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International audience; BackgroundLow income, a known prognostic indicator of various chronic respiratory diseases, has not been properly studied in idiopathic pulmonary fibrosis (IPF). We hypothesize that a low income has an adverse prognostic impact on IPF.MethodsPatients were selected from the French national prospective cohort COFI. Patients’ income was assessed through the median city-level income provided by the French National Institute of Statistics and Economic Studies according to their residential address. Patients were classified in two groups as “low income” vs. “higher income” depending on whether their annual income was estimated to be < or ≥18 170 €/year (the first quartile of the income distribution in the study population). The survival and progression-free survival (PFS) of the groups were compared by a log-rank test and a Cox model in multivariate analysis.Results200 patients were included. The average follow-up was 33.8 ± 22.7 months. Patients in the low income group were significantly more likely to be of non-European origin (p < 0.006), and to have at least one occupational exposure (p < 0.0001), and they tended to have a higher cumulative exposure to fine particles PM2.5 (p = 0.057). After adjusting for age, gender, forced vital capacity at inclusion, geographical origin, and occupational exposure having a low-income level was a factor associated with a worse PFS (HR: 1.81; CI95%: 1.24–2.62, p = 0.001) and overall survival (HR: 1.49; CI95%: 1.0006–2.23, p = 0.049).ConclusionsLow income appears to be a prognostic factor in IPF. IPF patients with low incomes may also be exposed more frequently to occupational exposures.

Resume Introduction La proteinose alveolaire pulmonaire auto-immune est une maladie rare, liee a l’accumulation de surfactant au niveau des alveoles. Observation Nous rapportons le cas d’un patient fumeur âge de 41 ans, entre dans la maladie par une insuffisance respiratoire aigue. Les grands lavages pulmonaires therapeutiques etaient efficaces seulement quelques semaines. Les injections sous-cutanees de GM-CSF n’ont pas apporte de benefice et les echanges plasmatiques ont alors ete essayes. Conclusion Il s’agit du cinquieme cas decrit d’utilisation de cette therapeutique dans le cadre d’une proteinose alveolaire pulmonaire auto-immune. Ce traitement fut inefficace chez notre patient.

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

OBJECTIVE: The WEGENT trial and other short-term studies suggested that azathioprine or methotrexate could effectively maintain granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) remission. Whether differences in relapse or adverse event rates would appear after discontinuation of those 2 maintenance regimens and longer follow-up remains unknown. METHODS: Long-term outcomes for the patients enrolled in the WEGENT trial were analyzed according to their randomization group. Parameters at trial entry were evaluated as potential prognostic factors for death, relapse or damage in multivariate models. RESULTS: Data were returned for 88.8% of the 126 original participants. Median [95% confidence interval] followup was 11.9 [11.3-12.5] years. For the azathioprine and methotrexate arms, respectively, the 10-year overall survival rates were 75.1% [64.8-86.9] and 79.9% [70.3-90.8] (P = 0.56), and relapse-free survival rates 26.3% [17.3-40.1] and 33.5% [23.5-47.7] (P = 0.29). No between-arm differences were observed for relapse, adverse events, damage, survival rates without severe side effects and survival rates without relapse and severe side effects. Considering only the 97 GPA patients, no between-arm survival differences were observed. Relapse-free survival was shorter for GPA than MPA patients but the multivariate analysis retained anti-PR3-ANCA-positivity, and not GPA, as being independently associated with relapse. CONCLUSION: This long-term analysis confirms that azathioprine and methotrexate are comparable options for maintaining GPA or MPA remission. Despite good overall survival, relapses, adverse events and damage remain matters of concern and further studies are needed to reduce them.

RésuméLe syndrome des antisynthétases correspond à une myopathie inflammatoire fréquemment associée à une atteinte pulmonaire, surtout parenchymateuse (pneumopathie infiltrante diffuse) et plus rarement vasculaire (hypertension pulmonaire). Devant un tableau clinique et radiologique évocateur, la présence d’anticorps anti-ARNt synthétases signe le diagnostic. Les plus fréquents de ces auto-anticorps sont les anti-Jo1, les anti-PL7 et les anti-PL12. De nombreuses manifestations cliniques extrathoraciques associées à l’atteinte pulmonaire peuvent orienter le diagnostic : myalgies ou déficit musculaire, phénomène de Raynaud, polyarthrite, fièvre et « mains de mécaniciens ». Une augmentation des créatine-phospho-kinases est quasi constante. Le recours à l’électromyogramme, à l’imagerie musculaire par résonance magnétique ou à l’histologie n’est pas systématique. Néanmoins, il existe une grande variabilité des symptômes et de leur sévérité d’un patient à l’autre ou au long de l’évolution de la maladie. L’atteinte pulmonaire est un facteur pronostic majeur et incite à traiter de manière intensive les patients, principalement par corticothérapie systémique, voire d’emblée par association corticoïdes et immunosuppresseurs. Mieux connaître cette pathologie qui est souvent de révélation pneumologique permettrait d’améliorer le diagnostic et la prise en charge thérapeutique, voire même le pronostic.SummaryAntisynthetase syndrome is an inflammatory myopathy frequently associated with pulmonary manifestations, especially interstitial lung diseases, and uncommonly pulmonary hypertension. In the context of a suggestive clinical and radiological picture, positive anti-RNA synthetase antibodies confirm the diagnosis. Anti-Jo1, anti-PL7, and anti-PL12 antibodies are the more commonly encountered. The presence of a number of extra-thoracic manifestations in association with pulmonary disease may suggest the diagnosis. These include: myalgia or muscular deficit, Raynaud's phenomenon, polyarthritis, fever, mechanics hands. Serum creatine kinase levels are usually increased. Electromyogram, muscular magnetic resonance imaging or muscle pathology are not mandatory to make the diagnosis. There is a high variability in symptoms and severity, between patients but also during the course of the disease in the same patient. The presence of an interstitial lung disease is a major prognostic factor and an indication for more intensive treatment, principally with systemic corticosteroids with or without immunosuppressive drugs. Improving respiratory physicians’ knowledge of this disease, which is often revealed by its pulmonary manifestations, should help diagnosis, therapeutic management, and possibly prognosis.

