) or strong surrogates of vasculitis (4%), of whom only 53% had ANCA. Mononeuritis multiplex was associated with systemic vasculitis (p = 0.005) and with the presence of ANCA (p

Introduction La fibrose pulmonaire idiopathique (FPI) est une affection rare et peu de donnees epidemiologiques sont disponibles en France. Ce projet vise a decrire les caracteristiques en vie reelle des patients atteints de FPI recevant un traitement anti-fibrosant, ainsi que leurs comorbidites et la mortalite. Methodes RaDiCo-PID est une cohorte longitudinale a long terme incluant des patients enfants et adultes atteints de pneumopathies interstitielles diffuses (PID) idiopathiques suivis dans des centres de reference et de competence de la filiere Respifil et des reseaux OrphaLung et Respirare. RaDiCo-PID comporte un sous-groupe de patients atteints de FPI. Nous presentons ici les caracteristiques de base des patients atteints de FPI apres 2 ans d’inclusion. Resultats Entre le 15 juin 2017 et le 4 septembre 2019, 1246 patients atteints de pneumopathie interstitielle diffuse ont ete inclus dans le registre Radico-PID dans 18 centres, dont 847 atteints de FPI (68 %). Les patients atteints de FPI etaient en majorite des hommes (82,7 %), avec un âge moyen de 72,5 ± 9 ans a l’inclusion et un index de masse corporelle moyen de 26,8 ± 4,3. Parmi les patients avec FPI, 44,6 % etaient des cas incidents avec une duree mediane entre le diagnostic et l’inclusion de 8,9 mois (Q1 = 0,9 et Q3 = 26,4) ; 25,3 % de ces patients avaient eu une biopsie. La capacite vitale forcee moyenne au diagnostic etait de 73,4 ± 25,0 % de la valeur theorique (n = 561), et la capacite de transfert du monoxyde de carbone moyenne au diagnostic etait de 39,6 ± 18,2 % (n = 498). Selon les donnees disponibles sur les traitements anti-fibrosants (n = 661), 347 patients ont ete traites, au moins une fois, par du nintedanib et 312 patients par de la pirfenidone ; 113 patients ont recu sequentiellement ces 2 molecules. Conclusion La cohorte Radico-PID fournit des donnees concretes precieuses sur les caracteristiques demographiques des patients, notamment au moment du diagnostic de FPI. Les effectifs actuels permettent d’envisager des analyses plus approfondies.

Improved knowledge has highlighted the importance of additional histological and clinico/radiological features for the diagnosis of Usual Interstitial Pneumonia(UIP)-non Idiopathic Pulmonary Fibrosis(IPF) patients. We present preliminary findings of bicentric revised UIP/IPF cases after a multidisciplinary discussion (MDD) according to the 2018 ATS/ERS/JRS/ALAT Guidelines. All 2002-2017 cases with diagnosis of IPF were retrieved. Histological review was performed considering features suggestive of other diagnoses, i.e.connective tissue diseases (CTD) (germinal centers, >4 lymphoid follicles/cm2, lymphocyte/plasma-cell ratio ≥1, lymphocytic pleuritis, vessel remodelling) and chronic hypersensitivity pneumonitis (CHP) (bridging fibrosis, peribronchial metaplasia, centrolobular fibroblastic foci, granulomas/giant-cells). Clinico/radiological data were reviewed and all cases were re-categorized after MDD. 62 cases were reviewed:in 47% the final diagnosis was IPF, in 11% IPF(likely), in 13% indeterminate IPF and in 29% non-IPF. Among the “indeterminate IPF”, the most prevalent diagnosis was CHP, while in the “non-IPF”, CHP and CTD were almost equally detected (see Figure). In conclusion, the rate of IPF diagnoses appears to have been overestimated. The current knowledge and good practice of MDD have significantly improved the diagnostic accuracy.

