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International audience; We aimed to assess the clinical significance of Krebs von den Lungen-6 (KL-6) in the diagnosis and severity of interstitial lung disease (ILD) in a French cohort of patients with systemic sclerosis (SSc). Serum KL-6 concentrations were measured with chemiluminescent enzyme immunoassay (CLEIA) in 75 SSc patients. Patients were divided into two groups according to the presence of interstitial lung disease (SSc-ILD versus SSc-without ILD) on chest High-Resolution Computed Tomography. Pulmonary function tests, main manifestations and severity of the lung disease (Medsger's severity scale) were collected. KL-6 serum concentrations were significantly higher in SSc-ILD patients than in those without ILD (p < 10(-4)) and were inversely correlated with forced vital capacity, total lung capacity and diffuse lung capacity of carbon monoxide. Serum KL-6 level superior to 872 U/ml appeared as the optimal cut-off value associated with ILD. Patients with a restrictive pulmonary syndrome and dyspnoea had significant higher KL-6 serum concentrations. SSc patients with anti-topoisomerase 1 antibodies had higher KL-6 serum levels than patients with anti-centromere antibodies (p < 10(- 4)). ILD and anti-topoisomerase 1 antibodies were independent factors associated with KL-6 in multivariate analysis. Interestingly, KL-6 serum concentrations positively increased with the patient lung severity. Our study confirms that KL-6 is an accurate biomarker for the diagnosis of SSc-ILD in a French cohort of patients. High KL-6 levels should prompt physicians to assess ILD with pulmonary imaging and pulmonary functions tests. Prospective clinical studies are still required to determine whether levels of KL-6 might predict progression of ILD as well as its usefulness in the timing of therapeutic intervention.

Background: Allergic bronchopulmonary mycosis (ABPM) is an underestimated allergic disease due to fungi. Most reported cases are caused by Aspergillus fumigatus (Af) and are referred to as allergic bronchopulmonary aspergillosis (ABPA). The main risk factor of ABPA is a history of lung disease, such as cystic fibrosis, asthma, or chronic obstructive pulmonary disease. The main diagnostic criteria for ABPA rely on the evaluation of humoral IgE and IgG responses to Af extracts, although these cannot discriminate Af sensitization and ABPA. Moreover, fungi other than Af have been incriminated. Flow cytometric evaluation of functional responses of basophils and lymphocytes in the context of allergic diseases is gaining momentum. Objectives: We hypothesized that the detection of functional responses through basophil and lymphocyte activation tests might be useful for ABPM diagnosis. We present here the results of a pilot study comparing the performance of these cellular assays vs. usual diagnostic criteria in a cystic fibrosis (CF) cohort. Methods: Ex vivo basophil activation test (BAT) is a diagnostic tool highlighting an immediate hypersensitivity mechanism against an allergen, e.g., through CD63 upregulation as an indirect measure of degranulation. Lymphocyte stimulation test (LST) relies on the upregulation of activation markers, such as CD69, after incubation with allergen(s), to explain delayed hypersensitivity. These assays were performed with Af, Penicillium, and Alternaria extracts in 29 adult CF patients. Results: BAT responses of ABPA patients were higher than those of sensitized or control CF patients. The highest LST result was for a woman who developed ABPA 3 months after the tests, despite the absence of specific IgG and IgE to Af at the time of the initial investigation. Conclusion: We conclude that basophil and lymphocyte activation tests could enhance the diagnosis of allergic mycosis, compared to usual humoral markers. Further studies with larger cohorts and addressing both mold extracts and mold relevant molecules are needed in order to confirm and extend the application of this personalized medicine approach.

Lung transplantation (LTx) is a valid therapeutic option for selected patients with end-stage lung disease. HLA-E seems to play a major role in the immune response to different viral infections and to affect transplantation outcome, in Hematopoietic Stem Cell Transplantation, for example. Two nonsynonymous alleles, HLA-E⁎01:01 and HLA-E⁎01:03, have functional differences, involving relative peptide affinity, cell surface expression, and potential lytic activity of NK cells. The aim of this retrospective study was to determine the impact of these two alleles for LTx recipients on anti-HLA alloimmunization risk, overall survival, and chronic rejection (CLAD). HLA-E was genotyped in 119 recipients who underwent LTx from 1998 to 2010 in a single transplantation center. In univariate analysis, both HLA-E homozygous states were associated with impaired overall survival compared to heterozygous HLA-E alleles (p=0.01). In multivariate analysis, HLA-E⁎01:03 allele showed increased CLAD occurrence when compared to homozygous HLA-E⁎01:01 status (HR: 3.563 (CI 95%, 1.016–12),p=0.047). HLA-E allele did not affect pathogen infection or the production ofde novoDSA. This retrospective study shows an uninvestigated, deleterious association of HLA-E alleles with LTx and requires verification using a larger cohort.

