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International audience; Lung transplantation (LTx) is the last-resort treatment for end-stage respiratory insufficiency, whatever its origin, and represents a steadily expanding field of endeavor. Major developments have been impelled over the years by painstaking efforts at LTx centers to improve donor and recipient selection, and multifaceted attempts have been made to meet the challenges raised by surgical management, perioperative care, and long-term medical complications. The number of procedures has increased, leading to improved post-LTx prognosis. One consequence of these multiple developments has been a pruning away of contraindications over time, which has, in some ways, complicated the patient selection process. With these considerations in mind, the Francophone Pulmonology Society (Société de Pneumology de Langue Française [SPLF]) has 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 has examined the most recent literature and evaluated the risk factors that continue to limit patient survival after LTx. Ideally, the objectives of LTx are to prolong life while 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.; La transplantation pulmonaire (TxP) constitue le traitement ultime de l’insuffisance respiratoire terminale quelle qu’en soit l’origine et voit son activité en permanente expansion. Le travail minutieux des centres de TxP portant sur la sélection des donneurs et des receveurs d’un greffon pulmonaire ainsi que de l’ensemble des efforts fournis pour relever les défis de la prise en charge chirurgicale, péri-opératoire et la gestion des complications médicales de la TxP à plus long terme ont permis une augmentation du nombre de procédures et l’amélioration du pronostic post-TxP. Les membres du groupe de travail de la Société de pneumologie de langue française (SPLF) ont réalisé une mise à jour des données connues de la littérature et analysé les facteurs de risque qui limitent les chances de survie après la TxP. L’objectif de ce travail a été de guider les pneumologues dans leur prise en charge de l’insuffisance respiratoire terminale, de les aider à identifier les patients potentiellement éligibles à la TxP et de déterminer selon quels délais les adresser à centre de TxP. Les objectifs de la TxP demeurent l’allongement de la vie et l’amélioration de la qualité de vie des malades. Les propositions faites dans ce document portent sur une ressource limitée et restent guidées par des principes éthiques décrits plus loin.

Sarcoidosis is a systemic granulomatous disease that can reduce life expectancy mainly due to pulmonary fibrosis resulting from granulomatous inflammation The lack of vascularization within pulmonary granulomas suggests that macrophages localized in the center of these structures are hypoxic. Hypoxia signaling pathways are known to be pro-inflammatory and pro-fibrotic in various pathological conditions. Recent data suggest an involvement of the transcription factor hypoxia-inducible factor (HIF) in the pathogenesis of sarcoidosis. This could represent a new research approach for the understanding and therapeutic management of sarcoidosis.

Few studies have examined the effects of air pollution in diffuse interstitial lung disease and they have focused on small numbers of patients. Most data are available in idiopathic pulmonary fibrosis and studies suggest that the level of exposure to pollutants may influence the development of acute exacerbations (ozone and NO

The epidemiology of chronic beryllium disease (CBD) in France is poorly understood. The aim of this study was to determine the number of prevalent cases of CBD in France between 2010 and 2014.We conducted a national survey using a specific questionnaire distributed by the professional pathology services.In total, 33 CBD cases were reported in France, with a diagnosis established between 1982 and 2014. 85% (28/33) of CBD cases resulted from professional exposure and mostly concerned foundry workers (39%). A definite diagnosis defined by the association of an abnormal beryllium lymphocyte proliferation test and of a granulomatous inflammatory response in the lung, was obtained in 29/33 cases (88%). The other cases were probable CBD, defined by a granulomatous lung disease with a beryllium exposure, but without evidence of beryllium sensitisation. The diagnosis of granulomatous disease was confirmed a mean of 4 years after the end of exposure. The median delay between diagnosis of a granulomatous disease and diagnosis of CBD was 2 years (range 0-38 years). A genetic predisposition was found in 14 of 17 tested patients (82%).In this study, we report 33 cases of CBD followed in France between 2010 and 2014. The poor understanding of CBD and the exposure leading to it, the late development after the end of exposure, the complexity of the diagnosis and the similarities with sarcoidosis may explain the small number of cases reported.