International audience; Carriers of telomerase related genes (TRG) mutation seem to present a worst prognosis with more common hematological complications after lung transplantation (LT) for pulmonary fibrosis. The aim of this study was to describe the outcomes after LT and identify pre-LT prognosis factors in a multicenter cohort of lung transplant recipients with TRG mutation.We retrospectively reviewed all identified patients with pathogenic TRG mutation (n=38; TERT, n=22, TERC, n=10, RTEL1, n=6) who received LT in France, Switzerland and Belgium between 2009 and 2018. The median age at LT was 54 years (46-59), 70% were male, and 60% had idiopathic pulmonary fibrosis (IPF). At diagnosis of pulmonary fibrosis, 84% had a hematological disease, including 8 with myelodysplasia, and 45% had a liver disease. After a median follow up of 2.2 years (1,2-3,7), 16 received a single LT, 22 a double LT and 2 a combined liver-LT.The overall post-LT median survival was 3.75 years (1.8-NA). Patients with myelodysplasia before LT had an increased risk of death after LT (HR= 4.12 (1.47-11.53) p=0.007). After LT, all patients showed anemia, 70% thrombocytopenia, and 60% neutropenia. Four patients showed severe liver disease: portal hypertension, cirrhosis. Sixteen patients (42%) experienced acute renal failure and 18 (47%) developed chronic renal insufficiency during follow up. Four developed chronic lung allograft dysfunction.Overall survival after LT supports LT in TRG mutation carriers. Careful evaluation at diagnosis, might limit LT indication for patients with established myelodysplasia.

BACKGROUND: Antibody mediated rejection (AMR) plays an important role in allograft dysfunction. Acute lung injury (ALI), endotheliitis, capillary inflammation and C4d positivity have been described as morphological features conventionally associated with lung AMR. A multidisciplinary, international task force reviewed AMR cases in the context of four face-to-face meetings. Septal widening was a frequent, striking histological feature recognized firstly and easily at low-power magnification. This study aimed to evaluate whether septal widening could represent an "alert" signal for AMR.METHODS: Following the face-to-face meetings that enabled the classification of cases as AMR or non-AMR, morphometry was performed on biopsies from 48 recipients with definite, probable and possible AMR, 31 controls (negative for any post-transplant injury) and 10 patients with non-immune related ALI.RESULTS: Mean alveolar septal thickness was greater in AMR patients than in controls (pCONCLUSIONS: Our data suggest that, even if unspecific as the other lesions conventionally associated with AMR, septal widening may represent an "alert" signal to look into lung AMR. A larger prospective study is mandatory to confirm the potential value of septal widening in the multidisciplinary approach of AMR.

Introduction Peu d’etudes ont analyse la survie et les differences de caracteristiques initailes des patients atteints de la fibrose pulmonaire idiopathique (FPI) selon le genre. L’objectif de l’etude etait d’explorer les differencesselon le genre dans une cohorte francaise de FPI. Methodes 236 patients atteints d’une FPI incidente ont ete inclus dans la cohorte prospective longitudinale multicentrique COhorte FIbrose (COFI), et a suivi pendant 5 ans. Les hommes et les femmes ont ete compares pour les caracteristiques a l’inclusion (test t, Qui-squared ou ANOVA) et une l’analyse de survie sans transplantation a ete realise (Log rank, modele de Cox). Resultats La population etait composee de 51 (22 %) femmes et 185 (78 %) hommes. A l’inclusion, les femmes avaient un age plus avance que les hommes, (âge > a 65 ans 78 % contre 61 %, p = 0,028), une proportion plus faible de fumeurs (p Conclusion Au moment du diagnostic de FPI, les femmes semblent avoir une meilleure CVF et une presentation radiologique distincte, possiblement du fait qu’elles ont ete moins exposees par rapport aux hommes. Toutefois, la survie sans transplantation reste comparable entre les hommes et les femmes. La diminution de l’acces a la transplantation pulmonaire chez les femmes pourrait etre due a l’âge et aux comorbidites.