Summary Introduction Alpha-1 antitrypsin, secreted by the liver, inhibits neutrophil elastase. Its deficiency favours the development of emphysema. Restoring a “protective” serum level in deficient patients should make it possible to inhibit the development of emphysema. State of the art Human plasma-derived alpha-1 antitrypsin is a blood-derived drug sold in France under the name Alfalastin®. The recommended posology is an I.V. administration of 60 mg/kg once a week. Human plasma-derived alpha-1 antitrypsin restores anti-elastase protection in the lower lung and prevents experimental emphysema induced by the elastasis of human neutrophils in hamster. The low number of patients with alpha-1 antitrypsin deficiency is one of the difficulties to perform sufficiently powerful randomised studies. However, randomised studies have reported the efficacy of human plasma-derived alpha-1 antitrypsin perfusions on mortality, FEV1 decline and the frequency of exacerbations. Randomised control trials have demonstrated the efficacy of human plasma-derived alpha-1 antitrypsin perfusions on the loss of lung density assessed by CT scan. Conclusion Augmentation therapy is simple in its conception and implementation, but it is expensive. However, there are currently no other solutions.

Acute eosinophilic pneumonia (AEP) has been reported following chloroquine or mefloquine exposure, both structurally related to piperaquine. We report a case of AEP with typical CT scan patterns, hypereosinophilia in blood (9.8 109/l), and bronchoalveolar lavage (78% of 600 000 cells/ml), 10 days after artenimol-piperaquine exposure in a 26-year-old man.

Initiative that emanated from the French National Reference Centre and the Network of Competence Centres for Rare Lung Diseases; International audience; Idiopathic pulmonary fibrosis (IPF) is the most frequent chronic idiopathic interstitial pneumonia in adults. The management of rare diseases in France has been organised by a national plan for rare diseases, which endorsed a network of expert centres for rare diseases throughout France. This article is an overview of the executive summary of the French guidelines for the management of IPF, an initiative that emanated from the French National Reference Centre and the Network of Regional Competence Centres for Rare Lung Diseases. This review aims at providing pulmonologists with a document that: 1) combines the current available evidence; 2) reviews practical modalities of diagnosis and management of IPF; and 3) is adapted to everyday medical practice. The French practical guidelines result from the combined efforts of a coordination committee, a writing committee and a multidisciplinary review panel, following recommendations from the Haute Autorité de Santé. All recommendations included in this article received at least 90% agreement by the reviewing panel. Herein, we summarise the main conclusions and practical recommendations of the French guidelines.

a Inra, UMR754, IFR 128, centre national de reference des maladies pulmonaires rares, centre de competences de l’hypertension pulmonaire, service de pneumologie, universite de Lyon, universite Claude-Bernard Lyon 1, hospices civils de Lyon, hopital Louis-Pradel, 28, rue du Doyen-Lepine, 69000 Lyon, France b CHU Bichat, centre de competences pour les maladies pulmonaires rares, 46, rue Henri-Huchard, 75877 Paris cedex 18, France

Resume Introduction La maladie a depots de chaines legeres d’immunoglobulines est une entite clinique rare caracterisee par des depots systemiques de chaines legeres d’immunoglobulines monoclonales. L’atteinte renale est quasiment constante tandis que les manifestations pulmonaires a type de lesions soit nodulaires soit diffuses, et notamment kystiques, sont exceptionnelles. Observation Nous rapportons l’observation d’un patient non fumeur, âge de 60 ans qui presentait un tableau d’insuffisance respiratoire chronique liee a une pneumopathie interstitielle diffuse caracterisee par des lesions kystiques destructrices a predominance apicale. Le diagnostic de maladie a depots de chaines legeres d’immunoglobulines a expression pulmonaire kystique a pu etre porte lors de la biopsie pulmonaire chirurgicale. L’atteinte extrapulmonaire se limitait a une infiltration des glandes salivaires. L’evolution malgre 12 cures de chimiotherapie a ete defavorable sur le plan fonctionnel et radiographique. Conclusion Cette observation est le quatrieme cas decrit de maladie kystique pulmonaire diffuse lie a des depots de chaines legeres d’immunoglobulines monoclonales. Elle souligne la necessite d’un bilan etiologique exhaustif afin de ne pas meconnaitre cette cause rare de maladie kystique qui semblerait etre liee a une lymphoproliferation primitivement pulmonaire. Le seul traitement reconnu efficace est la transplantation pulmonaire.

National audience; Introduction Les télomérases sont les enzymes assurant la synthèse des télomères, séquences d’ADN essentiels dans la protection des chromosomes. Les mutations des télomérases sont responsables, entre autres, d’anomalies hématologiques, pulmonaires (fibrose pulmonaire idiopathique) et hépatiques. Il n’y a que peu de données dans la littérature concernant les résultats des transplantations pulmonaires chez ces patients mutés. Cas clinique Nous rapportons le cas d’un jeune homme de 39 ans, souffrant de syndrome myélodysplasique associé à une fibrose pulmonaire, permettant de poser le diagnostic de téloméropathie (mutation de la sous-unité ARN ou TERC ; r.182delG, pseudoknot area). L’insuffisance médullaire est sévère : leucopénie à 1,3 G/L dont 0,54 G/L de PNN, anémie macrocytaire (Hb à 10,3 g/dL ; VGM à 120 fL) et thombopénie à 27 G/L. Le syndrome restrictif est également sévère avec une CPT à 60 % et une CVF à 82 % de la valeur prédite (% pred). Il s’associe à une altération de la membrane alvéolo-capillaire (DLCO corrigée sur l’hémoglobine à 31 % pred). Le patient a été récusé à la fois pour la transplantation médullaire et pour la transplantation pulmonaire malgré son jeune âge. La prise en charge est donc palliative : réhabilitation respiratoire, oxygénothérapie, puis nintedanib. Discussion Dans la littérature, les transplantations médullaires chez les patients présentant une mutation des télomérases s’associent à une dégradation de la fonction respiratoire, en lien avec la toxicité des traitements immunosuppresseurs, même en l’absence d’atteinte pulmonaire initiale. Par ailleurs, les complications infectieuses et hématologiques post-transplantations pulmonaires chez ces patients mutés semblent plus fréquentes et nécessitent souvent une adaptation des traitements anti-rejets. Ces risques post-transplantations paraissent plus importants en présence d’une thrombopénie sévère préopératoire. Ces données sont cependant limitées à trois études rétrospectives de petites tailles. Au total, ce jeune patient a été jugé inéligible à la transplantation médullaire et à la transplantation pulmonaire, respectivement à cause de l’insuffisance respiratoire et de l’insuffisance médullaire. Il est émis l’hypothèse que l’allègement de la thérapie immunosuppressive pourrait améliorer le devenir des patients mutés transplantés, sans majorer le risque de rejet, illustrant le concept d’immunosénescence. Mais cette hypothèse reste à être validée. Ce cas clinique souligne l’importance de reconnaître les signes évocateurs de téloméropathie, dans la mesure où le diagnostic impacte la prise en charge de la fibrose pulmonaire