Background:Methotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Its use has been associated with hypersensitivity pneumonitis and diffuse lung disease. Whether MTX exposure increases the risk of interstitial lung disease (ILD) in patients with RA is disputed.Objectives:We aimed to evaluate the association of antecedent MTX use with development of RA-ILD.Methods:Through a case-control study design with derivation and international validation samples, we examined the association of MTX exposure with ILD in 482 patients with RA-ILD and 741 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques.Results:Analysis of the derivation sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted odds ratio [OR], 0.48; 95% confidence interval [CI], 0.25 to 0.92; P=0.028), which was confirmed in the validation samples (pooled adjusted OR, 0.39; 95% CI, 0.23 to 0.68; PConclusion:Our results suggest that MTX is not a risk factor for RA-ILD and support a possible disease modifying effect of MTX on development of RA-ILD.Disclosure of Interests:Pierre-Antoine Juge: None declared, Joyce S. Lee Consultant of: Celgene, Genentech, Boehringer Ingelheim, Jessica Lau: None declared, Leticia Kawano: None declared, Jorge Rojas-Serrano: None declared, Marco Sebastiani: None declared, Gouri Koduri: None declared, Eric Matteson Grant/research support from: Pfizer, Consultant of: Boehringer Ingelheim, Gilead, TympoBio, Arena Pharmaceuticals, Speakers bureau: Simply Speaking, Karina Bonfiglioli Consultant of: Roche, Abbvie, Pfizer, Janssen and BMS, Marcio Sawamura: None declared, Ronaldo Kairalla: None declared, Lorenzo Cavagna: None declared, Emanuele Bozzalla Cassione: None declared, Andreina Manfredi: None declared, Mayra Mejia: None declared, Pedro Rodríguez Henríquez: None declared, Montserrat I. Gonzalez-Perez: None declared, Ramcés Falfan-Valencia: None declared, Ivette Buendia-Roldan: None declared, Glora Perez-Rubio: None declared, Esther Ebstein Consultant of: BMS, Employee of: BMS, Steven Gazal: None declared, Raphael Borie Consultant of: Roche, Boehringer Ingelheim, Sebastien Ottaviani: None declared, Caroline Kannengiesser: None declared, Benoît Wallaert Consultant of: Roche, Boehringer Ingelheim, Yurdagul Uzunhan Consultant of: Roche, Boehringer Ingelheim,, Hilario Nunes: None declared, Dominique Valeyre Consultant of: Astra Zeneca, Roche, Boehringer Ingelheim, Nathalie Saidenberg Kermanac’h: None declared, marie-Christophe Boissier: None declared, Lidwine Wemeau Stervinou Consultant of: Roche, Janssen, BMS, Boehringer Ingelheim, Rene-Marc Flipo Speakers bureau: Novartis, Janssen, Lilly, Sylvain Marchand-Adam Consultant of: Roche, Novartis, Boehringer Ingelheim, Pascal Richette: None declared, Yannick Allanore Shareholder of: Sanofi, Roche, Consultant of: Actelion, Bayer, BMS, Boehringer Ingelheim, Inventiva, Sanofi, Claire Dromer: None declared, Marie-Elise Truchetet: None declared, Christophe Richez Consultant of: Abbvie, Amgen, Mylan, Pfizer, Sandoz and UCB., Thierry Schaeverbeke: None declared, Huguette Lioté: None declared, Gabriel Thabut Employee of: Astra Zeneca, Kevin Deane Grant/research support from: Janssen, Consultant of: Inova, ThermoFisher, Janseen, BMS and Microdrop, Joshua Solomon: None declared, Tracy Doyle: None declared, Jay H. Ryu: None declared, Ivan O. Rosas Consultant of: Boehringer Ingelheim, Gerentech, Three Lakes Partners, V. Michael Holers Grant/research support from: Janssen, Celgene, and BMS, Catherine Boileau: None declared, Marie-Pierre Debray: None declared, Raphaël Porcher: None declared, David A. Schwartz Consultant of: NuMedii, Robert Vassallo Shareholder of: Pfizer, BMS, SunPharma, Bruno Crestani Shareholder of: Apellis, Boehringer Inghelheim, Medillune, Roche, Consultant of: Boehringer Ingelhiem, Astra Zeneca, Roche, Sanofi, Philippe Dieudé: None declared