Introduction La transplantation (TxP) est le seul traitement curatif de la fibrose pulmonaire idiopathique (FPI). Des traitements antifibrosants (pirfenidone et nintedanib), qui ralentissent l’evolution de la maladie, ont ete developpes recemment. Ils pourraient augmenter le risque de complications post-operatoires lors de la TxP des patients traites. L’objectif de cette etude etait d’evaluer l’association entre la prise d’un traitement antifibrosant et les complications apres une TxP. Methodes Il s’agit d’une etude retrospective multicentrique francaise, ayant inclus des patients atteints de FPI et ayant beneficie d’une TxP entre 2011 et 2018. Nous avons compare l’incidence des complications post operatoires (complications bronchiques et hemorragiques) et la survie des patients ayant recu ou non des antifibrosants au minimum un mois avant la TxP. Resultats Parmi les 205 patients inclus, 57 (27,8%) ont recu un traitement antifibrosant: pirfenidone pour 36 patients (63%) et nintedanib pour 21 patients (37%). La duree mediane de traitement antifibrosant avant la TxP etait de 532 jours. Il n’y avait pas de difference entre les deux groupes dans la survenue de complications anastomotiques bronchiques (p = 0,90), hemorragiques (p = 0,14) ou de cicatrisation cutanee (p = 0,65). La mortalite a 90 jours post-TxP dans le groupe traite etait significativement inferieure (7%) a celle du groupe controle (18,2%, p = 0,04). La mortalite a 30 jours post-TxP des deux groupes ne differait pas (p = 0,18). Le groupe traite presentait egalement moins de dysfonction primaire du greffon (DPG) (29,8%) que le groupe controle (43,2%, p = 0,01). Conclusion Les antifibrosants ne sont pas associes a une augmentation du risque de complications post-TxP et peuvent donc etre utilises sans risque avant la transplantation. Leur utilisation semble etre associee a une diminution de la DPG et de la mortalite a 90 jours. Cette difference de mortalite, deja rapportee par une equipe australienne [1] , devra cependant etre confirmee par d’autres etudes.

Introduction L’impact clinique et social de l’epidemie de COVID-19 chez les patients transplantes pulmonaire (TP) est encore mal connu. La region Grand-Est a ete l’une des plus severement touchee, obligeant de nombreux services hospitaliers a assurer un suivi par telemedecine. Avec cette etude, nous avons souhaite evaluer les consequences sociales et cliniques de cette epidemie ainsi que celles sur les comportements des patients TP suivis au CHU de Strasbourg, tout en cherchant a optimiser nos methodes de suivi a distance. Methodes Un questionnaire a ete soumis a l’ensemble des patients afin de collecter des informations sur leurs habitudes de vie, les moyens utilises pour se proteger contre la Covid-19 et tout evenement infectieux survenu au cours du mois de mars 2020. Dans ce contexte, nous avons egalement developpe un score specifique afin de quantifier les contacts sociaux de chaque patient et le risque de contagion infectieuse associe. Resultats Les donnees ont pu etre collectees chez 322 patients suivis dans notre centre (91,2 % de la cohorte). Les principales comorbidites retrouvees etaient l’hypertension arterielle (52,2 %), le diabete (47,5 %), et l’insuffisance renale chronique (40,4 %). Le respect des distanciations sociales et des gestes barrieres etait tres bien applique chez une majorite de patients. Parmi les patients, 43,8 % ont rapporte des symptomes infectieux et un traitement anti-infectieux a ete prescrit chez 15,8 % d’entre eux. Il n’y avait pas de difference en termes d’apparition de symptomes infectieux selon l’âge, le motif de transplantation, la presence d’un diabete ou l’obesite. Dix-neuf patients ont ete depistes pour la COVID-19, avec un diagnostic positif chez 4 d’entre eux, suivi d’une evolution clinique favorable pour chacun. Le score « contact-risque infectieux » etait significativement plus eleve chez les patients symptomatiques (p : 0,007), ceux ayant eu recours a une consultation medicale supplementaire (p Fig. 1 ). Conclusion Nous avons observe chez nos patients un mode de vie prudent et une bonne compliance aux gestes barrieres. Le risque d’etre infecte par la COVID-19 ne semblait pas plus important dans notre cohorte. Le score « contact-risque infectieux » a montre des resultats encourageants malgre un manque de specificite, et pourrait devenir un outil precieux pour le suivi clinique de nos patients.

Interstitial lung disease is a common, largely unrecognised feature of pulmonary GvHD after stem cell transplant http://ow.ly/Tnx83034yR0