International audience

Background: Heterozygous mutations in the SFTPA1 and SFTPA2 genes, encoding the surfactant protein SP-A1 and SP-A2 have been associated with rare forms of familial IIP and lung adenocarcinoma. We previously described 11 new heterozygous SFTPA1 and SFTPA2 variations in 13 unrelated patients including one newborn. The study aims to analyze the pathogenicity of those variations. Methods: We first analyzed the intrafamilial segregation of the identified variations with IIP and lung cancer. The production and the secretion of the mutant proteins were subsequently studied in HEK293T cells transiently expressing the SP-A proteins carrying the variations. Finally, SP-A expression was assessed on lung tissues of the patients. Results: In the studied families (38 adults, 3 children), the variations segregated with either IIP and/or lung cancer (37%) with an incomplete penetrance of the disease phenotype. The mean age at onset of the IIP was 45 years (0-68). Nine of the variations were located in the highly conserved carbohydrate recognition domain of the protein. In vitro, the mutant proteins were produced but their secretion was absent (n=9) or altered (n=2). The lung expression of SP-A studied in 3 unrelated patients showed an increased expression of SP-A in the cytoplasm of hypertrophic type 2 alveolar cells. Discussion and conclusion: The 11 identified SFTPA1 and SFTPA2 variations are pathogenic. They are associated with IIP and with an increased risk of lung cancer. They were identified mainly in adults but also in children. The pathophysiological consequences of their abnormal secretion/expression remain to be elucidated.

Background Chronic Lung Allograft Dysfunction (CLAD) is the main cause of morbidity and mortality after the first year following lung transplantation (LTx). Risk factors of CLAD have been extensively studied, but the association between gram-negative bacteria (GNB) bronchial colonization and the development of CLAD is controversial. The purpose of our study was to investigate the association between post-transplant recolonization with the same species or de-novo colonization with a new GNB species and CLAD. The same analysis was performed on a sub-group of patients at the strain level using Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry technique. Results Forty adult cystic fibrosis (CF) patients who underwent a first bilateral LTx in the University Hospital of Marseille, between January 2010 and December 2014, were included in the study. Patients with GNB de-novo colonization had a higher risk of developing CLAD (OR = 6.72, p = 0.04) and a lower rate of CLAD-free survival (p = 0.005) compared to patients with GNB recolonization. No conclusion could be drawn from the subgroup MALDI-TOF MS analysis at the strain level. Conclusion Post-LTx GNB airway recolonization seems to be a protective factor against CLAD, whereas de-novo colonization with a new species of GNB seems to be a risk factor for CLAD. Electronic supplementary material The online version of this article (10.1186/s12866-018-1231-7) contains supplementary material, which is available to authorized users.

International audience; We report 7 patients with interstitial lung disease seen at computed tomographic scan review. Coxiella burnetii infection was diagnosed in situ in 1 lung biopsy specimen. Q fever may be a cofactor of interstitial lung disease, especially in endemic areas.

