Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
AIM: To describe the main characteristics and the treatment of cryptococcosis in patients with sarcoidosis. DESIGN: Multicenter study including all patients notified at the French National Reference Center for Invasive Mycoses and Antifungals. METHODS: Retrospective chart review. Each case was compared with two controls without opportunistic infections. RESULTS: Eighteen cases of cryptococcosis complicating sarcoidosis were analyzed (13 men and 5 women). With 2749 cases of cryptococcosis registered in France during the inclusion period of this study, sarcoidosis accounted for 0.6% of all the cryptococcosis patients and for 2.9% of the cryptococcosis HIV-seronegative patients. Cryptococcosis and sarcoidosis were diagnosed concomitantly in four cases; while sarcoidosis was previously known in 14/18 patients, including 12 patients (67%) treated with steroids. The median rate of CD4 T cells was 145 per mm(3) (range: 55-1300) and not related to steroid treatment. Thirteen patients had cryptococcal meningitis (72%), three osteoarticular (17%) and four disseminated infections (22%). Sixteen patients (89%) presented a complete response to antifungal therapy. After a mean follow-up of 6 years, no death was attributable to cryptococcosis. Extra-thoracic sarcoidosis and steroids were independent risk factors of cryptococcosis in a logistic regression model adjusted with the sex of the patients. CONCLUSIONS: Cryptococcosis is a significant opportunistic infection during extra-thoracic sarcoidosis, which occurs in one-third of the cases in patients without any treatment; it is not associated to severe CD4 lymphocytopenia and has a good prognosis.
ISSN: 1460-2725

hal-00873410
https://hal.archives-ouvertes.fr/hal-00873410
DOI : 10.1093/qjmed/hct052
PUBMED : 23515400

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
INTRODUCTION: Light chain deposition disease is a rare clinical entity characterized by deposition of monoclonal immunoglobulin light chains in organs. The kidneys are almost always affected, while the lung manifestations that have been reported, including nodular or diffuse disease, especially cystic lesions, are unusual. CASE REPORT: We report the case of a 60-year-old man with a diffuse infiltrative lung disease characterized by numerous apical cysts. The diagnosis of light chain deposition cystic lung disease was obtained by surgical lung biopsy. Light chain deposits in the salivary glands were the only extrapulmonary manifestation. Despite 12 chemotherapy cycles, the patient's lung function and radiological appearances worsened. CONCLUSION: This is the fourth case describing a cystic lung disease due to light chain deposition in the literature. It highlights the need for comprehensive investigations so as not to miss this rare cause of cystic lung disease, which appears to be related to a primary pulmonary lymphoproliferative disorder. The only treatment that appears to be effective is lung transplantation.
ISSN: 0761-8425

hal-00873356
https://hal.archives-ouvertes.fr/hal-00873356
https://hal.archives-ouvertes.fr/hal-00873356/document
https://hal.archives-ouvertes.fr/hal-00873356/file/DA_pots_chaines_lA_gA_res_non_amyloides_version_finale.pdf
DOI : 10.1016/j.rmr.2013.02.003

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : 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
ISSN: 0761-8425

hal-01334065
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01334065
DOI : 10.1016/j.rmr.2016.04.018

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Background: Influenza is an important cause of serious illness and death, particularly in elderly and high-risk groups. Objectives Aim of this study was to identify factors associated with poor outcomes among adults hospitalized in France for laboratory-confirmed seasonal influenza. Study design Patients hospitalized for influenza were identified in a prospective, multicenter study carried out in French hospitals during three consecutive influenza seasons (2012–2015). Influenza virus infection was confirmed by reverse transcription polymerase chain reaction. Sociodemographic and clinical variables were compared according to the virus type and subtype. Risk factors for complications, intensive care unit (ICU) admission and death were analyzed by backward stepwise logistic regression. Results The study population consisted of 566 patients, of whom 56% were older than 65 years and 82% had underlying chronic illnesses. Type A influenza viruses infected 422 patients (75%), including subtype H3N2 in 239 patients (57%). The prior vaccine coverage rate was 38%. Complications occurred in 255 patients (45%), consisting mainly of pneumonia (n = 143, 30%) and respiratory failure (n = 116, 20%). Eighty-three patients (15%) were admitted to an ICU, and the in-hospital mortality rate was 4% (n = 21). Sixty-six patients (12%) received oseltamivir. Age over 65 years was the only identified risk factor for complications. Risk factors for ICU admission were an absence of vaccination, no oseltamivir administration before admission, pre-existing chronic respiratory disease, and current smoking. Age over 65 years and ICU admission were risk factors for death. Conclusions Older individuals and patients with underlying conditions are most at risk of influenza complications. Vaccination and early oseltamivir administration, both of which are recommended for these patients, appear to reduce ICU admissions
ISSN: 1386-6532

hal-01302409
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01302409
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01302409/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01302409/file/Factors%20associated%20with%20poor%20outcomes.pdf
DOI : 10.1016/j.jcv.2016.04.005