Introduction Les faibles revenus sont des indicateurs pronostiques connus dans diverses maladies respiratoires chroniques mais peu etudies dans la fibrose pulmonaire idiopathique (FPI). La FPI est la plus frequente et grave des pneumopathies interstitielles diffuses. Son histoire naturelle reste mal comprise. Nous faisons l’hypothese que les faibles revenus ont un impact pronostique dans la FPI. Methodes Les patients sont issus de la cohorte prospective multicentrique francaise COFI. Le revenu individuel n’etant pas disponible, il a ete estime a partir des donnees de l’Institut national de la statistique et des etudes economiques (INSEE) qui archive le revenu annuel median des habitants de toutes les villes ou arrondissements en France. Ce revenu annuel median a ete attribue a chaque patient en fonction de son domicile. Les patients ont ete separes en deux groupes, « faible revenu » et « revenu superieur », selon que le revenu annuel etait a 18 170 €/an (premier quartile de l’ensemble de la population incluse). La probabilite de survie sans progression (SSP) des groupes a ete comparee par un test du log-rank et un modele de Cox en analyse multivariee. Resultats Deux cent patients ont ete inclus et suivis pendant une moyenne de 33,8 ± 22,7 mois. A la fin de l’etude, 6 (3 %) ont ete perdus de vue, 17 (9 %) ont ete transplantes, et 120 (60 %) sont decedes. Les patients du groupe « faible revenu » etaient plus susceptibles d’etre d’origine non europeenne (p Conclusion Le revenu semble etre un facteur pronostique de la FPI, independant de l’âge, du sexe et de la severite de la maladie. Cet effet negatif pourrait etre lie a une exposition excessive aux polluants professionnels et/ou environnementaux chez les patients les plus defavorises. Des etudes futures utilisant une approche globale des facteurs socio-economiques, environnementaux et professionnels sont necessaires. Grants : (Legs Poix, no 637), PHRC (AOR 07076).

Introduction La dysfonction chronique du greffon (chronic lung allograft dysfunction [CLAD]), et particulierement le syndrome de bronchiolite obliterante, est le principal facteur impactant la survie a long terme. L’identification de marqueurs precoces de cette pathologie est aujourd’hui un enjeu majeur dans la prise en charge de ces patients. L’objectif de ce travail est de decrire le clinicome d’une cohorte strasbourgeoise de patients transplantes pulmonaires (cohorte MIBO) et d’identifier les facteurs de risques de dysfonction chronique du greffon a trois ans dans cette cohorte. Methodes La cohorte MIBO a ete constituee dans le cadre d’une monocentrique, prospective, analytique avec pour objectif final l’etude des microparticules membranaires dans le CLAD. Les patients inclus etaient representes par tout homme et femme âges de plus de 18 ans, sur liste d’attente de transplantation pulmonaire, suivis dans le pole de pathologie thoracique des hopitaux universitaires de Strasbourg (HUS). Les patients ont ete suivis dans le service de transplantation pulmonaire des HUS, permettant un recueil progressif des donnees cliniques, biologiques, bronchoscopiques et scanographiques. Resultats Cinquante-neuf patients ont ete inclus dans l’etude. A trois ans post-transplantation, 8 patients soit 13,8 %, presentaient un CLAD (4 BOS, 1 RAS, 3 mixte) d’apres les recommandations 2019 de l’ISHLT [1] . Une analyse descriptive detaillee a ete realisee. Une analyse comparative univariee entre les groupes avec et CLAD a egalement ete effectuee. Le temps d’ischemie maximal moyen etait significativement plus long chez les patients presentant un CLAD a 3 ans (425,5 minutes versus 358,7 minutes, p = 0,03). Le taux de CRP serique a 1 mois etait significativement plus bas dans le groupe avec CLAD ( Tableau 1 ). Conclusion Cinquante-neuf patients ont ete inclus dans la cohorte MIBO. Huit cas de CLAD ont ete identifies a 3 ans. Les groupes avec et sans CLAD ont ete compares. Le temps d’ischemie total et le taux de CRP a un mois etait significativement different entre les deux groupes. L’etude ulterieure des microparticules membranaire au sein de cette cohorte aura pour but d’identifier des marqueurs precoces de CLAD.