International audience; Pulmonary and systemic antifungal immunity influences quality of life and survival of people with cystic fibrosis. Aspergillus fumigatus (Af) induces specific IgG and IgE. Mast cells respond to IgE, IgG and direct interactions with Af. Mast cells are the source of the protease tryptase. We aimed at evaluating serum baseline tryptase as a potential biomarker of the Af-host interaction in cystic fibrosis patients. Serum baseline tryptase, IgE and IgG directed to Af extract and Af molecular allergens were measured in 76 cystic fibrosis patients. The main findings were (i) lower levels of serum baseline tryptase in patients displaying specific IgE to Af (p < 0.0001) and (ii) an association between tryptase levels and IgE or IgG responses to Af and ribotoxin (Asp f 1). These findings suggest that serum baseline tryptase is influenced by Af-host interactions and thus might be a marker for mast cell regulation and pulmonary immune defenses. (C) 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Introduction La transplantation pulmonaire (TxP) est une therapeutique reconnue pour des patients selectionnes avec une insuffisance respiratoire a un stade terminal. Compte tenu des difficultes d’accessibilite a la TxP pour des candidats toujours plus nombreux et eu egard l’inadequation entre le nombre de donneurs et de receveurs, des mesures correctives furent prises. Les criteres de prelevabilite furent elargis, parmi lesquels l’âge limite des donneurs (D) au-dela de 65 ans. Les equipes ont ete confrontees a l’acceptation des greffons ayant une difference d’âge importante d’avec le receveur (R), avec un impact mal connu sur la fonctionnalite du greffon a moyen et long terme. La large cohorte nationale COLT offrait l’opportunite de repondre a cette question. Methodes Etude retrospective sur des R apres une TxP dans 9 des 11 centres francais entre 2009 et 2013, inclus dans la cohorte longitudinale multicentrique COLT. Etaient exclus les TxP en Super-Urgence (SU), les receveurs decedes dans les 3 ans post-TxP sans dysfonction chronique du greffon (CLAD) et les re-transplantations. Les patients etaient repartis en trois groupes selon la difference d’âge donneur-receveur (DA) definie par soustraction de l’âge du R a celle du D. Trois groupes ont ete constitues : groupe (DA 10) dans lequel le D etait plus âge que le R de plus de 10 ans ; groupe (DA − 10 ; + 10) soit un D dont l’âge correspondait a celui du R a ± 10 ans. Le critere de jugement principal etait la survenue de CLAD en fonction de la DA. Il etait determine dans un second temps si la DA participait a la survenue de complications post operatoire, de complications precoces et tardives a 1 an et 3 ans. Resultats 331 patients inclus : 117 dans le groupe (DA 10). L’âge median des R etait de 47 ans [30 ; 58] et celui des D etait de 45 ans [31 ; 56]. Une CLAD a 3 ans etait observee chez 30 % des patients du groupe (DA 10). Aucun impact de la DA sur la survenue de CLAD a 3 ans n’a ete retrouve (p = 0,28), ni sur son delai d’apparition (p = 0,33). La DA n’a pas ete retrouvee comme un facteur de risque de complications precoces ou tardives. Conclusion Notre etude sur une large cohorte retrospective de TxP sur 3 ans n’a pas montre d’impact negatif a court et long termes d’une DA de 10 ans entre D et R sur la fonctionnalite du greffon apres une TxP.

Interaction between lung microbiota and inflammation is closely related to the pathogenesis of COPD exacerbation http://ow.ly/Z1B7o

Background: The surfactant protein A (SP)-A is a collectin implicated in surfactant homeostasis, local alveolar immune response, and epithelial repair after lung injury. SP-A is encoded by the SFTPA1 and SFTPA2 genes. The aim of this study was to search for mutations in SFTPA1 and SFTPA2 in adult patients with ILD. Methods: All SFTPA1 and SFTPA2 exons and flanking intronic sequences were analyzed in a large prospective study population of 160 apparently unrelated ILD patients with no telomerase, SFTPC or ABCA3 mutations. Results: 86 patients were diagnosed with a familial form of ILD, of whom 20 presented an association with a familial lung cancer. 63 patients were Discussion and conclusion: Altered SP-A expression may contribute to ILD pathophysiology. Data reported herein indicate that patients with ILD and a personal or familial lung cancer, and/or

International audience; no abstract

Rationale: Solid organ transplant recipients, especially after lung transplantation, are at increased risk for Mycobacterium tuberculosis pulmonary tuberculosis due to lifelong immunosuppression. Patient concerns: A 41-year-old woman underwent a second bilateral lung transplantation that was complicated by fatal pulmonary tuberculosis. Diagnoses: Histological examination of a lung biopsy performed 6 weeks after retransplantation revealed a caseating granuloma and necrosis. Acid-fast bacilli were identified as rifampicin-susceptible M. tuberculosis by real-time polymerase chain reaction (PCR), confirmed by culture 2 weeks later. Interventions: Our investigation led us to highly suspect that the transplanted lungs were the source of M. tuberculosis transmission. Lessons: In order to optimize diagnosis and treatment for lung recipients with latent or active tuberculosis, regular assessment of lower respiratory samples for M. tuberculosis, particularly during the 12-month period posttransplant should be implemented. Regarding donor-derived transmission, screening donor grafts with latent tuberculosis by M. tuberculosis real-time PCR in lymphoid and adipose tissues is an option that should be considered.