Lymphoedema, myelodysplasia, fibrosis and pulmonary alveolar proteinosis complicating a novel GATA2 mutation http://ow.ly/RHci303h8ks

Intra-alveolar hemorrhage (IAH) could be revealed by acute respiratory failure. The classic association of hemoptysis - anemia - radiological infiltrates is suggestive and has to be confirmed by broncho-alveolar lavage with Golde score. Etiologies included immune and non-immune diseases, with specific treatment for each. We report a case of IAH revealed by acute respiratory distress syndrome and anemia (3 g/dL), related to pulmonary and cerebral vasculitis without renal involvement. The patient was efficiently treated with corticosteroids and cyclophosphamide. This case highlights the critical role of BAL cytological analysis with Golde score, and the need for a rapid and accurate diagnosis in order to guide specific treatment. If histology is needed, renal biopsy even without renal involvement, or surgical lung biopsy is possible.

Resume Introduction Le syndrome des ongles jaunes est une entite rare, decrite pour la premiere fois en 1964, dont la physiopathologie reste encore mal connue. Sa definition repose sur une triade clinique associant des ongles jaunes, un lymphœdeme et des manifestations respiratoires chroniques comportant principalement epanchements pleuraux et dilatation des bronches. Observations Nous presentons une serie retrospective de cinq patients suivis pour un syndrome des ongles jaunes. Les patients, tous de sexe masculin, etaient âges de 52 a 71 ans (mediane = 56). Trois patients presentaient la triade complete ongles jaunes, epanchement pleural et lymphœdeme alors que les deux autres patients presentaient uniquement l’association ongles jaunes et bronchectasies. Les manifestations ungueales et rhinosinusiennes ont ete constamment retrouvees. Nous rapportons egalement l’existence de manifestations atypiques sous la forme d’un epanchement pleural transsudatif et d’un œdeme du visage. Un cancer etait associe chez deux de nos patients. Conclusions Le syndrome des ongles jaunes est une pathologie rare ; des diagnostics alternatifs, plus frequents, doivent etre elimines. Une neoplasie associee doit etre recherchee. Le traitement est purement symptomatique.

Background The drug 131 I-labeled lipiodol is used as internal radiotherapy for unresectable hepatocellular carcinoma. Although the drug was considered safe during preapproval studies, we observed several cases of interstitial pneumonia following its administration. Methods Cases were retrospectively identified through the drug safety unit database of Rennes University Hospital. Results From 1994 to 2009, interstitial pneumonia developed in 15 patients following 131 I-labeled lipiodol administration, with an estimated prevalence of 15.5 cases (95% CI, 7.7-23.2) per 1,000 treated patients. Mean age of the patients was 60 ± 8 years, and the male to female ratio was 6.5:1. All patients had cirrhosis, mainly related to long-term alcohol intoxication (n = 12). Most (n = 10) cases occurred after the second 131 I-labeled lipiodol injection. The median delay between last 131 I-labeled lipiodol administration and first respiratory symptoms was 30 days (interquartile range, 16.5-45 days). All patients presented with shortness of breath. Physical examination mostly revealed fever (n = 11) and bilateral crackles (n = 12). Chest CT scan showed bilateral ground-glass opacities (n = 8) with septal thickening, retraction, or both (n = 8). BAL (n = 7) was remarkable for increased neutrophils (n = 4) or CD8 + T cell count (n = 3). Despite corticosteroids, 12 (80%) patients died, mostly of untractable respiratory failure (n = 9). Median delay between last 131 I-labeled lipiodol injection and death was 63 days (interquartile range, 34-129 days). Conclusions Interstitial pneumonia may be a serious and not uncommon complication of 131 I-labeled lipiodol administration.

Resume Introduction Les anti-TNFα, desormais frequemment prescrits dans les rhumatismes inflammatoires, ont ete utilises avec succes dans le traitement des sarcoidoses extrapulmonaires refractaires, le TNFα etant implique dans la formation et l’entretien du granulome sarcoidosique. Paradoxalement, les anti-TNFα sont incrimines dans 23 cas d’apparition de granulomes associes a un tableau radioclinique compatible avec une sarcoidose. Observation Un homme de 54 ans, porteur d’une spondylarthrite ankylosante sous etanercept depuis deux ans, presentait un tableau de bronchite avec radiologiquement des macronodules et un infiltrat lobaire superieur droit. L’etanercept etait immediatement arrete. Le lavage bronchoalveolaire eliminait une cause infectieuse, notamment la tuberculose. La tomodensitometrie thoracique montrait des adenomegalies mediastinales, des nodules bilateraux et une micronodulation a predominance peribronchovasculaire evoquant fortement une sarcoidose. Une biopsie pulmonaire d’un nodule parenchymateux concluait a une granulomatose d’allure sarcoidosique. L’evolution a dix mois de l’arret de l’etanercept n’etant pas favorable, une corticotherapie etait debutee, permettant une amelioration clinique, radiologique et fonctionnelle. Conclusion Ce cas souligne l’interet de la recherche de complications pulmonaires au cours des traitements anti-TNFα. En particulier, s’il faut evoquer et eliminer en priorite une tuberculose, il ne faut pas meconnaitre la possibilite d’une granulomatose non infectieuse de type sarcoidose.