Objective To study patient survival and glycemic control before and after lung transplantation (LTx) according to the diabetes status in patients submitted to an organized management of diabetes mellitus (DM) at the Strasbourg University Hospital, France. Material and Methods Two hundred and sixty-seven LTx recipients were included retrospectively and analyzed according to diabetes status: pretransplant diabetes, new-onset diabetes mellitus after transplant (NODAT) or no diabetes. Organized DM management was coordinated by a diabetologist trained in DM management before and after transplantation and included pretransplant screening, a close monitoring of glycemia after transplant and optimized treatment before and after LTx. Results DM was well-controlled after transplantation: mean glycosylated hemoglobin and fasting blood glucose levels after LTx were 5.8 ± 0.2% and 5.4 ± 0.1 mmol/L respectively, in pretransplant DM patients and 5.7 ± 0.1% and 5.6 ± 0.2 mmol/L respectively, in NODAT patients. The overall median survival time was 8.3 ± 1.9 years. Pretransplant DM increased the risk of mortality (1.82-fold increase; 95% confidence interval, 1.08-3.06; P = .02) in LTx recipients. Conclusions Organized management of diabetes achieved very satisfactory glycemic control in both pretransplant DM and NODAT patients. However, no specific protocols have been created for managing DM following LTx. As DM continues to become an increasing comorbidity in LTx, there exist a significant need of studies in this area.

Introduction Les patients atteints d’une pneumopathie interstitielle diffuse associee a une mutation d’un gene regulateur du complexe telomerase (TRG) semblent presenter une moins bonne survie et des complications hematologiques plus frequentes apres transplantation pulmonaire (TxP). L’objectif de cette etude etait de determiner l’evolution apres TxP de ces patients dans une cohorte francaise. Methodes Tous les patients porteurs d’une mutation d’un TRG ayant eu une TxP en France entre 2009 et 2017 ont ete identifies par les centres de transplantation et le reseau francais OrphaLung. Resultats Vingt-sept patients ont ete inclus, dont 67 % etaient des hommes, avec des mutations de TERT (n = 17), TERC (n = 6), et RTEL1 (n = 4). Avant la greffe, 19 (70 %) presentaient une atteinte hematologique, dont 6 un syndrome myelodysplasique et 14 une hepatopathie. L’âge median lors de la TxP etait de 54 (± 9) ans. Apres la TxP, tous les patients presentaient une anemie, 74 % une thrombopenie, et 54 % une neutropenie. Quatre patients ont presente des complications hepatiques severes : une hemochromatose post transfusionnelle, une fibrose hepatique et deux patients une hypertension portale. 26 % ont presente une dysfonction chronique du greffon dans un delai median de 2,1 (± 1,3) ans. Quinze receveurs sont decedes (56 %) au cours du suivi. La mediane de survie apres la TP etait de 4,4 ans. La presence d’une myelodysplasie avant la TxP etait associee a une diminution de la survie (p Conclusion La survie apres TxP des patients porteurs d’une mutation d’un TRG est comparable a celle des patients sans mutation. Une TxP est possible apres un bilan exhaustif des comorbidites extra-respiratoires et une prise en charge post-greffe adaptee. La presence d’un syndrome myelodysplasique avant la greffe doit faire rediscuter le projet de greffe.

A 26-year-old man with a history of bilateral lung transplantation for pulmonary cystic fibrosis 6 months before was admitted in our institution for acute heart failure. Cardiac magnetic resonance imaging (CMR) showed an increased aortic output, as aortic flow assessed by velocity mapping was twofold the pulmonary flow, an occluded superior vena cava (SVC), and enlarged azygos vein. A systemic-to-pulmonary vein fistula (SAPVF) was suspected. The selective angiography showed numerous fistulae between intercostals, thyro-cervical, internal mammary arteries and pulmonary veins. The thoracic CT performed before the CMR, which was initially considered as normal, showed well these arteriovenous fistulae after 3D MIP reconstruction. This particular observation highlights the great value of multimodality imaging for the diagnosis of this rare pathology. The MR velocity mapping is a noninvasive imaging technique of great interest to guide the diagnosis of arteriovenous fistulae, and further indicating more invasive complementary imaging modalities like selective arterial angiography.

Herpes simplex virus (HSV) hepatitis is a rare and serious complication in immunocompromised patients. We report the case of an HSV hepatitis occurring 4 years after lung transplantation in a cystic fibrosis patient. The presentation was nonspecific, mimicking acute cholecystitis; orogenital signs were absent. The diagnosis was made based on viral cultures performed during cholecystectomy and confirmed by blood quantitative polymerase chain reaction. Although the diagnosis and treatment were delayed, the patient fully recovered with acyclovir, reduced immunosuppression, and intravenous immunoglobulins. The diagnostic difficulties, prognostic factors, and treatments of this infection are discussed.