International audience; The black Aspergillus group comprises A. niger and 18 other species, ă which are morphologically indistinguishable. Among this species subset, ă A. tubingensis, described in less than 30 human cases before 2014, is ă primarily isolated from ear, nose, and throat samples. Recently, ă matrix-assisted laser desorption/ionization time-of-flight mass ă spectrometry has emerged as a powerful technique to identify microbes in ă diagnostic settings. We applied thismethod to identify 1,720 filamentous ă fungi routinely isolated from clinical samples our laboratory over a ă two-year study period. Accordingly, we found 85 isolates of A. niger, 58 ă of A. tubingensis, and six other black Aspergillus (4 A. carbonarius and ă 2 A. japonicus). A. tubingensis was the fifth most frequent mold ă isolated in our mycology laboratory, primarily isolated from respiratory ă samples (40/58 isolates). In this study, we mainly aimed to describe the ă clinical pattern of Aspergillus tubingensis. ă We analyzed the clinical features of the patients in whom A. tubingensis ă had been isolated from 40 respiratory samples. Thirty patients suffered ă from cystic fibrosis, chronic obstructive pulmonary disease or other ă types of chronic respiratory failure. Strikingly, 20 patients were ă experiencing respiratory acute exacerbation at the time the sample was ă collected. Antifungal susceptibility testing of 36 A. tubingensis ă isolates showed lower amphotericin B MICs (P < 10(-4)) and higher ă itraconazole and voriconazole MICs (P < 10(-4) and P = .0331, ă respectively) compared with 36 A. niger isolates. Further studies are ă required to better establish the role that this fungus plays in human ă diseases, especially in the context of cystic fibrosis and chronic ă pulmonary diseases.

International audience; Lung transplantation (LTx) is a valid therapeutic option for selected ă patients with end-stage lung disease. HLA-E seems to play a major role ă in the immune response to different viral infections and to affect ă transplantation outcome, in Hematopoietic Stem Cell Transplantation, for ă example. Two nonsynonymous alleles, HLA-E*01:01 and HLA-E*01: 03, ă have functional differences, involving relative peptide affinity, cell ă surface expression, and potential lytic activity of NK cells. The aim of ă this retrospective study was to determine the impact of these two ă alleles for LTx recipients on anti-HLA alloimmunization risk, overall ă survival, and chronic rejection (CLAD). HLA-E was genotyped in 119 ă recipients who underwent LTx from 1998 to 2010 in a single ă transplantation center. In univariate analysis, both HLA-E homozygous ă states were associated with impaired overall survival compared to ă heterozygous HLA-E alleles (p = 0.01). In multivariate analysis, ă HLA-E*01:03 allele showed increased CLAD occurrence when compared to ă homozygous HLA-E*01:01 status (HR: 3.563 (CI 95%, 1.016-12), p = ă 0.047). HLA-E allele did not affect pathogen infection or the production ă of de novo DSA. This retrospective study shows an uninvestigated, ă deleterious association of HLA-E alleles with LTx and requires ă verification using a larger cohort.

Introduction En transplantation pulmonaire (TxP) dans le but de reduire les complications au niveau des anastomoses bronchiques (AB), les bronches souches issues du donneur sont coupees le plus courtes possibles, se limitant souvent a un ou deux anneaux cartilagineux, ce qui conduit a des AB tres proches de chaque carene secondaire. Si une complication anastomotique survient dans ce contexte, les protheses bronchiques droites ne sont pas toujours ideales et les protheses bronchiques bifurquees peuvent etre une meilleure option. Methodes Il s’agit d’une etude retrospective observationnelle monocentrique portant sur les patients ayant beneficie d’une TxP au CHU de Marseille entre juin 2010 et juin 2015. Tous les receveurs ayant eu une complication anastomotique necessitant la mise en place d’une prothese bronchique ont ete inclus. Une analyse en sous-groupe etait realisee chez les patients qui avaient beneficie de la mise en place d’une prothese bifurquee. Resultats Au total, 205 patients ont beneficie d’une TxP, ce qui represente 394 AB. Des complications anastomotiques ayant necessite la mise en place d’une endoprotheses sont survenues chez 16/205 patients (7,8 %), soit une baisse de 46,3 % par rapport a notre taux de complication anterieur. L’indication en premiere ou en deuxieme intention de prothese bifurquee etait retenue pour 10 patients. Leur taux de succes de mise en place etait de 90 %. Aucune migration de prothese bifurquee n’a ete notee. Le nombre moyen de complications etait de 0,37/patients/mois (0–3,84). Parmi les 9 patients porteurs d’une prothese bifurquee, 2 sont decedes avec leur prothese en place ; chez 5 des 7 autres (55,5 %), la prothese a pu etre retiree sans complication et sans recidive du probleme anastomotique avec un suivi moyen apres retrait de 751 jours (118–1443). Conclusion Depuis l’evolution des techniques chirurgicales d’AB dans notre centre de greffe, le taux de complications anastomotiques ayant necessite la mise en place de prothese bronchique a ete reduit de 46,3 %. Compte tenu du nouveau challenge anatomique, la mise en place de protheses bronchiques bifurquees siliconees pour traiter les complications anastomotiques est une technique faisable, efficace et bien toleree.