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
PURPOSE: Dairy farming is a risk factor for the development of chronic obstructive pulmonary disease (COPD). We assessed the prevalence of farming-induced COPD (FI-COPD) using a new screening device, and we analyzed symptoms and occupational risk factors. METHODS: We performed on-site screening study of bronchial obstruction using an electronic mini-spirometer (EMS) on an entire population of dairy farmers (n = 147) from two villages in Brittany, France. Suspected bronchial obstruction (FEV1/FEV6 <0.8) was confirmed with standardized lung function tests (FEV1/FVC ≤0.7). We assessed past medical histories, respiratory symptoms, and occupational tasks of subjects with bronchial obstruction; asthmatics were defined as atopic and/or reversible; smoking-induced COPD patients were defined as non-reversible, non-atopic with smoking histories (≥5 PY); and FI-COPD patients were defined as non-reversible, non-atopic, and non-smokers. RESULTS: Using the EMS, 30.6% (n = 45) of dairy farmers were suspected of bronchial obstruction and underwent standardized spirometry. The FEV1/FEV6 ratio and FEV1/FVC ratio were in good agreement (r² = 0.66, P < 0.0001). The prevalence of confirmed bronchial obstruction was 9.5% (n = 14), which included 4 asthmatics, 3 smoking-induced COPD subjects, and 7 FI-COPD subjects. All the COPD patients were GOLD Stage II, and none were aware of their respiratory disease. Foddering duration was significantly higher in FI-COPD subjects compared with non-obstructive subjects, with 44 versus 17 min/day, respectively. CONCLUSIONS: The EMS was a convenient mean of screening for bronchial obstruction, especially in on-site settings, and allowed us to diagnose FI-COPD in a non-spontaneously complaining dairy farmer population. Foddering was considered a significant risk factor.
ISSN: 0340-0131

hal-00872929
https://hal.archives-ouvertes.fr/hal-00872929
DOI : 10.1007/s00420-011-0708-6
PUBMED : 21986906

Éditeur(s) : HAL CCSD Wiley-VCH Verlag
Résumé : International audience
Saccharopolyspora rectivirgula is the principal cause of farmer's lung disease (FLD). Serodiagnosis is based on immunoprecipitation techniques or enzyme immunoassays with homemade crude antigens and is not standardized. We aimed to produce specific recombinant antigens for the development of a standardized ELISA. We recruited 41 patients and 43 healthy exposed controls from five university hospital pneumology departments in France and Switzerland. S. rectivirgula proteins were extracted, separated by 2D electrophoresis, and subjected to Western blotting, with sera from FLD patients or controls. FLD-specific proteins were identified by MS and were produced as recombinant antigens. The diagnostic performance of ELISA tests using the recombinant antigens was assessed with all the sera from FLD patients and controls. We identified 25 FLD-specific proteins, some of which play important roles in transport, nutrition, or virulence. We produced 17 of these proteins as recombinant antigens and assessed their suitability for inclusion in the ELISA test. A combination of three of these proteins (SR1FA, SR17, and SR22) proved remarkably effective at discriminating between patients and controls, with a sensitivity of 83% and a specificity of 77%. The recombinant antigens produced in this study constitute a major step toward the improvement of diagnostic performance and the standardization of FLD serodiagnosis.
ISSN: 1862-8346

hal-01115880
https://hal.archives-ouvertes.fr/hal-01115880
DOI : 10.1002/prca.201400024
PUBMED : 25264606