International audience; BACKGROUND: Due to its multisystemic nature, scleroderma is considered a relative contraindication to lung transplantation at many centers. However, recent studies suggest similar post-transplant outcomes in patients with scleroderma compared to those with other causes of interstitial lung disease (ILD). Furthermore, it remains unknown whether scleroderma-associated pulmonary arterial hypertension (PAH) influences post-transplant outcomes. Our objective in this study was to assess the indications, survival, and prognostic factors of lung or heart lung transplantation for scleroderma lung disease. METHODS: We retrospectively reviewed the data of 90 patients with scleroderma who underwent lung or heart lung transplantation between 1993 and 2016 at 14 European centers. International criteria were used to diagnose scleroderma. Pulmonary hypertension (PH) was diagnosed during right heart catheterization based on international guidelines. RESULTS: Survival rates after 1, 3, and 5 years were 81%, 68%, and 61%, respectively. By univariate analysis, borderline-significant associations with poorer survival were found for female gender (hazard ratio 2.11; 95% confidence interval [CI] 0.99 to 4.50; p = 0.05) and PAH as the reason for transplantation (hazard ratio 1.90; 95% CI 0.96 to 3.92; p = 0.06). When both these factors were present in combination, the risk of death was 3-fold that in males without PAH. The clinical and histologic presentation resembled veno-occlusive disease in 75% of patients with PAH. CONCLUSIONS: Post-transplant survival rates and freedom from chronic lung allograft dysfunction in patients with scleroderma were similar to those in patients with other reasons for lung transplantation. Female sex and PAH in combination was associated with lower survival. (C) 2018 International Society for Heart and Lung Transplantation. All rights reserved.

Cystic lung light chain deposition disease (LCDD) is a severe and rare form of nonamyloid kappa light chain deposits localized in the lung, potentially leading to end-stage respiratory insufficiency.To assess the outcome after lung transplantation (LT) in this setting with particular attention to disease recurrence.We conducted a retrospective multicenter study of seven patients who underwent LT for cystic lung LCDD in France between September 1992 and June 2012 in five centers.In total, five females and two males (mean age, 39.1 ± 5.3 yr) underwent one single LT or seven double LT (one retransplantation). Before LT, the patients showed a constant obstructive ventilatory pattern with low carbon monoxide diffusing capacity and resting hypoxemia. Lung computed tomography revealed widespread cysts with occasional micronodulations. No extrapulmonary disease or plasma cell neoplasm was detected. The serum-free kappa/lambda light chain ratio was increased in three cases. The median follow-up after LT was 56 months (range, 1-110 mo). Kaplan-Meier survival was 85.7, 85.7, and 64.3% at 1, 3, and 5 years, respectively. Three patients died from multiorgan failure (n = 1), chronic rejection (n = 1), and breast cancer (n = 1) at 23 days, 56 months, and 96 months, respectively. At the end of follow-up, no patients showed recurrence on imaging or histopathology.This small case series confirms that cystic lung LCDD is a severe disease limited to the lung, affecting mostly young females. LT appears to be a good therapeutic option allowing for satisfactory long-term survival. We found no evidence of recurrence of the disease after LT.