Introduction La sarcoidose est une pathologie inflammatoire systemique frequente. Dix a 30 % de ses patients vont developper une fibrose pulmonaire, ou une hypertension pulmonaire aboutissant au deces pour 5 % d’entre eux. Le dernier recours reste alors la transplantation pulmonaire. Il n’existe pas a ce jour de critere d’inscription en transplantation specifique de cette maladie. Les patients greffes pulmonaire pour sarcoidose semblent avoir une survie similaire aux autres indications de transplantation pulmonaire. Notre etude a pour objectif de definir le phenotype des patients atteints de sarcoidose les conduisant a la transplantation pulmonaire, evaluer la survie de ses patients et identifier des facteurs pronostics dans cette population. Methodes Il s’agit d’une etude de cohorte observationnelle, retrospective. Elle inclue les patients transplantes pulmonaire pour sarcoidose dans 17 centres de transplantation pulmonaire europeens, sur une periode allant du 01/01/1990 a 01/07/19. Le diagnostic de sarcoidose est affirme par des donnees cliniques radiologiques et une preuve histologique sur l’explant pulmonaire. Le recueil de donnee est effectue a partir des dossiers medicaux de maniere retrospective. Nous recueillons les donnees des TDM thoraciques pre-greffe avec une relecture a l’aide d’une grille de lecture standardisee. Resultats Au total, 123 patients sont inclus dans l’etude le 08/09/19. Soixante-trois patients presentaient une HTAP severe au moment du bilan pre-greffe et 60 n’en presentaient pas. S’il n’y avait pas de difference significative en termes de survie entre ses deux groupes. Une dysfonction primaire du greffon survenait chez 23(21 %) d’entre eux. Une recidive de sarcoidose sur le greffon prouvee histologiquement etait observe chez 9(10 %) des patients, le CLAD etait observe chez 39(33 %) d’entre eux au cours du suivi. Le taux de survie de la population generale est de 79 % et 55 % a 1 et 5 ans respectivement ( Fig. 1 ). La survie etait significativement meilleure pour les patients presentant pour les sujets de moins de 50 ans (p = 0,01), en l’absence de mismatch CMV (p Fig. 1 ). Conclusion Il s’agit de la plus importante cohorte de transplantes pour sarcoidose. La survie de cette population est similaire a d’autres indications de transplantation pulmonaire comme la fibrose pulmonaire idiopathique. Des analyses complementaires sont en cours pour definir des facteurs de risque de mortalite.

Resume Les comorbidites au cours de la fibrose pulmonaire idiopathique (FPI) sont nombreuses. Elles peuvent etre respiratoires ou extra-respiratoires. On retrouve le syndrome fibrose-emphyseme, qui peut se compliquer d’hypertension pulmonaire ou de cancer broncho-pulmonaire. Le cancer broncho-pulmonaire a une incidence pouvant aller jusqu’a 48 % dans une population de FPI, il s’agit generalement des carcinomes epidermoides, et le traitement ne peut etre envisage que dans une minorite de cas. Le syndrome d’apnee obstructive du sommeil est frequent, et doit etre systematiquement recherche chez tout patient presentant une FPI. Les facteurs de risque cardio-vasculaires ont une incidence plus elevee dans cette population, notamment l’hypertension arterielle et le surpoids. La connaissance de ces comorbidites et leur controle permet de reduite la mortalite et d’ameliorer la qualite de vie de ces patients.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure designed to explore mediastinal lymphadenopathy. Its use and indications have increased recently and severe, though rare, complications have been reported.EBUS-TBNA was performed in a 64-year-old patient presenting with mediastinal lymphadenopathy, probably due to sarcoidosis, but without histological proof. Within hours of the aspiration of subcarinal lymph nodes (station 7), the patient developed fever and dry cough associated with progressive dysphagia and dysphonia that persisted for four weeks. Mediastinitis was diagnosed after a CT-scan revealed a collection in the subcarinal space previously tapped using CT guidance. Intravenous antibiotics were started and both symptoms and the mediastinal collection resolved without need of a surgical procedure. The patient recovered fully.EBUS-TBNA is associated with a risk of mediastinitis that may manifest as an isolated fever arising within hours of the procedure. The pathogens responsible are usually contaminants from the oropharynx such as Streptococcus sp, probably inoculated directly into the mediastinum during transbronchial needle aspiration. Rapid diagnosis and treatment are necessary in order to reduce morbidity and mortality associated with mediastinitis.