Stump dehiscence after pneumonectomy is a cause of morbidity and mortality in patients treated for non-small-cell lung carcinoma. Surgical repair remains the treatment of choice but can be postponed or contraindicated. Bronchoscopic techniques may be an option with curative intent or as a bridge towards definitive surgery. The aim of the study is to evaluate the efficacy and the outcome of a new customised covered conical self-expandable metallic stent in the management of large bronchopleural fistulas complicating pneumonectomies.A case series using chart review of non-operable patients presenting with large bronchopleural fistulas (6mm) post-pneumonectomies as a definitive treatment with curative intent for non-small-cell lung carcinomas and requiring the use of a dedicated conical shaped stent in two tertiary referral centres.Seven patients presenting large post-pneumonectomy fistulas (between 6 and 12 mm) were included. Cessation of the air leak and clinical improvement was achieved in all the patients after stent placement. Stent-related complications (two migrations and one stent rupture) were successfully managed using bronchoscopic techniques in two patients and surgery in one. Mortality, mainly related to overwhelming sepsis, was 57%. Delayed definitive surgery was achieved successfully in three patients (43%).This case series assesses the short-term clinical efficacy of a new customised covered conical self-expandable metallic stent in the multidisciplinary management of large bronchopleural fistulas complicating pneumonectomies in patients deemed non-operable. Long-term benefits are jeopardised by infectious complications.

We studied the role of chronic exposure to ambiant air pollution on lung function level and evolution in lung transplant patients. The lung function of 525 lung transplant (LT) patients from the COLT cohort was followed-up. The 12-month average levels of air pollutants (Nitrogen dioxide (NO 2 ), fine particulate matters (PM 2.5 , PM 10 ) and ozone (O 3 )) were estimated at the home addresses of each patient. The effect of air pollutant exposure on FEV 1 level and change in FEV 1 both during the recovery and decline periodes were estimated using mixed linear regression models adjusted on recipient age, sex, smoking (donor and patient), body mass index, donor age, type of LT, underlying disease, sex and HLA mismatch, ischemia time, anti-HLA antibodies, Pseudomonas colonization, CMV infections, immunosuppression induction and acute rejection. The population included 54% of men and 81% of double LT (mean age 43yrs). The main underlying diseases were cystic fibrosis (40%), emphysema/COPD (34%) and pulmonary arterial hypertension (14%). Mean (sd) individual exposure levels were 15.2 (2.1), 22.1 (3.1), 18.1 (7.3) and 51.7 (8.2) µg/m 3 for PM 2.5 , PM 10 , NO 2 and O 3 , respectively. NO 2 exposure was significantly associated with lower FEV 1 levels measured during the recovery period and a non-significant trend was observed in the decline period (estimate (se) = -3.39(1.48) p=0.02 and -1.96(1.47) p=0.18). None of the air pollutants exposure was associated with change in FEV 1 . Our results suggest a potential deleterious effect of chronic exposure to NO 2 on FEV 1 level following LT and did not evidence an effect of air pollution on change in FEV 1 . Fundings: EU-FP7 SYSCLAD, Vaincre la Mucoviscidose, Association Gregory Lemarchal.

Introduction: Medium-term survival and functional outcome of patients requiring prolonged mechanical ventilation (PMV) ≥ 21 days after lung transplantation (LTx) remain unclear. Objectives and Methods: We conducted a post hoc analysis on a cohort of 82 adults patients who underwent consecutively LTx at the University Hospital of Marseille from January 2008 to May 2011 and who survived above 21 days postoperative. The main objectives were 1/to identify risk factors of VMP by univariate and multivariate analysis; 2/ to evaluate the impact of VMP on survival and functional outcome at 3 years after LTx. Results: 34 recipients required a PMV and 48 recipients did not (control group). Median duration follow-up was 1428 ± 847 days. Multivariate analysis identified graft volume reduction as the main independent risk factor for PMV (OR: 14.61, 95%CI: 1.35-157, p=0.02). Significant decrease in survival at 1, 2 and 3 years was observed in PVM group compared to controls (73.5%, 61.2%, 51% vs . 85.4%, 82.5%, 77.9%). Lung function was significantly impaired in PMV recipients compared to controls at 1 yr and 3 yrs with lower values of FEV1 (1681 ± 919ml and 1759 ± 250 ml vs. 2625 ± 1132 ml and 2626 ± 186 ml, p vs. 3450 ± 1176 ml and 3425 ± 188 ml, p vs. 555 ± 114 m and 564 ± 21 m) respectively. However no significant difference in the development of chronic allograft dysfunction at 3 yrs was observed between the 2 groups. Conclusion: Graft volume reduction was the main predictive factor of PMV. PMV limited recipient9 survival and lung functional outcome at medium-term after LTx.