Introduction Une enquete aupres de patients atteints de fibrose pulmonaire, idiopathique (FPI) ou avec une origine connue (non FPI) a ete menee a l’initiative des centres de reference et de competences pour les maladies pulmonaires rares. Methodes Au total, 265 patients ont repondu par courrier a un questionnaire auto-administre, dont 172 FPI (65 %) et 93 non FPI (35 %). Resultats Dans les memes proportions : 43 % des patients souhaitaient une reduction des delais de confirmation du diagnostic, 30 % eprouvaient des difficultes tres importantes lors d’une activite physique jusqu’a necessiter une aide y compris pour se rendre a l’hopital, et 18 % exprimaient le besoin d’une aide autour des soins palliatifs et la prise en charge de la douleur. Quelle que soit l’etiologie de la fibrose, 42 % des patients souhaitaient avoir un role plus actif dans le suivi de leur maladie, 67 % estimaient qu’une association de patients etait utile ; seuls 9 % adheraient a une association de patients principalement dans la FPI (7 %) grâce au pneumologue qui les avait informes de son existence. Cinquante pour cent auraient envie d’adherer a une association de patients et 38 % aimeraient se rendre disponibles pour aider les autres. Soixante-dix pour cent des patients interroges utilisaient internet a partir d’un ordinateur, peu utilise pour rechercher des informations complementaires sur la maladie (37 %), et rarement pour correspondre avec d’autres patients (5 %). Conclusion Cette enquete nationale originale a montre : de nombreuses similitudes entre les 2 sous populations de patients atteints de fibrose au niveau du vecu et des attentes, le meme souhait d’implication dans la prise en charge, et des opportunites de collaboration entre pneumologues et representants de patients.

OBJECTIVE To compare the one year survival after discharge from ICU of patients with chronic obstructive pulmonary disease (COPD) admitted for acute hypercapnic respiratory failure and who required mechanical ventilation. METHODS Retrospective cohort study on 130 patients, 52 patients were treated with non-invasive ventilation (NIV) and 78 patients with conventional mechanical ventilation (CMV). RESULTS In 73 patients the cause for respiratory failure could not be identified. Long-term survival was significantly better following NIV than with CMV (p=0.02 by log-rank testing), but the better prognosis associated with use of NIV was not found in patients with no documented cause for the respiratory failure. After adjusting for male gender, age>65 years, simplified acute physiology score II>35, prior long-term home oxygen therapy, treatment with steroids, FEV1

A new survey coordinated by the French expert centres for rare pulmonary diseases investigated French pulmonologists' diagnostic and therapeutic practice for idiopathic pulmonary fibrosis (IPF) and explored changes since a previous survey in 2011–2012. From May 16 to August 30, 2014, 524 pulmonologists were contacted. Those following at least one patient with IPF were invited to complete a questionnaire administered by telephone or e-mail. 166 (31.7%) pulmonologists, 161 (97%) of whom had participated to the first survey, completed the questionnaire. Of those, 46% and 52%, respectively, discussed the cases with radiologists and pathologists. Out of 144 pulmonologists practicing outside of expert centres, 80% indicated referring patients to those centres. The 2013 French practical guidelines for IPF were known by 92% of pulmonologists involved in IPF, 96% of whom considered them appropriate for practice. The multidisciplinary discussion form for IPF diagnosis was known by 74% and considered appropriate by 94%. Diagnosis and management resulted from multidisciplinary discussion in 50% of the cases. About 58% of patients were diagnosed with “mild to moderate IPF” as defined by forced vital capacity ≥50% of the predicted value and diffusing capacity for carbon monoxide ≥35% of predicted. At the time of the survey, 31% of physicians were using pirfenidone to treat patients with “mild-to-moderately severe IPF” and 30% generally prescribed no treatment. Substantial improvement has occurred since the 2011–2012 survey with regard to knowledge of guidelines and proper management of IPF. Early diagnosis still needs to be improved through the network of expert centres., A practice survey reveals important changes in the diagnosis and practical management of IPF http://ow.ly/Tuwr1

Findings from the WEGENT trial and other short-term studies have suggested that azathioprine (AZA) or methotrexate (MTX) could effectively maintain remission of granulomatosis with polyangiitis (Wegener's) (GPA) or microscopic polyangiitis (MPA). This study was undertaken to examine whether differences in rates of relapse or adverse events would appear after discontinuation of these 2 maintenance regimens, when assessed over a longer followup period.Long-term outcomes in patients enrolled in the WEGENT trial were analyzed according to their randomized treatment group (AZA or MTX). Parameters at trial entry were evaluated as potential prognostic factors for death, relapse, or damage in multivariate models.Data from 10 years of followup were available for 112 (88.8%) of the 126 original trial participants. The median followup time was 11.9 years (95% confidence interval [95% CI] 11.3-12.5 years). In patients receiving AZA and those receiving MTX, the 10-year overall survival rates were 75.1% (95% CI 64.8-86.9%) and 79.9% (95% CI 70.3-90.8%) (P = 0.56), respectively, and relapse-free survival rates were 26.3% (95% CI 17.3-40.1%) and 33.5% (95% CI 23.5-47.7%) (P = 0.29), respectively. No between-treatment differences were observed with regard to rates of relapse, adverse events, damage, survival without severe side effects, and survival without relapse and severe side effects. In analyses limited to the 97 patients with GPA, no between-treatment differences in survival rates were observed. The 10-year relapse-free survival rate was lower in patients with GPA than in patients with MPA. However, in the multivariate analysis, anti-proteinase 3 antineutrophil cytoplasmic antibody (ANCA) positivity, and not GPA, was retained as being independently associated with the relapse rate.The results of this long-term analysis confirm that AZA and MTX are comparable treatment options for maintaining remission of GPA or MPA. Despite achieving good overall survival with these treatments, relapse rates, adverse events, and damage remain matters of concern and further studies are needed to reduce their frequency in these ANCA-associated vasculitides.