Sarcoidosis is a granulomatous disease of unknown cause. This proteiform disease is characterized by an almost constant and often predominant lung involvement. The natural history of disease is difficult to predict at presentation. Diagnosis is based on a compatible clinical and radiological presentation and evidence of non-caseating granulomas. Exclusion of alternative diseases is also required according to clinical presentation. Biopsy samples of superficial lesions should be considered before other sites like per-endoscopic bronchial biopsies or endobronchial ultrasound-guided transbronchial needle aspiration. Therapeutic strategy for lung disease has to take into account the possible spontaneous resolution observed in newly diagnosed patients. Corticosteroids are the first choice when a treatment is decided, which concerns half of patients. Second and third line therapy are based respectively on immunosuppressive drugs and anti-TNFα drugs. Sarcoidosis mortality and morbidity are mainly linked to advanced pulmonary sarcoidosis - lung fibrosis, pulmonary hypertension, bronchial stenosis and chronic pulmonary aspergillosis. "Non anti-inflammatory" treatments have to be considered as well. Clinicians have an essential role in treatment indication, end-point targets and evaluation of response to treatment during follow-up and in finding the best benefice to risk balance. Progress made on pharmacogenetics may offer more personalized treatments for the patients.

Idiopathic pulmonary fibrosis (IPF) affects lung parenchyma with progressing fibrosis. In this study, we aimed to replicate MUC5B rs35705950 variants and determine new plausible candidate variants for IPF among four different European populations. We genotyped 26 IPF candidate loci in 165 IPF patients from four European countries, such as Czech Republic (n = 41), Germany (n = 33), Greece (n = 40), France (n = 51), and performed association study comparing observed variant distribution with that obtained in a genetically similar Czech healthy control population (n = 96) described in our earlier data report. A highly significant association for a promoter variant (rs35705950) of mucin encoding MUC5B gene was observed in all IPF populations, individually and combined [odds ratio (95% confidence interval); p-value as 5.23 (8.94-3.06); 1.80 × 10-11]. Another non-coding variant, rs7934606 in MUC2 was significant among German patients [2.85 (5.05-1.60); 4.03 × 10-4] and combined European IPF cases [2.18 (3.16-1.50); 3.73 × 10-5]. The network analysis for these variants indicated gene-gene and gene-phenotype interactions in IPF and lung biology. With replication of MUC5B rs35705950 previously reported in U.S. populations of European descent and indicating other plausible polymorphic variants relevant for IPF, we provide additional reference information for future extended functional and population studies aimed, ideally with inclusion of clinical parameters, at identification of IPF genetic markers. © 2016 Kishore, Žižková, Kocourková, Petrkova, Bouros, Nunes, Loštáková, Müller-Quernheim, Zissel, Kolek, Bouros,Valeyre and Petrek.

Sarcoidosis is a granulomatous disorder of unknown cause characterized by non-caseating granuloma in young adults. Cardiac involvement is rare and range from 2 to 75% depending on diagnostic criteria. Cardiac involvement in sarcoidosis may be asymptomatic or may manifest as rhythm/conduction troubles or congestive heart failure. The diagnosis and treatment of cardiac sarcoidosis may be challenging. However, advances have come in recent years from the use of cardiac MRI and