Éditeur(s) : HAL CCSD
Résumé : International audience
INTRODUCTION: The syndrome of combined pulmonary fibrosis and emphysema (CPFE) is characterized by imaging features consisting of the association of centrilobular and/or paraseptal emphysema and pulmonary fibrosis. Virtually all patients are smokers and thus at high risk of developing lung cancer. METHODS: This retrospective multicentre study was conducted by the Groupe d'Etudes et de Recherche sur les Maladies "Orphelines" Pulmonaires (GERM"O"P). RESULTS: A total of 47 patients presenting with lung cancer and CPFE syndrome were identified. All patients were smokers, with a mean of 47 pack-years. A pathological diagnosis of lung cancer was obtained for 38 (81%) patients. Histological type was squamous cell carcinoma in 17 (36%) patients, adenocarcinoma in 14 (30%), non-small-cell lung cancer not otherwise specified in three (6%), small-cell lung cancer in three (6%), and sarcomatoid carcinoma in one (2%). Overall, 20 of the 47 patients could not receive standard-of-care treatment for lung cancer, as per international recommendations or guidelines; this limitation was considered to be directly related to the CPFE syndrome in eight (40%) cases. CONCLUSION: Lung cancer in patients with CPFE syndrome represents a specific entity with a poor prognosis, that further represents the most characteristic and severe model of tobacco-related disease.
Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer

hal-01063912
https://hal.archives-ouvertes.fr/hal-01063912
DOI : 10.1097/JTO.0000000000000209
PUBMED : 25157769

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: Two antifibrotic drugs, pirfenidone and nintedanib, are approved by the European Medicines Agency and the US Food and Drug Administration for the treatment of idiopathic pulmonary fibrosis (IPF). In this analysis, treatment patterns of European patients with IPF were investigated to understand antifibrotic prescribing and identify unmet needs in IPF treatment practice. Methods: Between February and March 2016, respiratory physicians from France, Germany, Italy, Spain, and the UK participated in an online questionnaire designed to collect information on IPF treatment patterns in patients under their care. Patients were categorized as treated (received approved antifibrotics) or untreated (did not receive approved antifibrotics, but may have received other unapproved therapies). Classification of IPF diagnosis (confirmed/suspected) and severity ('mild'/'moderate'/'severe') for each patient was based on the individual physician's report. Patients' perspectives were not recorded in this study. Results: In total, 290 physicians responded to the questionnaire. Overall, 54% of patients with IPF did not receive treatment with an approved antifibrotic. More patients had a confirmed IPF diagnosis in the treated (84%) versus the untreated (51%) population. Of patients with a confirmed diagnosis, 40% did not receive treatment. The treated population was younger than the untreated population (67 vs 70 years, respectively; p = 0.01), with more frequent multidisciplinary team evaluation (83% vs 57%, respectively; p = 0.01). A higher proportion of untreated patients had forced vital capacity > 80% at diagnosis versus treated patients. Of patients with 'mild' IPF, 71% did not receive an approved antifibrotic versus 41% and 60% of patients with 'moderate' and 'severe' IPF, respectively. Conclusions: Despite the availability of antifibrotic therapies, many European patients with confirmed IPF do not receive approved antifibrotic treatment. Importantly, there appears to be a reluctance to treat patients with 'mild' or 'stable' disease, and instead adopt a 'watch and wait' approach. More education is required to address diagnostic uncertainty, poor understanding of IPF and its treatments, and issues of treatment access. There is a need to increase physician awareness of the benefits associated with antifibrotic treatment across the spectrum of IPF severity.
ISSN: 1471-2466

hal-01616061
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616061
DOI : 10.1186/s12890-017-0468-5
PUBMED : 28915874

Éditeur(s) : HAL CCSD
Résumé : International audience
o abstract
Journal of Thoracic Disease

hal-01319894
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01319894
DOI : 10.21037/jtd.2016.03.34
PUBMED : 27162684
PUBMEDCENTRAL : PMC4842784

Éditeur(s) : HAL CCSD
Résumé : International audience
Over the past few years, genetics has significantly improved the understanding of interstitial lung diseases (ILD)...
European Respiratory Journal

hal-01534151
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01534151
DOI : 10.1183/13993003.00407-2017
PUBMED : 28495697

Éditeur(s) : HAL CCSD
Résumé : National audience
Il existe différents facteurs déclenchant des exacerbations aiguës de BPCO (EA BPCO), principalement les infections, virales et bactériennes, mais sont également incriminés la pollution, l’arrêt des traitements de fond ou un terrain génétique spécifique...
Revue Des Maladies Respiratoires