Background: There is no recommendation for treating pulmonary hypertension (PH) when associated with chronic obstructive pulmonary disease (COPD). Objective: To evaluate the effect of PH-specific therapy in patients with COPD. Methods: All successive patients with severe PH [mean pulmonary arterial pressure (mPAP) ≥35 mm Hg] and COPD, who received specific PH medication and who underwent right heart catheterization at baseline and after 3-12 months of treatment, were analyzed from a prospective database. Results: Twenty-six patients were included with a median follow-up of 14 months. Mean forced expiratory volume in 1 s was 57 ± 20% of predicted, and mean forced expiratory volume in 1 s/forced vital capacity was 47 ± 12%. Dyspnea was New York Health Association classification stage (NYHA) II in 15%, NYHA III in 81% and NYHA IV in 4%. First-line treatments were endothelin receptor antagonists in 11 patients, phosphodiesterase-5 inhibitors in 11 patients, calcium blocker in 1 patient, combination therapy in 3 patients including 2 with a prostanoid. After 6 ± 3 months, pulmonary vascular resistance decreased from 8.5 ± 3 to 6.6 ± 2 Wood units (p < 0.001), with significant improvement of cardiac index from 2.44 ± 0.43 to 2.68 ± 0.63 liters × min × m-2 (p = 0.015) and mPAP from 48 ± 9 to 42 ± 10 mm Hg (p = 0.008). There was no significant difference in dyspnea, 6-min walking distance, echocardiographic parameters or N-terminal pro-brain natriuretic peptide levels. There was no significant difference in arterial oxygen saturation after 3-12 months of treatment. Conclusions: Specific PH medications may improve hemodynamic parameters in COPD patients with severe PH. Appropriate prospective randomized studies are needed to evaluate the potential long-term clinical benefit of treatment.

Pulmonary alveolar phospholipoproteinosis is a rare lung disease of unknown cause characterized by surfactant plugging of the alveoli. At the present time, surgical lung biopsy, long considered as the gold standard, is not necessary for positive diagnosis of pulmonary alveolar phospholipoproteinosis when computed tomography anomalies and analysis of bronchial lavage fluids present a typical pattern. Treatment requires abundant lavage, but the demonstration of anti-GM-CSF antibodies in primary forms opens new therapeutic perspectives.

Resume Introduction Dans certaines situations, telles les toux post-virales ou post-coqueluchoides, le clinicien est confronte a une toux chronique non productive que ne peuvent expliquer ni une inflammation sous-jacente, ni une erosion de l’epithelium, ni une broncho-constriction. Cette toux subaigue ou chronique constitue un veritable syndrome (toux maladie) cause et entretenu par le systeme nerveux central (SNC) et ses efferences ortho et parasympathiques, siege d’un reajustement fonctionnel ou interviennent des mecanismes de plasticite neuronale (intervention des recepteurs de type NMDA au glutamate). Etat des connaissances Les neurones situes dans la zone expiratoire des centres de la respiration (le complexe Pre-Boetzinger du tronc cerebral) font l’objet d’un apprentissage a la decharge (firing) , du fait d’une stimulation repetee des recepteurs NMDA ; ce phenomene est similaire au phenomene de potentialisation a long terme (PLT) base moleculaire de la memoire et de la neosynaptogenese. Ces donnees suggerent l’interet potentiel d’un antagonisme precoce des mecanismes d’amplification et donc de perennisation du reflexe de toux. Perspectives Une piste plus recente est envisageable, faisant intervenir les recepteurs de type 4 a la serotonine (5HT 4 ) antagonisant la depression respiratoire induite par les opiaces (fentanyl). Une surstimulation ou une surexpression de ces recepteurs, toujours dans la zone de Pre-Boetzinger, pourrait contribuer a l’accentuation du reflexe de toux. Conclusions Ces phenomenes d’amplification d’un reflexe meritent consideration car ils sont accessibles a la therapeutique, et antagonises precocement, devraient limiter l’extension de la toux chronique.

Resume La dyspnee est un symptome tres souvent present chez les patients lors de leurs dernieres semaines ou derniers jours de vie. Bien que tres peu d’etudes confirment l’efficacite de l’oxygenotherapie sur cette dyspnee, beaucoup d’entre eux beneficieront neanmoins d’un apport d’oxygene. Le but de ce travail, a partir d’entretiens avec des soignants, est de decrire et d’analyser les motivations, le ressenti de cette oxygenotherapie chez le personnel soignant d’une equipe de pneumologie et de souligner les elements qui pourraient influencer sa prescription. La fonction de l’oxygene, outre celle d’ameliorer l’hematose, s’etend a un authentique role de co-analgesique participant au confort du patient. Il permettrait aussi de limiter le risque d’asphyxie qui reste une angoisse majeure du patient hospitalise en pneumologie, de sa famille et des soignants. L’oxygenotherapie est peu contraignante, indolore. Encore faut-il eviter d’etre agressif et proscrire les masques a haute concentration. Le risque de secheresse des muqueuses nous oblige souvent a humidifier l’oxygene par des barboteurs bruyants. Ce bruit, plein de sens, est percu de facon contradictoire par une meme equipe soignante. Soit il correspond a une gene au recueillement et a l’intimite avec le patient, soit il se substitue a cette respiration qui se fait moins entendre et sa presence devient alors indispensable. Le confort qu’apporte l’oxygene au patient s’etend a sa famille mais aussi a toute l’equipe soignante, qui garde ainsi une capacite a faire, a donner quelque chose. Il correspond a un veritable lien avec cette vie qui va bientot s’eteindre. Bien que courante, la prescription d’oxygene a un patient en fin de vie est pleine de sens et son role s’etend bien au-dela d’un simple controle de l’hematose. Aussi perd-elle de son caractere banal.