Resume Introduction Les proprietes physico-chimiques du Beryllium (Be) sont cruciales pour les industries de haute technologie. L’inhalation de particules contenant du Be peut entrainer chez certains individus une sensibilisation specifique (BeS) et aboutir pour une partie d’entre eux a une granulomatose pulmonaire denommee « berylliose pulmonaire chronique » (BPC). Etat des connaissances Bien qu’il n’y ait pas de relation lineaire entre le niveau d’exposition au Be et les risques de BeS et de BPC, les expositions les plus elevees sont associees a un risque accru de BeS et de BPC. L’influence specifique de la composition chimique, de la solubilite et de la forme des differents composes de Be sur le risque de BeS et de BPC reste mal connue. Les particules insolubles de petit diametre sont probablement associees a un risque accru. Plusieurs etudes ont rapporte le role d’une predisposition genetique au risque de BeS et de BPC. Le role du HLA-DPβ1 Glu69 dans la sensibilisation au Be est actuellement le mieux etudie. Conclusion La sensibilisation et la BPC resultent de la conjonction d’une exposition au Be et de polymorphismes genetiques predisposant. La BPC est un modele pour la comprehension de la pathogenie de certaines granulomatoses pulmonaires idiopathiques comme la sarcoidose.

Aims: Pulmonary Langerhans cell histiocytosis (PLCH) is characterized by the presence of lesions containing numerous activated Langerhans cells (LCs). An uncontrolled immune response sustained by activated LCs seems to be involved in the pathogenesis of the disease. The aim of this study was to establish whether disruption of LC apoptosis related to the expression of the Bcl-2 family proteins is implicated in the maintenance of PLCH lesions. Methods: Six patients with PLCH were evaluated by morphological and immunohistochemical techniques to explore the incidence of apoptosis in pathological LCs and to characterize the expression of Bcl-2-related proteins by these cells. Results: Very few LCs present in PLCH lesions exhibited nuclear apoptotic changes or expressed cleaved caspase-3, whereas they all strongly expressed the anti-apoptotic molecule Bcl-xL. Interestingly, pulmonary LCs present in intervening lung tissue not involved by the pathological process and known to be immature dendritic cells did not express Bcl-2 family proteins. Conclusions: These findings suggest that activated LCs present within PLCH lesions are poorly susceptible to apoptosis and, thus, are able to sustain the pathological process by causing continuous local stimulation of T cells. Functional studies are needed, however, to demonstrate that they are actually resistant to programmed cell death.

The incidence of tuberculosis (TB) is currently increasing in HIV-infected patients living in Africa and Asia, where TB endemicity is high, reflecting the susceptibility of this group of patients to mycobacteria belonging to the TB group. In this population, extension of multiple resistance to anti-tuberculous drugs is also a matter of anxiety. HIV-induced immunosuppression modifies the clinical presentation of TB, resulting in atypical signs and symptoms, and more frequent extrapulmonary dissemination. The treatment of TB is also more difficult to manage in HIV-infected patients, particularly with regard to pharmacological interactions secondary to inhibition or induction of cytochrome P450 enzymes by protease inhibitors with rifampicin or rifabutin, respectively. Finally, immune restoration induced by highly active anti-retroviral therapy (HAART) in developed countries may be responsible for a paradoxical worsening of TB manifestations.

Background The expression of CXCR4 has been implicated in metastatic dissemination in different models of breast cancer and melanoma. In the present study, we evaluated CXCR4 expression in non-small-cell lung cancer (NSCLC) and the relationship between CXCR4 expression and the prognosis of stage I disease. Patients and methods Using immunohistochemical analysis, we retrospectively analyzed CXCR4 expression in specimens from 61 patients with completely resected pathologically confirmed stage I NSCLC for whom clinical follow-up data were available. Results In the present study, we have shown that: CXCR4 is expressed by tumor cells in stage I NSCLC; CXCR4 is located in the nucleus and/or in the cytoplasm of tumor cells; strong nuclear staining was observed in 17 cases (29.8%); patients whose tumors had CXCR4-positive nuclear staining had a significantly longer duration of survival than patients whose tumors had no nuclear expression (P = 0.039, log-rank test). Interestingly, the 5-year metastasis rates were 23.5% and 34.1% in patients with CXCR4-positive and CXCR4-negative nuclear expression, respectively (P = 0.2). Conclusion Strong CXCR4-positive nuclear staining was associated with a significantly better outcome in early-stage NSCLC. The mechanisms underlying this clinically and biologically important finding need to be further explored.