Droits : info:eu-repo/semantics/OpenAccess
hal-01560278
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560278
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560278/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560278/file/SJ_V6_final_-Jouneau_Facteurs_d%C3%A9clenchants_des_EA_BPCO.pdf
DOI : 10.1016/j.rmr.2017.03.005

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
The objective of this study is to assess the association of clinical manifestations of systemic sclerosis (SSc) with the absolute count of circulating blood monocyte subpopulations according to their membrane expression of CD16. Forty-eight consecutive patients fulfilling the 2013 ACR/EULAR classification criteria for SSc were included in this cross-sectional study. CD16+ monocyte absolute count was defined by flow cytometry and confronted to the clinical characteristics of SSc patients. Twenty-three healthy donors (HD) were randomly selected for comparison. SSc patients had an increased number of total circulating blood monocytes compared to HD (p < 0.001). The CD16- subpopulation absolute count was increased in SSc patients compared to HD (p < 0.001) but was similar in limited SSc (lSSc) and diffuse SSc (dSSc). On the contrary, the CD16+ population absolute count was increased in dSSc compared to both HD and lSSc patients (dSSc 0.071 Giga/L (+/- 0.034) vs HD 0.039 Giga/L (+/- 0.030), p < 0.01, and dSSc 0.071 Giga/L (+/- 0.034) vs lSSc 0.048 Giga/L (+/- 0.024), p < 0.05). The CD16+ monocyte subpopulation absolute count was significantly correlated with the severity of skin fibrosis evaluated by the modified Rodnan skin score (p < 0.001). The CD16+ monocyte subpopulation was also associated with pulmonary fibrosis (p < 0.05), with the severity of the restrictive ventilatory defect evaluated by total lung capacity (p < 0.05) and with the pulmonary function impairment reflected by diffusing capacity of the lungs for carbon monoxyde measures (p < 0.01). These results suggest that CD16+ monocytes are associated with the main fibrotic manifestations of SSc and their role in the pathogenesis of fibrosis in this autoimmune disorder should therefore be further considered.
ISSN: 0770-3198

hal-01560150
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560150
DOI : 10.1007/s10067-017-3597-6
PUBMED : 28293753

Éditeur(s) : HAL CCSD Paris, Masson et Cie
Résumé : National audience
Decreased frequency of pulmonary exacerbations, mainly related to immunomodulatory effects of macrolide antibiotics, has been demonstrated in bronchiectasis and chronic obstructive pulmonary diseases (COPD). Due to its tolerance, azithromycin is the antibiotic of choice for maintenance therapy at the dose of 250 mg per day or 500 mg × 3 per week (for body weight >55 kg). Maintenance therapy with macrolide could be proposed in selected patients with bronchiectasis or COPD with more than 3 acute exacerbations in the previous year or decreased lung function despite compliance with optimum treatment. The risk of sudden cardiac death with azithromycin is rare and controversial. It should be avoided in patients with a high baseline risk of cardiovascular disease, QT>450 msec, pulse rate>100 bpm and potential drug interactions, particularly those known to cause QT prolongation. It is recommended to search for hearing deficit (audiometry) and sputum culture positive for mycobacteria. Patients must also be aware that it can rapidly lead to macrolide resistance in commensal or pathogenic flora. Follow-up evaluation every 3 month can be proposed with medical history (hearing deficit) and electrocardiography. After one year, the treatment should be stopped in the absence of reduction in the frequency of exacerbations.
Points essentielsLes macrolides administrés au long cours permettent, grâce en partie à leurs propriétés anti-inflammatoires, de diminuer la fréquence des exacerbations dans la DDB et la BPCO.Du fait de sa tolérance, l’azithromycine est le macrolide de choix, pouvant être utilisé à la dose de 250 mg/j ou 500 mg 3 fois par semaine chez les patients de plus de 55 kg.Un traitement par macrolides au long cours pourrait être proposé à des patients atteints de DDB ou de BPCO ayant eu plus de 3 exacerbations l’année précédente ou ayant une dégradation de leur fonction respiratoire malgré un traitement de fond bien conduit.Du fait d’un risque rare et controversé de mort subite d’origine cardiaque, il ne doit pas être proposé en cas de pathologie cardiovasculaire évoluée, d’intervalle QT > 450 ms, de traitement pouvant allonger l’intervalle QT, de tachycardie > 100/min.Il est recommandé de s’assurer de l’absence de troubles auditifs (audiogramme) et de mycobactérie atypique dans les cultures des expectorations. Les patients doivent aussi être informés du risque d’apparition de résistance aux macrolides de la flore commensale et pathogène.Une surveillance clinique, avec en particulier la recherche de troubles auditifs et électrocardiographique, peut être proposée tous les 3 mois. L’absence de diminution de la fréquence des exacerbations, lors du bilan annuel, justifie l’arrêt du traitement.
ISSN: 0032-7867

hal-01073027
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01073027
DOI : 10.1016/j.lpm.2013.08.006
PUBMED : 24631048