RésuméLa protéinose alvéolaire pulmonaire (PAP) est une maladie rare caractérisée par l’accumulation alvéolaire de composants du surfactant qui gêne les échanges gazeux. Les PAP sont séparées en trois groupes : les PAP auto-immunes caractérisées par la présence d’anticorps sériques anti-GM-CSF qui sont les plus fréquentes ; les PAP secondaires à une maladie sous-jacente, le plus souvent hématologique, mais aussi à l’inhalation de toxiques et à des infections ; enfin, les PAP d’origine génétique. Le diagnostic de PAP est évoqué sur le scanner thoracique avec une pneumopathie infiltrante diffuse ayant un aspect classique de crazy paving, puis confirmé par l’aspect laiteux du lavage bronchoalvéolaire, et la présence de matériel lipoprotéinacé PAS positif. La confirmation du diagnostic de PAP par biopsie pulmonaire chirurgicale est désormais rarement nécessaire. La positivité des anticorps sériques anti-GM-CSF signe le caractère auto-immun de la maladie. Le traitement de référence des PAP auto-immunes est le « grand lavage pulmonaire thérapeutique ». En cas de maladie réfractaire, d’autres traitements sont disponibles, tels que le GM-CSF en injection sous-cutanée ou en aérosol et le rituximab. L’évolution de la maladie est imprévisible. Une évolution spontanément favorable ou même une guérison spontanée peuvent survenir et la survie actuarielle à 5ans est de 95 %. Les principales complications sont infectieuses.SummaryAlveolar proteinosis (AP) is a rare disease characterized by alveolar accumulation of surfactant components, which impairs gas exchange. AP is classified into three groups: auto-immune AP defined by the presence of plasma autoantibodies anti-GM-CSF, the most frequent form (90 % of all AP); secondary AP, mainly occurring as a consequence of haematological diseases, or following on from toxic inhalation or infections, and genetic AP, which affects almost exclusively children. AP diagnosis is suspected where chest CT-scan demonstrates interstitial lung disease with a crazy paving aspect; and confirmed by bronchoalveolar lavage, which has a milky appearance and contains periodic acid Schiff positive proteinaceous alveolar deposits. The use of surgical lung biopsy to confirm AP is less frequent nowadays. In this context, positive antibodies against GM-CSF indicates an auto-immune etiology of the AP. Concerning management, whole lung lavage is the gold standard therapy. In refractory AP, new treatments are available such as subcutaneous or inhaled GM-CSF supplementation, or rituximab infusions. The clinical course is unpredictable. Spontaneous improvement or even cure can occur, and the 5-year actuarial survival is 95 %. The most frequent complications are infectious etiology.

Specified galectins are known to play a role in regulating cell proliferation, differentiation, adhesion and migration. Po66, a mouse IgG1 monoclonal antibody produced by immunization against squamous cell cancer, reacts against a carbohydrate-binding protein (Po66-CBP), recently shown to be a member of the galectin family with a strong homology with galectin-8 (PCTA-1), identified as a human tumor-associated antigen. We studied Po66 in squamous metaplasia of the bronchi in order to determine whether it could be specifically involved in neoplastic conditions and if so, if it would be helpful in distinguishing metaplasia at risk of cancer. Twenty-eight formalin-fixed, paraffin-embedded archival tissues of 17 metaplasias with SCC, 3 metaplasia with distant neoplastic disease and 8 metaplasias with an inflammatory process, were immunostained using a streptavidin biotin peroxydase method. The squamous metaplasias were positively stained in non-neoplastic disease as well as in neoplastic processes. Expression was also observed in stromal and normal cells. Po66-CBP was not associated with a pre-neoplastic character. We discussed the expression of this intra-cellular component of galectin-8 according to the functions of galectins in cellular differentiation, host reaction against tumor, and inflammation.

To the Editors: Idiopathic pulmonary fibrosis (IPF) is the most frequent form of idiopathic interstitial pneumonia. It is a chronic, progressive and fatal disease of unknown aetiology, characterised by histological features of usual interstitial pneumonia (UIP). Disease progression is marked by worsening dyspnoea, progressive loss of lung volume, abnormal gas exchange and poor quality of life. Median survival after diagnosis is 3–5 yrs. Currently, pirfenidone is the only drug approved in Europe for the treatment in IPF, as it has been shown to slow the decline of lung function [1]. However, no effect on survival has been demonstrated until now. Somatostatin is an endogenous cyclic peptide initially identified as a regulator of growth hormone secretion. In humans, it has been shown to bind with equal efficiency to five receptors: sst1, sst2A, sst3, sst4 and sst5. We have recently shown that the sst2A receptor is highly expressed in fibrotic lung tissue in IPF patients and that the uptake of octreotide, a somatostatin analogue that has a high affinity for sst2A, is elevated in the lungs of IPF patients and is correlated with the severity of lung fibrosis [2, 3]. Octreotide has been widely used for the treatment of neuroendocrine tumours for >20 yrs. In this study, we investigated the safety and efficacy of octreotide as a therapy for IPF. This was an open-label, proof-of-concept, non-randomised, non-controlled, multicentre phase II study performed in France between October 2006 and April 2008 to evaluate the safety and efficacy of intramuscular long-acting octreotide in patients with IPF. The trial was registered with ClinicalTrials.gov (identifier number NCT00463983). Patients had to be aged ≥40 yrs and meet the diagnostic criteria for IPF described in the American Thoracic Society/European Respiratory Society consensus statement [4]. In patients aged

International audience; BACKGROUND: The drug (131)I-labeled lipiodol is used as internal radiotherapy for unresectable hepatocellular carcinoma. Although the drug was considered safe during preapproval studies, we observed several cases of interstitial pneumonia following its administration. METHODS: Cases were retrospectively identified through the drug safety unit database of Rennes University Hospital. RESULTS: From 1994 to 2009, interstitial pneumonia developed in 15 patients following (131)I-labeled lipiodol administration, with an estimated prevalence of 15.5 cases (95% CI, 7.7-23.2) per 1,000 treated patients. Mean age of the patients was 60 ± 8 years, and the male to female ratio was 6.5:1. All patients had cirrhosis, mainly related to long-term alcohol intoxication (n = 12). Most (n = 10) cases occurred after the second (131)I-labeled lipiodol injection. The median delay between last (131)I-labeled lipiodol administration and first respiratory symptoms was 30 days (interquartile range, 16.5-45 days). All patients presented with shortness of breath. Physical examination mostly revealed fever (n = 11) and bilateral crackles (n = 12). Chest CT scan showed bilateral ground-glass opacities (n = 8) with septal thickening, retraction, or both (n = 8). BAL (n = 7) was remarkable for increased neutrophils (n = 4) or CD8(+) T cell count (n = 3). Despite corticosteroids, 12 (80%) patients died, mostly of untractable respiratory failure (n = 9). Median delay between last (131)I-labeled lipiodol injection and death was 63 days (interquartile range, 34-129 days). CONCLUSIONS: Interstitial pneumonia may be a serious and not uncommon complication of (131)I-labeled lipiodol administration.