Lung transplantation (LTx) is a valid therapeutic option for selected patients with end-stage lung disease. Soluble HLA-G (sHLA-G) has been associated with increased graft survival and decreased rejection episodes in solid organ transplantation. HLA-G haplotypes named UTRs, defined by SNPs from both the 5′URR and 3′UTR, have been reported to reliably predict sHLA-G level. The aim of this retrospective study was to determine the impact of HLA-G alleles and UTR polymorphism from LTx recipients on anti-HLA allo-immunization risk, overall survival and chronic rejection (CLAD). HLA-G SNPs were genotyped in 124 recipients who underwent LTx from 1996 to 2010 in Marseille, 123 healthy individuals and 26 cystic fibrosis patients not requiring LTx. sHLA-G levels were measured for 38 LTx patients at D0, M3 and M12 and for 123 healthy donors. HLA-G*01:06∼UTR2 was associated with a worse evolution of cystic fibrosis (p = 0.005) but not of long-term survival post-LTx. HLA-G*01:04∼UTR3 haplotype was associated with lower levels of sHLA-G at D0 and M3 (p = 0.03), impaired long-term survival (p = 0.001), increased CLAD occurrence (p = 0.03) and the production of de novo donor-specific antibodies (DSA) at M3 (p = 0.01). This study is the first to show the deleterious association of different HLA-G alleles and UTRs in LTx.

Introduction Les patients candidats a une transplantation pulmonaire (TxP) peuvent presenter une dysfonction musculaire respiratoire (DMR), peu de donnees sont disponibles. L’objectif etait : – tester la faisabilite en routine des mesures non invasives de force des muscles respiratoires (FMR) ; – evaluer le lien potentiel entre DMR et difficultes de sevrage ventilatoire postoperatoire ( Tableau 1 ). Methodes Etude monocentrique prospective de mesures des pressions inspiratoires et expiratoires maximales a la bouche (PImax, PEmax), nasales (SNIP) (MicroRPM CareFusion®), chute de la CV en decubitus, EFR standard. Analyses statistiques : logiciel libre. Resultats Du 1/04 au 1/09 2015, 24 patients en attente de TxP ont effectue l’ensemble des tests ( Tableau 1 ). Sept (5 BPCO, 1 fibrose, 1 HTAP) avaient une DMR d’apres les SNIP et les PImax. Une analyse multifactorielle en composantes principales a identifie six composantes qui decrivent la variance V de l’ensemble des donnees recueillies : – potentiel a mobiliser des volumes (32 % de V) ; – mobilisation volumique reelle (24 %) ; – potentiel musculaire respiratoire global (16 %) ; – morphometrie (7 %) ; – âge (7 %) ; – potentiel fonctionnel diaphragmatique (4 %). Les SNIP sont correlees a la 1re (R2 =R2 0,73) et 6 eme (R2 = 0,54) dimensions. Sept sur 24 patients explores ont ete greffes durant l’etude dont 3 avaient une DMR ; 1 a eu un echec de sevrage ventilatoire non explique (22 jours de ventilation), sa SNIP preoperatoire etait a −34R2 cmH2O (40 % de la normale). Conclusion Les patients dyspneiques et oxygeno-requerant en attente de greffe sont capables de realiser des tests de FMR. Independamment des criteres fonctionnels et anthropometriques habituels, ces tests apportent une information complementaire significative. La SNIP semble le test le plus informatif. Une evaluation preoperatoire systematique pourrait identifier les patients a risque de difficulte de sevrage ventilatoire apres TxP. Remerciements A l’œuvre antituberculeuse pour leur contribution.

Introduction Peu de donnees sont disponibles sur l’influence de l’immunosuppression (IS) sur la cinetique de reconstitution des differentes sous-populations lymphocytaires du sang peripherique (SPLP) apres transplantation pulmonaire (TxP) et son impact sur le pronostic de l’allogreffe. Methodes Il s’agit d’une etude retrospective portant sur les patients ayant eu consecutivement une TxP au CHU de Marseille (France), entre decembre 2011 et juillet 2013, avec un suivi minimal d’un an apres la TxP. Les SPLP ont ete analysees par cytometrie en flux et evaluees en fonction des caracteristiques des receveurs (âge, sexe et pathologie) et du pronostic a court terme de l’allogreffe (infection et rejet). Resultats Cinquante-sept receveurs ont ete inclus et 1083 SPLP ont pu etre analysees. Sous l’influence du traitement d’induction (globulines anti-thymocytaires polyclonales de j1 a j3), le taux des lymphocytes (L) totaux, des LT (CD4+ et CD8+) et des cellules NK s’effondrent de j3 a j30 apres TP. Passee cette phase initiale, les LT et les NK remontent partiellement pour atteindre un plateau a partir de j200. Sous l’effet de l’IS de maintenance (axe sur les anticalcineurines), les LB chutent plus lentement et atteignent leur plus bas niveau a partir de j200, pour ensuite se stabiliser. Dans la 1 re annee post-TP, une lymphopenie T est plus marquee chez les receveurs (R) > 40 ans ( p Fig. 1 : moyennes ± IC des SPLP en fonction du temps. Courbes grises = R 40 ans. Abscisse = delai post-TxP (jours). Ordonnee = cell/mm 3 ). Cette lymphopenie T est associee a une incidence plus elevee de reactivation du CMV dans ce groupe ( p = 0,008), sans difference significative sur la survenue de rejet aigu dans le 1 re annee. Conclusion Les R > 40 ans ont une lymphopenie T precoce plus marquee avec une incidence plus elevee de reactivation du CMV. Cet element, qui rend compte d’une probable sensibilite accrue au traitement d’induction, suggere l’interet d’optimiser l’IS initiale chez les receveurs les plus âges.