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
INTRODUCTION: Hydroxyurea is an antimetabolite drug used in the treatment of myeloproliferative disorders. Common adverse effects include haematological, gastrointestinal cutaneous manifestations, and fever. Hydroxyurea-induced pneumonitis is unusual. CASE REPORT: A female patient was treated with hydroxyurea for polycythemia vera. She was admitted 20 days after commencing treatment with a high fever, productive cough, clear sputum and nausea. A chest CT-scan showed diffuse ground-glass opacities. Microbiological investigations were negative. The symptoms disappeared a few days after discontinuation of the drug and rechallenge led to a relapse of symptoms. CONCLUSION: Our case and 15 earlier cases of hydroxyurea-induced pneumonitis are reviewed. Two patterns of this disease may exist: an acute febrile form occurring within 1 month of introduction of hydroxyurea and a subacute form without fever. Even if uncommon, one should be aware of this complication of hydroxyurea.
Revue des Maladies Respiratoires

hal-01072996
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01072996
DOI : 10.1016/j.rmr.2013.09.001
PUBMED : 24878159

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The use of recombinant antigens has been shown to improve both the sensitivity and the standardization of the serological diagnosis of Farmer's lung disease (FLD). The aim of this study was to complete the panel of recombinant antigens available for FLD serodiagnosis with antigens of Lichtheimia corymbifera, known to be involved in FLD. L. corymbifera proteins were thus separated by 2D electrophoresis and subjected to western blotting with sera from 7 patients with FLD and 9 healthy exposed controls (HEC). FLD-associated immunoreactive proteins were identified by mass spectrometry based on a protein database specifically created for this study and subsequently produced as recombinant antigens. The ability of recombinant antigens to discriminate patients with FLD from controls was assessed by ELISA performed with sera from FLD patients (n = 41) and controls (n = 43) recruited from five university hospital pneumology departments of France and Switzerland. Forty-one FLD-associated immunoreactive proteins from L. corymbifera were identified. Six of them were produced as recombinant antigens. With a sensitivity and specificity of 81.4 and 77.3% respectively, dihydrolipoyl dehydrogenase was the most effective antigen for discriminating FLD patients from HEC. ELISA performed with the putative proteasome subunit alpha type as an antigen was especially specific (88.6%) and could thus be used for FLD confirmation. The production of recombinant antigens from L. corymbifera represents an additional step towards the development of a standardized ELISA kit for FLD diagnosis.
ISSN: 1932-6203

hal-01368315
https://hal.archives-ouvertes.fr/hal-01368315
DOI : 10.1371/journal.pone.0160888
PUBMED : 27490813
PUBMEDCENTRAL : PMC4973876

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
o abstract
ISSN: 1070-5287

hal-01158656
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01158656
DOI : 10.1097/MCP.0000000000000171
PUBMED : 26016584

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
RATIONALE: Optimal management of complicated parapneumonic effusions (CPPE) remains controversial. OBJECTIVES: to assess safety and efficacy of iterative therapeutic thoracentesis (ITTC), the first-line treatment of CPPE in Rennes University Hospital. METHODS: Patients with CPPE were identified through our computerized database. We retrospectively studied all cases of CPPE initially managed with ITTC in our institution between 2001 and 2010. ITTC failure was defined by the need for additional treatment (i.e. surgery or percutaneous drainage), or death. RESULTS: Seventy-nine consecutive patients were included. The success rate was 81% (n = 64). Only 3 patients (4%) were referred to thoracic surgery. The one-year survival rate was 88%. On multivariate analysis, microorganisms observed in pleural fluid after Gram staining and first thoracentesis volume ≥450 mL were associated with ITTC failure with adjusted odds-ratios of 7.65 [95% CI, 1.44-40.67] and 6.97 [95% CI, 1.86-26.07], respectively. The main complications of ITTC were iatrogenic pneumothorax (n = 5, 6%) and vasovagal reactions (n = 3, 4%). None of the pneumothoraces required chest tube drainage, and no hemothorax or re-expansion pulmonary edema was observed. CONCLUSIONS: Although not indicated in international recommendations, ITTC is safe and effective as first-line treatment of CPPE, with limited invasiveness.
ISSN: 1932-6203

hal-00945622
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00945622
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00945622/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00945622/file/fetchObject.pdf
PUBMED : 24400113