Resume Propos. – Cette mise au point concerne l’histiocytose langerhansienne, encore appelee histiocytose X ou granulomatose a cellules de Langerhans. La forme pulmonaire isolee de l’adulte est une affection rare qui touche preferentiellement le sujet jeune, fumeur. La maladie est caracterisee par des lesions granulomateuses s’attaquant aux bronchioles distales qu’elles detruisent progressivement, laissant place a des bronchiolectasies prenant l’aspect de kystes cicatriciels caracteristiques sur coupes. Les lesions florides sont riches en cellules de Langerhans, cellules presentatrices d’antigene appartenant a la lignee des cellules dendritiques, associees a des lymphocytes T et des eosinophiles. Le diagnostic repose en pratique clinique sur la convergence d’arguments epidemiologiques, cliniques, radiographiques et surtout tomodensitometriques (association typique de nodules et de kystes predominant dans les deux tiers superieurs des 2 champs pulmonaires). Une confirmation histopathologique, examen de reference, s’impose dans les formes moins typiques. L’evolution clinique est favorable dans au moins deux tiers des cas, la regression etant facilitee dans certains cas par le sevrage tabagique. Toutefois, le pronostic est plus reserve en cas de survenue a un âge tardif, de baisse severe du rapport VEMS/CV et de TLCO et la maladie peut alors reduire l’esperance de vie. Actualite et points forts. – La pathogenie de l’histiocytose langerhansienne pulmonaire demeure inconnue, mais plusieurs arguments suggerent qu’une reponse immunitaire incontrolee initiee par les cellules de Langerhans et dirigee contre l’epithelium bronchiolaire est a l’origine de la maladie. D’autres arguments suggerent la presence d’un terrain genetique particulier, favorisant par exemple une plus grande sensibilite des cellules de Langerhans a des facteurs (GM-CSF, entre autres) qui influencent leur croissance et leur survie. Perspectives. – Bien que la maladie demeure de cause inconnue, les progres recents concernant ses mecanismes immunopathologiques devraient favoriser a terme la mise au point de strategies therapeutiques nouvelles visant a reguler le nombre ou l’activation des cellules de Langerhans aux sites des lesions.

The case is reported of a patient with cavitary sarcoidosis complicated by an aspergilloma caused by an itraconazole-resistant strain of Aspergillus fumigatus, who was treated with voriconazole. The authors suggest that susceptibility testing of A. fumigatus strains is of value during long-term therapy with itraconazole, and that voriconazole may be a good option for treatment of patients infected with itraconazole-resistant strains of A. fumigatus.

Sarcoidosis or granulomatous reactions have rarely been reported in association with malignant melanoma (MM). We describe seven patients who presented with both granulomatous disease and MM, and discuss the physiopathological and prognostic significance of this association. In three patients, the granulomatosis was diagnosed as true sarcoidosis and in one patient, as tumour-associated granuloma. In three cases, designated here as atypical tumour-associated granulomatoses, the presence of clear-cut pulmonary granulomatous nodules was typical neither for sarcoidosis nor for tumour-associated granuloma and was highly suggestive of melanoma metastases. Mediastinal lymphadenopathy was present in every patient. In all seven patients, the question of mediastinal or pulmonary involvement or relapse of the MM was raised, but could be confirmed in only one patient. MM can be associated with granulomatous disease. Knowledge of this association has implications in the management of patients with MM.

Resume L'objectif de cette etude multicentrique, prospective, randomisee, en double aveugle, etait de comparer l'efficacite et la tolerance du cefotiam hexetil (CTM) a la dose de 400 mg matin et soir avec celles de l'amoxicilline/acide clavulanique (AAC) a la dose de 1 g matin et soir sur une periode de dix jours de traitement au cours d'une exacerbation de bronchite chronique. Cent cinquante sept patients adultes souffrant d'une exacerbation de bronchite chronique ont ete inclus par des pneumologues. Les deux populations etaient comparables a l'inclusion en ce qui concerne les donnees demographiques et la clinique. En fin de traitement, 92 % des patients du groupe cefotiam hexetil et 88 % du groupe amoxicilline/acide clavulanique etaient gueris apres analyse en intention de traiter, respectivement 96 % versus 94 % apres analyse en per protocol. Le nombre d'effets secondaires a ete moins frequent dans le groupe cefotiam hexetil (9 % versus 21 %). Cette difference etait statistiquement significative (p = 0,03). En conclusion, le cefotiam hexetil 400 mg matin et soir peut etre considere comme une bonne alternative therapeutique dans le traitement des exacerbations de bronchite chronique de l'adulte avec une efficacite equivalente et une tolerance meilleure que l'amoxicilline/acide clavulanique 1 g matin et soir.