Diffuse interstitial lung disease (DILD) is a heterogeneous group of lung disorders characterised histologically by diffuse inflammation and fibrosis affecting predominantly, but not exclusively, the pulmonary interstitium. Fundamental points for diagnosis: Previously identified DILD: eliminate pulmonary infection (intracellular and opportunistic pathogens, viruses), pulmonary embolus, pneumothorax, cardiogenic involvement, drug-associated toxicity and carcinomatous lymphangitis before concluding that it is an exacerbation of pulmonary fibrosis. The key examinations are high-definition (HD)-thoracic TDM, bronchoalveolar lavage (BAL), microbiological specimens and echocardiography. In the case of previous severe restrictive respiratory failure, the prognosis is extremely poor.

International audience; Pandoraea are considered emerging multidrug resistant pathogens in the context of cystic fibrosis. We report herein for the first time the case of a 30-year-old woman with cystic fibrosis, living in France, who was chronically infected with Pandoraea pulmonicola and who died of Pseudomonas aeruginosa sepsis 3 weeks after bilateral lung transplantation.

Background Cystic fibrosis (CF) lung microbiota consists of diverse species which are pathogens or opportunists or have unknown pathogenicity. Here we report the full characterization of a recently described multidrug resistant bacterium, Microbacterium yannicii, isolated from a CF patient who previously underwent lung transplantation. Results Our strain PS01 (CSUR-P191) is an aerobic, rod shaped, non-motile, yellow pigmented, gram positive, oxidase negative and catalase positive bacterial isolate. Full length 16S rRNA gene sequence showed 98.8% similarity with Microbacterium yannicii G72T type strain, which was previously isolated from Arabidopsis thaliana. The genome size is 3.95Mb, with an average G+C content of 69.5%. In silico DNA-DNA hybridization analysis between our Microbacterium yannicii PS01isolate in comparison with Microbacterium testaceum StLB037 and Microbacterium laevaniformans OR221 genomes revealed very weak relationship with only 28% and 25% genome coverage, respectively. Our strain, as compared to the type strain, was resistant to erythromycin because of the presence of a new erm 43 gene encoding a 23S rRNA N-6-methyltransferase in its genome which was not detected in the reference strain. Interestingly, our patient received azithromycin 250 mg daily for bronchiolitis obliterans syndrome for more than one year before the isolation of this bacterium. Conclusions Although significance of isolating this bacterium remains uncertain in terms of clinical evolution, this bacterium could be considered as an opportunistic human pathogen as previously reported for other species in this genus, especially in immunocompromised patients.

International audience; The epidemiology and the clinical implication of human parvovirus 4 (PARV4) in human populations is still under evaluation. The distribution of PARV4 DNA was determined in cohorts of French haemodialysis and lung transplant patients. Plasma samples (n=289) were tested for PARV4 by real-time PCR assay (ORF2), and amplification products selected at random were sequenced. Analysis of available serological and biological markers was also undertaken. Fifty-seven samples out of 185 (30.8%) were positive for PARV4 DNA in the cohort of haemodialysis patients. A higher prevalence of the virus was identified in individuals with markers of HBV infection. PARV4 was also identified in 14 out of 104 samples (13.5%) from lung transplant recipients, with no clear-cut association with available clinical markers. Point mutations located on the zone of real-time detection were identified for some amplification products. This study describes the detection of PARV4 in the blood of haemodialysis and lung transplanted patients with significant difference in prevalence in these two cohorts. Further studies will be needed in order to understand better both the potential implication in host health and the natural history of this virus.