Introduction Les mutations du complexe telomerase sont retrouvees chez environ 15 % des patients atteints de fibrose pulmonaire familiale et sont associees a des manifestations hepatiques, cutanees et hematologiques. La pirfenidone et le nintedanib permettent de ralentir le declin de la CVF et d’augmenter la survie des patients atteints de Fibrose Pulmonaire Idiopathique. Peu de donnees existent concernant l’efficacite et l’innocuite de ces traitements chez les patients porteurs d’une mutation du complexe telomerase. Methodes L’objectif de cette etude multicentrique retrospective, realisee dans le cadre du reseau OrphaLung des maladies pulmonaires rares, etait d’evaluer l’efficacite et la tolerance des traitements anti fibrosants chez des patients atteints de fibrose pulmonaire et porteurs d’une mutation du complexe telomerase. Resultats Nous avons identifie 109 patients dans 5 pays (Belgique, Espagne, France, Grece et Hollande) porteurs d’une mutation TERT (n = 82), TERC (n = 14), RTEL1 (n = 10) ou PARN (n = 3), Un diagnostic de FPI a ete pose chez 100 patients, 5 patients etaient atteints d’une PINS et 4 d’une Fibroelastose Pleuropulmonaire (PPFE). 44 patients ont recu du nintedanib, 39 de la pirfenidone et 26 ont recu les deux traitements de facon consecutive. L’âge moyen au diagnostic etait de 57,6 ± 13,6 ans. A l’initiation du traitement, la CVF moyenne etait de 80,8 % ± 20,2 % et la DLCO etait de 44,0 ± 13,7 %. La duree mediane de traitement etait de 354 jours [186,8–469,0]. Le traitement anti-fibrosant a ete arrete chez 18 patients pour progression de la maladie et chez 14 patients pour la survenue d’effets secondaires, principalement digestifs (nintedanib, n = 4 ; pirfenidone, n = 10). Le declin median de la CVF avant l’initiation du traitement etait de 24,0 mL[4,4–57,3] par mois. Apres initiation du traitement, le declin de la la CVF etait de 16,0 mL [4,4–48,7] par mois chez les patients traites par nintedanib et de 17,0 mL/mois [6,05 ; 39,7] chez les patients traites par pirfenidone. Conclusion Ces donnees retrospectives suggerent que les traitements anti-fibrosants sont bien toleres et ralentissent le declin de la CVF chez les patients atteints de fibrose pulmonaire et porteurs d’une mutation du complexe telomerase.

Introduction: Diabetes mellitus (DM) is a risk factor for mortality and morbidity after solid organ transplantation (kidney, liver). The objective of our study was to determine the effect of DM on survival and unscheduled hospitalizations after lung transplantation. Patients and methods: We included retrospectively 256 patients who received a single or double lung transplantation at Strasbourg University Hospital between 2004 and 2014. The indications for lung transplantation were: COPD (43,4%), cystic fibrosis (21,9%), and pulmonary fibrosis (19,2%). 80% were bilateral transplantations. We grouped the patients into 3 relevant categories of DM: pre- and post-transplant DM, new onset (>3 months) diabetes after transplantation (NODAT) and the control group of non-diabetic patients. Results: 78 patients had pre&post DM and 48 patients developed NODAT. Cystic fibrosis patients had the highest prevalence (50%) of pre&post DM and NODAT. We found a significant difference for unscheduled hospital stays between the 3 groups: the duration of hospital stays [mean±SD] was 86±121 days/year for pre&post DM patients, 50±67 days/year for NODAT, and 78±120 days/year for non-diabetic patients (p=0,032). We observed a worse survival after transplantation in pre&post DM compared to patients without pre-transplant DM (3-months median conditional survival: 6.3 ± 1.6 vs 8.8 ± 0.7 years, p = 0.016). There was no difference in survival for NODAT patients compared to non-diabetic patients (3 months conditional median survival: 10.5 ± 2 years versus 8.4 ± 1.6, NS). Conclusion: DM might have an impact on survival after lung transplantation. An organized and cooperative management of pre&post DM and NODAT seems warranted.

Background After lung transplantation, bronchial complications are one of the major concerns for surgeons and physicians. In the era of evolving immunosuppressive regimens and surgical approaches, we have reassessed risk factors for bronchial complications after lung transplantation. Methods We undertook a retrospective study of all consecutive lung transplantations performed at a single center from 2004 to 2014. We monitored the incidence of symptomatic bronchial complications. Demographic data of donors and recipients were also studied. Our objective was to evaluate the impact of 3 subsequent immunosuppressive regimens (including the use of induction therapy), and of a technical modification of bronchial anastomosis on the incidence of airway complications. Results We performed 270 consecutive lung transplantations during the study period. On multivariate analysis, bronchial complications were not directly associated with the different immunosuppressive regimens. In subgroup analysis, when comparing different immunosuppressive regimens, primary graft dysfunction within 72 hours (odds ratio [OR] = 2.55; p = 0.08), lung infection within the first month (OR = 2.96; p = 0.039), diabetes before transplantation (OR = 2.66; p = 0.11) and chronic obstructive pulmonary disease (OR = 2.20; p = 0.04) appeared as major risk factors (c-index = 0.77 on multivariate analysis). The use of a modified bronchial suture technique was associated with fewer bronchial complications (OR = 0.47; p = 0.059) (c-index = 0.71 on multivariate analysis). Conclusions The mode of immunosuppression had no influence on airway complications. We were able to reproduce the beneficial effect of a modified suture technique.