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
The natural history of pulmonary Langerhans cell histiocytosis (PLCH) has been unclear due to the absence of prospective studies. The rate of patients who experience an early progression of their disease is unknown. Additionally, conflicting effects of smoking cessation on the outcome of PLCH have been reported. In this prospective, multicentre study, 58 consecutive patients with newly diagnosed PLCH were comprehensively evaluated over a two-year period. Our objectives were to estimate the incidence of early progression of the disease and to evaluate the impact of smoking status on lung function outcomes. Lung function deterioration was defined as a decrease of at least 15% in FEV1 and/or FVC and/or DLCO, compared with baseline values. At each visit, smoking status was recorded based on the patients' self-reports and urinary cotinine measurements that were blinded for the patients. The cumulative incidence of lung function outcomes over time was estimated using the non-parametric Kaplan-Meier method. Multivariate Cox models with time-dependent covariates were used to calculate the hazards ratios of the lung function deterioration associated with smoking status with adjustment for potential confounders. The cumulative incidence of lung function deterioration at 24 months was 38% (22% for FEV1 and DLCO, and 9% for FVC). In the multivariate analysis, smoking status and PaO2 at inclusion were the only factors associated with the risk of lung function deterioration. The patients' smoking statuses markedly changed over time. Only 20% of the patients quit using tobacco for the entire study period. Nevertheless, being a non-smoker was associated with a decreased risk of subsequent lung function deterioration, even after adjustment for baseline predictive factors. By serial lung computed tomography, the extent of cystic lesions increased in only 11% of patients. Serial lung function evaluation on a three- to six-month basis is essential for the follow-up of patients with recently diagnosed PLCH to identify those who experience an early progression of their disease. These patients are highly addicted to tobacco, and robust efforts should be undertaken to include them in smoking cessation programs. ClinicalTrials.gov: No: NCT01225601 .
ISSN: 1750-1172

hal-01146047
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01146047
PUBMED : 25887097
DOI : 10.1186/s13023-015-0249-2

Éditeur(s) : HAL CCSD
Résumé : International audience
Decreased frequency of pulmonary exacerbations, mainly related to immunomodulatory effects of macrolide antibiotics, has been demonstrated in bronchiectasis and chronic obstructive pulmonary diseases (COPD). Due to its tolerance, azithromycin is the antibiotic of choice for maintenance therapy at the dose of 250 mg per day or 500 mg × 3 per week (for body weight extgreater55 kg). Maintenance therapy with macrolide could be proposed in selected patients with bronchiectasis or COPD with more than 3 acute exacerbations in the previous year or decreased lung function despite compliance with optimum treatment. The risk of sudden cardiac death with azithromycin is rare and controversial. It should be avoided in patients with a high baseline risk of cardiovascular disease, QT extgreater450 msec, pulse rate extgreater100 bpm and potential drug interactions, particularly those known to cause QT prolongation. It is recommended to search for hearing deficit (audiometry) and sputum culture positive for mycobacteria. Patients must also be aware that it can rapidly lead to macrolide resistance in commensal or pathogenic flora. Follow-up evaluation every 3 month can be proposed with medical history (hearing deficit) and electrocardiography. After one year, the treatment should be stopped in the absence of reduction in the frequency of exacerbations.
Presse Médicale (Paris, France: 1983)

hal-01063927
https://hal.archives-ouvertes.fr/hal-01063927
DOI : 10.1016/j.lpm.2013.08.006

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
Alveolar 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.
La 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 5 ans est de 95 %. Les principales complications sont infectieuses.
ISSN: 0761-8425

hal-01085907
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01085907
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01085907/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01085907/file/Prot%C3%A9inose%20alv%C3%A9olaire%20pulmonaire_accepted.pdf
DOI : 10.1016/j.rmr.2014.08.009