To the Editors: Antisynthetase syndrome (ASS) is characterised by an inflammatory myositis associated with interstitial lung disease (ILD) and antisynthetase antibodies. Other symptoms, including arthritis, Raynaud's phenomenon and mechanic's hands, are also associated with ASS. Several antisynthetase antibodies 1 have been described, with anti-Jo1 being the most common. Little is known about the clinical manifestations of ASS associated with anti-threonyl-tRNA synthetase antibodies (anti-PL7) 2–4, most probably because anti-PL7 antibodies are particularly rare (5% of myositis 5) and have not been routinely researched in the past. We conducted this retrospective multicentric study to describe the clinical, radiographic and biological manifestations of ASS in 12 patients. This retrospective study was conducted in five university hospitals. The patients were followed from 2000–2010 in the Depts of Pneumology (n = 7) and Internal Medicine (n = 5). 16 anti-PL7 positive patients were identified due to immunological laboratory databases. To exclude false-positive patients, we only included patients who successively tested positive for anti-PL7 twice (n = 13): the three patients tested only once did not disclose any symptoms in accordance with ASS. We excluded one patient for whom clinical data were missing. The 12 included patients tested positive for anti-PL7 antibodies at least twice by immunodot (immuno-DOT D-tek; Diasorin, Antony, France) and/or Western blot using protein extracts from Hep2 cells (n = 7 and n = 5, respectively). They presented with one or more ASS symptoms, including ILD and/or myositis. A search for anti-DNA and anti-extractable nuclear antigen antibodies was systematically performed, whereas rheumatoid factor and anti-citrullinated peptide were available in four and two patients, respectively. The characterisation of the ILD pattern was made by several radiologists who were all experienced in ILD and were based on the American Thoracic Society/European Respiratory Society 2002 consensus 6. Pulmonary hypertension was suspected by …

Drug-induced interstitial pneumonia is a severe disease that has been reportedly caused by more than 100 compounds, the most common being amiodarone, methotrexate and bleomycin. We report a case of fatal acute interstitial pneumonia occurring after a second injection of 131 I-labeled lipiodol for hepatocellular carcinoma treatment. Infectious pneumonia was ruled out and lung biopsy revealed a pattern of usual interstitial pneumonia. Despite early initiation of systemic corticosteroids and additionally, antioxidant medications, the patient’s condition gradually worsened and he died 24 days after admission. 131 I-labeled lipiodol-induced interstitial pneumonia is probably frequently undiagnosed. A better knowledge of this disease would help to estimate its true incidence and may impact on the perceived risk/benefit ratio for its treatment. Moreover, this may have consequences on the prescription of 131 I-labeled lipiodol.

We report the case of a recurrent right pneumothorax, revealing metastasis of an osteosarcoma, 40 months after complete remission. Seven years after surgical excision, the patient is still considered in complete remission. Pneumothorax is rarely the first manifestation of lung metastasis. Osteosarcoma is the most frequent primary tumor. Chest computed tomography detects excavated or subpleural lung metastasis. Differential diagnosis between benign and malignant bullous lesions is important because surgical excision affects survival in some malignancies.

International audience; In this retrospective study, we analyzed 17 patients presenting with pulmonary fibrosis and a positive ANCA testing. This group was compared with a control group of 12 patients with IPF and negative ANCA testing. Patients were 15 males and 2 females, with a mean age of 66 years. Eight patients were past smokers, 3 current smokers and 6 non-smokers. Lung function tests at diagnosis were as follows (% predicted): total lung capacity 73%+/-18, vital capacity 82%+/-23, forced expiratory volume in 1 s (FEV(1)) 88%+/-24, carbon monoxide diffusion capacity of the lung 49%+/-2 (% predicted). Bronchoalveolar lavage results showed an increased cellularity with increased neutrophils counts. High resolution computed tomography of the chest showed prominent fibrosis with some degree of ground-glass attenuation in all patients. These characteristics were similar to the control group. Microscopic polyangiitis (MPA) was a major complicating event in ANCA-positive patients, occurring in 7 patients (anti-myeloperoxidase specificity in 5 patients). Pulmonary fibrosis predated occurrence of MPA in 6 patients and was diagnosed concomitantly with MPA in 1 patient. During the follow-up, 10/17 patients died. The death was directly related to vasculitis in 3 patients. We conclude that patients with pulmonary fibrosis should be evaluated for the presence of ANCA. Patients with positive ANCA testing, particularly if anti-myeloperoxidase, should be carefully monitored to detect the occurrence of microscopic polyangiitis.

International audience; OBJECTIVE: To assess the efficacy of systemic corticosteroids (CS) alone as first-line treatment in patients with Churg-Strauss syndrome (CSS) without poor-prognosis factors, as defined by the Five-Factors Score (FFS), and to compare the efficacy and safety of oral azathioprine (AZA) versus intravenous pulse cyclophosphamide (CYC) as adjuvant immunosuppressive therapy for treatment failure or relapse. METHODS: This multicenter, prospective, randomized, open-label therapeutic trial included 72 patients with newly diagnosed CSS (FFS of 0) treated with CS alone. At treatment failure or relapse, patients were randomized to receive 6 months of oral AZA or 6 pulses of CYC. Analyses were performed according to an intent-to-treat strategy. RESULTS: The mean +/- SD followup was 56.2 +/- 31.7 months. Among the 72 patients studied, 93% achieved remission with CS therapy alone, and 35% relapsed, mainly during the first year of treatment. Among the 19 patients randomized to additional immunosuppression because of treatment failure or relapse, 5 of 10 receiving AZA and 7 of 9 receiving pulse CYC achieved remission, but the difference was not statistically significant. Survival rates in all patients at 1 and 5 years were 100% and 97%, respectively. At the end of followup, 79% of the patients whose disease was in remission required low-dose CS therapy, mainly to control respiratory disease. CS-related adverse events were observed in 31% of the 72 patients. CONCLUSION: In CSS patients with an FFS of 0, survival was excellent, confirming the predictive value of the FFS in this disease. First-line therapy with CS achieved remission in most patients, but relapses were common, and one-third of them required additional immunosuppressive therapy. AZA or pulse CYC was fairly effective in treating CS-resistant disease or major relapses. Over the long term, most patients continued to take oral CS, which might explain the high rate of CS-related adverse events.