Introduction La detection des variations spirometriques constitue l’element essentiel de la surveillance apres une TP. Le depistage et la prise en charge precoce des complications respiratoires pourraient ameliorer la fonctionnalite ulterieure du greffon et la survie du receveur. L’emploi de la teletransmission via Internet des mesures realisees par un spirometre electronique portable (Spirotel ® ) a domicile pourrait y participer. Objectifs Evaluer (1) impact des anomalies teletransmises ; (2) concordance avec le controle spirometrique a l’hopital ; (3) observance du patient au Spirotel ® . Methode et resultats Etude prospective observationnelle monocentrique portant sur 59 adultes ayant eu une TP au CHU de Marseille suivis par Spirotel ® quotidien a domicile entre 09/2013 et 06/2014. Un total de 285 visites ont ete realisees dont 34 etaient non programmees, liees a des anomalies cliniques seules (7) et du Spirotel ® (27). La correlation avec les valeurs controles etait satisfaisante avec un biais moyen du VEMS de +117 ml ( p ® avait une sensibilite de 65 % et une specificite de 84 % dans le depistage de complications averees. L’observance a la spirometrie et a la teletransmission etait respectivement de 48 % et 54 % pour la 1 re annee, et 36 % et 46 % a partir de la 2 e annee apres TP. Conclusion Notre etude rend compte de la faisabilite de la telesurveillance en ambulatoire et de son interet dans le depistage precoce des complications de l’allogreffe. Des etudes complementaires pourront permettre d’affiner les modalites de suivi apres TP apres optimisation de l’observance du patient a la tele-medecine.

Purpose Prolonged mechanical ventilation (PMV) and consequently longer ICU stays after lung transplantation (LTx), are serious complications but prognosis at medium and long term are not yet know. Our objectives were to identify patients requiring > 21 days of MV after the operation and the predictive factors of PMV, and to evaluate the impact of VMP on survival and functional outcomes at one post-transplant. Methods and Materials Observational retrospective analysis of data relating to 82 consecutive lung transplantation performed at the University Hospital of Marseille from January 2008 to May 2011, for which recipient’ survival was over 21 days. Donors’ and patients’ preoperative, intra operative and postoperative data were recorded. Results 34 recipients met our criteria of PMV and 48 patients did not met them (control group). None factor related to the characteristics of the donor and the recipient at the presurgical evaluation was predictive of PMV. Multivariable regression analysis retained the risk of lung volume reduction (OR 11.874, 95% CI: 1,16-121, 44, p = 0.04), and use of postoperative ECMO within 48 hours (OR 6695, 95% CI: 1,46-30, 75, p = 0.015). By freeing from context, only lung volume reduction stayed a predictive factor of PMV. A significant decrease in survival at 1, 2 and 3 years was observed in PMV patients compared to controls (73.5%, 61.2%, 51% vs. 85.4%, 82.5%, 77.9 %). Compared to controls, in patients who required PMV, lung function at 1 year was significantly impaired with a lowest value of FEV 1 (1681 ± 919 ml vs . 2625 ± 1132 ml, p = 0.001), FVC (2288 ± 1076 ml vs 3450 ± 1176 ml, p = 0.001), LTC (2288 ± 1076ml vs 3450 ± 1176 ml, p: 0.000). and PaO 2 (75.4 ± 10.4 mmHg vs. 85.7 ± 9.5 mmHg, p = 0.001). Conclusions Lung volume reduction appears to be a predictive factor for PMV after LTx. Patients who required PMV have a significantly decreased survival and a poorer lung function than controls at 1 year post-transplant.

International audience; no abstract

International audience

Background Mycobacterium lentiflavum is rarely isolated in respiratory tract samples from cystic fibrosis patients. We herein describe an unusually high prevalence of M. lentiflavum in such patients. Methods M. lentiflavum, isolated from the respiratory tract of cystic fibrosis patients, was identified using both rpoB partial sequencing and detected directly in the sputum by using real-time PCR targeting the smpB gene. Results M. lentiflavum emerged as the third most prevalent nontuberculous mycobacterial species isolated in cystic fibrosis patients in Marseille, France. Six such patients were all male, and two of them may have fulfilled the American Thoracic Society clinical and microbiological criteria for M. lentiflavum potential lung infection. Conclusions M. lentiflavum was the third most common mycobacteria isolated in cystic fibrosis patients, particularly in six male patients. M. lentiflavum outbreaks are emerging particularly in cystic fibrosis patients. Electronic supplementary material The online version of this article (doi:10.1186/s12890-015-0123-y) contains supplementary material, which is available to authorized users.

We report here the first case of a carbapenem-resistant Pseudomonas aeruginosa clinical isolate harboring the insertion sequence (IS) element ISPa1328 in the oprD gene in an idiopathic pulmonary fibrosis patient in France previously treated with imipenem.