CD4+ T lymphocytes play a major role in the pathophysiology of sarcoidosis. Many studies have investigated the immunological and genetic abnormalities in this disease. There are few studies concerning the metabolic pathways. Essentially they concern the pathways: STAT1, MAPK38, NF-κB, Galphai, cAMP and cGMP PDE and PEMT1. Using studies in the literature and results of our own work concerning some metabolic aspects of T lymphocytes in sarcoidosis, we present a revue of the various hypotheses, which involve dysfunction of cAMP signaling pathways, such as RAS/RAF/MEK/ERK in T lymphocytes, leading to a disorder of immunity.

Surgical biopsy of lung parenchyma can be used to establish a diagnosis in interstitial lung disease both of acute and chronic presentation. The present article summarizes the current indications, the therapeutic implications, the different surgical techniques and postoperative complications of the procedure. Common controversies and problems related to surgical lung biopsy are also presented.

Computed tomography is important for the diagnosis and follow-up of chronic diffuse interstitial lung diseases. Image quality has improved from each generation of scanner to the next and this continues to allow a better characterization of extent of pathology, or even the nature of the pathological process (potentially reversible inflammatory lesions compared to fibrotic lesions). The diagnostic imaging approach has evolved at the same time as technological developments. We initially thought in terms of the predominant lesions (nodular, alveolar consolidation, ground-glass opacity), and then moved to reasoning based on patterns, which are a combination of several elementary lesions (typically for the diagnosis of idiopathic pulmonary fibrosis). Nowadays, studies are focused on building models characterizing a specific disease and which combine several distinct patterns (typically for ground-glass opacity analysis). CT also allows a quantification of the extent of lung disease, which is linked to the prognosis of the disease and helps to monitor its progression. This quantification is usually based on visual criteria, the principles of which are summarized here. The development of automated quantification software could in the near future, be a support for the radiologist.

Sarcoidosis is a common disorder with heterogeneous severity. Corticosteroids are the cornerstone of its treatment and allow a disease remission but only with a suspensive effect. Immunosuppressive drugs, hydroxychloroquine and infliximab may be useful in some patients. Half of the patients recover spontaneously without any treatment. In the remaining patients, a treatment is necessary either at presentation or during the follow-up in the presence of a disease flare. Treatment duration should be of at least 12 months. The main indications of a systemic treatment include ophthalmologic, neurologic, cardiovascular, renal, laryngeal involvements, severe pulmonary manifestations, lupus pernio and marked hypercalcaemia. Initially, patients should receive prednisone or prednisolone at 0.5 to 1 mg/kg daily for 6 to 12 weeks to obtain a complete remission, and then followed by a gradual dose reduction every 6 to 12 weeks. After treatment completion, a 36-month duration monitoring is warranted to confirm recovery. Low-dose methotrexate and azathioprine are the most useful immunosuppressive drugs and are indicated in patients with of failure or contra-indication of corticosteroids or in those patients who needs a long term prednisone dose higher than 10 mg daily to control the sarcoidosis. Cyclophosphamide used is severe neurologic or heart involvement that is resistant to corticosteroids and other immunosuppressive drugs. Hydroxychloroquine and chloroquine are indicated in extensive skin lesions or as corticosteroids sparing agents. Infliximab can be useful in some severe sarcoidosis patients refractory to classical treatment, except for cardiac involvement. Topical corticosteroids can be used for limited skin involvement, anterior uveitis or cough. In the future, a more individualized treatment could be drawn from pharmacogenetic studies. The key point remains the availability of etiologic or innovative drugs for sarcoidosis refractory to currently available therapy.