Introduction La dilatation des bronches (DDB) est une maladie frequente dont le traitement est encore assez largement empirique. Le tiotropium est une molecule bien validee dans la broncho-pneumopathie chronique obstructive, et qui pourrait etre interessante dans la DDB, car on attend de ses proprietes anticholinergiques une action broncho-dilatatrice et une reduction des secretions bronchiques. L’objectif de l’etude etait d’evaluer le tiotropium dans la DDB. Patients et methodes Les donnees concernant les patients adultes atteints de DDB suivis au CHU de Rennes et ayant beneficie d’un traitement par tiotropium depuis sa mise sur le marche ont ete recueillies retrospectivement. Resultats Soixante et un patients ont ete inclus. L’âge moyen etait de 61,5 ans. Il existait une predominance feminine (64 %). Les donnees concernant le nombre d’exacerbations etaient disponibles pour 26 patients. Quatre-vingt-cinq pour cent des patients avaient presente au moins une exacerbation l’annee precedant la mise sous tiotropium contre 58 % l’annee suivante ( p = 0,046). Le nombre moyen par an d’exacerbations etait de 2,10 l’annee precedant la mise sous tiotropium contre 1,65 l’annee suivante ( p = 0,09). Les donnees concernant le nombre d’hospitalisations etaient disponibles chez 33 patients. Le nombre moyen par an d’hospitalisations etait de 0,61 l’annee precedant la mise sous tiotropium contre 0,39 l’annee suivante ( p = 0,11). Les donnees fonctionnelles respiratoires etaient disponibles chez 24 patients, aucune modification des parametres fonctionnels respiratoires n’a ete observee sous tiotropium. Conclusion Le tiotropium semble apporter un benefice sur la reduction des exacerbations chez les patients atteints de DDB.

International audience; Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases, regulated by endogenous tissue inhibitors (TIMPs) and inducer (EMMPRIN). The demonstration of a functional role of MMPs in pulmonary diseases raises the possibility of therapeutic intervention targeting MMP/TIMP balance to prevent pathological processes.

International audience; Extracellular matrix metalloproteinase inducer (EMMPRIN) was examined on bronchoalveolar lavage fluids (BALFs) and lung tissue from patients with fibrosis (usual interstitial pneumonia-idiopathic pulmonary fibrosis [UIP-IPF], n = 15; diffuse parenchymal lung diseases without IPF characteristics on computerized tomography scan, n = 8) and without fibrosis (n = 6). In UIP-IPF, EMMPRIN staining was increased in areas of fibrosis, mainly in macrophages and in epithelial cells. EMMPRIN was also found in the extracellular medium with significant levels in patients with lung fibrosis compared to subjects without fibrosis. Moreover, macrophages from patients with lung fibrosis spontaneously produce EMMPRIN. These findings show that EMMPRIN is increased in lung fibrosis.

Pulmonary alveolar phospholipoproteinosis is a rare lung disease of unknown cause characterized by surfactant plugging of the alveoli. At the present time, surgical lung biopsy, long considered as the gold standard, is not necessary for positive diagnosis of pulmonary alveolar phospholipoproteinosis when computed tomography anomalies and analysis of bronchial lavage fluids present a typical pattern. Treatment requires abundant lavage, but the demonstration of anti-GM-CSF antibodies in primary forms opens new therapeutic perspectives.

Study objectives Respiratory failure (RF) is a frequent cause of death among patients with bilateral bronchiectasis. An ICU admission is commonly required, and neither short-term or long-term outcomes have been studied. Design We performed a retrospective study over a 10-year period (January 1990 to March 2000). All patients with bilateral bronchiectasis admitted for the first time in the medical ICU for RF were reviewed. Patients with cystic fibrosis were excluded. Measurements and results Forty-eight patients (mean age ± SD, 63 ± 11 years; mean simplified acute physiology score [SAPS] II, 32 ± 12) of whom 25% received long-term oxygen therapy (LTOT) were identified. All the patients were treated with intensive medical care, associated with noninvasive ventilation in 13 patients (27%), and 26 patients (54%) required intubation. Nine patients (19%) died in the ICU. The 1-year mortality rate was 40%. Among the variables recorded at ICU admission, age > 65 years (p = 0.002), SAPS II score > 32 (p = 0.012), use of LTOT (p = 0.047), and intubation (p = 0.027) were associated with reduced survival in univariate analysis by Cox regression. Multivariate analysis by Cox proportional hazard model showed that age > 65 years (relative risk [RR], 2.70; 95% confidence interval [CI], 1.15 to 6.29) and use of LTOT (RR, 2.52; 95% CI, 1.15 to 5.54) were independently associated with reduced survival. Conclusions We performed the first study providing information related to the impact of the first ICU stay for RF on long-term outcomes for patients with bilateral bronchiectasis. Age > 65 years and prior use of LTOT were associated with reduced survival.

Resume Introduction L’hydroxyuree est un antimetabolite utilise dans le traitement des maladies myeloproliferatives. Ses effets secondaires habituels sont principalement hematologiques, gastro-intestinaux, cutanes et une fievre. Plus rarement, des pneumopathies ont ete decrites. Observation Nous en rapportons un cas chez une patiente traitee pour polyglobulie primitive. Elle fut hospitalisee 20 jours apres l’instauration d’un traitement par hydroxyuree en raison d’une fievre elevee, d’une toux et expectorations muqueuses associees a des nausees. Le scanner thoracique retrouvait des opacites diffuses en verre depoli. Les recherches microbiologiques ont ete negatives. Le tableau a regresse en quelques jours apres l’arret du traitement. La reintroduction du medicament a entraine une recidive des symptomes. Conclusion Ce cas vient completer 15 cas de la litterature a propos de pneumopathies induites par l’hydroxyuree. Deux formes en ont ete decrites : aigue, febrile, dans le mois apres introduction de l’hydroxyuree ; et une forme chronique et apyretique. Il faut savoir evoquer cette complication rare de l’hydroxyuree.